A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control.

PubMed

Killeen, G F; McKenzie, F E; Foy, B D; Schieffelin, C; Billingsley, P F; Beier, J C

2000-05-01

Malaria transmission intensity is modeled from the starting perspective of individual vector mosquitoes and is expressed directly as the entomologic inoculation rate (EIR). The potential of individual mosquitoes to transmit malaria during their lifetime is presented graphically as a function of their feeding cycle length and survival, human biting preferences, and the parasite sporogonic incubation period. The EIR is then calculated as the product of 1) the potential of individual vectors to transmit malaria during their lifetime, 2) vector emergence rate relative to human population size, and 3) the infectiousness of the human population to vectors. Thus, impacts on more than one of these parameters will amplify each other's effects. The EIRs transmitted by the dominant vector species at four malaria-endemic sites from Papua New Guinea, Tanzania, and Nigeria were predicted using field measurements of these characteristics together with human biting rate and human reservoir infectiousness. This model predicted EIRs (+/- SD) that are 1.13 +/- 0.37 (range = 0.84-1.59) times those measured in the field. For these four sites, mosquito emergence rate and lifetime transmission potential were more important determinants of the EIR than human reservoir infectiousness. This model and the input parameters from the four sites allow the potential impacts of various control measures on malaria transmission intensity to be tested under a range of endemic conditions. The model has potential applications for the development and implementation of transmission control measures and for public health education.

Radar Monitoring of Wetlands for Malaria Control

NASA Technical Reports Server (NTRS)

Pope, Kevin O.

1997-01-01

Malaria is perhaps the most serious human disease problem. It inflicts millions worldwide and is on the rise in many countries where it was once under control. This rise is in part due to the high costs, both economic and environmental, of current control programs. The search for more cost-effective means to combat malaria has focussed attention on new technologies, one of which is remote sensing. Remote sensing has become an important tool in the effort to control a variety of diseases worldwide and malaria is perhaps one of the most promising. This study is part of the malaria control effort in the Central American country of Belize, which has experienced a resurgence of malaria in the last two decades. The proposed project is a feasibility study of the use of Radarsat (and other similar radar systems) to monitor seasonal changes in the breeding sites of the anopheline mosquito, which is responsible for malaria transmission. We propose that spatial and temporal changes in anopheline mosquito production can be predicted by sensing where and when their breeding sites are flooded. Timely knowledge of anopheline mosquito production is a key factor in control efforts. Such knowledge can be used by local control agencies to direct their limited resources to selected areas and time periods when the human population is at greatest risk. Radar is a key sensor in this application because frequent cloud cover during the peak periods of malaria transmission precludes the use of optical sensors.

Simplified Models of Vector Control Impact upon Malaria Transmission by Zoophagic Mosquitoes

PubMed Central

Kiware, Samson S.; Chitnis, Nakul; Moore, Sarah J.; Devine, Gregor J.; Majambere, Silas; Merrill, Stephen; Killeen, Gerry F.

2012-01-01

Background High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as “very zoophagic,” meaning they feed occasionally (<10% of blood meals) upon humans, so personal protection interventions have negligible impact upon their survival. Methods and Findings We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with and without assuming reduced human infectivity, respectively) impacts of personal protection measures upon transmission. (3) Illustrate how appreciable indirect communal-level protection for non-users can be accrued through direct personal protection of users. (4) Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, community-wide protection of users and non-users alike may linearly relate to the efficacy of a user’s direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy (≥80%) are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. Conclusions Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact interventions using three field-measurable parameters; the proportion of human exposure to mosquitoes occurring when an intervention can be practically used, its protective efficacy when used, and the proportion of people using it. PMID:22701527

Malaria Distribution, Prevalence, Drug Resistance and Control in Indonesia

PubMed Central

Elyazar, Iqbal R.F.; Hay, Simon I.; Baird, J. Kevin

2011-01-01

Approximately 230 million people live in Indonesia. The country is also home to over 20 anopheline vectors of malaria which transmit all four of the species of Plasmodium that routinely infect humans. A complex mosaic of risk of infection across this 5000-km-long archipelago of thousands of islands and distinctive habitats seriously challenges efforts to control malaria. Social, economic and political dimensions contribute to these complexities. This chapter examines malaria and its control in Indonesia, from the earliest efforts by malariologists of the colonial Netherlands East Indies, through the Global Malaria Eradication Campaign of the 1950s, the tumult following the coup d’état of 1965, the global resurgence of malaria through the 1980s and 1990s and finally through to the decentralization of government authority following the fall of the authoritarian Soeharto regime in 1998. We detail important methods of control and their impact in the context of the political systems that supported them. We examine prospects for malaria control in contemporary decentralized and democratized Indonesia with multidrug-resistant malaria and greatly diminished capacities for integrated malaria control management programs. PMID:21295677

Human Antibody Responses to the Anopheles Salivary gSG6-P1 Peptide: A Novel Tool for Evaluating the Efficacy of ITNs in Malaria Vector Control

PubMed Central

Drame, Papa Makhtar; Poinsignon, Anne; Besnard, Patrick; Cornelie, Sylvie; Le Mire, Jacques; Toto, Jean-Claude; Foumane, Vincent; Dos-Santos, Maria Adelaide; Sembène, Mbacké; Fortes, Filomeno; Simondon, Francois; Carnevale, Pierre; Remoue, Franck

2010-01-01

To optimize malaria control, WHO has prioritised the need for new indicators to evaluate the efficacy of malaria vector control strategies. The gSG6-P1 peptide from gSG6 protein of Anopheles gambiae salivary glands was previously designed as a specific salivary sequence of malaria vector species. It was shown that the quantification of human antibody (Ab) responses to Anopheles salivary proteins in general and especially to the gSG6-P1 peptide was a pertinent biomarker of human exposure to Anopheles. The present objective was to validate this indicator in the evaluation of the efficacy of Insecticide Treated Nets (ITNs). A longitudinal evaluation, including parasitological, entomological and immunological assessments, was conducted on children and adults from a malaria-endemic area before and after the introduction of ITNs. Significant decrease of anti-gSG6-P1 IgG response was observed just after the efficient ITNs use. Interestingly, specific IgG Ab level was especially pertinent to evaluate a short-time period of ITNs efficacy and at individual level. However, specific IgG rose back up within four months as correct ITN use waned. IgG responses to one salivary peptide could constitute a reliable biomarker for the evaluation of ITN efficacy, at short- and long-term use, and provide a valuable tool in malaria vector control based on a real measurement of human-vector contact. PMID:21179476

Human antibody responses to the Anopheles salivary gSG6-P1 peptide: a novel tool for evaluating the efficacy of ITNs in malaria vector control.

PubMed

Drame, Papa Makhtar; Poinsignon, Anne; Besnard, Patrick; Cornelie, Sylvie; Le Mire, Jacques; Toto, Jean-Claude; Foumane, Vincent; Dos-Santos, Maria Adelaide; Sembène, Mbacké; Fortes, Filomeno; Simondon, Francois; Carnevale, Pierre; Remoue, Franck

2010-12-14

To optimize malaria control, WHO has prioritised the need for new indicators to evaluate the efficacy of malaria vector control strategies. The gSG6-P1 peptide from gSG6 protein of Anopheles gambiae salivary glands was previously designed as a specific salivary sequence of malaria vector species. It was shown that the quantification of human antibody (Ab) responses to Anopheles salivary proteins in general and especially to the gSG6-P1 peptide was a pertinent biomarker of human exposure to Anopheles. The present objective was to validate this indicator in the evaluation of the efficacy of Insecticide Treated Nets (ITNs). A longitudinal evaluation, including parasitological, entomological and immunological assessments, was conducted on children and adults from a malaria-endemic area before and after the introduction of ITNs. Significant decrease of anti-gSG6-P1 IgG response was observed just after the efficient ITNs use. Interestingly, specific IgG Ab level was especially pertinent to evaluate a short-time period of ITNs efficacy and at individual level. However, specific IgG rose back up within four months as correct ITN use waned. IgG responses to one salivary peptide could constitute a reliable biomarker for the evaluation of ITN efficacy, at short- and long-term use, and provide a valuable tool in malaria vector control based on a real measurement of human-vector contact.

Knowledge of human social and behavioral factors essential for the success of community malaria control intervention programs: The case of Lomahasha in Swaziland.

PubMed

Dlamini, Sabelo V; Liao, Chien-Wei; Dlamini, Zandile H; Siphepho, Jameson S; Cheng, Po-Ching; Chuang, Ting-Wu; Fan, Chia-Kwung

2017-04-01

Although malaria control programs have made rapid progress recently, they neglect important social and behavioral factors associated with the disease. Social, political, and cultural factors are involved in malaria control, and individuals in a community may be comfortable in behaving in ways that, to an outsider, may seem contrary to commonly held perceptions. Malaria control efforts can no longer afford to overlook the multidimensional human contexts that create and support varying notions of malaria and its prevention, treatment, and control. This study aimed to assess the knowledge and perceptions of malaria issues in the community, and to identify practices that support or hinder the progress of malaria control programs. A triangulation study involving individual interviews, focus group discussions, and observatory analysis between 2003 and 2010 at Lomahasha, a malarious community on the eastern border of Swaziland and Mozambique, was conducted. Results indicated that a high knowledge level and good perception of the disease were observed in the age group of < 40 years, contrary to those in higher age groups, among the Lomahasha community members. However, behavior of certain community groups includes practices that are not supportive of the national control program's aspirations, such as delay in seeking medical attention, staying outdoors until late, maintaining stagnant water in roadside excavations, and seeking medical assistance from wrong sources. Malpractices are more commonly observed among men, boys, and those who drink alcohol. This study suggests a thorough community diagnosis before all intervention programs for malaria control are instituted. Copyright © 2015. Published by Elsevier B.V.

A SIMPLIFIED MODEL FOR PREDICTING MALARIA ENTOMOLOGIC INOCULATION RATES BASED ON ENTOMOLOGIC AND PARASITOLOGIC PARAMETERS RELEVANT TO CONTROL

PubMed Central

KILLEEN, GERRY F.; McKENZIE, F. ELLIS; FOY, BRIAN D.; SCHIEFFELIN, CATHERINE; BILLINGSLEY, PETER F.; BEIER, JOHN C.

2008-01-01

Malaria transmission intensity is modeled from the starting perspective of individual vector mosquitoes and is expressed directly as the entomologic inoculation rate (EIR). The potential of individual mosquitoes to transmit malaria during their lifetime is presented graphically as a function of their feeding cycle length and survival, human biting preferences, and the parasite sporogonic incubation period. The EIR is then calculated as the product of 1) the potential of individual vectors to transmit malaria during their lifetime, 2) vector emergence rate relative to human population size, and 3) the infectiousness of the human population to vectors. Thus, impacts on more than one of these parameters will amplify each other’s effects. The EIRs transmitted by the dominant vector species at four malaria-endemic sites from Papua New Guinea, Tanzania, and Nigeria were predicted using field measurements of these characteristics together with human biting rate and human reservoir infectiousness. This model predicted EIRs (± SD) that are 1.13 ± 0.37 (range = 0.84–1.59) times those measured in the field. For these four sites, mosquito emergence rate and lifetime transmission potential were more important determinants of the EIR than human reservoir infectiousness. This model and the input parameters from the four sites allow the potential impacts of various control measures on malaria transmission intensity to be tested under a range of endemic conditions. The model has potential applications for the development and implementation of transmission control measures and for public health education. PMID:11289661

Characterizing Types of Human Mobility to Inform Differential and Targeted Malaria Elimination Strategies in Northeast Cambodia

PubMed Central

Peeters Grietens, Koen; Gryseels, Charlotte; Dierickx, Susan; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Uk, Sambunny; Phoeuk, Pisen; Suon, Sokha; Set, Srun; Gerrets, René; Hoibak, Sarah; Muela Ribera, Joan; Hausmann-Muela, Susanna; Tho, Sochantha; Durnez, Lies; Sluydts, Vincent; d’Alessandro, Umberto; Coosemans, Marc; Erhart, Annette

2015-01-01

Human population movements currently challenge malaria elimination in low transmission foci in the Greater Mekong Subregion. Using a mixed-methods design, combining ethnography (n = 410 interviews), malariometric data (n = 4996) and population surveys (n = 824 indigenous populations; n = 704 Khmer migrants) malaria vulnerability among different types of mobile populations was researched in the remote province of Ratanakiri, Cambodia. Different structural types of human mobility were identified, showing differential risk and vulnerability. Among local indigenous populations, access to malaria testing and treatment through the VMW-system and LLIN coverage was high but control strategies failed to account for forest farmers’ prolonged stays at forest farms/fields (61% during rainy season), increasing their exposure (p = 0.002). The Khmer migrants, with low acquired immunity, active on plantations and mines, represented a fundamentally different group not reached by LLIN-distribution campaigns since they were largely unregistered (79%) and unaware of the local VMW-system (95%) due to poor social integration. Khmer migrants therefore require control strategies including active detection, registration and immediate access to malaria prevention and control tools from which they are currently excluded. In conclusion, different types of mobility require different malaria elimination strategies. Targeting mobility without an in-depth understanding of malaria risk in each group challenges further progress towards elimination. PMID:26593245

Eliminating malaria in Malaysia: the role of partnerships between the public and commercial sectors in Sabah.

PubMed

Sanders, Kelly C; Rundi, Christina; Jelip, Jenarun; Rashman, Yusof; Smith Gueye, Cara; Gosling, Roly D

2014-01-21

Countries in the Asia Pacific region have made great progress in the fight against malaria; several are rapidly approaching elimination. However, malaria control programmes operating in elimination settings face substantial challenges, particularly around mobile migrant populations, access to remote areas and the diversity of vectors with varying biting and breeding behaviours. These challenges can be addressed through subnational collaborations with commercial partners, such as mining or plantation companies, that can conduct or support malaria control activities to cover employees. Such partnerships can be a useful tool for accessing high-risk populations and supporting malaria elimination goals. This observational qualitative case study employed semi-structured key informant interviews to describe partnerships between the Malaysian Malaria Control Programme (MCP), and private palm oil, rubber and acacia plantations in the state of Sabah. Semi-structured interview guides were used to examine resource commitments, incentives, challenges, and successes of the collaborations. Interviews with workers from private plantations and the state of Sabah MCP indicated that partnerships with the commercial sector had contributed to decreases in incidence at plantation sites since 1991. Several plantations contribute financial and human resources toward malaria control efforts and all plantations frequently communicate with the MCP to help monitor the malaria situation on-site. Management of partnerships between private corporations and government entities can be challenging, as prioritization of malaria control may change with annual profits or arrival of new management. Partnering with the commercial sector has been an essential operational strategy to support malaria elimination in Sabah. The successes of these partnerships rely on a common understanding that elimination will be a mutually beneficial outcome for employers and the general public. Best practices included consistent communication, developing government-staffed subsector offices for malaria control on-site, engaging commercial plantations to provide financial and human resources for malaria control activities, and the development of new worker screening programmes. The successes and challenges associated with partnerships between the public and commercial sector can serve as an example for other malaria-eliminating countries with large plantation sectors, and may also be applied to other sectors that employ migrant workers or have commercial enterprises in hard to reach areas.

Malaria Control and Elimination,1 Venezuela, 1800s–1970s

PubMed Central

Villegas, Leopoldo; Udhayakumar, Venkatachalam

2014-01-01

Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891–1920, malaria was endemic to >600,000 km2 of this country; malaria death rates led to major population decreases during 1891–1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905–1945. Early reports of malaria eradication in Venezuela helped spark the world’s interest in global eradication. We describe early approaches to malaria epidemiology in Venezuela and how this country developed an efficient control program and an approach to eradication. Arnoldo Gabaldón was a key policy maker during this development process. He directed malaria control in Venezuela from the late 1930s to the end of the 1970s and contributed to malaria program planning of the World Health Organization. We discuss how his efforts helped reduce the incidence of malaria in Venezuela and how his approach diverged from World Health Organization guidelines.

Malaria control and elimination, Venezuela, 1800s –1970s.

PubMed

Griffing, Sean M; Villegas, Leopoldo; Udhayakumar, Venkatachalam

2014-10-01

Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891–1920,malaria was endemic to >600,000 km2 of this country; malaria death rates led to major population decreases during 1891–1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905–1945. Early reports of malaria eradication in Venezuela helped spark the world's interest in global eradication. We describe early approaches to malaria epidemiology in Venezuela and how this country developed an efficient control program and an approach to eradication.Arnoldo Gabaldón was a key policy maker during this development process. He directed malaria control in Venezuela from the late 1930s to the end of the 1970s and contributed to malaria program planning of the World Health Organization.We discuss how his efforts helped reduce the incidence of malaria in Venezuela and how his approach diverged from World Health Organization guidelines.

Climate, environment and transmission of malaria.

PubMed

Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi

2016-06-01

Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political instability and health policies that have reduced the funds for vector control, combined with the presence of migratory flows from endemic countries.

Controlled Human Malaria Infection: Applications, Advances, and Challenges.

PubMed

Stanisic, Danielle I; McCarthy, James S; Good, Michael F

2018-01-01

Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration. Copyright © 2017 American Society for Microbiology.

Modelling malaria control by introduction of larvivorous fish.

PubMed

Lou, Yijun; Zhao, Xiao-Qiang

2011-10-01

Malaria creates serious health and economic problems which call for integrated management strategies to disrupt interactions among mosquitoes, the parasite and humans. In order to reduce the intensity of malaria transmission, malaria vector control may be implemented to protect individuals against infective mosquito bites. As a sustainable larval control method, the use of larvivorous fish is promoted in some circumstances. To evaluate the potential impacts of this biological control measure on malaria transmission, we propose and investigate a mathematical model describing the linked dynamics between the host-vector interaction and the predator-prey interaction. The model, which consists of five ordinary differential equations, is rigorously analysed via theories and methods of dynamical systems. We derive four biologically plausible and insightful quantities (reproduction numbers) that completely determine the community composition. Our results suggest that the introduction of larvivorous fish can, in principle, have important consequences for malaria dynamics, but also indicate that this would require strong predators on larval mosquitoes. Integrated strategies of malaria control are analysed to demonstrate the biological application of our developed theory.

Live attenuated pre-erythrocytic malaria vaccines.

PubMed

Keitany, Gladys J; Vignali, Marissa; Wang, Ruobing

2014-01-01

Although recent control measures have significantly reduced malaria cases and deaths in many endemic areas, an effective vaccine will be essential to eradicate this parasitic disease. Malaria vaccine strategies developed to date focus on different phases of the parasite's complex life cycle in the human host and mosquito vector, and include both subunit-based and whole-parasite vaccines. This review focuses on the 3 live-attenuated malaria vaccination strategies that have been tested in humans to date, and discusses their progress, challenges and the immune correlates of protection that have been identified.

Combining indoor and outdoor methods for controlling malaria vectors: an ecological model of endectocide-treated livestock and insecticidal bed nets.

PubMed

Yakob, Laith; Cameron, Mary; Lines, Jo

2017-03-13

Malaria is spread by mosquitoes that are increasingly recognised to have diverse biting behaviours. How a mosquito in a specific environment responds to differing availability of blood-host species is largely unknown and yet critical to vector control efficacy. A parsimonious mathematical model is proposed that accounts for a diverse range of host-biting behaviours and assesses their impact on combining long-lasting insecticidal nets (LLINs) with a novel approach to malaria control: livestock treated with insecticidal compounds ('endectocides') that kill biting mosquitoes. Simulations of a malaria control programme showed marked differences across biting ecologies in the efficacy of both LLINs as a stand-alone tool and the combination of LLINs with endectocide-treated cattle. During the intervals between LLIN mass campaigns, concordant use of endectocides is projected to reduce the bounce-back in malaria prevalence that can occur as LLIN efficacy decays over time, especially if replacement campaigns are delayed. Integrating these approaches can also dramatically improve the attainability of local elimination; endectocidal treatment schedules required to achieve this aim are provided for malaria vectors with different biting ecologies. Targeting blood-feeding mosquitoes by treating livestock with endectocides offers a potentially useful complement to existing malaria control programmes centred on LLIN distribution. This approach is likely to be effective against vectors with a wide range of host-preferences and biting behaviours, with the exception of species that are so strictly anthropophilic that most blood meals are taken on humans even when humans are much less available than non-human hosts. Identifying this functional relationship in wild mosquito populations and ascertaining the extent to which it differs, within as well as between species, is a critical next step before targets can be set for employing this novel approach and combination.

Malaria, a journey in time: in search of the lost myths and forgotten stories.

PubMed

Neghina, Raul; Neghina, Adriana Maria; Marincu, Iosif; Iacobiciu, Ioan

2010-12-01

The saga of malaria parasites precedes the history of humans. Malaria has always been part of the rising and decline of nations, of wars and of upheavals. People of ancient times attributed the malarial manifestations to supernatural influences. Myths about demons responsible for fevers and efforts to bring them under control were often mentioned in ancient articles and attested archaeologically. More than 4 millennia were required until malaria was finally demystified. From the ancient Chinese Canon of Medicine to Ronald Ross' milestone discovery, the humanity struggled to face one of the most debilitating diseases of mankind. This essay assesses the history of malaria from ancient mysteries until it was demystified. Its sections describe the attempts of humans from different times to understand and defeat malaria through supernatural practices, religious rites and medicine, and also their efforts mirrored in art and literary masterpieces.

Human ecology and behaviour in malaria control in tropical Africa

PubMed Central

MacCormack, C. P.

1984-01-01

Since about 250 BC, human modification of African environments has created increasingly favourable breeding conditions for Anopheles gambiae. Subsequent adaptations to the increased malaria risk are briefly described and reference is made to Macdonald's mathematical model for the disease. Since values for the variables in that model are high in tropical Africa, there is little possibility that simple, inexpensive, self-help primary health care initiatives can control malaria in the region. However, in combination with more substantial public health initiatives, simple primary health care activities might be done by communities to (1) prevent mosquitos from feeding on people, (2) prevent or reduce mosquito breeding, (3) destroy adult mosquitos, and (4) eliminate malaria parasites from human hosts. Lay methods of protection and self-care are examined and some topics for further research are indicated. Culturally appropriate health education methods are also suggested. PMID:6335685

Earth observation in support of malaria control and epidemiology: MALAREO monitoring approaches.

PubMed

Franke, Jonas; Gebreslasie, Michael; Bauwens, Ides; Deleu, Julie; Siegert, Florian

2015-06-03

Malaria affects about half of the world's population, with the vast majority of cases occuring in Africa. National malaria control programmes aim to reduce the burden of malaria and its negative, socioeconomic effects by using various control strategies (e.g. vector control, environmental management and case tracking). Vector control is the most effective transmission prevention strategy, while environmental factors are the key parameters affecting transmission. Geographic information systems (GIS), earth observation (EO) and spatial modelling are increasingly being recognised as valuable tools for effective management and malaria vector control. Issues previously inhibiting the use of EO in epidemiology and malaria control such as poor satellite sensor performance, high costs and long turnaround times, have since been resolved through modern technology. The core goal of this study was to develop and implement the capabilities of EO data for national malaria control programmes in South Africa, Swaziland and Mozambique. High- and very high resolution (HR and VHR) land cover and wetland maps were generated for the identification of potential vector habitats and human activities, as well as geoinformation on distance to wetlands for malaria risk modelling, population density maps, habitat foci maps and VHR household maps. These products were further used for modelling malaria incidence and the analysis of environmental factors that favour vector breeding. Geoproducts were also transferred to the staff of national malaria control programmes in seven African countries to demonstrate how EO data and GIS can support vector control strategy planning and monitoring. The transferred EO products support better epidemiological understanding of environmental factors related to malaria transmission, and allow for spatio-temporal targeting of malaria control interventions, thereby improving the cost-effectiveness of interventions.

Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission across Seven Diverse ICEMR Network Sites

PubMed Central

Wilson, Mark L.; Krogstad, Donald J.; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U.; Ndiaye, Daouda; Mathanga, Don P.; Eapen, Alex

2015-01-01

A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. PMID:26259941

Radar Monitoring of Wetlands for Malaria Control

NASA Technical Reports Server (NTRS)

Pope, Kevin O.

1997-01-01

Malaria is the most important vector-borne tropical disease (Collins and Paskewitz, 1995) and there is no simple and universally applicable form of vector control. While new methods such as malaria vaccine or genetic manipulation of mosquitoes are being explored in the laboratories, the need for more field research on malaria transmission remains very strong. For the foreseeable future many malaria programs must focus on controlling the vector, the anopheline mosquito, often under the specter of shrinking budgets. Therefore information on which human populations are at the greatest risk is especially valuable when allocating scarce resources. The goal of the Radar Monitoring of Wetlands for Malaria Control Project is to demonstrate the feasibility of using Radarsat or other comparable satellite radar imaging systems to determine where and when human populations are at greatest risk for contracting malaria. The study area is northern Belize, a region with abundant wetlands and a potentially serious malaria problem. A key aspect of this study is the analysis of multi-temporal satellite imagery to track seasonal flooding of anopheline mosquito breeding sites. Radarsat images of the test site in Belize have been acquired one to three times a month over the last year, however,, to date only one processed image has been received from the Alaska SAR Facility for analysis. Therefore analysis at this stage is focussed on determining the radar backscatter characteristics of known anopheline breeding sites, with future work to be dedicated toward seasonal changes.

To Live Like a Pig and Die Like a Dog: Environmental Implications for World War I in East Africa

DTIC Science & Technology

2009-12-03

held decisive advantages including greater numbers of troops, more robust logistics, and unchallenged control of the sea lines of communications...The Center for Disease Control defines malaria as “a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of...malaria parasites that can infect humans, Plasmodium falciparum remains indigenous to east 32 Center for Disease Control, “Malaria Home > Frequently

Spatial targeting of interventions against malaria.

PubMed Central

Carter, R.; Mendis, K. N.; Roberts, D.

2000-01-01

Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control. PMID:11196487

Spatial targeting of interventions against malaria.

PubMed

Carter, R; Mendis, K N; Roberts, D

2000-01-01

Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control.

Eliminating malaria in Malaysia: the role of partnerships between the public and commercial sectors in Sabah

PubMed Central

2014-01-01

Background Countries in the Asia Pacific region have made great progress in the fight against malaria; several are rapidly approaching elimination. However, malaria control programmes operating in elimination settings face substantial challenges, particularly around mobile migrant populations, access to remote areas and the diversity of vectors with varying biting and breeding behaviours. These challenges can be addressed through subnational collaborations with commercial partners, such as mining or plantation companies, that can conduct or support malaria control activities to cover employees. Such partnerships can be a useful tool for accessing high-risk populations and supporting malaria elimination goals. Methods This observational qualitative case study employed semi-structured key informant interviews to describe partnerships between the Malaysian Malaria Control Programme (MCP), and private palm oil, rubber and acacia plantations in the state of Sabah. Semi-structured interview guides were used to examine resource commitments, incentives, challenges, and successes of the collaborations. Results Interviews with workers from private plantations and the state of Sabah MCP indicated that partnerships with the commercial sector had contributed to decreases in incidence at plantation sites since 1991. Several plantations contribute financial and human resources toward malaria control efforts and all plantations frequently communicate with the MCP to help monitor the malaria situation on-site. Management of partnerships between private corporations and government entities can be challenging, as prioritization of malaria control may change with annual profits or arrival of new management. Conclusions Partnering with the commercial sector has been an essential operational strategy to support malaria elimination in Sabah. The successes of these partnerships rely on a common understanding that elimination will be a mutually beneficial outcome for employers and the general public. Best practices included consistent communication, developing government-staffed subsector offices for malaria control on-site, engaging commercial plantations to provide financial and human resources for malaria control activities, and the development of new worker screening programmes. The successes and challenges associated with partnerships between the public and commercial sector can serve as an example for other malaria-eliminating countries with large plantation sectors, and may also be applied to other sectors that employ migrant workers or have commercial enterprises in hard to reach areas. PMID:24443824

Malaria vaccine: the pros and cons.

PubMed

Saleh, J A; Yusuph, H; Zailani, S B; Aji, B

2010-01-01

Malaria is an important parasitic disease of humans caused by infection with a parasite of the genus Polasmodium and transmitted by female anopheles. Infection caused by P. falciparum is the most serious of all the other species (P. ovale, P. vivax and P. malariae) especially in terms of morbidity and mortality hence the reason why most of the research has been focussed on this species. The disease affects up to about 40 per cent of the world's population with around 300-500 million people currently infected and mainly in the tropics. It has a high morbidity and mortality especially in resource-poor tropical and subtropical regions with an economic fall of about US$ 12 billion annually in Africa alone. relevant literatures were reviewed from medical journals, library search and internet source. Other relevant websites like PATH, Malaria Vaccine Initiative and Global Fund were also visited to source for information. The key words employed were: malaria, vaccine, anopheles mosquito, insecticide treated bed-nets, pyrethroids and Plasmodium. several studies have underscored the need to develop an effective human malaria vaccine for the control and possible eradication of malaria across the globe with the view to reduce the morbidity and mortality associated with the disease, improve on the social and economic losses and also protect those at risk. It is very obvious that the need for effective human malaria vaccine is not only to serve those living in malaria endemic regions but also the non-immune travellers especially those travelling to malaria endemic areas; this would offer cost effective means of preventing the disease, reducing the morbidity and mortality associated with it in addition to closing the gap left by other control measures. It is very obvious that there is no single control measure known to be effective in the control of malaria, hence the need for combination of more than one method with the aim of achieving synergy in the total control and possible eradication of the disease. It suffices to say that despite the use of combination of more than one method (e.g., drugs treating patients, breaking the life cycle of the vector mosquito using larvicides, clearing swamps and other mosquito breeding sites), no much progress was made towards achieving this goal, hence the renewed interest especially with regards to vaccine development.

Increasing Incidence of Plasmodium knowlesi Malaria following Control of P. falciparum and P. vivax Malaria in Sabah, Malaysia

PubMed Central

William, Timothy; Rahman, Hasan A.; Jelip, Jenarun; Ibrahim, Mohammad Y.; Menon, Jayaram; Grigg, Matthew J.; Yeo, Tsin W.; Anstey, Nicholas M.; Barber, Bridget E.

2013-01-01

Background The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo and threatens the prospect of malaria elimination. However, little is known about the emergence of P. knowlesi, particularly in Sabah. We reviewed Sabah Department of Health records to investigate the trend of each malaria species over time. Methods Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory. We reviewed all available Department of Health malaria notification records from 1992–2011. Notifications of P. malariae and P. knowlesi were considered as a single group due to microscopic near-identity. Results From 1992–2011 total malaria notifications decreased dramatically, with P. falciparum peaking at 33,153 in 1994 and decreasing 55-fold to 605 in 2011, and P. vivax peaking at 15,857 in 1995 and decreasing 25-fold to 628 in 2011. Notifications of P. malariae/P. knowlesi also demonstrated a peak in the mid-1990s (614 in 1994) before decreasing to ≈100/year in the late 1990s/early 2000s. However, P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n = 59) and 2011 (n = 703). In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for 70%, 24% and 1% respectively of malaria notifications, compared to 30%, 31% and 35% in 2011. The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun in the southwest and progressed north-easterly. Conclusions A significant recent increase has occurred in P. knowlesi notifications following reduced transmission of the human Plasmodium species, and this trend threatens malaria elimination. Determination of transmission dynamics and risk factors for knowlesi malaria is required to guide measures to control this rising incidence. PMID:23359830

First case of a naturally acquired human infection with Plasmodium cynomolgi

PubMed Central

2014-01-01

Since 1960, a total of seven species of monkey malaria have been reported as transmissible to man by mosquito bite: Plasmodium cynomolgi, Plasmodium brasilianum, Plasmodium eylesi, Plasmodium knowlesi, Plasmodium inui, Plasmodium schwetzi and Plasmodium simium. With the exception of P. knowlesi, none of the other species has been found to infect humans in nature. In this report, it is described the first known case of a naturally acquired P. cynomolgi malaria in humans. The patient was a 39-year-old woman from a malaria-free area with no previous history of malaria or travel to endemic areas. Initially, malaria was diagnosed and identified as Plasmodium malariae/P. knowlesi by microscopy in the Terengganu State Health Department. Thick and thin blood films stained with 10% Giemsa were performed for microscopy examination. Molecular species identification was performed at the Institute for Medical Research (IMR, Malaysia) and in the Malaria & Emerging Parasitic Diseases Laboratory (MAPELAB, Spain) using different nested PCR methods. Microscopic re-examination in the IMR showed characteristics of Plasmodium vivax and was confirmed by a nested PCR assay developed by Snounou et al. Instead, a different PCR assay plus sequencing performed at the MAPELAB confirmed that the patient was infected with P. cynomolgi and not with P. vivax. This is the first report of human P. cynomolgi infection acquired in a natural way, but there might be more undiagnosed or misdiagnosed cases, since P. cynomolgi is morphologically indistinguishable from P. vivax, and one of the most used PCR methods for malaria infection detection may identify a P. cynomolgi infection as P. vivax. Simian Plasmodium species may routinely infect humans in Southeast Asia. New diagnostic methods are necessary to distinguish between the human and monkey malaria species. Further epidemiological studies, incriminating also the mosquito vector(s), must be performed to know the relevance of cynomolgi malaria and its implication on human public health and in the control of human malaria. The zoonotic malaria cannot be ignored in view of increasing interactions between man and wild animals in the process of urbanization. PMID:24564912

First case of a naturally acquired human infection with Plasmodium cynomolgi.

PubMed

Ta, Thuy H; Hisam, Shamilah; Lanza, Marta; Jiram, Adela I; Ismail, NorParina; Rubio, José M

2014-02-24

Since 1960, a total of seven species of monkey malaria have been reported as transmissible to man by mosquito bite: Plasmodium cynomolgi, Plasmodium brasilianum, Plasmodium eylesi, Plasmodium knowlesi, Plasmodium inui, Plasmodium schwetzi and Plasmodium simium. With the exception of P. knowlesi, none of the other species has been found to infect humans in nature. In this report, it is described the first known case of a naturally acquired P. cynomolgi malaria in humans.The patient was a 39-year-old woman from a malaria-free area with no previous history of malaria or travel to endemic areas. Initially, malaria was diagnosed and identified as Plasmodium malariae/P. knowlesi by microscopy in the Terengganu State Health Department. Thick and thin blood films stained with 10% Giemsa were performed for microscopy examination. Molecular species identification was performed at the Institute for Medical Research (IMR, Malaysia) and in the Malaria & Emerging Parasitic Diseases Laboratory (MAPELAB, Spain) using different nested PCR methods.Microscopic re-examination in the IMR showed characteristics of Plasmodium vivax and was confirmed by a nested PCR assay developed by Snounou et al. Instead, a different PCR assay plus sequencing performed at the MAPELAB confirmed that the patient was infected with P. cynomolgi and not with P. vivax.This is the first report of human P. cynomolgi infection acquired in a natural way, but there might be more undiagnosed or misdiagnosed cases, since P. cynomolgi is morphologically indistinguishable from P. vivax, and one of the most used PCR methods for malaria infection detection may identify a P. cynomolgi infection as P. vivax.Simian Plasmodium species may routinely infect humans in Southeast Asia. New diagnostic methods are necessary to distinguish between the human and monkey malaria species. Further epidemiological studies, incriminating also the mosquito vector(s), must be performed to know the relevance of cynomolgi malaria and its implication on human public health and in the control of human malaria.The zoonotic malaria cannot be ignored in view of increasing interactions between man and wild animals in the process of urbanization.

Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission Across Seven Diverse ICEMR Network Sites.

PubMed

Wilson, Mark L; Krogstad, Donald J; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U; Ndiaye, Daouda; Mathanga, Don P; Eapen, Alex

2015-09-01

A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. © The American Society of Tropical Medicine and Hygiene.

Host attraction and biting behaviour of Anopheles mosquitoes in South Halmahera, Indonesia.

PubMed

St Laurent, Brandyce; Burton, Timothy A; Zubaidah, Siti; Miller, Helen C; Asih, Puji B; Baharuddin, Amirullah; Kosasih, Sully; Shinta; Firman, Saya; Hawley, William A; Burkot, Thomas R; Syafruddin, Din; Sukowati, Supratman; Collins, Frank H; Lobo, Neil F

2017-08-02

Indonesia is home to a variety of malaria vectors whose specific bionomic traits remain largely uncharacterized. Species-specific behaviours, such as host feeding preferences, impact the dynamics of malaria transmission and the effectiveness of vector control interventions. To examine species-specific host attraction and feeding behaviours, a Latin square design was used to compare Anopheles mosquitoes attracted to human, cow, and goat-baited tents. Anopheles mosquitoes were collected hourly from the inside walls of each baited tent. Species were morphologically and then molecularly identified using rDNA ITS2 sequences. The head and thorax of individual specimens were analysed for Plasmodium DNA using PCR. Bloodmeals were identified using a multiplex PCR. A total of 1024, 137, and 74 Anopheles were collected over 12 nights in cow, goat, and human-baited tents, respectively. The species were identified as Anopheles kochi, Anopheles farauti s.s., Anopheles hackeri, Anopheles hinesorum, Anopheles indefinitus, Anopheles punctulatus, Anopheles tessellatus, Anopheles vagus, and Anopheles vanus, many of which are known to transmit human malaria. Molecular analysis of blood meals revealed a high level of feeding on multiple host species in a single night. Anopheles kochi, An. indefinitus, and An. vanus were infected with Plasmodium vivax at rates comparable to primary malaria vectors. The species distributions of Anopheles mosquitoes attracted to human, goat, and cow hosts were similar. Eight of nine sporozoite positive samples were captured with animal-baited traps, indicating that even predominantly zoophilic mosquitoes may be contributing to malaria transmission. Multiple host feeding and flexibility in blood feeding behaviour have important implications for malaria transmission, malaria control, and the effectiveness of intervention and monitoring methods, particularly those that target human-feeding vectors.

Resting and feeding preferences of Anopheles stephensi in an urban setting, perennial for malaria.

PubMed

Thomas, Shalu; Ravishankaran, Sangamithra; Justin, N A Johnson Amala; Asokan, Aswin; Mathai, Manu Thomas; Valecha, Neena; Montgomery, Jacqui; Thomas, Matthew B; Eapen, Alex

2017-03-10

The Indian city of Chennai is endemic for malaria and the known local malaria vector is Anopheles stephensi. Plasmodium vivax is the predominant malaria parasite species, though Plasmodium falciparum is present at low levels. The urban ecotype of malaria prevails in Chennai with perennial transmission despite vector surveillance by the Urban Malaria Scheme (UMS) of the National Vector Borne Disease Control Programme (NVBDCP). Understanding the feeding and resting preferences, together with the transmission potential of adult vectors in the area is essential in effective planning and execution of improved vector control measures. A yearlong survey was carried out in cattle sheds and human dwellings to check the resting, feeding preferences and transmission potential of An. stephensi. The gonotrophic status, age structure, resting and host seeking preferences were studied. The infection rate in An. stephensi and Anopheles subpictus were analysed by circumsporozoite ELISA (CS-ELISA). Adult vectors were found more frequently and at higher densities in cattle sheds than human dwellings. The overall Human Blood Index (HBI) was 0.009 indicating the vectors to be strongly zoophilic. Among the vectors collected from human dwellings, 94.2% were from thatched structures and the remaining 5.8% from tiled and asbestos structures. 57.75% of the dissected vectors were nulliparous whereas, 35.83% were monoparous and the rest 6.42% biparous. Sporozoite positivity rate was 0.55% (4/720) and 1.92% (1/52) for An. stephensi collected from cattle sheds and human dwellings, respectively. One adult An. subpictus (1/155) was also found to be infected with P. falciparum. Control of the adult vector populations can be successful only by understanding the resting and feeding preferences. The present study indicates that adult vectors predominantly feed on cattle and cattle sheds are the preferred resting place, possibly due to easy availability of blood meal source and lack of any insecticide or repellent pressure. Hence targeting these resting sites with cost effective, socially acceptable intervention tools, together with effective larval source management to reduce vector breeding, could provide an improved integrated vector management strategy to help drive down malaria transmission and assist in India's plan to eliminate malaria by 2030.

A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.

PubMed

Laurens, Matthew B; Duncan, Christopher J; Epstein, Judith E; Hill, Adrian V; Komisar, Jack L; Lyke, Kirsten E; Ockenhouse, Christian F; Richie, Thomas L; Roestenberg, Meta; Sauerwein, Robert W; Spring, Michele D; Talley, Angela K; Moorthy, Vasee S

2012-08-03

Early clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach.

PubMed

Mitsakakis, Konstantinos; Hin, Sebastian; Müller, Pie; Wipf, Nadja; Thomsen, Edward; Coleman, Michael; Zengerle, Roland; Vontas, John; Mavridis, Konstantinos

2018-02-03

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium , is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach

PubMed Central

Mitsakakis, Konstantinos; Hin, Sebastian; Wipf, Nadja; Coleman, Michael; Zengerle, Roland; Vontas, John; Mavridis, Konstantinos

2018-01-01

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach. PMID:29401670

Malaria vector control at a crossroads: public health entomology and the drive to elimination.

PubMed

Mnzava, Abraham P; Macdonald, Michael B; Knox, Tessa B; Temu, Emmanuel A; Shiff, Clive J

2014-09-01

Vector control has been at the core of successful malaria control. However, a dearth of field-oriented vector biologists threatens to undermine global reductions in malaria burden. Skilled cadres are needed to manage insecticide resistance, to maintain coverage with current interventions, to develop new paradigms for tackling 'residual' transmission and to target interventions as transmission becomes increasingly heterogeneous. Recognising this human resource crisis, in September 2013, WHO Global Malaria Programme issued guidance for capacity building in entomology and vector control, including recommendations for countries and implementing partners. Ministries were urged to develop long-range strategic plans for building human resources for public health entomology and vector control (including skills in epidemiology, geographic information systems, operational research and programme management) and to set in place the requisite professional posts and career opportunities. Capacity building and national ownership in all partner projects and a clear exit strategy to sustain human and technical resources after project completion were emphasised. Implementing partners were urged to support global and regional efforts to enhance public health entomology capacity. While the challenges inherent in such capacity building are great, so too are the opportunities to establish the next generation of public health entomologists that will enable programmes to continue on the path to malaria elimination. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Malaria in South Asia: Prevalence and control

PubMed Central

Kumar, Ashwani; Chery, Laura; Biswas, Chinmoy; Dubhashi, Nagesh; Dutta, Prafulla; Dua, Virendra Kumar; Kacchap, Mridula; Kakati, Sanjeeb; Khandeparkar, Anar; Kour, Dalip; Mahajanj, Satish N.; Maji, Ardhendu; Majumder, Partha; Mohanta, Jagadish; Mohapatra, Pradyumna K.; Narayanasamy, Krishnamoorthy; Roy, Krishnangshu; Shastri, Jayanthi; Valecha, Neena; Vikash, Rana; Wani, Reena; White, John; Rathod, Pradipsinh K

2013-01-01

The “Malaria Evolution in South Asia” (MESA) program project is an International Center of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. This US–India collaborative program will study the origin of genetic diversity of malaria parasites and their selection on the Indian subcontinent. This knowledge should contribute to a better understanding of unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. In this first of two reviews, we highlight malaria prevalence in India. In particular, we draw attention to variations in distribution of different human-parasites and different vectors, variation in drug resistance traits, and multiple forms of clinical presentations. Uneven malaria severity in India is often attributed to large discrepancies in health care accessibility as well as human migrations within the country and across neighboring borders. Poor access to health care goes hand in hand with poor reporting from some of the same areas, combining to possibly distort disease prevalence and death from malaria in some parts of India. Corrections are underway in the form of increased resources for disease control, greater engagement of village-level health workers for early diagnosis and treatment, and possibly new public–private partnerships activities accompanying traditional national malaria control programs in the most severely affected areas. A second accompanying review raises the possibility that, beyond uneven health care, evolutionary pressures may alter malaria parasites in ways that contribute to severe disease in India, particularly in the NE corridor of India bordering Myanmar Narayanasamy et al., 2012. PMID:22248528

Malaria in South Asia: prevalence and control.

PubMed

Kumar, Ashwani; Chery, Laura; Biswas, Chinmoy; Dubhashi, Nagesh; Dutta, Prafulla; Dua, Virendra Kumar; Kacchap, Mridula; Kakati, Sanjeeb; Khandeparkar, Anar; Kour, Dalip; Mahajan, Satish N; Maji, Ardhendu; Majumder, Partha; Mohanta, Jagadish; Mohapatra, Pradyumna K; Narayanasamy, Krishnamoorthy; Roy, Krishnangshu; Shastri, Jayanthi; Valecha, Neena; Vikash, Rana; Wani, Reena; White, John; Rathod, Pradipsinh K

2012-03-01

The "Malaria Evolution in South Asia" (MESA) program project is an International Center of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. This US-India collaborative program will study the origin of genetic diversity of malaria parasites and their selection on the Indian subcontinent. This knowledge should contribute to a better understanding of unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. In this first of two reviews, we highlight malaria prevalence in India. In particular, we draw attention to variations in distribution of different human-parasites and different vectors, variation in drug resistance traits, and multiple forms of clinical presentations. Uneven malaria severity in India is often attributed to large discrepancies in health care accessibility as well as human migrations within the country and across neighboring borders. Poor access to health care goes hand in hand with poor reporting from some of the same areas, combining to possibly distort disease prevalence and death from malaria in some parts of India. Corrections are underway in the form of increased resources for disease control, greater engagement of village-level health workers for early diagnosis and treatment, and possibly new public-private partnerships activities accompanying traditional national malaria control programs in the most severely affected areas. A second accompanying review raises the possibility that, beyond uneven health care, evolutionary pressures may alter malaria parasites in ways that contribute to severe disease in India, particularly in the NE corridor of India bordering Myanmar Narayanasamy et al., 2012. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Reservoir Characteristics on Malaria and its vector Abundance: A Case Study of the Bongo District of Ghana

NASA Astrophysics Data System (ADS)

Ofosu, E.; Awuah, E.; Annor, F. O.

2009-04-01

In the seven (7) administrative zones of the Bongo District of the Upper East Region of Ghana, the occurrences of malaria and relative abundance of the principal malaria vector, Anopheles species, were studied as a function of the presence and characteristics of reservoirs during the rainy season. Case studies in the sub-Sahara Africa indicate that malaria transmission may increase decrease or remain largely unchanged as a consequence of reservoir presence. Analysis made, shows that the distance from reservoir to settlement and surface area of reservoirs significantly affected adult Anopheles mosquito abundance. Percentage of inhabitants using insecticide treated nets, livestock population density, human population density and Anopheles mosquito abundance significantly affected the occurrence of malaria. The results suggest that vector control targeted at reservoir characteristics and larval control, and supplemented by high patronage of insecticide treated nets may be an effective approach for epidemic malaria control in the Bongo District. Key Words: Bongo District, Reservoir, Anopheles species, Malaria, Vector abundance.

Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon.

PubMed

Lell, Bertrand; Mordmüller, Benjamin; Dejon Agobe, Jean-Claude; Honkpehedji, Josiane; Zinsou, Jeannot; Mengue, Juliana Boex; Loembe, Marguerite Massinga; Adegnika, Ayola Akim; Held, Jana; Lalremruata, Albert; Nguyen, The Trong; Esen, Meral; Kc, Natasha; Ruben, Adam J; Chakravarty, Sumana; Lee Sim, B Kim; Billingsley, Peter F; James, Eric R; Richie, Thomas L; Hoffman, Stephen L; Kremsner, Peter G

2018-02-01

Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria-exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers ( P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms ( P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria.

Mosquito Infectivity and Parasitemia after Controlled Human Malaria Infection.

PubMed

Walk, Jona; van Gemert, Geert-Jan; Graumans, Wouter; Sauerwein, Robert; Bijker, Else M

2018-04-30

Controlled Human Malaria Infection (CHMI) has become an increasingly important tool for the evaluation of drugs and vaccines. Controlled Human Malaria Infection has been demonstrated to be a reproducible model; however, there is some variability in time to onset of parasitemia between volunteers and studies. At our center, mosquitoes infected with Plasmodium falciparum by membrane feeding have variable and high salivary gland sporozoite load (mean 78,415; range 26,500-160,500). To determine whether this load influences parasitemia after CHMI, we analyzed data from 13 studies. We found no correlation between the sporozoite load of a mosquito batch and time to parasitemia or parasite density of first-wave parasitemia. These findings support the use of infected mosquito bite as a reproducible means of inducing P. falciparum infection and suggest that within this range, salivary gland sporozoite load does not influence the stringency of a CHMI.

Therapeutic PD-L1 and LAG-3 blockade rapidly clears established blood-stage Plasmodium infection

PubMed Central

Butler, Noah S.; Moebius, Jacqueline; Pewe, Lecia L.; Traore, Boubacar; Doumbo, Ogobara K.; Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Crompton, Peter D.; Harty, John T.

2011-01-01

Plasmodium infection of erythrocytes induces clinical malaria. Parasite-specific CD4+ T cells correlate with reduced parasite burdens and severity of human malaria, and are required to control blood-stage infection in mice. However, the characteristics of CD4+ T cells that determine protection or parasite persistence remain unknown. Here we show that P. falciparum infection of humans increased expression of an inhibitory receptor (PD-1) associated with T cell dysfunction. In vivo blockade of PD-L1 and LAG-3 restored CD4+ T cell function, amplified T follicular helper cell and germinal center B cell and plasmablast numbers, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, which can be rescued to enhance parasite control using inhibitory therapies. PMID:22157630

mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa

PubMed Central

Eskenazi, Brenda; Quirós-Alcalá, Lesliam; Lipsitt, Jonah M.; Wu, Lemuel D.; Kruger, Philip; Ntimbane, Tzundzukani; Nawn, John Burns; Bornman, M. S. Riana; Seto, Edmund

2015-01-01

Recent estimates indicate that malaria has led to over half a million deaths worldwide, mostly to African children. Indoor residual spraying (IRS) of insecticides is one of the primary vector control interventions. However, current reporting systems do not obtain precise location of IRS events in relation to malaria cases, which poses challenges for effective and efficient malaria control. This information is also critical to avoid unnecessary human exposure to IRS insecticides. We developed and piloted a mobile-based application (mSpray) to collect comprehensive information on IRS spray events. We assessed the utility, acceptability and feasibility of using mSpray to gather improved homestead- and chemical-level IRS coverage data. We installed mSpray on 10 cell phones with data bundles, and pilot tested it with 13 users in Limpopo, South Africa. Users completed basic information (number of rooms/shelters sprayed; chemical used, etc.) on spray events. Upon submission, this information as well as geographic positioning system coordinates and time/date stamp were uploaded to a Google Drive Spreadsheet to be viewed in real time. We administered questionnaires, conducted focus groups, and interviewed key informants to evaluate the utility of the app. The low-cost, cell phone-based “mSpray” app was learned quickly by users, well accepted and preferred to the current paper-based method. We recorded 2,865 entries (99.1% had a GPS accuracy of 20 m or less) and identified areas of improvement including increased battery life. We also identified a number of logistic and user problems (e.g., cost of cell phones and cellular bundles, battery life, obtaining accurate GPS measures, user errors, etc.) that would need to be overcome before full deployment. Use of cell phone technology could increase the efficiency of IRS malaria control efforts by mapping spray events in relation to malaria cases, resulting in more judicious use of chemicals that are potentially harmful to humans and the environment. PMID:24769412

Push by a net, pull by a cow: can zooprophylaxis enhance the impact of insecticide treated bed nets on malaria control?

PubMed Central

2014-01-01

Background Mass insecticide treated bed net (ITN) deployment, and its associated coverage of populations at risk, had “pushed” a decline in malaria transmission. However, it is unknown whether malaria control is being enhanced by zooprophylaxis, i.e., mosquitoes diverted to feed on hosts different from humans, a phenomenon that could further reduce malaria entomological transmission risk in areas where livestock herding is common. Methods Between May and July 2009, we collected mosquitoes in 104 houses from three neighboring villages with high ITN coverage (over 80%), along Lake Victoria. We also performed a census of livestock in the area and georeferenced tethering points for all herds, as well as, mosquito larval habitats. Bloodmeal contents from sampled mosquitoes were analyzed, and each mosquito was individually tested for malaria sporozoite infections. We then evaluated the association of human density, ITN use, livestock abundance and larval habitats with mosquito abundance, bloodfeeding on humans and malaria sporozoite rate using generalized linear mixed effects models. Results We collected a total of 8123 mosquitoes, of which 1664 were Anopheles spp. malaria vectors over 295 household spray catches. We found that vector household abundance was mainly driven by the number of householders (P < 0.05), goats/sheep tethered around the house (P < 0.05) and ITNs, which halved mosquito abundance (P < 0.05). In general, similar patterns were observed for Anopheles arabiensis, but not An. gambiae s.s. and An. funestus s.s., whose density did not increase with the presence of livestock animals. Feeding on humans significantly increased in all species with the number of householders (P < 0.05), and only significantly decreased for An. arabiensis in the presence of cattle (P < 0.05). Only 26 Anopheles spp. vectors had malaria sporozoites with the sporozoite rate significantly decreasing as the proportion of cattle feeding mosquitoes increased (P < 0.05). Conclusion Our data suggest that cattle, in settings with large ITN coverage, have the potential to drive an unexpected “push-pull” malaria control system, where An. arabiensis mosquitoes “pushed” out of human contact by ITNs are likely being further “pulled” by cattle. PMID:24472517

Strengthening tactical planning and operational frameworks for vector control: the roadmap for malaria elimination in Namibia.

PubMed

Chanda, Emmanuel; Ameneshewa, Birkinesh; Angula, Hans A; Iitula, Iitula; Uusiku, Pentrina; Trune, Desta; Islam, Quazi M; Govere, John M

2015-08-05

Namibia has made tremendous gains in malaria control and the epidemiological trend of the disease has changed significantly over the past years. In 2010, the country reoriented from the objective of reducing disease morbidity and mortality to the goal of achieving malaria elimination by 2020. This manuscript outlines the processes undertaken in strengthening tactical planning and operational frameworks for vector control to facilitate expeditious malaria elimination in Namibia. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Namibia. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. To attain the goal of elimination in Namibia, systems are being strengthened to identify and clear all infections, and significantly reduce human-mosquito contact. Particularly, consolidating vector control for reducing transmission at the identified malaria foci will be critical for accelerated malaria elimination. Thus, guarding against potential challenges and the need for evidence-based and sustainable vector control instigated the strengthening of strategic frameworks by: adopting the integrated vector management (IVM) strategy; initiating implementation of the global plan for insecticide resistance management (GPIRM); intensifying malaria vector surveillance; improving data collection and reporting systems on DDT; updating the indoor residual spraying (IRS) data collection and reporting tool; and, improving geographical reconnaissance using geographical information system-based satellite imagery. Universal coverage with IRS and long-lasting insecticidal nets, supplemented by larval source management in the context of IVM and guided by vector surveillance coupled with rational operationalization of the GPIRM, will enable expeditious attainment of elimination in Namibia. However, national capacity to plan, implement, monitor and evaluate interventions will require adequate and sustained support for technical, physical infrastructure, and human and financial resources for entomology and vector control operations.

Malaria burden in human population of Quetta, Pakistan

PubMed Central

Tareen, A. M.; Rafique, M.; Wadood, A.; Qasim, M.; Rahman, H.; Shah, S. H.; Khan, K.; Pirkani, G. S.

2012-01-01

Malaria is a serious global health challenge, which is responsible for more than one million deaths a year. Malarial infection is more prevalent in developing countries including Pakistan. Significant efforts have been made to control malaria; however, due to socio-environmental factors, it remains a frequent problem in Quetta. The present study was undertaken to determine the malarial incidence, species prevalence, and its demographic evaluation in human population of Quetta, Pakistan. A total of 1831 subjects, comprising 1072 male and 759 female presenting symptoms of malaria, were included in this study. Blood samples from clinically suspected individuals were subjected to the standard immunochromatographic and malaria parasite smear analysis for malaria diagnosis. Out of 1831 subjects, 338 (18.45%) patients were positive for malarial parasite while the species prevalence was found as 276 (81.66%) and 62 (18.34%) for Plasmodium vivax, and Plasmodium falciparum, respectively. Furthermore, seasonal variations gradual increase in the prevalence rate. The age group of 21–30 years (30.47%) was found more prone to malaria. The suspected malaria cases were found more frequent in rural (72.1%) as compared to urban (27.9%). In addition, the malaria burden was high in urban area (22.89%) population as compared to the rural area (16.74%) population. It was observed that the highest disease occurrence was caused by P. vivax, which reflects a serious threat for public health. The current findings will be helpful to plan effective strategies to prevent and control malaria in this area. PMID:24688766

Quantifying cross-border movements and migrations for guiding the strategic planning of malaria control and elimination

PubMed Central

2014-01-01

Background Identifying human and malaria parasite movements is important for control planning across all transmission intensities. Imported infections can reintroduce infections into areas previously free of infection, maintain ‘hotspots’ of transmission and import drug resistant strains, challenging national control programmes at a variety of temporal and spatial scales. Recent analyses based on mobile phone usage data have provided valuable insights into population and likely parasite movements within countries, but these data are restricted to sub-national analyses, leaving important cross-border movements neglected. Methods National census data were used to analyse and model cross-border migration and movement, using East Africa as an example. ‘Hotspots’ of origin-specific immigrants from neighbouring countries were identified for Kenya, Tanzania and Uganda. Populations of origin-specific migrants were compared to distance from origin country borders and population size at destination, and regression models were developed to quantify and compare differences in migration patterns. Migration data were then combined with existing spatially-referenced malaria data to compare the relative propensity for cross-border malaria movement in the region. Results The spatial patterns and processes for immigration were different between each origin and destination country pair. Hotspots of immigration, for example, were concentrated close to origin country borders for most immigrants to Tanzania, but for Kenya, a similar pattern was only seen for Tanzanian and Ugandan immigrants. Regression model fits also differed between specific migrant groups, with some migration patterns more dependent on population size at destination and distance travelled than others. With these differences between immigration patterns and processes, and heterogeneous transmission risk in East Africa and the surrounding region, propensities to import malaria infections also likely show substantial variations. Conclusion This was a first attempt to quantify and model cross-border movements relevant to malaria transmission and control. With national census available worldwide, this approach can be translated to construct a cross-border human and malaria movement evidence base for other malaria endemic countries. The outcomes of this study will feed into wider efforts to quantify and model human and malaria movements in endemic regions to facilitate improved intervention planning, resource allocation and collaborative policy decisions. PMID:24886389

Aggressive active case detection: a malaria control strategy based on the Brazilian model.

PubMed

Macauley, Cameron

2005-02-01

Since 1996, the Brazilian Ministry of Health has adopted a malaria control strategy known as aggressive active case detection (AACD) in which most or all members of every community are tested and treated for malaria on a monthly basis. The strategy attempts to identify and treat cases of asymptomatic malaria, which, if untreated, continue to transmit the infection. Malaria remains uncontrolled because almost all health care systems in the world rely on passive case detection: the treatment of only symptomatic cases of malaria. Research has shown conclusively that asymptomatic cases exist in any population where malaria transmission is stable and incidence is high: therefore passive case detection simply will not succeed in breaking the cycle of transmission. Numerous case studies show that malaria has been successfully controlled on a regional or national level by mass blood surveys. AACD is an effective malaria control strategy if used in conjunction with other methods, especially when (1) an effective treatment exists, (2) influx of potential carriers of the infection can be monitored, and (3) people are inclined to cooperate with monthly blood testing. AACD requires access to rapid diagnostic tests (RDTs), microscopy supplies, extensive human resources, and prompt, affordable, and effective treatment. AACD is compared to PCD in terms of clinical efficacy and cost effectiveness in a case study of malaria in the Brazilian Yanomami Indians. Where it is feasible, AACD could drastically reduce the incidence of malaria and should be an integral part of the World Health Organization's Roll Back Malaria strategy.

Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites in Anopheles Vectors

PubMed Central

2014-01-01

The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria parasites in hotspots or suspected areas established in most endemic GMS countries implementing the National Malaria Control Programs, in addition to what is guided by the World Health Organization. PMID:25349605

Beer Consumption Increases Human Attractiveness to Malaria Mosquitoes

PubMed Central

Lefèvre, Thierry; Gouagna, Louis-Clément; Dabiré, Kounbobr Roch; Elguero, Eric; Fontenille, Didier; Renaud, François; Costantini, Carlo; Thomas, Frédéric

2010-01-01

Background Malaria and alcohol consumption both represent major public health problems. Alcohol consumption is rising in developing countries and, as efforts to manage malaria are expanded, understanding the links between malaria and alcohol consumption becomes crucial. Our aim was to ascertain the effect of beer consumption on human attractiveness to malaria mosquitoes in semi field conditions in Burkina Faso. Methodology/Principal Findings We used a Y tube-olfactometer designed to take advantage of the whole body odour (breath and skin emanations) as a stimulus to gauge human attractiveness to Anopheles gambiae (the primary African malaria vector) before and after volunteers consumed either beer (n = 25 volunteers and a total of 2500 mosquitoes tested) or water (n = 18 volunteers and a total of 1800 mosquitoes). Water consumption had no effect on human attractiveness to An. gambiae mosquitoes, but beer consumption increased volunteer attractiveness. Body odours of volunteers who consumed beer increased mosquito activation (proportion of mosquitoes engaging in take-off and up-wind flight) and orientation (proportion of mosquitoes flying towards volunteers' odours). The level of exhaled carbon dioxide and body temperature had no effect on human attractiveness to mosquitoes. Despite individual volunteer variation, beer consumption consistently increased attractiveness to mosquitoes. Conclusions/Significance These results suggest that beer consumption is a risk factor for malaria and needs to be integrated into public health policies for the design of control measures. PMID:20209056

Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica.

PubMed

Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José; Dolz, Gaby

2017-01-01

One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs.

Genetic Structure of Plasmodium falciparum and Elimination of Malaria, Comoros Archipelago

PubMed Central

Rebaudet, Stanislas; Bogreau, Hervé; Silaï, Rahamatou; Lepère, Jean-François; Bertaux, Lionel; Pradines, Bruno; Delmont, Jean; Gautret, Philippe; Parola, Philippe

2010-01-01

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands. PMID:21029525

An expanding toolkit for preclinical pre-erythrocytic malaria vaccine development: bridging traditional mouse malaria models and human trials

PubMed Central

Steel, Ryan WJ; Kappe, Stefan HI; Sack, Brandon K

2016-01-01

Malaria remains a significant public health burden with 214 million new infections and over 400,000 deaths in 2015. Elucidating relevant Plasmodium parasite biology can lead to the identification of novel ways to control and ultimately eliminate the parasite within geographic areas. Particularly, the development of an effective vaccine that targets the clinically silent pre-erythrocytic stages of infection would significantly augment existing malaria elimination tools by preventing both the onset of blood-stage infection/disease as well as spread of the parasite through mosquito transmission. In this Perspective, we discuss the role of small animal models in pre-erythrocytic stage vaccine development, highlighting how human liver-chimeric and human immune system mice are emerging as valuable components of these efforts. PMID:27855488

An expanding toolkit for preclinical pre-erythrocytic malaria vaccine development: bridging traditional mouse malaria models and human trials.

PubMed

Steel, Ryan Wj; Kappe, Stefan Hi; Sack, Brandon K

2016-12-01

Malaria remains a significant public health burden with 214 million new infections and over 400,000 deaths in 2015. Elucidating relevant Plasmodium parasite biology can lead to the identification of novel ways to control and ultimately eliminate the parasite within geographic areas. Particularly, the development of an effective vaccine that targets the clinically silent pre-erythrocytic stages of infection would significantly augment existing malaria elimination tools by preventing both the onset of blood-stage infection/disease as well as spread of the parasite through mosquito transmission. In this Perspective, we discuss the role of small animal models in pre-erythrocytic stage vaccine development, highlighting how human liver-chimeric and human immune system mice are emerging as valuable components of these efforts.

False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

PubMed Central

Gillet, Philippe; Mumba Ngoyi, Dieudonné; Lukuka, Albert; Kande, Viktor; Atua, Benjamin; van Griensven, Johan; Muyembe, Jean-Jacques; Jacobs, Jan; Lejon, Veerle

2013-01-01

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. PMID:23638201

The Anopheles gambiae transcriptome - a turning point for malaria control.

PubMed

Domingos, A; Pinheiro-Silva, R; Couto, J; do Rosário, V; de la Fuente, J

2017-04-01

Mosquitoes are important vectors of several pathogens and thereby contribute to the spread of diseases, with social, economic and public health impacts. Amongst the approximately 450 species of Anopheles, about 60 are recognized as vectors of human malaria, the most important parasitic disease. In Africa, Anopheles gambiae is the main malaria vector mosquito. Current malaria control strategies are largely focused on drugs and vector control measures such as insecticides and bed-nets. Improvement of current, and the development of new, mosquito-targeted malaria control methods rely on a better understanding of mosquito vector biology. An organism's transcriptome is a reflection of its physiological state and transcriptomic analyses of different conditions that are relevant to mosquito vector competence can therefore yield important information. Transcriptomic analyses have contributed significant information on processes such as blood-feeding parasite-vector interaction, insecticide resistance, and tissue- and stage-specific gene regulation, thereby facilitating the path towards the development of new malaria control methods. Here, we discuss the main applications of transcriptomic analyses in An. gambiae that have led to a better understanding of mosquito vector competence. © 2017 The Royal Entomological Society.

Insecticide-Treated Nets Can Reduce Malaria Transmission by Mosquitoes Which Feed Outdoors

PubMed Central

Govella, Nicodem J.; Okumu, Fredros O.; Killeen, Gerry F.

2010-01-01

Insecticide treated nets (ITNs) represent a powerful means for controlling malaria in Africa because the mosquito vectors feed primarily indoors at night. The proportion of human exposure that occurs indoors, when people are asleep and can conveniently use ITNs, is therefore very high. Recent evidence suggests behavioral changes by malaria mosquito populations to avoid contact with ITNs by feeding outdoors in the early evening. We adapt an established mathematical model of mosquito behavior and malaria transmission to illustrate how ITNs can achieve communal suppression of malaria transmission exposure, even where mosquito evade them and personal protection is modest. We also review recent reports from Tanzania to show that conventional mosquito behavior measures can underestimate the potential of ITNs because they ignore the importance of human movements. PMID:20207866

Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years.

PubMed

Mwangangi, Joseph M; Mbogo, Charles M; Orindi, Benedict O; Muturi, Ephantus J; Midega, Janet T; Nzovu, Joseph; Gatakaa, Hellen; Githure, John; Borgemeister, Christian; Keating, Joseph; Beier, John C

2013-01-08

Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya. Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates. Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90-0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010. Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission.

Travel history and malaria infection risk in a low-transmission setting in Ethiopia: a case control study

PubMed Central

2013-01-01

Background Malaria remains the leading communicable disease in Ethiopia, with around one million clinical cases of malaria reported annually. The country currently has plans for elimination for specific geographic areas of the country. Human movement may lead to the maintenance of reservoirs of infection, complicating attempts to eliminate malaria. Methods An unmatched case–control study was conducted with 560 adult patients at a Health Centre in central Ethiopia. Patients who received a malaria test were interviewed regarding their recent travel histories. Bivariate and multivariate analyses were conducted to determine if reported travel outside of the home village within the last month was related to malaria infection status. Results After adjusting for several known confounding factors, travel away from the home village in the last 30 days was a statistically significant risk factor for infection with Plasmodium falciparum (AOR 1.76; p=0.03) but not for infection with Plasmodium vivax (AOR 1.17; p=0.62). Male sex was strongly associated with any malaria infection (AOR 2.00; p=0.001). Conclusions Given the importance of identifying reservoir infections, consideration of human movement patterns should factor into decisions regarding elimination and disease prevention, especially when targeted areas are limited to regions within a country. PMID:23347703

Challenges for malaria elimination in Brazil.

PubMed

Ferreira, Marcelo U; Castro, Marcia C

2016-05-20

Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.

Factors that are associated with the risk of acquiring Plasmodium knowlesi malaria in Sabah, Malaysia: a case-control study protocol

PubMed Central

Grigg, M J; William, T; Drakeley, C J; Jelip, J; von Seidlein, L; Barber, B E; Fornace, K M; Anstey, N M; Yeo, T W; Cox, J

2014-01-01

Introduction Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission. Methods and analysis A population-based case–control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models. Ethics This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK. PMID:25149186

Persistent oscillations and backward bifurcation in a malaria model with varying human and mosquito populations: implications for control.

PubMed

Ngonghala, Calistus N; Teboh-Ewungkem, Miranda I; Ngwa, Gideon A

2015-06-01

We derive and study a deterministic compartmental model for malaria transmission with varying human and mosquito populations. Our model considers disease-related deaths, asymptomatic immune humans who are also infectious, as well as mosquito demography, reproduction and feeding habits. Analysis of the model reveals the existence of a backward bifurcation and persistent limit cycles whose period and size is determined by two threshold parameters: the vectorial basic reproduction number Rm, and the disease basic reproduction number R0, whose size can be reduced by reducing Rm. We conclude that malaria dynamics are indeed oscillatory when the methodology of explicitly incorporating the mosquito's demography, feeding and reproductive patterns is considered in modeling the mosquito population dynamics. A sensitivity analysis reveals important control parameters that can affect the magnitudes of Rm and R0, threshold quantities to be taken into consideration when designing control strategies. Both Rm and the intrinsic period of oscillation are shown to be highly sensitive to the mosquito's birth constant λm and the mosquito's feeding success probability pw. Control of λm can be achieved by spraying, eliminating breeding sites or moving them away from human habitats, while pw can be controlled via the use of mosquito repellant and insecticide-treated bed-nets. The disease threshold parameter R0 is shown to be highly sensitive to pw, and the intrinsic period of oscillation is also sensitive to the rate at which reproducing mosquitoes return to breeding sites. A global sensitivity and uncertainty analysis reveals that the ability of the mosquito to reproduce and uncertainties in the estimations of the rates at which exposed humans become infectious and infectious humans recover from malaria are critical in generating uncertainties in the disease classes.

Taking a Bite out of Malaria: Controlled Human Malaria Infection by Needle and Syringe

DTIC Science & Technology

2013-01-01

sporozoites (PfSPZ Challenge).1 Because of the potential of this “challenge in a bottle” to standardize and dramatically expand the use of controlled human...to CHMI5,6 since CHMI using mosquitoes that had fed on in vitro cultures of P. falciparum was introduced in 1986.14 Investigators frommultiple...conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint.15 Nevertheless, CHMI based upon the bites of

Relative roles of weather variables and change in human population in malaria: comparison over different states of India.

PubMed

Goswami, Prashant; Murty, Upadhayula Suryanarayana; Mutheneni, Srinivasa Rao; Krishnan, Swathi Trithala

2014-01-01

Pro-active and effective control as well as quantitative assessment of impact of climate change on malaria requires identification of the major drivers of the epidemic. Malaria depends on vector abundance which, in turn, depends on a combination of weather variables. However, there remain several gaps in our understanding and assessment of malaria in a changing climate. Most of the studies have considered weekly or even monthly mean values of weather variables, while the malaria vector is sensitive to daily variations. Secondly, rarely all the relevant meteorological variables have been considered together. An important question is the relative roles of weather variables (vector abundance) and change in host (human) population, in the change in disease load. We consider the 28 states of India, characterized by diverse climatic zones and changing population as well as complex variability in malaria, as a natural test bed. An annual vector load for each of the 28 states is defined based on the number of vector genesis days computed using daily values of temperature, rainfall and humidity from NCEP daily Reanalysis; a prediction of potential malaria load is defined by taking into consideration changes in the human population and compared with the reported number of malaria cases. For most states, the number of malaria cases is very well correlated with the vector load calculated with the combined conditions of daily values of temperature, rainfall and humidity; no single weather variable has any significant association with the observed disease prevalence. The association between vector-load and daily values of weather variables is robust and holds for different climatic regions (states of India). Thus use of all the three weather variables provides a reliable means of pro-active and efficient vector sanitation and control as well as assessment of impact of climate change on malaria.

Relative Roles of Weather Variables and Change in Human Population in Malaria: Comparison over Different States of India

PubMed Central

Goswami, Prashant; Murty, Upadhayula Suryanarayana; Mutheneni, Srinivasa Rao; Krishnan, Swathi Trithala

2014-01-01

Background Pro-active and effective control as well as quantitative assessment of impact of climate change on malaria requires identification of the major drivers of the epidemic. Malaria depends on vector abundance which, in turn, depends on a combination of weather variables. However, there remain several gaps in our understanding and assessment of malaria in a changing climate. Most of the studies have considered weekly or even monthly mean values of weather variables, while the malaria vector is sensitive to daily variations. Secondly, rarely all the relevant meteorological variables have been considered together. An important question is the relative roles of weather variables (vector abundance) and change in host (human) population, in the change in disease load. Method We consider the 28 states of India, characterized by diverse climatic zones and changing population as well as complex variability in malaria, as a natural test bed. An annual vector load for each of the 28 states is defined based on the number of vector genesis days computed using daily values of temperature, rainfall and humidity from NCEP daily Reanalysis; a prediction of potential malaria load is defined by taking into consideration changes in the human population and compared with the reported number of malaria cases. Results For most states, the number of malaria cases is very well correlated with the vector load calculated with the combined conditions of daily values of temperature, rainfall and humidity; no single weather variable has any significant association with the observed disease prevalence. Conclusion The association between vector-load and daily values of weather variables is robust and holds for different climatic regions (states of India). Thus use of all the three weather variables provides a reliable means of pro-active and efficient vector sanitation and control as well as assessment of impact of climate change on malaria. PMID:24971510

The Anopheles gambiae 2La chromosome inversion is associated with susceptibility to Plasmodium falciparum in Africa

PubMed Central

Riehle, Michelle M; Bukhari, Tullu; Gneme, Awa; Guelbeogo, Wamdaogo M; Coulibaly, Boubacar; Fofana, Abdrahamane; Pain, Adrien; Bischoff, Emmanuel; Renaud, Francois; Beavogui, Abdoul H; Traore, Sekou F; Sagnon, N’Fale; Vernick, Kenneth D

2017-01-01

Chromosome inversions suppress genetic recombination and establish co-adapted gene complexes, or supergenes. The 2La inversion is a widespread polymorphism in the Anopheles gambiae species complex, the major African mosquito vectors of human malaria. Here we show that alleles of the 2La inversion are associated with natural malaria infection levels in wild-captured vectors from West and East Africa. Mosquitoes carrying the more-susceptible allele (2L+a) are also behaviorally less likely to be found inside houses. Vector control tools that target indoor-resting mosquitoes, such as bednets and insecticides, are currently the cornerstone of malaria control in Africa. Populations with high levels of the 2L+a allele may form reservoirs of persistent outdoor malaria transmission requiring novel measures for surveillance and control. The 2La inversion is a major and previously unappreciated component of the natural malaria transmission system in Africa, influencing both malaria susceptibility and vector behavior. DOI: http://dx.doi.org/10.7554/eLife.25813.001 PMID:28643631

The Anopheles gambiae 2La chromosome inversion is associated with susceptibility to Plasmodium falciparum in Africa.

PubMed

Riehle, Michelle M; Bukhari, Tullu; Gneme, Awa; Guelbeogo, Wamdaogo M; Coulibaly, Boubacar; Fofana, Abdrahamane; Pain, Adrien; Bischoff, Emmanuel; Renaud, Francois; Beavogui, Abdoul H; Traore, Sekou F; Sagnon, N'Fale; Vernick, Kenneth D

2017-06-23

Chromosome inversions suppress genetic recombination and establish co-adapted gene complexes, or supergenes. The 2La inversion is a widespread polymorphism in the Anopheles gambiae species complex, the major African mosquito vectors of human malaria. Here we show that alleles of the 2La inversion are associated with natural malaria infection levels in wild-captured vectors from West and East Africa. Mosquitoes carrying the more-susceptible allele (2L+ a ) are also behaviorally less likely to be found inside houses. Vector control tools that target indoor-resting mosquitoes, such as bednets and insecticides, are currently the cornerstone of malaria control in Africa. Populations with high levels of the 2L+ a allele may form reservoirs of persistent outdoor malaria transmission requiring novel measures for surveillance and control. The 2La inversion is a major and previously unappreciated component of the natural malaria transmission system in Africa, influencing both malaria susceptibility and vector behavior.

Backward bifurcation and optimal control of Plasmodium Knowlesi malaria

NASA Astrophysics Data System (ADS)

Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

2014-07-01

A deterministic model for the transmission dynamics of Plasmodium Knowlesi malaria with direct transmission is developed. The model is analyzed using dynamical system techniques and it shows that the backward bifurcation occurs for some range of parameters. The model is extended to assess the impact of time dependent preventive (biological and chemical control) against the mosquitoes and vaccination for susceptible humans, while treatment for infected humans. The existence of optimal control is established analytically by the use of optimal control theory. Numerical simulations of the problem, suggest that applying the four control measure can effectively reduce if not eliminate the spread of Plasmodium Knowlesi in a community.

Malaria overdiagnosis and subsequent overconsumption of antimalarial drugs in Angola: Consequences and effects on human health.

PubMed

Manguin, Sylvie; Foumane, Vincent; Besnard, Patrick; Fortes, Filomeno; Carnevale, Pierre

2017-07-01

Microscopic blood smear examinations done in health centers of Angola demonstrated a large overdiagnosis of malaria cases with an average rate of errors as high as 85%. Overall 83% of patients who received Coartem ® had an inappropriate treatment. Overestimated malaria diagnosis was noticed even when specific symptoms were part of the clinical observation, antimalarial treatments being subsequently given. Then, malaria overdiagnosis has three main consequences, (i) the lack of data reliability is of great concern, impeding epidemiological records and evaluation of the actual influence of operations as scheduled by the National Malaria Control Programme; (ii) the large misuse of antimalarial drug can increase the selective pressure for resistant strain and can make a false consideration of drug resistant P. falciparum crisis; and (iii) the need of strengthening national health centers in term of human, with training in microscopy, and equipment resources to improve malaria diagnosis with a large scale use of rapid diagnostic tests associated with thick blood smears, backed up by a "quality control" developed by the national health authorities. Monitoring of malaria cases was done in three Angolan health centers of Alto Liro (Lobito town) and neighbor villages of Cambambi and Asseque (Benguéla Province) to evaluate the real burden of malaria. Carriers of Plasmodium among patients of newly-borne to 14 years old, with or without fever, were analyzed and compared to presumptive malaria cases diagnosed in these health centers. Presumptive malaria cases were diagnosed six times more than the positive thick blood smears done on the same children. In Alto Liro health center, the percentage of diagnosis error reached 98%, while in Cambambi and Asseque it was of 79% and 78% respectively. The percentage of confirmed malaria cases was significantly higher during the dry (20.2%) than the rainy (13.2%) season. These observations in three peripheral health centers confirmed what has already been noticed in other malaria endemic regions, and highlight the need for an accurate evaluation of the Malaria control programme implemented in Angola. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Modeling Methods to Determine Liver-to-blood Inocula and Parasite Multiplication Rates During Controlled Human Malaria Infection

PubMed Central

Douglas, Alexander D.; Edwards, Nick J.; Duncan, Christopher J. A.; Thompson, Fiona M.; Sheehy, Susanne H.; O'Hara, Geraldine A.; Anagnostou, Nicholas; Walther, Michael; Webster, Daniel P.; Dunachie, Susanna J.; Porter, David W.; Andrews, Laura; Gilbert, Sarah C.; Draper, Simon J.; Hill, Adrian V. S.; Bejon, Philip

2013-01-01

Controlled human malaria infection is used to measure efficacy of candidate malaria vaccines before field studies are undertaken. Mathematical modeling using data from quantitative polymerase chain reaction (qPCR) parasitemia monitoring can discriminate between vaccine effects on the parasite's liver and blood stages. Uncertainty regarding the most appropriate modeling method hinders interpretation of such trials. We used qPCR data from 267 Plasmodium falciparum infections to compare linear, sine-wave, and normal-cumulative-density-function models. We find that the parameters estimated by these models are closely correlated, and their predictive accuracy for omitted data points was similar. We propose that future studies include the linear model. PMID:23570846

Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica

PubMed Central

Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José

2017-01-01

One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs. PMID:28125696

In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.

PubMed

Liu, Xuewu; Wang, Yuanyuan; Liang, Jiao; Wang, Luojun; Qin, Na; Zhao, Ya; Zhao, Gang

2018-05-02

Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease. Here, we developed and used a virtual genome method to assign 33,314 genes from three human malaria parasites, namely, P. falciparum, P. knowlesi and P. vivax, and three rodent malaria parasites, namely, P. berghei, P. chabaudi and P. yoelii, to 4605 clusters. Each cluster consisted of genes whose protein sequences were significantly similar and was considered as a virtual gene. Comparing the enriched values of all clusters in human malaria parasites with those in rodent malaria parasites revealed 115 P. falciparum genes putatively responsible for parasitizing human erythrocytes. These genes are mainly located in the chromosome internal regions and participate in many biological processes, including membrane protein trafficking and thiamine biosynthesis. Meanwhile, 289 P. berghei genes were included in the rodent parasite-enriched clusters. Most are located in subtelomeric regions and encode erythrocyte surface proteins. Comparing cluster values in P. falciparum with those in P. vivax and P. knowlesi revealed 493 candidate genes linked to virulence. Some of them encode proteins present on the erythrocyte surface and participate in cytoadhesion, virulence factor trafficking, or erythrocyte invasion, but many genes with unknown function were also identified. Cerebral malaria is characterized by accumulation of infected erythrocytes at trophozoite stage in brain microvascular. To discover cerebral malaria-related genes, fast Fourier transformation (FFT) was introduced to extract genes highly transcribed at the trophozoite stage. Finally, 55 candidate genes were identified. Considering that parasite-infected erythrocyte surface protein 2 (PIESP2) contains gap-junction-related Neuromodulin_N domain and that anti-PIESP2 might provide protection against malaria, we chose PIESP2 for further experimental study. Our analysis revealed a limited number of genes linked to human disease in P. falciparum genome. These genes could be interesting targets for further functional characterization.

Vaccines to Accelerate Malaria Elimination and Eventual Eradication.

PubMed

Healer, Julie; Cowman, Alan F; Kaslow, David C; Birkett, Ashley J

2017-09-01

Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticide-impregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures. As the past 40 years of investment in this goal attests, this is no small feat. The malaria parasite is a highly complex organism, exquisitely adapted for survival under hostile conditions within human and mosquito hosts. Here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the host-parasite interaction. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Development and Assessment of Plant-Based Synthetic Odor Baits for Surveillance and Control of Malaria Vectors

PubMed Central

Nyasembe, Vincent O.; Tchouassi, David P.; Kirwa, Hillary K.; Foster, Woodbridge A.; Teal, Peter E. A.; Borgemeister, Christian; Torto, Baldwyn

2014-01-01

Background Recent malaria vector control measures have considerably reduced indoor biting mosquito populations. However, reducing the outdoor biting populations remains a challenge because of the unavailability of appropriate lures to achieve this. This study sought to test the efficacy of plant-based synthetic odor baits in trapping outdoor populations of malaria vectors. Methodology and Principal Finding Three plant-based lures ((E)-linalool oxide [LO], (E)-linalool oxide and (E)-β-ocimene [LO + OC], and a six-component blend comprising (E)-linalool oxide, (E)-β-ocimene, hexanal, β-pinene, limonene, and (E)-β-farnesene [Blend C]), were tested alongside an animal/human-based synthetic lure (comprising heptanal, octanal, nonanal, and decanal [Blend F]) and worn socks in a malaria endemic zone in the western part of Kenya. Mosquito Magnet-X (MM-X) and lightless Centre for Disease Control (CDC) light traps were used. Odor-baited traps were compared with traps baited with either solvent alone or solvent + carbon dioxide (controls) for 18 days in a series of randomized incomplete-block designs of days × sites × treatments. The interactive effect of plant and animal/human odor was also tested by combining LO with either Blend F or worn socks. Our results show that irrespective of trap type, traps baited with synthetic plant odors compared favorably to the same traps baited with synthetic animal odors and worn socks in trapping malaria vectors, relative to the controls. Combining LO and worn socks enhanced trap captures of Anopheles species while LO + Blend F recorded reduced trap capture. Carbon dioxide enhanced total trap capture of both plant- and animal/human-derived odors. However, significantly higher proportions of male and engorged female Anopheles gambiae s.l. were caught when the odor treatments did not include carbon dioxide. Conclusion and Significance The results highlight the potential of plant-based odors and specifically linalool oxide, with or without carbon dioxide, for surveillance and mass trapping of malaria vectors. PMID:24587059

Development and assessment of plant-based synthetic odor baits for surveillance and control of malaria vectors.

PubMed

Nyasembe, Vincent O; Tchouassi, David P; Kirwa, Hillary K; Foster, Woodbridge A; Teal, Peter E A; Borgemeister, Christian; Torto, Baldwyn

2014-01-01

Recent malaria vector control measures have considerably reduced indoor biting mosquito populations. However, reducing the outdoor biting populations remains a challenge because of the unavailability of appropriate lures to achieve this. This study sought to test the efficacy of plant-based synthetic odor baits in trapping outdoor populations of malaria vectors. Three plant-based lures ((E)-linalool oxide [LO], (E)-linalool oxide and (E)-β-ocimene [LO + OC], and a six-component blend comprising (E)-linalool oxide, (E)-β-ocimene, hexanal, β-pinene, limonene, and (E)-β-farnesene [Blend C]), were tested alongside an animal/human-based synthetic lure (comprising heptanal, octanal, nonanal, and decanal [Blend F]) and worn socks in a malaria endemic zone in the western part of Kenya. Mosquito Magnet-X (MM-X) and lightless Centre for Disease Control (CDC) light traps were used. Odor-baited traps were compared with traps baited with either solvent alone or solvent + carbon dioxide (controls) for 18 days in a series of randomized incomplete-block designs of days × sites × treatments. The interactive effect of plant and animal/human odor was also tested by combining LO with either Blend F or worn socks. Our results show that irrespective of trap type, traps baited with synthetic plant odors compared favorably to the same traps baited with synthetic animal odors and worn socks in trapping malaria vectors, relative to the controls. Combining LO and worn socks enhanced trap captures of Anopheles species while LO + Blend F recorded reduced trap capture. Carbon dioxide enhanced total trap capture of both plant- and animal/human-derived odors. However, significantly higher proportions of male and engorged female Anopheles gambiae s.l. were caught when the odor treatments did not include carbon dioxide. The results highlight the potential of plant-based odors and specifically linalool oxide, with or without carbon dioxide, for surveillance and mass trapping of malaria vectors.

mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa.

PubMed

Eskenazi, Brenda; Quirós-Alcalá, Lesliam; Lipsitt, Jonah M; Wu, Lemuel D; Kruger, Philip; Ntimbane, Tzundzukani; Nawn, John Burns; Bornman, M S Riana; Seto, Edmund

2014-07-01

Recent estimates indicate that malaria has led to over half a million deaths worldwide, mostly to African children. Indoor residual spraying (IRS) of insecticides is one of the primary vector control interventions. However, current reporting systems do not obtain precise location of IRS events in relation to malaria cases, which poses challenges for effective and efficient malaria control. This information is also critical to avoid unnecessary human exposure to IRS insecticides. We developed and piloted a mobile-based application (mSpray) to collect comprehensive information on IRS spray events. We assessed the utility, acceptability and feasibility of using mSpray to gather improved homestead- and chemical-level IRS coverage data. We installed mSpray on 10 cell phones with data bundles, and pilot tested it with 13 users in Limpopo, South Africa. Users completed basic information (number of rooms/shelters sprayed; chemical used, etc.) on spray events. Upon submission, this information as well as geographic positioning system coordinates and time/date stamp were uploaded to a Google Drive Spreadsheet to be viewed in real time. We administered questionnaires, conducted focus groups, and interviewed key informants to evaluate the utility of the app. The low-cost, cell phone-based "mSpray" app was learned quickly by users, well accepted and preferred to the current paper-based method. We recorded 2865 entries (99.1% had a GPS accuracy of 20 m or less) and identified areas of improvement including increased battery life. We also identified a number of logistic and user problems (e.g., cost of cell phones and cellular bundles, battery life, obtaining accurate GPS measures, user errors, etc.) that would need to be overcome before full deployment. Use of cell phone technology could increase the efficiency of IRS malaria control efforts by mapping spray events in relation to malaria cases, resulting in more judicious use of chemicals that are potentially harmful to humans and the environment. Copyright © 2014. Published by Elsevier Ltd.

Optimal control in a model of malaria with differential susceptibility

NASA Astrophysics Data System (ADS)

Hincapié, Doracelly; Ospina, Juan

2014-06-01

A malaria model with differential susceptibility is analyzed using the optimal control technique. In the model the human population is classified as susceptible, infected and recovered. Susceptibility is assumed dependent on genetic, physiological, or social characteristics that vary between individuals. The model is described by a system of differential equations that relate the human and vector populations, so that the infection is transmitted to humans by vectors, and the infection is transmitted to vectors by humans. The model considered is analyzed using the optimal control method when the control consists in using of insecticide-treated nets and educational campaigns; and the optimality criterion is to minimize the number of infected humans, while keeping the cost as low as is possible. One first goal is to determine the effects of differential susceptibility in the proposed control mechanism; and the second goal is to determine the algebraic form of the basic reproductive number of the model. All computations are performed using computer algebra, specifically Maple. It is claimed that the analytical results obtained are important for the design and implementation of control measures for malaria. It is suggested some future investigations such as the application of the method to other vector-borne diseases such as dengue or yellow fever; and also it is suggested the possible application of free software of computer algebra like Maxima.

Malaria Risk Factors in Kaligesing, Purworejo District, Central Java Province, Indonesia: A Case-control Study.

PubMed

Cahyaningrum, Pratiwi; Sulistyawati, Sulistyawati

2018-05-01

Malaria remains a public health concern worldwide, including Indonesia. Purworejo is a district in which endemic of malaria, they have re-setup to entering malaria elimination in 2021. Accordingly, actions must be taken to accelerate and guaranty that the goal will reach based on an understanding of the risk factors for malaria. Thus, we analysed malaria risk factors based on human and housing conditions in Kaligesing, Purworejo, Indonesia. A case-control study was carried out in Kaligesing subdistrict, Purworejo, Indonesia in July to August 2017. A structured questionnaire and checklist were used to collect data from 96 participants, who consisted of 48 controls and 48 cases. Univariate, bivariate, and multivariate analyses were performed. Bivariate analysis found that education level, the presence of a cattle cage within 100 m of the house, not sleeping under a bednet the previous night, and not closing the doors and windows from 6 p.m. to 5 a.m. were significantly ( p ≤0.25) associated with malaria. Of these factors, only not sleeping under a bednet the previous night and not closing the doors and windows from 6 p.m. to 5 a.m. were significantly associated with malaria. The findings of this study demonstrate that potential risk factor for Malaria should be paid of attention all the time, particularly for an area which is targeting Malaria elimination.

Progress and prospects for blood-stage malaria vaccines.

PubMed

Miura, Kazutoyo

2016-06-01

There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

Seasonal Abundance and Host-Feeding Patterns of Anopheline Vectors in Malaria Endemic Area of Iran

PubMed Central

Basseri, Hamidreza; Raeisi, Ahmad; Ranjbar Khakha, Mansoor; Pakarai, Abaas; Abdolghafar, Hassanzehi

2010-01-01

Seasonal abundance and tendency to feed on humans are important parameters to measure for effective control of malaria vectors. The objective of this study was to describe relation between feeding pattern, abundance, and resting behavior of four malaria vectors in southern Iran. This study was conducted in ten indicator villages (based on malaria incidence and entomological indices) in mountainous/hilly and plain regions situated south and southeastern Iran. Mosquito vectors were collected from indoor as well as outdoor shelters and the blood meals were examined by ELISA test. Over all 7654 female Anopheles spp. were captured, the most common species were Anopheles stephensi, An. culicifacies, An. fluviatilis, and An. d'thali. The overall human blood index was 37.50%, 19.83%, 16.4%, and 30.1% for An. fluviatilis, An. stephensi, An. culicifacies, and An. d'thali, respectively. In addition, An. fluviatilis fed on human blood during the entire year but the feeding behavior of An. stephensi and An. culicifacies varied according to seasons. Overall, the abundance of the female mosquito positive to human blood was 4.25% per human shelter versus 17.5% per animal shelter. This result indicates that the vectors had tendency to rest in animal shelters after feeding on human. Therefore, vector control measure should be planned based on such as feeding pattern, abundance, and resting behavior of these vectors in the area. PMID:21559055

Exploring the potential of using cattle for malaria vector surveillance and control: a pilot study in western Kenya.

PubMed

Njoroge, Margaret M; Tirados, Inaki; Lindsay, Steven W; Vale, Glyn A; Torr, Stephen J; Fillinger, Ulrike

2017-01-10

Malaria vector mosquitoes with exophilic and zoophilic tendencies, or with a high acceptance of alternative blood meal sources when preferred human blood-hosts are unavailable, may help maintain low but constant malaria transmission in areas where indoor vector control has been scaled up. This residual transmission might be addressed by targeting vectors outside the house. Here we investigated the potential of insecticide-treated cattle, as routinely used for control of tsetse and ticks in East Africa, for mosquito control. The malaria vector population in the study area was investigated weekly for 8 months using two different trapping tools: light traps indoors and cattle-baited traps (CBTs) outdoors. The effect of the application of the insecticide deltamethrin and the acaricide amitraz on cattle on host-seeking Anopheles arabiensis was tested experimentally in field-cages and the impact of deltamethrin-treated cattle explored under field conditions on mosquito densities on household level. CBTs collected on average 2.8 (95% CI: 1.8-4.2) primary [Anopheles gambiae (s.s.), An. arabiensis and An. funestus (s.s.)] and 6.3 (95% CI: 3.6-11.3) secondary malaria vectors [An. ivulorum and An. coustani (s.l.)] per trap night and revealed a distinct, complementary seasonality. At the same time on average only 1.4 (95% CI: 0.8-2.3) primary and 1.1 (95% CI: 0.6-2.0) secondary malaria vectors were collected per trap night with light traps indoors. Amitraz had no effect on survival of host-seeking An. arabiensis under experimental conditions but deltamethrin increased mosquito mortality (OR 19, 95% CI: 7-50), but only for 1 week. In the field, vector mortality in association with deltamethrin treatment was detected only with CBTs and only immediately after the treatment (OR 0.25, 95% CI: 0.13-0.52). Entomological sampling with CBTs highlights that targeting cattle for mosquito control has potential since it would not only target naturally zoophilic malaria vectors but also opportunistic feeders that lack access to human hosts as is expected in residual malaria transmission settings. However, the deltamethrin formulation tested here although used widely to treat cattle for tsetse and tick control, is not suitable for the control of malaria vectors since it causes only moderate initial mortality and has little residual activity.

Ivermectin: a complimentary weapon against the spread of malaria?

PubMed Central

Alout, Haoues; Foy, Brian

2017-01-01

Introduction Ivermectin has transformed the treatment of parasitic diseases and led to incommensurable benefits to humans and animals. Ivermectin is effective in treating several neglected infectious diseases and recently it has been shown to reduce malaria parasite transmission. Areas covered Malaria control strategies could benefit from the addition of ivermectin to interrupt the transmission cycle if it is a long lasting formulation or repeatedly administered. In turn, this will help also to control neglected infectious diseases where the elimination goal has been slower to achieve. Despite the relevance of using ivermectin for integrated and sustained disease control, there are still essential questions that remain to be addressed about safety and practicality. The efficacy in various malaria ecologies and the interaction between control tools, either drugs or insecticides, are also important to assess. Expert commentary Overlapping distribution of several infectious diseases reveals the benefit of integrating control programs against several infectious diseases into one strategy for cost effectiveness and to reach the elimination goals. The use of ivermectin to control malaria transmission will necessitate development and testing of long-lasting formulations or repeated treatments, and implementation of these treatments with other disease control tools may increase the chance of successful and sustained control. PMID:27960597

[Will climate and demography have a major impact on malaria in sub-Saharan Africa in the next 20 years?].

PubMed

Saugeon, C; Baldet, T; Akogbeto, M; Henry, M C

2009-04-01

The purpose of this review of the literature is to present factors possibly affecting the spread of malaria in sub-Saharan Africa over the next 20 years. Malaria is a vector-borne disease that depends on environmental and human constraints. The main environmental limitations involve susceptibility of the vector (mosquitoes of the Anopheles genus) and parasite (Plasmodium falciparum) to climate. Malaria is a stable, endemic disease over most of the African continent. Climatic change can only affect a few regions on the fringes of stable zones (e.g. altitude areas or Sahel) where malaria is an unstable, epidemic disease. Higher temperatures could induce a decrease of malaria transmission in regions of the Sahel or an increase in the highlands. The extent of these overall trends will depend on the unpredictable occurrence of major meteorological phenomenon as well as on human activities affecting the environment that could lead to dramatic but limited outbreaks in some locations. The most influential human factors could be runaway demographic growth and urban development. Estimations based on modeling studies indicate that urbanization will lead to a 53.5% drop in exposure to malaria by 2030. However this reduction could be less than expected because of adaptation of Anopheles gambiae and An. arabiensis, the main vectors of malaria in sub-Saharan Africa, to the urban environment as well as increasing vector resistance to insecticides. Another unforeseeable factor that could induce unexpected malaria epidemics is mass migration due to war or famine. Finally immunosuppressive illnesses (e.g. HIV and malnutrition) could alter individual susceptibility to malaria. Social constraints also include human activities that modify land use. In this regard land use (e.g. forest clearance and irrigation) is known to influence the burden of malaria that is itself dependent on local determinants of transmission. Overall the most important social constraint for the population will be access to malarial prevention and implementation action to control this scourge.

New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model.

PubMed

Limbach, Keith; Stefaniak, Maureen; Chen, Ping; Patterson, Noelle B; Liao, Grant; Weng, Shaojie; Krepkiy, Svetlana; Ekberg, Greg; Torano, Holly; Ettyreddy, Damodar; Gowda, Kalpana; Sonawane, Sharvari; Belmonte, Arnel; Abot, Esteban; Sedegah, Martha; Hollingdale, Michael R; Moormann, Ann; Vulule, John; Villasante, Eileen; Richie, Thomas L; Brough, Douglas E; Bruder, Joseph T

2017-07-03

A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development.

Does malaria epidemiology project Cameroon as 'Africa in miniature'?

PubMed

Mbenda, Huguette Gaelle Ngassa; Awasthi, Gauri; Singh, Poonam K; Gouado, Inocent; Das, Aparup

2014-09-01

Cameroon, a west-central African country with a ~ 20 million population, is commonly regarded as 'Africa in miniature' due to the extensive biological and cultural diversities of whole Africa being present in a single-country setting. This country is inhabited by ancestral human lineages in unique eco-climatic conditions and diverse topography. Over 90 percent Cameroonians are at risk of malaria infection, and ~ 41 percent have at least one episode of malaria each year. Historically, the rate of malaria infection in Cameroon has fluctuated over the years; the number of cases was about 2 million in 2010 and 2011. The Cameroonian malaria control programme faces an uphill task due to high prevalence of multidrug-resistant parasites and insecticide-resistant malaria vectors. Above all, continued human migration from the rural to urban areas as well as population exchange with adjoining countries, high rate of ecological instabilities caused by deforestation, poor housing, lack of proper sanitation and drainage system might have resulted in the recent increase in incidences of malaria and other vector-borne diseases in Cameroon. The available data on eco-environmental variability and intricate malaria epidemiology in Cameroon reflect the situation in the whole of Africa, and warrant the need for in-depth study by using modern surveillance tools for meaningful basic understanding of the malaria triangle (host-parasite-vector-environment).

Plasmodium knowlesi in humans: a review on the role of its vectors in Malaysia.

PubMed

Vythilingam, Indra

2010-04-01

Plasmodium knowlesi in humans is life threatening, is on the increase and has been reported from most states in Malaysia. Anopheles latens and Anopheles cracens have been incriminated as vectors. Malaria is now a zoonoses and is occurring in malaria free areas of Malaysia. It is also a threat to eco-tourism. The importance of the vectors and possible control measures is reviewed here.

Progress and prospects for blood-stage malaria vaccines

PubMed Central

Miura, Kazutoyo

2016-01-01

ABSTRACT There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. PMID:26760062

Factors that are associated with the risk of acquiring Plasmodium knowlesi malaria in Sabah, Malaysia: a case-control study protocol.

PubMed

Grigg, M J; William, T; Drakeley, C J; Jelip, J; von Seidlein, L; Barber, B E; Fornace, K M; Anstey, N M; Yeo, T W; Cox, J

2014-08-22

Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission. A population-based case-control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models. This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

PubMed Central

Bousema, Teun; Drakeley, Chris

2011-01-01

Summary: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed. PMID:21482730

Forecasting paediatric malaria admissions on the Kenya Coast using rainfall.

PubMed

Karuri, Stella Wanjugu; Snow, Robert W

2016-01-01

Malaria is a vector-borne disease which, despite recent scaled-up efforts to achieve control in Africa, continues to pose a major threat to child survival. The disease is caused by the protozoan parasite Plasmodium and requires mosquitoes and humans for transmission. Rainfall is a major factor in seasonal and secular patterns of malaria transmission along the East African coast. The goal of the study was to develop a model to reliably forecast incidences of paediatric malaria admissions to Kilifi District Hospital (KDH). In this article, we apply several statistical models to look at the temporal association between monthly paediatric malaria hospital admissions, rainfall, and Indian Ocean sea surface temperatures. Trend and seasonally adjusted, marginal and multivariate, time-series models for hospital admissions were applied to a unique data set to examine the role of climate, seasonality, and long-term anomalies in predicting malaria hospital admission rates and whether these might become more or less predictable with increasing vector control. The proportion of paediatric admissions to KDH that have malaria as a cause of admission can be forecast by a model which depends on the proportion of malaria admissions in the previous 2 months. This model is improved by incorporating either the previous month's Indian Ocean Dipole information or the previous 2 months' rainfall. Surveillance data can help build time-series prediction models which can be used to anticipate seasonal variations in clinical burdens of malaria in stable transmission areas and aid the timing of malaria vector control.

[Contribution of remote sensing to malaria control].

PubMed

Machault, V; Pages, F; Rogier, C

2009-04-01

Despite national and international efforts, malaria remains a major public health problem and the fight to control the disease is confronted by numerous hurdles. Study of space and time dynamics of malaria is necessary as a basis for making appropriate decision and prioritizing intervention including in areas where field data are rare and sanitary information systems are inadequate. Evaluation of malarial risk should also help anticipate the risk of epidemics as a basis for early warning systems. Since 1960-70 civilian satellites launched for earth observation have been providing information for the measuring or evaluating geo-climatic and anthropogenic factors related to malaria transmission and burden. Remotely sensed data gathered for several civilian or military studies have allowed setup of entomological, parasitological, and epidemiological risk models and maps for rural and urban areas. Mapping of human populations at risk has also benefited from remotely sensing. The results of the published studies show that remote sensing is a suitable tool for optimizing planning, efficacy and efficiency of malaria control.

A realistic host-vector transmission model for describing malaria prevalence pattern.

PubMed

Mandal, Sandip; Sinha, Somdatta; Sarkar, Ram Rup

2013-12-01

Malaria continues to be a major public health concern all over the world even after effective control policies have been employed, and considerable understanding of the disease biology have been attained, from both the experimental and modelling perspective. Interactions between different general and local processes, such as dependence on age and immunity of the human host, variations of temperature and rainfall in tropical and sub-tropical areas, and continued presence of asymptomatic infections, regulate the host-vector interactions, and are responsible for the continuing disease prevalence pattern.In this paper, a general mathematical model of malaria transmission is developed considering short and long-term age-dependent immunity of human host and its interaction with pathogen-infected mosquito vector. The model is studied analytically and numerically to understand the role of different parameters related to mosquitoes and humans. To validate the model with a disease prevalence pattern in a particular region, real epidemiological data from the north-eastern part of India was used, and the effect of seasonal variation in mosquito density was modelled based on local climactic data. The model developed based on general features of host-vector interactions, and modified simply incorporating local environmental factors with minimal changes, can successfully explain the disease transmission process in the region. This provides a general approach toward modelling malaria that can be adapted to control future outbreaks of malaria.

Advances in biosensors and optical assays for diagnosis and detection of malaria.

PubMed

Ragavan, K V; Kumar, Sanni; Swaraj, Shiva; Neethirajan, Suresh

2018-05-15

Vector-borne diseases are a major concern for human health globally, especially malaria in densely populated, less developed, tropical regions of the world. Malaria causes loss of human life and economic harm, and may spread through travelers to new regions. Though there are sufficient therapeutics available for the effective treatment and cure of malaria, it infects millions of people and claims several thousand lives every year. Early diagnosis of the infection can potentially prevent the spread of disease, save lives, and mitigate the financial impact. Conventional analytical techniques are being widely employed for malaria diagnosis, but with low sensitivity and selectivity. Due to the poor-resource settings where malaria outbreaks often occur, most conventional diagnostic methods are not affordable and hence not effective in detection and controlling the spread of the infection. However, biosensors have improved the scope for affordable malaria diagnosis. Advances in biotechnology and nanotechnology have provided novel recognition materials and transducer elements, discoveries which allow the fabrication of affordable biosensor platforms with improved attributes. The present work covers the advancement in biosensors with an introduction to malaria, followed by conventional methods of malaria diagnosis, malaria markers, novel recognition elements and the biosensor principle. Finally, a proactive role and a perspective on developed biosensor platforms are discussed with potential biomedical applications. Copyright © 2018. Published by Elsevier B.V.

Volatile biomarkers of symptomatic and asymptomatic malaria infection in humans

PubMed Central

Wanjiku, Caroline; Stanczyk, Nina M.; Pulido, Hannier; Betz, Heike S.

2018-01-01

Malaria remains among the world’s deadliest diseases, and control efforts depend critically on the availability of effective diagnostic tools, particularly for the identification of asymptomatic infections, which play a key role in disease persistence and may account for most instances of transmission but often evade detection by current screening methods. Research on humans and in animal models has shown that infection by malaria parasites elicits changes in host odors that influence vector attraction, suggesting that such changes might yield robust biomarkers of infection status. Here we present findings based on extensive collections of skin volatiles from human populations with high rates of malaria infection in Kenya. We report broad and consistent effects of malaria infection on human volatile profiles, as well as significant divergence in the effects of symptomatic and asymptomatic infections. Furthermore, predictive models based on machine learning algorithms reliably determined infection status based on volatile biomarkers. Critically, our models identified asymptomatic infections with 100% sensitivity, even in the case of low-level infections not detectable by microscopy, far exceeding the performance of currently available rapid diagnostic tests in this regard. We also identified a set of individual compounds that emerged as consistently important predictors of infection status. These findings suggest that volatile biomarkers may have significant potential for the development of a robust, noninvasive screening method for detecting malaria infections under field conditions. PMID:29760095

Forecasting Malaria in the Western Amazon

NASA Astrophysics Data System (ADS)

Pan, W. K.; Zaitchik, B. F.; Pizzitutti, F.; Berky, A.; Feingold, B.; Mena, C.; Janko, M.

2017-12-01

Reported cases of malaria in the western Amazon regions of Peru, Colombia and Ecuador have more than tripled since 2011. Responding to this epidemic has been challenging given large-scale environmental impacts and demographic changes combined with changing financial and political priorities. In Peru alone, malaria cases increased 5-fold since 2011. Reasons include changes in the Global Malaria Fund, massive flooding in 2012, the "mega" El Nino in 2016, and continued natural resource extraction via logging and mining. These challenges prompted the recent creation of the Malaria Cero program in 2017 with the goal to eradicate malaria by 2021. To assist in malaria eradiation, a team of investigators supported by NASA have been developing an Early Warning System for Malaria. The system leverages demographic, epidemiological, meteorological and land use/cover data to develop a four-component system that will improve detection of malaria across the western Amazon Basin. System components include a land data assimilation system (LDAS) to estimate past and future hydrological states and flux, a seasonal human population model to estimate population at risk and spatial connectivity to high risk transmission areas, a sub-regional statistical model to identify when and where observed malaria cases have exceeded those expected, and an Agent Based Model (ABM) to integrate human, environmental, and entomological transmission dynamics with potential strategies for control. Data include: daily case detection reports between 2000 and 2017 from all health posts in the region of Loreto in the northern Peruvian Amazon; LDAS outputs (precipitation, temperature, humidity, solar radiation) at a 1km and weekly scale; satellite-derived estimates of land cover; and human population size from census and health data. This presentation will provide an overview of components, focusing on how the system identifies an outbreak and plans for technology transfer.

External quality assurance of malaria nucleic acid testing for clinical trials and eradication surveillance.

PubMed

Murphy, Sean C; Hermsen, Cornelus C; Douglas, Alexander D; Edwards, Nick J; Petersen, Ines; Fahle, Gary A; Adams, Matthew; Berry, Andrea A; Billman, Zachary P; Gilbert, Sarah C; Laurens, Matthew B; Leroy, Odile; Lyke, Kristen E; Plowe, Christopher V; Seilie, Annette M; Strauss, Kathleen A; Teelen, Karina; Hill, Adrian V S; Sauerwein, Robert W

2014-01-01

Nucleic acid testing (NAT) for malaria parasites is an increasingly recommended diagnostic endpoint in clinical trials of vaccine and drug candidates and is also important in surveillance of malaria control and elimination efforts. A variety of reported NAT assays have been described, yet no formal external quality assurance (EQA) program provides validation for the assays in use. Here, we report results of an EQA exercise for malaria NAT assays. Among five centers conducting controlled human malaria infection trials, all centers achieved 100% specificity and demonstrated limits of detection consistent with each laboratory's pre-stated expectations. Quantitative bias of reported results compared to expected results was generally <0.5 log10 parasites/mL except for one laboratory where the EQA effort identified likely reasons for a general quantitative shift. The within-laboratory variation for all assays was low at <10% coefficient of variation across a range of parasite densities. Based on this study, we propose to create a Molecular Malaria Quality Assessment program that fulfills the need for EQA of malaria NAT assays worldwide.

Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study.

PubMed

Regules, Jason A; Cicatelli, Susan B; Bennett, Jason W; Paolino, Kristopher M; Twomey, Patrick S; Moon, James E; Kathcart, April K; Hauns, Kevin D; Komisar, Jack L; Qabar, Aziz N; Davidson, Silas A; Dutta, Sheetij; Griffith, Matthew E; Magee, Charles D; Wojnarski, Mariusz; Livezey, Jeffrey R; Kress, Adrian T; Waterman, Paige E; Jongert, Erik; Wille-Reece, Ulrike; Volkmuth, Wayne; Emerling, Daniel; Robinson, William H; Lievens, Marc; Morelle, Danielle; Lee, Cynthia K; Yassin-Rajkumar, Bebi; Weltzin, Richard; Cohen, Joe; Paris, Robert M; Waters, Norman C; Birkett, Ashley J; Kaslow, David C; Ballou, W Ripley; Ockenhouse, Christian F; Vekemans, Johan

2016-09-01

Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human malaria parasite infection (CHMI) and natural exposure. Immunization regimens, including a delayed fractional third dose, were assessed for potential increased protection against malaria and immunologic responses. In a phase 2a, controlled, open-label, study of healthy malaria-naive adults, 16 subjects vaccinated with a 0-, 1-, and 2-month full-dose regimen (012M) and 30 subjects who received a 0-, 1-, and 7-month regimen, including a fractional third dose (Fx017M), underwent CHMI 3 weeks after the last dose. Plasmablast heavy and light chain immunoglobulin messenger RNA sequencing and antibody avidity were evaluated. Protection against repeat CHMI was evaluated after 8 months. A total of 26 of 30 subjects in the Fx017M group (vaccine efficacy [VE], 86.7% [95% confidence interval [CI], 66.8%-94.6%]; P < .0001) and 10 of 16 in the 012M group (VE, 62.5% [95% CI, 29.4%-80.1%]; P = .0009) were protected against infection, and protection differed between schedules (P = .040, by the log rank test). The fractional dose boosting increased antibody somatic hypermutation and avidity and sustained high protection upon rechallenge. A delayed third fractional vaccine dose improved immunogenicity and protection against infection. Optimization of the RTS,S/AS01 immunization regimen may lead to improved approaches against malaria. NCT01857869. Published by Oxford University Press on behalf of the Infectious Diseases Society of America, 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

PubMed Central

Obiero, Joshua M.; Shekalaghe, Seif; Hermsen, Cornelus C.; Mpina, Maxmillian; Bijker, Else M.; Roestenberg, Meta; Teelen, Karina; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Daubenberger, Claudia A.; Hoffman, Stephen L.; Abdulla, Salim

2015-01-01

To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreserved Plasmodium falciparum sporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection of P. falciparum sporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexual P. falciparum lysate and another that, based on P. falciparum serology, resembled the malaria-naive Dutch cohort. Positive P. falciparum serology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparum antibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increase P. falciparum-specific in vitro recall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower in P. falciparum lysate-seropositive individuals than in seronegative individuals. In conclusion, positive P. falciparum lysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic. PMID:25776749

Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium.

PubMed

Faust, Christina; Dobson, Andrew P

2015-12-01

Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi , in Southeast Asia highlights the permeability of species barriers in Plasmodium . Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence-absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

Rapid and sensitive multiplex single-tube nested PCR for the identification of five human Plasmodium species.

PubMed

Saito, Takahiro; Kikuchi, Aoi; Kaneko, Akira; Isozumi, Rie; Teramoto, Isao; Kimura, Masatsugu; Hirasawa, Noriyasu; Hiratsuka, Masahiro

2018-06-01

Malaria is caused by five species of Plasmodium in humans. Microscopy is currently used for pathogen detection, requiring considerable training and technical expertise as the parasites are often difficult to differentiate morphologically. Rapid diagnostic tests are as reliable as microscopy and offer faster diagnoses but possess lower detection limits and are incapable of distinguishing among the parasitic species. To improve global health efforts towards malaria control, a rapid, sensitive, species-specific, and economically viable diagnostic method is needed. In this study, we designed a malaria diagnostic method involving a multiplex single-tube nested PCR targeting Plasmodium mitochondrial cytochrome c oxidase III and single-stranded tag hybridization chromatographic printed-array strip. The detection sensitivity was found to be at least 40 times higher than that of agarose gel electrophoresis with ethidium bromide. This system also enables the identification of both single- and mixed-species malaria infections. The assay was validated with 152 Kenyan samples; using nested PCR as the standard, the assay's sensitivity and specificity were 88.7% and 100.0%, respectively. The turnaround time required, from PCR preparation to signal detection, is 90min. Our method should improve the diagnostic speed, treatment efficacy, and control of malaria, in addition to facilitating surveillance within global malaria eradication programs. Copyright © 2018 Elsevier B.V. All rights reserved.

A sticky situation: the unexpected stability of malaria elimination

PubMed Central

Smith, David L.; Cohen, Justin M.; Chiyaka, Christinah; Johnston, Geoffrey; Gething, Peter W.; Gosling, Roly; Buckee, Caroline O.; Laxminarayan, Ramanan; Hay, Simon I.; Tatem, Andrew J.

2013-01-01

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame. PMID:23798693

Zoonotic Malaria – Global Overview and Research and Policy Needs

PubMed Central

Ramasamy, Ranjan

2014-01-01

The four main Plasmodium species that cause human malaria, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale, are transmitted between humans by mosquito vectors belonging to the genus Anopheles. It has recently become evident that Plasmodium knowlesi, a parasite that typically infects forest macaque monkeys, can be transmitted by anophelines to cause malaria in humans in Southeast Asia. Plasmodium knowlesi infections are frequently misdiagnosed microscopically as P. malariae. Direct human to human transmission of P. knowlesi by anophelines has not yet been established to occur in nature. Knowlesi malaria must therefore be presently considered a zoonotic disease. Polymerase chain reaction is now the definitive method for differentiating P. knowlesi from P. malariae and other human malaria parasites. The origin of P. falciparum and P. vivax in African apes are examples of ancient zoonoses that may be continuing at the present time with at least P. vivax, and possibly P. malariae and P. ovale. Other non-human primate malaria species, e.g., Plasmodium cynomolgi in Southeast Asia and Plasmodium brasilianum and Plasmodium simium in South America, can be transmitted to humans by mosquito vectors further emphasizing the potential for continuing zoonoses. The potential for zoonosis is influenced by human habitation and behavior as well as the adaptive capabilities of parasites and vectors. There is insufficient knowledge of the bionomics of Anopheles vector populations relevant to the cross-species transfer of malaria parasites and the real extent of malaria zoonoses. Appropriate strategies, based on more research, need to be developed for the prevention, diagnosis, and treatment of zoonotic malaria. PMID:25184118

A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria.

PubMed

Groger, Mirjam; Fischer, Hannah S; Veletzky, Luzia; Lalremruata, Albert; Ramharter, Michael

2017-03-11

Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.

Malaria Diagnostics in Clinical Trials

PubMed Central

Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

2013-01-01

Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

Malaria eradication in Mexico: Some historico-parasitological views oncold war, deadly fevers by Marcos Cueto, Ph.D

PubMed Central

Malagón, Filiberto

2008-01-01

This review of Professor Marcos Cueto's Cold War Deadly Fevers: Malaria Eradication in Mexico, 1955–1975 discusses some of the historical, sociological, political and parasitological topics included in Dr. Cueto's superbly well-informed volume. The reviewer, a parasitologist, follows the trail illuminated by Dr. Cueto through the foundations of the malaria eradication campaign; the release in Mexico of the first postage stamp in the world dedicated to malaria control; epidemiological facts on malarial morbidity and mortality in Mexico when the campaign began; the emergence of problem areas that impeded eradication; considerations on mosquitoes and malaria transmission in Mexico; the role of business and society in malaria eradication; the results of the campaign; the relationship between malaria and poverty; and the parasitological lessons to be learned from the history of malaria eradication campaigns. Dr. Cueto's excellent and well-informed exploration of malaria – not merely as a disease but as a social, economic and human problem – makes this book required reading.

A review of malaria transmission dynamics in forest ecosystems

PubMed Central

2014-01-01

Malaria continues to be a major health problem in more than 100 endemic countries located primarily in tropical and sub-tropical regions around the world. Malaria transmission is a dynamic process and involves many interlinked factors, from uncontrollable natural environmental conditions to man-made disturbances to nature. Almost half of the population at risk of malaria lives in forest areas. Forests are hot beds of malaria transmission as they provide conditions such as vegetation cover, temperature, rainfall and humidity conditions that are conducive to distribution and survival of malaria vectors. Forests often lack infrastructure and harbor tribes with distinct genetic traits, socio-cultural beliefs and practices that greatly influence malaria transmission dynamics. Here we summarize the various topographical, entomological, parasitological, human ecological and socio-economic factors, which are crucial and shape malaria transmission in forested areas. An in-depth understanding and synthesis of the intricate relationship of these parameters in achieving better malaria control in various types of forest ecosystems is emphasized. PMID:24912923

Small-scale land-use variability affects Anopheles spp. distribution and concomitant Plasmodium infection in humans and mosquito vectors in southeastern Madagascar.

PubMed

Zohdy, Sarah; Derfus, Kristin; Headrick, Emily G; Andrianjafy, Mbolatiana Tovo; Wright, Patricia C; Gillespie, Thomas R

2016-02-24

Deforestation and land-use change have the potential to alter human exposure to malaria. A large percentage of Madagascar's original forest cover has been lost to slash-and-burn agriculture, and malaria is one of the top causes of mortality on the island. In this study, the influence of land-use on the distribution of Plasmodium vectors and concomitant Plasmodium infection in humans and mosquito vectors was examined in the southeastern rainforests of Madagascar. From June to August 2013, health assessments were conducted on individuals living in sixty randomly selected households in six villages bordering Ranomafana National Park. Humans were screened for malaria using species-specific rapid diagnostic tests (RDTs), and surveyed about insecticide-treated bed net (ITN) usage. Concurrently, mosquitoes were captured in villages and associated forest and agricultural sites. All captured female Anopheline mosquitoes were screened for Plasmodium spp. using a circumsporozoite enzyme-linked immunosorbent assay (csELISA). Anopheles spp. dominated the mosquito communities of agricultural and village land-use sites, accounting for 41.4 and 31.4 % of mosquitoes captured respectively, whereas Anopheles spp. accounted for only 1.6 % of mosquitoes captured from forest sites. Interestingly, most Anopheles spp. (67.7 %) were captured in agricultural sites in close proximity to animal pens, and 90.8 % of Anopheles mosquitoes captured in agricultural sites were known vectors of malaria. Three Anopheline mosquitoes (0.7 %) were positive for malaria (Plasmodium vivax-210) and all positive mosquitoes were collected from agricultural or village land-use sites. Ten humans (3.7 %) tested were positive for P. falciparum, and 23.3 % of those surveyed reported never sleeping under ITNs. This study presents the first report of malaria surveillance in humans and the environment in southeastern Madagascar. These findings suggest that even during the winter, malaria species are present in both humans and mosquitoes; with P. falciparum found in humans, and evidence of P. vivax-210 in mosquito vectors. The presence of P. vivax in resident vectors, but not humans may relate to the high incidence of humans lacking the Duffy protein. The majority of mosquito vectors were found in agricultural land-use sites, in particular near livestock pens. These findings have the potential to inform and improve targeted malaria control and prevention strategies in the region.

The potential impact of integrated malaria transmission control on entomologic inoculation rate in highly endemic areas.

PubMed

Killeen, G F; McKenzie, F E; Foy, B D; Schieffelin, C; Billingsley, P F; Beier, J C

2000-05-01

We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas.

Infectivity of Plasmodium falciparum sporozoites determines emerging parasitemia in infected volunteers.

PubMed

McCall, Matthew B B; Wammes, Linda J; Langenberg, Marijke C C; van Gemert, Geert-Jan; Walk, Jona; Hermsen, Cornelus C; Graumans, Wouter; Koelewijn, Rob; Franetich, Jean-François; Chishimba, Sandra; Gerdsen, Max; Lorthiois, Audrey; van de Vegte, Marga; Mazier, Dominique; Bijker, Else M; van Hellemond, Jaap J; van Genderen, Perry J J; Sauerwein, Robert W

2017-06-21

Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical Plasmodium falciparum isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among P. falciparum isolates from distinct geographical locales. The observed heterogeneity in infectivity among strains underscores the value of assessing the protective efficacy of candidate malaria vaccines against heterologous strains in the CHMI model. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Border Malaria Associated with Multidrug Resistance on Thailand-Myanmar and Thailand-Cambodia Borders: Transmission Dynamic, Vulnerability, and Surveillance

PubMed Central

Bhumiratana, Adisak; Intarapuk, Apiradee; Sorosjinda-Nunthawarasilp, Prapa; Maneekan, Pannamas; Koyadun, Surachart

2013-01-01

This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world's most MDR falciparum and vivax malaria on these chaotic borders. PMID:23865048

ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.

PubMed

Sheehy, Susanne H; Duncan, Christopher J A; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian V S; Draper, Simon J

2012-12-01

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1-results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.

Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific

PubMed Central

Waltmann, Andreea; Koepfli, Cristian; Tessier, Natacha; Karl, Stephan; Fola, Abebe; Darcy, Andrew W.; Wini, Lyndes; Harrison, G. L. Abby; Barnadas, Céline; Jennison, Charlie; Karunajeewa, Harin; Boyd, Sarah; Whittaker, Maxine; Kazura, James; Bahlo, Melanie; Mueller, Ivo

2018-01-01

The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination. PMID:29373596

Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific.

PubMed

Waltmann, Andreea; Koepfli, Cristian; Tessier, Natacha; Karl, Stephan; Fola, Abebe; Darcy, Andrew W; Wini, Lyndes; Harrison, G L Abby; Barnadas, Céline; Jennison, Charlie; Karunajeewa, Harin; Boyd, Sarah; Whittaker, Maxine; Kazura, James; Bahlo, Melanie; Mueller, Ivo; Barry, Alyssa E

2018-01-01

The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination.

Zoophagic behaviour of anopheline mosquitoes in southwest Ethiopia: opportunity for malaria vector control.

PubMed

Massebo, Fekadu; Balkew, Meshesha; Gebre-Michael, Teshome; Lindtjørn, Bernt

2015-12-18

Increased understanding of the feeding behaviours of malaria vectors is important to determine the frequency of human-vector contact and to implement effective vector control interventions. Here we assess the relative feeding preferences of Anopheles mosquitoes in relation to cattle and human host abundance in southwest Ethiopia. We collected female Anopheles mosquitoes bi-weekly using Centers for Disease Control and prevention (CDC) light traps, pyrethrum spray catches (PSCs) and by aspirating from artificial pit shelters, and determined mosquito blood meal origins using a direct enzyme-linked immunosorbent assay (ELISA). Both Anopheles arabiensis Patton and An. marshalli (Theobald) showed preference of bovine blood meal over humans regardless of higher human population sizes. The relative feeding preference of An. arabiensis on bovine blood meal was 4.7 times higher than that of human blood. Anopheles marshalli was 6 times more likely to feed on bovine blood meal than humans. The HBI of An. arabiensis and An. marshalli significantly varied between the collection methods, whereas the bovine feeding patterns was not substantially influenced by collection methods. Even though the highest HBI of An. arabiensis and An. marshalli was from indoor CDC traps collections, a substantial number of An. arabiensis (65%) and An. marshalli (63%) had contact with cattle. Anopheles arabiensis (44%) and An. marshalli (41%) had clearly taken bovine blood meals outdoors, but they rested indoors. Anopheles mosquitoes are zoophagic and mainly feed on bovine blood meals than humans. Hence, it is important to consider treatment of cattle with appropriate insecticide to control the zoophagic malaria vectors in southwest Ethiopia. Systemic insecticides like ivermectin and its member eprinomectin could be investigated to control the pyrethroid insecticides resistant vectors.

[A history of malaria in modern Korea 1876-1945].

PubMed

Yeo, Insok

2011-06-30

Although it is not certain when malaria began to appear in Korea, malaria is believed to have been an endemic disease from ancient times. It was Dr. H. N. Allen (1858-1932) who made the first description and diagnosis of malaria in terms of Western medicine. In his first year report (1885) of Korean Government Hospital he mentioned malaria as the most prevalent disease. Very effective anti-malarial drug quinine was imported and it made great contribution in treating malaria. After Japan had annexed Korea in 1910, policies for public health system were fundamentally revised. Japan assumed control of Korean medical institutions and built high-quality Western hospitals for the health care of Japanese residents. The infectious diseases which were under special surveillance were cholera, typhoid fever, dysentery, typhus, scarlet fever, smallpox, and paratyphoid fever. Among chronic infectious diseases tuberculosis and leprosy were those under special control. Malaria, however, was not one of these specially controlled infectious diseases although it was widely spread throughout the peninsula. But serious studies on malaria were carried out by Japanese medical scientists. In particular, a Japanese parasitologist Kobayasi Harujiro(1884-1969) carried out extensive studies on human parasites, including malaria, in Korea. According to his study, most of the malaria in Korea turned out to be tertian fever. In spite of its high prevalence, malaria did not draw much attention from the colonial authorities and no serious measure was taken since tertian fever is a mild form of malaria caused by Plasmodium vivax and is not so much fatal as tropical malaria caused by P. falciparum. And tertian malaria was easily controlled by taking quinine. Although the majority of malaria in Korea was tertian fever, other types were not absent. Quartan fever was not rarely reported in 1930s. The attitude of colonial authorities toward malaria in Korea was contrasted with that in Taiwan. After Japan had set out to colonize Taiwan as a result of Sino-Japanese war, malaria in Taiwan was a big obstacle to the colonization process. Therefore, a lot of medical scientists were asked to engage the malaria research in order to handle health problems in colonized countries caused by malaria. Unlike the situation in Taiwan, malaria in Korea did not cause a serious health problem as in Taiwan. However, its risk was not negligible. In 1933 there were almost 130,000 malaria patients in Korea and 1,800 patients among them died of malaria. The Japanese Government General took measures to control malaria especially during the 1930s and the number of patients decreased. However, as Japan engaged in the World War II, the general hygienic state of the society worsened and the number of malarial patients increased. The worsened situation remains the same after Liberation (1945) and during the Korean war (1950-53).

Molecular approaches to epidemiology and clinical aspects of malaria.

PubMed

Brown, G V; Beck, H P; Molyneux, M; Marsh, K

2000-10-01

Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.

Unexpected anthropophily in the potential secondary malaria vectors Anopheles coustani s.l. and Anopheles squamosus in Macha, Zambia.

PubMed

Fornadel, Christen M; Norris, Laura C; Franco, Veronica; Norris, Douglas E

2011-08-01

Anopheles coustani s.l. and Anopheles squamosus are sub-Saharan mosquito species that have been implicated in malaria transmission. Although generally believed to be of negligible importance due to their overwhelmingly zoophilic behavior, An. coustani s.l. and An. squamosus made up a large proportion of the anophelines collected by human landing catches during the 2007-2008 and 2008-2009 rainy seasons in Macha, Zambia. Further, polymerase chain reaction-based blood meal identification showed that the majority of blood meals from these mosquito species caught in human-baited Centers for Disease Control light traps were from human hosts. Although no An. coustani s.l. or An. squamosus were found to be positive for Plasmodium, the demonstrated anthropophilic tendencies of these mosquitoes in southern Zambia suggest their potential as secondary malaria vectors.

Malaria transmission in Tripura: Disease distribution & determinants.

PubMed

Dev, Vas; Adak, Tridibes; Singh, Om P; Nanda, Nutan; Baidya, Bimal K

2015-12-01

Malaria is a major public health problem in Tripura and focal disease outbreaks are of frequent occurrence. The state is co-endemic for both Plasmodium falciparum and P. vivax and transmission is perennial and persistent. The present study was aimed to review data on disease distribution to prioritize high-risk districts, and to study seasonal prevalence of disease vectors and their bionomical characteristics to help formulate vector species-specific interventions for malaria control. Data on malaria morbidity in the State were reviewed retrospectively (2008-2012) for understanding disease distribution and transmission dynamics. Cross-sectional mass blood surveys were conducted in malaria endemic villages of South Tripura district to ascertain the prevalence of malaria and proportions of parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT. The study showed that malaria was widely prevalent and P. falciparum was the predominant infection (>90%), the remaining were P. vivax cases. The disease distribution, however, was uneven with large concentration of cases in districts of South Tripura and Dhalai coinciding with vast forest cover and tribal populations. Both Anopheles minimus s.s. and An. baimaii were recorded to be prevalent and observed to be highly anthropophagic and susceptible to DDT. Of these, An. minimus was incriminated (sporozoite infection rate 4.92%), and its bionomical characteristics revealed this species to be largely indoor resting and endophagic. For effective control of malaria in the state, it is recommended that diseases surveillance should be robust, and vector control interventions including DDT spray coverage, mass distribution of insecticide-treated nets/ long-lasting insecticidal nets should be intensified prioritizing population groups most at risk to avert impending disease outbreaks and spread of drug-resistant malaria.

Relationships between anopheline mosquitoes and topography in West Timor and Java, Indonesia.

PubMed

Ndoen, Ermi; Wild, Clyde; Dale, Pat; Sipe, Neil; Dale, Mike

2010-08-26

Malaria is a serious health issue in Indonesia. Mosquito control is one aspect of an integrated malaria management programme. To focus resources on priority areas, information is needed about the vectors and their habitats. This research aimed to identify the relationship between anopheline mosquitoes and topography in West Timor and Java. Study areas were selected in three topographic types in West Timor and Java. These were: coastal plain, hilly (rice field) and highland. Adult mosquitoes were captured landing on humans identified to species level and counted. Eleven species were recorded, four of which were significant for malaria transmission: Anopheles aconitus, Anopheles barbirostris, Anopheles subpictus and Anopheles sundaicus. Each species occupied different topographies, but only five were significantly associated: Anopheles annularis, Anopheles vagus and Anopheles subpictus (Java only) with hilly rice fields; Anopheles barbirostris, Anopheles maculatus and Anopheles subpictus (West Timor only) with coastal areas. Information on significant malaria vectors associated with specific topography is useful for planning the mosquito control aspect of malaria management.

Current Status of Malaria and Potential for Control

PubMed Central

Phillips, R. S.

2001-01-01

Malaria remains one of the world's worst health problems with 1.5 to 2.7 million deaths annually; these deaths are primarily among children under 5 years of age and pregnant women in sub-Saharan Africa. Of significance, more people are dying from malaria today than 30 years ago. This review considers the factors which have contributed to this gloomy picture, including those which relate to the vector, the female anopheline mosquito; to human activity such as creating new mosquito breeding sites, the impact of increased numbers of people, and how their migratory behavior can increase the incidence and spread of malaria; and the problems of drug resistance by the parasites to almost all currently available antimalarial drugs. In a selective manner, this review describes what is being done to ameliorate this situation both in terms of applying existing methods in a useful or even crucial role in control and prevention and in terms of new additions to the antimalarial armory that are being developed. Topics covered include biological control of mosquitoes, the use of insecticide-impregnated bed nets, transgenic mosquitoes manipulated for resistance to malaria parasites, old and new antimalarial drugs, drug resistance and how best to maintain the useful life of antimalarials, immunity to malaria and the search for antimalarial vaccines, and the malaria genome project and the potential benefits to accrue from it. PMID:11148010

Transmission blocking malaria vaccines: Assays and candidates in clinical development.

PubMed

Sauerwein, R W; Bousema, T

2015-12-22

Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

Optimal Control of Malaria Transmission using Insecticide Treated Nets and Spraying

NASA Astrophysics Data System (ADS)

Athina, D.; Bakhtiar, T.; Jaharuddin

2017-03-01

In this paper, we consider a model of the transmission of malaria which was developed by Silva and Torres equipped with two control variables, namely the use of insecticide treated nets (ITN) to reduce the number of human beings infected and spraying to reduce the number of mosquitoes. Pontryagin maximum principle was applied to derive the differential equation system as optimality conditions which must be satisfied by optimal control variables. The Mangasarian sufficiency theorem shows that Pontryagin maximum principle is necessary as well as sufficient conditions for optimization problem. The 4th-order Runge Kutta method was then performed to solve the differential equations system. The numerical results show that both controls given at once can reduce the number of infected individuals as well as the number of mosquitoes which reduce the impact of malaria transmission.

THE POTENTIAL IMPACT OF INTEGRATED MALARIA TRANSMISSION CONTROL ON ENTOMOLOGIC INOCULATION RATE IN HIGHLY ENDEMIC AREAS

PubMed Central

KILLEEN, GERRY F.; McKENZIE, F. ELLIS; FOY, BRIAN D.; SCHIEFFELIN, CATHERINE; BILLINGSLEY, PETER F.; BEIER, JOHN C.

2008-01-01

We have used a relatively simple but accurate model for predicting the impact of integrated transmission control on the malaria entomologic inoculation rate (EIR) at four endemic sites from across sub-Saharan Africa and the southwest Pacific. The simulated campaign incorporated modestly effective vaccine coverage, bed net use, and larval control. The results indicate that such campaigns would reduce EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25-fold reductions of EIR were predicted, implying that integrated control with a few modestly effective tools can meaningfully reduce malaria transmission in a range of endemic settings. The model accurately predicts the effects of bed nets and indoor spraying and demonstrates that they are the most effective tools available for reducing EIR. However, the impact of domestic adult vector control is amplified by measures for reducing the rate of emergence of vectors or the level of infectiousness of the human reservoir. We conclude that available tools, including currently neglected methods for larval control, can reduce malaria transmission intensity enough to alleviate mortality. Integrated control programs should be implemented to the fullest extent possible, even in areas of intense transmission, using simple models as decision-making tools. However, we also conclude that to eliminate malaria in many areas of intense transmission is beyond the scope of methods which developing nations can currently afford. New, cost-effective, practical tools are needed if malaria is ever to be eliminated from highly endemic areas. PMID:11289662

Controlling Malaria Using Livestock-Based Interventions: A One Health Approach

PubMed Central

Franco, Ana O.; Gomes, M. Gabriela M.; Rowland, Mark; Coleman, Paul G.

2014-01-01

Where malaria is transmitted by zoophilic vectors, two types of malaria control strategies have been proposed based on animals: using livestock to divert vector biting from people (zooprophylaxis) or as baits to attract vectors to insecticide sources (insecticide-treated livestock). Opposing findings have been obtained on malaria zooprophylaxis, and despite the success of an insecticide-treated livestock trial in Pakistan, where malaria vectors are highly zoophilic, its effectiveness is yet to be formally tested in Africa where vectors are more anthropophilic. This study aims to clarify the different effects of livestock on malaria and to understand under what circumstances livestock-based interventions could play a role in malaria control programmes. This was explored by developing a mathematical model and combining it with data from Pakistan and Ethiopia. Consistent with previous work, a zooprophylactic effect of untreated livestock is predicted in two situations: if vector population density does not increase with livestock introduction, or if livestock numbers and availability to vectors are sufficiently high such that the increase in vector density is counteracted by the diversion of bites from humans to animals. Although, as expected, insecticide-treatment of livestock is predicted to be more beneficial in settings with highly zoophilic vectors, like South Asia, we find that the intervention could also considerably decrease malaria transmission in regions with more anthropophilic vectors, like Anopheles arabiensis in Africa, under specific circumstances: high treatment coverage of the livestock population, using a product with stronger or longer lasting insecticidal effect than in the Pakistan trial, and with small (ideally null) repellency effect, or if increasing the attractiveness of treated livestock to malaria vectors. The results suggest these are the most appropriate conditions for field testing insecticide-treated livestock in an Africa region with moderately zoophilic vectors, where this intervention could contribute to the integrated control of malaria and livestock diseases. PMID:25050703

The Effect of Oral Anthelmintics on the Survivorship and Re-feeding Frequency of Anthropophilic Mosquito Disease Vectors

PubMed Central

Kobylinski, Kevin C.; Deus, Kelsey M.; Butters, Matt T.; Hongyu, Tan; Gray, Meg; Silva, Ines Marques da; Sylla, Massamba; Foy, Brian D.

2010-01-01

In the Tropics, there is substantial temporal and spatial overlap of diseases propagated by anthropophilic mosquito vectors (such as malaria and dengue) and human helminth diseases (such as onchocerciasis and lymphatic filariasis) that are treated though mass drug administrations (MDA). This overlap will result in mosquito vectors imbibing significant quantities of these drugs when they blood feed on humans. Since many anthelmintic drugs have broad anti-invertebrate effects, the possibility of combined helminth control and mosquito-borne disease control through MDA is apparent. It has been previously shown that ivermectin can reduce mosquito survivorship when administered in a blood meal, but more detailed examinations are needed if MDA is to ever be developed into a tool for malaria or dengue control. We examined concentrations of drugs that follow human pharmacokinetics after MDA and that matched with mosquito feeding times, for effects against the anthropophilic mosquito vectors Anopheles gambiae s.s. and Aedes aegypti. Ivermectin was the only human-approved MDA drug we tested that affected mosquito survivorship, and only An. gambiae s.s. were affected at concentrations respecting human pharmacokinetics at indicated doses. Ivermectin also delayed An. gambiae s.s. re-feeding frequency and defecation rates, and two successive ivermectin-spiked blood meals following human pharmacokinetic concentrations compounded mortality effects compared to controls. These findings suggest that ivermectin MDA in Africa may be used to decrease malaria transmission if MDAs were administered more frequently. Such a strategy would broaden the current scope of polyparasitism control already afforded by MDAs, and which is needed in many African villages simultaneously burdened by many parasitic diseases. PMID:20540931

Uncovering the transmission dynamics of Plasmodium vivax using population genetics

PubMed Central

Barry, Alyssa E.; Waltmann, Andreea; Koepfli, Cristian; Barnadas, Celine; Mueller, Ivo

2015-01-01

Population genetic analysis of malaria parasites has the power to reveal key insights into malaria epidemiology and transmission dynamics with the potential to deliver tools to support control and elimination efforts. Analyses of parasite genetic diversity have suggested that Plasmodium vivax populations are more genetically diverse and less structured than those of Plasmodium falciparum indicating that P. vivax may be a more ancient parasite of humans and/or less susceptible to population bottlenecks, as well as more efficient at disseminating its genes. These population genetic insights into P. vivax transmission dynamics provide an explanation for its relative resilience to control efforts. Here, we describe current knowledge on P. vivax population genetic structure, its relevance to understanding transmission patterns and relapse and how this information can inform malaria control and elimination programmes. PMID:25891915

Analysis of the spatial and temporal distribution of malaria in an area of Northern Guatemala with seasonal malaria transmission.

PubMed

Malvisi, Lucio; Troisi, Catherine L; Selwyn, Beatrice J

2018-06-23

The risk of malaria infection displays spatial and temporal variability that is likely due to interaction between the physical environment and the human population. In this study, we performed a spatial analysis at three different time points, corresponding to three cross-sectional surveys conducted as part of an insecticide-treated bed nets efficacy study, to reveal patterns of malaria incidence distribution in an area of Northern Guatemala characterized by low malaria endemicity. A thorough understanding of the spatial and temporal patterns of malaria distribution is essential for targeted malaria control programs. Two methods, the local Moran's I and the Getis-Ord G * (d), were used for the analysis, providing two different statistical approaches and allowing for a comparison of results. A distance band of 3.5 km was considered to be the most appropriate distance for the analysis of data based on epidemiological and entomological factors. Incidence rates were higher at the first cross-sectional survey conducted prior to the intervention compared to the following two surveys. Clusters or hot spots of malaria incidence exhibited high spatial and temporal variations. Findings from the two statistics were similar, though the G * (d) detected cold spots using a higher distance band (5.5 km). The high spatial and temporal variability in the distribution of clusters of high malaria incidence seems to be consistent with an area of unstable malaria transmission. In such a context, a strong surveillance system and the use of spatial analysis may be crucial for targeted malaria control activities.

ChAd63-MVA–vectored Blood-stage Malaria Vaccines Targeting MSP1 and AMA1: Assessment of Efficacy Against Mosquito Bite Challenge in Humans

PubMed Central

Sheehy, Susanne H; Duncan, Christopher JA; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian VS; Draper, Simon J

2012-01-01

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1—results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. PMID:23089736

Towards a framework for analyzing determinants of performance of community health workers in malaria prevention and control: a systematic review.

PubMed

Chipukuma, Helen Mwiinga; Zulu, Joseph Mumba; Jacobs, Choolwe; Chongwe, Gershom; Chola, Mumbi; Halwiindi, Hikabasa; Zgambo, Jessy; Michelo, Charles

2018-05-08

Community health workers (CHWs) are an important human resource in improving coverage of and success to interventions aimed at reducing malaria incidence. Evidence suggests that the performance of CHWs in malaria programs varies in different contexts. However, comprehensive frameworks, based on systematic reviews, to guide the analysis of determinants of performance of CHWs in malaria prevention and control programs are lacking. We systematically searched Google Scholar, Science Direct, and PubMed including reference lists that had English language publications. We included 16 full text articles that evaluated CHW performance in malaria control. Search terms were used and studies that had performance as an outcome of interest attributed to community-based interventions done by CHWs were included. Sixteen studies were included in the final review and were mostly on malaria Rapid Diagnosis and Treatment, as well as adherence to referral guidelines. Factors determining performance and effective implementation of CHW malaria programs included health system factors such as nature of training of CHWs; type of supervision including feedback process; availability of stocks, supplies, and job aids; nature of work environment and reporting systems; availability of financial resources and transport systems; types of remuneration; health staff confidence in CHWs; and workload. In addition, community dynamics such as nature of community connectedness and support from the community and utilization of services by the community also influenced performance. Furthermore, community health worker characteristics such marital status, sex, and CHW confidence levels also shaped CHW performance. Effectively analyzing and promoting the performance of CHWs in malaria prevention and control programs may require adopting a framework that considers health systems and community factors as well as community health worker characteristics.

Impact on Malaria Parasite Multiplication Rates in Infected Volunteers of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909

PubMed Central

Duncan, Christopher J. A.; Sheehy, Susanne H.; Ewer, Katie J.; Douglas, Alexander D.; Collins, Katharine A.; Halstead, Fenella D.; Elias, Sean C.; Lillie, Patrick J.; Rausch, Kelly; Aebig, Joan; Miura, Kazutoyo; Edwards, Nick J.; Poulton, Ian D.; Hunt-Cooke, Angela; Porter, David W.; Thompson, Fiona M.; Rowland, Ros; Draper, Simon J.; Gilbert, Sarah C.; Fay, Michael P.; Long, Carole A.; Zhu, Daming; Wu, Yimin; Martin, Laura B.; Anderson, Charles F.; Lawrie, Alison M.; Hill, Adrian V. S.; Ellis, Ruth D.

2011-01-01

Background Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. Results A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = −0.93 [95% CI: −1.0, −0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = −0.93 [95% CI: −0.99, −0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5–9], control group median 9 days [range 7–9]). Conclusions Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. Trial Registration ClinicalTrials.gov [NCT00984763] PMID:21799809

Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

PubMed Central

Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

2014-01-01

Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

Attacking the mosquito on multiple fronts: Insights from the Vector Control Optimization Model (VCOM) for malaria elimination.

PubMed

Kiware, Samson S; Chitnis, Nakul; Tatarsky, Allison; Wu, Sean; Castellanos, Héctor Manuel Sánchez; Gosling, Roly; Smith, David; Marshall, John M

2017-01-01

Despite great achievements by insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, it is unlikely these tools will be sufficient to eliminate malaria transmission on their own in many settings today. Fortunately, field experiments indicate that there are many promising vector control interventions that can be used to complement ITNs and/or IRS by targeting a wide range of biological and environmental mosquito resources. The majority of these experiments were performed to test a single vector control intervention in isolation; however, there is growing evidence and consensus that effective vector control with the goal of malaria elimination will require a combination of interventions. We have developed a model of mosquito population dynamic to describe the mosquito life and feeding cycles and to optimize the impact of vector control intervention combinations at suppressing mosquito populations. The model simulations were performed for the main three malaria vectors in sub-Saharan Africa, Anopheles gambiae s.s, An. arabiensis and An. funestus. We considered areas having low, moderate and high malaria transmission, corresponding to entomological inoculation rates of 10, 50 and 100 infective bites per person per year, respectively. In all settings, we considered baseline ITN coverage of 50% or 80% in addition to a range of other vector control tools to interrupt malaria transmission. The model was used to sweep through parameters space to select the best optimal intervention packages. Sample model simulations indicate that, starting with ITNs at a coverage of 50% (An. gambiae s.s. and An. funestus) or 80% (An. arabiensis) and adding interventions that do not require human participation (e.g. larviciding at 80% coverage, endectocide treated cattle at 50% coverage and attractive toxic sugar baits at 50% coverage) may be sufficient to suppress all the three species to an extent required to achieve local malaria elimination. The Vector Control Optimization Model (VCOM) is a computational tool to predict the impact of combined vector control interventions at the mosquito population level in a range of eco-epidemiological settings. The model predicts specific combinations of vector control tools to achieve local malaria elimination in a range of eco-epidemiological settings and can assist researchers and program decision-makers on the design of experimental or operational research to test vector control interventions. A corresponding graphical user interface is available for national malaria control programs and other end users.

Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

PubMed Central

Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.

2014-01-01

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995

Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.

PubMed

Lyke, Kirsten E; Ishizuka, Andrew S; Berry, Andrea A; Chakravarty, Sumana; DeZure, Adam; Enama, Mary E; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Manoj, Anita; Li, Minglin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; Kc, Natasha; Murshedkar, Tooba; Mendoza, Floreliz H; Gordon, Ingelise J; Zephir, Kathryn L; Holman, LaSonji A; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Saunders, Jamie G; Berkowitz, Nina M; Flynn, Barbara J; Nason, Martha C; Garver, Lindsay S; Laurens, Matthew B; Plowe, Christopher V; Richie, Thomas L; Graham, Barney S; Roederer, Mario; Sim, B Kim Lee; Ledgerwood, Julie E; Hoffman, Stephen L; Seder, Robert A

2017-03-07

A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 10 5 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls ( P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

The impact of phenotypic and genotypic G6PD deficiency on risk of plasmodium vivax infection: a case-control study amongst Afghan refugees in Pakistan.

PubMed

Leslie, Toby; Briceño, Marnie; Mayan, Ismail; Mohammed, Nasir; Klinkenberg, Eveline; Sibley, Carol Hopkins; Whitty, Christopher J M; Rowland, Mark

2010-05-25

The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A-) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06-0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037). G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.

Surveillance and Control of Malaria Transmission in Thailand using Remotely Sensed Meteorological and Environmental Parameters

NASA Technical Reports Server (NTRS)

Kiang, Richard K.; Adimi, Farida; Soika, Valerii; Nigro, Joseph

2007-01-01

These slides address the use of remote sensing in a public health application. Specifically, this discussion focuses on the of remote sensing to detect larval habitats to predict current and future endemicity and identify key factors that sustain or promote transmission of malaria in a targeted geographic area (Thailand). In the Malaria Modeling and Surveillance Project, which is part of the NASA Applied Sciences Public Health Applications Program, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) identification of the potential breeding sites for major vector species; 2) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity; 3) implementation of a dynamic transmission model to identify the key factors that sustain or intensify malaria transmission. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. !> Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of the remotely sensed parameters. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Discrete event simulations are used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results are in good agreement with mosquito vector and human malaria data acquired by Coleman et al. over 4.5 years in Kong Mong Tha, a remote village in western Thailand. Application of our models is not restricted to the Greater Mekong Subregion. Our models have been applied to malaria in Indonesia, Korea, and other regions in the world with similar success.

Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

PubMed

Uneke, C J

2008-06-01

Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial.

PubMed

Samuels, Aaron M; Awino, Nobert; Odongo, Wycliffe; Abong'o, Benard; Gimnig, John; Otieno, Kephas; Shi, Ya Ping; Were, Vincent; Allen, Denise Roth; Were, Florence; Sang, Tony; Obor, David; Williamson, John; Hamel, Mary J; Patrick Kachur, S; Slutsker, Laurence; Lindblade, Kim A; Kariuki, Simon; Desai, Meghna

2017-06-07

Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

Monitoring of Plasmodium infection in humans and potential vectors of malaria in a newly emerged focus in southern Iran

PubMed Central

Kalantari, Mohsen; Soltani, Zahra; Ebrahimi, Mostafa; Yousefi, Masoud; Amin, Masoumeh; Shafiei, Ayda; Azizi, Kourosh

2017-01-01

Despite control programs, which aim to eliminate malaria from Iran by 2025, transmission of malaria has not been removed from the country. This study aimed to monitor malaria from asymptomatic parasitaemia and clinical cases from about one year of active case surveillance and potential vectors of malaria in the newly emerged focus of Mamasani and Rostam, southern Iran during 2014–2015. Samples were collected and their DNAs were extracted for Polymerase Chain Reaction (PCR) assay using specific primers for detection of Plasmodium species. The Annual Parasite Incidence rate (API) was three cases per 1,000 population from 2,000 individuals in three villages. Parasites species were detected in 9 out of the 4,000 blood smear samples among which, 6 cases were indigenous and had no history of travels to endemic areas of malaria. Also, the prevalence rate of asymptomatic parasites was about 0.3%. Overall, 1073 Anopheles spp. were caught from 9 villages. Totally, 512 female samples were checked by PCR, which indicated that none of them was infected with Plasmodium. Despite new malaria local transmission in humans in Mamasani and Rostam districts, no infection with Plasmodium was observed in Anopheles species. Because of neighboring of the studied area to the re-emerged focus in Fars province (Kazerun) and important endemic foci of malaria in other southern provinces, such as Hormozgan and Kerman, monitoring of the vectors and reservoir hosts of Plasmodium species would be unavoidable. Application of molecular methods, such as PCR, can simplify access to the highest level of accuracy in malaria researches. PMID:28078947

Spatial and temporal distribution of falciparum malaria in China

PubMed Central

Lin, Hualiang; Lu, Liang; Tian, Linwei; Zhou, Shuisen; Wu, Haixia; Bi, Yan; Ho, Suzanne C; Liu, Qiyong

2009-01-01

Background Falciparum malaria is the most deadly among the four main types of human malaria. Although great success has been achieved since the launch of the National Malaria Control Programme in 1955, malaria remains a serious public health problem in China. This paper aimed to analyse the geographic distribution, demographic patterns and time trends of falciparum malaria in China. Methods The annual numbers of falciparum malaria cases during 1992–2003 and the individual case reports of each clinical falciparum malaria during 2004–2005 were extracted from communicable disease information systems in China Center for Diseases Control and Prevention. The annual number of cases and the annual incidence were mapped by matching them to corresponding province- and county-level administrative units in a geographic information system. The distribution of falciparum malaria by age, gender and origin of infection was analysed. Time-series analysis was conducted to investigate the relationship between the falciparum malaria in the endemic provinces and the imported falciparum malaria in non-endemic provinces. Results Falciparum malaria was endemic in two provinces of China during 2004–05. Imported malaria was reported in 26 non-endemic provinces. Annual incidence of falciparum malaria was mapped at county level in the two endemic provinces of China: Yunnan and Hainan. The sex ratio (male vs. female) for the number of cases in Yunnan was 1.6 in the children of 0–15 years and it reached 5.7 in the adults over 15 years of age. The number of malaria cases in Yunnan was positively correlated with the imported malaria of concurrent months in the non-endemic provinces. Conclusion The endemic area of falciparum malaria in China has remained restricted to two provinces, Yunnan and Hainan. Stable transmission occurs in the bordering region of Yunnan and the hilly-forested south of Hainan. The age and gender distribution in the endemic area is characterized by the predominance of adult men cases. Imported falciparum malaria in the non-endemic area of China, affected mainly by the malaria transmission in Yunnan, has increased both spatially and temporally. Specific intervention measures targeted at the mobile population groups are warranted. PMID:19523209

CD8+ T-cell mediated anti-malaria protection induced by malaria vaccines; assessment of hepatic CD8+ T cells by SCBC assay.

PubMed

Zhou, Jing; Kaiser, Alaina; Ng, Colin; Karcher, Rachel; McConnell, Tim; Paczkowski, Patrick; Fernandez, Cristina; Zhang, Min; Mackay, Sean; Tsuji, Moriya

2017-07-03

Malaria is a severe infectious disease with relatively high mortality, thus having been a scourge of humanity. There are a few candidate malaria vaccines that have shown a protective efficacy in humans against malaria. One of the candidate human malaria vaccines, which is based on human malaria sporozoites and called PfSPZ Vaccine, has been shown to protect a significant proportion of vaccine recipients from getting malaria. PfSPZ Vaccine elicits a potent response of hepatic CD8+ T cells that are specific for malaria antigens in non-human primates. To further characterize hepatic CD8+ T cells induced by the sporozoite-based malaria vaccine in a mouse model, we have used a cutting-edge Single-cell Barcode (SCBC) assay, a recently emerged approach/method for investigating the nature of T-cells responses during infection or cancer. Using the SCBC technology, we have identified a population of hepatic CD8+ T cells that are polyfunctional at a single cell level only in a group of vaccinated mice upon malaria challenge. The cytokines/chemokines secreted by these polyfunctional CD8+ T-cell subsets include MIP-1α, RANTES, IFN-γ, and/or IL-17A, which have shown to be associated with protective T-cell responses against certain pathogens. Therefore, a successful induction of such polyfunctional hepatic CD8+ T cells may be a key to the development of effective human malaria vaccine. In addition, the SCBC technology could provide a new level of diagnostic that will allow for a more accurate determination of vaccine efficacy.

Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon.

PubMed

Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G

2015-09-01

The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts.

Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

PubMed Central

Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G.

2015-01-01

Background The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. Methods We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Findings Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. Interpretation This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts. PMID:26501116

The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial

PubMed Central

2013-01-01

Background Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. Trial registration NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012. PMID:23374910

Epidemiology of Plasmodium vivax Malaria in Peru

PubMed Central

Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

2016-01-01

Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639

Role of Activins in Hepcidin Regulation during Malaria.

PubMed

Spottiswoode, Natasha; Armitage, Andrew E; Williams, Andrew R; Fyfe, Alex J; Biswas, Sumi; Hodgson, Susanne H; Llewellyn, David; Choudhary, Prateek; Draper, Simon J; Duffy, Patrick E; Drakesmith, Hal

2017-12-01

Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life-threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway and found that Bmp gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of Plasmodium berghei -infected mice; hepatic activin B was also upregulated at peak parasitemia during infection with Plasmodium chabaudi Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naive volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins do not stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signaling pathway is perturbed in malaria infection but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting. Copyright © 2017 Spottiswoode et al.

Re-imagining malaria: heterogeneity of human and mosquito behaviour in relation to residual malaria transmission in Cambodia.

PubMed

Gryseels, Charlotte; Durnez, Lies; Gerrets, René; Uk, Sambunny; Suon, Sokha; Set, Srun; Phoeuk, Pisen; Sluydts, Vincent; Heng, Somony; Sochantha, Tho; Coosemans, Marc; Peeters Grietens, Koen

2015-04-24

In certain regions in Southeast Asia, where malaria is reduced to forested regions populated by ethnic minorities dependent on slash-and-burn agriculture, malaria vector populations have developed a propensity to feed early and outdoors, limiting the effectiveness of long-lasting insecticide-treated nets (LLIN) and indoor residual spraying (IRS). The interplay between heterogeneous human, as well as mosquito behaviour, radically challenges malaria control in such residual transmission contexts. This study examines human behavioural patterns in relation to the vector behaviour. The anthropological research used a sequential mixed-methods study design in which quantitative survey research methods were used to complement findings from qualitative ethnographic research. The qualitative research existed of in-depth interviews and participant observation. For the entomological research, indoor and outdoor human landing collections were performed. All research was conducted in selected villages in Ratanakiri province, Cambodia. Variability in human behaviour resulted in variable exposure to outdoor and early biting vectors: (i) indigenous people were found to commute between farms in the forest, where malaria exposure is higher, and village homes; (ii) the indoor/outdoor biting distinction was less clear in forest housing often completely or partly open to the outside; (iii) reported sleeping times varied according to the context of economic activities, impacting on the proportion of infections that could be accounted for by early or nighttime biting; (iv) protection by LLINs may not be as high as self-reported survey data indicate, as observations showed around 40% (non-treated) market net use while (v) unprotected evening resting and deep forest activities impacted further on the suboptimal use of LLINs. The heterogeneity of human behaviour and the variation of vector densities and biting behaviours may lead to a considerable proportion of exposure occurring during times that people are assumed to be protected by the distributed LLINs. Additional efforts in improving LLIN use during times when people are resting in the evening and during the night might still have an impact on further reducing malaria transmission in Cambodia.

Phosphoethanolamine-N-methyltransferase is a potential biomarker for the diagnosis of P. knowlesi and P. falciparum malaria

PubMed Central

2018-01-01

Background Plasmodium knowlesi is recognised as the main cause of human malaria in Southeast Asia. The disease is often misdiagnosed as P. falciparum or P. malariae infections by microscopy, and the disease is difficult to eliminate due to its presence in both humans and monkeys. P. knowlesi infections can rapidly cause severe disease and require prompt diagnosis and treatment. No protein biomarker exists for the rapid diagnostic test (RDT) detection of P. knowlesi infections. Plasmodium knowlesi infections can be diagnosed by PCR. Methods and principal findings Phosphoethanolamine-N-methyltransferase (PMT) is involved in malaria lipid biosynthesis and is not found in the human host. The P. falciparum, P. vivax and P. knowlesi PMT proteins were recombinantly expressed in BL21(DE3) Escherichia coli host cells, affinity purified and used to raise antibodies in chickens. Antibodies against each recombinant PMT protein all detected all three recombinant proteins and the native 29 kDa P. falciparum PMT protein on western blots and in ELISA. Antibodies against a PMT epitope (PLENNQYTDEGVKC) common to all three PMT orthologues detected all three proteins. Antibodies against unique peptides from each orthologue of PMT, PfCEVEHKYLHENKE, PvVYSIKEYNSLKDC, PkLYPTDEYNSLKDC detected only the parent protein in western blots and P. falciparum infected red blood cell lysates or blood lysates spiked with the respective proteins. Similar concentrations of PfPMT and the control, PfLDH, were detected in the same parasite lysate. The recombinant PfPMT protein was detected by a human anti-malaria antibody pool. Conclusion PMT, like the pan-specific LDH biomarker used in RDT tests, is both soluble, present at comparable concentrations in the parasite and constitutes a promising antimalarial drug target. PMT is absent from the human proteome. PMT has the potential as a biomarker for human malaria and in particular as the first P. knowlesi specific protein with diagnostic potential for the identification of a P. knowlesi infection. PMID:29505599

Phosphoethanolamine-N-methyltransferase is a potential biomarker for the diagnosis of P. knowlesi and P. falciparum malaria.

PubMed

Krause, Robert G E; Goldring, J P Dean

2018-01-01

Plasmodium knowlesi is recognised as the main cause of human malaria in Southeast Asia. The disease is often misdiagnosed as P. falciparum or P. malariae infections by microscopy, and the disease is difficult to eliminate due to its presence in both humans and monkeys. P. knowlesi infections can rapidly cause severe disease and require prompt diagnosis and treatment. No protein biomarker exists for the rapid diagnostic test (RDT) detection of P. knowlesi infections. Plasmodium knowlesi infections can be diagnosed by PCR. Phosphoethanolamine-N-methyltransferase (PMT) is involved in malaria lipid biosynthesis and is not found in the human host. The P. falciparum, P. vivax and P. knowlesi PMT proteins were recombinantly expressed in BL21(DE3) Escherichia coli host cells, affinity purified and used to raise antibodies in chickens. Antibodies against each recombinant PMT protein all detected all three recombinant proteins and the native 29 kDa P. falciparum PMT protein on western blots and in ELISA. Antibodies against a PMT epitope (PLENNQYTDEGVKC) common to all three PMT orthologues detected all three proteins. Antibodies against unique peptides from each orthologue of PMT, PfCEVEHKYLHENKE, PvVYSIKEYNSLKDC, PkLYPTDEYNSLKDC detected only the parent protein in western blots and P. falciparum infected red blood cell lysates or blood lysates spiked with the respective proteins. Similar concentrations of PfPMT and the control, PfLDH, were detected in the same parasite lysate. The recombinant PfPMT protein was detected by a human anti-malaria antibody pool. PMT, like the pan-specific LDH biomarker used in RDT tests, is both soluble, present at comparable concentrations in the parasite and constitutes a promising antimalarial drug target. PMT is absent from the human proteome. PMT has the potential as a biomarker for human malaria and in particular as the first P. knowlesi specific protein with diagnostic potential for the identification of a P. knowlesi infection.

Integrated Approach to Malaria Control

PubMed Central

Shiff, Clive

2002-01-01

Malaria draws global attention in a cyclic manner, with interest and associated financing waxing and waning according to political and humanitarian concerns. Currently we are on an upswing, which should be carefully developed. Malaria parasites have been eliminated from Europe and North America through the use of residual insecticides and manipulation of environmental and ecological characteristics; however, in many tropical and some temperate areas the incidence of disease is increasing dramatically. Much of this increase results from a breakdown of effective control methods developed and implemented in the 1960s, but it has also occurred because of a lack of trained scientists and control specialists who live and work in the areas of endemic infection. Add to this the widespread resistance to the most effective antimalarial drug, chloroquine, developing resistance to other first-line drugs such as sulfadoxine-pyrimethamine, and resistance of certain vector species of mosquito to some of the previously effective insecticides and we have a crisis situation. Vaccine research has proceeded for over 30 years, but as yet there is no effective product, although research continues in many promising areas. A global strategy for malaria control has been accepted, but there are critics who suggest that the single strategy cannot confront the wide range of conditions in which malaria exists and that reliance on chemotherapy without proper control of drug usage and diagnosis will select for drug resistant parasites, thus exacerbating the problem. An integrated approach to control using vector control strategies based on the biology of the mosquito, the epidemiology of the parasite, and human behavior patterns is needed to prevent continued upsurge in malaria in the endemic areas. PMID:11932233

Contributions of Anopheles larval control to malaria suppression in tropical Africa: review of achievements and potential.

PubMed

Walker, K; Lynch, M

2007-03-01

Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets.

Reappraisal of known malaria resistance loci in a large multi-centre study

PubMed Central

Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

2015-01-01

Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

The Invisible and Indeterminable Value of Ecology: From Malaria Control to Ecological Research in the American South.

PubMed

Way, Albert G

2015-06-01

This essay tells the story of the Emory University Field Station, a malaria research station in southwest Georgia that operated from 1939 to 1958. Using the tools of environmental history and the history of science, it examines the station's founding, its fieldwork, and its place within the broader history of malaria control, eradication, and research. A joint effort of Emory University, the U.S. Public Health Service, and the Communicable Disease Center (CDC), this station was closely aligned with a broader movement of ideas about tropical diseases across the globe, but it also offers a case study of how science in the field can veer from mainstream thinking and official policy. As the CDC and other disease-fighting organizations were moving toward a global strategy of malaria eradication through the use of DDT, the Emory Field Station developed a postsanitarian approach to malaria. Drawing on resistance among American conservationists to environmental transformation in the name of malaria control, the station's staff embraced the science and worldview of ecology in an effort to lighten public health's hand on the land and to link human health to the environment in innovative, if sometimes opaque, ways. This essay, then, argues that the Emory Field Station represents an early confluence of ecology with the biomedical sciences, something very similar to what is now the important discipline of disease ecology.

Malaria

MedlinePlus

Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... Malaria is caused by a parasite that is passed to humans by the bite of infected anopheles ...

Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013.

PubMed

Genito, Christopher J; Beck, Zoltan; Phares, Timothy W; Kalle, Fanta; Limbach, Keith J; Stefaniak, Maureen E; Patterson, Noelle B; Bergmann-Leitner, Elke S; Waters, Norman C; Matyas, Gary R; Alving, Carl R; Dutta, Sheetij

2017-07-05

Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts of the world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30years of effort and resources invested in solving this problem. Antibodies to a malaria vaccine candidate circumsporozoite protein (CSP) can block invasion and can protect humans against malaria. We have manufactured the Falciparum Malaria Protein-013 (FMP013) vaccine based on the nearly full-length P. falciparum CSP 3D7 strain sequence. We report here immunogenicity and challenge data on FMP013 antigen in C57BL/6 mice formulated with two novel adjuvants of the Army Liposome Formulation (ALF) series and a commercially available adjuvant Montanide ISA 720 (Montanide) as a control. ALF is a liposomal adjuvant containing a synthetic monophosphoryl lipid A (3D-PHAD®). In our study, FMP013 was adjuvanted with ALF alone, ALF containing aluminum hydroxide (ALFA) or ALF containing QS-21 (ALFQ). Adjuvants ALF and ALFA induced similar antibody titers and protection against transgenic parasite challenge that were comparable to Montanide. ALFQ was superior to the other three adjuvants as it induced higher antibody titers with improved boosting after the third immunization, higher serum IgG2c titers, and enhanced protection. FMP013+ALFQ also augmented the numbers of splenic germinal center-derived activated B-cells and antibody secreting cells compared to Montanide. Further, FMP013+ALFQ induced antigen-specific IFN-γ ELISPOT activity, CD4 + T-cells and a T H 1-biased cytokine profile. These results demonstrate that soluble CSP can induce a potent and sterile protective immune response when formulated with the QS-21 containing adjuvant ALFQ. Comparative mouse immunogenicity data presented here were used as the progression criteria for an ongoing non-human primate study and a regulatory toxicology study in preparation for a controlled human malaria infection (CHMI) trial. Published by Elsevier Ltd.

Most outdoor malaria transmission by behaviourally-resistant Anopheles arabiensis is mediated by mosquitoes that have previously been inside houses.

PubMed

Killeen, Gerry F; Govella, Nicodem J; Lwetoijera, Dickson W; Okumu, Fredros O

2016-04-19

Anopheles arabiensis is stereotypical of diverse vectors that mediate residual malaria transmission globally, because it can feed outdoors upon humans or cattle, or enter but then rapidly exit houses without fatal exposure to insecticidal nets or sprays. Life histories of a well-characterized An. arabiensis population were simulated with a simple but process-explicit deterministic model and relevance to other vectors examined through sensitivity analysis. Where most humans use bed nets, two thirds of An. arabiensis blood feeds and half of malaria transmission events were estimated to occur outdoors. However, it was also estimated that most successful feeds and almost all (>98 %) transmission events are preceded by unsuccessful attempts to attack humans indoors. The estimated proportion of vector blood meals ultimately obtained from humans indoors is dramatically attenuated by availability of alternative hosts, or partial ability to attack humans outdoors. However, the estimated proportion of mosquitoes old enough to transmit malaria, and which have previously entered a house at least once, is far less sensitive to both variables. For vectors with similarly modest preference for cattle over humans and similar ability to evade fatal indoor insecticide exposure once indoors, >80 % of predicted feeding events by mosquitoes old enough to transmit malaria are preceded by at least one house entry event, so long as ≥40 % of attempts to attack humans occur indoors and humans outnumber cattle ≥4-fold. While the exact numerical results predicted by such a simple deterministic model should be considered only approximate and illustrative, the derived conclusions are remarkably insensitive to substantive deviations from the input parameter values measured for this particular An. arabiensis population. This life-history analysis, therefore, identifies a clear, broadly-important opportunity for more effective suppression of residual malaria transmission by An. arabiensis in Africa and other important vectors of residual transmission across the tropics. Improved control of predominantly outdoor residual transmission by An. arabiensis, and other modestly zoophagic vectors like Anopheles darlingi, which frequently enter but then rapidly exit from houses, may be readily achieved by improving existing technology for killing mosquitoes indoors.

Attributing Climate Conditions for Stable Malaria Transmission to Human Activity in sub-Saharan Africa

NASA Astrophysics Data System (ADS)

Sheldrake, L.; Mitchell, D.; Allen, M. R.

2015-12-01

Temperature and precipitation limit areas of stable malaria transmission, but the effects of climate change on the disease remain controversial. Previously, studies have not separated the influence of anthropogenic climate change and natural variability, despite being an essential step in the attribution of climate change impacts. Ensembles of 2900 simulations of regional climate in sub-Saharan Africa for the year 2013, one representing realistic conditions and the other how climate might have been in the absence of human influence, were used to force a P.falciparium climate suitability model developed by the Mapping Malaria Risk in Africa project. Strongest signals were detected in areas of unstable transmission, indicating their heightened sensitivity to climatic factors. Evidently, impacts of human-induced climate change were unevenly distributed: the probability of conditions being suitable for stable malaria transmission were substantially reduced (increased) in the Sahel (Greater Horn of Africa (GHOA), particularly in the Ethiopian and Kenyan highlands). The length of the transmission season was correspondingly shortened in the Sahel and extended in the GHOA, by 1 to 2 months, including in Kericho (Kenya), where the role of climate change in driving recent malaria occurrence is hotly contested. Human-induced warming was primarily responsible for positive anomalies in the GHOA, while reduced rainfall caused negative anomalies in the Sahel. The latter was associated with anthropogenic impacts on the West African Monsoon, but uncertainty in the RCM's ability to reproduce precipitation trends in the region weakens confidence in the result. That said, outputs correspond well with broad-scale changes in observed endemicity, implying a potentially important contribution of anthropogenic climate change to the malaria burden during the past century. Results support the health-framing of climate risk and help indicate hotspots of climate vulnerability, providing information to direct control interventions and investment, and allude to climate injustices. Extending methods, such as by using multiple climate and malaria models and investigating trends over longer timescales, would make results more generally applicable and improve their policy relevance.

Epidemiology of Plasmodium vivax in Indonesia.

PubMed

Surjadjaja, Claudia; Surya, Asik; Baird, J Kevin

2016-12-28

Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. © The American Society of Tropical Medicine and Hygiene.

Epidemiology of Plasmodium vivax in Indonesia

PubMed Central

Surjadjaja, Claudia; Surya, Asik; Baird, J. Kevin

2016-01-01

Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax. The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. PMID:27708185

Malaria transmission and vector behaviour in a forested malaria focus in central Vietnam and the implications for vector control

PubMed Central

2010-01-01

Background In Vietnam, malaria is becoming progressively restricted to specific foci where human and vector characteristics alter the known malaria epidemiology, urging for alternative or adapted control strategies. Long-lasting insecticidal hammocks (LLIH) were designed and introduced in Ninh Thuan province, south-central Vietnam, to control malaria in the specific context of forest malaria. An entomological study in this specific forested environment was conducted to assess the behavioural patterns of forest and village vectors and to assess the spatio-temporal risk factors of malaria transmission in the province. Methods Five entomological surveys were conducted in three villages in Ma Noi commune and in five villages in Phuoc Binh commune in Ninh Thuan Province, south-central Vietnam. Collections were made inside the village, at the plot near the slash-and-burn fields in the forest and on the way to the forest. All collected mosquito species were subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium in the head-thoracic portion of individual mosquitoes after morphological identification. Collection data were analysed by use of correspondence and multivariate analyses. Results The mosquito density in the study area was low with on average 3.7 anopheline bites per man-night and 17.4 culicine bites per man-night. Plasmodium-infected mosquitoes were only found in the forest and on the way to the forest. Malaria transmission in the forested malaria foci was spread over the entire night, from dusk to dawn, but was most intense in the early evening as nine of the 13 Plasmodium positive bites occurred before 21H. The annual entomological inoculation rate of Plasmodium falciparum was 2.2 infective bites per person-year to which Anopheles dirus s.s. and Anopheles minimus s.s. contributed. The Plasmodium vivax annual entomological inoculation rate was 2.5 infective bites per person-year with Anopheles sawadwongporni, Anopheles dirus s.s. and Anopheles pampanai as vectors. Conclusion The vector behaviour and spatio-temporal patterns of malaria transmission in Southeast Asia impose new challenges when changing objectives from control to elimination of malaria and make it necessary to focus not only on the known main vector species. Moreover, effective tools to prevent malaria transmission in the early evening and in the early morning, when the treated bed net cannot be used, need to be developed. PMID:21182774

Malaria transmission and vector behaviour in a forested malaria focus in central Vietnam and the implications for vector control.

PubMed

Van Bortel, Wim; Trung, Ho Dinh; Hoi, Le Xuan; Van Ham, Nguyen; Van Chut, Nguyen; Luu, Nguyen Dinh; Roelants, Patricia; Denis, Leen; Speybroeck, Niko; D'Alessandro, Umberto; Coosemans, Marc

2010-12-23

In Vietnam, malaria is becoming progressively restricted to specific foci where human and vector characteristics alter the known malaria epidemiology, urging for alternative or adapted control strategies. Long-lasting insecticidal hammocks (LLIH) were designed and introduced in Ninh Thuan province, south-central Vietnam, to control malaria in the specific context of forest malaria. An entomological study in this specific forested environment was conducted to assess the behavioural patterns of forest and village vectors and to assess the spatio-temporal risk factors of malaria transmission in the province. Five entomological surveys were conducted in three villages in Ma Noi commune and in five villages in Phuoc Binh commune in Ninh Thuan Province, south-central Vietnam. Collections were made inside the village, at the plot near the slash-and-burn fields in the forest and on the way to the forest. All collected mosquito species were subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium in the head-thoracic portion of individual mosquitoes after morphological identification. Collection data were analysed by use of correspondence and multivariate analyses. The mosquito density in the study area was low with on average 3.7 anopheline bites per man-night and 17.4 culicine bites per man-night. Plasmodium-infected mosquitoes were only found in the forest and on the way to the forest. Malaria transmission in the forested malaria foci was spread over the entire night, from dusk to dawn, but was most intense in the early evening as nine of the 13 Plasmodium positive bites occurred before 21H. The annual entomological inoculation rate of Plasmodium falciparum was 2.2 infective bites per person-year to which Anopheles dirus s.s. and Anopheles minimus s.s. contributed. The Plasmodium vivax annual entomological inoculation rate was 2.5 infective bites per person-year with Anopheles sawadwongporni, Anopheles dirus s.s. and Anopheles pampanai as vectors. The vector behaviour and spatio-temporal patterns of malaria transmission in Southeast Asia impose new challenges when changing objectives from control to elimination of malaria and make it necessary to focus not only on the known main vector species. Moreover, effective tools to prevent malaria transmission in the early evening and in the early morning, when the treated bed net cannot be used, need to be developed.

The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial

PubMed Central

Bradley, John; Knight, Philip; Stone, William; Osoti, Victor; Makori, Euniah; Owaga, Chrispin; Odongo, Wycliffe; China, Pauline; Shagari, Shehu; Doumbo, Ogobara K.; Sauerwein, Robert W.; Kariuki, Simon; Drakeley, Chris; Stevenson, Jennifer; Cox, Jonathan

2016-01-01

Background Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons. Conclusions Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear. Trial registration ClinicalTrials.gov NCT01575613 PMID:27071072

Malaria Modeling using Remote Sensing and GIS Technologies

NASA Technical Reports Server (NTRS)

Kiang, Richard

2004-01-01

Malaria has been with the human race since the ancient time. In spite of the advances of biomedical research and the completion of genomic mapping of Plasmodium falciparum, the exact mechanisms of how the various strains of parasites evade the human immune system and how they have adapted and become resistant to multiple drugs remain elusive. Perhaps because of these reasons, effective vaccines against malaria are still not available. Worldwide, approximately one to three millions deaths are attributed to malaria annually. With the increased availability of remotely sensed data, researchers in medical entomology, epidemiology and ecology have started to associate environmental and ecological variables with malaria transmission. In several studies, it has been shown that transmission correlates well with certain environmental and ecological parameters, and that remote sensing can be used to measure these determinants. In a NASA project, we have taken a holistic approach to examine how remote sensing and GIs can contribute to vector and malaria controls. To gain a better understanding of the interactions among the possible promoting factors, we have been developing a habitat model, a transmission model, and a risk prediction model, all using remote sensing data as input. Our objectives are: 1) To identify the potential breeding sites of major vector species and the locations for larvicide and insecticide applications in order to reduce costs, lessen the chance of developing pesticide resistance, and minimize the damage to the environment; 2) To develop a malaria transmission model characterizing the interactions among hosts, vectors, parasites, landcover and environment in order to identify the key factors that sustain or intensify malaria transmission, and 3) To develop a risk model to predict the occurrence of malaria and its transmission intensity using epidemiological data and satellite-derived or ground-measured environmental and meteorological data.

Severe Flooding and Malaria Transmission in the Western Ugandan Highlands: Implications for Disease Control in an Era of Global Climate Change.

PubMed

Boyce, Ross; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Metlay, Joshua P; Band, Lawrence; Siedner, Mark J

2016-11-01

 There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa.  We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations between villages (1) at high versus low elevations, (2) with versus without rivers, and (3) upstream versus downstream before and after severe flooding that occurred in Kasese District, Western Region, Uganda, in May 2013.  During the study period, 7596 diagnostic tests were performed, and 1285 patients were admitted with a diagnosis of malaria. We observed that extreme flooding resulted in an increase of approximately 30% in the risk of an individual having a positive result of a malaria diagnostic test in the postflood period in villages bordering a flood-affected river, compared with villages farther from a river, with a larger relative impact on upstream versus downstream villages (adjusted rate ratio, 1.91 vs 1.33).  Extreme precipitation such as the flooding described here may pose significant challenges to malaria control programs and will demand timely responses to mitigate deleterious impacts on human health. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Mapping Physiological Suitability Limits for Malaria in Africa Under Climate Change.

PubMed

Ryan, Sadie J; McNally, Amy; Johnson, Leah R; Mordecai, Erin A; Ben-Horin, Tal; Paaijmans, Krijn; Lafferty, Kevin D

2015-12-01

We mapped current and future temperature suitability for malaria transmission in Africa using a published model that incorporates nonlinear physiological responses to temperature of the mosquito vector Anopheles gambiae and the malaria parasite Plasmodium falciparum. We found that a larger area of Africa currently experiences the ideal temperature for transmission than previously supposed. Under future climate projections, we predicted a modest increase in the overall area suitable for malaria transmission, but a net decrease in the most suitable area. Combined with human population density projections, our maps suggest that areas with temperatures suitable for year-round, highest-risk transmission will shift from coastal West Africa to the Albertine Rift between the Democratic Republic of Congo and Uganda, whereas areas with seasonal transmission suitability will shift toward sub-Saharan coastal areas. Mapping temperature suitability places important bounds on malaria transmissibility and, along with local level demographic, socioeconomic, and ecological factors, can indicate where resources may be best spent on malaria control.

Mapping physiological suitability limits for malaria in Africa under climate change

USGS Publications Warehouse

Ryan, Sadie J.; McNally, Amy; Johnson, Leah R.; Mordecai, Erin A.; Ben-Horin, Tal; Paaijmans, Krijn P.; Lafferty, Kevin D.

2015-01-01

We mapped current and future temperature suitability for malaria transmission in Africa using a published model that incorporates nonlinear physiological responses to temperature of the mosquito vector Anopheles gambiae and the malaria parasite Plasmodium falciparum. We found that a larger area of Africa currently experiences the ideal temperature for transmission than previously supposed. Under future climate projections, we predicted a modest increase in the overall area suitable for malaria transmission, but a net decrease in the most suitable area. Combined with human population density projections, our maps suggest that areas with temperatures suitable for year-round, highest-risk transmission will shift from coastal West Africa to the Albertine Rift between the Democratic Republic of Congo and Uganda, whereas areas with seasonal transmission suitability will shift toward sub-Saharan coastal areas. Mapping temperature suitability places important bounds on malaria transmissibility and, along with local level demographic, socioeconomic, and ecological factors, can indicate where resources may be best spent on malaria control.

Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study.

PubMed

Grigg, Matthew J; Cox, Jonathan; William, Timothy; Jelip, Jenarun; Fornace, Kimberly M; Brock, Patrick M; von Seidlein, Lorenz; Barber, Bridget E; Anstey, Nicholas M; Yeo, Tsin W; Drakeley, Christopher J

2017-06-09

The emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk. We did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR-confirmed malaria who presented to two primary referral hospitals serving the adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria-negative community controls per case, who were matched by village within 2 weeks of case detection. We obtained questionnaire data on demographics, behaviour, and residential malaria risk factors, and we also assessed glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression models to evaluate exposure risk between P knowlesi cases and controls, and between P knowlesi and human-only Plasmodium spp malaria cases. From Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled 229 cases with P knowlesi malaria mono-infection and 91 cases with other Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched to P knowlesi cases and 270 matched to non- P knowlesi cases. Age 15 years or older (adjusted odds ratio [aOR] 4·16, 95% CI 2·09-8·29, p<0·0001), male gender (4·20, 2·54-6·97, p<0·0001), plantation work (3·50, CI, 1·34-9·15, p=0·011), sleeping outside (3·61, 1·48-8·85, p=0·0049), travel (2·48, 1·45-4·23, p=0·0010), being aware of the presence of monkeys in the past 4 weeks (3·35, 1·91-5·88, p<0·0001), and having open eaves or gaps in walls (2·18, 1·33-3·59, p=0·0021) were independently associated with increased risk of symptomatic P knowlesi infection. Farming occupation (aOR 1·89, 95% CI 1·07-3·35, p=0·028), clearing vegetation (1·89, 1·11-3·22, p=0·020), and having long grass around the house (2·08, 1·25-3·46, p=0·0048) increased risk for P knowlesi infection but not other Plasmodium spp infection. G6PD deficiency seemed to be protective against P knowlesi (aOR 0·20, 95% CI 0·04-0·96, p=0·045), as did residual insecticide spraying of household walls (0·52, 0·31-0·87, p=0·014), with the presence of young sparse forest (0·35, 0·20-0·63, p=00040) and rice paddy around the house (0·16, 0·03-0·78, 0·023) also associated with decreased risk. Adult men working in agricultural areas were at highest risk of knowlesi malaria, although peri-domestic transmission also occurrs. Human behavioural factors associated with P knowlesi transmission could be targeted in future public health interventions. United Kingdom Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.

Epidemiology of Plasmodium vivax Malaria in Peru.

PubMed

Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E; Moreno, Marta; Lescano, Andres G; Sanchez, Juan F; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M

2016-12-28

Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine-primaquine for P. vivax Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. © The American Society of Tropical Medicine and Hygiene.

Recent advances in malaria drug discovery.

PubMed

Lanteri, Charlotte A; Johnson, Jacob D; Waters, Norman C

2007-06-01

Malaria is responsible for over 300 million clinical cases annually and claims the lives of approximately 1-2 million. With a disease that has plagued humanity throughout history, one would think that better control measures would be in place to decrease the mortality and morbidity associated with malaria. Due to malaria drug resistance, an increase in the number of clinical infections and deaths is soon likely to be observed. Therefore, there is a push to identify and introduce new drug entities for malaria treatment and prophylaxis. In an effort to develop new malaria drugs, several different approaches have been implemented. These include the use of drug combinations of either new or existing antimalarials, exploitation of natural products, identification of resistance reversal or sensitizing agents and the targeting of specific malarial enzymes. Past experience has shown that introduction of the same chemical entities, such as quinolines and antifolates, results in only limited efficacy with resistance developing rapidly within one year of introduction. New approaches to drug discovery should identify novel chemotypes which circumvent the parasite's disposition to drug resistance. This review summarizes current efforts in malaria drug discovery as uncovered in recent patent literature.

Two complement receptor one alleles have opposing associations with cerebral malaria and interact with α+thalassaemia.

PubMed

Opi, D Herbert; Swann, Olivia; Macharia, Alexander; Uyoga, Sophie; Band, Gavin; Ndila, Carolyne M; Harrison, Ewen M; Thera, Mahamadou A; Kone, Abdoulaye K; Diallo, Dapa A; Doumbo, Ogobara K; Lyke, Kirsten E; Plowe, Christopher V; Moulds, Joann M; Shebbe, Mohammed; Mturi, Neema; Peshu, Norbert; Maitland, Kathryn; Raza, Ahmed; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N; Rowe, J Alexandra

2018-04-25

Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One ( CR1 ) gene, named Sl2 and McC b , occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, we estimate the relationship between Sl2 and McC b and malaria phenotypes, and find they have opposing associations. The Sl2 polymorphism is associated with markedly reduced odds of cerebral malaria and death, while the McC b polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and α + thalassaemia, with the protective association of Sl2 greatest in children with normal α-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies. © 2018, Opi et al.

Impact of interventions on malaria in internally displaced persons along the China-Myanmar border: 2011-2014.

PubMed

Zhou, Guofa; Lo, Eugenia; Zhong, Daibin; Wang, Xiaoming; Wang, Ying; Malla, Sameer; Lee, Ming-Chieh; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

2016-09-15

Internally displaced persons (IDP) represent vulnerable populations whose public health conditions merit special attention. In the China-Myanmar border area, human movement and resettlements of IDP can influence malaria transmission. Comparison of disease incidence and vector densities between IDP camps and surrounding local villages allows for better understanding of current epidemiology and to evaluate the effectiveness of interventions in the region. Malaria and vector surveillance was conducted in three IDP camps and three local villages neighbouring the camps along the China-Myanmar border in Myanmar. Clinical malaria cases were collected from seven hospitals/clinics from April 2011 to December 2014. Malaria vector population dynamics were monitored using CDC light traps. The use of malaria preventive measures and information on aid agencies and their activities was obtained through questionnaire surveys. Malaria was confirmed in 1832 patients. Of these cases, 85.4 % were Plasmodium vivax and 11.4 % were Plasmodium falciparum malaria. Annual malaria incidence rates were 38.8 and 127.0 cases/1000 person year in IDP camps and local villages, respectively. Older children of 5-14 years had the highest incidence rate in the camps regardless of gender, while male adults had significantly higher incidence rates than females in local villages and females child-bearing age had significantly lower risk to malaria in IDP camps compare to local villages. Seasonal malaria outbreaks were observed both in the IDP camps and in the local villages from May to August 2013. The proportion of P. vivax remained unchanged in local villages but increased by approximately tenfold in IDP camps from 2011 to 2014. Anopheles vector density was tenfold higher in local villages compared to IDP camps (2.0:0.2 females/trap/night). Over 99 % of households in both communities owned bed nets. While long-lasting insecticidal nets accounted for 61 % of nets used in IDPs, nearly all residents of local villages owned regular nets without insecticide-impregnation. There were more active aid agencies in the camps than in local villages. Malaria in IDP camps was significantly lower than the surrounding villages through effective control management. The observation of P. vivax outbreaks in the study area highlights the need for increased control efforts. Expansion of malaria intervention strategies in IDP camps to local surrounding villages is critical to malaria control in the border area.

NITRIC OXIDE FOR THE ADJUNCTIVE TREATMENT OF SEVERE MALARIA: HYPOTHESIS AND RATIONALE

PubMed Central

Hawkes, Michael; Opoka, Robert Opika; Namasopo, Sophie; Miller, Christopher; Conroy, Andrea L.; Serghides, Lena; Kim, Hani; Thampi, Nisha; Liles, W. Conrad; John, Chandy C.; Kain, Kevin C.

2011-01-01

We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor L-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215). PMID:21745716

Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and Immunity.

PubMed

Minkah, Nana K; Schafer, Carola; Kappe, Stefan H I

2018-01-01

Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans. The ultimate goal is to develop humanized mouse systems in which a Plasmodium infection closely reproduces all stages of a parasite infection in humans, including pre-erythrocytic infection, blood stage infection and its associated pathology, transmission as well as the human immune response to infection. Here, we discuss current humanized mouse models and the future directions that should be taken to develop next-generation models for human malaria parasite research.

Impact of environmental changes and human-related factors on the potential malaria vector, Anopheles labranchiae (Diptera: Culicidae), in Maremma, Central Italy.

PubMed

Boccolini, D; Toma, L; Di Luca, M; Severini, F; Cocchi, M; Bella, A; Massa, A; Mancini Barbieri, F; Bongiorno, G; Angeli, L; Pontuale, G; Raffaelli, I; Fausto, A M; Tamburro, A; Romi, R

2012-07-01

The Maremma Plain (central Italy) was hyper-endemic for malaria until the mid-20th century, when a national campaign for malaria elimination drastically reduced the presence of the main vector Anopheles labranchiae Falleroni. However, the introduction of rice cultivation over 30 yr ago has led to an increase in the An. labranchiae population and concern over possible malaria reemergence. We studied the impact of anthropogenic environmental changes on the abundance and distribution of An. labranchiae in Maremma, focusing on rice fields, the main breeding sites. Adults and larvae were collected in three main areas with diverse ecological characteristics. Data were collected on human activity, land use, and seasonal climatic and demographic variations. We also interviewed residents and tourists regarding their knowledge of malaria. Our findings showed that the most important environmental changes have occurred along the coast; An. labranchiae foci are present throughout the area, with massive reproduction strictly related to rice cultivation in coastal areas. Although the abundance of this species has drastically decreased over the past 30 yr, it remains high and, together with climatic conditions and the potential introduction of gametocyte carriers, it may represent a threat for the occurrence of autochthonous malaria cases. Our findings suggest the need for the continuous monitoring of An. labranchiae in the study area. In addition to entomological surveillance, more detailed knowledge of human-induced environmental changes is needed, so as to have a more complete database that can be used for vector-control plans and for properly managing emergencies related to autochthonous introduced cases.

Dynamics of the Major Histocompatibility Complex Class I Processing and Presentation Pathway in the Course of Malaria Parasite Development in Human Hepatocytes: Implications for Vaccine Development

PubMed Central

Ma, Jinxia; Trop, Stefanie; Baer, Samantha; Rakhmanaliev, Elian; Arany, Zita; Dumoulin, Peter; Zhang, Hao; Romano, Julia; Coppens, Isabelle; Levitsky, Victor; Levitskaya, Jelena

2013-01-01

Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of the MHC class I pathway exhibit largely unaltered expression in malaria-infected hepatocytes until very late stages of parasite development. Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells. We further demonstrate that ectopic expression of circumsporozoite protein does not alter expression of critical genes of the MHC class I pathway and its response to pro-inflammatory cytokines. In addition, we identified supra-cellular structures, which arose at late stages of parasite replication, possessed the characteristic morphology of merosomes and exhibited nearly complete loss of surface MHC class I expression. These data have multiple implications for our understanding of natural T-cell immunity against malaria and may promote development of novel, efficient anti-malaria vaccines overcoming immune escape of the parasite in the liver. PMID:24086507

An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays

PubMed Central

Hancock, P.A; Thomas, M.B; Godfray, H.C.J

2008-01-01

It has recently been proposed that mosquito vectors of human diseases, particularly malaria, may be controlled by spraying with fungal biopesticides that increase the rate of adult mortality. Though fungal pathogens do not cause instantaneous mortality, they can kill mosquitoes before they are old enough to transmit disease. A model is developed (i) to explore the potential for fungal entomopathogens to reduce significantly infectious mosquito populations, (ii) to assess the relative value of the many different fungal strains that might be used, and (iii) to help guide the tactical design of vector-control programmes. The model follows the dynamics of different classes of adult mosquitoes with the risk of mortality due to the fungus being assumed to be a function of time since infection (modelled using the Weibull distribution). It is shown that substantial reductions in mosquito numbers are feasible for realistic assumptions about mosquito, fungus and malaria biology and moderate to low daily fungal infection probability. The choice of optimal fungal strain and spraying regime is shown to depend on local mosquito and malaria biology. Fungal pathogens may also influence the ability of mosquitoes to transmit malaria and such effects are shown to further reduce vectorial capacity. PMID:18765347

Spatial modeling of malaria incidence rates in Sistan and Baluchistan province, Islamic Republic of Iran.

PubMed

Salehi, Masoud; Mohammad, Kazem; Farahani, Mahmud M; Zeraati, Hojjat; Nourijelyani, Keramat; Zayeri, Farid

2008-12-01

To identify the effect of environmental factors on malaria risk, and to visualize spatial map of malaria standard incidence rates in Sistan and Baluchistan province, Islamic Republic of Iran. In this cross-sectional study, the data from 42,162 registered new malaria cases from 21 March 2001 (Iranian new year) to 21 of March 2006 were studied. To describe the statistical association between environmental factors and malaria risk, a generalized linear mixed model approach was utilized. In addition, we used the second ordered stationary Kriging, and a variogram to determine the appropriate spatial correlation structure among the malaria standard incidence rates, and provide a proper malaria risk map in the area under study. The obtained results from the spatial modeling revealed that humidity (p=0.0004), temperature (p<0.0001), and elevation (p<0.0001) were positively, and precipitation (p=0.0029) was inversely correlated with the malaria risk. Moreover, the malaria risk map based on the predicted values showed that the south part of this province (Baluchistan), has a higher risk of malaria, compared to the northern area (Sistan). Since the effective environmental factors on malaria risk are out of human's control, the health policy makers in this province should pay more attention to the areas with high temperature, elevation, and humidity, as well as, low rainfall districts.

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.

PubMed

Hodgson, Susanne H; Ewer, Katie J; Bliss, Carly M; Edwards, Nick J; Rampling, Thomas; Anagnostou, Nicholas A; de Barra, Eoghan; Havelock, Tom; Bowyer, Georgina; Poulton, Ian D; de Cassan, Simone; Longley, Rhea; Illingworth, Joseph J; Douglas, Alexander D; Mange, Pooja B; Collins, Katharine A; Roberts, Rachel; Gerry, Stephen; Berrie, Eleanor; Moyle, Sarah; Colloca, Stefano; Cortese, Riccardo; Sinden, Robert E; Gilbert, Sarah C; Bejon, Philip; Lawrie, Alison M; Nicosia, Alfredo; Faust, Saul N; Hill, Adrian V S

2015-04-01

Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development. NCT01623557. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Changes in malaria burden and transmission in sentinel sites after the roll-out of long-lasting insecticidal nets in Papua New Guinea.

PubMed

Hetzel, Manuel W; Reimer, Lisa J; Gideon, Gibson; Koimbu, Gussy; Barnadas, Céline; Makita, Leo; Siba, Peter M; Mueller, Ivo

2016-06-14

Papua New Guinea exhibits a complex malaria epidemiology due to diversity in malaria parasites, mosquito vectors, human hosts, and their natural environment. Heterogeneities in transmission and burden of malaria at various scales are likely to affect the success of malaria control interventions, and vice-versa. This manuscript assesses changes in malaria prevalence, incidence and transmission in sentinel sites following the first national distribution of long-lasting insecticidal nets (LLINs). Before and after the distribution of LLINs, data collection in six purposively selected sentinel sites included clinical surveillance in the local health facility, household surveys and entomological surveys. Not all activities were carried out in all sites. Mosquitoes were collected by human landing catches. Diagnosis of malaria infection in humans was done by rapid diagnostic test, light microscopy and PCR for species confirmation. Following the roll-out of LLINs, the average monthly malaria incidence rate dropped from 13/1,000 population to 2/1,000 (incidence rate ratio = 0.12; 95 % CI: 0.09-0.17; P < 0.001). The average population prevalence of malaria decreased from 15.7 % pre-LLIN to 4.8 % post-LLIN (adjusted odds ratio = 0.26; 95 % CI: 0.20-0.33; P < 0.001). In general, reductions in incidence and prevalence were more pronounced in infections with P. falciparum than with P. vivax. Additional morbidity indicators (anaemia, splenomegaly, self-reported fever) showed a decreasing trend in most sites. Mean Anopheles man biting rates decreased from 83 bites/person/night pre-LLIN to 31 post-LLIN (P = 0.008). Anopheles species composition differed between sites but everywhere diversity was lower post-LLIN. In two sites, post-LLIN P. vivax infections in anophelines had decreased but P. falciparum infections had increased despite the opposite observation in humans. LLIN distribution had distinct effects on P. falciparum and P. vivax. Higher resilience of P. vivax may be attributed to relapses from hypnozoites and other biological characteristics favouring the transmission of P. vivax. The effect on vector species composition varied by location which is likely to impact on the effectiveness of LLINs. In-depth and longer-term epidemiological and entomological investigations are required to understand when and where residual transmission occurs and whether observed changes are sustained.

Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.

PubMed

Hodgson, Susanne H; Juma, Elizabeth; Salim, Amina; Magiri, Charles; Njenga, Daniel; Molyneux, Sassy; Njuguna, Patricia; Awuondo, Ken; Lowe, Brett; Billingsley, Peter F; Cole, Andrew O; Ogwang, Caroline; Osier, Faith; Chilengi, Roma; Hoffman, Stephen L; Draper, Simon J; Ogutu, Bernhards; Marsh, Kevin

2015-04-28

Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries. An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa. This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested. Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.

Methodological problems and amendments to demonstrate effects of temperature on the epidemiology of malaria. A new perspective on the highland epidemics in Madagascar, 1972-89.

PubMed

Bouma, Menno Jan

2003-01-01

There is a growing consensus that changes in climate will have major consequences for human health through a reduction in the availability of food and an increasing frequency of natural disasters. However, the contribution of higher temperatures to vector-borne diseases, particularly malaria, remains controversial despite the known biological dependence of both vector and pathogen on climate. Misconceptions and inappropriate use of variables and methods have contributed to the controversy. At present there appears to be more support for non-climatic explanations to account for the resurgence of malaria in the African highlands, e.g. the deterioration of malaria control and the development of drug resistance. An attempt is made here to show that dismissing temperature as a driving force in the case of malaria is premature. Using a de-trended time-series of malaria incidence in Madagascar between 1972 and 1989 indicated that a minimum temperature during 2 months at the start of the transmission season can account for most of the variability between years (r2 = 0.66). These months correspond with the months when the human-vector (Anopheles gambiae sensu lato) contact is greatest. The relationship between El Niño Southern Oscillation (ENSO) and temperature (r = 0.79), and ENSO and malaria (r = 0.64), suggests that there might be an increased epidemic risk during post-Niño years in the Madagascar highlands and therefore warrants increased vigilance and extended control efforts in the first half of 2003. This review suggests that the rejection of climate-disease associations in studies so far published may not have used biologically relevant climate parameters. It highlights the importance of identifying more relevant parameters during critical periods of the transmission season in order to aid epidemic forecasting and to assess the potential impact of global warming.

Malaria Elimination: Time to Target All Species.

PubMed

Lover, Andrew A; Baird, J Kevin; Gosling, Roly; Price, Ric

2018-05-14

Important strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again under discussion. If the ambitious goal of eradication is to be achieved by 2040, all species of Plasmodium infecting humans will need to be targeted with evidence-based and concerted interventions. In this perspective, the potential barriers to achieving global malaria elimination are discussed with respect to the related diversities in host, parasite, and vector populations. We argue that control strategies need to be reorientated from a sequential attack on each species, dominated by Plasmodium falciparum to one that targets all species in parallel. A set of research themes is proposed to mitigate the potential setbacks on the pathway to a malaria-free world.

Hospitalizations and Costs Incurred at the Facility Level after Scale-up of Malaria Control: Pre-Post Comparisons from Two Hospitals in Zambia

PubMed Central

Comfort, Alison B.; van Dijk, Janneke H.; Mharakurwa, Sungano; Stillman, Kathryn; Gabert, Rose; Korde, Sonali; Nachbar, Nancy; Derriennic, Yann; Musau, Stephen; Hamazakaza, Petan; Zyambo, Khozya D.; Zyongwe, Nancy M.; Hamainza, Busiku; Thuma, Philip E.

2014-01-01

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with < 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions. PMID:24218409

Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminths attending Kampala International University Teaching Hospital, in Uganda.

PubMed

Bwanika, Richard; Kato, Charles D; Welishe, Johnson; Mwandah, Daniel C

2018-01-01

Malaria and helminths share the same geographical distribution in tropical Africa. Studies of the interaction of helminth and malaria co-infection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. This study aimed to determine Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminth attending Kampala International University Teaching Hospital (KIU). A case control study of 240 patients were recruited at KIU teaching hospital. Patients with Plasmodium falciparum malaria were 55 (22.9%) and those with soil-borne helminths were 63 (26.3%). The controls were 89 (37.1%), while those co-infected with Plasmodium falciparum malaria and soil-borne helminths were 33 (13.8%). Cases were defined as having a positive blood smear for P. falciparum malaria, those with helminths or co-infections of the two. Negative controls were those with a negative blood smear for P. falciparum malaria and those with no stool parasitic infections. Patients presenting with signs and symptoms of malaria or those suspected of having helminths were recruited for the study. A panel of five cytokines (IFN-γ, TNF-α, IL-6, TGF-β and IL-10) were assayed from plasma samples in patients with and without Plasmodium falciparum malaria, patients with and without helminth, and then those co-infected with the two diseases diagnosis was done using thick blood smears stained with 10% Giemsa and stool examination was done following the Kato Katz technique following standard procedures. The prevalence of Plasmodium falciparum malaria by sex was 28 (11.7%) and 27 (11.3%) in male and female respectively. The overall prevalence of soil borne helminth was 26.3%, and among those harbouring helminths, 13.8% were co-infected with Plasmodium falciparum. Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and health controls for IFN-γ (P = 0.023), IL-10 (P = 0.008) and TGF-β (P = 0.0001). Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and patients co-infected with Plasmodium falciparum malaria and soil borne helminth for IL-10 (P = 0.004), IL-6 (P = 0.011) and TGF-β (P = 0.003). An up-regulation of IFN-γ during Plasmodium falciparum malaria and an up-regulation of IL-10 and TGF-β in soil borne helminth infections was demonstrated. We demonstrate that co-infections of Plasmodium falciparum and soil borne helminth lead to an up-regulation of IL-10 and IL-6 and a down-regulation of TGF-β. Trial registration No17/10-16.

The Impact of Phenotypic and Genotypic G6PD Deficiency on Risk of Plasmodium vivax Infection: A Case-Control Study amongst Afghan Refugees in Pakistan

PubMed Central

Leslie, Toby; Briceño, Marnie; Mayan, Ismail; Mohammed, Nasir; Klinkenberg, Eveline; Sibley, Carol Hopkins; Whitty, Christopher J. M.; Rowland, Mark

2010-01-01

Background The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A−) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. Methods and Findings A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06–0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02–0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15–0.94], p = 0.037). Conclusions G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy. Please see later in the article for the Editors' Summary PMID:20520804

Polysaccharides from the Chinese medicinal herb Achyranthes bidentata enhance anti-malarial immunity during Plasmodium yoelii 17XL infection in mice.

PubMed

Zhu, Xiaotong; Pan, Yanyan; Zheng, Li; Cui, Liwang; Cao, Yaming

2012-02-20

Clinical immunity to malaria in human populations is developed after repeated exposure to malaria. Regulation and balance of host immune responses may lead to optimal immunity against malaria parasite infection. Polysaccharides (ABPS) derived from the Chinese herb ox knee Achyranthes bidentata possess immuno-modulatory functions. The aim of this study is to use the rodent malaria model Plasmodium yoelii 17XL (P. y17XL) to examine whether pretreatment with ABPS will modulate host immunity against malaria infection and improve the outcome of the disease. To determine whether ABPS could modulate immunity against malaria, mice were pretreated with ABPS prior to blood-stage infection by P. y17XL. Host survival and parasitaemia were monitored daily. The effect of pretreatment on host immune responses was studied through the quantitation of cytokines, dendritic cell populations, and natural regulatory T cells (Treg). Pretreatment with ABPS prior to infection significantly extended the survival time of mice after P. y17XL infection. At three and five days post-infection, ABPS pretreated mice developed stronger Th1 immune responses against malaria infection with the number of F4/80+CD36+ macrophages and levels of IFN-γ, TNF-α and nitric oxide being significantly higher than in the control group. More importantly, ABPS-treated mice developed more myeloid (CD11c+CD11b+) and plasmacytoid dendritic cells (CD11c+CD45R+/B220+) than control mice. ABPS pretreatment also resulted in modulated expression of MHC-II, CD86, and especially Toll-like receptor 9 by CD11c+ dendritic cells. In comparison, pretreatment with ABPS did not alter the number of natural Treg or the production of the anti-inflammatory cytokine IL-10. Pretreatment with the immuno-modulatory ABPS selectively enhanced Th1 immune responses to control the proliferation of malaria parasites, and prolonged the survival of mice during subsequent malaria infection.

The contribution of Plasmodium chabaudi to our understanding of malaria

PubMed Central

Stephens, Robin; Culleton, Richard L.; Lamb, Tracey J.

2014-01-01

Malaria kills close to a million people every year, mostly children under the age of five. In the drive towards the development of an effective vaccine and new chemotherapeutic targets for malaria, field-based studies on human malaria infection and laboratory-based studies using animal models of malaria offer complementary opportunities to further our understanding of the mechanisms behind malaria infection and pathology. We outline here the parallels between the Plasmodium chabaudi mouse model of malaria and human malaria. We will highlight the contribution of P. chabaudi to our understanding of malaria in particular, how the immune response in malaria infection is initiated and regulated, its role in pathology, and how immunological memory is maintained. We will also discuss areas where new tools have opened up potential areas of exploration using this invaluable model system. PMID:22100995

The use of a GIS-based malaria information system for malaria research and control in South Africa.

PubMed

Martin, Carrin; Curtis, Bronwyn; Fraser, Colleen; Sharp, Brian

2002-12-01

The paper aims to outline the innovative development and application of a Geographical Information System based Malaria Information System for malaria research and control in South Africa. This system is a product of collaboration between the Malaria Control Programmes and the Malaria Research Programme of the Medical Research Council of South Africa. The ability of such a system to process data timeously into a usable format is discussed, as well as its relevance to malaria research, appropriate malaria control measures, tourism, and social and economic development.

Ikonos-derived malaria transmission risk in northwestern Thailand.

PubMed

Sithiprasasna, Ratana; Ugsang, Donald M; Honda, Kiyoshi; Jones, James W; Singhasivanon, Pratap

2005-01-01

We mapped overall malaria cases and located each field observed major malaria vector breeding habitat using Global Positioning System (GPS) instruments from September 2000 to October 2003 around the three malaria-endemic villages of Ban Khun Huay, Ban Pa Dae, and Ban Tham Seau, Mae Sod district, Tak Province, Thailand. The land-use/land-cover classifications of the three villages and surrounding areas were performed on IKONOS satellite images acquired on 12 November 2001 with a spatial resolution of 1 x 1 m. Stream network was delineated and displayed. Proximity analysis was performed on the locations of the houses with and without malaria cases within a 1.5 km buffer from An. minimus immature mosquito breeding habitats, mainly stream margins. The 1.5 km used in our proximity analysis was arbitrarily estimated based on the An. minimus flight range. A statistical t-test at 5% significance level was performed to evaluate whether houses with malaria cases have higher proximities to streams than houses without malaria cases. The result shows no significant difference between proximity to streams between houses with malaria cases and houses without malaria cases. We suspect that the actual flight range of An. minimus may be greater than 1.5 km. The An. minimus larval habitat deserves more detailed investigation. Further studies on human behavior contrary to that required for adequate malaria control among these three villages are also recommended.

Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population.

PubMed

Sinha, Swapnil; Mishra, Shrawan K; Sharma, Shweta; Patibandla, Phani K; Mallick, Prashant K; Sharma, Surya K; Mohanty, Sanjib; Pati, Sudhanshu S; Mishra, Saroj K; Ramteke, Bheshaj K; Bhatt, Rm; Joshi, Hema; Dash, Aditya P; Ahuja, Ramesh C; Awasthi, Shally; Venkatesh, Vimala; Habib, Saman

2008-01-14

Susceptibility/resistance to Plasmodium falciparum malaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in the TNF and FCGR2A genes in determining severity/resistance to P. falciparum malaria in Indian subjects. Allelic frequency distribution in populations across India was first determined by typing genetic variants of the TNF enhancer and the FCGR2A G/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfotrade mark version 3.4. A novel single nucleotide polymorphism (SNP) at position -76 was identified in the TNF enhancer along with other reported variants. Five TNF enhancer SNPs and the FCGR2A R131H (G/A) SNP were analyzed for association with severity of P. falciparum malaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions. TNF -1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcgammaRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context of P. falciparum severity/resistance in the Indian population. Association of specific TNF and FCGR2A SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.

Polymorphisms of TNF-enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population

PubMed Central

Sinha, Swapnil; Mishra, Shrawan K; Sharma, Shweta; Patibandla, Phani K; Mallick, Prashant K; Sharma, Surya K; Mohanty, Sanjib; Pati, Sudhanshu S; Mishra, Saroj K; Ramteke, Bheshaj K; Bhatt, RM; Joshi, Hema; Dash, Aditya P; Ahuja, Ramesh C; Awasthi, Shally; Venkatesh, Vimala; Habib, Saman

2008-01-01

Background Susceptibility/resistance to Plasmodium falciparum malaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in the TNF and FCGR2A genes in determining severity/resistance to P. falciparum malaria in Indian subjects. Methods Allelic frequency distribution in populations across India was first determined by typing genetic variants of the TNF enhancer and the FCGR2A G/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfo™ version 3.4. Results A novel single nucleotide polymorphism (SNP) at position -76 was identified in the TNF enhancer along with other reported variants. Five TNF enhancer SNPs and the FCGR2A R131H (G/A) SNP were analyzed for association with severity of P. falciparum malaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions. TNF -1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcγRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context of P. falciparum severity/resistance in the Indian population. Conclusion Association of specific TNF and FCGR2A SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India. PMID:18194515

Parasite-based malaria diagnosis: Are Health Systems in Uganda equipped enough to implement the policy?

PubMed Central

2012-01-01

Background Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda. Methods In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD. Results Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months’ long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs. Conclusion Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems. PMID:22920954

Effects of human and mosquito migrations on the dynamical behavior of the spread of malaria

NASA Astrophysics Data System (ADS)

Beay, Lazarus Kalvein; Kasbawati, Toaha, Syamsuddin

2017-03-01

Malaria is one of infectious diseases which become the main public health problem especially in Indonesia. Mathematically, the spread of malaria can be modeled to predict the outbreak of the disease. This research studies about mathematical model of the spread of malaria which takes into consideration the migration of human and mosquito populations. By determining basic reproduction number of the model, we analyze effects of migration parameter with respect to the reduction of malaria outbreak. Sensitivity analysis of basic reproduction number shows that mosquito migration has greater effect in reducing the outbreak of malaria compared with human migration. Basic reproduction number of the model is monotonically decreasing as mosquito migration increasing. We then confirm the analytic result by doing numerical simulation. The results show that migrations in human and mosquito populations have big influences in eliminating and eradicating the disease from the system.

Epidemiology of forest malaria in central Vietnam: a large scale cross-sectional survey.

PubMed

Erhart, Annette; Ngo, Duc Thang; Phan, Van Ky; Ta, Thi Tinh; Van Overmeir, Chantal; Speybroeck, Niko; Obsomer, Valerie; Le, Xuan Hung; Le, Khanh Thuan; Coosemans, Marc; D'alessandro, Umberto

2005-12-08

In Vietnam, a large proportion of all malaria cases and deaths occurs in the central mountainous and forested part of the country. Indeed, forest malaria, despite intensive control activities, is still a major problem which raises several questions about its dynamics.A large-scale malaria morbidity survey to measure malaria endemicity and identify important risk factors was carried out in 43 villages situated in a forested area of Ninh Thuan province, south central Vietnam. Four thousand three hundred and six randomly selected individuals, aged 10-60 years, participated in the survey. Rag Lays (86%), traditionally living in the forest and practising "slash and burn" cultivation represented the most common ethnic group. The overall parasite rate was 13.3% (range [0-42.3] while Plasmodium falciparum seroprevalence was 25.5% (range [2.1-75.6]). Mapping of these two variables showed a patchy distribution, suggesting that risk factors other than remoteness and forest proximity modulated the human-vector interactions. This was confirmed by the results of the multivariate-adjusted analysis, showing that forest work was a significant risk factor for malaria infection, further increased by staying in the forest overnight (OR= 2.86; 95%CI [1.62; 5.07]). Rag Lays had a higher risk of malaria infection, which inversely related to education level and socio-economic status. Women were less at risk than men (OR = 0.71; 95%CI [0.59; 0.86]), a possible consequence of different behaviour. This study confirms that malaria endemicity is still relatively high in this area and that the dynamics of transmission is constantly modulated by the behaviour of both humans and vectors. A well-targeted intervention reducing the "vector/forest worker" interaction, based on long-lasting insecticidal material, could be appropriate in this environment.

Epidemiology of forest malaria in central Vietnam: a large scale cross-sectional survey

PubMed Central

Erhart, Annette; Thang, Ngo Duc; Van Ky, Phan; Tinh, Ta Thi; Van Overmeir, Chantal; Speybroeck, Niko; Obsomer, Valerie; Hung, Le Xuan; Thuan, Le Khanh; Coosemans, Marc; D'alessandro, Umberto

2005-01-01

In Vietnam, a large proportion of all malaria cases and deaths occurs in the central mountainous and forested part of the country. Indeed, forest malaria, despite intensive control activities, is still a major problem which raises several questions about its dynamics. A large-scale malaria morbidity survey to measure malaria endemicity and identify important risk factors was carried out in 43 villages situated in a forested area of Ninh Thuan province, south central Vietnam. Four thousand three hundred and six randomly selected individuals, aged 10–60 years, participated in the survey. Rag Lays (86%), traditionally living in the forest and practising "slash and burn" cultivation represented the most common ethnic group. The overall parasite rate was 13.3% (range [0–42.3] while Plasmodium falciparum seroprevalence was 25.5% (range [2.1–75.6]). Mapping of these two variables showed a patchy distribution, suggesting that risk factors other than remoteness and forest proximity modulated the human-vector interactions. This was confirmed by the results of the multivariate-adjusted analysis, showing that forest work was a significant risk factor for malaria infection, further increased by staying in the forest overnight (OR= 2.86; 95%CI [1.62; 5.07]). Rag Lays had a higher risk of malaria infection, which inversely related to education level and socio-economic status. Women were less at risk than men (OR = 0.71; 95%CI [0.59; 0.86]), a possible consequence of different behaviour. This study confirms that malaria endemicity is still relatively high in this area and that the dynamics of transmission is constantly modulated by the behaviour of both humans and vectors. A well-targeted intervention reducing the "vector/forest worker" interaction, based on long-lasting insecticidal material, could be appropriate in this environment. PMID:16336671

Geographic information system (GIS) maps and malaria control monitoring: intervention coverage and health outcome in distal villages of Khammouane province, Laos

PubMed Central

Shirayama, Yoshihisa; Phompida, Samlane; Shibuya, Kenji

2009-01-01

Background Insecticide-treated nets (ITNs) are a key intervention to control malaria. The intervention coverage varies as a consequence of geographical accessibility to remote villages and limitations of financial and human resources for the intervention. People's adherence to the intervention, i.e., proper use of ITNs, also affects malaria health outcome. The study objective is to explore the impact of the intervention coverage and people's adherence to the intervention on malaria health outcome among targeted villages in various geographic locations. Methods Geographic information system (GIS) maps were developed using the data collected in an active case detection survey in Khammouane province, Laos. The survey was conducted using rapid diagnostic tests (RDTs) and a structured questionnaire at 23 sites in the province from June to July, the rainy season, in 2005. A total of 1,711 villagers from 403 households participated in the survey. Results As indicated on the GIS maps, villages with malaria cases, lower intervention coverage, and lower adherence were identified. Although no malaria case was detected in most villages with the best access to the district center, several cases were detected in the distal villages, where the intervention coverage and adherence to the intervention remained relatively lower. Conclusion Based on the data and maps, it was demonstrated that malaria remained unevenly distributed within districts. Balancing the intervention coverage in the distal villages with the overall coverage and continued promotion of the proper use of ITNs are necessary for a further reduction of malaria cases in the province. PMID:19772628

Geographic information system (GIS) maps and malaria control monitoring: intervention coverage and health outcome in distal villages of Khammouane province, Laos.

PubMed

Shirayama, Yoshihisa; Phompida, Samlane; Shibuya, Kenji

2009-09-22

Insecticide-treated nets (ITNs) are a key intervention to control malaria. The intervention coverage varies as a consequence of geographical accessibility to remote villages and limitations of financial and human resources for the intervention. People's adherence to the intervention, i.e., proper use of ITNs, also affects malaria health outcome. The study objective is to explore the impact of the intervention coverage and people's adherence to the intervention on malaria health outcome among targeted villages in various geographic locations. Geographic information system (GIS) maps were developed using the data collected in an active case detection survey in Khammouane province, Laos. The survey was conducted using rapid diagnostic tests (RDTs) and a structured questionnaire at 23 sites in the province from June to July, the rainy season, in 2005. A total of 1,711 villagers from 403 households participated in the survey. As indicated on the GIS maps, villages with malaria cases, lower intervention coverage, and lower adherence were identified. Although no malaria case was detected in most villages with the best access to the district center, several cases were detected in the distal villages, where the intervention coverage and adherence to the intervention remained relatively lower. Based on the data and maps, it was demonstrated that malaria remained unevenly distributed within districts. Balancing the intervention coverage in the distal villages with the overall coverage and continued promotion of the proper use of ITNs are necessary for a further reduction of malaria cases in the province.

Current status of Plasmodium knowlesi vectors: a public health concern?

PubMed

Vythilingam, I; Wong, M L; Wan-Yussof, W S

2018-01-01

Plasmodium knowlesi a simian malaria parasite is currently affecting humans in Southeast Asia. Malaysia has reported the most number of cases and P. knowlesi is the predominant species occurring in humans. The vectors of P. knowlesi belong to the Leucosphyrus group of Anopheles mosquitoes. These are generally described as forest-dwelling mosquitoes. With deforestation and changes in land-use, some species have become predominant in farms and villages. However, knowledge on the distribution of these vectors in the country is sparse. From a public health point of view it is important to know the vectors, so that risk factors towards knowlesi malaria can be identified and control measures instituted where possible. Here, we review what is known about the knowlesi malaria vectors and ascertain the gaps in knowledge, so that future studies could concentrate on this paucity of data in-order to address this zoonotic problem.

A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

PubMed Central

Phillips, Margaret A.; Lotharius, Julie; Marsh, Kennan; White, John; Dayan, Anthony; White, Karen L.; Njoroge, Jacqueline W.; El Mazouni, Farah; Lao, Yanbin; Kokkonda, Sreekanth; Tomchick, Diana R.; Deng, Xiaoyi; Laird, Trevor; Bhatia, Sangeeta N.; March, Sandra; Ng, Caroline L.; Fidock, David A.; Wittlin, Sergio; Lafuente-Monasterio, Maria; Benito, Francisco Javier Gamo; Alonso, Laura Maria Sanz; Martinez, Maria Santos; Jimenez-Diaz, Maria Belen; Bazaga, Santiago Ferrer; Angulo-Barturen, Iñigo; Haselden, John N.; Louttit, James; Cui, Yi; Sridhar, Arun; Zeeman, Anna-Marie; Kocken, Clemens; Sauerwein, Robert; Dechering, Koen; Avery, Vicky M.; Duffy, Sandra; Delves, Michael; Sinden, Robert; Ruecker, Andrea; Wickham, Kristina S.; Rochford, Rosemary; Gahagen, Janet; Iyer, Lalitha; Riccio, Ed; Mirsalis, Jon; Bathhurst, Ian; Rueckle, Thomas; Ding, Xavier; Campo, Brice; Leroy, Didier; Rogers, M. John; Rathod, Pradipsinh K.; Burrows, Jeremy N.; Charman, Susan A.

2015-01-01

Malaria is one of the most significant causes of childhood mortality but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy to administer drug combinations with broad ranging activity against all manifestations of the disease. DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria. We describe studies profiling the biological activity, pharmacological and pharmacokinetic properties, and safety of DSM265, which supported its advancement to human trials. DSM265 is highly selective towards DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drug-resistant parasite isolates. Favorable pharmacokinetic properties of DSM265 are predicted to provide therapeutic concentrations for more than 8 days after a single oral dose in the range of 200–400 mg. DSM265 was well tolerated in repeat dose and cardiovascular safety studies in mice and dogs, was not mutagenic, and was inactive against panels of human enzymes/receptors. The excellent safety profile, blood and liver-stage activity, and predicted long human half-life position DSM265 as a new potential drug combination partner for either single-dose treatment or once weekly chemoprevention. DSM265 has advantages over current treatment options that are dosed daily or are inactive on the parasite liver-stage PMID:26180101

Hidden burden of malaria in Indian women.

PubMed

Sharma, Vinod P

2009-12-08

Malaria is endemic in India with an estimated 70-100 million cases each year (1.6-1.8 million reported by NVBDCP); of this 50-55% are Plasmodium vivax and 45-50% Plasmodium falciparum. A recent study on malaria in pregnancy reported from undivided Madhya Pradesh state (includes Chhattisgarh state), that an estimated over 220,000 pregnant women contract malaria infection each year. Malaria in pregnancy caused- abortions 34.5%; stillbirths 9%; and maternal deaths 0.45%. Bulk of this tragic outcome can be averted by following the Roll Back Malaria/WHO recommendations of the use of malaria prevention i.e. indoor residual spraying (IRS)/insecticide-treated bed nets (ITN) preferably long-lasting treated bed nets (LLIN); intermittent preventive therapy (IPT); early diagnosis, prompt and complete treatment using microscopic/malaria rapid diagnostics test (RDT) and case management. High incidence in pregnancy has arisen because of malaria surveillance lacking coverage, lack of age and sex wise data, staff shortages, and intermittent preventive treatment (IPT) applicable in high transmission states/pockets is not included in the national drug policy- an essential component of fighting malaria in pregnancy in African settings. Inadequate surveillance and gross under-reporting has been highlighted time and again for over three decades. As a result the huge problem of malaria in pregnancy reported occasionally by researchers has remained hidden. Malaria in pregnancy may quicken severity in patients with drug resistant parasites, anaemia, endemic poverty, and malnutrition. There is, therefore, urgent need to streamline malaria control strategies to make a difference in tackling this grim scenario in human health.

Acceptability of a herd immunity-focused, transmission-blocking malaria vaccine in malaria-endemic communities in the Peruvian Amazon: an exploratory study.

PubMed

White, Sara E; Harvey, Steven A; Meza, Graciela; Llanos, Alejandro; Guzman, Mitchel; Gamboa, Dionicia; Vinetz, Joseph M

2018-04-27

A transmission-blocking vaccine (TBV) to prevent malaria-infected humans from infecting mosquitoes has been increasingly considered as a tool for malaria control and elimination. This study tested the hypothesis that a malaria TBV would be acceptable among residents of a malaria-hypoendemic region. The study was carried out in six Spanish-speaking rural villages in the Department of Loreto in the Peruvian Amazon. These villages comprise a cohort of 430 households associated with the Peru-Brazil International Centre for Excellence in Malaria Research. Individuals from one-third (143) of enrolled households in an ongoing longitudinal, prospective cohort study in 6 communities in Loreto, Peru, were randomly selected to participate by answering a pre-validated questionnaire. All 143 participants expressed desire for a malaria vaccine in general; only 1 (0.7%) expressed unwillingness to receive a transmission-blocking malaria vaccine. Injection was considered most acceptable for adults (97.2%); for children drops in the mouth were preferred (96.8%). Acceptability waned marginally with the prospect of multiple injections (83.8%) and different projected efficacies at 70 and 50% (90.1 and 71.8%, respectively). Respondents demonstrated clear understanding that the vaccine was for community, rather than personal, protection against malaria infection. In this setting of the Peruvian Amazon, a transmission-blocking malaria vaccine was found to be almost universally acceptable. This study is the first to report that residents of a malaria-endemic region have been queried regarding a malaria vaccine strategy that policy-makers in the industrialized world often dismiss as altruistic.

Human population, urban settlement patterns and their impact on Plasmodium falciparum malaria endemicity.

PubMed

Tatem, Andrew J; Guerra, Carlos A; Kabaria, Caroline W; Noor, Abdisalan M; Hay, Simon I

2008-10-27

The efficient allocation of financial resources for malaria control and the optimal distribution of appropriate interventions require accurate information on the geographic distribution of malaria risk and of the human populations it affects. Low population densities in rural areas and high population densities in urban areas can influence malaria transmission substantially. Here, the Malaria Atlas Project (MAP) global database of Plasmodium falciparum parasite rate (PfPR) surveys, medical intelligence and contemporary population surfaces are utilized to explore these relationships and other issues involved in combining malaria risk maps with those of human population distribution in order to define populations at risk more accurately. First, an existing population surface was examined to determine if it was sufficiently detailed to be used reliably as a mask to identify areas of very low and very high population density as malaria free regions. Second, the potential of international travel and health guidelines (ITHGs) for identifying malaria free cities was examined. Third, the differences in PfPR values between surveys conducted in author-defined rural and urban areas were examined. Fourth, the ability of various global urban extent maps to reliably discriminate these author-based classifications of urban and rural in the PfPR database was investigated. Finally, the urban map that most accurately replicated the author-based classifications was analysed to examine the effects of urban classifications on PfPR values across the entire MAP database. Masks of zero population density excluded many non-zero PfPR surveys, indicating that the population surface was not detailed enough to define areas of zero transmission resulting from low population densities. In contrast, the ITHGs enabled the identification and mapping of 53 malaria free urban areas within endemic countries. Comparison of PfPR survey results showed significant differences between author-defined 'urban' and 'rural' designations in Africa, but not for the remainder of the malaria endemic world. The Global Rural Urban Mapping Project (GRUMP) urban extent mask proved most accurate for mapping these author-defined rural and urban locations, and further sub-divisions of urban extents into urban and peri-urban classes enabled the effects of high population densities on malaria transmission to be mapped and quantified. The availability of detailed, contemporary census and urban extent data for the construction of coherent and accurate global spatial population databases is often poor. These known sources of uncertainty in population surfaces and urban maps have the potential to be incorporated into future malaria burden estimates. Currently, insufficient spatial information exists globally to identify areas accurately where population density is low enough to impact upon transmission. Medical intelligence does however exist to reliably identify malaria free cities. Moreover, in Africa, urban areas that have a significant effect on malaria transmission can be mapped.

Review of DoD Malaria Research Programs,

DTIC Science & Technology

1992-05-01

the irraliated sporozoite vaccine. Work in the mouse model system and then extrapolate to human malarias. Study naturally acquired immune ...recombinant vaccines. Work simultaneously in the mouse model system and with human malarias. 3. Identify targets and mechanisms of protective immunity not...multivalent vaccines that attack these same targets. 3. Working again in the mouse model, non- human primate model, andI human systems we

Impact of malaria and helminth infections on immunogenicity of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Tanzania.

PubMed

Brown, Joelle; Baisley, Kathy; Kavishe, Bazil; Changalucha, John; Andreasen, Aura; Mayaud, Philippe; Gumodoka, Balthazar; Kapiga, Saidi; Hayes, Richard; Watson-Jones, Deborah

2014-01-23

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. There was some evidence that participants with malaria had increased GMTs compared to those without malaria. The data show high HPV immunogenicity regardless of the presence of malaria and helminth infections. The mechanism and significance for the increase in GMT in those with malaria is unknown. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

PubMed Central

2012-01-01

Background Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low. Methods One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district. Results Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts. Conclusions Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings. PMID:22424570

Malaria in Uganda: challenges to control on the long road to elimination. I. Epidemiology and current control efforts

PubMed Central

Yeka, Adoke; Gasasira, Anne; Mpimbaza, Arthur; Achan, Jane; Nankabirwa, Joaniter; Nsobya, Sam; Staedke, Sarah G.; Donnelly, Martin J.; Wabwire-Mangen, Fred; Talisuna, Ambrose; Dorsey, Grant; Kamya, Moses R.; Rosenthal, Philip J.

2011-01-01

Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected. PMID:21420377

Climate change and altitudinal structuring of malaria vectors in south-western Cameroon: their relation to malaria transmission.

PubMed

Tanga, M C; Ngundu, W I; Judith, N; Mbuh, J; Tendongfor, N; Simard, Frédéric; Wanji, S

2010-07-01

An entomological survey was conducted in Cameroon between October 2004 and September 2005, in nine localities targeted for malaria vector control based on adult productivity and variability. Mosquitoes were collected by human-landing catches (HLCs) and pyrethrum spray catches. A total of 12 500 anophelines were collected and dissected: Anopheles gambiae s.l. (56.86%), An. funestus s.l. (32.57%), An. hancocki (9.38%), and An. nili (1.18%). Applying PCR revealed that specimens of the An. funestus group were An. funestus s.s. and An. gambiae complex were mostly An. melas and An. gambiae s.s. of the M and S molecular forms with the M forms being the most predominant. The natural distribution patterns of Anopheles species were largely determined by altitude with some species having unique environmental tolerance limits. A human blood index (HBI) of 99.05% was recorded. Mean probability of daily survival of the malaria vectors was 0.92, with annual mean life expectancy of 21.9 days and the expectation of infective life was long with a mean of 7.4 days. The high survival rates suggest a high vector potential for the species. This information enhances the development of a more focused and informed vector control intervention. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Parasites and progress: ethical decision-making and the Santee-Cooper Malaria study, 1944-1949.

PubMed

Slater, Leo; Humphreys, Margaret

2008-01-01

As part of a mid-1940s malaria research program, U.S. Public Health Service researchers working in South Carolina chose to withhold treatment from a group of subjects while testing the efficacy of a new insecticide. Research during World War II had generated new tools to fight malaria, including the insecticide DDT and the medication chloroquine. The choices made about how to conduct research in one of the last pockets of endemic malaria in the United States reveal much about prevailing attitudes and assumptions with regard to malaria control. We describe this research and explore the ethical choices inherent in the tension between environmentally based interventions and the individual health needs of the population living within the study domain. The singular focus on the mosquito and its lifecycle led some researchers to view the humans in their study area as little more than parasite reservoirs, an attitude fueled by the frustrating disappearance of malaria just when the scientists were on the verge of establishing the efficacy of a powerful new agent in the fight against malaria. This analysis of their choices has relevance to broader questions in public health ethics.

Why is malaria associated with poverty? Findings from a cohort study in rural Uganda.

PubMed

Tusting, Lucy S; Rek, John; Arinaitwe, Emmanuel; Staedke, Sarah G; Kamya, Moses R; Cano, Jorge; Bottomley, Christian; Johnston, Deborah; Dorsey, Grant; Lindsay, Steve W; Lines, Jo

2016-08-04

Malaria control and sustainable development are linked, but implementation of 'multisectoral' intervention is restricted by a limited understanding of the causal pathways between poverty and malaria. We investigated the relationships between socioeconomic position (SEP), potential determinants of SEP, and malaria in Nagongera, rural Uganda. Socioeconomic information was collected for 318 children aged six months to 10 years living in 100 households, who were followed for up to 36 months. Mosquito density was recorded using monthly light trap collections. Parasite prevalence was measured routinely every three months and malaria incidence determined by passive case detection. First, we evaluated the association between success in smallholder agriculture (the primary livelihood source) and SEP. Second, we explored socioeconomic risk factors for human biting rate (HBR), parasite prevalence and incidence of clinical malaria, and spatial clustering of socioeconomic variables. Third, we investigated the role of selected factors in mediating the association between SEP and malaria. Relative agricultural success was associated with higher SEP. In turn, high SEP was associated with lower HBR (highest versus lowest wealth index tertile: Incidence Rate Ratio 0.71, 95 % confidence intervals (CI) 0.54-0.93, P = 0.01) and lower odds of malaria infection in children (highest versus lowest wealth index tertile: adjusted Odds Ratio 0.52, 95 % CI 0.35-0.78, P = 0.001), but SEP was not associated with clinical malaria incidence. Mediation analysis suggested that part of the total effect of SEP on malaria infection risk was explained by house type (24.9 %, 95 % CI 15.8-58.6 %) and food security (18.6 %, 95 % CI 11.6-48.3 %); however, the assumptions of the mediation analysis may not have been fully met. Housing improvements and agricultural development interventions to reduce poverty merit further investigation as multisectoral interventions against malaria. Further interdisplinary research is needed to understand fully the complex pathways between poverty and malaria and to develop strategies for sustainable malaria control.

Is Global Warming likely to cause an increased incidence of Malaria?

PubMed

Nabi, Sa; Qader, Ss

2009-03-01

The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by climatic conditions because of its direct relationship with the mosquito population, it is widely assumed that its incidence is likely to increase in a future warmer world.This review article discusses the two contradictory views regarding the association of global warming with an increased incidence of malaria. On one hand, there are many who believe that there is a strong association between the recent increase in malaria incidence and global warming. They predict that as global warming continues, malaria is set to spread in locations where previously it was limited, due to cooler climate. On the other hand, several theories have been put forward which are quite contrary to this prediction. There are multiple other factors which are accountable for the recent upsurge of malaria: for example drug resistance, mosquito control programs, public health facilities, and living standards.

Cost effective malaria risk control using remote sensing and environmental data

NASA Astrophysics Data System (ADS)

Rahman, Md. Z.; Roytman, Leonid; Kadik, Abdel Hamid

2012-06-01

Malaria transmission in many part of the world specifically in Bangladesh and southern African countries is unstable and epidemic. An estimate of over a million cases is reported annually. Malaria is heterogeneous, potentially due to variations in ecological settings, socio-economic status, land cover, and agricultural practices. Malaria control only relies on treatment and supply of bed networks. Drug resistance to these diseases is widespread. Vector control is minimal. Malaria control in those countries faces many formidable challenges such as inadequate accessibility to effective treatment, lack of trained manpower, inaccessibility of endemic areas, poverty, lack of education, poor health infrastructure and low health budgets. Health facilities for malaria management are limited, surveillance is inadequate, and vector control is insufficient. Control can only be successful if the right methods are used at the right time in the right place. This paper aims to improve malaria control by developing malaria risk maps and risk models using satellite remote sensing data by identifying, assessing, and mapping determinants of malaria associated with environmental, socio-economic, malaria control, and agricultural factors.

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

PubMed Central

2010-01-01

Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

Combining Synthetic Human Odours and Low-Cost Electrocuting Grids to Attract and Kill Outdoor-Biting Mosquitoes: Field and Semi-Field Evaluation of an Improved Mosquito Landing Box

PubMed Central

Matowo, Nancy S.; Koekemoer, Lizette L.; Moore, Sarah J.; Mmbando, Arnold S.; Mapua, Salum A.; Coetzee, Maureen; Okumu, Fredros O.

2016-01-01

Background On-going malaria transmission is increasingly mediated by outdoor-biting vectors, especially where indoor insecticidal interventions such as long-lasting insecticide treated nets (LLINs) are widespread. Often, the vectors are also physiologically resistant to insecticides, presenting major obstacles for elimination. We tested a combination of electrocuting grids with synthetic odours as an alternative killing mechanism against outdoor-biting mosquitoes. Methods An odour-baited device, the Mosquito Landing Box (MLB), was improved by fitting it with low-cost electrocuting grids to instantly kill mosquitoes attracted to the odour lure, and automated photo switch to activate attractant-dispensing and mosquito-killing systems between dusk and dawn. MLBs fitted with one, two or three electrocuting grids were compared outdoors in a malaria endemic village in Tanzania, where vectors had lost susceptibility to pyrethroids. MLBs with three grids were also tested in a large semi-field cage (9.6×9.6×4.5m), to assess effects on biting-densities of laboratory-reared Anopheles arabiensis on volunteers sitting near MLBs. Results Significantly more mosquitoes were killed when MLBs had two or three grids, than one grid in wet and dry seasons (P<0.05). The MLBs were highly efficient against Mansonia species and malaria vector, An. arabiensis. Of all mosquitoes, 99% were non-blood fed, suggesting host-seeking status. In the semi-field, the MLBs reduced mean number of malaria mosquitoes attempting to bite humans fourfold. Conclusion The improved odour-baited MLBs effectively kill outdoor-biting malaria vector mosquitoes that are behaviourally and physiologically resistant to insecticidal interventions e.g. LLINs. The MLBs reduce human-biting vector densities even when used close to humans, and are insecticide-free, hence potentially antiresistance. The devices could either be used as surveillance tools or complementary mosquito control interventions to accelerate malaria elimination where outdoor transmission is significant. PMID:26789733

Somatosensory discrimination deficits following pediatric cerebral malaria.

PubMed

Dugbartey, A T; Spellacy, F J; Dugbartey, M T

1998-09-01

Pathologic studies of central nervous system damage in human falciparum malaria indicate primary localization in the cerebral white matter. We report a sensory-perceptual investigation of 20 Ghanaian children with a recent history of cerebral malaria who were age-, gender-, and education-matched with 20 healthy control subjects. Somatosensory examinations failed to show any evidence of hemianesthesia, pseudohemianesthesia, or extinction to double simultaneous tactile stimulation. While unilateral upper limb testing revealed intact unimanual tactile roughness discrimination, bimanual tactile discrimination, however, was significantly impaired in the cerebral malaria group. A strong negative correlation (r = -0.72) between coma duration and the bimanual tactile roughness discrimination test was also found. An inefficiency in the integrity of callosal fibers appear to account for our findings, although alternative subcortical mechanisms known to be involved in information transfer across the cerebral hemispheres may be compromised as well.

Angiotensin II Moderately Decreases Plasmodium Infection and Experimental Cerebral Malaria in Mice.

PubMed

Gallego-Delgado, Julio; Baravian, Charlotte; Edagha, Innocent; Ty, Maureen C; Ruiz-Ortega, Marta; Xu, Wenyue; Rodriguez, Ana

2015-01-01

Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria.

Studies on malaria and Anopheles balabacensis in Cambodia

PubMed Central

Eyles, Don E.; Wharton, R. H.; Cheong, W. H.; Warren, McWilson

1964-01-01

During the past few years Anopheles balabacensis has come to be recognized as a very important human malaria vector in Thailand and the Indochinese area, but little has been published on its bionomics except from North Borneo. Studies of the feeding habits of A. balabacensis in Cambodia showed it to be predominantly a forest mosquito. It was readily attracted to monkeys in the forest canopy but also readily attacked man on the ground. Very few of this species were attracted to domestic animals. Malaria infections were found more frequently in mosquitos captured in villages, but a significant number were infected from the forest beyond flight range of human habitation. The human population showed a high percentage of persons infected with malaria, Plasmodium falciparum predominating. Cambodian monkeys were found also to be infected with P. cynomolgi. Although none of thirteen monkeys injected with sporozoites from wild-caught mosquitos came down with malaria, it was concluded that A. balabacensis probably was the vector of both human and monkey malaria and that the risk of cross-infection was considerable if monkey malarias infective to man exist in the area. PMID:14122444

Economic burden of malaria on businesses in Ghana: a case for private sector investment in malaria control.

PubMed

Nonvignon, Justice; Aryeetey, Genevieve Cecilia; Malm, Keziah L; Agyemang, Samuel Agyei; Aubyn, Vivian N A; Peprah, Nana Yaw; Bart-Plange, Constance N; Aikins, Moses

2016-09-06

Despite the significant gains made globally in reducing the burden of malaria, the disease remains a major public health challenge, especially in sub-Saharan Africa (SSA) including Ghana. There is a significant gap in financing malaria control globally. The private sector could become a significant source of financing malaria control. To get the private sector to appreciate the need to invest in malaria control, it is important to provide evidence of the economic burden of malaria on businesses. The objective of this study, therefore, was to estimate the economic burden on malaria on businesses in Ghana, so as to stimulate the sector's investment in malaria control. Data covering 2012-2014 were collected from 62 businesses sampled from Greater Accra, Ashanti and Western Regions of Ghana, which have the highest concentration of businesses in the country. Data on the cost of businesses' spending on treatment and prevention of malaria in staff and their dependants as well as staff absenteeism due to malaria and expenditure on other health-related activities were collected. Views of business leaders on the effect of malaria on their businesses were also compiled. The analysis was extrapolated to cover 5828 businesses across the country. The results show that businesses in Ghana lost about US$6.58 million to malaria in 2014, 90 % of which were direct costs. A total of 3913 workdays were lost due to malaria in firms in the study sample during the period 2012-2014. Businesses in the study sample spent an average of 0.5 % of the annual corporate returns on treatment of malaria in employees and their dependants, 0.3 % on malaria prevention, and 0.5 % on other health-related corporate social responsibilities. Again business leaders affirmed that malaria affects their businesses' efficiency, employee attendance and productivity and expenses. Finally, about 93 % of business leaders expressed the need private sector investment in malaria control. The economic burden of malaria on businesses in Ghana cannot be underestimated. This, together with business leaders' acknowledgement that it is important for private sector investment in malaria control, provides motivation for engagement of the private sector in financing malaria control activities.

Sustainable malaria control: transdisciplinary approaches for translational applications

PubMed Central

2012-01-01

With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities. PMID:23268712

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

PubMed

Mordmüller, Benjamin; Surat, Güzin; Lagler, Heimo; Chakravarty, Sumana; Ishizuka, Andrew S; Lalremruata, Albert; Gmeiner, Markus; Campo, Joseph J; Esen, Meral; Ruben, Adam J; Held, Jana; Calle, Carlos Lamsfus; Mengue, Juliana B; Gebru, Tamirat; Ibáñez, Javier; Sulyok, Mihály; James, Eric R; Billingsley, Peter F; Natasha, K C; Manoj, Anita; Murshedkar, Tooba; Gunasekera, Anusha; Eappen, Abraham G; Li, Tao; Stafford, Richard E; Li, Minglin; Felgner, Phil L; Seder, Robert A; Richie, Thomas L; Sim, B Kim Lee; Hoffman, Stephen L; Kremsner, Peter G

2017-02-23

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 10 4 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 10 3 (group I) or 1.28 × 10 4 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 10 4 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Modeling the impact of Plasmodium falciparum sexual stage immunity on the composition and dynamics of the human infectious reservoir for malaria in natural settings.

PubMed

Ouédraogo, André Lin; Eckhoff, Philip A; Luty, Adrian J F; Roeffen, Will; Sauerwein, Robert W; Bousema, Teun; Wenger, Edward A

2018-05-01

Malaria transmission remains high in Sub-Saharan Africa despite large-scale implementation of malaria control interventions. A comprehensive understanding of the transmissibility of infections to mosquitoes may guide the design of more effective transmission reducing strategies. The impact of P. falciparum sexual stage immunity on the infectious reservoir for malaria has never been studied in natural settings. Repeated measurements were carried out at start-wet, peak-wet and dry season, and provided data on antibody responses against gametocyte/gamete antigens Pfs48/45 and Pfs230 as anti-gametocyte immunity. Data on high and low-density infections and their infectiousness to anopheline mosquitoes were obtained using quantitative molecular methods and mosquito feeding assays, respectively. An event-driven model for P. falciparum sexual stage immunity was developed and fit to data using an agent based malaria model infrastructure. We found that Pfs48/45 and Pfs230 antibody densities increased with increasing concurrent gametocyte densities; associated with 55-70% reduction in oocyst intensity and achieved up to 44% reduction in proportions of infected mosquitoes. We showed that P. falciparum sexual stage immunity significantly reduces transmission of microscopic (p < 0.001) but not submicroscopic (p = 0.937) gametocyte infections to mosquitoes and that incorporating sexual stage immunity into mathematical models had a considerable impact on the contribution of different age groups to the infectious reservoir of malaria. Human antibody responses to gametocyte antigens are likely to be dependent on recent and concurrent high-density gametocyte exposure and have a pronounced impact on the likelihood of onward transmission of microscopic gametocyte densities compared to low density infections. Our mathematical simulations indicate that anti-gametocyte immunity is an important factor for predicting and understanding the composition and dynamics of the human infectious reservoir for malaria.

[Current status of malaria control knowledge awareness of primary and sec- ondary school students in Xuzhou City].

PubMed

Sun, Xing-sheng; Li, Li; Zhang, Kan-kan

2015-12-01

To understand the current status of malaria control knowledge awareness of primary and secondary school students and its influencing factors in Yunlong District, Xuzhou City, so as to provide the evidence for improving the malaria prevention work. A total of 800 students from 4 urban and rural primary and secondary schools were randomly selected and investigated with questionnaires. The total awareness rate of malaria control knowledge was 61.27%, and the awareness rates of symptoms of malaria and malaria prevention were only 38.99% and 57.59% respectively. The main approach of obtaining the malaria control knowledge was media (51.52%). The univariate analysis showed that sex, area and different education levels affected the awareness rates of malaria control knowledge (P < 0.05), and the Logistic analysis showed that the awareness rate of malaria control knowledge of country students was lower than that of urban students (P < 0.05), and the awareness rate of malaria control knowledge of the secondary school students was higher than that of the primary school students (P < 0.05). The awareness rate of malaria control knowledge of primary and secondary school students in Yunlong District is lower than that required by the national standard. Therefore, the health education of malaria control should be strengthened, especially in countryside school students and primary school students.

Initiating malaria control programs in the third world: directives for short- and long-term solutions.

PubMed

Basu, Sanjay

2002-01-01

Although malaria is a growing problem affecting several hundred million people each year, many malarial countries lack successful disease control programs. Worldwide malaria incidence rates are dramatically increasing, generating fear among many people who are witnessing malaria control initiatives fail. In this paper, we explore two options for malaria control in poor countries: (1) the production and distribution of a malaria vaccine and (2) the control of mosquitoes that harbor the malaria parasite. We first demonstrate that the development of a malaria vaccine is indeed likely, although it will take several years to produce because of both biological obstacles and insufficient research support. The distribution of such a vaccine, as suggested by some economists, will require that wealthy states promise a market to pharmaceutical companies who have traditionally failed to investigate diseases affecting the poorest of nations. But prior to the development of a malaria vaccine, we recommend the implementation of vector control pro- grams, such as those using Bti toxin, in regions with low vector capacity. Our analysis indicates that both endogenous programs in malarial regions and molecular approaches to parasite control will provide pragmatic solutions to the malaria problem. But the successful control of malaria will require sustained support from wealthy nations, without whom vaccine development and vector control programs will likely fail.

Consistent Safety and Infectivity in Sporozoite Challenge Model of Plasmodium vivax in Malaria-Naive Human Volunteers

PubMed Central

Herrera, Sócrates; Solarte, Yezid; Jordán-Villegas, Alejandro; Echavarría, Juan Fernando; Rocha, Leonardo; Palacios, Ricardo; Ramírez, Óscar; Vélez, Juan D.; Epstein, Judith E.; Richie, Thomas L.; Arévalo-Herrera, Myriam

2011-01-01

A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (−) subjects were randomly allocated into three (A–C) groups and were exposed to the bites of 2–4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (−) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials. PMID:21292872

Participatory Risk Mapping of Malaria Vector Exposure in Northern South America using Environmental and Population Data

PubMed Central

Fuller, D.O.; Troyo, A.; Alimi, T.O.; Beier, J.C.

2014-01-01

Malaria elimination remains a major public health challenge in many tropical regions, including large areas of northern South America. In this study, we present a new high spatial resolution (90 × 90 m) risk map for Colombia and surrounding areas based on environmental and human population data. The map was created through a participatory multi-criteria decision analysis in which expert opinion was solicited to determine key environmental and population risk factors, different fuzzy functions to standardize risk factor inputs, and variable factor weights to combine risk factors in a geographic information system. The new risk map was compared to a map of malaria cases in which cases were aggregated to the municipio (municipality) level. The relationship between mean municipio risk scores and total cases by muncípio showed a weak correlation. However, the relationship between pixel-level risk scores and vector occurrence points for two dominant vector species, Anopheles albimanus and An. darlingi, was significantly different (p < 0.05) from a random point distribution, as was a pooled point distribution for these two vector species and An. nuneztovari. Thus, we conclude that the new risk map derived based on expert opinion provides an accurate spatial representation of risk of potential vector exposure rather than malaria transmission as shown by the pattern of malaria cases, and therefore it may be used to inform public health authorities as to where vector control measures should be prioritized to limit human-vector contact in future malaria outbreaks. PMID:24976656

Anopheles culicifacies sibling species in Odisha, eastern India: First appearance of Anopheles culicifacies E and its vectorial role in malaria transmission.

PubMed

Das, Mumani; Das, Biswadeep; Patra, Aparna P; Tripathy, Hare K; Mohapatra, Namita; Kar, Santanu K; Hazra, Rupenangshu K

2013-07-01

To identify the Anopheles culicifacies sibling species complex and study their vectorial role in malaria endemic regions of Odisha. Mosquitoes were collected from 6 malaria endemic districts using standard entomological collection methods. An. culicifacies sibling species were identified by multiplex polymerase chain reaction (PCR) using cytochrome oxidase subunit II (COII) region of mitochondrial DNA. Plasmodium falciparum (Pf) sporozoite rate and human blood fed percentage (HBF) were estimated by PCR using Pf- and human-specific primers. Sequencing and phylogenetic analysis were performed to confirm the type of sibling species of An. culicifacies found in Odisha. Multiplex PCR detected An. culicifacies sibling species A, B, C, D and E in the malaria endemic regions of Odisha. An. culicifacies E was detected for the first time in Odisha, which was further confirmed by molecular phylogenetics. Highest sporozoite rate and HBF percentage were observed in An. culicifacies E in comparison with other sibling species. An. culicifacies E collected from Nawarangapur, Nuapara and Keonjhar district showed high HBF percentage and sporozoite rates. An. culicifacies B was the most abundant species, followed by An. culicifacies C and E. High sporozoite rate and HBF of An. culicifacies E indicated that it plays an important role in malaria transmission in Odisha. Appropriate control measures against An. culicifacies E at an early stage are needed to prevent further malaria transmission in Odisha. © 2013 Blackwell Publishing Ltd.

How well are malaria maps used to design and finance malaria control in Africa?

PubMed

Omumbo, Judy A; Noor, Abdisalan M; Fall, Ibrahima S; Snow, Robert W

2013-01-01

Rational decision making on malaria control depends on an understanding of the epidemiological risks and control measures. National Malaria Control Programmes across Africa have access to a range of state-of-the-art malaria risk mapping products that might serve their decision-making needs. The use of cartography in planning malaria control has never been methodically reviewed. An audit of the risk maps used by NMCPs in 47 malaria endemic countries in Africa was undertaken by examining the most recent national malaria strategies, monitoring and evaluation plans, malaria programme reviews and applications submitted to the Global Fund. The types of maps presented and how they have been used to define priorities for investment and control was investigated. 91% of endemic countries in Africa have defined malaria risk at sub-national levels using at least one risk map. The range of risk maps varies from maps based on suitability of climate for transmission; predicted malaria seasons and temperature/altitude limitations, to representations of clinical data and modelled parasite prevalence. The choice of maps is influenced by the source of the information. Maps developed using national data through in-country research partnerships have greater utility than more readily accessible web-based options developed without inputs from national control programmes. Although almost all countries have stratification maps, only a few use them to guide decisions on the selection of interventions allocation of resources for malaria control. The way information on the epidemiology of malaria is presented and used needs to be addressed to ensure evidence-based added value in planning control. The science on modelled impact of interventions must be integrated into new mapping products to allow a translation of risk into rational decision making for malaria control. As overseas and domestic funding diminishes, strategic planning will be necessary to guide appropriate financing for malaria control.

A historical perspective on malaria control in Brazil

PubMed Central

Griffing, Sean Michael; Tauil, Pedro Luiz; Udhayakumar, Venkatachalam; Silva-Flannery, Luciana

2015-01-01

Malaria has always been an important public health problem in Brazil. The early history of Brazilian malaria and its control was powered by colonisation by Europeans and the forced relocation of Africans as slaves. Internal migration brought malaria to many regions in Brazil where, given suitableAnopheles mosquito vectors, it thrived. Almost from the start, officials recognised the problem malaria presented to economic development, but early control efforts were hampered by still developing public health control and ignorance of the underlying biology and ecology of malaria. Multiple regional and national malaria control efforts have been attempted with varying success. At present, the Amazon Basin accounts for 99% of Brazil’s reported malaria cases with regional increases in incidence often associated with large scale public works or migration. Here, we provide an exhaustive summary of primary literature in English, Spanish and Portuguese regarding Brazilian malaria control. Our goal was not to interpret the history of Brazilian malaria control from a particular political or theoretical perspective, but rather to provide a straightforward, chronological narrative of the events that have transpired in Brazil over the past 200 years and identify common themes. PMID:26517649

Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines.

PubMed

Stanisic, Danielle I; Liu, Xue Q; De, Sai Lata; Batzloff, Michael R; Forbes, Tanya; Davis, Christopher B; Sekuloski, Silvana; Chavchich, Marina; Chung, Wendy; Trenholme, Katharine; McCarthy, James S; Li, Tao; Sim, B Kim Lee; Hoffman, Stephen L; Good, Michael F

2015-04-07

The ability to undertake controlled human malaria infection (CHMI) studies for preliminary evaluation of malaria vaccine candidates and anti-malaria drug efficacy has been limited by the need for access to sporozoite infected mosquitoes, aseptic, purified, cryopreserved sporozoites or blood-stage malaria parasites derived ex vivo from malaria infected individuals. Three different strategies are described for the manufacture of clinical grade cultured malaria cell banks suitable for use in CHMI studies. Good Manufacturing Practices (GMP)-grade Plasmodium falciparum NF54, clinically isolated 3D7, and research-grade P. falciparum 7G8 blood-stage malaria parasites were cultured separately in GMP-compliant facilities using screened blood components and then cryopreserved to produce three P. falciparum blood-stage malaria cell banks. These cell banks were evaluated according to specific criteria (parasitaemia, identity, viability, sterility, presence of endotoxin, presence of mycoplasma or other viral agents and in vitro anti-malarial drug sensitivity of the cell bank malaria parasites) to ensure they met the criteria to permit product release according to GMP requirements. The P. falciparum NF54, 3D7 and 7G8 cell banks consisted of >78% ring stage parasites with a ring stage parasitaemia of >1.4%. Parasites were viable in vitro following thawing. The cell banks were free from contamination with bacteria, mycoplasma and a broad panel of viruses. The P. falciparum NF54, 3D7 and 7G8 parasites exhibited differential anti-malarial drug susceptibilities. The P. falciparum NF54 and 3D7 parasites were susceptible to all anti-malaria compounds tested, whereas the P. falciparum 7G8 parasites were resistant/had decreased susceptibility to four compounds. Following testing, all defined release criteria were met and the P. falciparum cell banks were deemed suitable for release. Ethical approval has been obtained for administration to human volunteers. The production of cultured P. falciparum blood-stage malaria cell banks represents a suitable approach for the generation of material suitable for CHMI studies. A key feature of this culture-based approach is the ability to take research-grade material through to a product suitable for administration in clinical trials.

Expression of Plasmodium falciparum Circumsporozoite Proteins in Escherichia coli for Potential Use in a Human Malaria Vaccine

NASA Astrophysics Data System (ADS)

Young, James F.; Hockmeyer, Wayne T.; Gross, Mitchell; Ripley Ballou, W.; Wirtz, Robert A.; Trosper, James H.; Beaudoin, Richard L.; Hollingdale, Michael R.; Miller, Louis H.; Diggs, Carter L.; Rosenberg, Martin

1985-05-01

The circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum may be the most promising target for the development of a malaria vaccine. In this study, proteins composed of 16, 32, or 48 tandem copies of a tetrapeptide repeating sequence found in the CS protein were efficiently expressed in the bacterium Escherichia coli. When injected into mice, these recombinant products resulted in the production of high titers of antibodies that reacted with the authentic CS protein on live sporozoites and blocked sporozoite invasion of human hepatoma cells in vitro. These CS protein derivatives are therefore candidates for a human malaria vaccine.

Prevention and control of malaria and sleeping sickness in Africa: where are we and where are we going?

PubMed

Corbel, Vincent; Henry, Marie-Claire

2011-03-16

The International Symposium on Malaria and Human African Trypanosomiasis: New Strategies for their Prevention & Control was held 7-8 October, 2010 in Cotonou, Benin with about 250 participants from 20 countries. This scientific event aimed at identifying the gaps and research priorities in the prevention and control of malaria and sleeping sickness in Africa and to promote exchange between North and South in the fields of medical entomology, epidemiology, immunology and parasitology. A broad range of influential partners from academia (scientists), stakeholders, public health workers and industry attempted the meeting and about 40 oral communications and 20 posters were presented by phD students and internationally-recognized scientists from the North and the South. Finally, a special award ceremony was held to recognize efforts in pioneer work conducted by staff involved in the diagnostic of the Sleeping illness in West Africa with partnership and assistance from WHO and Sanofi-Aventis group.

Using Hydrologic Modeling to Screen Potential Environmental Management Methods for Malaria Vector Control in Niger

NASA Astrophysics Data System (ADS)

Gianotti, R. L.; Bomblies, A.; Eltahir, E. A.

2008-12-01

This study describes the use of HYDREMATS, a physically-based distributed hydrology model, to investigate environmental management methods for malaria vector control in the Sahelian village of Banizoumbou, Niger. The model operates at fine spatial and temporal scales to enable explicit simulation of individual pool dynamics and isolation of mosquito breeding habitats. The results showed that leveling of topographic depressions where temporary breeding habitats form during the rainy season could reduce the persistence time of a pool to less than the time needed for establishment of mosquito breeding, approximately 7 days. Increasing the surface soil permeability by ploughing could also reduce the persistence time of a pool but this technique was not as effective as leveling. Therefore it is considered that leveling should be the preferred of the two options where possible. This investigation demonstrates that management methods that modify the hydrologic environment have significant potential to contribute to malaria vector control and human health improvement in Sahelian Africa.

A Time Series Analysis: Weather Factors, Human Migration and Malaria Cases in Endemic Area of Purworejo, Indonesia, 2005–2014

PubMed Central

REJEKI, Dwi Sarwani Sri; NURHAYATI, Nunung; AJI, Budi; MURHANDARWATI, E. Elsa Herdiana; KUSNANTO, Hari

2018-01-01

Background: Climatic and weather factors become important determinants of vector-borne diseases transmission like malaria. This study aimed to prove relationships between weather factors with considering human migration and previous case findings and malaria cases in endemic areas in Purworejo during 2005–2014. Methods: This study employed ecological time series analysis by using monthly data. The independent variables were the maximum temperature, minimum temperature, maximum humidity, minimum humidity, precipitation, human migration, and previous malaria cases, while the dependent variable was positive malaria cases. Three models of count data regression analysis i.e. Poisson model, quasi-Poisson model, and negative binomial model were applied to measure the relationship. The least Akaike Information Criteria (AIC) value was also performed to find the best model. Negative binomial regression analysis was considered as the best model. Results: The model showed that humidity (lag 2), precipitation (lag 3), precipitation (lag 12), migration (lag1) and previous malaria cases (lag 12) had a significant relationship with malaria cases. Conclusion: Weather, migration and previous malaria cases factors need to be considered as prominent indicators for the increase of malaria case projection. PMID:29900134

Habitat suitability and ecological niche profile of major malaria vectors in Cameroon

PubMed Central

2009-01-01

Background Suitability of environmental conditions determines a species distribution in space and time. Understanding and modelling the ecological niche of mosquito disease vectors can, therefore, be a powerful predictor of the risk of exposure to the pathogens they transmit. In Africa, five anophelines are responsible for over 95% of total malaria transmission. However, detailed knowledge of the geographic distribution and ecological requirements of these species is to date still inadequate. Methods Indoor-resting mosquitoes were sampled from 386 villages covering the full range of ecological settings available in Cameroon, Central Africa. Using a predictive species distribution modeling approach based only on presence records, habitat suitability maps were constructed for the five major malaria vectors Anopheles gambiae, Anopheles funestus, Anopheles arabiensis, Anopheles nili and Anopheles moucheti. The influence of 17 climatic, topographic, and land use variables on mosquito geographic distribution was assessed by multivariate regression and ordination techniques. Results Twenty-four anopheline species were collected, of which 17 are known to transmit malaria in Africa. Ecological Niche Factor Analysis, Habitat Suitability modeling and Canonical Correspondence Analysis revealed marked differences among the five major malaria vector species, both in terms of ecological requirements and niche breadth. Eco-geographical variables (EGVs) related to human activity had the highest impact on habitat suitability for the five major malaria vectors, with areas of low population density being of marginal or unsuitable habitat quality. Sunlight exposure, rainfall, evapo-transpiration, relative humidity, and wind speed were among the most discriminative EGVs separating "forest" from "savanna" species. Conclusions The distribution of major malaria vectors in Cameroon is strongly affected by the impact of humans on the environment, with variables related to proximity to human settings being among the best predictors of habitat suitability. The ecologically more tolerant species An. gambiae and An. funestus were recorded in a wide range of eco-climatic settings. The other three major vectors, An. arabiensis, An. moucheti, and An. nili, were more specialized. Ecological niche and species distribution modelling should help improve malaria vector control interventions by targeting places and times where the impact on vector populations and disease transmission can be optimized. PMID:20028559

Habitat suitability and ecological niche profile of major malaria vectors in Cameroon.

PubMed

Ayala, Diego; Costantini, Carlo; Ose, Kenji; Kamdem, Guy C; Antonio-Nkondjio, Christophe; Agbor, Jean-Pierre; Awono-Ambene, Parfait; Fontenille, Didier; Simard, Frédéric

2009-12-23

Suitability of environmental conditions determines a species distribution in space and time. Understanding and modelling the ecological niche of mosquito disease vectors can, therefore, be a powerful predictor of the risk of exposure to the pathogens they transmit. In Africa, five anophelines are responsible for over 95% of total malaria transmission. However, detailed knowledge of the geographic distribution and ecological requirements of these species is to date still inadequate. Indoor-resting mosquitoes were sampled from 386 villages covering the full range of ecological settings available in Cameroon, Central Africa. Using a predictive species distribution modeling approach based only on presence records, habitat suitability maps were constructed for the five major malaria vectors Anopheles gambiae, Anopheles funestus, Anopheles arabiensis, Anopheles nili and Anopheles moucheti. The influence of 17 climatic, topographic, and land use variables on mosquito geographic distribution was assessed by multivariate regression and ordination techniques. Twenty-four anopheline species were collected, of which 17 are known to transmit malaria in Africa. Ecological Niche Factor Analysis, Habitat Suitability modeling and Canonical Correspondence Analysis revealed marked differences among the five major malaria vector species, both in terms of ecological requirements and niche breadth. Eco-geographical variables (EGVs) related to human activity had the highest impact on habitat suitability for the five major malaria vectors, with areas of low population density being of marginal or unsuitable habitat quality. Sunlight exposure, rainfall, evapo-transpiration, relative humidity, and wind speed were among the most discriminative EGVs separating "forest" from "savanna" species. The distribution of major malaria vectors in Cameroon is strongly affected by the impact of humans on the environment, with variables related to proximity to human settings being among the best predictors of habitat suitability. The ecologically more tolerant species An. gambiae and An. funestus were recorded in a wide range of eco-climatic settings. The other three major vectors, An. arabiensis, An. moucheti, and An. nili, were more specialized. Ecological niche and species distribution modelling should help improve malaria vector control interventions by targeting places and times where the impact on vector populations and disease transmission can be optimized.

Targeting male mosquito swarms to control malaria vector density

PubMed Central

Sawadogo, Simon Peguedwinde; Niang, Abdoulaye; Bilgo, Etienne; Millogo, Azize; Maïga, Hamidou; Dabire, Roch K.; Tripet, Frederic; Diabaté, Abdoulaye

2017-01-01

Malaria control programs are being jeopardized by the spread of insecticide resistance in mosquito vector populations. It has been estimated that the spread of resistance could lead to an additional 120000 deaths per year, and interfere with the prospects for sustained control or the feasibility of achieving malaria elimination. Another complication for the development of resistance management strategies is that, in addition to insecticide resistance, mosquito behavior evolves in a manner that diminishes the impact of LLINs and IRS. Mosquitoes may circumvent LLIN and IRS control through preferential feeding and resting outside human houses and/or being active earlier in the evening before people go to sleep. Recent developments in our understanding of mosquito swarming suggest that new tools targeting mosquito swarms can be designed to cut down the high reproductive rate of malaria vectors. Targeting swarms of major malaria vectors may provide an effective control method to counteract behavioral resistance developed by mosquitoes. Here, we evaluated the impact of systematic spraying of swarms of Anopheles gambiae s.l. using a mixed carbamate and pyrethroid aerosol. The impact of this intervention on vector density, female insemination rates and the age structure of males was measured. We showed that the resulting mass killing of swarming males and some mate-seeking females resulted in a dramatic 80% decrease in population size compared to a control population. A significant decrease in female insemination rate and a significant shift in the age structure of the male population towards younger males incapable of mating were observed. This paradigm-shift study therefore demonstrates that targeting primarily males rather than females, can have a drastic impact on mosquito population. PMID:28278212

Development of replication-deficient adenovirus malaria vaccines.

PubMed

Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

2017-03-01

Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

Genetic Analysis and Species Specific Amplification of the Artemisinin Resistance-Associated Kelch Propeller Domain in P. falciparum and P. vivax

PubMed Central

Talundzic, Eldin; Chenet, Stella M.; Goldman, Ira F.; Patel, Dhruviben S.; Nelson, Julia A.; Plucinski, Mateusz M.; Barnwell, John W.; Udhayakumar, Venkatachalam

2015-01-01

Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong Subregion and now poses a threat to malaria control and prevention. Recent work has identified mutations in the kelch propeller domain of the P. falciparum K13 gene to be associated artemisinin resistance as defined by delayed parasite clearance and ex vivo ring stage survival assays. Species specific primers for the two most prevalent human malaria species, P. falciparum and P. vivax, were designed and tested on multiple parasite isolates including human, rodent, and non- humans primate Plasmodium species. The new protocol described here using the species specific primers only amplified their respective species, P. falciparum and P. vivax, and did not cross react with any of the other human malaria Plasmodium species. We provide an improved species specific PCR and sequencing protocol that could be effectively used in areas where both P. falciparum and P. vivax are circulating. To design this improved protocol, the kelch gene was analyzed and compared among different species of Plasmodium. The kelch propeller domain was found to be highly conserved across the mammalian Plasmodium species. PMID:26292024

Genetic Analysis and Species Specific Amplification of the Artemisinin Resistance-Associated Kelch Propeller Domain in P. falciparum and P. vivax.

PubMed

Talundzic, Eldin; Chenet, Stella M; Goldman, Ira F; Patel, Dhruviben S; Nelson, Julia A; Plucinski, Mateusz M; Barnwell, John W; Udhayakumar, Venkatachalam

2015-01-01

Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong Subregion and now poses a threat to malaria control and prevention. Recent work has identified mutations in the kelch propeller domain of the P. falciparum K13 gene to be associated artemisinin resistance as defined by delayed parasite clearance and ex vivo ring stage survival assays. Species specific primers for the two most prevalent human malaria species, P. falciparum and P. vivax, were designed and tested on multiple parasite isolates including human, rodent, and non- humans primate Plasmodium species. The new protocol described here using the species specific primers only amplified their respective species, P. falciparum and P. vivax, and did not cross react with any of the other human malaria Plasmodium species. We provide an improved species specific PCR and sequencing protocol that could be effectively used in areas where both P. falciparum and P. vivax are circulating. To design this improved protocol, the kelch gene was analyzed and compared among different species of Plasmodium. The kelch propeller domain was found to be highly conserved across the mammalian Plasmodium species.

Discourse on malaria elimination: where do forcibly displaced persons fit in these discussions?

PubMed Central

2013-01-01

Background Individuals forcibly displaced are some of the poorest people in the world, living in areas where infrastructure and services are at a bare minimum. Out of a total of 10,549,686 refugees protected and assisted by the United Nations High Commissioner for Refugees globally, 6,917,496 (65.6%) live in areas where malaria is transmitted. Historically, national malaria control programmes have excluded displaced populations. Results The current discourse on malaria elimination rarely includes discussion of forcibly displaced persons who reside within malaria-eliminating countries. Of the 100 malaria-endemic countries, 64 are controlling malaria and 36 are in some stage of elimination. Of these, 30 malaria-controlling countries and 13 countries in some phase of elimination host displaced populations of ≥50,000, even though 13 of the 36 (36.1%) malaria-elimination countries host displaced populations of ≥50,000 people. Discussion Now is the time for the malaria community to incorporate forcibly displaced populations residing within malarious areas into malaria control activities. Beneficiaries, whether they are internally displaced persons or refugees, should be viewed as partners in the delivery of malaria interventions and not simply as recipients. Conclusion Until equitable and sustainable malaria control includes everyone residing in an endemic area, the goal of malaria elimination will not be met. PMID:23575209

Modeling Combinations of Pre-erythrocytic Plasmodium falciparum Malaria Vaccines.

PubMed

Walker, Andrew S; Lourenço, José; Hill, Adrian V S; Gupta, Sunetra

2015-12-01

Despite substantial progress in the control of Plasmodium falciparum infection due to the widespread deployment of insecticide-treated bed nets and artemisinin combination therapies, malaria remains a prolific killer, with over half a million deaths estimated to have occurred in 2013 alone. Recent evidence of the development of resistance to treatments in both parasites and their mosquito vectors has underscored the need for a vaccine. Here, we use a mathematical model of the within-host dynamics of P. falciparum infection, fit to data from controlled human malaria infection clinical trials, to predict the efficacy of co-administering the two most promising subunit vaccines, RTS,S/AS01 and ChAd63-MVA ME-TRAP. We conclude that currently available technologies could be combined to induce very high levels of sterile efficacy, even in immune-naive individuals. © The American Society of Tropical Medicine and Hygiene.

Factors influencing the use of topical repellents: implications for the effectiveness of malaria elimination strategies

PubMed Central

Gryseels, Charlotte; Uk, Sambunny; Sluydts, Vincent; Durnez, Lies; Phoeuk, Pisen; Suon, Sokha; Set, Srun; Heng, Somony; Siv, Sovannaroth; Gerrets, René; Tho, Sochantha; Coosemans, Marc; Peeters Grietens, Koen

2015-01-01

In Cambodia, despite an impressive decline in prevalence over the last 10 years, malaria is still a public health problem in some parts of the country. This is partly due to vectors that bite early and outdoors reducing the effectiveness of measures such as Long-Lasting Insecticidal Nets. Repellents have been suggested as an additional control measure in such settings. As part of a cluster-randomized trial on the effectiveness of topical repellents in controlling malaria infections at community level, a mixed-methods study assessed user rates and determinants of use. Repellents were made widely available and Picaridin repellent reduced 97% of mosquito bites. However, despite high acceptability, daily use was observed to be low (8%) and did not correspond to the reported use in surveys (around 70%). The levels of use aimed for by the trial were never reached as the population used it variably across place (forest, farms and villages) and time (seasons), or in alternative applications (spraying on insects, on bed nets, etc.). These findings show the key role of human behavior in the effectiveness of malaria preventive measures, questioning whether malaria in low endemic settings can be reduced substantially by introducing measures without researching and optimizing community involvement strategies. PMID:26574048

Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions

PubMed Central

2018-01-01

SUMMARY Transcriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactions in vitro under tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling. PMID:29695497

Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions.

PubMed

Lee, Hyun Jae; Georgiadou, Athina; Otto, Thomas D; Levin, Michael; Coin, Lachlan J; Conway, David J; Cunnington, Aubrey J

2018-06-01

Transcriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactions in vitro under tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling. Copyright © 2018 Lee et al.

Hydrology of malaria: Model development and application to a Sahelian village

NASA Astrophysics Data System (ADS)

Bomblies, Arne; Duchemin, Jean-Bernard; Eltahir, Elfatih A. B.

2008-12-01

We present a coupled hydrology and entomology model for the mechanistic simulation of local-scale response of malaria transmission to hydrological and climatological determinants in semiarid, desert fringe environments. The model is applied to the Sahel village of Banizoumbou, Niger, to predict interannual variability in malaria vector mosquito populations that lead to variations in malaria transmission. Using a high-resolution, small-scale distributed hydrology model that incorporates remotely sensed data for land cover and topography, we simulate the formation and persistence of the pools constituting the primary breeding habitat of Anopheles gambiae s.l. mosquitoes, the principal regional malaria vector mosquitoes. An agent-based mosquito population model is coupled to the distributed hydrology model, with aquatic-stage and adult-stage components. Through a dependence of aquatic-stage mosquito development and adult emergence on pool persistence, we model small-scale hydrology as a dominant control of mosquito abundance. For each individual adult mosquito, the model tracks attributes relevant to population dynamics and malaria transmission, which are updated as mosquitoes interact with their environment, humans, and animals. Weekly field observations were made in 2005 and 2006. A 16% increase in rainfall between the two years was accompanied by a 132% increase in mosquito abundance between 2005 and 2006. The model reproduces mosquito population variability at seasonal and interannual timescales and highlights individual pool persistence as a dominant control. Future developments of the presented model can be used in the evaluation of impacts of climate change on malaria, as well as the a priori evaluation of environmental management-based interventions.

Malaria vector populations across ecological zones in Guinea Conakry and Mali, West Africa.

PubMed

Coulibaly, Boubacar; Kone, Raymond; Barry, Mamadou S; Emerson, Becky; Coulibaly, Mamadou B; Niare, Oumou; Beavogui, Abdoul H; Traore, Sekou F; Vernick, Kenneth D; Riehle, Michelle M

2016-04-08

Malaria remains a pervasive public health problem in sub-Saharan West Africa. Here mosquito vector populations were explored across four sites in Mali and the Republic of Guinea (Guinea Conakry). The study samples the major ecological zones of malaria-endemic regions in West Africa within a relatively small distance. Mosquito vectors were sampled from larval pools, adult indoor resting sites, and indoor and outdoor human-host seeking adults. Mosquitoes were collected at sites spanning 350 km that represented arid savannah, humid savannah, semi-forest and deep forest ecological zones, in areas where little was previously known about malaria vector populations. 1425 mosquito samples were analysed by molecular assays to determine species, genetic attributes, blood meal sources and Plasmodium infection status. Anopheles gambiae and Anopheles coluzzii were the major anophelines represented in all collections across the ecological zones, with A. coluzzii predominant in the arid savannah and A. gambiae in the more humid sites. The use of multiple collection methodologies across the sampling sites allows assessment of potential collection bias of the different methods. The L1014F kdr insecticide resistance mutation (kdr-w) is found at high frequency across all study sites. This mutation appears to have swept almost to fixation, from low frequencies 6 years earlier, despite the absence of widespread insecticide use for vector control. Rates of human feeding are very high across ecological zones, with only small fractions of animal derived blood meals in the arid and humid savannah. About 30 % of freshly blood-fed mosquitoes were positive for Plasmodium falciparum presence, while the rate of mosquitoes with established infections was an order of magnitude lower. The study represents detailed vector characterization from an understudied area in West Africa with endemic malaria transmission. The deep forest study site includes the epicenter of the 2014 Ebola virus epidemic. With new malaria control interventions planned in Guinea, these data provide a baseline measure and an opportunity to assess the outcome of future interventions.

Malaria in the WHO Southeast Asia region.

PubMed

Kondrashin, A V

1992-09-01

Malaria endemic countries in the southeast Asia region include Bangladesh, Bhutan, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, and Thailand. Population movement and rapid urbanization, both largely caused by unemployment, and environmental deterioration change the malaria pattern. They also increase the incidence of drug-resistant malaria, especially resistance to 4-aminoquinolines. In India, Plasmodium falciparum is linked to the density and distribution of tribals, and, in southern Thailand, rubber tappers have the highest malaria incidence rate (46.29%). Since the population is young and the young are highly sensitive to malaria infection, the region has low community immunity. High malaria priority areas are forests, forested hills, forest fringe areas, developmental project sites, and border areas. High risk groups include infants, young children, pregnant women, and mobile population groups. Malaria incidence is between 2.5-2.8 million cases, and the slide positivity rate is about 3%. P. falciparum constitutes 40% for all malaria cases. In 1988 in India, there were 222 malaria deaths. Malaria is the 7th most common cause of death in Thailand. 3 of the 19 Anopheline species are resistant to at least 1 insecticide, particularly DDT. Posteradication epidemics surfaced in the mid-1970s. Malaria control programs tend to use the primary health care and integration approach to malaria control. Antiparasite measures range from a single-dose of an antimalarial to mass drug administration. Residual spraying continues to be the main strategy of vector control. Some other vector control measures are fish feeding on mosquito larvae, insecticide impregnated mosquito nets, and repellents. Control programs also have health education activities. India allocates the highest percentage of its total health budget to malaria control (21.54%). Few malariology training programs exist in the region. Slowly processed surveillance data limit the countries' ability to forecast and to combat malaria epidemics. Almost all control programs have a special research unit but capabilities are limited. Political commitment is needed to control malaria.

Changes in the burden of malaria following scale up of malaria control interventions in Mutasa District, Zimbabwe.

PubMed

Mharakurwa, Sungano; Mutambu, Susan L; Mberikunashe, Joseph; Thuma, Philip E; Moss, William J; Mason, Peter R

2013-07-01

To better understand trends in the burden of malaria and their temporal relationship to control activities, a survey was conducted to assess reported cases of malaria and malaria control activities in Mutasa District, Zimbabwe. Data on reported malaria cases were abstracted from available records at all three district hospitals, three rural hospitals and 25 rural health clinics in Mutasa District from 2003 to 2011. Malaria control interventions were scaled up through the support of the Roll Back Malaria Partnership, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and The President's Malaria Initiative. The recommended first-line treatment regimen changed from chloroquine or a combination of chloroquine plus sulphadoxine/pyrimethamine to artemisinin-based combination therapy, the latter adopted by 70%, 95% and 100% of health clinics by 2008, 2009 and 2010, respectively. Diagnostic capacity improved, with rapid diagnostic tests (RDTs) available in all health clinics by 2008. Vector control consisted of indoor residual spraying and distribution of long-lasting insecticidal nets. The number of reported malaria cases initially increased from levels in 2003 to a peak in 2008 but then declined 39% from 2008 to 2010. The proportion of suspected cases of malaria in older children and adults remained high, ranging from 75% to 80%. From 2008 to 2010, the number of RDT positive cases of malaria decreased 35% but the decrease was greater for children younger than five years of age (60%) compared to older children and adults (26%). The burden of malaria in Mutasa District decreased following the scale up of malaria control interventions. However, the persistent high number of cases in older children and adults highlights the need for strategies to identify locally effective control measures that target all age groups.

Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

PubMed Central

Rutledge, Gavin G.; Böhme, Ulrike; Sanders, Mandy; Reid, Adam J.; Cotton, James A.; Maiga-Ascofare, Oumou; Djimdé, Abdoulaye A.; Apinjoh, Tobias O.; Amenga-Etego, Lucas; Manske, Magnus; Barnwell, John W.; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Anstey, Nicholas M.; Auburn, Sarah; Price, Ric N.; McCarthy, James S.; Kwiatkowski, Dominic P.; Newbold, Chris I.; Berriman, Matthew; Otto, Thomas D.

2017-01-01

Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri)1. These species are prevalent across most regions in which malaria is endemic2,3 and are often undetectable by light microscopy4, rendering their study in human populations difficult5. The exact evolutionary relationship of these species to the other human-infective species has been contested6,7. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole. PMID:28117441

Preventing Superinfection in Malaria Spreads with Repellent and Medical Treatment Policy

NASA Astrophysics Data System (ADS)

Fitri, Fanny; Aldila, Dipo

2018-03-01

Malaria is a kind of a vector-borne disease. That means this disease needs a vector (in this case, the anopheles mosquito) to spread. In this article, a mathematical model for malaria disease spread will be discussed. The model is constructed as a seven-dimensional of a non-linear ordinary differential equation. The interventions of treatment for infected humans and use of repellent are included in the model to see how these interventions could be considered as alternative ways to control the spread of malaria. Analysis will be made of the disease-free equilibrium point along with its local stability criteria, construction of the next generation matrix which followed with the sensitivity analysis of basic reproduction number. We found that both medical treatment and repellent intervention succeeded in reducing the basic reproduction number as the endemic indicator of the model. Finally, some numerical simulations are given to give a better interpretation of the analytical results.

New repellent effective against African malaria mosquito Anopheles gambiae: implications for vector control.

PubMed

Hodson, C N; Yu, Y; Plettner, E; Roitberg, B D

2016-12-01

Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) is a vector for Plasmodium, the causative agent of malaria. Current control strategies to reduce the impact of malaria focus on reducing the frequency of mosquito attacks on humans, thereby decreasing Plasmodium transmission. A need for new repellents effective against Anopheles mosquitoes has arisen because of changes in vector behaviour as a result of control strategies and concern over the health impacts of current repellents. The response of A. gambiae to potential repellents was investigated through an electroantennogram screen and the most promising of these candidates (1-allyloxy-4-propoxybenzene, 3c{3,6}) chosen for behavioural testing. An assay to evaluate the blood-host seeking behaviour of A. gambiae towards a simulated host protected with this repellent was then performed. The compound 3c{3,6} was shown to be an effective repellent, causing mosquitoes to reduce their contact with a simulated blood-host and probe less at the host odour. Thus, 3c{3,6} may be an effective repellent for the control of A. gambiae. © 2016 The Royal Entomological Society.

Landscape Ecology and Epidemiology of Malaria Associated with Rubber Plantations in Thailand: Integrated Approaches to Malaria Ecotoping

PubMed Central

Kaewwaen, Wuthichai

2015-01-01

The agricultural land use changes that are human-induced changes in agroforestry ecosystems and in physical environmental conditions contribute substantially to the potential risks for malaria transmission in receptive areas. Due to the pattern and extent of land use change, the risks or negatively ecosystemic outcomes are the results of the dynamics of malaria transmission, the susceptibility of human populations, and the geographical distribution of malaria vectors. This review focused basically on what are the potential effects of agricultural land use change as a result of the expansion of rubber plantations in Thailand and how significant the ecotopes of malaria-associated rubber plantations (MRP) are. More profoundly, this review synthesized the novel concepts and perspectives on applied landscape ecology and epidemiology of malaria, as well as approaches to determine the degree to which an MRP ecotope as fundamental landscape scale can establish malaria infection pocket(s). Malaria ecotoping encompasses the integrated approaches and tools applied to or used in modeling malaria transmission. The scalability of MRP ecotope depends upon its unique landscape structure as it is geographically associated with the infestation or reinfestation of Anopheles vectors, along with the attributes that are epidemiologically linked with the infections. The MRP ecotope can be depicted as the hotspot such that malaria transmission is modeled upon the MRP factors underlying human settlements and movement activities, health behaviors, land use/land cover change, malaria vector population dynamics, and agrienvironmental and climatic conditions. The systemic and uniform approaches to malaria ecotoping underpin the stratification of the potential risks for malaria transmission by making use of remotely sensed satellite imagery or landscape aerial photography using unmanned aerial vehicle (UAV), global positioning systems (GPS), and geographical information systems (GIS). PMID:25838822

Good performances but short lasting efficacy of Actellic 50 EC Indoor Residual Spraying (IRS) on malaria transmission in Benin, West Africa

PubMed Central

2014-01-01

Background The National Malaria Control Program (NMCP) has been using pirimiphos methyl for the first time for indoor residual spraying (IRS) in Benin. The first round was a success with a significant decrease of entomological indicators of malaria transmission in the treated districts. We present the results of the entomological impact on malaria transmission. Entomologic parameters in the control area were compared with those in intervention sites. Methods Mosquito collections were carried out in three districts in the Atacora-Dongo region of which two were treated with pirimiphos methyl (Actellic 50EC) (Tanguiéta and Kouandé) and the untreated (Copargo) served as control. Anopheles gambiae s.l. populations were sampled monthly by human landing catch. In addition, window exit traps and pyrethrum spray catches were performed to assess exophagic behavior of Anopheles vectors. In the three districts, mosquito collections were organized to follow the impact of pirimiphos methyl IRS on malaria transmission and possible changes in the behavior of mosquitoes. The residual activity of pirimiphos methyl in the treated walls was also assessed using WHO bioassay test. Results A significant reduction (94.25%) in human biting rate was recorded in treated districts where an inhabitant received less than 1 bite of An. gambiae per night. During this same time, the entomological inoculation rate (EIR) dramatically declined in the treated area (99.24% reduction). We also noted a significant reduction in longevity of the vectors and an increase in exophily induced by pirimiphos methyl on An. gambiae. However, no significant impact was found on the blood feeding rate. Otherwise, the low residual activity of Actellic 50 EC, which is three months, is a disadvantage. Conclusion Pirimiphos methyl was found to be effective for IRS in Benin. However, because of the low persistence of Actellic 50EC used in this study on the treated walls, the recourse to another more residual formulation of pirimiphos methyl is required. PMID:24886499

Strengthening the policy setting process for global malaria control and elimination.

PubMed

D'Souza, Bianca J; Newman, Robert D

2012-01-27

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.

A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor (DSM421) with improved drug-like properties for treatment and prevention of malaria

PubMed Central

Phillips, Margaret A.; White, Karen L.; Kokkonda, Sreekanth; Deng, Xiaoyi; White, John; Mazouni, Farah El; Marsh, Kennan; Tomchick, Diana R.; Manjalanagara, Krishne; Rudra, Kakali Rani; Wirjanata, Grennady; Noviyanti, Rintis; Price, Ric N; Marfurt, Jutta; Shackleford, David M.; Chiu, Francis C.K.; Campbell, Michael; Jimenez-Diaz, Maria Belen; Bazaga, Santiago Ferrer; Angulo-Barturen, Iñigo; Martinez, Maria Santos; Lafuente-Monasterio, Maria; Kaminsky, Werner; Silue, Kigbafori; Zeeman, Anne-Marie; Kocken, Clemens; Leroy, Didier; Blasco, Benjamin; Rossignol, Emilie; Rueckle, Thomas; Matthews, Dave; Burrows, Jeremy N.; Waterson, David; Palmer, Michael J.; Rathod, Pradipsinh K.; Charman, Susan A.

2016-01-01

The emergence of drug resistant malaria parasites continues to hamper efforts to control this lethal disease. Dihydroorotate dehydrogenase has recently been validated as a new target for the treatment of malaria and a selective inhibitor (DSM265) of the Plasmodium enzyme is currently in clinical development. With the goal of identifying a backup compound to DSM265, we explored replacement of the SF5-aniline moiety of DSM265 with a series of CF3-pyridinyls, while maintaining the core triazolopyrimidine scaffold. This effort led to the identification of DSM421, which has improved solubility, lower intrinsic clearance and increased plasma exposure after oral dosing compared to DSM265, while maintaining a long predicted human half-life. Its improved physical and chemical properties will allow it to be formulated more readily than DSM265. DSM421 showed excellent efficacy in the SCID mouse model of P. falciparum malaria that supports the prediction of a low human dose (<200 mg). Importantly DSM421 showed equal activity against both P. falciparum and P. vivax field isolates, while DSM265 was more active on P. falciparum. DSM421 has the potential to be developed as a single dose cure or once-weekly chemopreventative for both P. falciparum and P. vivax malaria leading to its advancement as a preclinical development candidate. PMID:27641613

Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia.

PubMed

Lubis, Inke N D; Wijaya, Hendri; Lubis, Munar; Lubis, Chairuddin P; Divis, Paul C S; Beshir, Khalid B; Sutherland, Colin J

2017-04-01

As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province. A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi. Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%). Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Plasmodium knowlesi malaria an emerging public health problem in Hulu Selangor, Selangor, Malaysia (2009-2013): epidemiologic and entomologic analysis.

PubMed

Vythilingam, Indra; Lim, Yvonne Al; Venugopalan, Balan; Ngui, Romano; Leong, Cherng Shii; Wong, Meng Li; Khaw, LokeTim; Goh, XiangTing; Yap, NanJiun; Sulaiman, Wan Yusoff Wan; Jeffery, John; Zawiah, Ab Ghani Ct; Nor Aszlina, Ismail; Sharma, Reuben Sk; Yee Ling, Lau; Mahmud, Rohela

2014-09-15

While transmission of the human Plasmodium species has declined, a significant increase in Plasmodium knowlesi/Plasmodium malariae cases was reported in Hulu Selangor, Selangor, Malaysia. Thus, a study was undertaken to determine the epidemiology and the vectors involved in the transmission of knowlesi malaria. Cases of knowlesi/malariae malaria in the Hulu Selangor district were retrospectively reviewed and analyzed from 2009 to 2013. Mosquitoes were collected from areas where cases occurred in order to determine the vectors. Leucosphyrus group of mosquitoes were genetically characterized targeting the nuclear internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c oxidase subunit I (CO1). In addition, temporal and spatial analyses were carried out for human cases and vectors. Of the 100 microscopy diagnosed P. knowlesi/P. malariae cases over the 5 year period in the Hulu Selangor district, there was predominance of P. knowlesi/P. malariae cases among the young adults (ages 20-39 years; 67 cases; 67%). The majority of the infected people were involved in occupations related to agriculture and forestry (51; 51%). No death was recorded in all these cases.Five hundred and thirty five mosquitoes belonging to 14 species were obtained during the study. Anopheles maculatus was the predominant species (49.5%) followed by Anopheles letifer (13.1%) and Anopheles introlatus (11.6%). Molecular and phylogenetic analysis confirmed the species of the Leucosphyrus group to be An. introlatus. In the present study, only An. introlatus was positive for oocysts. Kernel Density analysis showed that P. knowlesi hotspot areas overlapped with areas where the infected An. introlatus was discovered. This further strengthens the hypothesis that An. introlatusis is the vector for P. knowlesi in the Hulu Selangor district.Unless more information is obtained on the vectors as well as macaque involved in the transmission, it will be difficult to plan effective control strategies. The utilization of modern analytical tools such as GIS (Geographic Information System) is crucial in estimating hotspot areas for targeted control strategies. Anopheles introlatus has been incriminated as vector of P. knowlesi in Hulu Selangor. The cases of P. knowlesi are on the increase and further research using molecular techniques is needed.

Combining fungal biopesticides and insecticide-treated bednets to enhance malaria control.

PubMed

Hancock, Penelope A

2009-10-01

In developing strategies to control malaria vectors, there is increased interest in biological methods that do not cause instant vector mortality, but have sublethal and lethal effects at different ages and stages in the mosquito life cycle. These techniques, particularly if integrated with other vector control interventions, may produce substantial reductions in malaria transmission due to the total effect of alterations to multiple life history parameters at relevant points in the life-cycle and transmission-cycle of the vector. To quantify this effect, an analytically tractable gonotrophic cycle model of mosquito-malaria interactions is developed that unites existing continuous and discrete feeding cycle approaches. As a case study, the combined use of fungal biopesticides and insecticide treated bednets (ITNs) is considered. Low values of the equilibrium EIR and human prevalence were obtained when fungal biopesticides and ITNs were combined, even for scenarios where each intervention acting alone had relatively little impact. The effect of the combined interventions on the equilibrium EIR was at least as strong as the multiplicative effect of both interventions. For scenarios representing difficult conditions for malaria control, due to high transmission intensity and widespread insecticide resistance, the effect of the combined interventions on the equilibrium EIR was greater than the multiplicative effect, as a result of synergistic interactions between the interventions. Fungal biopesticide application was found to be most effective when ITN coverage was high, producing significant reductions in equilibrium prevalence for low levels of biopesticide coverage. By incorporating biological mechanisms relevant to vectorial capacity, continuous-time vector population models can increase their applicability to integrated vector management.

Optimal insecticide-treated bed-net coverage and malaria treatment in a malaria-HIV co-infection model.

PubMed

Mohammed-Awel, Jemal; Numfor, Eric

2017-03-01

We propose and study a mathematical model for malaria-HIV co-infection transmission and control, in which malaria treatment and insecticide-treated nets are incorporated. The existence of a backward bifurcation is established analytically, and the occurrence of such backward bifurcation is influenced by disease-induced mortality, insecticide-treated bed-net coverage and malaria treatment parameters. To further assess the impact of malaria treatment and insecticide-treated bed-net coverage, we formulate an optimal control problem with malaria treatment and insecticide-treated nets as control functions. Using reasonable parameter values, numerical simulations of the optimal control suggest the possibility of eliminating malaria and reducing HIV prevalence significantly, within a short time horizon.

Lessons on malaria control in the ethnic minority regions in Northern Myanmar along the China border, 2007-2014.

PubMed

Wang, Ru-Bo; Dong, Jia-Qiang; Xia, Zhi-Gui; Cai, Tao; Zhang, Qing-Feng; Zhang, Yao; Tian, Yang-Hui; Sun, Xiao-Ying; Zhang, Guang-Yun; Li, Qing-Pu; Xu, Xiao-Yu; Li, Jia-Yin; Zhang, Jun

2016-10-06

For many countries where malaria is endemic, the burden of malaria is high in border regions. In ethnic minority areas along the Myanmar-China border, residents have poor access to medical care for diagnosis and treatment, and there have been many malaria outbreaks in such areas. Since 2007, with the support of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), a malaria control project was introduced to reduce the malaria burden in several ethnic minority regions. A malaria control network was established during the period from 2007 to 2014. Multiple malaria interventions, including diagnosis, treatment, distribution of LLINs and health education, were conducted to improve the accessibility and quality of malaria control services for local residents. Annual cross-sectional surveys were conducted to evaluate intervention coverage and indicators of malaria transmission. In ethnic minority regions where a malaria control network was established, both the annual malaria incidence (19.1 per thousand per year, in 2009; 8.7, in 2014) and malaria prevalence (13.6 % in 2008; 0.43 % in 2014) decreased dramatically during the past 5-6 years. A total of 851 393 febrile patients were detected, 202 598 malaria cases (including confirmed cases and suspected cases) were treated, and 759 574 LLINs were delivered to populations at risk. Of households in 2012, 73.9 % had at least one ITNs/LLINs (vs. 28.3 %, in 2008), and 50.7 % of children less than 5 years and 50.3 % of pregnant women slept under LLINs the night prior to their visit. Additionally, malaria knowledge was improved in 68.4 % of residents. There has been great success in improving malaria control in these regions from 2007 to 2014. Malaria burdens have decreased, especially in KOK and WA. The continued maintenance of sustainable malaria control networks in these regions may be a long-term process, due to regional conflicts and the lack of funds, technology, and health workers. Furthermore, information and scientific support from the international community should be offered to these ethnic minority regions to uphold recent achievements.

Applications and limitations of Centers for Disease Control and Prevention miniature light traps for measuring biting densities of African malaria vector populations: a pooled-analysis of 13 comparisons with human landing catches.

PubMed

Briët, Olivier J T; Huho, Bernadette J; Gimnig, John E; Bayoh, Nabie; Seyoum, Aklilu; Sikaala, Chadwick H; Govella, Nicodem; Diallo, Diadier A; Abdullah, Salim; Smith, Thomas A; Killeen, Gerry F

2015-06-18

Measurement of densities of host-seeking malaria vectors is important for estimating levels of disease transmission, for appropriately allocating interventions, and for quantifying their impact. The gold standard for estimating mosquito-human contact rates is the human landing catch (HLC), where human volunteers catch mosquitoes that land on their exposed body parts. This approach necessitates exposure to potentially infectious mosquitoes, and is very labour intensive. There are several safer and less labour-intensive methods, with Centers for Disease Control light traps (LT) placed indoors near occupied bed nets being the most widely used. This paper presents analyses of 13 studies with paired mosquito collections of LT and HLC to evaluate these methods for their consistency in sampling indoor-feeding mosquitoes belonging to the two major taxa of malaria vectors across Africa, the Anopheles gambiae sensu lato complex and the Anopheles funestus s.l. group. Both overall and study-specific sampling efficiencies of LT compared with HLC were computed, and regression methods that allow for the substantial variations in mosquito counts made by either method were used to test whether the sampling efficacy varies with mosquito density. Generally, LT were able to collect similar numbers of mosquitoes to the HLC indoors, although the relative sampling efficacy, measured by the ratio of LT:HLC varied considerably between studies. The overall best estimate for An. gambiae s.l. was 1.06 (95% credible interval: 0.68-1.64) and for An. funestus s.l. was 1.37 (0.70-2.68). Local calibration exercises are not reproducible, since only in a few studies did LT sample proportionally to HLC, and there was no geographical pattern or consistent trend with average density in the tendency for LT to either under- or over-sample. LT are a crude tool at best, but are relatively easy to deploy on a large scale. Spatial and temporal variation in mosquito densities and human malaria transmission exposure span several orders of magnitude, compared to which the inconsistencies of LT are relatively small. LT, therefore, remain an invaluable and safe alternative to HLC for measuring indoor malaria transmission exposure in Africa.

T cell-derived IL-10 and its impact on the regulation of host responses during malaria.

PubMed

Freitas do Rosario, Ana Paula; Langhorne, Jean

2012-05-15

Despite intense research, malaria still is the one of the most devastating diseases killing more people than any other parasitic infection. In an attempt to control the infection, the host immune system produces a potent pro-inflammatory response. However, this response is also associated with complications, such as severe anaemia, hypoglycaemia and cerebral malaria. This pronounced production of pro-inflammatory cytokines response is a common feature of malaria caused by parasites infecting humans as well as rodents and primates. A balance between pro- and anti-inflammatory responses may be fundamental to the elimination of the parasite without inducing excessive host pathology. IL-10 is a key cytokine that has been shown to have an important regulatory function in establishing this balance in malaria. Here we discuss which cells can produce IL-10 during infection, and present an overview of the evidence showing that T-cell derived IL-10 plays an important role in regulating malaria pathology. Many different subsets of T cells can produce IL-10, however, evidence is accumulating that it is effector Th1 CD4(+) T cells which provide the crucial source that down-regulates inflammatory pathology during blood-stage malaria infections. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

The Hydrology of Malaria: Model Development and Application to a Sahelian Village

NASA Astrophysics Data System (ADS)

Bomblies, A.; Duchemin, J.; Eltahir, E. A.

2008-12-01

We present a coupled hydrology and entomology model for the mechanistic simulation of local-scale response of malaria transmission to hydrological and climatological determinants in semi-arid, desert fringe environments. The model is applied to the Sahel village of Banizoumbou, Niger, to predict interannual variability in malaria vector mosquito populations which lead to variations in malaria transmission. Using a high-resolution, small-scale distributed hydrology model that incorporates remotely-sensed data for land cover and topography, we simulate the formation and persistence of the pools constituting the primary breeding habitat of Anopheles gambiae s.l. mosquitoes, the principal regional malaria vector mosquitoes. An agent-based mosquito population model is coupled to the distributed hydrology model, with aquatic stage and adult stage components. For each individual adult mosquito, the model tracks attributes relevant to population dynamics and malaria transmission, which are updated as mosquitoes interact with their environment, humans, and animals. Weekly field observations were made in 2005 and 2006. The model reproduces mosquito population variability at seasonal and interannual time scales, and highlights individual pool persistence as a dominant control. Future developments to the presented model can be used in the evaluation of impacts of climate change on malaria, as well as the a priori evaluation of environmental management-based interventions.

Safety and Immunogenicity of Heterologous Prime-Boost Immunisation with Plasmodium falciparum Malaria Candidate Vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in Healthy Gambian and Kenyan Adults

PubMed Central

Kimani, Domtila; Jagne, Ya Jankey; Sheehy, Susanne H.; Bliss, Carly M.; Duncan, Christopher J. A.; Collins, Katharine A.; Garcia Knight, Miguel A.; Kimani, Eva; Anagnostou, Nicholas A.; Berrie, Eleanor; Moyle, Sarah; Gilbert, Sarah C.; Spencer, Alexandra J.; Soipei, Peninah; Mueller, Jenny; Okebe, Joseph; Colloca, Stefano; Cortese, Riccardo; Viebig, Nicola K.; Roberts, Rachel; Gantlett, Katherine; Lawrie, Alison M.; Nicosia, Alfredo; Imoukhuede, Egeruan B.; Bejon, Philip; Urban, Britta C.; Flanagan, Katie L.; Ewer, Katie J.; Chilengi, Roma; Hill, Adrian V. S.; Bojang, Kalifa

2013-01-01

Background Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI). Methodology We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns. Results ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC). Conclusions ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted. Trial Registration Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430 PMID:23526949

Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults.

PubMed

Ogwang, Caroline; Afolabi, Muhammed; Kimani, Domtila; Jagne, Ya Jankey; Sheehy, Susanne H; Bliss, Carly M; Duncan, Christopher J A; Collins, Katharine A; Garcia Knight, Miguel A; Kimani, Eva; Anagnostou, Nicholas A; Berrie, Eleanor; Moyle, Sarah; Gilbert, Sarah C; Spencer, Alexandra J; Soipei, Peninah; Mueller, Jenny; Okebe, Joseph; Colloca, Stefano; Cortese, Riccardo; Viebig, Nicola K; Roberts, Rachel; Gantlett, Katherine; Lawrie, Alison M; Nicosia, Alfredo; Imoukhuede, Egeruan B; Bejon, Philip; Urban, Britta C; Flanagan, Katie L; Ewer, Katie J; Chilengi, Roma; Hill, Adrian V S; Bojang, Kalifa

2013-01-01

Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI). We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns. ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC). ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted. Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430.

Controlling vector-borne disease and adapting to climate change with novel research on disease forecasting to target new vector control materials and technologies

USDA-ARS?s Scientific Manuscript database

Population growth, frontier agricultural expansion, and urbanization transform the landscape and the surrounding ecosystem, affecting climate and interactions between animals and humans, and significantly influencing the transmission dynamics and geographic distribution of malaria, dengue and other ...

From malaria control to eradication: The WHO perspective.

PubMed

Mendis, Kamini; Rietveld, Aafje; Warsame, Marian; Bosman, Andrea; Greenwood, Brian; Wernsdorfer, Walther H

2009-07-01

Efforts to control malaria have been boosted in the past few years with increased international funding and greater political commitment. Consequently, the reported malaria burden is being reduced in a number of countries throughout the world, including in some countries in tropical Africa where the burden of malaria is greatest. These achievements have raised new hopes of eradicating malaria. This paper summarizes the outcomes of a World Health Organization's expert meeting on the feasibility of such a goal. Given the hindsight and experience of the Global Malaria Eradication Programme of the 1950s and 1960s, and current knowledge of the effectiveness of antimalarial tools and interventions, it would be feasible to effectively control malaria in all parts of the world and greatly reduce the enormous morbidity and mortality of malaria. It would also be entirely feasible to eliminate malaria from countries and regions where the intensity of transmission is low to moderate, and where health systems are strong. Elimination of malaria requires a re-orientation of control activity, moving away from a population-based coverage of interventions, to one based on a programme of effective surveillance and response. Sustained efforts will be required to prevent the resurgence of malaria from where it is eliminated. Eliminating malaria from countries where the intensity of transmission is high and stable such as in tropical Africa will require more potent tools and stronger health systems than are available today. When such countries have effectively reduced the burden of malaria, the achievements will need to be consolidated before a programme re-orientation towards malaria elimination is contemplated. Malaria control and elimination are under the constant threat of the parasite and vector mosquito developing resistance to medicines and insecticides, which are the cornerstones of current antimalarial interventions. The prospects of malaria eradication, therefore, rest heavily on the outcomes of research and development for new and improved tools. Malaria control and elimination are complementary objectives in the global fight against malaria.

Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

PubMed Central

Ade, Maria Paz; Baird, J. Kevin; Cheng, Qin; Cunningham, Jane; Dhorda, Mehul; Drakeley, Chris; Felger, Ingrid; Gamboa, Dionicia; Harbers, Matthias; Herrera, Socrates; Lucchi, Naomi; Mayor, Alfredo; Mueller, Ivo; Sattabongkot, Jetsumon; Ratsimbason, Arsène; Richards, Jack; Tanner, Marcel; González, Iveth J.

2017-01-01

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria. PMID:28369085

Conquering the intolerable burden of malaria: what's new, what's needed: a summary.

PubMed

Breman, Joel G; Alilio, Martin S; Mills, Anne

2004-08-01

Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria vaccine becomes deployed, consideration must be given to disease burden, cost-effectiveness, financing, delivery systems, and approval by regulatory agencies. Key to evaluation of vaccine effectiveness will be collection and prompt analysis of epidemiologic information. Training of persons in every aspect of malaria research and control is essential for programs to succeed. The Multilateral Initiative on Malaria (MIM) is actively promoting research capacity strengthening and has established networks of institutions and scientists throughout the African continent, most of whom are now linked by modern information-sharing networks. Evidence over the past century is that successful control malaria programs have been linked to strong research activities. To ensure effective coordination and cooperation between the growing number of research and control coalitions forming in support of malaria activities, an umbrella group is needed. With continued support for scientists and control workers globally, particularly in low-income malarious countries, the long-deferred dream of malaria elimination can become a reality. Copyright 2004 The American Society of Tropical Medicine and Hygiene

Malaria ecotypes and stratification.

PubMed

Schapira, Allan; Boutsika, Konstantina

2012-01-01

To deal with the variability of malaria, control programmes need to stratify their malaria problem into a number of smaller units. Such stratification may be based on the epidemiology of malaria or on its determinants such as ecology. An ecotype classification was developed by the World Health Organization (WHO) around 1990, and it is time to assess its usefulness for current malaria control as well as for malaria modelling on the basis of published research. Journal and grey literature was searched for articles on malaria or Anopheles combined with ecology or stratification. It was found that all malaria in the world today could be assigned to one or more of the following ecotypes: savanna, plains and valleys; forest and forest fringe; foothill; mountain fringe and northern and southern fringes; desert fringe; coastal and urban. However, some areas are in transitional or mixed zones; furthermore, the implications of any ecotype depend on the biogeographical region, sometimes subregion, and finally, the knowledge on physiography needs to be supplemented by local information on natural, anthropic and health system processes including malaria control. Ecotyping can therefore not be seen as a shortcut to determine control interventions, but rather as a framework to supplement available epidemiological and entomological data so as to assess malaria situations at the local level, think through the particular risks and opportunities and reinforce intersectoral action. With these caveats, it does however emerge that several ecotypic distinctions are well defined and have relatively constant implications for control within certain biogeographic regions. Forest environments in the Indo-malay and the Neotropics are, with a few exceptions, associated with much higher malaria risk than in adjacent areas; the vectors are difficult to control, and the anthropic factors also often converge to impose constraints. Urban malaria in Africa is associated with lower risk than savanna malaria; larval control may be considered though its role is not so far well established. In contrast, urban malaria in the Indian subcontinent is associated with higher risks than most adjacent rural areas, and larval control has a definite, though not exclusive, role. Simulation modelling of cost-effectiveness of malaria control strategies in different scenarios should prioritize ecotypes where malaria control encounters serious technical problems. Further field research on malaria and ecology should be interdisciplinary, especially with geography, and pay more attention to juxtapositions and to anthropic elements, especially migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Understanding Human-Plasmodium falciparum Immune Interactions Uncovers the Immunological Role of Worms

PubMed Central

Roussilhon, Christian; Brasseur, Philippe; Agnamey, Patrice; Pérignon, Jean-Louis; Druilhe, Pierre

2010-01-01

Background Former studies have pointed to a monocyte-dependant effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies. Methods and Findings We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate. Conclusion The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies. PMID:20174576

Cost of malaria control in China: Henan's consolidation programme from community and government perspectives.

PubMed Central

Jackson, Sukhan; Sleigh, Adrian C.; Liu, Xi-Li

2002-01-01

OBJECTIVE: To assist with strategic planning for the eradication of malaria in Henan Province, China, which reached the consolidation phase of malaria control in 1992, when only 318 malaria cases were reported. METHODS: We conducted a prospective two-year study of the costs for Henan's malaria control programme. We used a cost model that could also be applied to other malaria programmes in mainland China, and analysed the cost of the three components of Henan's malaria programme: suspected malaria case management, vector surveillance, and population blood surveys. Primary cost data were collected from the government, and data on suspected malaria patients were collected in two malaria counties (population 2 093 100). We enlisted the help of 260 village doctors in six townships or former communes (population 247 762), and studied all 12 325 reported cases of suspected malaria in their catchment areas in 1994 and 1995. FINDINGS: The average annual government investment in malaria control was estimated to be US$ 111 516 (case-management 59%; active blood surveys 25%; vector surveillance 12%; and contingencies and special projects 4%). The average cost (direct and indirect) for patients seeking treatment for suspected malaria was US$ 3.48, equivalent to 10 days' income for rural residents. Each suspected malaria case cost the government an average of US$ 0.78. CONCLUSION: Further cuts in government funding will increase future costs when epidemic malaria returns; investment in malaria control should therefore continue at least at current levels of US$ 0.03 per person at risk. PMID:12219157

Population Density, Climate Variables and Poverty Synergistically Structure Spatial Risk in Urban Malaria in India

PubMed Central

Santos-Vega, Mauricio; Bouma, Menno J; Kohli, Vijay; Pascual, Mercedes

2016-01-01

Background The world is rapidly becoming urban with the global population living in cities projected to double by 2050. This increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. In particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. Interestingly India, as opposed to Africa, harbors a mosquito vector, Anopheles stephensi, which thrives in the man-made environments of cities and acts as the vector for both Plasmodium vivax and Plasmodium falciparum, making the malaria problem a truly urban phenomenon. Here we address the role and determinants of within-city spatial heterogeneity in the incidence patterns of vivax malaria, and then draw comparisons with results for falciparum malaria. Methodology/principal findings Statistical analyses and a phenomenological transmission model are applied to an extensive spatio-temporal dataset on cases of Plasmodium vivax in the city of Ahmedabad (Gujarat, India) that spans 12 years monthly at the level of wards. A spatial pattern in malaria incidence is described that is largely stationary in time for this parasite. Malaria risk is then shown to be associated with socioeconomic indicators and environmental parameters, temperature and humidity. In a more dynamical perspective, an Inhomogeneous Markov Chain Model is used to predict vivax malaria risk. Models that account for climate factors, socioeconomic level and population size show the highest predictive skill. A comparison to the transmission dynamics of falciparum malaria reinforces the conclusion that the spatio-temporal patterns of risk are strongly driven by extrinsic factors. Conclusion/significance Climate forcing and socio-economic heterogeneity act synergistically at local scales on the population dynamics of urban malaria in this city. The stationarity of malaria risk patterns provides a basis for more targeted intervention, such as vector control, based on transmission ‘hotspots’. This is especially relevant for P. vivax, a more resilient parasite than P. falciparum, due to its ability to relapse and the operational shortcomings of delivering a “radical cure”. PMID:27906962

Population Density, Climate Variables and Poverty Synergistically Structure Spatial Risk in Urban Malaria in India.

PubMed

Santos-Vega, Mauricio; Bouma, Menno J; Kohli, Vijay; Pascual, Mercedes

2016-12-01

The world is rapidly becoming urban with the global population living in cities projected to double by 2050. This increase in urbanization poses new challenges for the spread and control of communicable diseases such as malaria. In particular, urban environments create highly heterogeneous socio-economic and environmental conditions that can affect the transmission of vector-borne diseases dependent on human water storage and waste water management. Interestingly India, as opposed to Africa, harbors a mosquito vector, Anopheles stephensi, which thrives in the man-made environments of cities and acts as the vector for both Plasmodium vivax and Plasmodium falciparum, making the malaria problem a truly urban phenomenon. Here we address the role and determinants of within-city spatial heterogeneity in the incidence patterns of vivax malaria, and then draw comparisons with results for falciparum malaria. Statistical analyses and a phenomenological transmission model are applied to an extensive spatio-temporal dataset on cases of Plasmodium vivax in the city of Ahmedabad (Gujarat, India) that spans 12 years monthly at the level of wards. A spatial pattern in malaria incidence is described that is largely stationary in time for this parasite. Malaria risk is then shown to be associated with socioeconomic indicators and environmental parameters, temperature and humidity. In a more dynamical perspective, an Inhomogeneous Markov Chain Model is used to predict vivax malaria risk. Models that account for climate factors, socioeconomic level and population size show the highest predictive skill. A comparison to the transmission dynamics of falciparum malaria reinforces the conclusion that the spatio-temporal patterns of risk are strongly driven by extrinsic factors. Climate forcing and socio-economic heterogeneity act synergistically at local scales on the population dynamics of urban malaria in this city. The stationarity of malaria risk patterns provides a basis for more targeted intervention, such as vector control, based on transmission 'hotspots'. This is especially relevant for P. vivax, a more resilient parasite than P. falciparum, due to its ability to relapse and the operational shortcomings of delivering a "radical cure".

Is Global Warming likely to cause an increased incidence of Malaria?

PubMed Central

Nabi, SA; Qader, SS

2009-01-01

The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by climatic conditions because of its direct relationship with the mosquito population, it is widely assumed that its incidence is likely to increase in a future warmer world. This review article discusses the two contradictory views regarding the association of global warming with an increased incidence of malaria. On one hand, there are many who believe that there is a strong association between the recent increase in malaria incidence and global warming. They predict that as global warming continues, malaria is set to spread in locations where previously it was limited, due to cooler climate. On the other hand, several theories have been put forward which are quite contrary to this prediction. There are multiple other factors which are accountable for the recent upsurge of malaria: for example drug resistance, mosquito control programs, public health facilities, and living standards. PMID:21483497

Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials.

PubMed

Love, Melissa S; Millholland, Melanie G; Mishra, Satish; Kulkarni, Swapnil; Freeman, Katie B; Pan, Wenxi; Kavash, Robert W; Costanzo, Michael J; Jo, Hyunil; Daly, Thomas M; Williams, Dewight R; Kowalska, M Anna; Bergman, Lawrence W; Poncz, Mortimer; DeGrado, William F; Sinnis, Photini; Scott, Richard W; Greenbaum, Doron C

2012-12-13

Plasmodium falciparum pathogenesis is affected by various cell types in the blood, including platelets, which can kill intraerythrocytic malaria parasites. Platelets could mediate these antimalarial effects through human defense peptides (HDPs), which exert antimicrobial effects by permeabilizing membranes. Therefore, we screened a panel of HDPs and determined that human platelet factor 4 (hPF4) kills malaria parasites inside erythrocytes by selectively lysing the parasite digestive vacuole (DV). PF4 rapidly accumulates only within infected erythrocytes and is required for parasite killing in infected erythrocyte-platelet cocultures. To exploit this antimalarial mechanism, we tested a library of small, nonpeptidic mimics of HDPs (smHDPs) and identified compounds that kill P. falciparum by rapidly lysing the parasite DV while sparing the erythrocyte plasma membrane. Lead smHDPs also reduced parasitemia in a murine malaria model. Thus, identifying host molecules that control parasite growth can further the development of related molecules with therapeutic potential. Copyright © 2012 Elsevier Inc. All rights reserved.

The mode of action of spatial repellents and their impact on vectorial capacity of Anopheles gambiae sensu stricto.

PubMed

Ogoma, Sheila B; Ngonyani, Hassan; Simfukwe, Emmanuel T; Mseka, Antony; Moore, Jason; Maia, Marta F; Moore, Sarah J; Lorenz, Lena M

2014-01-01

Malaria vector control relies on toxicity of insecticides used in long lasting insecticide treated nets and indoor residual spraying. This is despite evidence that sub-lethal insecticides reduce human-vector contact and malaria transmission. The impact of sub-lethal insecticides on host seeking and blood feeding of mosquitoes was measured. Taxis boxes distinguished between repellency and attraction inhibition of mosquitoes by measuring response of mosquitoes towards or away from Transfluthrin coils and humans. Protective effective distance of coils and long-term effects on blood feeding were measured in the semi-field tunnel and in a Peet Grady chamber. Laboratory reared pyrethroid susceptible Anopheles gambiae sensu stricto mosquitoes were used. In the taxis boxes, a higher proportion of mosquitoes (67%-82%) were activated and flew towards the human in the presence of Transfluthrin coils. Coils did not hinder attraction of mosquitoes to the human. In the semi-field Tunnel, coils placed 0.3 m from the human reduced feeding by 86% (95% CI [0.66; 0.95]) when used as a "bubble" compared to 65% (95% CI [0.51; 0.76]) when used as a "point source". Mosquitoes exposed to coils inside a Peet Grady chamber were delayed from feeding normally for 12 hours but there was no effect on free flying and caged mosquitoes exposed in the semi-field tunnel. These findings indicate that airborne pyrethroids minimize human-vector contact through reduced and delayed blood feeding. This information is useful for the development of target product profiles of spatial repellent products that can be used to complement mainstream malaria vector control tools.

Vector movement underlies avian malaria at upper elevation in Hawaii: implications for transmission of human malaria.

PubMed

Freed, Leonard A; Cann, Rebecca L

2013-11-01

With climate warming, malaria in humans and birds at upper elevations is an emerging infectious disease because development of the parasite in the mosquito vector and vector life history are both temperature dependent. An enhanced-mosquito-movement model from climate warming predicts increased transmission of malaria at upper elevation sites that are too cool for parasite development in the mosquito vector. We evaluate this model with avian malaria (Plasmodium relictum) at 1,900-m elevation on the Island of Hawaii, with air temperatures too low for sporogony in the vector (Culex quinquefasciatus). On a well-defined site over a 14-year period, 10 of 14 species of native and introduced birds became infected, several epizootics occurred, and the increase in prevalence was driven more by resident species than by mobile species that could have acquired their infections at lower elevations. Greater movement of infectious mosquitoes from lower elevations now permits avian malaria to spread at 1,900 m in Hawaii, in advance of climate warming at that elevation. The increase in malaria at upper elevations due to dispersal of infectious mosquitoes is a real alternative to temperature for the increased incidence of human malaria in tropical highlands.

[Global trends in malaria control. Progress and topical tasks in malaria control programs].

PubMed

Kondrashin, A V; Baranova, A M; Morozova, L F; Stepanova, E V

2011-01-01

This communication is the first in the series consisting of two publications describing the present state of malaria control and elimination in the world. The global malaria situation in 2009-2010 demonstrated a considerable situation as compared to the previous years. This improvement is associated with a considerable global increase of investments made by both national governments and world society to the malaria control programs. Spectacular progress has been achieved even in the areas of the most infection-affected African countries situated to the south of the Sahara Desert. It has been estimated that malaria cases in the world declined from 233, 000,000 in 2000 to 225,000,000 in 2009. Malaria mortality decreased from 985,000 in 2000 to 781,000 in 2009. To maintain the results achieved and to further reduce the problem of malaria worldwide, it is necessary to ensure a long-term political and financial support for malaria control programs at the national and international levels.

Enhancing the application of effective malaria interventions in Africa through training.

PubMed

Ijumba, Jasper N; Kitua, Andrew Y

2004-08-01

Africa bears more than 90% of the entire global malaria disease burden. Surprisingly, even with the current renewed interest in malaria prevention and control and the enabling environment resulting from the Roll Back Malaria initiative and the political commitment made by the African Presidents at the Abuja Summit, there are still no significant initiatives for strengthening capacity for malaria control through training within the African continent itself. The Center for Enhancement of Effective Malaria Interventions (CEEMI) has been established in Dar es Salaam, Tanzania for results-oriented training. It is intended to provide the needed skills for identifying and solving malaria control problems and providing incentives to malaria control workers in their work performance. The intention is to produce implementers with leadership skills for planning and managing malaria control activities and who can use strategic thinking in improving their work performance. To sustain political commitment and support and to sensitize the community on malaria issues, the CEEMI, in collaboration with the Ministry of Health (National Malaria Control Program), the Institute of Journalism and Mass Communication of the University of Dar es Salaam, and the Commonwealth Broadcasting Association have already conducted malaria seminars for Tanzanian Members of Parliament and journalists from Kenya, Malawi, Tanzania, and Uganda. Additionally, a diploma course in health communication is being developed for journalists and for the same purpose. Also being developed is a training module for "Council Malaria Focal Person." This is aimed at complementing the Roll Back Malaria initiative to meet the Abuja targets of reducing morbidity and mortality due to malaria by 50% by 2010. Copyright 2004 The American Society of Tropical Medicine and Hygiene

Strengthening public health pesticide management in countries endemic with malaria or other major vector-borne diseases: an evaluation of three strategies.

PubMed

van den Berg, Henk; Yadav, Rajpal S; Zaim, Morteza

2014-09-18

Public health pesticides has been the mainstay control of vectors of malaria and other diseases, and public health pests, but there is increasing concern over how these pesticides are being managed. Poor pesticide management could lead to risks to human health and the environment, or diminish the effectiveness of interventions. Strategies for strengthening the management of public health pesticides, from manufacture to disposal, should be evaluated to propose future directions. The process and outcomes of three strategies were studied in five regions of the WHO (African Region, Eastern Mediterranean Region, South-East Asia Region, Western Pacific Region, and American Region) and 13 selected countries. These strategies are: regional policy development, in-depth country support and thematic support across countries. Consensus, frameworks and action plans on public health pesticide management were developed at regional level. Country support for situation analysis and national action planning highlighted weaknesses over the entire spectrum of pesticide management practices, mainly related to malaria control. The thematic support on pesticide quality control contributed to structural improvements on a priority issue for malaria control across countries. The three strategies showed promising and complementary results, but guidelines and tools for implementation of the strategies should be further improved. Increased national and international priority should be given to support the development of policy, legislation and capacity that are necessary for sound management of public health pesticides.

Current status and challenge of Human Parasitology teaching in China

PubMed Central

Peng, Hong-Juan; Zhang, Chao; Wang, Chun-Mei; Chen, Xiao-Guang

2012-01-01

Parasitic infection profile in China has been changed greatly with the rapid economic development in China since the 1980s, such as the tremendous decreased infection rate of the soil-borne helminthiasis, the elimination of filariasis, the control of malaria, and the initiation to eradicate malaria in 2020. Some food-borne parasitic infections have increased such as Clonorchiasis, Cysticercosis, and Echinococcosis, probably because of the increased chances of eating out. This trend directly affected the status of Human Parasitology teaching in medical universities, such as the shorten length of this course, re-adjusted contents structure and teaching manners, even the change of the name of this course. In this paper, we analyzed the current status and challenges of Human Parasitology teaching in medical universities, and discussed the requisite contents and manners in course delivery and measures to improve the quality of Human Parasitology teaching in China. PMID:23265609

Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test

PubMed Central

Hommel, Benjamin; Charuel, Jean-Luc; Jaureguiberry, Stéphane; Arnaud, Laurent; Courtin, Regis; Kassab, Petra; Prendki, Virginie; Paris, Luc; Ghillani-Dalbin, Pascale; Thellier, Marc; Caumes, Eric; Amoura, Zahir; Mazier, Dominique; Musset, Lucile; Buffet, Pierre; Miyara, Makoto

2014-01-01

Background Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). Methods We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. Results We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. Conclusion In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy. PMID:24551116

Identification of Plasmodium spp. in Neotropical primates of Maranhense Amazon in Northeast Brazil.

PubMed

Figueiredo, Mayra Araguaia Pereira; Di Santi, Silvia Maria; Manrique, Wilson Gómez; André, Marcos Rogério; Machado, Rosangela Zacarias

2017-01-01

In the Brazilian Amazon region, malaria caused by Plasmodium malariae is considered to be a zoonosis because of cross-transfer of the parasite between humans and Neotropical primates. To contribute information on this issue, we investigated occurrences of natural infection with Plasmodium sp. among Neotropical primates in the Maranhense Amazon (Amazon region of the state of Maranhão), in the northeastern region of Brazil. Blood samples were collected from 161 Neotropical primates of six species that were caught in an environmental reserve (Sítio Aguahy) and from captive primates (CETAS-Wildlife Screening Center, municipality of São Luís), in Maranhão. Plasmodium sp. was diagnosed based on light microscopy, PCR, qPCR and LAMP for amplification of the 18S rRNA gene. Serum samples were also assayed by means of indirect immunofluorescence for IgG antibodies against P. malariae/P. brasilianum, P. falciparum and P. berghei. Parasites were detected through light microscopy on five slides from captive primates (four Sapajus spp. and one Callithrix jacchus). In the molecular tests, 34.16% (55/161) and 29.81% (48/161) of the animals sampled were positive in the qPCR and PCR assays, respectively. In the PCR, 47/48 animals were positive for P. malariae/P. brasilianum; of these, eight were free-living primates and 39 from CETAS, São Luís. One sample showed a band in the genus-specific reaction, but not in the second PCR reaction. Anti-P. malariae/P. brasilianum IgG antibodies were detected in four serum samples from Sapajus spp. in captivity. In this study, circulation of P. malariae/P. brasilianum in Neotropical primates was confirmed, with low levels of parasitemia and low levels of antibodies. The importance of these animals as reservoirs of human malaria in the region studied is still unknown. This scenario has an impact on control and elimination of malaria in this region.

[Investigation on knowledge of malaria prevention and control in residents of Suining County].

PubMed

Tang, Yue-e

2014-08-01

To understand the status of knowledge of malaria prevention and control in residents of Suining County, so as to provide the reference for improving the implementation of malaria elimination. Nine villages in 3 townships (3 villages per township) were randomly selected as the study areas, and 200 residents aged above 15 years of each village were investigated with questionnaire for the knowledge of malaria prevention and control. The awareness rates of "malaria transmission way", main symptoms of malaria", "life-threatening of falciparum malaria", "how to treat malaria", and "how to prevent malaria" were 96.27%, 95.01%, 81.46%, 98.19% and 96.27%, respectively. There were no significant differences between the different genders and among the different areas (all P >0.05), but there were significant differences among different age groups (all P <0.05). The awareness of malaria prevention and control in residents of Suining County is relatively high, which means the health education is effective.

Perceived role and its enhancing factors among the village health volunteers regarding malaria control in rural myanmar.

PubMed

Aung, P Linn; Silawan, Tassanee; Rawiworrakul, Tassanee; Min, Myo

2018-01-01

Village health volunteers (VHVs) are key agents for malaria control in community. The Myanmar Medical Association-Malaria (MMA-Malaria) Project has promoted effective malaria control in endemic and high-risk townships by supporting roles of VHVs. To assess the roles of VHVs on malaria control and factors enhancing their roles in rural Myanmar. A cross-sectional study was conducted in five townships where the MMA-Malaria Project has been implemented. One hundred and fifty VHVs were sampled from five townships by simple random sampling. Data were collected by trained interviewers using structured questionnaires, which covered sociodemographic, supportive, motivational factors, and roles of malaria control. Studied variables were described by proportions, means, and standard deviations and were analyzed for their association by odds ratio with 95% confidence interval and Chi-square tests. Most of VHVs (96%) expected to demonstrate good roles on malaria control, but only 44.0% exhibited current roles at a good level. Factors enhancing their roles were female (P = 0.037), family income ≥50,001 kyat/month (P < 0.015), time serving as a volunteer 1-2 years (P = 0.006), good knowledge of malaria control (P < 0.001), good family support (P < 0.001), good community support (P < 0.001), and good motivational factors (P = 0.002). VHVs are key agents for malaria control in community. Most of VHVs expected to demonstrate good roles on malaria control, but less than half of them exhibited current roles at a good level. The systems and program for improving VHVs' knowledge, encouraging family and community support, and promoting motivation are essential for their better roles.

76 FR 13619 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Funding...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Institute Pasteur of Madagascar and the Centers for Disease Control and Prevention on Malaria and Vector... Malaria Prevention and Control in the Republic of Uganda as Part of the President's Malaria Initiative... Institute Pasteur of Madagascar and the Centers for Disease Control and Prevention on Malaria and Vector...

The economics of malaria control and elimination: a systematic review.

PubMed

Shretta, Rima; Avanceña, Anton L V; Hatefi, Arian

2016-12-12

Declining donor funding and competing health priorities threaten the sustainability of malaria programmes. Elucidating the cost and benefits of continued investments in malaria could encourage sustained political and financial commitments. The evidence, although available, remains disparate. This paper reviews the existing literature on the economic and financial cost and return of malaria control, elimination and eradication. A review of articles that were published on or before September 2014 on the cost and benefits of malaria control and elimination was performed. Studies were classified based on their scope and were analysed according to two major categories: cost of malaria control and elimination to a health system, and cost-benefit studies. Only studies involving more than two control or elimination interventions were included. Outcomes of interest were total programmatic cost, cost per capita, and benefit-cost ratios (BCRs). All costs were converted to 2013 US$ for standardization. Of the 6425 articles identified, 54 studies were included in this review. Twenty-two were focused on elimination or eradication while 32 focused on intensive control. Forty-eight per cent of studies included in this review were published on or after 2000. Overall, the annual per capita cost of malaria control to a health system ranged from $0.11 to $39.06 (median: $2.21) while that for malaria elimination ranged from $0.18 to $27 (median: $3.00). BCRs of investing in malaria control and elimination ranged from 2.4 to over 145. Overall, investments needed for malaria control and elimination varied greatly amongst the various countries and contexts. In most cases, the cost of elimination was greater than the cost of control. At the same time, the benefits of investing in malaria greatly outweighed the costs. While the cost of elimination in most cases was greater than the cost of control, the benefits greatly outweighed the cost. Information from this review provides guidance to national malaria programmes on the cost and benefits of malaria elimination in the absence of data. Importantly, the review highlights the need for more robust economic analyses using standard inputs and methods to strengthen the evidence needed for sustained financing for malaria elimination.

Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model

PubMed Central

Dunachie, Susanna; Berthoud, Tamara; Hill, Adrian V.S.; Fletcher, Helen A.

2015-01-01

Introduction The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. Methods We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. Results Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. Conclusions These results represent novel insights into the immune repertoires involved in malaria vaccination. PMID:26256523

Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model.

PubMed

Dunachie, Susanna; Berthoud, Tamara; Hill, Adrian V S; Fletcher, Helen A

2015-09-29

The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. These results represent novel insights into the immune repertoires involved in malaria vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Knowledge, attitude, and practice about malaria: Socio-demographic implications for malaria control in rural Ghana.

PubMed

Assan, Abraham; Takian, Amirhossein; Hanafi-Bojd, Ahmad Ali; Rahimiforoushani, Abbas; Nematolahi, Shahrzad

2017-11-01

Despite continuing international attention to malaria prevention, the disease remains a global public health problem. We investigated socio-demographic factors influencing knowledge, attitudes, and practices about malaria in rural Ghana. Our survey looked at 354 households. Mean knowledge score was higher among individuals with a history of volunteers having visited their households to educate them about malaria; families with 4-6 members; and males. Households with at least one under-five-aged child also had significantly higher knowledge scores. Households with at least one pregnant woman evinced a positive attitude towards malaria prevention. National malaria control strategies have achieved positive results in the fight against malaria. Nonetheless, multipronged community-based health strategies that integrate malaria programs and population growth control initiatives may be able to reach by 2030 the sustainable development goal of eliminating malaria.

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

PubMed

Payne, Ruth O; Milne, Kathryn H; Elias, Sean C; Edwards, Nick J; Douglas, Alexander D; Brown, Rebecca E; Silk, Sarah E; Biswas, Sumi; Miura, Kazutoyo; Roberts, Rachel; Rampling, Thomas W; Venkatraman, Navin; Hodgson, Susanne H; Labbé, Geneviève M; Halstead, Fenella D; Poulton, Ian D; Nugent, Fay L; de Graaf, Hans; Sukhtankar, Priya; Williams, Nicola C; Ockenhouse, Christian F; Kathcart, April K; Qabar, Aziz N; Waters, Norman C; Soisson, Lorraine A; Birkett, Ashley J; Cooke, Graham S; Faust, Saul N; Woods, Colleen; Ivinson, Karen; McCarthy, James S; Diggs, Carter L; Vekemans, Johan; Long, Carole A; Hill, Adrian V S; Lawrie, Alison M; Dutta, Sheetij; Draper, Simon J

2016-06-01

Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. NCT02044198. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01

PubMed Central

Payne, Ruth O.; Milne, Kathryn H.; Elias, Sean C.; Edwards, Nick J.; Douglas, Alexander D.; Brown, Rebecca E.; Silk, Sarah E.; Biswas, Sumi; Miura, Kazutoyo; Roberts, Rachel; Rampling, Thomas W.; Venkatraman, Navin; Hodgson, Susanne H.; Labbé, Geneviève M.; Halstead, Fenella D.; Poulton, Ian D.; Nugent, Fay L.; de Graaf, Hans; Sukhtankar, Priya; Williams, Nicola C.; Ockenhouse, Christian F.; Kathcart, April K.; Qabar, Aziz N.; Waters, Norman C.; Soisson, Lorraine A.; Birkett, Ashley J.; Cooke, Graham S.; Faust, Saul N.; Woods, Colleen; Ivinson, Karen; McCarthy, James S.; Diggs, Carter L.; Vekemans, Johan; Long, Carole A.; Hill, Adrian V. S.; Lawrie, Alison M.; Dutta, Sheetij; Draper, Simon J.

2016-01-01

Background. Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. Methods. Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. Results. FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. Conclusions. FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. Clinical Trials Registration. NCT02044198. PMID:26908756

Integrated vector management for malaria control

PubMed Central

Beier, John C; Keating, Joseph; Githure, John I; Macdonald, Michael B; Impoinvil, Daniel E; Novak, Robert J

2008-01-01

Integrated vector management (IVM) is defined as "a rational decision-making process for the optimal use of resources for vector control" and includes five key elements: 1) evidence-based decision-making, 2) integrated approaches 3), collaboration within the health sector and with other sectors, 4) advocacy, social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has been made in developing and promoting IVM for national malaria control programmes in Africa at a time when successful malaria control programmes are scaling-up with insecticide-treated nets (ITN) and/or indoor residual spraying (IRS) coverage. While interventions using only ITNs and/or IRS successfully reduce transmission intensity and the burden of malaria in many situations, it is not clear if these interventions alone will achieve those critical low levels that result in malaria elimination. Despite the successful employment of comprehensive integrated malaria control programmes, further strengthening of vector control components through IVM is relevant, especially during the "end-game" where control is successful and further efforts are required to go from low transmission situations to sustained local and country-wide malaria elimination. To meet this need and to ensure sustainability of control efforts, malaria control programmes should strengthen their capacity to use data for decision-making with respect to evaluation of current vector control programmes, employment of additional vector control tools in conjunction with ITN/IRS tactics, case-detection and treatment strategies, and determine how much and what types of vector control and interdisciplinary input are required to achieve malaria elimination. Similarly, on a global scale, there is a need for continued research to identify and evaluate new tools for vector control that can be integrated with existing biomedical strategies within national malaria control programmes. This review provides an overview of how IVM programmes are being implemented, and provides recommendations for further development of IVM to meet the goals of national malaria control programmes in Africa. PMID:19091038

Preventive Medicine in World War 2. Volume 6. Communicable Diseases. Malaria

DTIC Science & Technology

1963-01-01

important in lighting disease as in fighting the human enemy. Rut this seemingly obvious fact was almost completely forgotten in the early months of...personnel and supplies. The military exiH-rieiiiv taught miri ’ again thnt the prevention of malaria is neither automatic nor simple Inn is com- pounded of...oversea lliralt-rs where turn were exposed to malaria, in order to determine whether this drug iimlil te-t a« a causal prophylactic in human malaria

Simulating the spread of malaria using a generic transmission model for mosquito-borne infectious diseases

NASA Astrophysics Data System (ADS)

Kon, Cynthia Mui Lian; Labadin, Jane

2016-06-01

Malaria is a critical infection caused by parasites which are spread to humans through mosquito bites. Approximately half of the world's population is in peril of getting infected by malaria. Mosquito-borne diseases have a standard behavior where they are transmitted in the same manner, only through vector mosquito. Taking this into account, a generic spatial-temporal model for transmission of multiple mosquito-borne diseases had been formulated. Our interest is to reproduce the actual cases of different mosquito-borne diseases using the generic model and then predict future cases so as to improve control and target measures competently. In this paper, we utilize notified weekly malaria cases in four districts in Sarawak, Malaysia, namely Kapit, Song, Belaga and Marudi. The actual cases for 36 weeks, which is from week 39 in 2012 to week 22 in 2013, are compared with simulations of the generic spatial-temporal transmission mosquito-borne diseases model. We observe that the simulation results display corresponding result to the actual malaria cases in the four districts.

Malaria resurgence: a systematic review and assessment of its causes

PubMed Central

2012-01-01

Background Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today’s successful malaria control programmes. PMID:22531245

Using a geographical information system to plan a malaria control programme in South Africa.

PubMed Central

Booman, M.; Durrheim, D. N.; La Grange, K.; Martin, C.; Mabuza, A. M.; Zitha, A.; Mbokazi, F. M.; Fraser, C.; Sharp, B. L.

2000-01-01

INTRODUCTION: Sustainable control of malaria in sub-Saharan Africa is jeopardized by dwindling public health resources resulting from competing health priorities that include an overwhelming acquired immunodeficiency syndrome (AIDS) epidemic. In Mpumalanga province, South Africa, rational planning has historically been hampered by a case surveillance system for malaria that only provided estimates of risk at the magisterial district level (a subdivision of a province). METHODS: To better map control programme activities to their geographical location, the malaria notification system was overhauled and a geographical information system implemented. The introduction of a simplified notification form used only for malaria and a carefully monitored notification system provided the good quality data necessary to support an effective geographical information system. RESULTS: The geographical information system displays data on malaria cases at a village or town level and has proved valuable in stratifying malaria risk within those magisterial districts at highest risk, Barberton and Nkomazi. The conspicuous west-to-east gradient, in which the risk rises sharply towards the Mozambican border (relative risk = 4.12, 95% confidence interval = 3.88-4.46 when the malaria risk within 5 km of the border was compared with the remaining areas in these two districts), allowed development of a targeted approach to control. DISCUSSION: The geographical information system for malaria was enormously valuable in enabling malaria risk at town and village level to be shown. Matching malaria control measures to specific strata of endemic malaria has provided the opportunity for more efficient malaria control in Mpumalanga province. PMID:11196490

Optimal control for Malaria disease through vaccination

NASA Astrophysics Data System (ADS)

Munzir, Said; Nasir, Muhammad; Ramli, Marwan

2018-01-01

Malaria is a disease caused by an amoeba (single-celled animal) type of plasmodium where anopheles mosquito serves as the carrier. This study examines the optimal control problem of malaria disease spread based on Aron and May (1982) SIR type models and seeks the optimal solution by minimizing the prevention of the spreading of malaria by vaccine. The aim is to investigate optimal control strategies on preventing the spread of malaria by vaccination. The problem in this research is solved using analytical approach. The analytical method uses the Pontryagin Minimum Principle with the symbolic help of MATLAB software to obtain optimal control result and to analyse the spread of malaria with vaccination control.

Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL/6 Mice.

PubMed

Blank, Jannike; Behrends, Jochen; Jacobs, Thomas; Schneider, Bianca E

2016-02-01

Cerebral malaria (CM) is the most severe complication of human infection with Plasmodium falciparum. The mechanisms predisposing to CM are still not fully understood. Proinflammatory immune responses are required for the control of blood-stage malaria infection but are also implicated in the pathogenesis of CM. A fine balance between pro- and anti-inflammatory immune responses is required for parasite clearance without the induction of host pathology. The most accepted experimental model to study human CM is Plasmodium berghei ANKA (PbANKA) infection in C57BL/6 mice that leads to the development of a complex neurological syndrome which shares many characteristics with the human disease. We applied this model to study the outcome of PbANKA infection in mice previously infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is coendemic with malaria in large regions in the tropics, and mycobacteria have been reported to confer some degree of unspecific protection against rodent Plasmodium parasites in experimental coinfection models. We found that concomitant M. tuberculosis infection did not change the clinical course of PbANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. The immunological environments in spleen and brain did not differ between singly infected and coinfected animals; instead, the overall cytokine and T cell responses in coinfected mice were comparable to those in animals solely infected with PbANKA. Our data suggest that M. tuberculosis coinfection is not able to change the outcome of PbANKA-induced disease, most likely because the inflammatory response induced by the parasite rapidly dominates in mice previously infected with M. tuberculosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Can water-level management reduce malaria mosquito abundance around large dams in sub-Saharan Africa?

PubMed Central

Wilson, G. Glenn; Ryder, Darren; Tekie, Habte; Petros, Beyene

2018-01-01

Background Water level management has been suggested as a potential tool to reduce malaria around large reservoirs. However, no field-based test has been conducted to assess the effect of water level management on mosquito larval abundance in African settings. The objective of the present study is to evaluate the effects of water level drawdown rates on mosquito larval abundance. Methods Twelve experimental dams were constructed on the foreshore of the Koka Dam in Ethiopia. These were grouped into four daily water drawdown treatments, each with three replicates: no water-level drawdown (Group 1; Control), 10 mm.d-1 (Group 2), 15 mm.d-1 (Group 3) and 20 mm.d-1 (Group 4). Larval sampling was conducted weekly for a period of 6 weeks each in the main malaria transmission season (October to November 2013) and subsequent dry season (February to March 2014). Larval densities were compared among treatments over time using repeated measures Analysis of Variance (ANOVA). Results A total of 284 Anopheles mosquito larvae were collected from the experimental dams during the study period. Most (63.4%; n = 180) were collected during the main malaria transmission season while the remaining (36.6%; n = 104) were collected during the dry season. Larvae comprised four Anopheles species, dominated by Anopheles arabiensis (48.1% of total larval samples; n = 136) and An. pharoensis (33.2%; n = 94). Mean larval density was highest in control treatment dams with stable water levels throughout the study, and decreased significantly (P < 0.05) with increasing water drawdown rates in both seasons. During the main transmission season, anopheline larval density was generally lower by 30%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, compared with the control dams (Group 1). In the dry season, larval density was reduced by 45%, 70% and 84% in Groups 2, Group 3 and Group 4, respectively, when compared to the control dams. Conclusion Increased water drawdown rates were associated with lower mosquito larval abundance. Water level management could thus serve as a potential control measure for malaria vectors around reservoirs by regulating the persistence of shallow shoreline breeding habitats. Dam operators and water resource managers should consider incorporating water level management as a malaria control mechanism into routine dam operations to manage the risk of malaria transmission to human populations around reservoirs. PMID:29672560

A refined estimate of the malaria burden in Niger.

PubMed

Doudou, Maimouna Halidou; Mahamadou, Aboubacar; Ouba, Ibrahim; Lazoumar, Ramatoulaye; Boubacar, Binta; Arzika, Ibrahim; Zamanka, Halima; Ibrahim, Maman L; Labbo, Rabiou; Maiguizo, Seydou; Girond, Florian; Guillebaud, Julia; Maazou, Abani; Fandeur, Thierry

2012-03-27

The health authorities of Niger have implemented several malaria prevention and control programmes in recent years. These interventions broadly follow WHO guidelines and international recommendations and are based on interventions that have proved successful in other parts of Africa. Most performance indicators are satisfactory but, paradoxically, despite the mobilization of considerable human and financial resources, the malaria-fighting programme in Niger seems to have stalled, as it has not yet yielded the expected significant decrease in malaria burden. Indeed, the number of malaria cases reported by the National Health Information System has actually increased by a factor of five over the last decade, from about 600,000 in 2000 to about 3,000,000 in 2010. One of the weaknesses of the national reporting system is that the recording of malaria cases is still based on a presumptive diagnosis approach, which overestimates malaria incidence. An extensive nationwide survey was carried out to determine by microscopy and RDT testing, the proportion of febrile patients consulting at health facilities for suspected malaria actually suffering from the disease, as a means of assessing the magnitude of this problem and obtaining a better estimate of malaria morbidity in Niger. In total, 12,576 febrile patients were included in this study; 57% of the slides analysed were positive for the malaria parasite during the rainy season, when transmission rates are high, and 9% of the slides analysed were positive during the dry season, when transmission rates are lower. The replacement of microscopy methods by rapid diagnostic tests resulted in an even lower rate of confirmation, with only 42% of cases testing positive during the rainy season, and 4% during the dry season. Fever alone has a low predictive value, with a low specificity and sensitivity. These data highlight the absolute necessity of confirming all reported malaria cases by biological diagnosis methods, to increase the accuracy of the malaria indicators used in monitoring and evaluation processes and to improve patient care in the more remote areas of Niger. This country extends over a large range of latitudes, resulting in the existence of three major bioclimatic zones determining vector distribution and endemicity. This survey showed that the number of cases of presumed malaria reported in health centres in Niger is largely overestimated. The results highlight inadequacies in the description of the malaria situation and disease risk in Niger, due to the over-diagnosis of malaria in patients with simple febrile illness. They point out the necessity of confirming all cases of suspected malaria by biological diagnosis methods and the need to take geographic constraints into account more effectively, to improve malaria control and to adapt the choice of diagnostic method to the epidemiological situation in the area concerned. Case confirmation will thus also require a change in behaviour, through the training of healthcare staff, the introduction of quality control, greater supervision of the integrated health centres, the implementation of good clinical practice and a general optimization of the use of available diagnostic methods.

Role of non-human primates in malaria vaccine development: Memorandum from a WHO Meeting*

PubMed Central

1988-01-01

This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations. PMID:3266112

Cost analysis of a school-based comprehensive malaria program in primary schools in Sikasso region, Mali.

PubMed

Maccario, Roberta; Rouhani, Saba; Drake, Tom; Nagy, Annie; Bamadio, Modibo; Diarra, Seybou; Djanken, Souleymane; Roschnik, Natalie; Clarke, Siân E; Sacko, Moussa; Brooker, Simon; Thuilliez, Josselin

2017-06-12

The expansion of malaria prevention and control to school-aged children is receiving increasing attention, but there are still limited data on the costs of intervention. This paper analyses the costs of a comprehensive school-based intervention strategy, delivered by teachers, that included participatory malaria educational activities, distribution of long lasting insecticide-treated nets (LLIN), and Intermittent Parasite Clearance in schools (IPCs) in southern Mali. Costs were collected alongside a randomised controlled trial conducted in 80 primary schools in Sikasso Region in Mali in 2010-2012. Cost data were compiled between November 2011 and March 2012 for the 40 intervention schools (6413 children). A provider perspective was adopted. Using an ingredients approach, costs were classified by cost category and by activity. Total costs and cost per child were estimated for the actual intervention, as well as for a simpler version of the programme more suited for scale-up by the government. Univariate sensitivity analysis was performed. The economic cost of the comprehensive intervention was estimated to $10.38 per child (financial cost $8.41) with malaria education, LLIN distribution and IPCs costing $2.13 (20.5%), $5.53 (53.3%) and $2.72 (26.2%) per child respectively. Human resources were found to be the key cost driver, and training costs were the greatest contributor to overall programme costs. Sensitivity analysis showed that an adapted intervention delivering one LLIN instead of two would lower the economic cost to $8.66 per child; and that excluding LLIN distribution in schools altogether, for example in settings where malaria control already includes universal distribution of LLINs at community-level, would reduce costs to $4.89 per child. A comprehensive school-based control strategy may be a feasible and affordable way to address the burden of malaria among schoolchildren in the Sahel.

Field Evaluation of a Push-Pull System to Reduce Malaria Transmission

PubMed Central

Menger, David J.; Omusula, Philemon; Holdinga, Maarten; Homan, Tobias; Carreira, Ana S.; Vandendaele, Patrice; Derycke, Jean-Luc; Mweresa, Collins K.; Mukabana, Wolfgang Richard; van Loon, Joop J. A.; Takken, Willem

2015-01-01

Malaria continues to place a disease burden on millions of people throughout the tropics, especially in sub-Saharan Africa. Although efforts to control mosquito populations and reduce human-vector contact, such as long-lasting insecticidal nets and indoor residual spraying, have led to significant decreases in malaria incidence, further progress is now threatened by the widespread development of physiological and behavioural insecticide-resistance as well as changes in the composition of vector populations. A mosquito-directed push-pull system based on the simultaneous use of attractive and repellent volatiles offers a complementary tool to existing vector-control methods. In this study, the combination of a trap baited with a five-compound attractant and a strip of net-fabric impregnated with micro-encapsulated repellent and placed in the eaves of houses, was tested in a malaria-endemic village in western Kenya. Using the repellent delta-undecalactone, mosquito house entry was reduced by more than 50%, while the traps caught high numbers of outdoor flying mosquitoes. Model simulations predict that, assuming area-wide coverage, the addition of such a push-pull system to existing prevention efforts will result in up to 20-fold reductions in the entomological inoculation rate. Reductions of such magnitude are also predicted when mosquitoes exhibit a high resistance against insecticides. We conclude that a push-pull system based on non-toxic volatiles provides an important addition to existing strategies for malaria prevention. PMID:25923114

Detection of 1014F kdr mutation in four major Anopheline malaria vectors in Indonesia.

PubMed

Syafruddin, Din; Hidayati, Anggi P N; Asih, Puji B S; Hawley, William A; Sukowati, Supratman; Lobo, Neil F

2010-11-08

Malaria is a serious public health problem in Indonesia, particularly in areas outside Java and Bali. The spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. To better understand patterns of transmission and resistance in Indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, Purworejo in Central Java, South Lampung District in Sumatera and South Halmahera District in North Mollucca. Mosquitoes were collected from the three areas through indoor and outdoor human landing catches (HLC) and indoor restinging catches. Specimens were identified morphologically by species and kept individually in 1.5 ml Eppendorf microtube. A fragment of the VGSC gene from 95 mosquito samples was sequenced and kdr allelic variation determined. The molecular analysis of these anopheline mosquitoes revealed the existence of the 1014F allele in 4 major malaria vectors from South Lampung. These species include, Anopheles sundaicus, Anopheles aconitus, Anopheles subpictus and Anopheles vagus. The 1014F allele was not found in the other areas. The finding documents the presence of this mutant allele in Indonesia, and implies that selection pressure on the Anopheles population in this area has occurred. Further studies to determine the impact of the resistance allele on the efficacy of pyrethroids in control programmes are needed.

Detection of 1014F kdr mutation in four major Anopheline malaria vectors in Indonesia

PubMed Central

2010-01-01

Background Malaria is a serious public health problem in Indonesia, particularly in areas outside Java and Bali. The spread of resistance to the currently available anti-malarial drugs or insecticides used for mosquito control would cause an increase in malaria transmission. To better understand patterns of transmission and resistance in Indonesia, an integrated mosquito survey was conducted in three areas with different malaria endemicities, Purworejo in Central Java, South Lampung District in Sumatera and South Halmahera District in North Mollucca. Methods Mosquitoes were collected from the three areas through indoor and outdoor human landing catches (HLC) and indoor restinging catches. Specimens were identified morphologically by species and kept individually in 1.5 ml Eppendorf microtube. A fragment of the VGSC gene from 95 mosquito samples was sequenced and kdr allelic variation determined. Results The molecular analysis of these anopheline mosquitoes revealed the existence of the 1014F allele in 4 major malaria vectors from South Lampung. These species include, Anopheles sundaicus, Anopheles aconitus, Anopheles subpictus and Anopheles vagus. The 1014F allele was not found in the other areas. Conclusion The finding documents the presence of this mutant allele in Indonesia, and implies that selection pressure on the Anopheles population in this area has occurred. Further studies to determine the impact of the resistance allele on the efficacy of pyrethroids in control programmes are needed. PMID:21054903

Control of malaria in the Comoro Islands over the past century.

PubMed

Chakir, Ismaël; Said, Ali Ibrahim; Affane, Bacar; Jambou, Ronan

2017-09-26

The Comoros are an archipelago located in the Indian Ocean between the eastern coasts of Africa and north of Madagascar. Malaria transmission appeared late in the 19th century due to the intensification of human migration. The story of malaria transmission for the past century is depicted to provide useful lessons for the future. Currently, malaria transmission occurs differently on each island; thus, control strategies must be adapted for each particular island. Tentative malaria control in Comoros has a long history of success and failure. This study reviews the data available as a basis for recommendations for the future. There has been much effort to reach a pre-eradication state in Anjouan and Moheli, but only control steps have been taken in the Great Comoro. To date, the primary strategy used is mass treatment of the population using artemisinin-based combination therapy (ACT), which is similar to the strategy deployed during the 1950s in other countries. ACT appears efficient in two of the three islands; however, the sustainability of the strategy is unknown. This sustainability is compromised by (i) the huge level of uncontrolled exchange between the Comoro Islands and their neighbours, increasing the risk of introducing ACT-resistant strains, (ii) the use of large quantities of pesticides for agriculture usually associated with the resistance of mosquitoes, and (iii) the cost of the actions themselves. In view of the history of malaria in this area, the first recommendation is to enhance the training of health workers and the population. The second step is to establish a national strategy to assess malaria and related factors, which is currently lacking. A survey to assess the drug sensitivity of the parasites is particularly important in a context of low transmission associated with mass treatment of the population. The last point should be to secure financial support, which is not obvious in a context of pre-elimination. The Comoro Islands are thus a living laboratory to experiments with strategies for elimination, but the future is complex.

Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya.

PubMed

Ingasia, Luicer A; Cheruiyot, Jelagat; Okoth, Sheila Akinyi; Andagalu, Ben; Kamau, Edwin

2016-04-01

Transmission intensity, movement of human and vector hosts, biogeographical features, and malaria control measures are some of the important factors that determine Plasmodium falciparum parasite genetic variability and population structure. Kenya has different malaria ecologies which might require different disease intervention methods. Refined parasite population genetic studies are critical for informing malaria control and elimination strategies. This study describes the genetic diversity and population structure of P. falciparum parasites from the different malaria ecological zones in Kenya. Twelve multi-locus microsatellite (MS) loci previously described were genotyped in 225 P. falciparum isolates collected between 2012 and 2013 from five sites; three in lowland endemic regions (Kisumu, Kombewa, and Malindi) and two in highland, epidemic regions (Kisii and Kericho). Parasites from the lowland endemic and highland epidemic regions of western Kenya had high genetic diversity compared to coastal lowland endemic region of Kenya [Malindi]. The Kenyan parasites had a mean genetic differentiation index (FST) of 0.072 (p=0.011). The multi-locus genetic analysis of the 12 MS revealed all the parasites had unique haplotypes. Significant linkage disequilibrium (LD) was observed in all the five parasite populations. Kisumu had the most significant index of association values (0.16; p<0.0001) whereas Kisii had the least significant index of association values (0.03; p<0.0001). Our data suggest high genetic diversity in Kenyan parasite population with the exception of parasite from Malindi where malaria has been on the decline. The presence of significant LD suggests that there is occurrence of inbreeding in the parasite population. Parasite populations from Kisii showed the strongest evidence for epidemic population structure whereas the rest of the regions showed panmixia. Defining the genetic diversity of the parasites in different ecological regions of Kenya after introduction of the artemether-lumefantrine is important in refining the spread of drug resistant strains and malaria transmission for more effective control and eventual elimination of malaria in Kenya. Copyright © 2015. Published by Elsevier B.V.

Malaria's contribution to World War One - the unexpected adversary.

PubMed

Brabin, Bernard J

2014-12-16

Malaria in the First World War was an unexpected adversary. In 1914, the scientific community had access to new knowledge on transmission of malaria parasites and their control, but the military were unprepared, and underestimated the nature, magnitude and dispersion of this enemy. In summarizing available information for allied and axis military forces, this review contextualizes the challenge posed by malaria, because although data exist across historical, medical and military documents, descriptions are fragmented, often addressing context specific issues. Military malaria surveillance statistics have, therefore, been summarized for all theatres of the War, where available. These indicated that at least 1.5 million solders were infected, with case fatality ranging from 0.2 -5.0%. As more countries became engaged in the War, the problem grew in size, leading to major epidemics in Macedonia, Palestine, Mesopotamia and Italy. Trans-continental passages of parasites and human reservoirs of infection created ideal circumstances for parasite evolution. Details of these epidemics are reviewed, including major epidemics in England and Italy, which developed following home troop evacuations, and disruption of malaria control activities in Italy. Elsewhere, in sub-Saharan Africa many casualties resulted from high malaria exposure combined with minimal control efforts for soldiers considered semi-immune. Prevention activities eventually started but were initially poorly organized and dependent on local enthusiasm and initiative. Nets had to be designed for field use and were fundamental for personal protection. Multiple prevention approaches adopted in different settings and their relative utility are described. Clinical treatment primarily depended on quinine, although efficacy was poor as relapsing Plasmodium vivax and recrudescent Plasmodium falciparum infections were not distinguished and managed appropriately. Reasons for this are discussed and the clinical trial data summarized, as are controversies that arose from attempts at quinine prophylaxis (quininization). In essence, the First World War was a vast experiment in political, demographic, and medical practice which exposed large gaps in knowledge of tropical medicine and unfortunately, of malaria. Research efforts eventually commenced late in the War to address important clinical questions which established a platform for more effective strategies, but in 1918 this relentless foe had outwitted and weakened both allied and axis powers.

A new world malaria map: Plasmodium falciparum endemicity in 2010.

PubMed

Gething, Peter W; Patil, Anand P; Smith, David L; Guerra, Carlos A; Elyazar, Iqbal R F; Johnston, Geoffrey L; Tatem, Andrew J; Hay, Simon I

2011-12-20

Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.

The dominant Anopheles vectors of human malaria in the Americas: occurrence data, distribution maps and bionomic précis

PubMed Central

2010-01-01

Background An increasing knowledge of the global risk of malaria shows that the nations of the Americas have the lowest levels of Plasmodium falciparum and P. vivax endemicity worldwide, sustained, in part, by substantive integrated vector control. To help maintain and better target these efforts, knowledge of the contemporary distribution of each of the dominant vector species (DVS) of human malaria is needed, alongside a comprehensive understanding of the ecology and behaviour of each species. Results A database of contemporary occurrence data for 41 of the DVS of human malaria was compiled from intensive searches of the formal and informal literature. The results for the nine DVS of the Americas are described in detail here. Nearly 6000 occurrence records were gathered from 25 countries in the region and were complemented by a synthesis of published expert opinion range maps, refined further by a technical advisory group of medical entomologists. A suite of environmental and climate variables of suspected relevance to anopheline ecology were also compiled from open access sources. These three sets of data were then combined to produce predictive species range maps using the Boosted Regression Tree method. The predicted geographic extent for each of the following species (or species complex*) are provided: Anopheles (Nyssorhynchus) albimanus Wiedemann, 1820, An. (Nys.) albitarsis*, An. (Nys.) aquasalis Curry, 1932, An. (Nys.) darlingi Root, 1926, An. (Anopheles) freeborni Aitken, 1939, An. (Nys.) marajoara Galvão & Damasceno, 1942, An. (Nys.) nuneztovari*, An. (Ano.) pseudopunctipennis* and An. (Ano.) quadrimaculatus Say, 1824. A bionomics review summarising ecology and behaviour relevant to the control of each of these species was also compiled. Conclusions The distribution maps and bionomics review should both be considered as a starting point in an ongoing process of (i) describing the distributions of these DVS (since the opportunistic sample of occurrence data assembled can be substantially improved) and (ii) documenting their contemporary bionomics (since intervention and control pressures can act to modify behavioural traits). This is the first in a series of three articles describing the distribution of the 41 global DVS worldwide. The remaining two publications will describe those vectors found in (i) Africa, Europe and the Middle East and (ii) in Asia. All geographic distribution maps are being made available in the public domain according to the open access principles of the Malaria Atlas Project. PMID:20712879

Helminth-infected patients with malaria: a low profile transmission hub?

PubMed

Nacher, Mathieu

2012-11-15

Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.

Ranking malaria risk factors to guide malaria control efforts in African highlands.

PubMed

Protopopoff, Natacha; Van Bortel, Wim; Speybroeck, Niko; Van Geertruyden, Jean-Pierre; Baza, Dismas; D'Alessandro, Umberto; Coosemans, Marc

2009-11-25

Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies. A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through "classification and regression trees", an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density. In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors.

More than just immune evasion: Hijacking complement by Plasmodium falciparum.

PubMed

Schmidt, Christoph Q; Kennedy, Alexander T; Tham, Wai-Hong

2015-09-01

Malaria remains one of the world's deadliest diseases. Plasmodium falciparum is responsible for the most severe and lethal form of human malaria. P. falciparum's life cycle involves two obligate hosts: human and mosquito. From initial entry into these hosts, malaria parasites face the onslaught of the first line of host defence, the complement system. In this review, we discuss the complex interaction between complement and malaria infection in terms of hosts immune responses, parasite survival and pathogenesis of severe forms of malaria. We will focus on the role of complement receptor 1 and its associated polymorphisms in malaria immune complex clearance, as a mediator of parasite rosetting and as an entry receptor for P. falciparum invasion. Complement evasion strategies of P. falciparum parasites will also be highlighted. The sexual forms of the malaria parasites recruit the soluble human complement regulator Factor H to evade complement-mediated killing within the mosquito host. A novel evasion strategy is the deployment of parasite organelles to divert complement attack from infective blood stage parasites. Finally we outline the future challenge to understand the implications of these exploitation mechanisms in the interplay between successful infection of the host and pathogenesis observed in severe malaria. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spatially variable risk factors for malaria in a geographically heterogeneous landscape, western Kenya: an explorative study.

PubMed

Homan, Tobias; Maire, Nicolas; Hiscox, Alexandra; Di Pasquale, Aurelio; Kiche, Ibrahim; Onoka, Kelvin; Mweresa, Collins; Mukabana, Wolfgang R; Ross, Amanda; Smith, Thomas A; Takken, Willem

2016-01-04

Large reductions in malaria transmission and mortality have been achieved over the last decade, and this has mainly been attributed to the scale-up of long-lasting insecticidal bed nets and indoor residual spraying with insecticides. Despite these gains considerable residual, spatially heterogeneous, transmission remains. To reduce transmission in these foci, researchers need to consider the local demographical, environmental and social context, and design an appropriate set of interventions. Exploring spatially variable risk factors for malaria can give insight into which human and environmental characteristics play important roles in sustaining malaria transmission. On Rusinga Island, western Kenya, malaria infection was tested by rapid diagnostic tests during two cross-sectional surveys conducted 3 months apart in 3632 individuals from 790 households. For all households demographic data were collected by means of questionnaires. Environmental variables were derived using Quickbird satellite images. Analyses were performed on 81 project clusters constructed by a traveling salesman algorithm, each containing 50-51 households. A standard linear regression model was fitted containing multiple variables to determine how much of the spatial variation in malaria prevalence could be explained by the demographic and environmental data. Subsequently, a geographically-weighted regression (GWR) was performed assuming non-stationarity of risk factors. Special attention was taken to investigate the effect of residual spatial autocorrelation and local multicollinearity. Combining the data from both surveys, overall malaria prevalence was 24%. Scan statistics revealed two clusters which had significantly elevated numbers of malaria cases compared to the background prevalence across the rest of the study area. A multivariable linear model including environmental and household factors revealed that higher socioeconomic status, outdoor occupation and population density were associated with increased malaria risk. The local GWR model improved the model fit considerably and the relationship of malaria with risk factors was found to vary spatially over the island; in different areas of the island socio-economic status, outdoor occupation and population density were found to be positively or negatively associated with malaria prevalence. Identification of risk factors for malaria that vary geographically can provide insight into the local epidemiology of malaria. Examining spatially variable relationships can be a helpful tool in exploring which set of targeted interventions could locally be implemented. Supplementary malaria control may be directed at areas, which are identified as at risk. For instance, areas with many people that work outdoors at night may need more focus in terms of vector control. Trialregister.nl NTR3496-SolarMal, registered on 20 June 2012.

CD8 T-cell-mediated protection against liver-stage malaria: lessons from a mouse model

PubMed Central

Van Braeckel-Budimir, Natalija; Harty, John T.

2014-01-01

Malaria is a major global health problem, with severe mortality in children living in sub-Saharan Africa, and there is currently no licensed, effective vaccine. However, vaccine-induced protection from Plasmodium infection, the causative agent of malaria, was established for humans in small clinical trials and for rodents in the 1960s. Soon after, a critical role for memory CD8 T cells in vaccine-induced protection against Plasmodium liver-stage infection was established in rodent models and is assumed to apply to humans. However, these seminal early studies have led to only modest advances over the ensuing years in our understanding the basic features of memory CD8 T cells required for protection against liver-stage Plasmodium infection, an issue which has likely impeded the development of effective vaccines for humans. Given the ethical and practical limitations in gaining mechanistic insight from human vaccine and challenge studies, animal models still have an important role in dissecting the basic parameters underlying memory CD8 T-cell immunity to Plasmodium. Here, we will highlight recent data from our own work in the mouse model of Plasmodium infection that identify quantitative and qualitative features of protective memory CD8 T-cell responses. Finally, these lessons will be discussed in the context of recent findings from clinical trials of vaccine-induced protection in controlled human challenge models. PMID:24936199

Challenges and prospects for dengue and malaria control in Thailand, Southeast Asia.

PubMed

Corbel, Vincent; Nosten, Francois; Thanispong, Kanutcharee; Luxemburger, Christine; Kongmee, Monthathip; Chareonviriyaphap, Theeraphap

2013-12-01

Despite significant advances in the search for potential dengue vaccines and new therapeutic schemes for malaria, the control of these diseases remains difficult. In Thailand, malaria incidence is falling whereas that of dengue is rising, with an increase in the proportion of reported severe cases. In the absence of antiviral therapeutic options for acute dengue, appropriate case management reduces mortality. However, the interruption of transmission still relies on vector control measures that are currently insufficient to curtail the cycle of epidemics. Drug resistance in malaria parasites is increasing, compromising malaria control and elimination. Deficiencies in our knowledge of vector biology and vectorial capacity also hinder public health efforts for vector control. Challenges to dengue and malaria control are discussed, and research priorities identified. Copyright © 2013. Published by Elsevier Ltd.

Frequent blood feeding enables insecticide-treated nets to reduce transmission by mosquitoes that bite predominately outdoors.

PubMed

Russell, Tanya L; Beebe, Nigel W; Bugoro, Hugo; Apairamo, Allan; Chow, Weng K; Cooper, Robert D; Collins, Frank H; Lobo, Neil F; Burkot, Thomas R

2016-03-10

The effectiveness of vector control on malaria transmission by long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) depends on the vectors entering houses to blood feed and rest when people are inside houses. In the Solomon Islands, significant reductions in malaria have been achieved in the past 20 years with insecticide-treated bed nets, IRS, improved diagnosis and treatment with artemisinin combination therapies; despite the preference of the primary vector, Anopheles farauti, to feed outdoors and early in the evening and thereby avoid potential exposure to insecticides. Rational development of tools to complement LLINs and IRS by attacking vectors outdoor requires detailed knowledge of the biology and behaviours of the target species. Malaria transmission in Central Province, Solomon Islands was estimated by measuring the components comprising the entomological inoculation rate (EIR) as well as the vectorial capacity of An. farauti. In addition, the daily and seasonal biting behaviour of An. farauti, was examined and the duration of the feeding cycle was estimated with a mark-release-recapture experiment. Anopheles farauti was highly exophagic with 72% captured by human landing catches (HLC) outside of houses. Three-quarters (76%) of blood feeding on humans was estimated to occur before 21.00 h. When the hourly location of humans was considered, the proportion of exposure to mosquito bites on humans occurring indoors (πi) was only 0.130 ± 0.129. Peak densities of host seeking An. farauti occurred between October and January. The annual EIR was estimated to be 2.5 for 2012 and 33.2 for 2013. The length of the feeding cycle was 2.1 days. The short duration of the feeding cycle by this species offers an explanation for the substantial control of malaria that has been achieved in the Solomon Islands by LLINs and IRS. Anopheles farauti is primarily exophagic and early biting, with 13% of mosquitoes entering houses to feed late at night during each feeding cycle. The two-day feeding cycle of An. farauti requires females to take 5-6 blood meals before the extrinsic incubation period (EIP) is completed; and this could translate into substantial population-level mortality by LLINs or IRS before females would be infectious to humans with Plasmodium falciparum and Plasmodium vivax. Although An. farauti is primarily exophagic, the indoor vector control tools recommended by the World Health Organization (LLINs and IRS) can still provide an important level of control. Nonetheless, elimination will likely require vector control tools that target other bionomic vulnerabilities to suppress transmission outdoors and that complement the control provided by LLINs and IRS.

Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

PubMed Central

Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

2012-01-01

When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

A push-pull system to reduce house entry of malaria mosquitoes

PubMed Central

2014-01-01

Background Mosquitoes are the dominant vectors of pathogens that cause infectious diseases such as malaria, dengue, yellow fever and filariasis. Current vector control strategies often rely on the use of pyrethroids against which mosquitoes are increasingly developing resistance. Here, a push-pull system is presented, that operates by the simultaneous use of repellent and attractive volatile odorants. Method/Results Experiments were carried out in a semi-field set-up: a traditional house which was constructed inside a screenhouse. The release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip oil e.o. and delta-undecalactone, from the four corners of the house resulted in significant reductions of 45% to 81.5% in house entry of host-seeking malaria mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by simultaneously repelling mosquitoes from the house (push) and removing them from the experimental set-up using attractant-baited traps (pull). Conclusions The outcome of this study suggests that a push-pull system based on attractive and repellent volatiles may successfully be employed to target mosquito vectors of human disease. Reductions in house entry of malaria vectors, of the magnitude that was achieved in these experiments, would likely affect malaria transmission. The repellents used are non-toxic and can be used safely in a human environment. Delta-undecalactone is a novel repellent that showed higher effectiveness than the established repellent PMD. These results encourage further development of the system for practical implementation in the field. PMID:24674451

Monkey Malaria in a European Traveler Returning from Malaysia

PubMed Central

Marti, Hanspeter; Felger, Ingrid; Müller, Dania; Jokiranta, T. Sakari

2008-01-01

In 2007, a Finnish traveler was infected in Peninsular Malaysia with Plasmodium knowlesi, a parasite that usually causes malaria in monkeys. P. knowlesi has established itself as the fifth Plasmodium species that can cause human malaria. The disease is potentially life-threatening in humans; clinicians and laboratory personnel should become more aware of this pathogen in travelers. PMID:18760013

In vivo imaging in NHP models of malaria: challenges, progress and outlooks.

PubMed

Beignon, Anne-Sophie; Le Grand, Roger; Chapon, Catherine

2014-02-01

Animal models of malaria, mainly mice, have made a large contribution to our knowledge of host-pathogen interactions and immune responses, and to drug and vaccine design. Non-human primate (NHP) models for malaria are admittedly under-used, although they are probably closer models than mice for human malaria; in particular, NHP models allow the use of human pathogens (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi). NHPs, whether natural hosts or experimentally challenged with a simian Plasmodium, can also serve as robust pre-clinical models. Some simian parasites are closely related to a human counterpart, with which they may share a common ancestor, and display similar major features with the human infection and pathology. NHP models allow longitudinal studies, from the early events following sporozoite inoculation to the later events, including analysis of organs and tissues, particularly liver, spleen, brain and bone marrow. NHP models have one other significant advantage over mouse models: NHPs are our closest relatives and thus their biology is very similar to ours. Recently developed in vivo imaging tools have provided insight into malaria parasite infection and disease in mouse models. One advantage of these tools is that they limit the need for invasive procedures, such as tissue biopsies. Many such technologies are now available for NHP studies and provide new opportunities for elucidating host/parasite interactions. The aim of this review is to bring the malaria community up to date on what is currently possible and what soon will be, in terms of in vivo imaging in NHP models of malaria, to consider the pros and the cons of the various techniques, and to identify challenges. © 2013.

Assessment of the impact of the malaria elimination programme on the burden of disease morbidity in endemic areas of Iran.

PubMed

Sheikhzadeh, Khodadad; Haghdoost, Ali Akbar; Bahrampour, Abbas; Zolala, Farzaneh; Raeisi, Ahmad

2016-04-14

Controlling and preventive measures considerably reduced malaria incidence in Iran over the past few years, which confined the endemic areas to some regions in the southeastern Iran. The National Malaria Elimination Programme commenced in 2010. With regard to the presumption that the elimination programme interventions have accelerated the declining trend of malaria incidence across the endemic areas of Iran, the present study attempted to assess the effectiveness of the elimination programme by reviewing malaria incidence status, over a 14-year period, and comparing the trend of malaria incidence across malaria-endemic areas between the control and pre-elimination phase, and the elimination phase. A retrospective analysis of malaria surveillance data was conducted in a 14-year period (2001-2014), using multilevel Poisson regression. The epidemiological malaria maps and indicators also were developed and compared between the control and pre-elimination phase, and the elimination phase. The mean of malaria incidence was 2.2 (1.7-2.7) for the entire study period. This rate was 3.4 (2.6-4.1) in the control and pre-elimination phase, and 0.41 (0.25-0.57) for the elimination phase. During the malaria elimination phase, the decline of annual malaria incidence had significantly accelerated and autochthonous cases had the greatest difference in malaria incidence decline (compared to the control and pre-elimination phase), whereas, falciparum cases had the lowest difference in malaria incidence decline, followed by non-Iranian and imported cases. Furthermore, there was a decline in Iranians to non-Iranians ratio and an increase in the ratios of over 15 to under 15, as well as male to female, in the elimination phase in comparison to the control and pre-elimination phase. It seems that the decline of malaria transmission, which has been initiated over the past few years, has accelerated as a result of the elimination programme, and Iran is approaching the goals set regarding the elimination of this disease.

Malaria successes and challenges in Asia.

PubMed

Bhatia, Rajesh; Rastogi, Rakesh Mani; Ortega, Leonard

2013-12-01

Asia ranks second to Africa in terms of malaria burden. In 19 countries of Asia, malaria is endemic and 2.31 billion people or 62% of the total population in these countries are at risk of malaria. In 2010, WHO estimated around 34.8 million cases and 45,600 deaths due to malaria in Asia. In 2011, 2.7 million cases and > 2000 deaths were reported. India, Indonesia, Myanmar and Pakistan are responsible for >85% of the reported cases (confirmed) and deaths in Asia. In last 10 yr, due to availability of donor's fund specially from Global fund, significant progress has been made by the countries in Asia in scaling-up malaria control interventions which were instrumental in reducing malaria morbidity and mortality significantly. There is a large heterogeneity in malaria epidemiology in Asia. As a result, the success in malaria control/elimination is also diverse. As compared to the data of the year 2000, out of 19 malaria endemic countries, 12 countries were able to reduce malaria incidence (microscopically confirmed cases only) by 75%. Two countries, namely Bangladesh and Malaysia are projected to reach 75% reduction by 2015 while India is projected to reach 50-75% only by 2015. The trend could not be assessed in four countries, namely Indonesia, Myanmar, Pakistan and Timor-Leste due to insufficient consistent data. Numerous key challenges need to be addressed to sustain the gains and eliminate malaria in most parts of Asia. Some of these are to control the spread of resistance in Plasmodium falciparum to artemisinin, control of outdoor transmission, control of vivax malaria and ensuring universal coverage of key interventions. Asia has the potential to influence the malaria epidemiology all over the world as well as to support the global efforts in controlling and eliminating malaria through production of quality-assured ACTs, RDTs and long-lasting insecticidal nets.

Geospatial tools for the identification of a malaria corridor in Estado Sucre, a Venezuelan north-eastern state.

PubMed

Delgado-Petrocelli, Laura; Camardiel, Alberto; Aguilar, Víctor Hugo; Martinez, Néstor; Córdova, Karenia; Ramos, Santiago

2011-05-01

Landscape ecology research relies on frameworks based on geographical information systems (GIS), geostatistics and spatial-feature relationships. With regard to health, the approach consists of systems analysis using a set of powerful tools aimed at the reduction of community vulnerability through improved public policies. The north-oriental malaria focus, one of five such foci in Venezuela, situated in the north-eastern part of the Estado Sucre state, unites several social and environmental features and functions as an epidemiological corridor, i.e. an endemic zone characterised by permanent interaction between the mosquito vector and the human host allowing a continuous persistence of the malaria lifecycle. A GIS was developed based on official cartography with thematic overlays depicting malaria distribution, socio-economic conditions, basic environmental information and specific features associated with the natural wetlands present in the area. Generally, malaria foci are continuously active but when the malaria situation was modelled in the north-oriental focus, a differential, spatio-temporal distribution pattern situation was found, i.e. a situation oscillating between very active and dormant transmission. This pattern was displayed by spatial and statistical analysis based on the model generated in this study and the results were confirmed by municipal and county malaria records. Control of malaria, keeping the incidence at a permanently low level within the regional population, should be possible if these results are taken into account when designing and implementing epidemiological surveillance policies.

The path of malaria vaccine development: challenges and perspectives.

PubMed

Arama, C; Troye-Blomberg, M

2014-05-01

Malaria is a life-threatening disease caused by parasites of the Plasmodium genus. In many parts of the world, the parasites have developed resistance to a number of antimalarial agents. Key interventions to control malaria include prompt and effective treatment with artemisinin-based combination therapies, use of insecticidal nets by individuals at risk and active research into malaria vaccines. Protection against malaria through vaccination was demonstrated more than 30 years ago when individuals were vaccinated via repeated bites by Plasmodium falciparum-infected and irradiated but still metabolically active mosquitoes. However, vaccination with high doses of irradiated sporozoites injected into humans has long been considered impractical. Yet, following recent success using whole-organism vaccines, the approach has received renewed interest; it was recently reported that repeated injections of irradiated sporozoites increased protection in 80 vaccinated individuals. Other approaches include subunit malaria vaccines, such as the current leading candidate RTS,S (consisting of fusion between a portion of the P. falciparum-derived circumsporozoite protein and the hepatitis B surface antigen), which has been demonstrated to induce reasonably good protection. Although results have been encouraging, the level of protection is generally considered to be too low to achieve eradication of malaria. There is great interest in developing new and better formulations and stable delivery systems to improve immunogenicity. In this review, we will discuss recent strategies to develop efficient malaria vaccines. © 2014 The Association for the Publication of the Journal of Internal Medicine.

The economic and social burden of malaria.

PubMed

Sachs, Jeffrey; Malaney, Pia

2002-02-07

Where malaria prospers most, human societies have prospered least. The global distribution of per-capita gross domestic product shows a striking correlation between malaria and poverty, and malaria-endemic countries also have lower rates of economic growth. There are multiple channels by which malaria impedes development, including effects on fertility, population growth, saving and investment, worker productivity, absenteeism, premature mortality and medical costs.

Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

PubMed Central

2012-01-01

Background Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected. Methods From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxine-pyrimethamine (SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed. Results Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy. Conclusions In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressing transmission are more likely to be evident where transmission is already low or effective vector control is widely implemented. PMID:22513162

Application of loop analysis for evaluation of malaria control interventions.

PubMed

Yasuoka, Junko; Jimba, Masamine; Levins, Richard

2014-04-09

Despite continuous efforts and recent rapid expansion in the financing and implementation of malaria control interventions, malaria still remains one of the most devastating global health issues. Even in countries that have been successful in reducing the incidence of malaria, malaria control is becoming more challenging because of the changing epidemiology of malaria and waning community participation in control interventions. In order to improve the effectiveness of interventions and to promote community understanding of the necessity of continued control efforts, there is an urgent need to develop new methodologies that examine the mechanisms by which community-based malaria interventions could reduce local malaria incidence. This study demonstrated how the impact of community-based malaria control interventions on malaria incidence can be examined in complex systems by qualitative analysis combined with an extensive review of literature. First, sign digraphs were developed through loop analysis to analyse seven interventions: source reduction, insecticide/larvicide use, biological control, treatment with anti-malarials, insecticide-treated mosquito net/long-lasting insecticidal net, non-chemical personal protection measures, and educational intervention. Then, for each intervention, the sign digraphs and literature review were combined to analyse a variety of pathways through which the intervention can influence local malaria incidence as well as interactions between variables involved in the system. Through loop analysis it is possible to see whether increases in one variable qualitatively increases or decreases other variables or leaves them unchanged and the net effect of multiple, interacting variables. Qualitative analysis, specifically loop analysis, can be a useful tool to examine the impact of community-based malaria control interventions. Without relying on numerical data, the analysis was able to describe pathways through which each intervention could influence malaria incidence on the basis of the qualitative patterns of the interactions between variables in complex systems. This methodology is generalizable to various disease control interventions at different levels, and can be utilized by a variety of stakeholders such as researchers, community leaders and policy makers to better plan and evaluate their community-based disease control interventions.

Application of loop analysis for evaluation of malaria control interventions

PubMed Central

2014-01-01

Background Despite continuous efforts and recent rapid expansion in the financing and implementation of malaria control interventions, malaria still remains one of the most devastating global health issues. Even in countries that have been successful in reducing the incidence of malaria, malaria control is becoming more challenging because of the changing epidemiology of malaria and waning community participation in control interventions. In order to improve the effectiveness of interventions and to promote community understanding of the necessity of continued control efforts, there is an urgent need to develop new methodologies that examine the mechanisms by which community-based malaria interventions could reduce local malaria incidence. Methods This study demonstrated how the impact of community-based malaria control interventions on malaria incidence can be examined in complex systems by qualitative analysis combined with an extensive review of literature. First, sign digraphs were developed through loop analysis to analyse seven interventions: source reduction, insecticide/larvicide use, biological control, treatment with anti-malarials, insecticide-treated mosquito net/long-lasting insecticidal net, non-chemical personal protection measures, and educational intervention. Then, for each intervention, the sign digraphs and literature review were combined to analyse a variety of pathways through which the intervention can influence local malaria incidence as well as interactions between variables involved in the system. Through loop analysis it is possible to see whether increases in one variable qualitatively increases or decreases other variables or leaves them unchanged and the net effect of multiple, interacting variables. Results Qualitative analysis, specifically loop analysis, can be a useful tool to examine the impact of community-based malaria control interventions. Without relying on numerical data, the analysis was able to describe pathways through which each intervention could influence malaria incidence on the basis of the qualitative patterns of the interactions between variables in complex systems. This methodology is generalizable to various disease control interventions at different levels, and can be utilized by a variety of stakeholders such as researchers, community leaders and policy makers to better plan and evaluate their community-based disease control interventions. PMID:24713031

Modeling malaria control intervention effect in KwaZulu-Natal, South Africa using intervention time series analysis.

PubMed

Ebhuoma, Osadolor; Gebreslasie, Michael; Magubane, Lethumusa

The change of the malaria control intervention policy in South Africa (SA), re-introduction of dichlorodiphenyltrichloroethane (DDT), may be responsible for the low and sustained malaria transmission in KwaZulu-Natal (KZN). We evaluated the effect of the re-introduction of DDT on malaria in KZN and suggested practical ways the province can strengthen her already existing malaria control and elimination efforts, to achieve zero malaria transmission. We obtained confirmed monthly malaria cases in KZN from the malaria control program of KZN from 1998 to 2014. The seasonal autoregressive integrated moving average (SARIMA) intervention time series analysis (ITSA) was employed to model the effect of the re-introduction of DDT on confirmed monthly malaria cases. The result is an abrupt and permanent decline of monthly malaria cases (w 0 =-1174.781, p-value=0.003) following the implementation of the intervention policy. The sustained low malaria cases observed over a long period suggests that the continued usage of DDT did not result in insecticide resistance as earlier anticipated. It may be due to exophagic malaria vectors, which renders the indoor residual spraying not totally effective. Therefore, the feasibility of reducing malaria transmission to zero in KZN requires other reliable and complementary intervention resources to optimize the existing ones. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Seasonal genetic partitioning in the neotropical malaria vector, Anopheles darlingi

PubMed Central

2014-01-01

Background Anopheles darlingi is the main malaria mosquito vector in the Amazonia region. In spite of being considered a riverine, forest-dwelling species, this mosquito is becoming more abundant in peri-urban areas, increasing malaria risk. This has been associated with human-driven environmental changes such as deforestation. Methods Microsatellites were used to characterize A. darlingi from seven localities along the Madeira River, Rondônia (Brazil), collected in the early and late periods of the rainy season. Results Two genetically distinct subpopulations were detected: one (subpopulation A) was associated with the late rainfall period and seems to be ecologically closer to the typical forest A. darlingi; the other (subpopulation B) was associated with the early rainfall period and is probably more adapted to drier conditions by exploiting permanent anthropogenic breeding sites. Results suggest also a pattern of asymmetric introgression, with more subpopulation A alleles introgressed into subpopulation B. Both subpopulations (and admixed mosquitoes) presented similar malaria infection rates, highlighting the potential for perennial malaria transmission in the region. Conclusions The co-occurrence of two genetically distinct subpopulations of A. darlingi adapted to different periods of rainfall may promote a more perennial transmission of malaria throughout the year. These findings, in a context of strong environmental impact due to deforestation and dam construction, have serious implications for malaria epidemiology and control in the Amazonian region. PMID:24885508

Health research ethics in malaria vector trials in Africa

PubMed Central

2010-01-01

Malaria mosquito research in Africa as elsewhere is just over a century old. Early trials for development of mosquito control tools were driven by colonial enterprises and war efforts; they were, therefore, tested in military or colonial settings. The failure of those tools and environmental concerns, coupled with the desperate need for integrated malaria control strategies, has necessitated the development of new malaria mosquito control tools, which are to be tested on humans, their environment and mosquito habitats. Ethical concerns start with phase 2 trials, which pose limited ethical dilemmas. Phase 3 trials, which are undertaken on vulnerable civilian populations, pose ethical dilemmas ranging from individual to community concerns. It is argued that such trials must abide by established ethical principles especially safety, which is mainly enshrined in the principle of non-maleficence. As there is total lack of experience with many of the promising candidate tools (eg genetically modified mosquitoes, entomopathogenic fungi, and biocontrol agents), great caution must be exercised before they are introduced in the field. Since malaria vector trials, especially phase 3 are intrusive and in large populations, individual and community respect is mandatory, and must give great priority to community engagement. It is concluded that new tools must be safe, beneficial, efficacious, effective, and acceptable to large populations in the short and long-term, and that research benefits should be equitably distributed to all who bear the brunt of the research burdens. It is further concluded that individual and institutional capacity strengthening should be provided, in order to undertake essential research, carry out scientific and ethical review, and establish competent regulatory frameworks. PMID:21144083

The use of transgenic parasites in malaria vaccine research.

PubMed

Othman, Ahmad Syibli; Marin-Mogollon, Catherin; Salman, Ahmed M; Franke-Fayard, Blandine M; Janse, Chris J; Khan, Shahid M

2017-07-01

Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.

A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria.

PubMed

Giddam, Ashwini Kumar; Reiman, Jennifer M; Zaman, Mehfuz; Skwarczynski, Mariusz; Toth, Istvan; Good, Michael F

2016-10-15

Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRBCs. Killed blood stage parasites were encapsulated within liposomes that are targeted to antigen presenting cells (APCs). Mannosylated lipid core peptides (MLCPs) were used as targeting ligands for the liposome-encapsulated parasite antigens. MLCP-liposomes, but not unmannosylated liposomes, were taken-up efficiently by APCs which then significantly upregulated expression of MHC-ll and costimulatory molecules, CD80 and CD86. Two such vaccines using rodent model systems were constructed - one with Plasmodium chabaudi and the other with P. yoelii. MLCP-liposome vaccines were able to control the parasite burden and extended the survival of mice. Thus, we have demonstrated an alternative delivery system to attenuated pRBCs with similar vaccine efficacy and added clinical advantages. Such liposomes are promising candidates for a human malaria vaccine. Attenuated whole parasite-based vaccines, by incorporating all parasite antigens, are very promising candidates, but issues relating to production, storage and safety concerns are significantly slowing their development. We therefore developed a semi-synthetic whole parasite malaria vaccine that is easily manufactured and stored. Two such prototype vaccines (a P. chabaudi and a P. yoelii vaccine) have been constructed. They are non-infectious, highly immunogenic and give good protection profiles. This semi-synthetic delivery platform is an exciting strategy to accelerate the development of a licensed malaria vaccine. Moreover, this strategy can be potentially applied to a wide range of pathogens. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

PubMed Central

2010-01-01

Background Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum. Results A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina® Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme. Conclusions This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations. PMID:20846421

Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases

PubMed Central

Faure, Eric

2014-01-01

In nature, organisms are commonly infected by an assemblage of different parasite species or by genetically distinct parasite strains that interact in complex ways. Linked to co-infections, pathocoenosis, a term proposed by M. Grmek in 1969, refers to a pathological state arising from the interactions of diseases within a population and to the temporal and spatial dynamics of all of the diseases. In the long run, malaria was certainly one of the most important component of past pathocoenoses. Today this disease, which affects hundreds of millions of individuals and results in approximately one million deaths each year, is always highly endemic in over 20% of the world and is thus co-endemic with many other diseases. Therefore, the incidences of co-infections and possible direct and indirect interactions with Plasmodium parasites are very high. Both positive and negative interactions between malaria and other diseases caused by parasites belonging to numerous taxa have been described and in some cases, malaria may modify the process of another disease without being affected itself. Interactions include those observed during voluntary malarial infections intended to cure neuro-syphilis or during the enhanced activations of bacterial gastro-intestinal diseases and HIV infections. Complex relationships with multiple effects should also be considered, such as those observed during helminth infections. Moreover, reports dating back over 2000 years suggested that co- and multiple infections have generally deleterious consequences and analyses of historical texts indicated that malaria might exacerbate both plague and cholera, among other diseases. Possible biases affecting the research of etiological agents caused by the protean manifestations of malaria are discussed. A better understanding of the manner by which pathogens, particularly Plasmodium, modulate immune responses is particularly important for the diagnosis, cure, and control of diseases in human populations. PMID:25484866

Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

PubMed

Guiyedi, Vincent; Chanseaud, Youri; Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-04-25

Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children. To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

PubMed Central

Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-01-01

Background Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. Methodology To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. Results/Conclusion The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM. PMID:17460756

DDT, global strategies, and a malaria control crisis in South America.

PubMed

Roberts, D R; Laughlin, L L; Hsheih, P; Legters, L J

1997-01-01

Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria-endemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides.

DDT, global strategies, and a malaria control crisis in South America.

PubMed Central

Roberts, D. R.; Laughlin, L. L.; Hsheih, P.; Legters, L. J.

1997-01-01

Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria-endemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides. PMID:9284373

Lives saved from malaria prevention in Africa--evidence to sustain cost-effective gains.

PubMed

Korenromp, Eline L

2012-03-28

Lives saved have become a standard metric to express health benefits across interventions and diseases. Recent estimates of malaria-attributable under-five deaths prevented using the Lives Saved tool (LiST), extrapolating effectiveness estimates from community-randomized trials of scale-up of insecticide-treated nets (ITNs) in the 1990s, confirm the substantial impact and good cost-effectiveness that ITNs have achieved in high-endemic sub-Saharan Africa. An even higher cost-effectiveness would likely have been found if the modelling had included the additional indirect mortality impact of ITNs on preventing deaths from other common child illnesses, to which malaria contributes as a risk factor. As conventional ITNs are being replaced by long-lasting insecticidal nets and scale-up is expanded to target universal coverage for full, all-age populations at risk, enhanced transmission reduction may--above certain thresholds--enhance the mortality impact beyond that observed in the trials of the 1990s. On the other hand, lives saved by ITNs might fall if improved malaria case management with artemisinin-based combination therapy averts the deaths that ITNs would otherwise prevent.Validation and updating of LiST's simple assumption of a universal, fixed coverage-to-mortality-reduction ratio will require enhanced national programme and impact monitoring and evaluation. Key indicators for time trend analysis include malaria-related mortality from population-based surveys and vital registration, vector control and treatment coverage from surveys, and parasitologically-confirmed malaria cases and deaths recorded in health facilities. Indispensable is triangulation with dynamic transmission models, fitted to long-term trend data on vector, parasite and human populations over successive phases of malaria control and elimination.Sound, locally optimized budget allocation including on monitoring and evaluation priorities will benefit much if policy makers and programme planners use planning tools such as LiST - even when predictions are less certain than often understood. The ultimate success of LiST for supporting malaria prevention may be to prove its linear predictions less and less relevant.

Challenges and prospects for malaria elimination in the Greater Mekong Subregion

PubMed Central

Cui, Liwang; Yan, Guiyun; Sattabongkot, Jetsumon; Chen, Bin; Cao, Yaming; Fan, Qi; Parker, Daniel; Sirichaisinthop, Jeeraphat; Su, Xin-zhuan; Yang, Henglin; Yang, Zhaoqing; Wang, Baomin; Zhou, Guofa

2011-01-01

Despite significant improvement in the malaria situation of the Greater Mekong Subregion (GMS), malaria control for the region continues to face a multitude of challenges. The extremely patchy malaria distribution, especially along international borders, makes disease surveillance and targeted control difficult. The vector systems are also diverse with dramatic differences in habitat ecology, biting behavior, and vectorial capacity, and there is a lack of effective transmission surveillance and control tools. Finally, in an era of heavy deployment of artemisinin-based combination therapies, the region acts as an epicenter of drug resistance, with the emergence of artemisinin resistant P. falciparum posing a threat to both regional and global malaria elimination campaigns. This problem is further exacerbated by the circulation of counterfeit and substandard artemisinin drugs. Accordingly, this Southeast Asian Malaria Research Center, consisting of a consortium of US and regional research institutions, has proposed four interlinked projects to address these most urgent problems in malaria control. The aims of these projects will help to substantially improve our understanding of malaria epidemiology, vector systems and their roles in malaria transmission, as well as the mechanisms of drug resistance in parasites. Through the training of next-generation scientists in malaria research, this program will help build up and strengthen regional research infrastructure and capacities, which are essential for sustained malaria control in this region. PMID:21515238

DDT and Malaria Prevention: Addressing the Paradox

PubMed Central

Bouwman, Hindrik; van den Berg, Henk; Kylin, Henrik

2011-01-01

Background The debate regarding dichlorodiphenyltrichloroethane (DDT) in malaria prevention and human health is polarized and can be classified into three positions: anti-DDT, centrist-DDT, pro-DDT. Objective We attempted to arrive at a synthesis by matching a series of questions on the use of DDT for indoor residual spraying (IRS) with literature and insights, and to identify options and opportunities. Discussion Overall, community health is significantly improved through all available malaria control measures, which include IRS with DDT. Is DDT “good”? Yes, because it has saved many lives. Is DDT safe as used in IRS? Recent publications have increasingly raised concerns about the health implications of DDT. Therefore, an unqualified statement that DDT used in IRS is safe is untenable. Are inhabitants and applicators exposed? Yes, and to high levels. Should DDT be used? The fact that DDT is “good” because it saves lives, and “not safe” because it has health and environmental consequences, raises ethical issues. The evidence of adverse human health effects due to DDT is mounting. However, under certain circumstances, malaria control using DDT cannot yet be halted. Therefore, the continued use of DDT poses a paradox recognized by a centrist-DDT position. At the very least, it is now time to invoke precaution. Precautionary actions could include use and exposure reduction. Conclusions There are situations where DDT will provide the best achievable health benefit, but maintaining that DDT is safe ignores the cumulative indications of many studies. In such situations, addressing the paradox from a centrist-DDT position and invoking precaution will help design choices for healthier lives. PMID:21245017

A Research Agenda to Underpin Malaria Eradication

PubMed Central

Alonso, Pedro L.; Brown, Graham; Arevalo-Herrera, Myriam; Binka, Fred; Chitnis, Chetan; Collins, Frank; Doumbo, Ogobara K.; Greenwood, Brian; Hall, B. Fenton; Levine, Myron M.; Mendis, Kamini; Newman, Robert D.; Plowe, Christopher V.; Rodríguez, Mario Henry; Sinden, Robert; Slutsker, Laurence; Tanner, Marcel

2011-01-01

The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda—primarily directed towards reducing morbidity and mortality—with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda. PMID:21311579

Malaria control in Nicaragua: social and political influences on disease transmission and control activities.

PubMed

Garfield, R

1999-07-31

Throughout Central America, a traditional malaria control strategy (depending on heavy use of organic pesticides) became less effective during the 1970s. In Nicaragua, an alternative strategy, based on frequent local epidemiological assessments and community participation, was developed in the 1980s. Despite war-related social instability, and continuing vector resistance, this approach was highly successful. By the end of the contra war, there finally existed organisational and ecological conditions that favoured improved malaria control. Yet the expected improvements did not occur. In the 1990s, Nicaragua experienced its worst recorded malaria epidemics. This situation was partly caused by the country's macroeconomic structural adjustment programme. Volunteers now take fewer slides and provide less treatment, malaria control workers are less motivated by the spirit of public service, and some malaria control stations charge for diagnosis or treatment. To "roll back malaria", in Nicaragua at least, will require the roll-back of some erroneous aspects of structural adjustment.

Vector bionomics and malaria transmission along the Thailand-Myanmar border: a baseline entomological survey.

PubMed

Kwansomboon, N; Chaumeau, V; Kittiphanakun, P; Cerqueira, D; Corbel, V; Chareonviriyaphap, T

2017-06-01

Baseline entomological surveys were conducted in four sentinel sites along the Thailand-Myanmar border to address vector bionomics and malaria transmission in the context of a study on malaria elimination. Adult Anopheles mosquitoes were collected using human-landing catch and cow-bait collection in four villages during the rainy season from May-June, 2013. Mosquitoes were identified to species level by morphological characters and by AS-PCR. Sporozoite indexes were determined on head/thoraces of primary and secondary malaria vectors using real-time PCR. A total of 4,301 anopheles belonging to 12 anopheline taxa were identified. Anopheles minimus represented >98% of the Minimus Complex members (n=1,683), whereas the An. maculatus group was composed of two dominant species, An. sawadwongporni and An. maculatus. Overall, 25 Plasmodium-positive mosquitoes (of 2,323) were found, representing a sporozoite index of 1.1% [95%CI 0.66-1.50]. The transmission intensity as measured by the EIR strongly varied according to the village (ANOVA, F=17.67, df=3, P<0.0001). Our findings highlight the diversity and complexity of the biting pattern of malaria vectors along the Thailand-Myanmar border that represent a formidable challenge for malaria control and elimination. © 2017 The Society for Vector Ecology.

Intraerythrocytic Killing of Malaria Parasites

DTIC Science & Technology

1989-05-12

immunity (23, 24) and its relevance to human malaria (25). 4. The effect of the B- thalassemia mutation on ralaria-infectcd mice arid the role of the spleen...detected. Thus, Pc96 shares a cross-reactive epitope with these three primate malaria antigens. 4. Effect of B- thalassemia on malaria-infected mice and...B- thalassemia against malaria, rodent malaria parasites were studied in C57BL/6J mice with B- thalassemia , in mice in which the thalassemia had been

Avian and simian malaria: do they have a cancer connection?

PubMed

Ward, Martin; Benelli, Giovanni

2017-03-01

It has been claimed that infectious agents transmitted by mosquitoes (Diptera: Culicidae) may have a greater connection to cancer then hitherto supposed and that the immune system struggles to recognize and fight some of these infectious agents. One of the claims made is that there is a connection between human malaria and brain cancers in the USA. However, the USA declared itself free of human malaria in the last century, yet cancer incidences remain high, suggesting any overall cancer connection is slight. Two fundamental questions arise from the possible mosquito-cancer connection. Firstly, if mosquitoes are able to vector some pathogens and parasites linked with cancer pathogenesis, why has the fact not been discovered decades ago? Secondly, if there is a connection (other than in relation to Burkett's lymphoma), what is its extent? The answers may well lie with the various types of malarias known to exist. The discovery in humans of the simian malaria, caused by Plasmodium knowlesi, suggests that other forms of simian or even avian malaria may be capable of survival in humans, albeit at low levels of parasitemia, and humans may be a dead-end host. Other carcinogenic infectious agents transmitted by mosquitoes may also go undetected because either no one is looking for them, or they are looking in wrong anatomical locations and/or with inadequate tools. Research on false negative test results with respect to many infectious agents is sadly lacking, so its extent is unknown. However, electronic and other media provide numerous instances of patients failing to be diagnosed for both human malaria and Lyme's disease, to take just two examples. This review suggests that to shed light on a potential mosquito-cancer connection, more research is required to establish whether other simian and avian forms of malaria play a part. If so, then they potentially provide unique markers for early cancer detection.

Ecology of Anopheles darlingi Root with respect to vector importance: a review

PubMed Central

2011-01-01

Anopheles darlingi is one of the most important malaria vectors in the Americas. In this era of new tools and strategies for malaria and vector control it is essential to have knowledge on the ecology and behavior of vectors in order to evaluate appropriateness and impact of control measures. This paper aims to provide information on the importance, ecology and behavior of An. darlingi. It reviews publications that addressed ecological and behavioral aspects that are important to understand the role and importance of An. darlingi in the transmission of malaria throughout its area of distribution. The results show that Anopheles darlingi is especially important for malaria transmission in the Amazon region. Although numerous studies exist, many aspects determining the vectorial capacity of An. darlingi, i.e. its relation to seasons and environmental conditions, its gonotrophic cycle and longevity, and its feeding behavior and biting preferences, are still unknown. The vector shows a high degree of variability in behavioral traits. This makes it difficult to predict the impact of ongoing changes in the environment on the mosquito populations. Recent studies indicate a good ability of An. darlingi to adapt to environments modified by human development. This allows the vector to establish populations in areas where it previously did not exist or had been controlled to date. The behavioral variability of the vector, its adaptability, and our limited knowledge of these impede the establishment of effective control strategies. Increasing our knowledge of An. darlingi is necessary. PMID:21923902

Malaria eradication: the economic, financial and institutional challenge.

PubMed

Mills, Anne; Lubell, Yoel; Hanson, Kara

2008-12-11

Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic development, the costs and consequences of the various tools and mixes of tools employed in control and eradication, issues concerning the extension of coverage of interventions and service delivery approaches, especially those that can reach the poorest, research on the processes of formulating and implementing malaria control and eradication policies, at both international and national levels, research on financing issues, at global and national levels.

Malaria eradication: the economic, financial and institutional challenge

PubMed Central

Mills, Anne; Lubell, Yoel; Hanson, Kara

2008-01-01

Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: ∘ issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic development ∘ the costs and consequences of the various tools and mixes of tools employed in control and eradication ∘ issues concerning the extension of coverage of interventions and service delivery approaches, especially those that can reach the poorest ∘ research on the processes of formulating and implementing malaria control and eradication policies, at both international and national levels ∘ research on financing issues, at global and national levels. PMID:19091035

Out of Africa: origins and evolution of the human malaria parasites Plasmodium falciparum and Plasmodium vivax.

PubMed

Loy, Dorothy E; Liu, Weimin; Li, Yingying; Learn, Gerald H; Plenderleith, Lindsey J; Sundararaman, Sesh A; Sharp, Paul M; Hahn, Beatrice H

2017-02-01

Plasmodium falciparum and Plasmodium vivax account for more than 95% of all human malaria infections, and thus pose a serious public health challenge. To control and potentially eliminate these pathogens, it is important to understand their origins and evolutionary history. Until recently, it was widely believed that P. falciparum had co-evolved with humans (and our ancestors) over millions of years, whilst P. vivax was assumed to have emerged in southeastern Asia following the cross-species transmission of a parasite from a macaque. However, the discovery of a multitude of Plasmodium spp. in chimpanzees and gorillas has refuted these theories and instead revealed that both P. falciparum and P. vivax evolved from parasites infecting wild-living African apes. It is now clear that P. falciparum resulted from a recent cross-species transmission of a parasite from a gorilla, whilst P. vivax emerged from an ancestral stock of parasites that infected chimpanzees, gorillas and humans in Africa, until the spread of the protective Duffy-negative mutation eliminated P. vivax from human populations there. Although many questions remain concerning the biology and zoonotic potential of the P. falciparum- and P. vivax-like parasites infecting apes, comparative genomics, coupled with functional parasite and vector studies, are likely to yield new insights into ape Plasmodium transmission and pathogenesis that are relevant to the treatment and prevention of human malaria. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa.

PubMed

Yé, Yazoume; Eisele, Thomas P; Eckert, Erin; Korenromp, Eline; Shah, Jui A; Hershey, Christine L; Ivanovich, Elizabeth; Newby, Holly; Carvajal-Velez, Liliana; Lynch, Michael; Komatsu, Ryuichi; Cibulskis, Richard E; Moore, Zhuzhi; Bhattarai, Achuyt

2017-09-01

Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India

PubMed Central

Sharma, V. P.

2012-01-01

Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination. PMID:23391787

Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India.

PubMed

Sharma, V P

2012-12-01

Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination.

Epidemiology of forest malaria in Central Vietnam: the hidden parasite reservoir.

PubMed

Thanh, Pham Vinh; Van Hong, Nguyen; Van Van, Nguyen; Van Malderen, Carine; Obsomer, Valérie; Rosanas-Urgell, Anna; Grietens, Koen Peeters; Xa, Nguyen Xuan; Bancone, Germana; Chowwiwat, Nongnud; Duong, Tran Thanh; D'Alessandro, Umberto; Speybroeck, Niko; Erhart, Annette

2015-02-19

After successfully reducing the malaria burden to pre-elimination levels over the past two decades, the national malaria programme in Vietnam has recently switched from control to elimination. However, in forested areas of Central Vietnam malaria elimination is likely to be jeopardized by the high occurrence of asymptomatic and submicroscopic infections as shown by previous reports. This paper presents the results of a malaria survey carried out in a remote forested area of Central Vietnam where we evaluated malaria prevalence and risk factors for infection. After a full census (four study villages = 1,810 inhabitants), the study population was screened for malaria infections by standard microscopy and, if needed, treated according to national guidelines. An additional blood sample on filter paper was also taken in a random sample of the population for later polymerase chain reaction (PCR) and more accurate estimation of the actual burden of malaria infections. The risk factor analysis for malaria infections was done using survey multivariate logistic regression as well as the classification and regression tree method (CART). A total of 1,450 individuals were screened. Malaria prevalence by microscopy was 7.8% (ranging from 3.9 to 10.9% across villages) mostly Plasmodium falciparum (81.4%) or Plasmodium vivax (17.7%) mono-infections; a large majority (69.9%) was asymptomatic. By PCR, the prevalence was estimated at 22.6% (ranging from 16.4 to 42.5%) with a higher proportion of P. vivax mono-infections (43.2%). The proportion of sub-patent infections increased with increasing age and with decreasing prevalence across villages. The main risk factors were young age, village, house structure, and absence of bed net. This study confirmed that in Central Vietnam a substantial part of the human malaria reservoir is hidden. Additional studies are urgently needed to assess the contribution of this hidden reservoir to the maintenance of malaria transmission. Such evidence will be crucial for guiding elimination strategies.

The spatial and temporal patterns of falciparum and vivax malaria in Perú: 1994–2006

PubMed Central

Chowell, Gerardo; Munayco, Cesar V; Escalante, Ananias A; McKenzie, F Ellis

2009-01-01

Background Malaria is the direct cause of approximately one million deaths worldwide each year, though it is both preventable and curable. Increasing the understanding of the transmission dynamics of falciparum and vivax malaria and their relationship could suggest improvements for malaria control efforts. Here the weekly number of malaria cases due to Plasmodium falciparum (1994–2006) and Plasmodium vivax (1999–2006) in Perú at different spatial scales in conjunction with associated demographic, geographic and climatological data are analysed. Methods Malaria periodicity patterns were analysed through wavelet spectral analysis, studied patterns of persistence as a function of community size and assessed spatial heterogeneity via the Lorenz curve and the summary Gini index. Results Wavelet time series analyses identified annual cycles in the incidence of both malaria species as the dominant pattern. However, significant spatial heterogeneity was observed across jungle, mountain and coastal regions with slightly higher levels of spatial heterogeneity for P. vivax than P. falciparum. While the incidence of P. falciparum has been declining in recent years across geographic regions, P. vivax incidence has remained relatively steady in jungle and mountain regions with a slight decline in coastal regions. Factors that may be contributing to this decline are discussed. The time series of both malaria species were significantly synchronized in coastal (ρ = 0.9, P < 0.0001) and jungle regions (ρ = 0.76, P < 0.0001) but not in mountain regions. Community size was significantly associated with malaria persistence due to both species in jungle regions, but not in coastal and mountain regions. Conclusion Overall, findings highlight the importance of highly refined spatial and temporal data on malaria incidence together with demographic and geographic information in improving the understanding of malaria persistence patterns associated with multiple malaria species in human populations, impact of interventions, detection of heterogeneity and generation of hypotheses. PMID:19558695

Dynamics of climate-based malaria transmission model with age-structured human population

NASA Astrophysics Data System (ADS)

Addawe, Joel; Pajimola, Aprimelle Kris

2016-10-01

In this paper, we proposed to study the dynamics of malaria transmission with periodic birth rate of the vector and an age-structure for the human population. The human population is divided into two compartments: pre-school (0-5 years) and the rest of the human population. We showed the existence of a disease-free equilibrium point. Using published epidemiological parameters, we use numerical simulations to show potential effect of climate change in the dynamics of age-structured malaria transmission. Numerical simulations suggest that there exists an asymptotically attractive solution that is positive and periodic.

"We don't want our clothes to smell smoke": changing malaria control practices and opportunities for integrated community-based management in Baringo, Kenya.

PubMed

Amadi, Jacinter A; Olago, Daniel O; Ong'amo, George O; Oriaso, Silas O; Nyamongo, Isaac K; Estambale, Benson B A

2018-05-09

The decline in global malaria cases is attributed to intensified utilization of primary vector control interventions and artemisinin-based combination therapies (ACTs). These strategies are inadequate in many rural areas, thus adopting locally appropriate integrated malaria control strategies is imperative in these heterogeneous settings. This study aimed at investigating trends and local knowledge on malaria and to develop a framework for malaria control for communities in Baringo, Kenya. Clinical malaria cases obtained from four health facilities in the riverine and lowland zones were used to analyse malaria trends for the 2005-2014 period. A mixed method approach integrating eight focus group discussions, 12 key informant interviews, 300 survey questionnaires and two stakeholders' consultative forums were used to assess local knowledge on malaria risk and develop a framework for malaria reduction. Malaria cases increased significantly during the 2005-2014 period (tau = 0.352; p < 0.001) in the riverine zone. March, April, May, June and October showed significant increases compared to other months. Misconceptions about the cause and mode of malaria transmission existed. Gender-segregated outdoor occupation such as social drinking, farm activities, herding, and circumcision events increased the risk of mosquito bites. A positive relationship occurred between education level and opinion on exposure to malaria risk after dusk (χ 2  = 2.70, p < 0.05). There was over-reliance on bed nets, yet only 68% (204/300) of respondents owned at least one net. Complementary malaria control measures were under-utilized, with 90% of respondents denying having used either sprays, repellents or burnt cow dung or plant leaves over the last one year before the study was conducted. Baraza, radios, and mobile phone messages were identified as effective media for malaria information exchange. Supplementary strategies identified included unblocking canals, clearing Prosopis bushes, and use of community volunteers and school clubs to promote social behaviour change. The knowledge gap on malaria transmission should be addressed to minimize the impacts and enhance uptake of appropriate malaria management mechanisms. Implementing community-based framework can support significant reductions in malaria prevalence by minimizing both indoor and outdoor malaria transmissions.

Plasmodium knowlesi malaria in humans is widely distributed and potentially life-threatening

PubMed Central

Cox-Singh, Janet; Davis, Timothy M. E.; Lee, Kim-Sung; Shamsul, Sunita S. G.; Matusop, Asmad; Ratnam, Shanmuga; Rahman, Hasan A.; Conway, David J; Singh, Balbir

2008-01-01

Background Until recently, Plasmodium knowlesi malaria in humans was misdiagnosed as P. malariae. The present objectives were to determine the geographic distribution of P. knowlesi in the human population in Malaysia and to investigate four suspected fatal cases. Methods Sensitive and specific nested-PCR was used to identify all Plasmodium species present in blood from i) 960 patients with malaria hospitalized in Sarawak, Malaysian Borneo from 2001-2006, ii) 54 P. malariae archival blood-films from 15 districts in Sabah, Malaysian Borneo (2003–2005) and four districts in Pahang, Peninsular Malaysia (2004–2005), and iii) suspected knowlesi fatalities. In the four latter cases, available clinical and laboratory data were reviewed. Results P. knowlesi DNA was detected in 266 of 960 (27·7%) of the samples from Sarawak hospitals, 41 of 49 (83·7%) from Sabah and all 5 from Pahang. Only P. knowlesi DNA was detected in archival blood films from the 4 fatal cases. All were hyperparasitemic and developed marked hepatorenal dysfunction. Conclusions Human infections with P. knowlesi, commonly misidentified as the more benign P. malariae, are widely distributed across Malaysian Borneo and extend to Peninsular Malaysia. Because P. knowlesi replicates every 24 hours, rapid diagnosis and prompt effective treatment are essential. In the absence of a specific routine diagnostic test for knowlesi malaria, we recommend that patients in, or who have travelled to, South-east Asia who are ill with a ‘P. malariae’ hyperparasitemia diagnosis by microscopy should receive intensive management as appropriate for severe falciparum malaria. PMID:18171245

Increased malaria transmission around irrigation schemes in Ethiopia and the potential of canal water management for malaria vector control.

PubMed

Kibret, Solomon; Wilson, G Glenn; Tekie, Habte; Petros, Beyene

2014-09-13

Irrigation schemes have been blamed for the increase in malaria in many parts of sub-Saharan Africa. However, proper water management could help mitigate malaria around irrigation schemes in this region. This study investigates the link between irrigation and malaria in Central Ethiopia. Larval and adult mosquitoes were collected fortnightly between November 2009 and October 2010 from two irrigated and two non-irrigated (control) villages in the Ziway area, Central Ethiopia. Daily canal water releases were recorded during the study period and bi-weekly correlation analysis was done to determine relationships between canal water releases and larval/adult vector densities. Blood meal sources (bovine vs human) and malaria sporozoite infection were tested using enzyme-linked immunosorbent assay (ELISA). Monthly malaria data were also collected from central health centre of the study villages. Monthly malaria incidence was over six-fold higher in the irrigated villages than the non-irrigated villages. The number of anopheline breeding habitats was 3.6 times higher in the irrigated villages than the non-irrigated villages and the most common Anopheles mosquito breeding habitats were waterlogged field puddles, leakage pools from irrigation canals and poorly functioning irrigation canals. Larval and adult anopheline densities were seven- and nine-fold higher in the irrigated villages than in the non-irrigated villages, respectively, during the study period. Anopheles arabiensis was the predominant species in the study area. Plasmodium falciparum sporozoite rates of An. arabiensis and Anopheles pharoensis were significantly higher in the irrigated villages than the non-irrigated villages. The annual entomological inoculation rate (EIR) calculated for the irrigated and non-irrigated villages were 34.8 and 0.25 P. falciparum infective bites per person per year, respectively. A strong positive correlation was found between bi-weekly anopheline larval density and canal water releases. Similarly, there was a strong positive correlation between bi-weekly vector density and canal water releases lagged by two weeks. Furthermore, monthly malaria incidence was strongly correlated with monthly vector density lagged by a month in the irrigated villages. The present study revealed that the irrigation schemes resulted in intensified malaria transmission due to poor canal water management. Proper canal water management could reduce vector abundance and malaria transmission in the irrigated villages.

Controlling imported malaria cases in the United States of America.

PubMed

Dembele, Bassidy; Yakubu, Abdul-Aziz

2017-02-01

We extend the mathematical malaria epidemic model framework of Dembele et al. and use it to ``capture" the 2013 Centers for Disease Control and Prevention (CDC) reported data on the 2011 number of imported malaria cases in the USA. Furthermore, we use our ``fitted" malaria models for the top 20 countries of malaria acquisition by USA residents to study the impact of protecting USA residents from malaria infection when they travel to malaria endemic areas, the impact of protecting residents of malaria endemic regions from mosquito bites and the impact of killing mosquitoes in those endemic areas on the CDC number of imported malaria cases in USA. To significantly reduce the number of imported malaria cases in USA, for each top 20 country of malaria acquisition by USA travelers, we compute the optimal proportion of USA international travelers that must be protected against malaria infection and the optimal proportion of mosquitoes that must be killed.

Transcriptome of the adult female malaria mosquito vector Anopheles albimanus.

PubMed

Martínez-Barnetche, Jesús; Gómez-Barreto, Rosa E; Ovilla-Muñoz, Marbella; Téllez-Sosa, Juan; García López, David E; Dinglasan, Rhoel R; Ubaida Mohien, Ceereena; MacCallum, Robert M; Redmond, Seth N; Gibbons, John G; Rokas, Antonis; Machado, Carlos A; Cazares-Raga, Febe E; González-Cerón, Lilia; Hernández-Martínez, Salvador; Rodríguez López, Mario H

2012-05-30

Human Malaria is transmitted by mosquitoes of the genus Anopheles. Transmission is a complex phenomenon involving biological and environmental factors of humans, parasites and mosquitoes. Among more than 500 anopheline species, only a few species from different branches of the mosquito evolutionary tree transmit malaria, suggesting that their vectorial capacity has evolved independently. Anopheles albimanus (subgenus Nyssorhynchus) is an important malaria vector in the Americas. The divergence time between Anopheles gambiae, the main malaria vector in Africa, and the Neotropical vectors has been estimated to be 100 My. To better understand the biological basis of malaria transmission and to develop novel and effective means of vector control, there is a need to explore the mosquito biology beyond the An. gambiae complex. We sequenced the transcriptome of the An. albimanus adult female. By combining Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut, cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a single, high-quality assembly containing 16,669 transcripts, 92% of which mapped to the An. darlingi genome and covered 90% of the core eukaryotic genome. Bidirectional comparisons between the An. gambiae, An. darlingi and An. albimanus predicted proteomes allowed the identification of 3,772 putative orthologs. More than half of the transcripts had a match to proteins in other insect vectors and had an InterPro annotation. We identified several protein families that may be relevant to the study of Plasmodium-mosquito interaction. An open source transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was developed to facilitate public access to the data generated by this and future transcriptome projects. We have explored the adult female transcriptome of one important New World malaria vector, An. albimanus. We identified protein-coding transcripts involved in biological processes that may be relevant to the Plasmodium lifecycle and can serve as the starting point for searching targets for novel control strategies. Our data increase the available genomic information regarding An. albimanus several hundred-fold, and will facilitate molecular research in medical entomology, evolutionary biology, genomics and proteomics of anopheline mosquito vectors. The data reported in this manuscript is accessible to the community via the VectorBase website (http://www.vectorbase.org/Other/AdditionalOrganisms/).

Dynamical Behavior of a Malaria Model with Discrete Delay and Optimal Insecticide Control

NASA Astrophysics Data System (ADS)

Kar, Tuhin Kumar; Jana, Soovoojeet

In this paper we have proposed and analyzed a simple three-dimensional mathematical model related to malaria disease. We consider three state variables associated with susceptible human population, infected human population and infected mosquitoes, respectively. A discrete delay parameter has been incorporated to take account of the time of incubation period with infected mosquitoes. We consider the effect of insecticide control, which is applied to the mosquitoes. Basic reproduction number is figured out for the proposed model and it is shown that when this threshold is less than unity then the system moves to the disease-free state whereas for higher values other than unity, the system would tend to an endemic state. On the other hand if we consider the system with delay, then there may exist some cases where the endemic equilibrium would be unstable although the numerical value of basic reproduction number may be greater than one. We formulate and solve the optimal control problem by considering insecticide as the control variable. Optimal control problem assures to obtain better result than the noncontrol situation. Numerical illustrations are provided in support of the theoretical results.

Exploring the impact of house screening intervention on entomological indices and incidence of malaria in Arba Minch town, southwest Ethiopia: A randomized control trial.

PubMed

Getawen, Solomon Kinde; Ashine, Temesgen; Massebo, Fekadu; Woldeyes, Daniel; Lindtjørn, Bernt

2018-05-01

House is the major site for malaria infection where most human-vector contact takes place. Hence, improving housing might reduce the risk of malaria infection by limiting house entry of vectors. This study aimed to explore the impact of screening doors and windows with wire meshes on density and entomological inoculation rate (EIR) of malaria vector, and malaria incidence, and assess the acceptability, durability, and cost of the intervention. The susceptibility status of malaria vector was also assessed. A two-arm randomized trial was done in Arba Minch Town, southwest Ethiopia. 92 houses were randomly included in the trial. The baseline entomological and malaria prevalence data were collected. The mosquito sampling was done twice per household per month by Centers for Diseases Control and Prevention (CDC) light traps for six months. The baseline prevalence of malaria was assessed by testing 396 (83% of the 447 study participants) household members in all the eligible houses. The 92 houses were then randomized into control and intervention groups using mosquito and malaria prevalence baseline data to make the two groups comparable except the intervention. Then, we put wire-mesh on doors and windows of 46 houses. Post-screening mosquito collection was done in each household twice per month for three months. Each household member was visited twice per month for six months to assess malaria episodes. The frequency of damage to different structure of screening was measured twice. In-depth interview was conducted with 24 purposely selected household heads from intervention group. Speciation of Anopheles mosquito was done by morphological key, and the circum-sporozoite proteins (CSPs) analysis was done using enzyme-linked immunosorbent assay. A generalized estimating equation with a negative binomial distribution was used to assess the impact of the intervention on the indoor density of vectors. Clinical malaria case data were analyzed using Poisson regression with generalized linear model. Screening doors and windows reduced the indoor density of An. arabiensis by 48% (mean ratio of intervention to control = 0.85/1.65; 0.52) (P = .001). Plasmodium falciparum CSP rate was 1.6% (3/190) in the intervention houses, while it was 2.7% (10/372) in the control houses. The protective efficacy of screening intervention from CSP positive An. arabiensis was 41% (mean ratio of intervention to control = 1.6/2.7; 0.59), but was not statistically significant (P = .6). The EIR of An. arabiensis was 1.91 in the intervention group, whereas it was 6.45 in the control group. 477 participants were followed for clinical malaria (50.1% from intervention and 49.9% from the control group). Of 49 RDT positive cases, 45 were confirmed to be positive with microscopy. 80% (n = 36) cases were due to P. falciparum and the rest 20% (n = 9) were due to P. vivax. The incidence of P. falciparum in the intervention group was lower (IRR: 0.39, 95% CI: 0.2-0.80; P = .01) than in the control group. Using incidence of P. falciparum infection, the protective efficacy of intervention was 61% (95% CI: 18-83; P = .007). 97.9% of screened windows and 63.8% of screened doors were intact after eleven months of installation. Malaria mosquito was resistance (mortality rate of 75%) to the insecticide used for bed nets treatment. Almost all participants of intervention arm were willing to continue using screened doors and windows. Screening doors and windows reduced the indoor exposure to malaria vectors. The intervention is effective, durable and well-accepted. Hence, the existing interventions can be supplemented with house screening intervention for further reduction and ultimately elimination of malaria by reducing insecticide pressure on malaria vectors. However, further research could be considered in broad setting on different housing improvement and in the way how to scale-up for wider community. Copyright © 2018 Elsevier B.V. All rights reserved.

Situation of Sri Lanka, where autochthonous malaria is no longer a problem, and other infections dominate, such as dengue, leptospirosis and rickettsioses.

PubMed

Agampodi, Suneth; Wijerathne, Buddhika; Weerakoon, Kosala

2016-10-01

Sri Lanka achieved a major milestone in communicable disease control in 2012 by reporting zero incidence of autochthonous malaria. However, reduction of malaria was associated with concurrent increase of several tropical diseases. This review looks into the time trends and epidemiology of these communicable diseases in Sri Lanka. Reduction of malaria cases coincides with an increase of dengue, leptospirosis and rickettsioses in Sri Lanka. Although the case fatality rate of dengue has reduced and maintained below 1%, leptospirosis in clinical management is questionable. Despite having national focal points for control and prevention, these emerging diseases are completely out of control. Whether the holding back of vector control activities of malaria after a successful control programme is having an effect on emergence of other vector-borne diseases should be studied. The communicable disease control programme in Sri Lanka should be further strengthened with availability of proper and rapid diagnostic facilities. Malaria control could not be considered as a great achievement due to the fact that other emerging infectious diseases are replacing malaria.

Malaria in Uganda: challenges to control on the long road to elimination. I. Epidemiology and current control effort

PubMed Central

Yeka, Adoke; Gasasira, Anne; Mpimbaza, Arthur; Achan, Jane; Nankabirwa, Joaniter; Nsobya, Sam; Staedke, Sarah G.; Donnelly, Martin J.; Wabwire-Mangen, Fred; Talisuna, Ambrose; Dorsey, Grant; Kamya, Moses R.; Rosenthal, Philip J.

2012-01-01

In the recent past there have been several reports of successes in malaria control, leading some public health experts to conclude that Africa is witnessing an epidemiological transition, from an era of failed malaria control to progression from successful control to elimination. Successes in control have been attributed to increased international donor support leading to increased intervention coverage. However, these changes are not uniform across Africa. In Uganda, where baseline transmission is very high and intervention coverage not yet to scale, the malaria burden is not declining and has even likely increased in the last decade. In this article we present perspectives for the future for Uganda and other malaria endemic countries with high baseline transmission intensity and significant health system challenges. For these high burden areas,malaria elimination is currently not feasible, and early elimination programs are inappropriate, as they would further fragment already fragmented and inefficient malaria control systems. Rather, health impacts will be maximized by aiming to achieve universal coverage of proven interventions in the context of a strengthened health system. PMID:21756863

Biosurveillance Technology: Providing Situational Awareness through Increased Information Sharing

DTIC Science & Technology

2011-09-01

Sri Lanka, there are “separate vertical programmes [sic] to control and monitor malaria , filariasis, leprosy, respiratory diseases, human rabies...Biohazard Detection System CAP Common Alerting Protocol CDC Centers for Disease Control and Prevention CDC HAN Centers for Disease Control and Prevention...LCDHD Preparedness Program running, I always had complete and total faith that you had everything under control and you would excel at every task. To

Malaria in Brazil, Colombia, Peru and Venezuela: current challenges in malaria control and elimination.

PubMed

Recht, Judith; Siqueira, André M; Monteiro, Wuelton M; Herrera, Sonia M; Herrera, Sócrates; Lacerda, Marcus V G

2017-07-04

In spite of significant progress towards malaria control and elimination achieved in South America in the 2000s, this mosquito-transmitted tropical disease remains an important public health concern in the region. Most malaria cases in South America come from Amazon rain forest areas in northern countries, where more than half of malaria is caused by Plasmodium vivax, while Plasmodium falciparum malaria incidence has decreased in recent years. This review discusses current malaria data, policies and challenges in four South American Amazon countries: Brazil, Colombia, Peru and the Bolivarian Republic of Venezuela. Challenges to continuing efforts to further decrease malaria incidence in this region include: a significant increase in malaria cases in recent years in Venezuela, evidence of submicroscopic and asymptomatic infections, peri-urban malaria, gold mining-related malaria, malaria in pregnancy, glucose-6-phosphate dehydrogenase (G6PD) deficiency and primaquine use, and possible under-detection of Plasmodium malariae. Some of these challenges underscore the need to implement appropriate tools and procedures in specific regions, such as a field-compatible molecular malaria test, a P. malariae-specific test, malaria diagnosis and appropriate treatment as part of regular antenatal care visits, G6PD test before primaquine administration for P. vivax cases (with weekly primaquine regimen for G6PD deficient individuals), single low dose of primaquine for P. falciparum malaria in Colombia, and national and regional efforts to contain malaria spread in Venezuela urgently needed especially in mining areas. Joint efforts and commitment towards malaria control and elimination should be strategized based on examples of successful regional malaria fighting initiatives, such as PAMAFRO and RAVREDA/AMI.

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

PubMed Central

Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

2013-01-01

Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

Current vector control challenges in the fight against malaria.

PubMed

Benelli, Giovanni; Beier, John C

2017-10-01

The effective and eco-friendly control of Anopheles vectors plays a key role in any malaria management program. Integrated Vector Management (IVM) suggests making use of the full range of vector control tools available. The strategies for IVM require novel technologies to control outdoor transmission of malaria. Despite the wide number of promising control tools tested against mosquitoes, current strategies for malaria vector control used in most African countries are not sufficient to achieve successful malaria control. The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS. Larvicidal treatments can be useful, but are not recommended for rural areas. The research needed to improve the quality and delivery of mosquito vector control should focus on (i) optimization of processes and methods for vector control delivery; (ii) monitoring of vector populations and biting activity with reliable techniques; (iii) the development of effective and eco-friendly tools to reduce the burden or locally eliminate malaria and other mosquito-borne diseases; (iv) the careful evaluation of field suitability and efficacy of new mosquito control tools to prove their epidemiological impact; (v) the continuous monitoring of environmental changes which potentially affect malaria vector populations; (vi) the cooperation among different disciplines, with main emphasis on parasitology, tropical medicine, ecology, entomology, and ecotoxicology. A better understanding of behavioral ecology of malaria vectors is required. Key ecological obstacles that limit the effectiveness of vector control include the variation in mosquito behavior, development of insecticide resistance, presence of behavioral avoidance, high vector biodiversity, competitive and food web interactions, lack of insights on mosquito dispersal and mating behavior, and the impact of environmental changes on mosquito ecological traits. Overall, the trans-disciplinary cooperation among parasitologists and entomologists is crucial to ensure proper evaluation of the epidemiological impact triggered by novel mosquito vector control strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

Fighting malaria in Madhya Pradesh (Central India): Are we loosing the battle?

PubMed Central

Singh, Neeru; Dash, Aditya P; Thimasarn, Krongthong

2009-01-01

Malaria control in Madhya Pradesh is complex because of vast tracts of forest with tribal settlement. Fifty four million individuals of various ethnic origins, accounting for 8% of the total population of India, contributed 30% of total malaria cases, 60% of total falciparum cases and 50% of malaria deaths in the country. Ambitious goals to control tribal malaria by launching "Enhanced Malaria Control Project" (EMCP) by the National Vector Borne Disease Control Programme (NVBDCP), with the World Bank assistance, became effective in September 1997 in eight north Indian states. Under EMCP, the programme used a broader mix of new interventions, i.e. insecticide-treated bed nets, spraying houses with effective residual insecticides, use of larvivorous fishes, rapid diagnostic tests for prompt diagnosis, treatment of the sick with effective radical treatment and increased public awareness and IEC. However, the challenge is to scale up these services. A retrospective analysis of data on malaria morbidity and associated mortality reported under the existing surveillance system of the Madhya Pradesh (Central India) for the years 1996–2007 was carried out to determine the impact of EMCP on malaria morbidity and associated mortality. Analysis revealed that despite the availability of effective intervention tools for the prevention and control of malaria, falciparum malaria remains uncontrolled and deaths due to malaria have increased. Precisely, the aim of this epidemiological analysis is to draw lessons applicable to all international aid efforts, bureaucracy, policy makers and programme managers in assessing its project performance as a new Global Malaria Action Plan is launched with ambitious goal of reducing malaria and its elimination by scaling up the use of existing tools. PMID:19419588

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

PubMed

Bennett, Jason W; Yadava, Anjali; Tosh, Donna; Sattabongkot, Jetsumon; Komisar, Jack; Ware, Lisa A; McCarthy, William F; Cowden, Jessica J; Regules, Jason; Spring, Michele D; Paolino, Kristopher; Hartzell, Joshua D; Cummings, James F; Richie, Thomas L; Lumsden, Joanne; Kamau, Edwin; Murphy, Jittawadee; Lee, Cynthia; Parekh, Falgunee; Birkett, Ashley; Cohen, Joe; Ballou, W Ripley; Polhemus, Mark E; Vanloubbeeck, Yannick F; Vekemans, Johan; Ockenhouse, Christian F

2016-02-01

A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls. The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period. This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy

PubMed Central

Bennett, Jason W.; Yadava, Anjali; Tosh, Donna; Sattabongkot, Jetsumon; Komisar, Jack; Ware, Lisa A.; McCarthy, William F.; Cowden, Jessica J.; Regules, Jason; Spring, Michele D.; Paolino, Kristopher; Hartzell, Joshua D.; Cummings, James F.; Richie, Thomas L.; Lumsden, Joanne; Kamau, Edwin; Murphy, Jittawadee; Lee, Cynthia; Parekh, Falgunee; Birkett, Ashley; Cohen, Joe; Ballou, W. Ripley; Polhemus, Mark E.; Vanloubbeeck, Yannick F.; Vekemans, Johan; Ockenhouse, Christian F.

2016-01-01

Background A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. Methods We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15μg, 30μg, or 60μg respectively of VMP001, all formulated in 500μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls. Results The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period. Significance This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials. PMID:26919472

Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission

PubMed Central

Yilmaz, Bahtiyar; Portugal, Silvia; Tran, Tuan M.; Gozzelino, Raffaella; Ramos, Susana; Gomes, Joana; Regalado, Ana; Cowan, Peter J.; d’Apice, Anthony J.F.; Chong, Anita S.; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.; Silveira, Henrique; Soares, Miguel P.

2014-01-01

Summary Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans. PaperFlick PMID:25480293

Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.

PubMed

Zhang, De-Liang; Wu, Jian; Shah, Binal N; Greutélaers, Katja C; Ghosh, Manik C; Ollivierre, Hayden; Su, Xin-Zhuan; Thuma, Philip E; Bedu-Addo, George; Mockenhaupt, Frank P; Gordeuk, Victor R; Rouault, Tracey A

2018-03-30

Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPN Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research.

PubMed

Siciliano, Giulia; Alano, Pietro

2015-01-01

The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have been essential to unveil mechanisms of parasite gene expression and to develop in vivo imaging approaches in mouse malaria models. Mainly the human malaria parasite Plasmodium falciparum and the rodent parasite P. berghei have been engineered to express bioluminescent reporters in almost all the developmental stages of the parasite along its complex life cycle between the insect and the vertebrate hosts. Plasmodium lines expressing conventional and improved luciferase reporters are now gaining a central role to develop cell based assays in the much needed search of new antimalarial drugs and to open innovative approaches for both fundamental and applied research in malaria.

Hysteresis in simulations of malaria transmission

NASA Astrophysics Data System (ADS)

Yamana, Teresa K.; Qiu, Xin; Eltahir, Elfatih A. B.

2017-10-01

Malaria transmission is a complex system and in many parts of the world is closely related to climate conditions. However, studies on environmental determinants of malaria generally consider only concurrent climate conditions and ignore the historical or initial conditions of the system. Here, we demonstrate the concept of hysteresis in malaria transmission, defined as non-uniqueness of the relationship between malaria prevalence and concurrent climate conditions. We show the dependence of simulated malaria transmission on initial prevalence and the initial level of human immunity in the population. Using realistic time series of environmental variables, we quantify the effect of hysteresis in a modeled population. In a set of numerical experiments using HYDREMATS, a field-tested mechanistic model of malaria transmission, the simulated maximum malaria prevalence depends on both the initial prevalence and the initial level of human immunity in the population. We found the effects of initial conditions to be of comparable magnitude to the effects of interannual variability in environmental conditions in determining malaria prevalence. The memory associated with this hysteresis effect is longer in high transmission settings than in low transmission settings. Our results show that efforts to simulate and forecast malaria transmission must consider the exposure history of a location as well as the concurrent environmental drivers.

Simulation of the Impact of Climate Variability on Malaria Transmission in the Sahel

NASA Astrophysics Data System (ADS)

Bomblies, A.; Eltahir, E.; Duchemin, J.

2007-12-01

A coupled hydrology and entomology model for simulation of malaria transmission and malaria transmitting mosquito population dynamics is presented. Model development and validation is done using field data and observations collected at Banizoumbou and Zindarou, Niger spanning three wet seasons, from 2005 through 2007. The primary model objective is the accurate determination of climate variability effects on village scale malaria transmission. Malaria transmission dependence on climate variables is highly nonlinear and complex. Temperature and humidity affect mosquito longevity, temperature controls parasite development rates in the mosquito as well as subadult mosquito development rates, and precipitation determines the formation and persistence of adequate breeding pools. Moreover, unsaturated zone hydrology influences overland flow, and climate controlled evapotranspiration rates and root zone uptake therefore also influence breeding pool formation. High resolution distributed hydrologic simulation allows representation of the small-scale ephemeral pools that constitute the primary habitat of Anopheles gambiae mosquitoes, the dominant malaria vectors in the Niger Sahel. Remotely sensed soil type, vegetation type, and microtopography rasters are used to assign the distributed parameter fields for simulation of the land surface hydrologic response to precipitation and runoff generation. Predicted runoff from each cell flows overland and into topographic depressions, with explicit representation of infiltration and evapotranspiration. The model's entomology component interacts with simulated pools. Subadult (aquatic stage) mosquito breeding is simulated in the pools, and water temperature dependent stage advancement rates regulate adult mosquito emergence into the model domain. Once emerged, adult mosquitoes are tracked as independent individual agents that interact with their immediate environment. Attributes relevant to malaria transmission such as gonotrophic state, infected and infectious states, age, and location relative to human population are tracked for each individual. The model operates at a resolution consistent with the characteristic scale of relevant ecological processes. Microhabitat exploitation and spatial structure of the mosquito population surrounding villages is reproduced in this manner. The resulting coupled model predicts not only malaria transmission's response to interannual climate variability, but can also evaluate land use change effects on malaria transmission. The late Professor Andrew Spielman of the Harvard School of Public Health provided medical entomology expertise and was a part of this effort.

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

PubMed Central

Hemingway, Janet; Shretta, Rima; Wells, Timothy N. C.; Bell, David; Djimdé, Abdoulaye A.; Achee, Nicole; Qi, Gao

2016-01-01

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication. PMID:26934361

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

PubMed

Hemingway, Janet; Shretta, Rima; Wells, Timothy N C; Bell, David; Djimdé, Abdoulaye A; Achee, Nicole; Qi, Gao

2016-03-01

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.

Plasmodium knowlesi from archival blood films: Further evidence that human infections are widely distributed and not newly emergent in Malaysian Borneo

PubMed Central

Lee, Kim-Sung; Cox-Singh, Janet; Brooke, George; Matusop, Asmad; Singh, Balbir

2009-01-01

Human infections with Plasmodium knowlesi have been misdiagnosed by microscopy as Plasmodium malariae due to their morphological similarities. Although microscopy-identified P. malariae cases have been reported in the state of Sarawak (Malaysian Borno) as early as 1952, recent epidemiological studies suggest the absence of indigenous P. malariae infections. The present study aimed to determine the past incidence and distribution of P. knowlesi infections in the state of Sarawak based on archival blood films from patients diagnosed by microscopy as having P. malariae infections. Nested PCR assays were used to identify Plasmodium species in DNA extracted from 47 thick blood films collected in 1996 from patients in seven different divisions throughout the state of Sarawak. Plasmodium knowlesi DNA was detected in 35 (97.2%) of 36 blood films that were positive for Plasmodium DNA, with patients originating from all seven divisions. Only one sample was positive for P. malariae DNA. This study provides further evidence of the widespread distribution of human infections with P. knowlesi in Sarawak and its past occurrence. Taken together with data from previous studies, our findings suggest that P. knowlesi malaria is not a newly emergent disease in humans. PMID:19358848

Slow and fast dynamics model of a Malaria with Sickle-Cell genetic disease with multi-stage infections of the mosquitoes population

NASA Astrophysics Data System (ADS)

Dewi Siawanta, Shanti; Adi-Kusumo, Fajar; Irwan Endrayanto, Aluicius

2018-03-01

Malaria, which is caused by Plasmodium, is a common disease in tropical areas. There are three types of Plasmodium i.e. Plasmodium Vivax, Plasmodium Malariae, and Plasmodium Falciparum. The most dangerous cases of the Malaria are mainly caused by the Plasmodium Falciparum. One of the important characteristics for the Plasmodium infection is due to the immunity of erythrocyte that contains HbS (Haemoglobin Sickle-cell) genes. The individuals who has the HbS gene has better immunity against the disease. In this paper, we consider a model that shows the spread of malaria involving the interaction between the mosquitos population, the human who has HbS genes population and the human with normal gene population. We do some analytical and numerical simulation to study the basic reproduction ratio and the slow-fast dynamics of the phase-portrait. The slow dynamics in our model represents the response of the human population with HbS gene to the Malaria disease while the fast dynamics show the response of the human population with the normal gene to the disease. The slow and fast dynamics phenomena are due to the fact that the population of the individuals who have HbS gene is much smaller than the individuals who has normal genes.

“Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes”

PubMed Central

Neafsey, Daniel E.; Waterhouse, Robert M.; Abai, Mohammad R.; Aganezov, Sergey S.; Alekseyev, Max A.; Allen, James E.; Amon, James; Arcà, Bruno; Arensburger, Peter; Artemov, Gleb; Assour, Lauren A.; Basseri, Hamidreza; Berlin, Aaron; Birren, Bruce W.; Blandin, Stephanie A.; Brockman, Andrew I.; Burkot, Thomas R.; Burt, Austin; Chan, Clara S.; Chauve, Cedric; Chiu, Joanna C.; Christensen, Mikkel; Costantini, Carlo; Davidson, Victoria L.M.; Deligianni, Elena; Dottorini, Tania; Dritsou, Vicky; Gabriel, Stacey B.; Guelbeogo, Wamdaogo M.; Hall, Andrew B.; Han, Mira V.; Hlaing, Thaung; Hughes, Daniel S.T.; Jenkins, Adam M.; Jiang, Xiaofang; Jungreis, Irwin; Kakani, Evdoxia G.; Kamali, Maryam; Kemppainen, Petri; Kennedy, Ryan C.; Kirmitzoglou, Ioannis K.; Koekemoer, Lizette L.; Laban, Njoroge; Langridge, Nicholas; Lawniczak, Mara K.N.; Lirakis, Manolis; Lobo, Neil F.; Lowy, Ernesto; MacCallum, Robert M.; Mao, Chunhong; Maslen, Gareth; Mbogo, Charles; McCarthy, Jenny; Michel, Kristin; Mitchell, Sara N.; Moore, Wendy; Murphy, Katherine A.; Naumenko, Anastasia N.; Nolan, Tony; Novoa, Eva M.; O'Loughlin, Samantha; Oringanje, Chioma; Oshaghi, Mohammad A.; Pakpour, Nazzy; Papathanos, Philippos A.; Peery, Ashley N.; Povelones, Michael; Prakash, Anil; Price, David P.; Rajaraman, Ashok; Reimer, Lisa J.; Rinker, David C.; Rokas, Antonis; Russell, Tanya L.; Sagnon, N'Fale; Sharakhova, Maria V.; Shea, Terrance; Simão, Felipe A.; Simard, Frederic; Slotman, Michel A.; Somboon, Pradya; Stegniy, Vladimir; Struchiner, Claudio J.; Thomas, Gregg W.C.; Tojo, Marta; Topalis, Pantelis; Tubio, José M.C.; Unger, Maria F.; Vontas, John; Walton, Catherine; Wilding, Craig S.; Willis, Judith H.; Wu, Yi-Chieh; Yan, Guiyun; Zdobnov, Evgeny M.; Zhou, Xiaofan; Catteruccia, Flaminia; Christophides, George K.; Collins, Frank H.; Cornman, Robert S.; Crisanti, Andrea; Donnelly, Martin J.; Emrich, Scott J.; Fontaine, Michael C.; Gelbart, William; Hahn, Matthew W.; Hansen, Immo A.; Howell, Paul I.; Kafatos, Fotis C.; Kellis, Manolis; Lawson, Daniel; Louis, Christos; Luckhart, Shirley; Muskavitch, Marc A.T.; Ribeiro, José M.; Riehle, Michael A.; Sharakhov, Igor V.; Tu, Zhijian; Zwiebel, Laurence J.; Besansky, Nora J.

2015-01-01

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover, but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts. PMID:25554792

Analysis of the El Niño/La Niña-Southern Oscillation variability and malaria in the Estado Sucre, Venezuela.

PubMed

Delgado-Petrocelli, Laura; Córdova, Karenia; Camardiel, Alberto; Aguilar, Víctor H; Hernández, Denise; Ramos, Santiago

2012-09-01

The last decade has seen an unprecedented, worldwide acceleration of environmental and climate changes. These processes impact the dynamics of natural systems, which include components associated with human communities such as vector-borne diseases. The dynamics of environmental and climate variables, altered by global change as reported by the Intergovernmental Panel on Climate Change, affect the distribution of many tropical diseases. Complex systems, e.g. the El Niño/La Niña-Southern Oscillation (ENSO), in which environmental variables operate synergistically, can provoke the reemergence and emergence of vector-borne diseases at new sites. This research investigated the influence of ENSO events on malaria incidence by determining the relationship between climate variations, expressed as warm, cold and neutral phases, and their relation to the number of malaria cases in some north-eastern municipalities of Venezuela (Estado Sucre) during the period 1990-2000. Significant differences in malaria incidence were found, particularly in the La Niña ENSO phases (cold) of moderate intensity. These findings should be taken into account for surveillance and control in the future as they shed light on important indicators that can lead to reduced vulnerability to malaria.

Optimal control problems of epidemic systems with parameter uncertainties: application to a malaria two-age-classes transmission model with asymptomatic carriers.

PubMed

Mwanga, Gasper G; Haario, Heikki; Capasso, Vicenzo

2015-03-01

The main scope of this paper is to study the optimal control practices of malaria, by discussing the implementation of a catalog of optimal control strategies in presence of parameter uncertainties, which is typical of infectious diseases data. In this study we focus on a deterministic mathematical model for the transmission of malaria, including in particular asymptomatic carriers and two age classes in the human population. A partial qualitative analysis of the relevant ODE system has been carried out, leading to a realistic threshold parameter. For the deterministic model under consideration, four possible control strategies have been analyzed: the use of Long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic and asymptomatic individuals. The numerical results show that using optimal control the disease can be brought to a stable disease free equilibrium when all four controls are used. The Incremental Cost-Effectiveness Ratio (ICER) for all possible combinations of the disease-control measures is determined. The numerical simulations of the optimal control in the presence of parameter uncertainty demonstrate the robustness of the optimal control: the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the designing of cost-effective strategies for disease controls with multiple interventions, even under considerable uncertainty of model parameters. Copyright © 2014 Elsevier Inc. All rights reserved.

No evidence for positive selection at two potential targets for malaria transmission-blocking vaccines in Anopheles gambiae s.s.

PubMed

Crawford, Jacob E; Rottschaefer, Susan M; Coulibaly, Boubacar; Sacko, Madjou; Niaré, Oumou; Riehle, Michelle M; Traore, Sékou F; Vernick, Kenneth D; Lazzaro, Brian P

2013-06-01

Human malaria causes nearly a million deaths in sub-Saharan Africa each year. The evolution of drug-resistance in the parasite and insecticide resistance in the mosquito vector has complicated control measures and made the need for new control strategies more urgent. Anopheles gambiae s.s. is one of the primary vectors of human malaria in Africa, and parasite-transmission-blocking vaccines targeting Anopheles proteins have been proposed as a possible strategy to control the spread of the disease. However, the success of these hypothetical technologies would depend on the successful ability to broadly target mosquito populations that may be genetically heterogeneous. Understanding the evolutionary pressures shaping genetic variation among candidate target molecules offers a first step towards evaluating the prospects of successfully deploying such technologies. We studied the population genetics of genes encoding two candidate target proteins, the salivary gland protein saglin and the basal lamina structural protein laminin, in wild populations of the M and S molecular forms of A. gambiae in Mali. Through analysis of intraspecific genetic variation and interspecific comparisons, we found no evidence of positive natural selection at the genes encoding these proteins. On the contrary, we found evidence for particularly strong purifying selection at the laminin gene. These results provide insight into the patterns of genetic diversity of saglin and laminin, and we discuss these findings in relation to the potential development of these molecules as vaccine targets. Copyright © 2013 Elsevier B.V. All rights reserved.

Declining malaria, rising of dengue and Zika virus: insights for mosquito vector control.

PubMed

Benelli, Giovanni; Mehlhorn, Heinz

2016-05-01

The fight against mosquito-borne diseases is a challenge of huge public health importance. To our mind, 2015 was an extraordinary year for malaria control, due to three hot news: the Nobel Prize to Youyou Tu for the discovery of artemisinin, the development of the first vaccine against Plasmodium falciparum malaria [i.e. RTS,S/AS01 (RTS,S)], and the fall of malaria infection rates worldwide, with special reference to sub-Saharan Africa. However, there are major challenges that still deserve attention, in order to boost malaria prevention and control. Indeed, parasite strains resistant to artemisinin have been detected, and RTS,S vaccine does not offer protection against Plasmodium vivax malaria, which predominates in many countries outside of Africa. Furthermore, the recent outbreaks of Zika virus infections, occurring in South America, Central America and the Caribbean, represent the most recent of four arrivals of important arboviruses in the Western Hemisphere, over the last 20 years. Zika virus follows dengue (which slyly arrived in the hemisphere over decades and became more aggressive in the 1990s), West Nile virus (emerged in 1999) and chikungunya (emerged in 2013). Notably, there are no specific treatments for these arboviruses. The emerging scenario highlights that the effective and eco-friendly control of mosquito vectors, with special reference to highly invasive species such as Aedes aegypti and Aedes albopictus, is crucial. The concrete potential of screening plant species as sources of metabolites for parasitological purposes is worthy of attention, as elucidated by the Y. Tu's example. Notably, plant-borne molecules are often effective at few parts per million against Aedes, Ochlerotatus, Anopheles and Culex young instars, can be used for the rapid synthesis of mosquitocidal nanoformulations and even employed to prepare cheap repellents with low human toxicity. In addition, behaviour-based control tools relying to the employ of sound traps and the manipulation of swarming behaviour (i.e. "lure and kill" approach) are discussed. The importance of further research on the chemical cues routing mosquito swarming and mating dynamics is highlighted. Besides radiation, transgenic and symbiont-based mosquito control approaches, an effective option may be the employ of biological control agents of mosquito young instars, in the presence of ultra-low quantities of nanoformulated botanicals, which boost their predation rates.

Malaria in selected non-Amazonian countries of Latin America.

PubMed

Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Angel; Padilla, Julio Cesar; Escalante, Ananias A; Beier, John C; Herrera, Socrates

2012-03-01

Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent's contribution to the global malaria burden is small, at least 1-1.2 million malaria cases are reported annually. Sixty percent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2%) followed by P. falciparum (25.7%) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by the Pan American Health Organization/World Health Organization (PAHO/WHO) and several other partners), have made great investments for malaria control in the region. We describe here the current status of malaria in a non-Amazonian region comprising several countries of South and Central America participating in the Centro Latino Americano de Investigación en Malaria (CLAIM), an International Center of Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID). Copyright © 2011 Elsevier B.V. All rights reserved.

Malaria in selected non-Amazonian countries of Latin America

PubMed Central

Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Ángel; Padilla, Julio Cesar; Escalante, Ananias A.; Beier, John C.; Herrera, Socrates

2011-01-01

Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent’s contribution to the global malaria burden is small, at least 1 to 1.2 million malaria cases are reported annually. Sixty per cent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2 %) followed by P. falciparum (25.7 %) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by the Pan American Health Organization/World Health Organization (PAHO/WHO) and several other partners), have made great investments for malaria control in the region. We describe here the current status of malaria in a non-Amazonian region comprising several countries of South and Central America participating in the Centro Latino Americano de Investigación en Malaria (CLAIM), an International Center of Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). PMID:21741349

Funding for malaria control 2006-2010: a comprehensive global assessment.

PubMed

Pigott, David M; Atun, Rifat; Moyes, Catherine L; Hay, Simon I; Gething, Peter W

2012-07-28

The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world. As the ongoing climate of financial uncertainty places strains on investment in global health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease. A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010. Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk. Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect. US$8.9 billion was disbursed for malaria control and elimination programmes over the study period. Africa had the largest levels of funding per capita-at-risk, with most nations supported primarily by international aid. Countries of the Americas, in contrast, were supported typically through national government funding. Disbursements and government funding in Asia were far lower with a large variation in funding patterns. Nations with relatively high and low levels of funding are discussed. Global funding for malaria control is substantially less than required. Inequity in funding is pronounced in some regions particularly when considering the distinct goals of malaria control and malaria elimination. Efforts to sustain and increase international investment in malaria control should be informed by evidence-based assessment of funding equity.

Funding for malaria control 2006–2010: A comprehensive global assessment

PubMed Central

2012-01-01

Background The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world. As the ongoing climate of financial uncertainty places strains on investment in global health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease. Methods A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010. Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk. Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect. Results US$8.9 billion was disbursed for malaria control and elimination programmes over the study period. Africa had the largest levels of funding per capita-at-risk, with most nations supported primarily by international aid. Countries of the Americas, in contrast, were supported typically through national government funding. Disbursements and government funding in Asia were far lower with a large variation in funding patterns. Nations with relatively high and low levels of funding are discussed. Conclusions Global funding for malaria control is substantially less than required. Inequity in funding is pronounced in some regions particularly when considering the distinct goals of malaria control and malaria elimination. Efforts to sustain and increase international investment in malaria control should be informed by evidence-based assessment of funding equity. PMID:22839432

Anophelines species and the receptivity and vulnerability to malaria transmission in the Pantanal wetlands, Central Brazil

PubMed Central

Marinho-e-Silva, Mariana; Sallum, Maria Anice Mureb; Rosa-Freitas, Maria Goreti; Lourenço-de-Oliveira, Ricardo; Silva-do-Nascimento, Teresa Fernandes

2018-01-01

BACKGROUND Studies on malaria vectors in the Pantanal biome, Central Brazil, were conducted more than half a century ago. OBJECTIVES To update anopheline records and assess receptivity and vulnerability to malaria transmission. METHODS Five-day anopheline collections were conducted bimonthly in Salobra, Mato Grosso do Sul state, for one year. Indoors, mosquitoes were collected from their resting places, while in open fields, they were captured using protected human-baited and horse-baited traps near the house and at the Miranda River margin, respectively. Hourly biting activity outdoors was also assessed. Secondary data were collected on the arrival of tourists, economic projects, and malaria cases. FINDINGS A total of 24,894 anophelines belonging to 13 species were caught. The main Brazilian malaria vector Anopheles darlingi was the predominant species, followed by An. triannulatus s.l. Hourly variation in anopheline biting showed three main peaks occurring at sunset, around midnight, and at sunrise, the first and last being the most prominent. The highest density of all species was recorded near the river margin and during the transition period between the rainy and early dry seasons. This coincides with the time of main influx of outsider workers and tourists, whose activities mostly occur in the open fields and frequently start before sunrise and last until sunset. Some of these individuals originate from neighbouring malaria-endemic countries and states, and are likely responsible for the recorded imported and introduced malaria cases. MAIN CONCLUSION Pantanal is a malaria-prone area in Brazil. Surveillance and anopheline control measures must be applied to avoid malaria re-emergence in the region. PMID:29236930

TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon.

PubMed

Brasil, Larissa W; Barbosa, Laila R A; de Araujo, Felipe J; da Costa, Allyson G; da Silva, Luan D O; Pinheiro, Suzana K; de Almeida, Anne C G; Kuhn, Andrea; Vitor-Silva, Sheila; de Melo, Gisely C; Monteiro, Wuelton M; de Lacerda, Marcus V G; Ramasawmy, Rajendranath

2017-03-13

Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon. This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp ® DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP. Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r 2  = 0.037; D' = 0.27). These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.

Plasmodium falciparum Malaria Endemicity in Indonesia in 2010

PubMed Central

Elyazar, Iqbal R. F.; Gething, Peter W.; Patil, Anand P.; Rogayah, Hanifah; Kusriastuti, Rita; Wismarini, Desak M.; Tarmizi, Siti N.; Baird, J. Kevin; Hay, Simon I.

2011-01-01

Background Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010. Methods Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006–2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985–2009). After quality control, 2,516 were included into a national database of age-standardized 2–10 year old PfPR data (PfPR2–10) for endemicity mapping. A Bayesian MBG procedure was used to create a predicted surface of PfPR2–10 endemicity with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population count surface. Results We estimate 132.8 million people in Indonesia, lived at risk of P. falciparum transmission in 2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in stable transmission. Among those exposed to stable risk, the vast majority were at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk (0.01%). More people in western Indonesia lived in unstable rather than stable transmission zones. In contrast, fewer people in eastern Indonesia lived in unstable versus stable transmission areas. Conclusion While further feasibility assessments will be required, the immediate prospects for sustained control are good across much of the archipelago and medium term plans to transition to the pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas of Papua will clearly present the greatest challenge. This P. falciparum endemicity map allows malaria control agencies and their partners to comprehensively assess the region-specific prospects for reaching pre-elimination, monitor and evaluate the effectiveness of future strategies against this 2010 baseline and ultimately improve their evidence-based malaria control strategies. PMID:21738634

Fya/Fyb antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria

PubMed Central

King, Christopher L.; Adams, John H.; Xianli, Jia; Grimberg, Brian T.; McHenry, Amy M.; Greenberg, Lior J.; Siddiqui, Asim; Howes, Rosalind E.; da Silva-Nunes, Monica; Ferreira, Marcelo U.; Zimmerman, Peter A.

2011-01-01

Plasmodium vivax (Pv) is a major cause of human malaria and is increasing in public health importance compared with falciparum malaria. Pv is unique among human malarias in that invasion of erythrocytes is almost solely dependent on the red cell's surface receptor, known as the Duffy blood-group antigen (Fy). Fy is an important minor blood-group antigen that has two immunologically distinct alleles, referred to as Fya or Fyb, resulting from a single-point mutation. This mutation occurs within the binding domain of the parasite's red cell invasion ligand. Whether this polymorphism affects susceptibility to clinical vivax malaria is unknown. Here we show that Fya, compared with Fyb, significantly diminishes binding of Pv Duffy binding protein (PvDBP) at the erythrocyte surface, and is associated with a reduced risk of clinical Pv in humans. Erythrocytes expressing Fya had 41–50% lower binding compared with Fyb cells and showed an increased ability of naturally occurring or artificially induced antibodies to block binding of PvDBP to their surface. Individuals with the Fya+b− phenotype demonstrated a 30–80% reduced risk of clinical vivax, but not falciparum malaria in a prospective cohort study in the Brazilian Amazon. The Fya+b− phenotype, predominant in Southeast Asian and many American populations, would confer a selective advantage against vivax malaria. Our results also suggest that efficacy of a PvDBP-based vaccine may differ among populations with different Fy phenotypes. PMID:22123959

Fy(a)/Fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria.

PubMed

King, Christopher L; Adams, John H; Xianli, Jia; Grimberg, Brian T; McHenry, Amy M; Greenberg, Lior J; Siddiqui, Asim; Howes, Rosalind E; da Silva-Nunes, Monica; Ferreira, Marcelo U; Zimmerman, Peter A

2011-12-13

Plasmodium vivax (Pv) is a major cause of human malaria and is increasing in public health importance compared with falciparum malaria. Pv is unique among human malarias in that invasion of erythrocytes is almost solely dependent on the red cell's surface receptor, known as the Duffy blood-group antigen (Fy). Fy is an important minor blood-group antigen that has two immunologically distinct alleles, referred to as Fy(a) or Fy(b), resulting from a single-point mutation. This mutation occurs within the binding domain of the parasite's red cell invasion ligand. Whether this polymorphism affects susceptibility to clinical vivax malaria is unknown. Here we show that Fy(a), compared with Fy(b), significantly diminishes binding of Pv Duffy binding protein (PvDBP) at the erythrocyte surface, and is associated with a reduced risk of clinical Pv in humans. Erythrocytes expressing Fy(a) had 41-50% lower binding compared with Fy(b) cells and showed an increased ability of naturally occurring or artificially induced antibodies to block binding of PvDBP to their surface. Individuals with the Fy(a+b-) phenotype demonstrated a 30-80% reduced risk of clinical vivax, but not falciparum malaria in a prospective cohort study in the Brazilian Amazon. The Fy(a+b-) phenotype, predominant in Southeast Asian and many American populations, would confer a selective advantage against vivax malaria. Our results also suggest that efficacy of a PvDBP-based vaccine may differ among populations with different Fy phenotypes.

A case of severe Plasmodium knowlesi in a splenectomized patient.

PubMed

Boo, Yang Liang; Lim, Hong Tak; Chin, Pek Woon; Lim, Suat Yee; Hoo, Fan Kee

2016-02-01

Plasmodium knowlesi, a zoonotic malaria, is now considered the fifth species of Plasmodium causing malaria in humans. With its 24-hour erythrocytic stage of development, it has raised concern regarding its high potential in replicating and leading to severe illness. Spleen is an important site for removal of parasitized red blood cells and generating immunity. We reported a case of knowlesi malaria in a non-immune, splenectomized patient. We observed the delay in parasite clearance, high parasitic counts, and severe illness at presentation. A thorough search through literature revealed several case reports on falciparum and vivax malaria in splenectomized patients. However, literature available for knowlesi malaria in splenectomized patient is limited. Further studies need to be carried out to clarify the role of spleen in host defense against human malaria especially P. knowlesi. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Plasmodium berghei ANKA (PbA) infection of C57BL/6J mice: a model of severe malaria.

PubMed

de Oca, Marcela Montes; Engwerda, Christian; Haque, Ashraful

2013-01-01

The term "severe malaria" refers to a wide spectrum of syndromes in Plasmodium-infected humans including cerebral malaria (CM), respiratory distress, severe anemia, liver dysfunction, and hypoglycemia. Mouse models have been employed to further our understanding of the pathology and immune responses that occur during Plasmodium infection. Evidence of brain, liver, lung, and spleen pathology, as well as anemia and tissue-sequestration of parasites, has been reported in various strains of inbred mice. While no single mouse model mimics all the various clinical manifestations of severe malaria in humans, here we describe a detailed protocol for Plasmodium berghei ANKA infection of C57BL/6J mice. For many years, this model has been referred to as "experimental cerebral malaria," but in fact recapitulates many of the symptoms and pathologies observed in most severe malaria syndromes.

Environmental management: a re-emerging vector control strategy.

PubMed

Ault, S K

1994-01-01

Vector control may be accomplished by environmental management (EM), which consists of permanent or long-term modification of the environment, temporary or seasonal manipulation of the environment, and modifying or changing our life styles and practices to reduce human contact with infective vectors. The primary focus of this paper is EM in the control of human malaria, filariasis, arboviruses, Chagas' disease, and schistosomiasis. Modern EM developed as a discipline based primarily in ecologic principles and lessons learned from the adverse environmental impacts of rural development projects. Strategies such as the suppression of vector populations through the provision of safe water supplies, proper sanitation, solid waste management facilities, sewerage and excreta disposal systems, water manipulation in dams and irrigation systems, vector diversion by zooprophylaxis, and vector exclusion by improved housing, are discussed with appropriate examples. Vectors of malaria, filariasis, Chagas' disease, and schistosomiasis have been controlled by drainage or filling aquatic breeding sites, improved housing and sanitation, the use of expanded polystyrene beads, zooprophylaxis, or the provision of household water supplies. Community participation has been effective in the suppression of dengue vectors in Mexico and the Dominican Republic. Alone or combined with other vector control methods, EM has been proven to be a successful approach to vector control in a number of places. The future of EM in vector control looks promising.

IDOMAL: an ontology for malaria.

PubMed

Topalis, Pantelis; Mitraka, Elvira; Bujila, Ioana; Deligianni, Elena; Dialynas, Emmanuel; Siden-Kiamos, Inga; Troye-Blomberg, Marita; Louis, Christos

2010-08-10

Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures. The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium. The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO). The latter is currently being developed in the frame of a large international collaborative effort. IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.

[Evaluation of effect of prevention and control system for imported falciparum malaria in Hanjiang District].

PubMed

She, Guo-lin; Ma, Yu-Cai; Wang, Fu-biao

2013-08-01

To analyze the current situation of the comprehensive prevention and control system for imported falciparum malaria in Hanjiang District and evaluate its effect. According to the Management Scheme on Control of Imported Falciparum Malaria in Yangzhou City, the comprehensive prevention and control system for imported falciparum malaria was implemented, and the relevant malaria data were collected and analyzed statistically. The data included plasmodium blood test ratio of fever patients among exported labors and those returned, the ratio of laboratory-confirmed cases among all reported cases of falciparum malaria, the ratio of falciparum malaria patients who received the standard treatment within 24 hours after onset, etc from 2010 to 2012. After the implementation of the comprehensive prevention and control system, the confirmation ratio of falciparum malaria cases within 24 hours following first visit has reached 60.47%, the average time from first visit to confirmation has shortened to 1.8 d, and the average time from onset to confirmation has shortened to 3.7 d. The health education coverage ratio was 100%, the health knowledge awareness ratio was 95.56%, the ratio of patients seeking treatment on own initiative was 100%, the laboratory-confirmed ratio was 100%, and the ratio of standard treatment after malaria diagnosis was 100%. The comprehensive prevention and control system carried out by Hanjiang District has made remarkable achievements.

Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa

PubMed Central

Yé, Yazoume; Eisele, Thomas P.; Eckert, Erin; Korenromp, Eline; Shah, Jui A.; Hershey, Christine L.; Ivanovich, Elizabeth; Newby, Holly; Carvajal-Velez, Liliana; Lynch, Michael; Komatsu, Ryuichi; Cibulskis, Richard E.; Moore, Zhuzhi; Bhattarai, Achuyt

2017-01-01

Abstract. Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality. PMID:28990923

Implementing Impact Evaluations of Malaria Control Interventions: Process, Lessons Learned, and Recommendations

PubMed Central

Hershey, Christine L.; Bhattarai, Achuyt; Florey, Lia S.; McElroy, Peter D.; Nielsen, Carrie F.; Yé, Yazoume; Eckert, Erin; Franca-Koh, Ana Cláudia; Shargie, Estifanos; Komatsu, Ryuichi; Smithson, Paul; Thwing, Julie; Mihigo, Jules; Herrera, Samantha; Taylor, Cameron; Shah, Jui; Mouzin, Eric; Yoon, Steven S.; Salgado, S. René

2017-01-01

Abstract. As funding for malaria control increased considerably over the past 10 years resulting in the expanded coverage of malaria control interventions, so did the need to measure the impact of these investments on malaria morbidity and mortality. Members of the Roll Back Malaria (RBM) Partnership undertook impact evaluations of malaria control programs at a time when there was little guidance in terms of the process for conducting an impact evaluation of a national-level malaria control program. The President’s Malaria Initiative (PMI), as a member of the RBM Partnership, has provided financial and technical support for impact evaluations in 13 countries to date. On the basis of these experiences, PMI and its partners have developed a streamlined process for conducting the evaluations with a set of lessons learned and recommendations. Chief among these are: to ensure country ownership and involvement in the evaluations; to engage stakeholders throughout the process; to coordinate evaluations among interested partners to avoid duplication of efforts; to tailor the evaluation to the particular country context; to develop a standard methodology for the evaluations and a streamlined process for completion within a reasonable time; and to develop tailored dissemination products on the evaluation for a broad range of stakeholders. These key lessons learned and resulting recommendations will guide future impact evaluations of malaria control programs and other health programs. PMID:28990921

Vaccines against malaria-still a long way to go.

PubMed

Matuschewski, Kai

2017-08-01

Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.

Malaria vector species in Colombia - A review

PubMed Central

Montoya-Lerma, James; Solarte, Yezid A; Giraldo-Calderón, Gloria Isabel; Quiñones, Martha L; Ruiz-López, Freddy; Wilkerson, Richard C; González, Ranulfo

2016-01-01

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species’ geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species. PMID:21881778

Towards eliminating malaria in high endemic countries: the roles of community health workers and related cadres and their challenges in integrated community case management for malaria: a systematic review.

PubMed

Sunguya, Bruno F; Mlunde, Linda B; Ayer, Rakesh; Jimba, Masamine

2017-01-03

Human resource for health crisis has impaired global efforts against malaria in highly endemic countries. To address this, the World Health Organization (WHO) recommended scaling-up of community health workers (CHWs) and related cadres owing to their documented success in malaria and other disease prevention and management. Evidence is inconsistent on the roles and challenges they encounter in malaria interventions. This systematic review aims to summarize evidence on roles and challenges of CHWs and related cadres in integrated community case management for malaria (iCCM). This systematic review retrieved evidence from PubMed, CINAHL, ISI Web of Knowledge, and WHO regional databases. Terms extracted from the Boolean phrase used for PubMed were also used in other databases. The review included studies with Randomized Control Trial, Quasi-experimental, Pre-post interventional, Longitudinal and cohort, Cross-sectional, Case study, and Secondary data analysis. Because of heterogeneity, only narrative synthesis was conducted for this review. A total of 66 articles were eligible for analysis out of 1380 studies retrieved. CHWs and related cadre roles in malaria interventions included: malaria case management, prevention including health surveillance and health promotion specific to malaria. Despite their documented success, CHWs and related cadres succumb to health system challenges. These are poor and unsustainable finance for iCCM, workforce related challenges, lack of and unsustainable supply of medicines and diagnostics, lack of information and research, service delivery and leadership challenges. Community health workers and related cadres had important preventive, case management and promotive roles in malaria interventions. To enable their effective integration into the health systems, the identified challenges should be addressed. They include: introducing sustainable financing on iCCM programmes, tailoring their training to address the identified gaps, improving sustainable supply chain management of malaria drugs and diagnostics, and addressing regulatory challenges in the local contexts.

Co-infections of malaria and geohelminthiasis in two rural communities of Nkassomo and Vian in the Mfou health district, Cameroon.

PubMed

Zeukeng, Francis; Tchinda, Viviane Hélène Matong; Bigoga, Jude Daiga; Seumen, Clovis Hugues Tiogang; Ndzi, Edward Shafe; Abonweh, Géraldine; Makoge, Valérie; Motsebo, Amédée; Moyou, Roger Somo

2014-10-01

Human co-infection with malaria and helmimths is ubiquitous throughout Africa. Nevertheless, its public health significance on malaria severity remains poorly understood. To contribute to a better understanding of epidemiology and control of this co-infection in Cameroon, a cross-sectional study was carried out to assess the prevalence of concomitant intestinal geohelminthiasis and malaria, and to evaluate its association with malaria and anaemia in Nkassomo and Vian. Finger prick blood specimens from a total of 263 participants aged 1-95 years were collected for malaria microscopy, assessment of haemoglobin levels, and molecular identification of Plasmodium species by PCR. Fresh stool specimens were also collected for the identification and quantification of geohelminths by the Kato-Katz method. The prevalence of malaria, geohelminths, and co-infections were 77.2%, 28.6%, and 22.1%, respectively. Plasmodium falciparum was the only malaria parasite species identified with mean parasite density of 111 (40; 18,800) parasites/µl of blood. The geohelminths found were Ascaris lumbricoides (21.6%) and Trichuris trichiura (10.8%), with mean parasite densities of 243 (24; 3,552) and 36 (24; 96) eggs/gram of faeces, respectively. Co-infections of A. lumbricoides and P. falciparum were the most frequent and correlated positively. While no significant difference was observed on the prevalences of single and co-infections between the two localities, there was a significant difference in the density of A. lumbricoides infection between the two localities. The overall prevalence of anaemia was 42%, with individuals co-infected with T. trichiura and P. falciparum (60%) being the most at risk. While the prevalence of malaria and anaemia were inversely related to age, children aged 5-14 years were more susceptible to geohelminthiasis and their co-infections with malaria. Co-existence of geohelminths and malaria parasites in Nkassomo and Vian enhances the occurrence of co-infections, and consequently, increases the risk for anaemia.

The feasibility of introducing rapid diagnostic tests for malaria in drug shops in Uganda.

PubMed

Mbonye, Anthony K; Ndyomugyenyi, Richard; Turinde, Asaph; Magnussen, Pascal; Clarke, Siân; Chandler, Clare

2010-12-21

National malaria control programmes and international agencies are keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria. The high proportion of the Ugandan population seeking care at drug shops makes these outlets attractive as providers of malaria RDTs. However, there is no precedent for blood testing at drug shops and little is known about how such tests might be perceived and used. Understanding use of drug shops by communities in Uganda is essential to inform the design of interventions to introduce RDTs. We conducted a qualitative study, with 10 community focus group discussions, and 18 in-depth interviews with drug shop attendants, health workers and district health officials. The formative study was carried out in Mukono district, central Uganda an area of high malaria endemicity from May-July 2009. Drug shops were perceived by the community as important in treating malaria and there was awareness among most drug sellers and the community that not all febrile illnesses were malaria. The idea of introducing RDTs for malaria diagnosis in drug shops was attractive to most respondents. It was anticipated that RDTs would improve access to effective treatment of malaria, offset high costs associated with poor treatment, and avoid irrational drug use. However, communities did express fear that drug shops would overprice RDTs, raising the overall treatment cost for malaria. Other fears included poor adherence to the RDT result, reuse of RDTs leading to infections and fear that RDTs would be used to test for human immune deficiency virus (HIV). All drug shops visited had no record on patient data and referral of cases to health units was noted to be poor. These results not only provide useful lessons for implementing the intervention study but have wide implications for scaling up malaria treatment in drug shops.

Malaria control aimed at the entire population in KwaZulu-Natal negates the need for policies to prevent malaria in pregnancy.

PubMed

Tsoka-Gwegweni, J M; Kleinschmidt, I

2013-01-24

South Africa has no policy to prevent malaria in pregnancy, despite the adverse effects of the disease in pregnancy. However, malaria control measures consisting of indoor residual spraying and specific antimalarial treatment have been in place since the 1970s. Information on the burden of malaria in pregnancy in South Africa is needed to indicate whether a specific policy for malaria prevention in pregnancy is necessary. To determine the burden of malaria in pregnancy in KwaZulu-Natal (KZN) province, South Africa. Pregnant women were enrolled at their first antenatal care visit to three health facilities in Umkhanyakude health district in northern KZN during May 2004 - September 2005 and followed up until delivery. Data collection included demographic details, current and previous malaria infection during pregnancy, haemoglobin concentrations and birth outcomes. Of the 1 406 study participants, more than a quarter were younger than 20 years of age, and more than 90% were unemployed and unmarried. Although 33.2% of the women were anaemic, this was not related to malaria. The prevalence and incidence of malaria were very low, and low birth weight was only weakly associated with malaria (1/10). The low burden of malaria in these pregnant women suggests that they have benefited from malaria control strategies in the study area. The implication is that additional measures specific for malaria prevention in pregnancy are not required. However, ongoing monitoring is needed to ensure that malaria prevalence remains low.

Using Rainfall and Temperature Data in the Evaluation of National Malaria Control Programs in Africa.

PubMed

Thomson, Madeleine C; Ukawuba, Israel; Hershey, Christine L; Bennett, Adam; Ceccato, Pietro; Lyon, Bradfield; Dinku, Tufa

2017-09-01

Since 2010, the Roll Back Malaria (RBM) Partnership, including National Malaria Control Programs, donor agencies (e.g., President's Malaria Initiative and Global Fund), and other stakeholders have been evaluating the impact of scaling up malaria control interventions on all-cause under-five mortality in several countries in sub-Saharan Africa. The evaluation framework assesses whether the deployed interventions have had an impact on malaria morbidity and mortality and requires consideration of potential nonintervention influencers of transmission, such as drought/floods or higher temperatures. Herein, we assess the likely effect of climate on the assessment of the impact malaria interventions in 10 priority countries/regions in eastern, western, and southern Africa for the President's Malaria Initiative. We used newly available quality controlled Enhanced National Climate Services rainfall and temperature products as well as global climate products to investigate likely impacts of climate on malaria evaluations and test the assumption that changing the baseline period can significantly impact on the influence of climate in the assessment of interventions. Based on current baseline periods used in national malaria impact assessments, we identify three countries/regions where current evaluations may overestimate the impact of interventions (Tanzania, Zanzibar, Uganda) and three countries where current malaria evaluations may underestimate the impact of interventions (Mali, Senegal and Ethiopia). In four countries (Rwanda, Malawi, Mozambique, and Angola) there was no strong difference in climate suitability for malaria in the pre- and post-intervention period. In part, this may be due to data quality and analysis issues.

Tackling the malaria problem in the South-East Asia Region: need for a change in policy?

PubMed

Bharati, Kaushik; Ganguly, N K

2013-01-01

Malaria is largely neglected in the South-East Asia Region (SEAR), although it has the highest number of people susceptible to the disease. Malaria in the SEAR exhibits special epidemiological characteristics such as "forest malaria" and malaria due to migration across international borders. The Greater Mekong Subregion (GMS) has been a focal-point for the emergence of drug resistant malaria. With the recent emergence of artemisinin resistance, coupled with the limited availability of insecticides, malaria control efforts in the SEAR face a steep challenge. Indirect man-made factors such as climate change, as well as direct man-made factors such as the circulation of counterfeit drugs have added to the problem. Increased monitoring, surveillance, pharmacovigilance as well as cross-border collaboration are required to address these problems. Regional networking and data-sharing will keep all stakeholders updated about the status of various malaria control programmes in the SEAR. Cutting-edge technologies such as GIS/GPS (geographical information system/global positioning system) systems and mobile phones can provide information in "real-time". A holistic and sustained approach to malaria control by integrated vector management (IVM) is suggested, in which all the stakeholder countries work collaboratively as a consortium. This approach will address the malaria problem in a collective manner so that malaria control can be sustained over time.

Re-imagining malaria--a platform for reflections to widen horizons in malaria control.

PubMed

Hausmann-Muela, Susanna; Eckl, Julian

2015-04-24

Ongoing political-economic discussions that take stock of social and societal determinants of health present an opportunity for productive dialogue on why current approaches to malaria control and elimination need to be broadened, and how this may be accomplished. They invite us, for example, to look beyond malaria as a disease, to appreciate the experiences of malaria-afflicted populations, to transcend techno-centric approaches, to investigate social conflicts around malaria, to give voice to the communities engaged in bottom-up approaches, and to revisit lessons learned in the past. While contributions from all disciplines are invited to this discussion, social scientists are particularly encouraged to participate. They have struggled in the past to find an appropriate platform within the malaria community that provides them the opportunity to address researchers from other disciplines, malaria practitioners, and policy makers. The Malaria Journal's new thematic series on 're-imagining malaria' offers them this opportunity. The goal of the series is to encourage transdisciplinary thinking, to stimulate discussion, to promote constructive criticism, and to gather overlooked experiences that help to reflect on implicit assumptions. Overall it aims at widening horizons in malaria control.

Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria

PubMed Central

Sundararaman, Sesh A.; Liu, Weimin; Keele, Brandon F.; Learn, Gerald H.; Bittinger, Kyle; Mouacha, Fatima; Ahuka-Mundeke, Steve; Manske, Magnus; Sherrill-Mix, Scott; Li, Yingying; Malenke, Jordan A.; Delaporte, Eric; Laurent, Christian; Mpoudi Ngole, Eitel; Kwiatkowski, Dominic P.; Shaw, George M.; Rayner, Julian C.; Peeters, Martine; Sharp, Paul M.; Bushman, Frederic D.; Hahn, Beatrice H.

2013-01-01

Wild-living chimpanzees and gorillas harbor a multitude of Plasmodium species, including six of the subgenus Laverania, one of which served as the progenitor of Plasmodium falciparum. Despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. Here, we used Plasmodium species-specific PCR, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern Cameroon for ape Laverania infections. Among 1,402 blood samples, we found 1,000 to be Plasmodium mitochondrial DNA (mtDNA) positive, all of which contained human parasites as determined by sequencing and/or restriction enzyme digestion. To exclude low-abundance infections, we subjected 514 of these samples to 454 sequencing, targeting a region of the mtDNA genome that distinguishes ape from human Laverania species. Using algorithms specifically developed to differentiate rare Plasmodium variants from 454-sequencing error, we identified single and mixed-species infections with P. falciparum, Plasmodium malariae, and/or Plasmodium ovale. However, none of the human samples contained ape Laverania parasites, including the gorilla precursor of P. falciparum. To characterize further the diversity of P. falciparum in Cameroon, we used single-genome amplification to amplify 3.4-kb mtDNA fragments from 229 infected humans. Phylogenetic analysis identified 62 new variants, all of which clustered with extant P. falciparum, providing further evidence that P. falciparum emerged following a single gorilla-to-human transmission. Thus, unlike Plasmodium knowlesi-infected macaques in southeast Asia, African apes harboring Laverania parasites do not seem to serve as a recurrent source of human malaria, a finding of import to ongoing control and eradication measures. PMID:23569255

Levels and interactions of plasma xanthine oxidase, catalase and liver function parameters in Nigerian children with Plasmodium falciparum infection.

PubMed

Iwalokun, B A; Bamiro, S B; Ogunledun, A

2006-12-01

Elevated plasma levels of xanthine oxidase and liver function parameters have been associated with inflammatory events in several human diseases. While xanthine oxidase provides in vitro protection against malaria, its pathophysiological functions in vivo and interactions with liver function parameters remain unclear. This study examined the interactions and plasma levels of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32), and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age-matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100-550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850-87100 parasites/microL) was observed in the malarial children. Further comparison with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05) lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4 U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the asymptomatic and symptomatic malaria children studied. 75% of control, 45% of asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05) correlations between liver function parameters and xanthine oxidase (r=0.57-0.64) only in the severe malaria group. We conclude that elevated levels of XO and liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in Nigerian children, with both parameters interacting differently to modulate the catalase response in asymptomatic and symptomatic falciparum malaria.

Factors influencing malaria control policy-making in Kenya, Uganda and Tanzania.

PubMed

Mutero, Clifford M; Kramer, Randall A; Paul, Christopher; Lesser, Adriane; Miranda, Marie Lynn; Mboera, Leonard E G; Kiptui, Rebecca; Kabatereine, Narcis; Ameneshewa, Birkinesh

2014-08-08

Policy decisions for malaria control are often difficult to make as decision-makers have to carefully consider an array of options and respond to the needs of a large number of stakeholders. This study assessed the factors and specific objectives that influence malaria control policy decisions, as a crucial first step towards developing an inclusive malaria decision analysis support tool (MDAST). Country-specific stakeholder engagement activities using structured questionnaires were carried out in Kenya, Uganda and Tanzania. The survey respondents were drawn from a non-random purposeful sample of stakeholders, targeting individuals in ministries and non-governmental organizations whose policy decisions and actions are likely to have an impact on the status of malaria. Summary statistics across the three countries are presented in aggregate. Important findings aggregated across countries included a belief that donor preferences and agendas were exerting too much influence on malaria policies in the countries. Respondents on average also thought that some relevant objectives such as engaging members of parliament by the agency responsible for malaria control in a particular country were not being given enough consideration in malaria decision-making. Factors found to influence decisions regarding specific malaria control strategies included donor agendas, costs, effectiveness of interventions, health and environmental impacts, compliance and/acceptance, financial sustainability, and vector resistance to insecticides. Malaria control decision-makers in Kenya, Uganda and Tanzania take into account health and environmental impacts as well as cost implications of different intervention strategies. Further engagement of government legislators and other policy makers is needed in order to increase funding from domestic sources, reduce donor dependence, sustain interventions and consolidate current gains in malaria.

Use of remote sensing to identify spatial risk factors for malaria in a region of declining transmission: a cross-sectional and longitudinal community survey.

PubMed

Moss, William J; Hamapumbu, Harry; Kobayashi, Tamaki; Shields, Timothy; Kamanga, Aniset; Clennon, Julie; Mharakurwa, Sungano; Thuma, Philip E; Glass, Gregory

2011-06-10

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa. Further malaria control will require targeted control strategies based on evidence of risk. The objective of this study was to identify environmental risk factors for malaria transmission using remote sensing technologies to guide malaria control interventions in a region of declining burden of malaria. Satellite images were used to construct a sampling frame for the random selection of households enrolled in prospective longitudinal and cross-sectional surveys of malaria parasitaemia in Southern Province, Zambia. A digital elevation model (DEM) was derived from the Shuttle Radar Topography Mission version 3 DEM and used for landscape characterization, including landforms, elevation, aspect, slope, topographic wetness, topographic position index and hydrological models of stream networks. A total of 768 individuals from 128 randomly selected households were enrolled over 21 months, from the end of the rainy season in April 2007 through December 2008. Of the 768 individuals tested, 117 (15.2%) were positive by malaria rapid diagnostic test (RDT). Individuals residing within 3.75 km of a third order stream were at increased risk of malaria. Households at elevations above the baseline elevation for the region were at decreasing risk of having RDT-positive residents. Households where new infections occurred were overlaid on a risk map of RDT positive households and incident infections were more likely to be located in high-risk areas derived from prevalence data. Based on the spatial risk map, targeting households in the top 80th percentile of malaria risk would require malaria control interventions directed to only 24% of the households. Remote sensing technologies can be used to target malaria control interventions in a region of declining malaria transmission in southern Zambia, enabling a more efficient use of resources for malaria elimination.

Artemisinin resistance in rodent malaria - mutation in the AP2 adaptor μ-chain suggests involvement of endocytosis and membrane protein trafficking

PubMed Central

2013-01-01

Background The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. Because artemisinin derivatives are now used in the most effective anti-malarial therapy, resistance to artemisinin would be catastrophic. Indeed, studies suggest that artemisinin resistance has already appeared in natural infections. Understanding the mechanisms of resistance would help to prolong the effective lifetime of these drugs. Genetic markers of resistance are therefore required urgently. Previously, a mutation in a de-ubiquitinating enzyme was shown to confer artemisinin resistance in the rodent malaria parasite Plasmodium chabaudi. Methods Here, for a mutant P. chabaudi malaria parasite and its immediate progenitor, the in vivo artemisinin resistance phenotypes and the mutations arising using Illumina whole-genome re-sequencing were compared. Results An increased artemisinin resistance phenotype is accompanied by one non-synonymous substitution. The mutated gene encodes the μ-chain of the AP2 adaptor complex, a component of the endocytic machinery. Homology models indicate that the mutated residue interacts with a cargo recognition sequence. In natural infections of the human malaria parasite P. falciparum, 12 polymorphisms (nine SNPs and three indels) were identified in the orthologous gene. Conclusion An increased artemisinin-resistant phenotype occurs along with a mutation in a functional element of the AP2 adaptor protein complex. This suggests that endocytosis and trafficking of membrane proteins may be involved, generating new insights into possible mechanisms of resistance. The genotypes of this adaptor protein can be evaluated for its role in artemisinin responses in human infections of P. falciparum. PMID:23561245

Plasmodium immunomics.

PubMed

Doolan, Denise L

2011-01-01

The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed. Copyright © 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Predicting potential ranges of primary malaria vectors and malaria in northern South America based on projected changes in climate, land cover and human population.

PubMed

Alimi, Temitope O; Fuller, Douglas O; Qualls, Whitney A; Herrera, Socrates V; Arevalo-Herrera, Myriam; Quinones, Martha L; Lacerda, Marcus V G; Beier, John C

2015-08-20

Changes in land use and land cover (LULC) as well as climate are likely to affect the geographic distribution of malaria vectors and parasites in the coming decades. At present, malaria transmission is concentrated mainly in the Amazon basin where extensive agriculture, mining, and logging activities have resulted in changes to local and regional hydrology, massive loss of forest cover, and increased contact between malaria vectors and hosts. Employing presence-only records, bioclimatic, topographic, hydrologic, LULC and human population data, we modeled the distribution of malaria and two of its dominant vectors, Anopheles darlingi, and Anopheles nuneztovari s.l. in northern South America using the species distribution modeling platform Maxent. Results from our land change modeling indicate that about 70,000 km(2) of forest land would be lost by 2050 and 78,000 km(2) by 2070 compared to 2010. The Maxent model predicted zones of relatively high habitat suitability for malaria and the vectors mainly within the Amazon and along coastlines. While areas with malaria are expected to decrease in line with current downward trends, both vectors are predicted to experience range expansions in the future. Elevation, annual precipitation and temperature were influential in all models both current and future. Human population mostly affected An. darlingi distribution while LULC changes influenced An. nuneztovari s.l. distribution. As the region tackles the challenge of malaria elimination, investigations such as this could be useful for planning and management purposes and aid in predicting and addressing potential impediments to elimination.

Automated image processing method for the diagnosis and classification of malaria on thin blood smears.

PubMed

Ross, Nicholas E; Pritchard, Charles J; Rubin, David M; Dusé, Adriano G

2006-05-01

Malaria is a serious global health problem, and rapid, accurate diagnosis is required to control the disease. An image processing algorithm to automate the diagnosis of malaria on thin blood smears is developed. The image classification system is designed to positively identify malaria parasites present in thin blood smears, and differentiate the species of malaria. Images are acquired using a charge-coupled device camera connected to a light microscope. Morphological and novel threshold selection techniques are used to identify erythrocytes (red blood cells) and possible parasites present on microscopic slides. Image features based on colour, texture and the geometry of the cells and parasites are generated, as well as features that make use of a priori knowledge of the classification problem and mimic features used by human technicians. A two-stage tree classifier using backpropogation feedforward neural networks distinguishes between true and false positives, and then diagnoses the species (Plasmodium falciparum, P. vivax, P. ovale or P. malariae) of the infection. Malaria samples obtained from the Department of Clinical Microbiology and Infectious Diseases at the University of the Witwatersrand Medical School are used for training and testing of the system. Infected erythrocytes are positively identified with a sensitivity of 85% and a positive predictive value (PPV) of 81%, which makes the method highly sensitive at diagnosing a complete sample provided many views are analysed. Species were correctly determined for 11 out of 15 samples.

Mass screening and treatment on the basis of results of a Plasmodium falciparum-specific rapid diagnostic test did not reduce malaria incidence in Zanzibar.

PubMed

Cook, Jackie; Xu, Weiping; Msellem, Mwinyi; Vonk, Marlotte; Bergström, Beatrice; Gosling, Roly; Al-Mafazy, Abdul-Wahid; McElroy, Peter; Molteni, Fabrizio; Abass, Ali K; Garimo, Issa; Ramsan, Mahdi; Ali, Abdullah; Mårtensson, Andreas; Björkman, Anders

2015-05-01

Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission. Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission. Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-.3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas. Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

PubMed Central

Kosaisavee, Varakorn; Suwanarusk, Rossarin; Chua, Adeline C. Y.; Kyle, Dennis E.; Malleret, Benoit; Zhang, Rou; Imwong, Mallika; Imerbsin, Rawiwan; Ubalee, Ratawan; Sámano-Sánchez, Hugo; Yeung, Bryan K. S.; Ong, Jessica J. Y.; Lombardini, Eric; Nosten, François; Tan, Kevin S. W.; Bifani, Pablo; Snounou, Georges; Rénia, Laurent

2017-01-01

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi–infected human reticulocytes that are strikingly similar to those observed for P vivax. These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria. PMID:28698207

The Role of Malaria Microscopy Training and Refresher Training Courses in Malaria Control Program in Iran during 2001 - 2011.

PubMed

Nateghpour, M; Edrissian, Ghh; Raeisi, A; Motevalli-Haghi, A; Farivar, L; Mohseni, Gh; Rahimi-Froushani, A

2012-01-01

Malaria is still one of the most important infectious diseases in the world. The disease also is a public health problem in south and southeast of Iran. This study programmed to show the correlation between regular malaria microscopy training and refresher training courses and control of malaria in Iran. Three types of training courses were conducted in this programme including; five - day, ten - day and bimonthly training courses. Each of the training courses contained theoretical and practical sections and training impact was evaluated by practical examination and multiple-choice quizzes through pre and post tests. Distribution pattern of the participants in the training and refresher training courses showed that the most participants were from Sistan & Baluchistan and Hormozgan provinces where malaria is endemic and most cases of the infection come out from these malarious areas. A total of 695 identified individuals were participated in the training courses. A significant conversely correlation was found between conducting malaria microscopy training courses and annual malaria cases in Iran. Conducting a suitable programme for malaria microscopy training and refresher training plays an important role in the control of malaria in endemic areas. Obviously, the decrease of malaria cases in Iran has been achieved due to some activities that malaria diagnosis training was one of them.

Changes in malaria morbidity and mortality in Mpumalanga Province, South Africa (2001- 2009): a retrospective study

PubMed Central

2012-01-01

Background Malaria remains a serious epidemic threat in Mpumalanga Province. In order to appropriately target interventions to achieve substantial reduction in the burden of malaria and ultimately eliminate the disease, there is a need to track progress of malaria control efforts by assessing the time trends and evaluating the impact of current control interventions. This study aimed to assess the changes in the burden of malaria in Mpumalanga Province during the past eight malaria seasons (2001/02 to 2008/09) and whether indoor residual spraying (IRS) and climate variability had an effect on these changes. Methods This is a descriptive retrospective study based on the analysis of secondary malaria surveillance data (cases and deaths) in Mpumalanga Province. Data were extracted from the Integrated Malaria Information System. Time series model (Autoregressive Integrated Moving Average) was used to assess the association between climate and malaria. Results Within the study period, a total of 35,191 cases and 164 deaths due to malaria were notified in Mpumalanga Province. There was a significant decrease in the incidence of malaria from 385 in 2001/02 to 50 cases per 100,000 population in 2008/09 (P < 0.005). The incidence and case fatality (CFR) rates for the study period were 134 cases per 100,000 and 0.54%, respectively. Mortality due to malaria was lower in infants and children (CFR < 0.5%) and higher in those >65 years, with the mean CFR of 2.1% as compared to the national target of 0.5%. A distinct seasonal transmission pattern was found to be significantly related to changes in rainfall patterns (P = 0.007). A notable decline in malaria case notification was observed following apparent scale-up of IRS coverage from 2006/07 to 2008/09 malaria seasons. Conclusions Mpumalanga Province has achieved the goal of reducing malaria morbidity and mortality by over 70%, partly as a result of scale-up of IRS intervention in combination with other control strategies. These results highlight the need to continue with IRS together with other control strategies until interruption in local malaria transmission is completely achieved. However, the goal to eliminate malaria as a public health problem requires efforts to be directed towards the control of imported malaria cases; development of strategies to interrupt local transmission; and maintaining high quality surveillance and reporting system. PMID:22239855

Plasmodium knowlesi: from severe zoonosis to animal model.

PubMed

Cox-Singh, Janet; Culleton, Richard

2015-06-01

Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of optimal control strategies to HIV-malaria co-infection dynamics

NASA Astrophysics Data System (ADS)

Fatmawati; Windarto; Hanif, Lathifah

2018-03-01

This paper presents a mathematical model of HIV and malaria co-infection transmission dynamics. Optimal control strategies such as malaria preventive, anti-malaria and antiretroviral (ARV) treatments are considered into the model to reduce the co-infection. First, we studied the existence and stability of equilibria of the presented model without control variables. The model has four equilibria, namely the disease-free equilibrium, the HIV endemic equilibrium, the malaria endemic equilibrium, and the co-infection equilibrium. We also obtain two basic reproduction ratios corresponding to the diseases. It was found that the disease-free equilibrium is locally asymptotically stable whenever their respective basic reproduction numbers are less than one. We also conducted a sensitivity analysis to determine the dominant factor controlling the transmission. sic reproduction numbers are less than one. We also conducted a sensitivity analysis to determine the dominant factor controlling the transmission. Then, the optimal control theory for the model was derived analytically by using Pontryagin Maximum Principle. Numerical simulations of the optimal control strategies are also performed to illustrate the results. From the numerical results, we conclude that the best strategy is to combine the malaria prevention and ARV treatments in order to reduce malaria and HIV co-infection populations.

How molecular epidemiology studies can support the National Malaria Control Program in Papua New Guinea.

PubMed

Koepfli, Cristian; Barry, Alyssa; Javati, Sarah; Timinao, Lincoln; Nate, Elma; Mueller, Ivo; Barnadas, Celine

2014-01-01

Papua New Guinea (PNG) is undertaking intensified efforts to control malaria. The National Malaria Control Program aims to reduce the burden of disease by large-scale distribution of insecticide-treated bednets, improved diagnosis and implementation of new treatments. A scientific program monitoring the effect of these interventions, including molecular epidemiology studies, closely accompanies the program. Laboratory assays have been developed in (or transferred to) PNG to measure prevalence of infection and intensity of transmission as well as potential resistance to currently used drugs. These assays help to assess the impact of the National Malaria Control Program, and they reveal a much clearer picture of malaria epidemiology in PNG. In addition, analysis of the geographical clustering of parasites aids in selecting areas where intensified control will be most successful. This paper gives an overview of current research and recently completed studies in the molecular epidemiology of malaria conducted in Papua New Guinea.

Risk Factors for Border Malaria in a Malaria Elimination Setting: A Retrospective Case-Control Study in Yunnan, China

PubMed Central

Xu, Jian-Wei; Liu, Hui; Zhang, Yu; Guo, Xiang-Rui; Wang, Jia-Zhi

2015-01-01

A retrospective case-control study was conducted to identify risk factors for border malaria in a malaria elimination setting of Yunnan Province, China. The study comprised 214 cases and 428 controls. The controls were individually matched to the cases on the basis of residence, age, and gender. In addition, statistical associations are based on matched analyses. The frequencies of imported, male, adult, and vivax malaria cases were respectively 201 (93.9%), 194 (90.7%), 210 (98.1%), and 176 (82.2%). Overnight stay in Myanmar within the prior month was independently associated with malaria infection (odds ratio [OR] 159.5, 95% confidence interval [CI] 75.1–338.9). In particular, stays in lowland and foothill (OR 5.5, 95% CI 2.5–11.8) or mid-hill (OR 42.8, 95% CI 5.1–319.8) areas, or near streamlets (OR 15.3, 95% CI 4.3–55.2) or paddy field or pools (OR10.1, 95% CI 4.4–55.8) were found to be independently associated with malaria. Neither forest exposure nor use of vector control measures was associated with malaria. In conclusion, travel to lowland and foothill or mid-hill hyperendemic areas, especially along the waterside in Myanmar, was found to be the highest risk factor for malaria. In considering the limitations of the study, further investigations are needed to identify the major determinants of malaria risk and develop new strategies for malaria elimination on China-Myanmar border. PMID:25601994

[Malaria and HIV infection: clinical and biological aspects at Donka National Hospital in Conakry, Guinea].

PubMed

Bald, I; Camara, A; Baldé, O; Magassouba, N F; Bah, M S; Makanéra, A; Gamy, E P

2010-08-01

Malaria and HIV/AIDS are two of the most widespread infectious diseases encountered in sub-Saharan Africa. Even minor interactions between these two diseases could have substantial effects on public health. The purpose of this study was to investigate associations between malaria and HIV infection. Study was carried out over an 8-month period (April 1, 2003 to November 30, 2003) in the Tropical and Infectious Diseases Department of the Donka National Hospital in Conakry, Guinea. A total of 89 malaria patients including 41 cases with HIV infection and 48 controls without HIV infection were included. All patients were hospitalized during the study and provided informed consent. Results showed that malaria affected all age groups in the same proportion. Mean patient age was 34 years (range, 15 and 76 years). Males were more frequently infected with a sex ratio of 1.05. The average number of malaria episodes was higher in cases (malaria with HIV-infection than in controls (malaria without HIV infection). Hyperthermia was observed in most cases (68.29%) and controls (77.08%). Severe anemia was observed in 26.82% of cases versus 10.41% of controls. Low parasite density was observed in 73.17% of cases as compared to 68.75% of controls. The recovery rate was higher in the control group than in case group: 27.08% versus 14.63%. The death rate was higher in the case group than in the control group: 21.95% versus 6.25%. These findings demonstrate a link between malaria and HIV. The frequency of malaria episodes was higher in patients with HIV infection than patients without HIV infection and the outcome of malarial episodes was better in patients without HIV infection.

Direct detection of falciparum and non-falciparum malaria DNA from a drop of blood with high sensitivity by the dried-LAMP system.

PubMed

Hayashida, Kyoko; Kajino, Kiichi; Simukoko, Humphrey; Simuunza, Martin; Ndebe, Joseph; Chota, Amos; Namangala, Boniface; Sugimoto, Chihiro

2017-01-13

Because of the low sensitivity of conventional rapid diagnostic tests (RDTs) for malaria infections, the actual prevalence of the diseases, especially those caused by non-Plasmodium falciparum (non-Pf) species, in asymptomatic populations remain less defined in countries lacking in well-equipped facilities for accurate diagnoses. Our direct blood dry LAMP system (CZC-LAMP) was applied to the diagnosis of malaria as simple, rapid and highly sensitive method as an alternative for conventional RDTs in malaria endemic areas where laboratory resources are limited. LAMP primer sets for mitochondria DNAs of Plasmodium falciparum (Pf) and human-infective species other than Pf (non-Pf; P. vivax, P. ovale, P. malariae) were designed and tested by using human blood DNA samples from 74 residents from a malaria endemic area in eastern Zambia. These malaria dry-LAMPs were optimized for field or point-of-care operations, and evaluated in the field at a malaria endemic area in Zambia with 96 human blood samples. To determine the sensitivities and specificities, results obtained by the on-site LAMP diagnosis were compared with those by the nested PCR and nucleotide sequencing of its product. The dry LAMPs showed the sensitivities of 89.7% for Pf and 85.7% for non-Pf, and the specificities of 97.2% for Pf and 100% for non-Pf, with purified blood DNA samples. The direct blood LAMP diagnostic methods, in which 1 μl of anticoagulated blood were used as the template, showed the sensitivities of 98.1% for Pf, 92.1% for non-Pf, and the specificities of 98.1% for Pf, 100% for non-Pf. The prevalences of P. falciparum, P. malariae and P. ovale in the surveyed area were 52.4, 25.3 and 10.6%, respectively, indicating high prevalence of asymptomatic carriers in endemic areas in Zambia. We have developed new field-applicable malaria diagnostic tests. The malaria CZC-LAMPs showed high sensitivity and specificity to both P. falciparum and non-P. falciparum. These malaria CZC-LAMPs provide new means for rapid, sensitive and reliable point-of-care diagnosis for low-density malaria infections, and are expected to help update current knowledge of malaria epidemiology, and can contribute to the elimination of malaria from endemic areas.

Water resources implications of integrating malaria control into the operation of an Ethiopian dam

NASA Astrophysics Data System (ADS)

Reis, Julia; Culver, Teresa B.; McCartney, Matthew; Lautze, Jonathan; Kibret, Solomon

2011-09-01

This paper investigates the water resources implications of using a method of hydrological control to reduce malaria around the Koka reservoir in central Ethiopia. This method is based on recent findings that malaria is transmitted from the shoreline of the Koka reservoir, and on a similar method that was used to control malaria some 80 yr ago in the United States. To assess the feasibility of implementing hydrological control at Koka, we considered the potential impact of the modified management regime on the benefits derived from current uses of the reservoir water (i.e., hydropower, irrigation, flood control, water supply, and downstream environmental flows). We used the HEC-ResSim model to simulate lowering the reservoir by a rate designed to disrupt larval development, which is expected to reduce the abundance of adult mosquito vectors and therefore reduce malaria transmission during the season in which transmission of the disease peaks. A comparison was made of major reservoir uses with and without the malaria control measure. In the 26-yr simulation, application of the malaria control measure increased total average annual electricity generation from 87.6 GWh × y-1 to 92.2 GWh × y-1 (i.e., a 5.3% increase) but resulted in a small decline in firm power generation (i.e., guaranteed at 99.5% reliability) from 4.16 MW to 4.15 MW (i.e., a 0.2% decrease). Application of the malaria control measure did not impact the ability of the reservoir to meet downstream irrigation demand and reduced the number of days of downstream flooding from 28 to 24 d. These results indicate that targeted use of hydrological control for malaria vector management could be undertaken without sacrificing the key benefits of reservoir operation.

DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum CSP and AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity

PubMed Central

Chuang, Ilin; Sedegah, Martha; Cicatelli, Susan; Spring, Michele; Polhemus, Mark; Tamminga, Cindy; Patterson, Noelle; Guerrero, Melanie; Bennett, Jason W.; McGrath, Shannon; Ganeshan, Harini; Belmonte, Maria; Farooq, Fouzia; Abot, Esteban; Banania, Jo Glenna; Huang, Jun; Newcomer, Rhonda; Rein, Lisa; Litilit, Dianne; Richie, Nancy O.; Wood, Chloe; Murphy, Jittawadee; Sauerwein, Robert; Hermsen, Cornelus C.; McCoy, Andrea J.; Kamau, Edwin; Cummings, James; Komisar, Jack; Sutamihardja, Awalludin; Shi, Meng; Epstein, Judith E.; Maiolatesi, Santina; Tosh, Donna; Limbach, Keith; Angov, Evelina; Bergmann-Leitner, Elke; Bruder, Joseph T.; Doolan, Denise L.; King, C. Richter; Carucci, Daniel; Dutta, Sheetij; Soisson, Lorraine; Diggs, Carter; Hollingdale, Michael R.; Ockenhouse, Christian F.; Richie, Thomas L.

2013-01-01

Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. Methodology/Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. Trial Registration ClinicalTrials.govNCT00870987. PMID:23457473

Malaria among gold miners in southern Pará, Brazil: estimates of determinants and individual costs.

PubMed

Vosti, S A

1990-01-01

As malaria grows more prevalent in the Amazon frontier despite increased expenditures by disease control authorities, national and regional tropical disease control strategies are being called into question. The current crisis involving traditional control/eradication methods has broadened the search for feasible and effective malaria control strategies--a search that necessarily includes an investigation of the roles of a series of individual and community-level socioeconomic characteristics in determining malaria prevalence rates, and the proper methods of estimating these links. In addition, social scientists and policy makers alike know very little about the economic costs associated with malarial infections. In this paper, I use survey data from several Brazilian gold mining areas to (a) test the general reliability of malaria-related questionnaire response data, and suggest categorization methods to minimize the statistical influence of exaggerated responses, (b) estimate three statistical models aimed at detecting the socioeconomic determinants of individual malaria prevalence rates, and (c) calculate estimates of the average cost of a single bout of malaria. The results support the general reliability of survey response data gathered in conjunction with malaria research. Once the effects of vector exposure were controlled for, individual socioeconomic characteristics were only weakly linked to malaria prevalence rates in these very special miners' communities. Moreover, the socioeconomic and exposure links that were significant did not depend on the measure of malaria adopted. Finally, individual costs associated with malarial infections were found to be a significant portion of miners' incomes.

Lessons from malaria control to help meet the rising challenge of dengue.

PubMed

Anders, Katherine L; Hay, Simon I

2012-12-01

Achievements in malaria control could inform efforts to control the increasing global burden of dengue. Better methods for quantifying dengue endemicity-equivalent to parasite prevalence surveys and endemicity mapping used for malaria-would help target resources, monitor progress, and advocate for investment in dengue prevention. Success in controlling malaria has been attributed to widespread implementation of interventions with proven efficacy. An improved evidence base is needed for large-scale delivery of existing and novel interventions for vector control, alongside continued investment in dengue drug and vaccine development. Control of dengue is unlikely to be achieved without coordinated international financial and technical support for national programmes, which has proven effective in reducing the global burden of malaria. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reduced prevalence of malaria infection in children living in houses with window screening or closed eaves on Bioko Island, equatorial Guinea.

PubMed

Bradley, John; Rehman, Andrea M; Schwabe, Christopher; Vargas, Daniel; Monti, Feliciano; Ela, Camilo; Riloha, Matilde; Kleinschmidt, Immo

2013-01-01

Previous studies demonstrated that fewer mosquitoes enter houses which are screened or have closed eaves. There is little evidence about the effect on malaria infection in humans that changes in house construction may have. This study examines the impact of protective housing improvements on malaria infection on Bioko Island. Data from the annual malaria indicator surveys between 2009 and 2012 were used to assess trends in housing characteristics and their effect on RDT confirmed malaria infection in household members. Odds ratios were adjusted for socio-economic status of the household.22726 children between the ages of 2 and 14 years were tested for P. falciparum. Prevalence of infection in those living in houses with open eaves was 23.0% compared to 18.8% for those living in houses with closed eaves (OR = 0.81, 95% CI 0.67 - 0.98). The prevalence of infection for children in screened houses was 9.1% versus 20.1% for those living in unscreened houses (OR = 0.44, 95% CI 0.27 - 0.71). The proportion of houses with closed eaves increased from 66.0% in 2009 to 74.3% in 2012 (test for trend p = 0.01). The proportion of screened houses remained unchanged over time at 1.3%. As a malaria control intervention, house modification has the advantages that it is not affected by the growing threat of insecticide resistance; it protects all household members equally and at all times while indoors; and it offers protection against a number of vector borne diseases. The study provides evidence in support of efforts to regulate or encourage housing improvements which impede vector access into residences as part of an integrated vector control approach to complement existing measures which have been only partially successful in reducing malaria transmission in some parts of Bioko.

Reduced Prevalence of Malaria Infection in Children Living in Houses with Window Screening or Closed Eaves on Bioko Island, Equatorial Guinea

PubMed Central

Bradley, John; Rehman, Andrea M.; Schwabe, Christopher; Vargas, Daniel; Monti, Feliciano; Ela, Camilo; Riloha, Matilde; Kleinschmidt, Immo

2013-01-01

Background Previous studies demonstrated that fewer mosquitoes enter houses which are screened or have closed eaves. There is little evidence about the effect on malaria infection in humans that changes in house construction may have. This study examines the impact of protective housing improvements on malaria infection on Bioko Island. Methodology/Principal Findings Data from the annual malaria indicator surveys between 2009 and 2012 were used to assess trends in housing characteristics and their effect on RDT confirmed malaria infection in household members. Odds ratios were adjusted for socio-economic status of the household.22726 children between the ages of 2 and 14 years were tested for P. falciparum. Prevalence of infection in those living in houses with open eaves was 23.0% compared to 18.8% for those living in houses with closed eaves (OR = 0.81, 95% CI 0.67 - 0.98). The prevalence of infection for children in screened houses was 9.1% versus 20.1% for those living in unscreened houses (OR = 0.44, 95% CI 0.27 - 0.71). The proportion of houses with closed eaves increased from 66.0% in 2009 to 74.3% in 2012 (test for trend p = 0.01). The proportion of screened houses remained unchanged over time at 1.3%. Conclusion/Significance As a malaria control intervention, house modification has the advantages that it is not affected by the growing threat of insecticide resistance; it protects all household members equally and at all times while indoors; and it offers protection against a number of vector borne diseases. The study provides evidence in support of efforts to regulate or encourage housing improvements which impede vector access into residences as part of an integrated vector control approach to complement existing measures which have been only partially successful in reducing malaria transmission in some parts of Bioko. PMID:24236191

Malaria Elimination Campaigns in the Lake Kariba Region of Zambia: A Spatial Dynamical Model

PubMed Central

Nikolov, Milen; Bever, Caitlin A.; Upfill-Brown, Alexander; Hamainza, Busiku; Miller, John M.; Eckhoff, Philip A.; Wenger, Edward A.; Gerardin, Jaline

2016-01-01

As more regions approach malaria elimination, understanding how different interventions interact to reduce transmission becomes critical. The Lake Kariba area of Southern Province, Zambia, is part of a multi-country elimination effort and presents a particular challenge as it is an interconnected region of variable transmission intensities. In 2012–13, six rounds of mass test-and-treat drug campaigns were carried out in the Lake Kariba region. A spatial dynamical model of malaria transmission in the Lake Kariba area, with transmission and climate modeled at the village scale, was calibrated to the 2012–13 prevalence survey data, with case management rates, insecticide-treated net usage, and drug campaign coverage informed by surveillance. The model captured the spatio-temporal trends of decline and rebound in malaria prevalence in 2012–13 at the village scale. Various interventions implemented between 2016–22 were simulated to compare their effects on reducing regional transmission and achieving and maintaining elimination through 2030. Simulations predict that elimination requires sustaining high coverage with vector control over several years. When vector control measures are well-implemented, targeted mass drug campaigns in high-burden areas further increase the likelihood of elimination, although drug campaigns cannot compensate for insufficient vector control. If infections are regularly imported from outside the region into highly receptive areas, vector control must be maintained within the region until importations cease. Elimination in the Lake Kariba region is possible, although human movement both within and from outside the region risk damaging the success of elimination programs. PMID:27880764

Malaria Theranostics using Hemozoin-Generated Vapor Nanobubbles

PubMed Central

Hleb, Ekaterina Y. Lukianova-; Lapotko, Dmitri O.

2014-01-01

Malaria remains a widespread and deadly infectious human disease, with increasing diagnostic and therapeutic challenges due to the drug resistance and aggressiveness of malaria infection. Early detection and innovative approaches for parasite destruction are needed. The high optical absorbance and nano-size of hemozoin crystals have been exploited to detect and mechanically destroy the malaria parasite in a single theranostic procedure. Transient vapor nanobubbles are generated around hemozoin crystals in malaria parasites in infected erythrocytes in response to a single short laser pulse. Optical scattering signals of the nanobubble report the presence of the malaria parasite. The mechanical impact of the same nanobubble physically destroys the parasite in nanoseconds in a drug-free manner. Laser-induced nanobubble treatment of human blood in vitro results in destruction of up to 95% of parasites after a single procedure, and delivers an 8-fold better parasiticidal efficacy compared to standard chloroquine drug treatment. The mechanism of destruction is highly selective for malaria infected red cells and does not harm neighboring, uninfected erythrocytes. Thus, laser pulse-induced vapor nanobubble generation around hemozoin supports both rapid and highly specific detection and destruction of malaria parasites in one theranostic procedure. PMID:24883125

Malaria theranostics using hemozoin-generated vapor nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Lapotko, Dmitri O

2014-01-01

Malaria remains a widespread and deadly infectious human disease, with increasing diagnostic and therapeutic challenges due to the drug resistance and aggressiveness of malaria infection. Early detection and innovative approaches for parasite destruction are needed. The high optical absorbance and nano-size of hemozoin crystals have been exploited to detect and mechanically destroy the malaria parasite in a single theranostic procedure. Transient vapor nanobubbles are generated around hemozoin crystals in malaria parasites in infected erythrocytes in response to a single short laser pulse. Optical scattering signals of the nanobubble report the presence of the malaria parasite. The mechanical impact of the same nanobubble physically destroys the parasite in nanoseconds in a drug-free manner. Laser-induced nanobubble treatment of human blood in vitro results in destruction of up to 95% of parasites after a single procedure, and delivers an 8-fold better parasiticidal efficacy compared to standard chloroquine drug treatment. The mechanism of destruction is highly selective for malaria infected red cells and does not harm neighboring, uninfected erythrocytes. Thus, laser pulse-induced vapor nanobubble generation around hemozoin supports both rapid and highly specific detection and destruction of malaria parasites in one theranostic procedure.

History of malaria control in Tajikistan and rapid malaria appraisal in an agro-ecological setting.

PubMed

Matthys, Barbara; Sherkanov, Tohir; Karimov, Saifudin S; Khabirov, Zamonidin; Mostowlansky, Till; Utzinger, Jürg; Wyss, Kaspar

2008-10-26

Reported malaria cases in rice growing areas in western Tajikistan were at the root of a rapid appraisal of the local malaria situation in a selected agro-ecological setting where only scarce information was available. The rapid appraisal was complemented by a review of the epidemiology and control of malaria in Tajikistan and Central Asia from 1920 until today. Following a resurgence in the 1990s, malaria transmission has been reduced considerably in Tajikistan as a result of concerted efforts by the government and international agencies. The goal for 2015 is transmission interruption, with control interventions and surveillance currently concentrated in the South, where foci of Plasmodium vivax and Plasmodium falciparum persist. The rapid malaria appraisal was carried out in six communities of irrigated rice cultivation during the peak of malaria transmission (August/September 2007) in western Tajikistan. In a cross-sectional survey, blood samples were taken from 363 schoolchildren and examined for Plasmodium under a light microscope. A total of 56 farmers were interviewed about agricultural activities and malaria. Potential Anopheles breeding sites were characterized using standardized procedures. A literature review on the epidemiology and control of malaria in Tajikistan was conducted. One case of P. vivax was detected among the 363 schoolchildren examined (0.28%). The interviewees reported to protect themselves against mosquito bites and used their own concepts on fever conditions, which do not distinguish between malaria and other diseases. Three potential malaria vectors were identified, i.e. Anopheles superpictus, Anopheles pulcherrimus and Anopheles hyrcanus in 58 of the 73 breeding sites examined (79.5%). Rice paddies, natural creeks and man-made ponds were the most important Anopheles habitats. The presence of malaria vectors and parasite reservoirs, low awareness of, and protection against malaria in the face of population movements and inadequate surveillance may render local communities vulnerable to potential epidemics. To attain malaria transmission interruption in Tajikistan by 2015, there is a need for rigorous surveillance along with strengthening of primary health care facilities for effective case management, and possibly a more differentiated vector control strategy based on additional local evidence.

The Origin of Malignant Malaria

USDA-ARS?s Scientific Manuscript database

Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

Factoring quality laboratory diagnosis into the malaria control agenda for sub-Saharan Africa.

PubMed

Aidoo, Michael

2013-09-01

Recent progress in malaria control in sub-Saharan Africa has been achieved primarily through provision of insecticide-treated nets, indoor residual spraying, and antimalarial drugs. Although these interventions are important, proper case identification and accurate measurement of their impact depend on quality diagnostic testing. Current availability of diagnostic testing for malaria in sub-Saharan Africa is inadequate to support disease management, prevention programs, and surveillance needs. Challenges faced include a dearth of skilled workforce, inadequate health systems infrastructure, and lack of political will. A coordinated approach to providing pre-service clinical and laboratory training together with systems that support a scale-up of laboratory services could provide means not only for effective malaria case management but also, management of non-malaria febrile illnesses, disease surveillance, and accurate control program evaluation. A synthesis of the challenges faced in ensuring quality malaria testing and how to include this information in the malaria control and elimination agenda are presented.

Using Rainfall and Temperature Data in the Evaluation of National Malaria Control Programs in Africa

PubMed Central

Thomson, Madeleine C.; Ukawuba, Israel; Hershey, Christine L.; Bennett, Adam; Ceccato, Pietro; Lyon, Bradfield; Dinku, Tufa

2017-01-01

Abstract. Since 2010, the Roll Back Malaria (RBM) Partnership, including National Malaria Control Programs, donor agencies (e.g., President's Malaria Initiative and Global Fund), and other stakeholders have been evaluating the impact of scaling up malaria control interventions on all-cause under-five mortality in several countries in sub-Saharan Africa. The evaluation framework assesses whether the deployed interventions have had an impact on malaria morbidity and mortality and requires consideration of potential nonintervention influencers of transmission, such as drought/floods or higher temperatures. Herein, we assess the likely effect of climate on the assessment of the impact malaria interventions in 10 priority countries/regions in eastern, western, and southern Africa for the President's Malaria Initiative. We used newly available quality controlled Enhanced National Climate Services rainfall and temperature products as well as global climate products to investigate likely impacts of climate on malaria evaluations and test the assumption that changing the baseline period can significantly impact on the influence of climate in the assessment of interventions. Based on current baseline periods used in national malaria impact assessments, we identify three countries/regions where current evaluations may overestimate the impact of interventions (Tanzania, Zanzibar, Uganda) and three countries where current malaria evaluations may underestimate the impact of interventions (Mali, Senegal and Ethiopia). In four countries (Rwanda, Malawi, Mozambique, and Angola) there was no strong difference in climate suitability for malaria in the pre- and post-intervention period. In part, this may be due to data quality and analysis issues. PMID:28990912

Annotated Differentially Expressed Salivary Proteins of Susceptible and Insecticide-Resistant Mosquitoes of Anopheles stephensi

PubMed Central

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Raghavendra, Kamaraju; Sharma, Arun

2015-01-01

Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito—parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins may play a role in regulating mosquito biting behavior patterns and may have implications in the development of malaria parasites in resistant mosquitoes during parasite transmission. PMID:25742511

Annotated differentially expressed salivary proteins of susceptible and insecticide-resistant mosquitoes of Anopheles stephensi.

PubMed

Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Raghavendra, Kamaraju; Sharma, Arun

2015-01-01

Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito-parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins may play a role in regulating mosquito biting behavior patterns and may have implications in the development of malaria parasites in resistant mosquitoes during parasite transmission.

Strengthening malaria prevention and control: integrating West African militaries' malaria control efforts. The inaugural meeting of the West African Malaria Task Force, April 24-26, 2013, Accra, Ghana.

PubMed

McCollum, Jeffrey T; Hanna, Refaat; Halbach, Alaina C; Cummings, James F

2015-01-01

From April 24 to 26, 2013, the Armed Forces Health Surveillance Center and the U.S. Africa Command cosponsored the inaugural meeting of the West Africa Malaria Task Force in Accra, Ghana. The meeting's purpose was to identify common challenges, explore regional and transcontinental collaborations, and to share knowledge about best practices in the fight against malaria in West Africa. Military representatives from Benin, Burkina Faso, Ghana, Liberia, Niger, Nigeria, Senegal, and Togo participated in the Task Force; various U.S. Government agencies were also represented, including the Department of Defense, the Centers for Disease Control and Prevention, and the Agency for International Development. African nation participants presented brief overviews of their military's malaria prevention and control measures, surveillance programs, diagnostic capabilities, and treatment regimens emphasizing gaps within existing programs. Representatives from U.S. agencies discussed activities and capabilities relevant for the region, challenges and lessons learned regarding malaria, and highlighted opportunities for enhanced partnerships to counter malaria in West Africa. This article summarizes the major conclusions of the Task Force meeting, identifies relevant focus areas for future Task Force activities, and outlines opportunities for further inclusion of West African militaries to improve regional malaria surveillance and control efforts. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Renewed mobilization against malaria.

PubMed

1991-01-01

1 million people die in the world from malaria annually, 800,000 of whom are 5 year old children in Sub-Sahara Africa. Further it affects 270 million people. In fact, 110 million develop malaria, 90 million of whom are from Sub-Saharan Africa. Thus WHO has introduced a new world initiative for malaria control to reverse the worsening trend that began in the mid 1970s. In October 1991, 150 officials from 50 African, Asian, and Latin American countries and participants from UN cooperation and development agencies and bilateral agencies attended an interregional conference at the WHO Regional office for Africa in Brazzaville, Congo. It strove to evaluate malaria situations specific to Africa, to update the malaria control plan in Africa, and to contribute to the development of an implementable world strategy. This world strategy needs to consider the local situation and encourage participation of the government and people of affected countries. Further individuals, communities, and various sectors of the national economy including those involved in health, education, development, and agriculture need to participate in malaria control. In addition, for this strategy to work, most countries must strengthen the management and financing of health services to meet their needs. For example, local populations must share local operating costs such as those for essential drugs and mosquito control operations. Community participation must also include personal protection such as impregnated bed nets and environmental measures. Besides malaria control must be integrated into the existing health system at country, provincial, and peripheral levels. In sum, improved case management, control of malaria transmission, and prevention and control of epidemics form the basis for the new strategy.

"Alert-Audit-Act": assessment of surveillance and response strategy for malaria elimination in three low-endemic settings of Myanmar in 2016.

PubMed

Kyaw, Aye Mon Mon; Kathirvel, Soundappan; Das, Mrinalini; Thapa, Badri; Linn, Nay Yi Yi; Maung, Thae Maung; Lin, Zaw; Thi, Aung

2018-01-01

Myanmar, a malaria endemic country of Southeast Asia, adopted surveillance and response strategy similar to "1-3-7" Chinese strategy to achieve sub-national elimination in six low-endemic region/states of the country. Among these, Yangon, Bago-East, and Mon region/states have implemented this malaria surveillance and response strategy with modification in 2016. The current study was conducted to assess the case notification, investigation, classification, and response strategy (NICR) in these three states. This was a retrospective cohort study using routine program data of all patients with malaria diagnosed and reported under the National Malaria Control Programme in 2016 from the above three states. As per the program, all malaria cases need to be notified within 1 day and investigated within 3 days of diagnosis and response to control (active case detection and control) should be taken for all indigenous malaria cases within 7 days of diagnosis. A total of 959 malaria cases were diagnosed from the study area in 2016. Of these, the case NICR details were available only for 312 (32.5%) malaria cases. Of 312 cases, the case notification, investigation, and classification were carried out within 3 days of malaria diagnosis in 95.5% cases (298/312). Of 208 indigenous malaria cases (66.7%, 208/312), response to control was taken in 96.6% (201/208) within 7 days of diagnosis. The timeline at each stage of the strategy namely case notification, investigation, classification, and response to control was followed, and response action was taken in nearly all indigenous malaria cases for the available case information. Strengthening of health information and monitoring system is needed to avoid missing information. Future research on feasibility of mobile/tablet-based surveillance system and providing response to all cases including imported malaria can be further studied.

Virus Infection Stages and Distinct Th1 or Th17/Th22 T-Cell Responses in Malaria/SHIV Coinfection Correlate with Different Outcomes of Disease

PubMed Central

Ryan-Payseur, Bridgett; Ali, Zahida; Huang, Dan; Chen, Crystal Y.; Yan, Lin; Wang, Richard C.; Collins, William E.; Wang, Yunqi

2011-01-01

Background. Malaria and AIDS represent 2 leading causes of death from infectious diseases worldwide, and their high geographic overlap means coinfection is prevalent. It remains unknown whether distinct immune responses during coinfection with malaria and human immunodeficiency virus (HIV) affect clinical outcomes. Methods. We tested this hypothesis by employing macaque models of coinfection with malaria and simian-human immunodeficiency virus (SHIV). Results. Plasmodium fragile malaria coinfection of acutely SHIV-infected macaques induced hyperimmune activation and remarkable expansion of CD4+ and CD8+ T effector cells de novo producing interferon γ or tumor necrosis factor α. Malaria-driven cellular hyperactivation/expansion and high-level Th1-cytokines enhanced SHIV disease characterized by increasing CD4+ T-cell depletion, profound lymphoid depletion or destruction, and even necrosis in lymph nodes and spleens. Importantly, malaria/SHIV-mediated depletion, destruction, and necrosis in lymphoid tissues led to bursting parasite replication and fatal virus-associated malaria. Surprisingly, chronically SHIV-infected macaques without AIDS employed different defense mechanisms during malaria coinfection, and mounted unique ∼200-fold expansion of interleukin 17+/interleukin 22+ T effectors with profound Th1 suppression. Such remarkable expansion of Th17/Th22 cells and inhibition of Th1 response coincided with development of immunity against fatal virus-associated malaria without accelerating SHIV disease. Conclusions. These novel findings suggest that virus infection status and selected Th1 or Th17/Th22 responses after malaria/AIDS-virus coinfection correlate with distinct outcomes of virus infection and malaria. PMID:21921207

A global assessment of closed forests, deforestation and malaria risk

PubMed Central

GUERRA, C. A.; SNOW, R. W.; HAY, S. I.

2011-01-01

Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria. Amongst the anthropogenic drivers of change, deforestation is arguably the most conspicuous, and its rate is projected to increase in the coming decades. The canonical epidemiological understanding is that deforestation increases malaria risk in Africa and the Americas and diminishes it in South–east Asia. Partial support for this position is provided here, through a systematic review of the published literature on deforestation, malaria and the relevant vector bionomics. By using recently updated boundaries for the spatial limits of malaria and remotely-sensed estimates of tree cover, it has been possible to determine the population at risk of malaria in closed forest, at least for those malaria-endemic countries that lie within the main blocks of tropical forest. Closed forests within areas of malaria risk cover approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South–east Asia. The corresponding human populations at risk of malaria within these forests total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By coupling these numbers with the country-specific rates of deforestation, it has been possible to rank malaria-endemic countries according to their potential for change in the population at risk of malaria, as the result of deforestation. The on-going research aimed at evaluating these relationships more quantitatively, through the Malaria Atlas Project (MAP), is highlighted. PMID:16630376

Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar.

PubMed

Baltzell, Kimberly A; Shakely, Deler; Hsiang, Michelle; Kemere, Jordan; Ali, Abdullah Suleiman; Björkman, Anders; Mårtensson, Andreas; Omar, Rahila; Elfving, Kristina; Msellem, Mwinyi; Aydin-Schmidt, Berit; Rosenthal, Philip J; Greenhouse, Bryan

2013-02-01

We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was > 4,000 parasites/μL in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients.

Does Magnetic Field Affect Malaria Parasite Replication in Human Red Blood Cells?

NASA Technical Reports Server (NTRS)

Chanturiya, Alexandr N.; Glushakova, Svetlana; Yin, Dan; Zimmerberg, Joshua

2004-01-01

Digestion of red blood cell (RBC) hemoglobin by the malaria parasite results in the formation of paramagnetic hemazoin crystals inside the parasite body. A number of reports suggest that magnetic field interaction with hamazoin crystals significantly reduces the number of infected cells in culture, and thus magnetic field can be used to combat malaria. We studies the effects of magnetic filed on the Plasmodium falciparum asexual life cycle inside RBCs under various experimental conditions. No effect was found during prolonged exposure of infected RBCs to constant magnetic fields up to 6000 Gauss. Infected RBCs were also exposed, under temperature-controlled conditions, to oscillating magnetic fields with frequencies in the range of 500-20000 kHz, and field strength 30-600 Gauss. This exposure often changed the proportion of different parasite stages in treated culture compared to controls. However, no significant effect on parasitemia was observed in treated cultures. This result indicates that the magnetic field effect on Plasmodium falciparum is negligible, or that hypothetical negative and positive effects on different stages within one 48-hour compensate each other.

Tackling the malaria problem in the South-East Asia Region: Need for a change in policy?

PubMed Central

Bharati, Kaushik; Ganguly, N. K.

2013-01-01

Malaria is largely neglected in the South-East Asia Region (SEAR), although it has the highest number of people susceptible to the disease. Malaria in the SEAR exhibits special epidemiological characteristics such as “forest malaria” and malaria due to migration across international borders. The Greater Mekong Subregion (GMS) has been a focal-point for the emergence of drug resistant malaria. With the recent emergence of artemisinin resistance, coupled with the limited availability of insecticides, malaria control efforts in the SEAR face a steep challenge. Indirect man-made factors such as climate change, as well as direct man-made factors such as the circulation of counterfeit drugs have added to the problem. Increased monitoring, surveillance, pharmacovigilance as well as cross-border collaboration are required to address these problems. Regional networking and data-sharing will keep all stakeholders updated about the status of various malaria control programmes in the SEAR. Cutting-edge technologies such as GIS/GPS (geographical information system/global positioning system) systems and mobile phones can provide information in “real-time”. A holistic and sustained approach to malaria control by integrated vector management (IVM) is suggested, in which all the stakeholder countries work collaboratively as a consortium. This approach will address the malaria problem in a collective manner so that malaria control can be sustained over time. PMID:23481050

Evaluation of Commercial Agrochemicals as New Tools for Malaria Vector Control.

PubMed

Hoppé, Mark; Hueter, Ottmar F; Bywater, Andy; Wege, Philip; Maienfisch, Peter

2016-10-01

Malaria is a vector-borne and life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. The vector control insecticide market represents a small fraction of the crop protection market and is estimated to be valued at up to $500 million at the active ingredient level. Insecticide resistance towards the current WHOPES-approved products urgently requires the development of new tools to protect communities against the transmission of malaria. The evaluation of commercial products for malaria vector control is a viable and cost effective strategy to identify new malaria vector control products. Several examples of such spin-offs from crop protection insecticides are already evidencing the success of this strategy, namely pirimiphos-methyl for indoor residual sprays and spinosad, diflubenzuron, novaluron, and pyriproxifen for mosquito larvae control, a supplementary technology for control of malaria vectors. In our study the adulticidal activities of 81 insecticides representing 23 insecticidal modes of action classes, 34 fungicides from 6 fungicidal mode of action classes and 15 herbicides from 2 herbicidal modes of action classes were tested in a newly developed screening system. WHOPES approved insecticides for malaria vector control consistently caused 80-100% mortality of adult Anopheles stephensi at application rates between 0.2 and 20 mg active ingradient (AI) litre -1 . Chlorfenapyr, fipronil, carbosulfan and endosulfan showed the expected good activity. Four new insecticides and three fungicides with promising activity against adult mosquitoes were identified, namely the insecticides acetamiprid, thiamethoxam, thiocyclam and metaflumizone and the fungicides diflumetorin, picoxystrobin, and fluazinam. Some of these compounds certainly deserve to be further evaluated for malaria vector control. This is the first report describing good activity of commercial fungicides against malaria vectors.

Potential of household environmental resources and practices in eliminating residual malaria transmission: a case study of Tanzania, Burundi, Malawi and Liberia.

PubMed

Semakula, Henry M; Song, Guobao; Zhang, Shushen; Achuu, Simon P

2015-09-01

The increasing protection gaps of insecticide-treated nets and indoor-residual spraying methods against malaria have led to an emergence of residual transmission in sub-Saharan Africa and thus, supplementary strategies to control mosquitoes are urgently required. To assess household environmental resources and practices that increase or reduce malaria risk among children under-five years of age in order to identify those aspects that can be adopted to control residual transmission. Household environmental resources, practices and malaria test results were extracted from Malaria Indicators Survey datasets for Tanzania, Burundi, Malawi and Liberia with 16,747 children from 11,469 households utilised in the analysis. Logistic regressions were performed to quantify the contribution of each factor to malaria occurrence. Cattle rearing reduced malaria risk between 26%-49% while rearing goats increased the risk between 26%-32%. All piped-water systems reduced malaria risk between 30%-87% (Tanzania), 48%-95% (Burundi), 67%-77% (Malawi) and 58%-73 (Liberia). Flush toilets reduced malaria risk between 47%-96%. Protected-wells increased malaria risk between 19%-44%. Interestingly, boreholes increased malaria risk between 19%-75%. Charcoal use reduced malaria risk between 11%-49%. Vector control options for tackling mosquitoes were revealed based on their risk levels. These included cattle rearing, installation of piped-water systems and flush toilets as well as use of smokeless fuels.

Integrating child health services into malaria control services of village malaria workers in remote Cambodia: service utilization and knowledge of malaria management of caregivers.

PubMed

Hasegawa, Aya; Yasuoka, Junko; Ly, Po; Nguon, Chea; Jimba, Masamine

2013-08-23

Malaria and other communicable diseases remain major threats in developing countries. In Cambodia, village malaria workers (VMWs) have been providing malaria control services in remote villages to cope with the disease threats. In 2009, the VMW project integrated child health services into the original malaria control services. However, little has been studied about the utilization of VMWs' child health services. This study aimed to identify determinants of caregivers' VMW service utilization for childhood illness and caregivers' knowledge of malaria management. A cross-sectional study was conducted in 36 VMW villages of Kampot and Kampong Thom provinces in July-September 2012. An equal number of VMW villages with malaria control services only (M) and those with malaria control plus child health services (M+C) were selected from each province. Using structured questionnaires, 800 caregivers of children under five and 36 VMWs, one of the two VMWs who was providing VMW services in each study village were interviewed. Among the caregivers, 23% in M villages and 52% in M+C villages utilized VMW services for childhood illnesses. Determinants of caregivers' utilization of VMWs in M villages included their VMWs' length of experience (AOR = 11.80, 95% confidence interval [CI] = 4.46-31.19) and VMWs' service quality (AOR = 2.04, CI = 1.01-4.11). In M+C villages, VMWs' length of experience (AOR = 2.44, CI = 1.52-3.94) and caregivers' wealth index (AOR = 0.35, CI = 0.18-0.68) were associated with VMW service utilization. Meanwhile, better service quality of VMWs (AOR = 3.21, CI = 1.34-7.66) and caregivers' literacy (AOR = 9.91, CI = 4.66-21.05) were positively associated with caregivers' knowledge of malaria management. VMWs' service quality and length of experience are important determinants of caregivers' utilization of VMWs' child health services and their knowledge of malaria management. Caregivers are seeking VMWs' support for childhood illnesses even if they are providing only malaria control services. This underlines the importance of scaling-up VMWs' capacity by adding child health services of good quality, which will result in improving child health status in remote Cambodia.

Perceptions of malaria control and prevention in an era of climate change: a cross-sectional survey among CDC staff in China.

PubMed

Tong, Michael Xiaoliang; Hansen, Alana; Hanson-Easey, Scott; Cameron, Scott; Xiang, Jianjun; Liu, Qiyong; Liu, Xiaobo; Sun, Yehuan; Weinstein, Philip; Han, Gil-Soo; Williams, Craig; Bi, Peng

2017-03-31

Though there was the significant decrease in the incidence of malaria in central and southwest China during the 1980s and 1990s, there has been a re-emergence of malaria since 2000. A cross-sectional survey was conducted amongst the staff of eleven Centers for Disease Control and Prevention (CDC) in China to gauge their perceptions regarding the impacts of climate change on malaria transmission and its control and prevention. Descriptive analysis was performed to study CDC staff's knowledge, attitudes, perceptions and suggestions for malaria control in the face of climate change. A majority (79.8%) of CDC staff were concerned about climate change and 79.7% believed the weather was becoming warmer. Most participants (90.3%) indicated climate change had a negative effect on population health, 92.6 and 86.8% considered that increasing temperatures and precipitation would influence the transmission of vector-borne diseases including malaria. About half (50.9%) of the surveyed staff indicated malaria had re-emerged in recent years, and some outbreaks were occurring in new geographic areas. The main reasons for such re-emergence were perceived to be: mosquitoes in high-density, numerous imported cases, climate change, poor environmental conditions, internal migrant populations, and lack of health awareness. This study found most CDC staff endorsed the statement that climate change had a negative impact on infectious disease transmission. Malaria had re-emerged in some areas of China, and most of the staff believed that this can be managed. However, high densities of mosquitoes and the continuous increase in imported cases of malaria in local areas, together with environmental changes are bringing about critical challenges to malaria control in China. This study contributes to an understanding of climate change related perceptions of malaria control and prevention amongst CDC staff. It may help to formulate in-house training guidelines, community health promotion programmes and policies to improve the capacity of malaria control and prevention in the face of climate change in China.

Enhancing Human Health Using Space Imagery: Summary of Research

NASA Technical Reports Server (NTRS)

Finarelli, Margaret G.

2002-01-01

The International Space University (ISU) 2002 Summer Session was conducted in Pomona, California, June 29-August 30, 2002. Ninety-nine professionals and students from thirty-one countries attended the Summer Session. More than half of these students participated in the Student Research Design Project entitled, "HI-STAR: Health Improvements through Space Technologies and Resources." ISU's interdisciplinary Student Research Design Projects are intended to have great educational value for the participants and, at the same time, to result in a product that will be useful to the field. The HI-STAR project was a success on both counts. The mission of the ISU students' effort on HI-STAR was to develop and promote a global strategy to help combat malaria using space technology. Like the tiny yet powerful mosquito, HI-STAR is a small program that aspires to make a difference. Timely detection of malaria danger zones is essential to help health authorities and policy makers make decisions about how to manage limited resources for combating malaria. In 2001, the technical support network for prevention and control of malaria epidemics published a study called "Malaria Early Warning Systems: Concepts, Indicators and Partners." This study, funded by Roll Back Malaria, a World Health Organization initiative, offered a framework for a monitoring and early warning system. HI-STAR seeks to build on this proposal and enhance the space elements of the suggested framework. Malaria disease dynamics and distributions are related to environmental variables. From space, environmental conditions that support the growth of mosquito populations can be monitored, Malaria-specific information can be gathered from satellite-borne remote sensing instruments and ground-based sensors. This information can be integrated via geographic information systems (GIS) into a Malaria Information System (MIS) that can provide assessment analyses and risk maps as output. HI-STAR defines and suggests the development of an active MIS as a low-cost tool to help organizations plan their efforts to fight malaria.

CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection

PubMed Central

Dong, Yuemei; Simões, Maria L.

2018-01-01

Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants developed into adult mosquitoes that showed profound suppression of infection with both human and rodent malaria parasites at the oocyst and sporozoite stages. FREP1 inactivation, however, resulted in fitness costs including a significantly lower blood-feeding propensity, fecundity and egg hatching rate, a retarded pupation time, and reduced longevity after a blood meal. PMID:29518156

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

PubMed

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-09

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

PubMed

Brancucci, Nicolas M B; Gerdt, Joseph P; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D; Laffitte, Marie-Claude; Clark, Martha A; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T; Adams, John H; Voss, Till S; Waters, Andrew P; Jiang, Rays H Y; Clardy, Jon; Marti, Matthias

2017-12-14

Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes.

PubMed

Neafsey, Daniel E; Waterhouse, Robert M; Abai, Mohammad R; Aganezov, Sergey S; Alekseyev, Max A; Allen, James E; Amon, James; Arcà, Bruno; Arensburger, Peter; Artemov, Gleb; Assour, Lauren A; Basseri, Hamidreza; Berlin, Aaron; Birren, Bruce W; Blandin, Stephanie A; Brockman, Andrew I; Burkot, Thomas R; Burt, Austin; Chan, Clara S; Chauve, Cedric; Chiu, Joanna C; Christensen, Mikkel; Costantini, Carlo; Davidson, Victoria L M; Deligianni, Elena; Dottorini, Tania; Dritsou, Vicky; Gabriel, Stacey B; Guelbeogo, Wamdaogo M; Hall, Andrew B; Han, Mira V; Hlaing, Thaung; Hughes, Daniel S T; Jenkins, Adam M; Jiang, Xiaofang; Jungreis, Irwin; Kakani, Evdoxia G; Kamali, Maryam; Kemppainen, Petri; Kennedy, Ryan C; Kirmitzoglou, Ioannis K; Koekemoer, Lizette L; Laban, Njoroge; Langridge, Nicholas; Lawniczak, Mara K N; Lirakis, Manolis; Lobo, Neil F; Lowy, Ernesto; MacCallum, Robert M; Mao, Chunhong; Maslen, Gareth; Mbogo, Charles; McCarthy, Jenny; Michel, Kristin; Mitchell, Sara N; Moore, Wendy; Murphy, Katherine A; Naumenko, Anastasia N; Nolan, Tony; Novoa, Eva M; O'Loughlin, Samantha; Oringanje, Chioma; Oshaghi, Mohammad A; Pakpour, Nazzy; Papathanos, Philippos A; Peery, Ashley N; Povelones, Michael; Prakash, Anil; Price, David P; Rajaraman, Ashok; Reimer, Lisa J; Rinker, David C; Rokas, Antonis; Russell, Tanya L; Sagnon, N'Fale; Sharakhova, Maria V; Shea, Terrance; Simão, Felipe A; Simard, Frederic; Slotman, Michel A; Somboon, Pradya; Stegniy, Vladimir; Struchiner, Claudio J; Thomas, Gregg W C; Tojo, Marta; Topalis, Pantelis; Tubio, José M C; Unger, Maria F; Vontas, John; Walton, Catherine; Wilding, Craig S; Willis, Judith H; Wu, Yi-Chieh; Yan, Guiyun; Zdobnov, Evgeny M; Zhou, Xiaofan; Catteruccia, Flaminia; Christophides, George K; Collins, Frank H; Cornman, Robert S; Crisanti, Andrea; Donnelly, Martin J; Emrich, Scott J; Fontaine, Michael C; Gelbart, William; Hahn, Matthew W; Hansen, Immo A; Howell, Paul I; Kafatos, Fotis C; Kellis, Manolis; Lawson, Daniel; Louis, Christos; Luckhart, Shirley; Muskavitch, Marc A T; Ribeiro, José M; Riehle, Michael A; Sharakhov, Igor V; Tu, Zhijian; Zwiebel, Laurence J; Besansky, Nora J

2015-01-02

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts. Copyright © 2015, American Association for the Advancement of Science.

Chimpanzee Malaria Parasites Related to Plasmodium ovale in Africa

PubMed Central

Duval, Linda; Nerrienet, Eric; Rousset, Dominique; Sadeuh Mba, Serge Alain; Houze, Sandrine; Fourment, Mathieu; Le Bras, Jacques; Robert, Vincent; Ariey, Frederic

2009-01-01

Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes. PMID:19436742

Malaria rapid diagnostic tests.

PubMed

Wilson, Michael L

2012-06-01

Global efforts to control malaria are more complex than those for other infectious diseases, in part because of vector transmission, the complex clinical presentation of Plasmodium infections, >1 Plasmodium species causing infection, geographic distribution of vectors and infection, and drug resistance. The World Health Organization approach to global malaria control focuses on 2 components: vector control and diagnosis and treatment of clinical malaria. Although microscopy performed on peripheral blood smears remains the most widely used diagnostic test and the standard against which other tests are measured, rapid expansion of diagnostic testing worldwide will require use of other diagnostic approaches. This review will focus on the malaria rapid diagnostic test (MRDT) for detecting malaria parasitemia, both in terms of performance characteristics of MRDTs and how they are used under field conditions. The emphasis will be on the performance and use of MRDTs in regions of endemicity, particularly sub-Saharan Africa, where most malaria-related deaths occur.

Factors Influencing Prevention and Control of Malaria among Pregnant Women Resident in Urban Slums, Southern Ghana.

PubMed

Dako-Gyeke, Mavis; Kofie, Humphrey M

2015-03-01

Throughout Africa and particularly in Ghana, there are concerns about malaria infection during pregnancy. This study aimed to investigate factors that influence malaria prevention and control practices among pregnant women residing in Chorkor and Korle-Gonno in Accra, Ghana. One hundred and twenty pregnant women between ages 18-49 were randomly recruited during antenatal sessions at a maternity facility in Accra, as participants for the study. An interviewer-administered questionnaire was used to collect data, which were analysed using SPSS version16.0. It was found that in Chorkor and Korle-Gonno, 57.4% and 42.6% participants respectively reported having been infected with malaria during their current pregnancy. There was no significant relationship between religious beliefs of participants and their malaria prevention and control practices (X2 = 0.28, P = .53). However, there was a significant relationship between malaria prevention and control practices of participants and their income earning (X2 = 53.94, P = .00) and employment (X2 = 61.76, P = .00) statuses. With the exception of ethnicity (X2 = 35.62, P =.22), other socio-cultural conditions had a significant relationship with malaria prevention and control practices of the participants. The findings suggest the need to consider and integrate factors, such as poverty and poor living conditions in malaria prevention and control strategies.

The Biological Control of the Malaria Vector

PubMed Central

Kamareddine, Layla

2012-01-01

The call for malaria control, over the last century, marked a new epoch in the history of this disease. Many control strategies targeting either the Plasmodium parasite or the Anopheles vector were shown to be effective. Yet, the emergence of drug resistant parasites and insecticide resistant mosquito strains, along with numerous health, environmental, and ecological side effects of many chemical agents, highlighted the need to develop alternative tools that either complement or substitute conventional malaria control approaches. The use of biological means is considered a fundamental part of the recently launched malaria eradication program and has so far shown promising results, although this approach is still in its infancy. This review presents an overview of the most promising biological control tools for malaria eradication, namely fungi, bacteria, larvivorous fish, parasites, viruses and nematodes. PMID:23105979

The invasive American weed parthenium hysterophorus can negatively impact malaria control in Africa

USDA-ARS?s Scientific Manuscript database

The direct negative effects of invasive plant species on agriculture and biodiversity are well known, but their indirect effects on human health, and particularly their interactions with disease-transmitting vectors, remains poorly explored. This study sought to investigate the impact of the invasiv...

Rapid immunochromatographic diagnosis and Rolling Back Malaria--experiences from an African control program.

PubMed

Durrheim, D N; Govere, J; la Grange, J J; Mabuza, A

2001-01-01

Malaria is a re-emerging disease in much of Africa. In response, the World Health Organization launched the Roll Back Malaria (RBM) initiative. One of six key principles adopted is the early detection of malaria cases. However, the importance of definitive diagnosis and potential value of field deployment of rapid malaria tests in RBM has been largely ignored. The Lowveld Region of Mpumalanga Province, South Africa, is home to a predominantly non-immune population, of approximately 850000 inhabitants, who are at risk of seasonal Plasmodium falciparum malaria. Malaria treatment in this area is usually only initiated on detection of malaria parasites in the peripheral bloodstream, as many other rickettsial and viral febrile illness mimic malaria. The malaria control programme traditionally relied on light microscopy of Giemsa-stained thick blood films for malaria diagnosis. This review summarizes operational research findings that led to the introduction of rapid malaria card tests for primary diagnosis of malaria throughout the Mpumalanga malaria area. Subsequent operational research and extensive experience over a four-year period since introducing the ICT Malaria Pf test appears to confirm the local appropriateness of this diagnostic modality. A laboratory is not required and clinic staff are empowered to make a prompt definitive diagnosis, limiting delays in initiating correct therapy. The simple, accurate and rapid non-microscopic means now available for diagnosing malaria could play an important role in Rolling Back Malaria in selected areas.

Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates.

PubMed

Gómez-Pérez, Gloria P; Legarda, Almudena; Muñoz, Jose; Sim, B Kim Lee; Ballester, María Rosa; Dobaño, Carlota; Moncunill, Gemma; Campo, Joseph J; Cisteró, Pau; Jimenez, Alfons; Barrios, Diana; Mordmüller, Benjamin; Pardos, Josefina; Navarro, Mireia; Zita, Cecilia Justino; Nhamuave, Carlos Arlindo; García-Basteiro, Alberto L; Sanz, Ariadna; Aldea, Marta; Manoj, Anita; Gunasekera, Anusha; Billingsley, Peter F; Aponte, John J; James, Eric R; Guinovart, Caterina; Antonijoan, Rosa M; Kremsner, Peter G; Hoffman, Stephen L; Alonso, Pedro L

2015-08-07

Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ administered IM than DVI to achieve the same parasite kinetics. These results allow for translation of CHMI from research to routine use, and inoculation of PfSPZ by IM and DVI regimens. ClinicalTrials.gov NCT01771848.

Secreted HSP Vaccine for Malaria Prophylaxis

DTIC Science & Technology

2015-10-01

Award Number: W81XWH-13-2-0098 TITLE: Secreted HSP Vaccine for Malaria Prophylaxis PRINCIPAL INVESTIGATOR: Dr. Natasa Strbo CONTRACTING...REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Secreted HSP Vaccine for Malaria ...We have also started manufacturing GMP-grade vaccine material for use in non-human primate studies . 15. SUBJECT TERMS- Malaria , Plasmodium

Current management and prevention of malaria in pregnancy: a review.

PubMed

Agboghoroma, C O

2014-01-01

Pregnant women suffer more frequent and severe malaria than non-pregnant women. Malaria in pregnancy contributes to the high maternal and perinatal morbidity and mortality in Africa. To review the burden and highlight the current management and prevention strategies for control of malaria in pregnancy in Africa. Papers for this review were identified by searches of PubMed and Google, and references from relevant articles. Search terms were "malaria", "malaria in pregnancy", "Malaria during pregnancy" and "antimalarial drug". Only papers published in English between 1983 and 2013 were included. In malarial endemic areas, acquired partial malarial immunity is not effective during pregnancy. Pregnant women are prone to frequent malaria infections which may be severe or asymptomatic but associated with placental parasitization. Malaria contributes 2-15% to maternal anaemia, 13-70% to intrauterine growth restriction, 8-14% to low birth weight, 8-36% to prematurity, 3-8% to infant deaths and 2.9-17.6% to maternal mortality. The control of malaria in pregnancy is currently predicated on three main strategies: 1) Prompt and effective case management of malaria; 2).Use of Insecticide-treated nets; and 3).Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine. Artemisinin-based combined therapy is the recommended treatment for uncomplicated malaria in the second and third trimesters of pregnancy, while quinine is used in the first trimester and for severe cases of malaria at any gestational age. The control of malaria during pregnancy should be an integral part of efforts to reduce maternal and perinatal morbidity and mortality in Africa.

Age-Specific Malaria Mortality Rates in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya, 2003–2010

PubMed Central

Desai, Meghna; Buff, Ann M.; Khagayi, Sammy; Byass, Peter; Amek, Nyaguara; van Eijk, Annemieke; Slutsker, Laurence; Vulule, John; Odhiambo, Frank O.; Phillips-Howard, Penelope A.; Lindblade, Kimberly A.; Laserson, Kayla F.; Hamel, Mary J.

2014-01-01

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003–2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003–2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5–14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003–2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions. PMID:25180495

[Control of malaria transmission in a gold-mining area in Amapá State, Brazil, with participation by private enterprise].

PubMed

Couto AA; Calvosa, V S; Lacerda, R; Castro, F; Santa Rosa, E; Nascimento, J M

2001-01-01

This paper reports on the epidemiological characterization of malaria following implementation of a program to control the endemic in a gold-mining area in northern Amapá State. The study focuses on total malaria cases in Amapá and the impact of the disease on the population, as represented by the Mineração Novo Astro S/A company and its employees as well as the community of Vila de Lourenço in the municipality of Calçoene, and adjacent gold miners. The effect of control measures in the program area is indicated by a significant reduction in malaria incidence and malaria-related morbidity and mortality. The importance of participation by private enterprise is emphasized, particularly in large projects for the control of endemic diseases (notably malaria) in the Amazon Region.

Application of GIS to predict malaria hotspots based on Anopheles arabiensis habitat suitability in Southern Africa

NASA Astrophysics Data System (ADS)

Gwitira, Isaiah; Murwira, Amon; Zengeya, Fadzai M.; Shekede, Munyaradzi Davis

2018-02-01

Malaria remains a major public health problem and a principal cause of morbidity and mortality in most developing countries. Although malaria still presents health problems, significant successes have been recorded in reducing deaths resulting from the disease. As malaria transmission continues to decline, control interventions will increasingly depend on the ability to define high-risk areas known as malaria hotspots. Therefore, there is urgent need to use geospatial tools such as geographic information system to detect spatial patterns of malaria and delineate disease hot spots for better planning and management. Thus, accurate mapping and prediction of seasonality of malaria hotspots is an important step towards developing strategies for effective malaria control. In this study, we modelled seasonal malaria hotspots as a function of habitat suitability of Anopheles arabiensis (A. Arabiensis) as a first step towards predicting likely seasonal malaria hotspots that could provide guidance in targeted malaria control. We used Geographical information system (GIS) and spatial statistic methods to identify seasonal hotspots of malaria cases at the country level. In order to achieve this, we first determined the spatial distribution of seasonal malaria hotspots using the Getis Ord Gi* statistic based on confirmed positive malaria cases recorded at health facilities in Zimbabwe over four years (1996-1999). We then used MAXENT technique to model habitat suitability of A. arabiensis from presence data collected from 1990 to 2002 based on bioclimatic variables and altitude. Finally, we used autologistic regression to test the extent to which malaria hotspots can be predicted using A. arabiensis habitat suitability. Our results show that A. arabiensis habitat suitability consistently and significantly (p < 0.05) predicts malaria hotspots from 1996 to 1999. Overall, our results show that malaria hotspots can be predicted using A. arabiensis habitat suitability, suggesting the possibility of developing models for malaria early warning based on vector habitat suitability.

Malaria control: achievements, problems and strategies.

PubMed

Nájera, J A

2001-06-01

Even if history has not always been the Magistra vitae, Cicero expected it to be, it should provide, as Baas said, a mirror in which to observe and compare the past and present in order to draw therefrom well-grounded conclusions for the future. Based on this belief, this paper aims to provide an overview of the foundations and development of malaria control policies during the XX century. It presents an analysis of the conflicting tendencies which shaped the development of these policies and which appear to have oscillated between calls for frontal attack in an all-out campaign and calls for sustainable gains, even if slow. It discusses the various approaches to the control of malaria, their achievements and their limitations, not only to serve as a background to understand better the foundations of current policies, but also to prevent that simplistic generalisations may again lead to exaggerated expectations and disillusion. The first part of the paper is devoted to the development of malaria control during the first half of the century, characterised by the ups and downs in the reliance on mosquito control as the control measure applicable everywhere. The proliferation of "man-made-malaria", which accompanied the push for economic development in most of the endemic countries, spurred the need for control interventions and, while great successes were obtained in many specific projects, the general campaigns proposed by the enthusiasts of vector control faced increasing difficulties in their practical implementation in the field. Important events, which may be considered representative of this period are, on the campaign approach, the success of Gorgas in the Panama Canal, but also the failure of the Mian Mir project in India; while on the developmental approach, the Italian and Dutch schools of malariology, the Tennessee Valley and the development of malaria sanitation, included the so called species sanitation. The projection of these developments to a global scale was steered by the Malaria Commission of the League of Nations and greatly supported by the Rockefeller Foundation. Perhaps the most important contribution of this period was the development of malaria epidemiology, including the study of the genesis of epidemics and their possible forecasting and prevention. Although the great effectiveness of DDT was perhaps the main determinant for proposing the global eradication of the disease in the 1950s, it was the confidence in the epidemiological knowledge and the prestige of malariology, which gave credibility to the proposal at the political level. The second part deals with the global malaria eradication campaign of the 1950s and 1960s. It recognises the enormous impact of the eradication effort in the consolidation of the control successes of the first half of the century, as well as its influence in the development of planning of health programmes. Nevertheless, it also stresses the negative influence that the failure to achieve its utopian expectations had on the general disappointment and slow progress of malaria control, which characterised the last third of the century. The paper then analyses the evolution of malaria control funding, which often appears out of tune with political statements. The fourth part is devoted to the search for realistic approaches to malaria control, leading to the adoption of the global malaria control strategy in Amsterdam in 1992, and the challenge, at the end of the century, to rally forces commensurate with the magnitude of the problem, while aiming at realistic objectives. After discussing the conflicting views on the relations between malaria and socio-economic development and the desirable integration of malaria control into sustainable development, the paper ends with some considerations on the perspectives of malaria control, as seen by the author in early 1998, just before the launching of the current Roll Back Malaria initiative by WHO.