[Current management of imported severe malaria].

PubMed

Venanzi, E; López-Vélez, R

2016-09-01

Severe malaria is a diagnostic and therapeutic emergency with great impact worldwide for incidence and mortality. The clinical presentation of severe malaria can be very polymorphic and rapidly progressing. Therefore a correct diagnosis and an early and adequate antiparasitic and support therapy are essential. This paper attempts to outline the diagnosis frame and the treatment of severe malaria for adults, paediatric patients and for pregnant.

Steady progress toward a malaria vaccine.

PubMed

Lyke, Kirsten E

2017-10-01

Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection. Novel vaccines such as RTS,S/AS01E are on the edge of licensure, but old techniques have resurged with the ability to deliver vialed, whole organism vaccines. Novel adjuvants, multistage/multiantigen approaches and transmission blocking vaccines all contribute to a multipronged battle plan to conquer malaria. Vaccines are the most cost-effective tools to control infectious diseases, yet the complexity of malaria has frustrated all attempts to develop an effective product. This review concentrates on recent advances in malaria vaccine development that lend hope that a vaccine can be produced and malaria eradicated.

Costs of eliminating malaria and the impact of the global fund in 34 countries.

PubMed

Zelman, Brittany; Kiszewski, Anthony; Cotter, Chris; Liu, Jenny

2014-01-01

International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). Countries have made substantial progress, but achieving elimination requires sustained finances to interrupt transmission and prevent reintroduction. Since 2011, global financing for malaria has declined, fueling concerns that further progress will be impeded, especially for current malaria-eliminating countries that may face resurgent malaria if programs are disrupted. This study aims to 1) assess past total and Global Fund funding to the 34 current malaria-eliminating countries, and 2) estimate their future funding needs to achieve malaria elimination and prevent reintroduction through 2030. Historical funding is assessed against trends in country-level malaria annual parasite incidences (APIs) and income per capita. Following Kizewski et al. (2007), program costs to eliminate malaria and prevent reintroduction through 2030 are estimated using a deterministic model. The cost parameters are tailored to a package of interventions aimed at malaria elimination and prevention of reintroduction. The majority of Global Fund-supported countries experiencing increases in total funding from 2005 to 2010 coincided with reductions in malaria APIs and also overall GNI per capita average annual growth. The total amount of projected funding needed for the current malaria-eliminating countries to achieve elimination and prevent reintroduction through 2030 is approximately US$8.5 billion, or about $1.84 per person at risk per year (PPY) (ranging from $2.51 PPY in 2014 to $1.43 PPY in 2030). Although external donor funding, particularly from the Global Fund, has been key for many malaria-eliminating countries, sustained and sufficient financing is critical for furthering global malaria elimination. Projected cost estimates for elimination provide policymakers with an indication of the level of financial resources that should be mobilized to achieve malaria elimination goals.

Malaria vaccine clinical trials: what’s on the horizon

PubMed Central

Moreno, Alberto; Joyner, Chester

2015-01-01

Significant progress towards a malaria vaccine, specifically for Plasmodium falciparum, has been made in the past few years with the completion of numerous clinical trials. Each trial has utilized a unique combination of antigens, delivery platforms, and adjuvants, and the data that has been obtained provides critical information that has poises the research community for the development of next generation malaria vaccines. Despite the progress towards a P. falciparum vaccine, P. vivax vaccine research requires more momentum and additional investigations to identify novel vaccine candidates. In this review, recently completed and ongoing malaria vaccine clinical trials as well as vaccine candidates that are in the development pipeline are reviewed. Perspectives for future research using post-genomic mining, nonhuman primate models, and systems biology are also discussed. PMID:26172291

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

[Malaria is still a leading cause of fever and death among children and pregnant women in Africa in 2015].

PubMed

Doumbo, Ogobara; Fall, Ibrahima Socé; Niaré, Doumbo

2016-03-01

The prevalence and morbidity of P. vivax, P. ovale (curisi et wallikeri) and P. malariae remain underestimated. However important progress has been made. According to the WHO World Malaria report between 2000 and 2015 the malaria incidence has decreased by 42% while the incidence of malaria deaths has decreased by 66%. This is the result of the important progress made in scaling up the main interventions such the rapid diagnosis test, Artemisinin-based combination therapies, long lasting insecticide treated nets, indoor residual house spraying, intermittent preventive treatment during pregnancy (IPTp-SP), Seasonal Malaria Chemoprophylaxis with combined antimalarial (SMClAQ-SP). In the Sahel region with a highly seasonal transmission, the use of SMC resulted in a reduction of malaria morbidity for 80% and a reduce mortality for 58%. Malaria elimination efforts are going on in many countries in Swaziland, South Africa, Namibia, Zanzibar (United Republic of Tanzania), Bioko Island (Equatorial Guinea), Sao Tome and Principe, Cape Verde, and maybe Senegal. For the time being only countries in Northern Africa and few in East Africa (Mauritius) have reached the elimination of local transmission. Despite the progress made near 500,000 malaria deaths occur annually in the African Region with 10-15% leading to disabling sequels and low school performance in children. Reaching the target of 80% for preventive and treatment interventions remain a challenge in many countries in Africa. It's important to keep in mind that the Abuja targets and MGDs were not reached by most African countries. In addition, among 12 million children eligible for SMC only 35% were covered despite the availability of resources in 2014. A huge global stock out of ACT. AQ-SP is possible. The development of an effective vaccine has been disappointing with a limited effectiveness of the RTS,S. The emerging resistance to Artemisinin derivate in South-East Asia and its possible expansion to Africa is of big concern. Anopheles gambiae resistance to pyrethroid make to situation even more complex. The situation can worsen because of factor such as climate change and socio-political crisis. Therefore the malaria situation in Africa is still of big concern despite the progress highlighted. Innovative a robust approach is needed with strong government commitment and partners support to lead battle. A new hope is emerging with the development of candidate vaccine from whole sporozoïte, the other candidates vaccines blocking the transmission in phase 1b and the new SMC Plus strategy (AQ-SP+Azithromycine). Conclusion: lessons learnt from the malaria eradication era in the 50s must be factored in while developing the malaria elimination strategy for Africa by 2030.

Reducing empiricism in malaria vaccine design.

PubMed

Moorthy, Vasee S; Kieny, Marie Paule

2010-03-01

Gains in the control of malaria and the promising progress of a malaria vaccine that is partly efficacious do not reduce the need for a high-efficacy vaccine in the longer term. Evidence supports the feasibility of developing a highly efficacious malaria vaccine. However, design of candidate malaria vaccines remains empirical and is necessarily based on many unproven assumptions because much of the knowledge needed to design vaccines and to predict efficacy is not available. Data to inform key questions of vaccine science might allow the design of vaccines to progress to a less empirical stage, for example through availability of assay results associated with vaccine efficacy. We discuss six strategic gaps in knowledge that contribute to empiricism in the design of vaccines. Comparative evaluation, assay and model standardisation, greater sharing of information, collaboration and coordination between groups, and rigorous evaluation of existing datasets are steps that can be taken to enable reductions in empiricism over time. 2010 Elsevier Ltd. All rights reserved.

Plasmodium vivax Landscape in Brazil: Scenario and Challenges

PubMed Central

Siqueira, Andre M.; Mesones-Lapouble, Oscar; Marchesini, Paola; Sampaio, Vanderson de Souza; Brasil, Patricia; Tauil, Pedro L.; Fontes, Cor Jesus; Costa, Fabio T. M.; Daniel-Ribeiro, Cláudio Tadeu; Lacerda, Marcus V. G.; Damasceno, Camila P.; Santelli, Ana Carolina S.

2016-01-01

Brazil is the largest country of Latin America, with a considerable portion of its territoritory within the malaria-endemic Amazon region in the North. Furthermore, a considerable portion of its territory is located within the Amazon region in the north. As a result, Brazil has reported half of the total malaria cases in the Americas in the last four decades. Recent progress in malaria control has been accompanied by an increasing proportion of Plasmodium vivax, underscoring a need for a better understanding of management and control of this species and associated challenges. Among these challenges, the contribution of vivax malaria relapses, earlier production of gametocytes (compared with Plasmodium falciparum), inexistent methods to diagnose hypnozoite carriers, and decreasing efficacy of available antimalarials need to be addressed. Innovative tools, strategies, and technologies are needed to achieve further progress toward sustainable malaria elimination. Further difficulties also arise from dealing with the inherent socioeconomic and environmental particularities of the Amazon region and its dynamic changes. PMID:27708190

State of inequality in malaria intervention coverage in sub-Saharan African countries.

PubMed

Galactionova, Katya; Smith, Thomas A; de Savigny, Don; Penny, Melissa A

2017-10-18

Scale-up of malaria interventions over the last decade have yielded a significant reduction in malaria transmission and disease burden in sub-Saharan Africa. We estimated economic gradients in the distribution of these efforts and of their impacts within and across endemic countries. Using Demographic and Health Surveys we computed equity metrics to characterize the distribution of malaria interventions in 30 endemic countries proxying economic position with an asset-wealth index. Gradients were summarized in a concentration index, tabulated against level of coverage, and compared among interventions, across countries, and against respective trends over the period 2005-2015. There remain broad differences in coverage of malaria interventions and their distribution by wealth within and across countries. In most, economic gradients are lacking or favor the poorest for vector control; malaria services delivered through the formal healthcare sector are much less equitable. Scale-up of interventions in many countries improved access across the wealth continuum; in some, these efforts consistently prioritized the poorest. Expansions in control programs generally narrowed coverage gaps between economic strata; gradients persist in countries where growth was slower in the poorest quintile or where baseline inequality was large. Despite progress, malaria is consistently concentrated in the poorest, with the degree of inequality in burden far surpassing that expected given gradients in the distribution of interventions. Economic gradients in the distribution of interventions persist over time, limiting progress toward equity in malaria control. We found that, in countries with large baseline inequality in the distribution of interventions, even a small bias in expansion favoring the least poor yielded large gradients in intervention coverage while pro-poor growth failed to close the gap between the poorest and least poor. We demonstrated that dimensions of disadvantage compound for the poor; a lack of economic gradients in the distribution of malaria services does not translate to equity in coverage nor can it be interpreted to imply equity in distribution of risk or disease burden. Our analysis testifies to the progress made by countries in narrowing economic gradients in malaria interventions and highlights the scope for continued monitoring of programs with respect to equity.

Review of research on malaria*

PubMed Central

Lepes, T.

1974-01-01

This review of progress in malaria research over the periods 1951-1970 and 1970-1973 indicates the results so far achieved in research on the parasite, on the immune response of the host, and on the vector; refers to the means of controlling or eradicating malaria that have been developed in recent years; and outlines the present status of the malaria control and eradication programme. Although impressive results have already been achieved in malaria research, more systematization and concentration of efforts are required if real breakthroughs are to be made. The experience gained in this respect is discussed. PMID:4613499

Vertical and horizontal equity of funding for malaria control: a global multisource funding analysis for 2006-2010.

PubMed

Barrenho, Eliana; Miraldo, Marisa; Shaikh, Mujaheed; Atun, Rifat

2017-01-01

International and domestic funding for malaria is critically important to achieve the Sustainable Development Goals. Its equitable distribution is key in ensuring that the available, scarce, resources are deployed efficiently for improved progress and a sustained response that enables eradication. We used concentration curves and concentration indices to assess inequalities in malaria funding by different donors across countries, measuring both horizontal and vertical equity. Horizontal equity assesses whether funding is distributed in proportion to health needs, whereas vertical equity examines whether unequal economic needs are addressed by appropriately unequal funding. We computed the Health Inequity Index and the Kakwani Index to assess the former and the latter, respectively. We used data from the World Bank, Global Fund, Unicef, President's Malaria Initiative and the Malaria Atlas Project to assess the distribution of funding against need for 94 countries. National gross domestic product per capita was used as a proxy for economic need and 'population-at-risk' for health need. The level and direction of inequity varies across funding sources. Unicef and the President's Malaria Initiative were the most horizontally inequitable ( pro-poor ). Inequity as shown by the Health Inequity Index for Unicef decreased from -0.40 (P<0.05) in 2006 to -0.25 (P<0.10) in 2008, and increased again to -0.58 (P<0.01) in 2009. For President's Malaria Initiative, it increased from -0.19 (P>0.10) in 2006 to -0.38 (P<0.05) in 2008, and decreased to -0.36 (P<0.10) in 2010. Domestic funding was inequitable ( pro-rich ) with inequity increasing from 0.28 (P<0.01) in 2006 to 0.39 (P<0.01) in 2009, and then decreasing to 0.22 (P<0.10) in 2010. Funding from the World Bank and the Global Fund was distributed proportionally according to need. In terms of vertical inequity, all sources were progressive: Unicef and the President's Malaria Initiative were the most progressive with the Kakwani Indices ranging from -0.97 (P<0.01) to -1.29 (P<0.01), and -0.90 (P<0.01) to -1.10 (P<0.01), respectively. Our results suggest that external funding of malaria treatment tends to be allocated to countries with higher health and economic need but not in proportion to their relative health need and income when compared to other countries. While malaria eradication might require funders to disproportionally allocate funding that goes beyond (financial and health) need, our analysis highlights that funders might potentially be targeting in excess certain countries. Regular assessments of need and greater coordination among donors are necessary for equitable resource allocation, to improve and sustain progress with malaria control and elimination.

Advances in nanomedicines for malaria treatment.

PubMed

Aditya, N P; Vathsala, P G; Vieira, V; Murthy, R S R; Souto, E B

2013-12-01

Malaria is an infectious disease that mainly affects children and pregnant women from tropical countries. The mortality rate of people infected with malaria per year is enormous and became a public health concern. The main factor that has contributed to the success of malaria proliferation is the increased number of drug resistant parasites. To counteract this trend, research has been done in nanotechnology and nanomedicine, for the development of new biocompatible systems capable of incorporating drugs, lowering the resistance progress, contributing for diagnosis, control and treatment of malaria by target delivery. In this review, we discussed the main problems associated with the spread of malaria and the most recent developments in nanomedicine for anti-malarial drug delivery. © 2013.

Progress with new malaria vaccines.

PubMed Central

Webster, Daniel; Hill, Adrian V. S.

2003-01-01

Malaria is a parasitic disease of major global health significance that causes an estimated 2.7 million deaths each year. In this review we describe the burden of malaria and discuss the complicated life cycle of Plasmodium falciparum, the parasite responsible for most of the deaths from the disease, before reviewing the evidence that suggests that a malaria vaccine is an attainable goal. Significant advances have recently been made in vaccine science, and we review new vaccine technologies and the evaluation of candidate malaria vaccines in human and animal studies worldwide. Finally, we discuss the prospects for a malaria vaccine and the need for iterative vaccine development as well as potential hurdles to be overcome. PMID:14997243

Biosecurity and Open-Source Biology: The Promise and Peril of Distributed Synthetic Biological Technologies.

PubMed

Evans, Nicholas G; Selgelid, Michael J

2015-08-01

In this article, we raise ethical concerns about the potential misuse of open-source biology (OSB): biological research and development that progresses through an organisational model of radical openness, deskilling, and innovation. We compare this organisational structure to that of the open-source software model, and detail salient ethical implications of this model. We demonstrate that OSB, in virtue of its commitment to openness, may be resistant to governance attempts.

"Malaria and Primary education in Mali: a longitudinal study in the village of Donéguébougou."

PubMed Central

Sissoko, Mahamadou S; Toure, Ousmane B; Kamate, Paul; Berthelemy, Jean-Claude; Doumbo, Ogobara K

2010-01-01

This article assesses the role of malaria and certain social determinants on primary education, especially on educational achievement in Donéguébougou, a small village in a malaria-endemic area near Bamako, Mali. Field data was collected by the authors between November 2007 and June 2008 on 227 schoolchildren living in Donéguébougou. Various malaria indicators and econometric models were used to explain the variation in cognitive abilities, teachers' evaluation scores, school progression and absences. Malaria is the primary cause of school absences. Fixed effects estimates showed that asymptomatic malaria and the presence of falciparum malaria parasites had a direct correlation with educational achievement and cognitive performance. The evidence suggests that the correlation is causal. PMID:20413198

Impact of Malaria in Pregnancy as Latin America Approaches Elimination.

PubMed

Yanow, Stephanie K; Gavina, Kenneth; Gnidehou, Sedami; Maestre, Amanda

2016-05-01

In Latin America, four million pregnancies are at risk of malaria annually, but malaria in pregnancy is largely overlooked. As countries progress toward malaria elimination, targeting reservoirs of transmission is a priority. Pregnant women are an important risk group because they harbor asymptomatic infections and dormant liver stages of Plasmodium vivax that cause relapses. Of significant concern is the discovery that most infections in pregnant women fail to be detected by routine diagnostics. We review here recent findings on malaria in pregnancy within Latin America. We focus on the Amazon basin and Northwest Colombia, areas that harbor the greatest burden of malaria, and propose that more sensitive diagnostics and active surveillance at antenatal clinics will be necessary to eliminate malaria from these final frontiers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Status of vaccine research and development of vaccines for malaria.

PubMed

Birkett, Ashley J

2016-06-03

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Development of a transmission-blocking malaria vaccine: progress, challenges, and the path forward.

PubMed

Nunes, Julia K; Woods, Colleen; Carter, Terrell; Raphael, Theresa; Morin, Merribeth J; Diallo, Diadier; Leboulleux, Didier; Jain, Sanjay; Loucq, Christian; Kaslow, David C; Birkett, Ashley J

2014-09-29

New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

malERA: An updated research agenda for basic science and enabling technologies in malaria elimination and eradication

PubMed Central

2017-01-01

Basic science holds enormous power for revealing the biological mechanisms of disease and, in turn, paving the way toward new, effective interventions. Recognizing this power, the 2011 Research Agenda for Malaria Eradication included key priorities in fundamental research that, if attained, could help accelerate progress toward disease elimination and eradication. The Malaria Eradication Research Agenda (malERA) Consultative Panel on Basic Science and Enabling Technologies reviewed the progress, continuing challenges, and major opportunities for future research. The recommendations come from a literature of published and unpublished materials and the deliberations of the malERA Refresh Consultative Panel. These areas span multiple aspects of the Plasmodium life cycle in both the human host and the Anopheles vector and include critical, unanswered questions about parasite transmission, human infection in the liver, asexual-stage biology, and malaria persistence. We believe an integrated approach encompassing human immunology, parasitology, and entomology, and harnessing new and emerging biomedical technologies offers the best path toward addressing these questions and, ultimately, lowering the worldwide burden of malaria. PMID:29190277

Malaria in the Republic of Djibouti, 1998–2009

PubMed Central

Ollivier, Lénaïck; Nevin, Remington L.; Darar, Houssein Y.; Bougère, Jacques; Saleh, Moustapha; Gidenne, Stéphane; Maslin, Jérôme; Anders, Dietmar; Decam, Christophe; Todesco, Alain; Khaireh, Bouh A.; Ahmed, Ammar A.

2011-01-01

Historically, native populations in the Republic of Djibouti have experienced only low and unstable malaria transmission and intermittent epidemics. In recent years, efforts at malaria control have been aggressively pursued. This study was performed to inform revised malaria prevention recommendations for military service members and international travelers to the country. Laboratory-confirmed cases of malaria documented at large medical facilities and within military and civilian health care systems in the Republic of Djibouti from 1998 to 2009 were reviewed. In recent years, fewer than 5% of febrile cases among the three largest passive surveillance systems were laboratory-confirmed as malaria, and incidence of confirmed malaria was well below 1/1,000 persons/year. As efforts in the Republic of Djibouti progress toward elimination, and in conjunction with continued efforts at surveillance, emphasizing mosquito-avoidance measures and standby emergency treatment will become reasonable recommendations for malaria prevention. PMID:21896822

Malaria in the Republic of Djibouti, 1998-2009.

PubMed

Ollivier, Lénaïck; Nevin, Remington L; Darar, Houssein Y; Bougère, Jacques; Saleh, Moustapha; Gidenne, Stéphane; Maslin, Jérôme; Anders, Dietmar; Decam, Christophe; Todesco, Alain; Khaireh, Bouh A; Ahmed, Ammar A

2011-09-01

Historically, native populations in the Republic of Djibouti have experienced only low and unstable malaria transmission and intermittent epidemics. In recent years, efforts at malaria control have been aggressively pursued. This study was performed to inform revised malaria prevention recommendations for military service members and international travelers to the country. Laboratory-confirmed cases of malaria documented at large medical facilities and within military and civilian health care systems in the Republic of Djibouti from 1998 to 2009 were reviewed. In recent years, fewer than 5% of febrile cases among the three largest passive surveillance systems were laboratory-confirmed as malaria, and incidence of confirmed malaria was well below 1/1,000 persons/year. As efforts in the Republic of Djibouti progress toward elimination, and in conjunction with continued efforts at surveillance, emphasizing mosquito-avoidance measures and standby emergency treatment will become reasonable recommendations for malaria prevention.

[The imminent peril in the law of July the fifth 2011, two years later: the impact on health?].

PubMed

Mondoloni, A; Buard, M; Nargeot, J; Vacheron, M-N

2014-12-01

In 1938, the French government decided to enact a first legislation to enforce admission of the mentally ill to hospitals. Later in 1990, the law took into consideration the evolution of practices with an increase of free admissions and the right to maintain the mentally ill in cities. Three types of psychiatric hospitalization were defined: free, on third party request and for involuntary confinement. A review had theoretically to be conducted every 5 years. In practice this was not the case, probably due to the balance between individual freedom, patient care and public safety always hard to find. However, considering the imperative European harmonization and the fact the Constitutional Council declared a double unconstitutionality of the law, the Act of July 5th was enacted in a hurry during the summer 2011. The Act defines the "rights and the protection of people subject to psychiatric care and methods of coverage". In this document, we will briefly review the context of this law. We will also explore the clinical implications of the very innovative measure: the "péril imminent". We will use the admissions at the Sainte-Anne hospital in Paris in 2010 to 2012. Three major key points were introduced in the law: a judge controls an agreeable release after 15 days and 6 months of continuous hospitalization. The law let the new possibility to provide ambulatory cares under constraints, and these to make an involuntary confinement without a third party request, using the "imminent peril". This law implies the involvement of the judge and the lawyer. This one has to defend a client who needs care, he controls the formal validity of decisions concerning the patient. To provide treatment without consent in "imminent peril" to someone, conditions are requested: these mental disorders make his consent impossible and his mental state requires immediate care with immediate care of constant medical monitoring justifying a full hospitalization or regular medical monitoring for support under another form of full hospitalization (Article L.3212. 1 of the Code of Public Health). Moreover, a demand for care by a third party has also to be impossible to obtain and an imminent peril to the person's health has to exist, supported by a medical certificate from a doctor who does not belong to the patient's psychiatric hospital. The imminent peril would be an immediate danger to the health or life of the patient. What has been the impact of this law adopted in emergency at Sainte-Anne hospital? This psychiatric hospital is in charge of the population in southern Paris, where reside about 655,000 people. This work observes the evolution of the type of hospitalization and care before and after the adoption of the law. We can observe an overall increase in entries under constraints. There is a decrease in admissions for involuntary confinement for the benefit of imminent peril. This imminent peril corresponds to only a small proportion of hospitalizations without consent but are rising between 2011 and 2012, perhaps in part due to a better understanding of the law. But this progression is to monitor to ensure compliance with the restrictive conditions laid down by this law. Also note that the imminent peril may be used at the refusal of the family or entourage to make the demand for care. The number of hospitalizations at the request of a third party with two certificates is down, which is probably due to a change in status of the CPOA, emergency structure within Sainte-Anne, which is no longer seen as extraterritorial. The imminent peril has advantages: it allows access to the care of people isolated and desocialized, of people whose identity is unknown, of pathological travellers. It avoids hospitalization at the request of the representative of the State for social reasons and not for risks to the safety of persons, even when this type of hospitalization is more stigmatizing and often more difficult to remove. It protects the entourage sometimes, when the family is ambivalent or hostile to care, or has been designated as a persecutor. The imminent peril also has disadvantages. One of them is the risk of its misuse to allow rapid hospitalization without taking the time to seek a third party. The imminent danger made when there is an entourage but which refuses to request care can undermine the development work on information about the disease, the need for care and treatment and the importance of the involvement of the entourage in the care plan. The alliance with the patient may be compromised. In some cases, a decision of care by the request of the representative of the State is more appropriate than the "imminent peril". The "imminent peril" may be preferred because of the administrative burden of prefectural measures when patient presents clinical improvement and we would go up to the ambulatory care in a care program. Yet, the use of a symbolic third, carrying authority, can avoid the too direct confrontation with the patient. Do not use it can complicate the management of the patient. Finally, with desocialized patients, imminent peril can facilitate access to care, but not continuity of care. Indeed, for the care program it is necessary to have an address for the patient. Once the crisis is not to develop a plan of care. Finally in some situations of desocialized patients, the imminent peril can promote access to care but not the continuity of care as to the care program it is necessary to have an address for the patient. Once the crisis is past, it is impossible to implement a program of care. The Law of 5 July 2011 marks a change in the practice of psychiatrists. Take into account the fundamental rights of the patient and to harmonize legislation at EU level was necessary. Some measures are designed to promote access to care as the "imminent peril", we now need to be vigilant to ensure that it is not diverted to promote an increase in care under constraints and that psychiatrists remain in an obligation of means and not of result. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Health, human rights, and malaria control: historical background and current challenges.

PubMed

Brentlinger, Paula E

2006-01-01

Malaria, a parasitic infection, causes hundreds of millions of disease episodes and more than a million deaths every year, nearly all of them occurring in the poorer and more vulnerable sectors of the world's developing countries. In spite of the great burden of suffering caused by malaria, the human rights implications of this disease have not been well described. This article summarizes important associations between the spread of malaria and human rights abuses (such as those associated with slavery and armed conflict) and between poverty, socio-economic inequity, and access to malaria-control measures. The author concludes that malaria control merits inclusion as a core element in global strategies to achieve progressive realization of the right to health.

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.

Mapping residual transmission for malaria elimination

PubMed Central

Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

2015-01-01

Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections. In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show ‘malariogenic potential’, a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination. DOI: http://dx.doi.org/10.7554/eLife.09520.001 PMID:26714110

Vertical and horizontal equity of funding for malaria control: a global multisource funding analysis for 2006–2010

PubMed Central

Barrenho, Eliana; Miraldo, Marisa; Shaikh, Mujaheed; Atun, Rifat

2017-01-01

Background International and domestic funding for malaria is critically important to achieve the Sustainable Development Goals. Its equitable distribution is key in ensuring that the available, scarce, resources are deployed efficiently for improved progress and a sustained response that enables eradication. Methods We used concentration curves and concentration indices to assess inequalities in malaria funding by different donors across countries, measuring both horizontal and vertical equity. Horizontal equity assesses whether funding is distributed in proportion to health needs, whereas vertical equity examines whether unequal economic needs are addressed by appropriately unequal funding. We computed the Health Inequity Index and the Kakwani Index to assess the former and the latter, respectively. We used data from the World Bank, Global Fund, Unicef, President’s Malaria Initiative and the Malaria Atlas Project to assess the distribution of funding against need for 94 countries. National gross domestic product per capita was used as a proxy for economic need and ‘population-at-risk’ for health need. Findings The level and direction of inequity varies across funding sources. Unicef and the President’s Malaria Initiative were the most horizontally inequitable (pro-poor). Inequity as shown by the Health Inequity Index for Unicef decreased from −0.40 (P<0.05) in 2006 to −0.25 (P<0.10) in 2008, and increased again to −0.58 (P<0.01) in 2009. For President’s Malaria Initiative, it increased from −0.19 (P>0.10) in 2006 to −0.38 (P<0.05) in 2008, and decreased to −0.36 (P<0.10) in 2010. Domestic funding was inequitable (pro-rich) with inequity increasing from 0.28 (P<0.01) in 2006 to 0.39 (P<0.01) in 2009, and then decreasing to 0.22 (P<0.10) in 2010. Funding from the World Bank and the Global Fund was distributed proportionally according to need. In terms of vertical inequity, all sources were progressive: Unicef and the President’s Malaria Initiative were the most progressive with the Kakwani Indices ranging from −0.97 (P<0.01) to −1.29 (P<0.01), and −0.90 (P<0.01) to −1.10 (P<0.01), respectively. Conclusion Our results suggest that external funding of malaria treatment tends to be allocated to countries with higher health and economic need but not in proportion to their relative health need and income when compared to other countries. While malaria eradication might require funders to disproportionally allocate funding that goes beyond (financial and health) need, our analysis highlights that funders might potentially be targeting in excess certain countries. Regular assessments of need and greater coordination among donors are necessary for equitable resource allocation, to improve and sustain progress with malaria control and elimination. PMID:29333287

Malaria incidence in Myanmar 2005-2014: steady but fragile progress towards elimination.

PubMed

Mu, Thet Thet; Sein, Aye Aye; Kyi, Tint Tint; Min, Myo; Aung, Ne Myo; Anstey, Nicholas M; Kyaw, Myat Phone; Soe, Chit; Kyi, Mar Mar; Hanson, Josh

2016-10-18

There has been an impressive recent reduction in the global incidence of malaria, but the development of artemisinin resistance in the Greater Mekong Region threatens this progress. Increasing artemisinin resistance is particularly important in Myanmar, as it is the country in the Greater Mekong Region with the greatest malaria burden. If malaria is to be eliminated in the region, it is essential to define the spatial and temporal epidemiology of the disease in Myanmar to inform control strategies optimally. Between the years 2005 and 2014 there was an 81.1 % decline in the reported annual incidence of malaria in Myanmar (1341.8 cases per 100,000 population to 253.3 cases per 100,000 population). In the same period, there was a 93.5 % decline in reported annual mortality from malaria (3.79 deaths per 100,000 population to 0.25 deaths per 100,000 population) and a 87.2 % decline in the proportion of hospitalizations due to malaria (7.8 to 1.0 %). Chin State had the highest reported malaria incidence and mortality at the end of the study period, although socio-economic and geographical factors appear a more likely explanation for this finding than artemisinin resistance. The reduced malaria burden coincided with significant upscaling of disease control measures by the national government with support from international partners. These programmes included the training and deployment of over 40,000 community health care workers, the coverage of over 60 % of the at-risk population with insecticide-treated bed nets and significant efforts to improve access to artemesinin-based combination treatment. Beyond these malaria-specific programmes, increased general investment in the health sector, changing population demographics and deforestation are also likely to have contributed to the decline in malaria incidence seen over this time. There has been a dramatic fall in the burden of malaria in Myanmar since 2005. However, with the rise of artemisinin resistance, continued political, financial and scientific commitment is required if the ambitious goal of malaria elimination in the country is to be realized.

Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

PubMed

Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

2008-06-25

Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

Malaria vaccines: past, present and future.

PubMed

von Seidlein, Lorenz; Bejon, Philip

2013-12-01

The currently available malaria control tools have allowed malaria elimination in many regions but there remain many regions where malaria control has made little progress. A safe and protective malaria vaccine would be a huge asset for malaria control. Despite the many challenges, efforts continue to design and evaluate malaria vaccine candidates. These candidates target different stages in the life cycle of Plasmodia. The most advanced vaccine candidates target the pre-erythrocytic stages in the life cycle of the parasite and include RTS,S/AS01, which has progressed through clinical development to the stage that it may be licensed in 2015. Attenuated whole-parasite vaccine candidates are highly protective, but there are challenges to manufacture and to administration. Cellular immunity is targeted by the prime-boost approach. Priming vectors trigger only modest responses but these are focused on the recombinant antigen. Boosting vectors trigger strong but broad non-specific responses. The heterologous sequence produces strong immunological responses to the recombinant antigen. Candidates that target the blood stages of the parasite have to result in an immune response that is more effective than the response to an infection to abort or control the infection of merozoites and hence disease. Finally, the sexual stages of the parasite offer another target for vaccine development, which would prevent the transmission of malaria. Today it seems unlikely that any candidate targeting a single antigen will provide complete protection against an organism of the complexity of Plasmodium. A systematic search for vaccine targets and combinations of antigens may be a more promising approach.

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.

Low uptake of preventive interventions among malaria cases in Swaziland: towards malaria elimination

PubMed Central

Dlamini, N.; Zulu, Z.; Dlamini, S.; Kunene, S.; Sikhondze, W.; Owiti, P.; Geoffroy, E.; Zachariah, R.; Mengestu, T. K.

2018-01-01

Settings: Swaziland is striving to achieve sustainable malaria elimination. Three preventive interventions are vital for reaching this goal: 1) effective household utilisation of long-lasting insecticide nets (LLINs), 2) indoor residual spraying (IRS), and 3) provision of chemoprophylaxis for those travelling to malaria-endemic areas. Objectives: To assess the uptake of preventive intervention among confirmed malaria cases. Design: A longitudinal study using nation-wide programme data from 2010 to 2015. Data on malaria cases from health facilities were sourced from the Malaria Surveillance Database System. Results: Of a total 2568 confirmed malaria cases in Swaziland, 2034 (79%) had complete data on case investigations and were included in the analysis. Of 341 (17%) individuals who owned LLINs, 169 (8%) used them; 338 (17%) had IRS and 314 (15%) slept in sprayed structures. Of 1403 travellers to areas at high malaria risk, 59 (4%) used any form of malaria prevention, including chemoprophylaxis. Conclusion: The uptake of all three key malaria prevention interventions is low, and could threaten the progress made thus far toward malaria elimination. Efforts to improve this situation, including qualitative research to understand the reasons for low uptake, are urgently needed. PMID:29713591

New insight-guided approaches to detect, cure, prevent and eliminate malaria.

PubMed

Kumar, Sushil; Kumari, Renu; Pandey, Richa

2015-05-01

New challenges posed by the development of resistance against artemisinin-based combination therapies (ACTs) as well as previous first-line therapies, and the continuing absence of vaccine, have given impetus to research in all areas of malaria control. This review portrays the ongoing progress in several directions of malaria research. The variants of RTS,S and apical membrane antigen 1 (AMA1) are being developed and test adapted as multicomponent and multistage malaria control vaccines, while many other vaccine candidates and methodologies to produce antigens are under experimentation. To track and prevent the spread of artemisinin resistance from Southeast Asia to other parts of the world, rolling circle-enhanced enzyme activity detection (REEAD), a time- and cost-effective malaria diagnosis in field conditions, and a DNA marker associated with artemisinin resistance have become available. Novel mosquito repellents and mosquito trapping and killing techniques much more effective than the prevalent ones are undergoing field testing. Mosquito lines stably infected with their symbiotic wild-type or genetically engineered bacteria that kill sympatric malaria parasites are being constructed and field tested for stopping malaria transmission. A complementary approach being pursued is the addition of ivermectin-like drug molecules to ACTs to cure malaria and kill mosquitoes. Experiments are in progress to eradicate malaria mosquito by making it genetically male sterile. High-throughput screening procedures are being developed and used to discover molecules that possess long in vivo half life and are active against liver and blood stages for the fast cure of malaria symptoms caused by simple or relapsing and drug-sensitive and drug-resistant types of varied malaria parasites, can stop gametocytogenesis and sporogony and could be given in one dose. Target-based antimalarial drug designing has begun. Some of the putative next-generation antimalarials that possess in their scaffold structure several of the desired properties of malaria cure and control are exemplified by OZ439, NITD609, ELQ300 and tafenoquine that are already undergoing clinical trials, and decoquinate, usnic acid, torin-2, ferroquine, WEHI-916, MMV396749 and benzothiophene-type N-myristoyltransferase (NMT) inhibitors, which are candidates for future clinical usage. Among these, NITD609, ELQ300, decoquinate, usnic acid, torin-2 and NMT inhibitors not only cure simple malaria and are prophylactic against simple malaria, but they also cure relapsing malaria.

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.

Rapid diagnostic tests for malaria

PubMed Central

Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

2015-01-01

Abstract Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID:26668438

Emerging roles for hemostatic dysfunction in malaria pathogenesis.

PubMed

O'Sullivan, Jamie M; Preston, Roger J S; O'Regan, Niamh; O'Donnell, James S

2016-05-12

Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum-infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance. © 2016 by The American Society of Hematology.

Static and dynamic light scattering of healthy and malaria-parasite invaded red blood cells

NASA Astrophysics Data System (ADS)

Park, Yongkeun; Diez-Silva, Monica; Fu, Dan; Popescu, Gabriel; Choi, Wonshik; Barman, Ishan; Suresh, Subra; Feld, Michael S.

2010-03-01

We present the light scattering of individual Plasmodium falciparum-parasitized human red blood cells (Pf-RBCs), and demonstrate progressive alterations to the scattering signal arising from the development of malaria-inducing parasites. By selectively imaging the electric fields using quantitative phase microscopy and a Fourier transform light scattering technique, we calculate the light scattering maps of individual Pf-RBCs. We show that the onset and progression of pathological states of the Pf-RBCs can be clearly identified by the static scattering maps. Progressive changes to the biophysical properties of the Pf-RBC membrane are captured from dynamic light scattering.

Assessing causal mechanistic interactions: a peril ratio index of synergy based on multiplicativity.

PubMed

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the 'peril'. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the 'peril ratio index of synergy based on multiplicativity' (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of 'relative excess risk due to interaction'. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines.

PubMed

Fowkes, Freya J I; Simpson, Julie A; Beeson, James G

2013-10-30

Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links.

PubMed

Simon, G G

2016-01-01

The neglected tropical diseases (NTDs) are the most common infections of humans in Sub-Saharan Africa. Virtually all of the population living below the World Bank poverty figure is affected by one or more NTDs. New evidence indicates a high degree of geographic overlap between the highest-prevalence NTDs (soil-transmitted helminths, schistosomiasis, onchocerciasis, lymphatic filariasis, and trachoma) and malaria and HIV, exhibiting a high degree of co-infection. Recent research suggests that NTDs can affect HIV and AIDS, tuberculosis (TB), and malaria disease progression. A combination of immunological, epidemiological, and clinical factors can contribute to these interactions and add to a worsening prognosis for people affected by HIV/AIDS, TB, and malaria. Together these results point to the impacts of the highest-prevalence NTDs on the health outcomes of malaria, HIV/AIDS, and TB and present new opportunities to design innovative public health interventions and strategies for these 'big three' diseases. This analysis describes the current findings of research and what research is still needed to strengthen the knowledge base of the impacts NTDs have on the big three. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Current and cumulative malaria infections in a setting embarking on elimination: Amhara, Ethiopia.

PubMed

Yalew, Woyneshet G; Pal, Sampa; Bansil, Pooja; Dabbs, Rebecca; Tetteh, Kevin; Guinovart, Caterina; Kalnoky, Michael; Serda, Belendia A; Tesfay, Berhane H; Beyene, Belay B; Seneviratne, Catherine; Littrell, Megan; Yokobe, Lindsay; Noland, Gregory S; Domingo, Gonzalo J; Getachew, Asefaw; Drakeley, Chris; Steketee, Richard W

2017-06-08

Since 2005, Ethiopia has aggressively scaled up malaria prevention and case management. As a result, the number of malaria cases and deaths has significantly declined. In order to track progress towards the elimination of malaria in Amhara Region, coverage of malaria control tools and current malaria transmission need to be documented. A cross-sectional household survey oversampling children under 5 years of age was conducted during the dry season in 2013. A bivalent rapid diagnostic test (RDT) detecting both Plasmodium falciparum and Plasmodium vivax and serology assays using merozoite antigens from both these species were used to assess the prevalence of malaria infections and exposure to malaria parasites in 16 woredas (districts) in Amhara Region. 7878 participants were included, with a mean age of 16.8 years (range 0.5-102.8 years) and 42.0% being children under 5 years of age. The age-adjusted RDT-positivity for P. falciparum and P. vivax infection was 1.5 and 0.4%, respectively, of which 0.05% presented as co-infections. Overall age-adjusted seroprevalence was 30.0% for P. falciparum, 21.8% for P. vivax, and seroprevalence for any malaria species was 39.4%. The prevalence of RDT-positive infections varied by woreda, ranging from 0.0 to 8.3% and by altitude with rates of 3.2, 0.7, and 0.4% at under 2000, 2000-2500, and >2500 m, respectively. Serological analysis showed heterogeneity in transmission intensity by area and altitude and evidence for a change in the force of infection in the mid-2000s. Current and historic malaria transmission across Amhara Region show substantial variation by age and altitude with some settings showing very low or near-zero transmission. Plasmodium vivax infections appear to be lower but relatively more stable across geography and altitude, while P. falciparum is the dominant infection in the higher transmission, low-altitude areas. Age-dependent seroprevalence analyses indicates a drop in transmission occurred in the mid-2000s, coinciding with malaria control scale-up efforts. As malaria parasitaemia rates get very low with elimination efforts, serological evaluation may help track progress to elimination.

Malaria Control and Elimination in Sri Lanka: Documenting Progress and Success Factors in a Conflict Setting

PubMed Central

Abeyasinghe, Rabindra R.; Galappaththy, Gawrie N. L.; Smith Gueye, Cara; Kahn, James G.; Feachem, Richard G. A.

2012-01-01

Background Sri Lanka has a long history of malaria control, and over the past decade has had dramatic declines in cases amid a national conflict. A case study of Sri Lanka's malaria programme was conducted to characterize the programme and explain recent progress. Methods The case study employed qualitative and quantitative methods. Data were collected from published and grey literature, district-level and national records, and thirty-three key informant interviews. Expenditures in two districts for two years – 2004 and 2009 – were compiled. Findings Malaria incidence in Sri Lanka has declined by 99.9% since 1999. During this time, there were increases in the proportion of malaria infections due to Plasmodium vivax, and the proportion of infections occurring in adult males. Indoor residual spraying and distribution of long-lasting insecticide-treated nets have likely contributed to the low transmission. Entomological surveillance was maintained. A strong passive case detection system captures infections and active case detection was introduced. When comparing conflict and non-conflict districts, vector control and surveillance measures were maintained in conflict areas, often with higher coverage reported in conflict districts. One of two districts in the study reported a 48% decline in malaria programme expenditure per person at risk from 2004 to 2009. The other district had stable malaria spending. Conclusions/Significance Malaria is now at low levels in Sri Lanka – 124 indigenous cases were found in 2011. The majority of infections occur in adult males and are due to P. vivax. Evidence-driven policy and an ability to adapt to new circumstances contributed to this decline. Malaria interventions were maintained in the conflict districts despite an ongoing war. Sri Lanka has set a goal of eliminating malaria by the end of 2014. Early identification and treatment of infections, especially imported ones, together with effective surveillance and response, will be critical to achieving this goal. PMID:22952642

The Malaria Transition on the Arabian Peninsula: Progress toward a Malaria-Free Region between 1960–2010

PubMed Central

Snow, Robert W.; Amratia, Punam; Zamani, Ghasem; Mundia, Clara W.; Noor, Abdisalan M.; Memish, Ziad A.; Al Zahrani, Mohammad H.; Al Jasari, Adel; Fikri, Mahmoud; Atta, Hoda

2014-01-01

The transmission of malaria across the Arabian Peninsula is governed by the diversity of dominant vectors and extreme aridity. It is likely that where malaria transmission was historically possible it was intense and led to a high disease burden. Here, we review the speed of elimination, approaches taken, define the shrinking map of risk since 1960 and discuss the threats posed to a malaria-free Arabian Peninsula using the archive material, case data and published works. From as early as the 1940s, attempts were made to eliminate malaria on the peninsula but were met with varying degrees of success through to the 1970s; however, these did result in a shrinking of the margins of malaria transmission across the peninsula. Epidemics in the 1990s galvanised national malaria control programmes to reinvigorate control efforts. Before the launch of the recent global ambition for malaria eradication, countries on the Arabian Peninsula launched a collaborative malaria-free initiative in 2005. This initiative led a further shrinking of the malaria risk map and today locally acquired clinical cases of malaria are reported only in Saudi Arabia and Yemen, with the latter contributing to over 98% of the clinical burden. PMID:23548086

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.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

PubMed Central

2013-01-01

Background Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. Discussion The Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Conclusions Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine. PMID:24228861

Immune thrombocytopenia associated with malaria: a case report.

PubMed

Miloudi, Mouhcine; Sbaai, Mohammed; Fatihi, Jamal

2017-10-01

The association of immune thrombocytopenic with malaria is a rare event. We describ the case of a young soldier who, after returning from Central Africa, presented a fever associated with petechial purpura and gingivorrhagia, hemogram showed deep thrombocytopenia and macrocytic normochrome anemia, thick peripheral blood smears confirmed the diagnosis of Plasmodium falciparum malaria, the patient was treated with quinine, but deep thrombocytopenia and hemorrhagic manifestations persisted, the patient then underwent corticosteroid therapy, with favorable evolution and progressive normalization of platelets.

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.

NIAID meeting report: improving malaria vaccine strategies through the application of immunological principles.

PubMed

Mo, Annie X Y; Augustine, Alison Deckhut

2014-02-26

A highly efficacious vaccine to prevent malaria infection or clinical disease is still far from reality despite several decades of intensive effort and a growing global commitment in malaria vaccine development. Further understanding of the mechanisms required for induction of effective host immune responses and maintenance of long-term protective immunity is needed to facilitate rational approaches for vaccine design and evaluation. The National Institute of Allergy and Infectious Diseases (NIAID) conducted a workshop on June 18-19, 2012 with experts in the fields of malaria vaccine development, malaria immunology, and basic immunology to address issues associated with improving our current understanding of malaria vaccine immunity. This report summarizes the discussion and major recommendations generated by the workshop participants regarding the application of recent advances in basic immunology and state-of-the-art immunological tools to improve progress and help address current challenges and knowledge gaps in malaria vaccine development. Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

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.

Malaria in the Traveller: How to Manage Before Departure and Evaluate Upon Return

PubMed Central

Hahn, William O.; Pottinger, Paul S.

2015-01-01

Malaria is the clinical syndrome when a patient experiences symptoms in response to infection with one of several strains of the Plasmodium parasite. This manuscript is intended for healthcare providers to become familiar with some of the basics of care of the patient who is travelling to or returning from an area with ongoing malaria transmission. The specific focus of is on patients from non-endemic areas who plan on travel for a finite period to an area where malaria is endemic. Emphasis will be on placed on prevention and diagnosis. Risk factors for malaria acquisition will be discussed. We will have an evidence-based discussion of personal protective equipment, choice of chemoprophylactic agent, and pre-departure counseling that includes a discussion of malaria in the immunosuppressed patient. We will also review when to suspect malaria in a patient returning from an endemic area and the importance of rapid diagnostic tests in the diagnostic investigations. Finally, we will discuss how malaria is a sepsis syndrome that can progress quickly in populations with no pre-existing immunity. PMID:26900114

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.

Community case management of malaria using ACT and RDT in two districts in Zambia: achieving high adherence to test results using community health workers

PubMed Central

2011-01-01

Background Access to prompt and effective treatment is a cornerstone of the current malaria control strategy. Delays in starting appropriate treatment is a major contributor to malaria mortality. WHO recommends home management of malaria using artemisininbased combination therapy (ACT) and Rapid Diagnostic tests (RDTs) as one of the strategies for improving access to prompt and efective malaria case management. Methods A prospective evaluation of the effectiveness of using community health workers (CHWs) as delivery points for ACT and RDTs in the home management of malaria in two districts in Zambia. Results CHWs were able to manage malaria fevers by correctly interpreting RDT results and appropriately prescribing antimalarials. All severe malaria cases and febrile non-malaria fevers were referred to a health facility for further management. There were variations in malaria prevalence between the two districts and among the villages in each district. 100% and 99.4% of the patients with a negative RDT result were not prescribed an antimalarial in the two districts respectively. No cases progressed to severe malaria and no deaths were recorded during the study period. Community perceptions were positive. Conclusion CHWs are effective delivery points for prompt and effective malaria case management at community level. Adherence to test results is the best ever reported in Zambia. Further areas of implementation research are discussed. PMID:21651827

Progress towards malaria elimination in Zimbabwe with special reference to the period 2003-2015.

PubMed

Sande, Shadreck; Zimba, Moses; Mberikunashe, Joseph; Tangwena, Andrew; Chimusoro, Anderson

2017-07-24

An intensive effort to control malaria in Zimbabwe has produced dramatic reductions in the burden of the disease over the past 13 years. The successes have prompted the Zimbabwe's National Malaria Control Programme to commit to elimination of malaria. It is critical to analyse the changes in the morbidity trends based on surveillance data, and scrutinize reorientation to strategies for elimination. This is a retrospective study of available Ministry of Health surveillance data and programme reports, mostly from 2003 to 2015. Malaria epidemiological data were drawn from the National Health Information System database. Data on available resources, malaria control strategies, morbidity and mortality trends were analysed, and opportunities for Zimbabwe malaria elimination agenda was perused. With strong government commitment and partner support, the financial gap for malaria programming shrank by 91.4% from about US$13 million in 2012 to US$1 million in 2015. Vector control comprises indoor residual house spraying (IRS) and long-lasting insecticidal nets, and spray coverage increased from 28% in 2003 to 95% in 2015. Population protected by IRS increased also from 20 to 96% for the same period. In 2009, diagnostics improved from clinical to parasitological confirmation either by rapid diagnostic tests or microscopy. Artemisinin-based combination therapy was used to treat malaria following chloroquine resistance in 2000, and sulfadoxine-pyrimethamine in 2004. In 2003, there were 155 malaria cases per 1000 populations reported from all health facilities throughout the country. The following decade witnessed a substantial decline in cases to only 22 per 1000 populations in 2012. A resurgence was reported in 2013 (29/1000) and 2014 (39/1000), thereafter morbidity declined to 29 cases per 1000 populations, only to the same level as in 2013. Overall, morbidity declined by 81% from 2003 to 2015. Inpatient malaria deaths per 100,000 populations doubled in 4 years, from 2/100,000 to 4/100,000 populations in 2012-2015 respectively. Twenty of the 47 moderate to high burdened districts were upgraded from control to malaria pre-elimination between 2012 and 2015. A significant progress to reduce malaria transmission in Zimbabwe has been made. While a great potential and opportunities to eliminate malaria in the country exist, elimination is not a business as usual approach. Instead, it needs an improved, systematic and new programmatic strategy supported strongly by political will, sustained funding, good leadership, community engagement, and a strong monitoring and evaluation system all year round until the cessation of local transmission.

Continuous multistep synthesis of perillic acid from limonene by catalytic biofilms under segmented flow.

PubMed

Willrodt, Christian; Halan, Babu; Karthaus, Lisa; Rehdorf, Jessica; Julsing, Mattijs K; Buehler, Katja; Schmid, Andreas

2017-02-01

The efficiency of biocatalytic reactions involving industrially interesting reactants is often constrained by toxification of the applied biocatalyst. Here, we evaluated the combination of biologically and technologically inspired strategies to overcome toxicity-related issues during the multistep oxyfunctionalization of (R)-(+)-limonene to (R)-(+)-perillic acid. Pseudomonas putida GS1 catalyzing selective limonene oxidation via the p-cymene degradation pathway and recombinant Pseudomonas taiwanensis VLB120 were evaluated for continuous perillic acid production. A tubular segmented-flow biofilm reactor was used in order to relieve oxygen limitations and to enable membrane mediated substrate supply as well as efficient in situ product removal. Both P. putida GS1 and P. taiwanensis VLB120 developed a catalytic biofilm in this system. The productivity of wild-type P. putida GS1 encoding the enzymes for limonene bioconversion was highly dependent on the carbon source and reached 34 g L tube -1  day -1 when glycerol was supplied. More than 10-fold lower productivities were reached irrespective of the applied carbon source when the recombinant P. taiwanensis VLB120 harboring p-cymene monooxygenase and p-cumic alcohol dehydrogenase was used as biocatalyst. The technical applicability for preparative perillic acid synthesis in the applied system was verified by purification of perillic acid from the outlet stream using an anion exchanger resin. This concept enabled the multistep production of perillic acid and which might be transferred to other reactions involving volatile reactants and toxic end-products. Biotechnol. Bioeng. 2017;114: 281-290. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Changes in the pattern of mortality following the eradication of hyperendemic malaria from a highly susceptible community

PubMed Central

Giglioli, George

1972-01-01

The population of the sugar estates of the Guyana coastlands was 110 000 in 1966; malaria was eradicated between 1945 and 1951. A study has been made of the pattern of mortality before and after malaria eradication, during the 30-year period from 1937 to 1966. The decline in general mortality has greatly exceeded the fall in mortality specifically related to malaria and has continued for almost 10 years after registration of the last death from malaria. In infants, mortality has been reduced, mainly through a decline in the number of deaths from prematurity and congenital debility that were due mainly to malaria and its sequelae in the expectant mother. In children (1-14 years of age) the decline has resulted from the disappearance of malaria and chronic nephritis as causes of death. In adults, mortality has fallen mainly through the progressive decline in the incidence of a number of diseases not overtly related to malaria: acute and chronic respiratory diseases, chronic nephritis, and the anaemias. Cardiovascular diseases, on the contrary, have shown a tendency to increase since malaria was brought under control. PMID:4624339

Supplementation with multivitamins and vitamin A and incidence of malaria among HIV-infected Tanzanian women.

PubMed

Olofin, Ibironke O; Spiegelman, Donna; Aboud, Said; Duggan, Christopher; Danaei, Goodarz; Fawzi, Wafaie W

2014-12-01

HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age. HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites. Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study. Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria.

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

Malaria treatment using novel nano-based drug delivery systems.

PubMed

Baruah, Uday Krishna; Gowthamarajan, Kuppusamy; Vanka, Ravisankar; Karri, Veera Venkata Satyanarayana Reddy; Selvaraj, Kousalya; Jojo, Gifty M

2017-08-01

We reside in an era of technological innovation and advancement despite which infectious diseases like malaria remain to be one of the greatest threats to the humans. Mortality rate caused by malaria disease is a huge concern in the twenty-first century. Multiple drug resistance and nonspecific drug targeting of the most widely used drugs are the main reasons/drawbacks behind the failure in malarial therapy. Dose-related toxicity because of high doses is also a major concern. Therefore, to overcome these problems nano-based drug delivery systems are being developed to facilitate site-specific or target-based drug delivery and hence minimizing the development of resistance progress and dose-dependent toxicity issues. In this review, we discuss about the shortcomings in treating malaria and how nano-based drug delivery systems can help in curtailing the infectious disease malaria.

Strategic roles for behaviour change communication in a changing malaria landscape.

PubMed

Koenker, Hannah; Keating, Joseph; Alilio, Martin; Acosta, Angela; Lynch, Matthew; Nafo-Traore, Fatoumata

2014-01-02

Strong evidence suggests that quality strategic behaviour change communication (BCC) can improve malaria prevention and treatment behaviours. As progress is made towards malaria elimination, BCC becomes an even more important tool. BCC can be used 1) to reach populations who remain at risk as transmission dynamics change (e.g. mobile populations), 2) to facilitate identification of people with asymptomatic infections and their compliance with treatment, 3) to inform communities of the optimal timing of malaria control interventions, and 4) to explain changing diagnostic concerns (e.g. increasing false negatives as parasite density and multiplicity of infections fall) and treatment guidelines. The purpose of this commentary is to highlight the benefits and value for money that BCC brings to all aspects of malaria control, and to discuss areas of operations research needed as transmission dynamics change.

Strategic roles for behaviour change communication in a changing malaria landscape

PubMed Central

2014-01-01

Strong evidence suggests that quality strategic behaviour change communication (BCC) can improve malaria prevention and treatment behaviours. As progress is made towards malaria elimination, BCC becomes an even more important tool. BCC can be used 1) to reach populations who remain at risk as transmission dynamics change (e.g. mobile populations), 2) to facilitate identification of people with asymptomatic infections and their compliance with treatment, 3) to inform communities of the optimal timing of malaria control interventions, and 4) to explain changing diagnostic concerns (e.g. increasing false negatives as parasite density and multiplicity of infections fall) and treatment guidelines. The purpose of this commentary is to highlight the benefits and value for money that BCC brings to all aspects of malaria control, and to discuss areas of operations research needed as transmission dynamics change. PMID:24383426

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

PubMed

Greenwood, Brian; Dicko, Alassane; Sagara, Issaka; Zongo, Issaka; Tinto, Halidou; Cairns, Matthew; Kuepfer, Irene; Milligan, Paul; Ouedraogo, Jean-Bosco; Doumbo, Ogobara; Chandramohan, Daniel

2017-05-02

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.

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

The Promises and Perils of Clinical Chemoprevention: 1980–2030

Cancer.gov

Frank L. Meyskens, Jr, MD, Professor of Medicine and Biological Chemistry; Director, Chao Family Comprehensive Cancer Center; and Senior Associate Dean of Health Sciences, University of California, Irvine, CA, presented "The Promises and Perils of Clinical Chemoprevention: 1980–2030".

Standards, Accountability, and School Reform: Perils and Pitfalls.

ERIC Educational Resources Information Center

Sheldon, Kennon M.; Biddle, Bruce J.

1998-01-01

Examines current debates about educational standards, accountability, and school reform from the perspective of Deci and Ryan's Self-Determination Theory. Research reveals various perils associated with rigid standards, narrow accountability, and tangible sanctions that can debase student and teacher motivation and performance. Alternative…

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

Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

PubMed

Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

2017-08-01

An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

Plasmodium vivax malaria vaccines: why are we where we are?

PubMed

Reyes-Sandoval, Arturo; Bachmann, Martin F

2013-12-01

Malaria is one of the few diseases in which morbidity is still measured in hundreds of millions of cases every year. Plasmodium vivax and Plasmodium falciparum are responsible for nearly all the malaria cases in the world and despite difficulties in obtaining an exact number, estimates indicate an astonishing 349-552 million clinical cases of malaria due to P. falciparum in 2007 and between 132-391 million clinical episodes due to P. vivax in 2009. It is becoming evident that eradication of malaria will be an arduous task and P. vivax will be one of the most difficult species to eliminate and perhaps become the last standing malaria parasite. Indeed, in countries that succeed in decreasing the disease burden, nearly all the remaining malaria cases are caused by P. vivax. Such resilience is mainly due to the sophisticated mechanism that the parasite has evolved to remain dormant for months or years forming hypnozoites, a small structure in the liver that will be a major hurdle in the efforts toward malaria eradication. Furthermore, while clinical trials of vaccines against P. falciparum are making fast progress, a very different picture is seen with P. vivax, where only few candidates are currently active in clinical trials.

Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach

PubMed Central

Wassmer, Samuel C.; Taylor, Terrie E.; Rathod, Pradipsinh K.; Mishra, Saroj K.; Mohanty, Sanjib; Arevalo-Herrera, Myriam; Duraisingh, Manoj T.; Smith, Joseph D.

2015-01-01

More than a century after the discovery of Plasmodium spp. parasites, the pathogenesis of severe malaria is still not well understood. The majority of malaria cases are caused by Plasmodium falciparum and Plasmodium vivax, which differ in virulence, red blood cell tropism, cytoadhesion of infected erythrocytes, and dormant liver hypnozoite stages. Cerebral malaria coma is one of the most severe manifestations of P. falciparum infection. Insights into its complex pathophysiology are emerging through a combination of autopsy, neuroimaging, parasite binding, and endothelial characterizations. Nevertheless, important questions remain regarding why some patients develop life-threatening conditions while the majority of P. falciparum-infected individuals do not, and why clinical presentations differ between children and adults. For P. vivax, there is renewed recognition of severe malaria, but an understanding of the factors influencing disease severity is limited and remains an important research topic. Shedding light on the underlying disease mechanisms will be necessary to implement effective diagnostic tools for identifying and classifying severe malaria syndromes and developing new therapeutic approaches for severe disease. This review highlights progress and outstanding questions in severe malaria pathophysiology and summarizes key areas of pathogenesis research within the International Centers of Excellence for Malaria Research program. PMID:26259939

Computer Vision Malaria Diagnostic Systems-Progress and Prospects.

PubMed

Pollak, Joseph Joel; Houri-Yafin, Arnon; Salpeter, Seth J

2017-01-01

Accurate malaria diagnosis is critical to prevent malaria fatalities, curb overuse of antimalarial drugs, and promote appropriate management of other causes of fever. While several diagnostic tests exist, the need for a rapid and highly accurate malaria assay remains. Microscopy and rapid diagnostic tests are the main diagnostic modalities available, yet they can demonstrate poor performance and accuracy. Automated microscopy platforms have the potential to significantly improve and standardize malaria diagnosis. Based on image recognition and machine learning algorithms, these systems maintain the benefits of light microscopy and provide improvements such as quicker scanning time, greater scanning area, and increased consistency brought by automation. While these applications have been in development for over a decade, recently several commercial platforms have emerged. In this review, we discuss the most advanced computer vision malaria diagnostic technologies and investigate several of their features which are central to field use. Additionally, we discuss the technological and policy barriers to implementing these technologies in low-resource settings world-wide.

Drug targets for resistant malaria: Historic to future perspectives.

PubMed

Kumar, Sahil; Bhardwaj, T R; Prasad, D N; Singh, Rajesh K

2018-05-11

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980-2017.

PubMed

Burton, Robert A; Chévez, José Eduardo Romero; Sauerbrey, Mauricio; Guinovart, Caterina; Hartley, Angela; Kirkwood, Geoffrey; Boslego, Matthew; Gavidia, Mirna Elizabeth; Alemán Escobar, Jaime Enrique; Turkel, Rachel; Steketee, Richard W; Slutsker, Laurence; Schneider, Kammerle; Kent Campbell, Carlos C

2018-05-14

A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum . A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators-distributed throughout the country by strata and informed via the national surveillance system-enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador's experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.

Mapping malaria risk and vulnerability in the United Republic of Tanzania: a spatial explicit model.

PubMed

Hagenlocher, Michael; Castro, Marcia C

2015-01-01

Outbreaks of vector-borne diseases (VBDs) impose a heavy burden on vulnerable populations. Despite recent progress in eradication and control, malaria remains the most prevalent VBD. Integrative approaches that take into account environmental, socioeconomic, demographic, biological, cultural, and political factors contributing to malaria risk and vulnerability are needed to effectively reduce malaria burden. Although the focus on malaria risk has increasingly gained ground, little emphasis has been given to develop quantitative methods for assessing malaria risk including malaria vulnerability in a spatial explicit manner. Building on a conceptual risk and vulnerability framework, we propose a spatial explicit approach for modeling relative levels of malaria risk - as a function of hazard, exposure, and vulnerability - in the United Republic of Tanzania. A logistic regression model was employed to identify a final set of risk factors and their contribution to malaria endemicity based on multidisciplinary geospatial information. We utilized a Geographic Information System for the construction and visualization of a malaria vulnerability index and its integration into a spatially explicit malaria risk map. The spatial pattern of malaria risk was very heterogeneous across the country. Malaria risk was higher in Mainland areas than in Zanzibar, which is a result of differences in both malaria entomological inoculation rate and prevailing vulnerabilities. Areas of high malaria risk were identified in the southeastern part of the country, as well as in two distinct "hotspots" in the northwestern part of the country bordering Lake Victoria, while concentrations of high malaria vulnerability seem to occur in the northwestern, western, and southeastern parts of the mainland. Results were visualized using both 10×10 km(2) grids and subnational administrative units. The presented approach makes an important contribution toward a decision support tool. By decomposing malaria risk into its components, the approach offers evidence on which factors could be targeted for reducing malaria risk and vulnerability to the disease. Ultimately, results offer relevant information for place-based intervention planning and more effective spatial allocation of resources.

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.

Bioconversion of R-(+)-limonene to perillic acid by the yeast Yarrowia lipolytica

PubMed Central

Ferrara, Maria Antonieta; Almeida, Débora S.; Siani, Antonio C.; Lucchetti, Leonardo; Lacerda, Paulo S.B.; Freitas, André; Tappin, Marcelo R.R.; Bon, Elba P.S.

2013-01-01

Perillyl derivatives are increasingly important due to their flavouring and antimicrobial properties as well as their potential as anticancer agents. These terpenoid species, which are present in limited amounts in plants, may be obtained via bioconversion of selected monoterpene hydrocarbons. In this study, seventeen yeast strains were screened for their ability to oxidize the exocyclic methyl group in the p-menthene moiety of limonene into perillic acid. Of the yeast tested, the highest efficiency was observed for Yarrowia lipolytica ATCC 18942. The conversion of R (+)-limonene by Y. lipolytica was evaluated by varying the pH (3 to 8) and the temperature (25 to 30 °C) in a reaction medium containing 0.5% v/v limonene and 10 g/L of stationary phase cells (dry weight). The best results, corresponding to 564 mg/L of perillic acid, were obtained in buffered medium at pH 7.1 that was incubated at 25 °C for 48 h. The stepwise addition of limonene increased the perillic acid concentration by over 50%, reaching 855 mg/L, whereas the addition of glucose or surfactant to the reaction medium did not improve the bioconversion process. The use of Y. lipolytica showed promise for ease of further downstream processing, as perillic acid was the sole oxidised product of the bioconversion reaction. Moreover, bioprocesses using safe and easy to cultivate yeast cells have been favoured in industry. PMID:24688495

Averting a malaria disaster: will insecticide resistance derail malaria control?

PubMed

Hemingway, Janet; Ranson, Hilary; Magill, Alan; Kolaczinski, Jan; Fornadel, Christen; Gimnig, John; Coetzee, Maureen; Simard, Frederic; Roch, Dabiré K; Hinzoumbe, Clément Kerah; Pickett, John; Schellenberg, David; Gething, Peter; Hoppé, Mark; Hamon, Nicholas

2016-04-23

World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Malaria vaccines and the new malaria agenda.

PubMed

Greenwood, B M; Targett, G A T

2011-11-01

The development of an effective malaria vaccine has taken many decades, but there is now a good chance that the first malaria vaccine will be licensed within the next few years. However, this vaccine (RTS,S) will not be fully effective, and more efficacious, second-generation vaccines will be needed. Good progress is being made in the development of potential vaccines directed at each of the three main stages of the parasite's life cycle, with a variety of different approaches, but many challenges remain, e.g. overcoming the problem of polymorphism in many key parasite antigens. It is likely vaccines that are effective enough to block transmission, and thus contribute to increasing drives towards malaria elimination, will need to contain antigens from different stages of the parasite's life cycle. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Malaria. A renewed assault on an old and deadly foe.

PubMed

Marshall, E

2000-10-20

After languishing for decades in the scientific backwaters, malaria research is suddenly being swept into the mainstream. Money is beginning to pour in from international finance and aid organizations, giving researchers who have been doggedly pursuing an intractable foe with limited resources the means to follow new leads. But on the ground, the disease is unyielding, and the current weapons are losing their effectiveness. In a series of related stories, Science explores the World Health Organization's crusade that aims to cut malaria mortality in half over the next 10 years, conditions on the front lines of clinical research in Africa, the challenges that have slowed development of a so-far elusive vaccine, renewed interest in a Chinese herbal remedy that could aid in the fight against drug-resistant malaria, progress in attacking the Plasmodium parasite through its genome, and the dream of building a malaria-proof mosquito.

The March Toward Malaria Vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-12-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

The March Toward Malaria Vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26590432

The march toward malaria vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26324116

The march toward malaria vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-11-27

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

Protective role of brain water channel AQP4 in murine cerebral malaria

PubMed Central

Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood; Agre, Peter

2013-01-01

Tragically common among children in sub-Saharan Africa, cerebral malaria is characterized by rapid progression to coma and death. In this study, we used a model of cerebral malaria appearing in C57BL/6 WT mice after infection with the rodent malaria parasite Plasmodium berghei ANKA. Expression and cellular localization of the brain water channel aquaporin-4 (AQP4) was investigated during the neurological syndrome. Semiquantitative real-time PCR comparing uninfected and infected mice showed a reduction of brain AQP4 transcript in cerebral malaria, and immunoblots revealed reduction of brain AQP4 protein. Reduction of brain AQP4 protein was confirmed in cerebral malaria by quantitative immunogold EM; however, polarized distribution of AQP4 at the perivascular and subpial astrocyte membranes was not altered. To further examine the role of AQP4 in cerebral malaria, WT mice and littermates genetically deficient in AQP4 were infected with P. berghei. Upon development of cerebral malaria, WT and AQP4-null mice exhibited similar increases in width of perivascular astroglial end-feet in brain. Nevertheless, the AQP4-null mice exhibited more severe signs of cerebral malaria with greater brain edema, although disruption of the blood–brain barrier was similar in both groups. In longitudinal studies, cerebral malaria appeared nearly 1 d earlier in the AQP4-null mice, and reduced survival was noted when chloroquine rescue was attempted. We conclude that the water channel AQP4 confers partial protection against cerebral malaria. PMID:23277579

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.

Clinical implications of asymptomatic Plasmodium falciparum infections in Malawi.

PubMed

Buchwald, Andrea G; Sixpence, Alick; Chimenya, Mabvuto; Damson, Milius; Sorkin, John D; Wilson, Mark L; Seydel, Karl; Hochman, Sarah; Mathanga, Don P; Taylor, Terrie E; Laufer, Miriam K

2018-05-16

Asymptomatic Plasmodium falciparum infections are common in Malawi, however, the implications of these infections for the burden of malaria illness are unknown. Whether asymptomatic infections eventually progress to malaria illness, persist without causing symptoms, or clear spontaneously remains undetermined. We identified asymptomatic infections and evaluated the associations between persistent asymptomatic infections and malaria illness. Children and adults (N = 120) who presented at a health facility with uncomplicated malaria were followed monthly for two years. During follow-up visits, participants with malaria symptoms were tested and treated if positive. Samples from all visits were tested for parasites using both microscopy and PCR, and all malaria infections underwent genotyping. Cox frailty models were used to estimate the temporal association between asymptomatic infections and malaria illness episodes. Mixed models were used to estimate the odds of clinical symptoms associated with new versus persistent infections. Participants had a median follow-up time of 720 days. Asymptomatic infections were detected during 23% of visits. Persistent asymptomatic infections were associated with decreased risk of malaria illness in all ages (HR 0.50, p < 0.001). When asymptomatic infections preceded malaria illness, newly acquired infections were detected at 92% of subsequent clinical episodes, independent of presence of persistent infections. Malaria illness among children was more likely due to newly acquired infections (OR 1.4, 95%CI 1.3-1.5) than to persistent infections. Asymptomatic P. falciparum infections are associated with decreased incidence of malaria illness but do not protect against disease when new infection occurs.

Campus-Corporate Partnerships: Payoffs and Perils.

ERIC Educational Resources Information Center

Hunt, Todd

A continuing partnership, such as between Johnson & Johnson and the public relations program in the School of Communication, Information and Library Studies at Rutgers, the State University, New Brunswick, New Jersey, sees the development of various benefits as well as perils. Such relationships begin with a contact phase, followed by…

Quantitative genome re-sequencing defines multiple mutations conferring chloroquine resistance in rodent malaria

PubMed Central

2012-01-01

Background Drug resistance in the malaria parasite Plasmodium falciparum severely compromises the treatment and control of malaria. A knowledge of the critical mutations conferring resistance to particular drugs is important in understanding modes of drug action and mechanisms of resistances. They are required to design better therapies and limit drug resistance. A mutation in the gene (pfcrt) encoding a membrane transporter has been identified as a principal determinant of chloroquine resistance in P. falciparum, but we lack a full account of higher level chloroquine resistance. Furthermore, the determinants of resistance in the other major human malaria parasite, P. vivax, are not known. To address these questions, we investigated the genetic basis of chloroquine resistance in an isogenic lineage of rodent malaria parasite P. chabaudi in which high level resistance to chloroquine has been progressively selected under laboratory conditions. Results Loci containing the critical genes were mapped by Linkage Group Selection, using a genetic cross between the high-level chloroquine-resistant mutant and a genetically distinct sensitive strain. A novel high-resolution quantitative whole-genome re-sequencing approach was used to reveal three regions of selection on chr11, chr03 and chr02 that appear progressively at increasing drug doses on three chromosomes. Whole-genome sequencing of the chloroquine-resistant parent identified just four point mutations in different genes on these chromosomes. Three mutations are located at the foci of the selection valleys and are therefore predicted to confer different levels of chloroquine resistance. The critical mutation conferring the first level of chloroquine resistance is found in aat1, a putative aminoacid transporter. Conclusions Quantitative trait loci conferring selectable phenotypes, such as drug resistance, can be mapped directly using progressive genome-wide linkage group selection. Quantitative genome-wide short-read genome resequencing can be used to reveal these signatures of drug selection at high resolution. The identities of three genes (and mutations within them) conferring different levels of chloroquine resistance generate insights regarding the genetic architecture and mechanisms of resistance to chloroquine and other drugs. Importantly, their orthologues may now be evaluated for critical or accessory roles in chloroquine resistance in human malarias P. vivax and P. falciparum. PMID:22435897

Epidemiology of malaria in pregnancy in central India.

PubMed Central

Singh, N.; Shukla, M. M.; Sharma, V. P.

1999-01-01

Analysis of three years of data from a malaria clinic operated by the Indian Council of Medical Research (ICMR) in the Government Medical College Hospital in Jabalpur, central India, showed a high malaria prevalence among pregnant women, which was statistically highly significant (P < 0.0001) compared with the situation among nonpregnant women. Cerebral malaria was a common complication of severe Plasmodium falciparum infection, with a high mortality during pregnancy, requiring immediate attention. The study also showed that malaria infection was more frequent in primigravidae, falling progressively with increasing parity. Mean parasite densities were significantly higher in pregnant women compared with nonpregnant women for both P. falciparum (P < 0.001; df = 137) and P. vivax (P < 0.05; df = 72) infection. Pregnant women with falciparum or vivax malaria were significantly more anaemic than noninfected pregnant women or infected nonpregnant women. The average weight of 155 neonates from infected mothers was 350 g less than that of 175 neonates from noninfected mothers. This difference in birth weight was statistically significant for both P. falciparum (P < 0.0001; df = 278) and P. vivax (P < 0.0001; df = 223) infection. Congenital malaria was not recorded. We conclude that pregnant women from this geographical area require systematic intervention owing to their high susceptibility to malaria during pregnancy and the puerperium. PMID:10444880

Deforestation and Malaria on the Amazon Frontier: Larval Clustering of Anopheles darlingi (Diptera: Culicidae) Determines Focal Distribution of Malaria

PubMed Central

Barros, Fábio S. M.; Honório, Nildimar A.

2015-01-01

We performed bimonthly mosquito larval collections during 1 year, in an agricultural settlement in the Brazilian Amazon, as well as an analysis of malaria incidence in neighboring houses. Water collections located at forest fringes were more commonly positive for Anopheles darlingi larvae and Kulldorff spatial analysis pinpointed significant larval clusters at sites directly beneath forest fringes, which were called larval “hotspots.” Remote sensing identified 43 “potential” hotspots. Sampling of these areas revealed an 85.7% positivity rate for A. darlingi larvae. Malaria was correlated with shorter distances to potential hotpots and settlers living within 400 m of potential hotspots had a 2.60 higher risk of malaria. Recently arrived settlers, usually located closer to the tip of the triangularly shaped deforestation imprints of side roads, may be more exposed to malaria due to their proximity to the forest fringe. As deforestation progresses, transmission decreases. However, forest remnants inside deforested areas conferred an increased risk of malaria. We propose a model for explaining frontier malaria in the Amazon: because of adaptation of A. darlingi to the forest fringe ecotone, humans are exposed to an increased transmission risk when in proximity to these areas, especially when small dams are created on naturally running water collections. PMID:26416110

Driving towards malaria elimination in Botswana by 2018: progress on case-based surveillance, 2013–2014

PubMed Central

Edwards, J.; Namboze, J.; Butt, W.; Moakofhi, K.; Obopile, M.; Manzi, M.; Takarinda, K. C.; Zachariah, R.; Owiti, P.; Oumer, N.; Mosweunyane, T.

2018-01-01

Background: Reliable information reporting systems ensure that all malaria cases are tested, treated and tracked to avoid further transmission. Botswana aimed to eliminate malaria by 2018, and surveillance is key. This study focused on assessing the uptake of the new malaria case-based surveillance (CBS) system introduced in 2012, which captures information on malaria cases reported in the Integrated Disease Surveillance and Response (IDSR) system. Methods: This was a retrospective descriptive study based on routine data focusing on Ngami, Chobe and Okavango, three high-risk districts in Botswana. Aggregated data variables were extracted from the IDSR and compared with data from the CBS. Results: The IDSR reported 456 malaria cases in 2013 and 1346 in 2014, of which respectively only 305 and 884 were reported by the CBS. The CBS reported 34% fewer cases than the IDSR system, indicating substantial differences between the two systems. The key malaria indicators with the greatest variability among the districts included in the study were case identification number and date of diagnosis. Conclusion: The IDSR and CBS systems are essential for malaria elimination, as shown by the significant gaps in reporting between the two systems. These findings highlight the need for further investigation into these discrepancies. Strengthening the CBS system will help to reach the objective of malaria elimination in Botswana. PMID:29713590

Driving towards malaria elimination in Botswana by 2018: progress on case-based surveillance, 2013-2014.

PubMed

Motlaleng, M; Edwards, J; Namboze, J; Butt, W; Moakofhi, K; Obopile, M; Manzi, M; Takarinda, K C; Zachariah, R; Owiti, P; Oumer, N; Mosweunyane, T

2018-04-25

Background: Reliable information reporting systems ensure that all malaria cases are tested, treated and tracked to avoid further transmission. Botswana aimed to eliminate malaria by 2018, and surveillance is key. This study focused on assessing the uptake of the new malaria case-based surveillance (CBS) system introduced in 2012, which captures information on malaria cases reported in the Integrated Disease Surveillance and Response (IDSR) system. Methods: This was a retrospective descriptive study based on routine data focusing on Ngami, Chobe and Okavango, three high-risk districts in Botswana. Aggregated data variables were extracted from the IDSR and compared with data from the CBS. Results: The IDSR reported 456 malaria cases in 2013 and 1346 in 2014, of which respectively only 305 and 884 were reported by the CBS. The CBS reported 34% fewer cases than the IDSR system, indicating substantial differences between the two systems. The key malaria indicators with the greatest variability among the districts included in the study were case identification number and date of diagnosis. Conclusion: The IDSR and CBS systems are essential for malaria elimination, as shown by the significant gaps in reporting between the two systems. These findings highlight the need for further investigation into these discrepancies. Strengthening the CBS system will help to reach the objective of malaria elimination in Botswana.

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

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.

Operational research on malaria control and elimination: a review of projects published between 2008 and 2013.

PubMed

Zhou, Shui-sen; Rietveld, Aafje E C; Velarde-Rodriguez, Mar; Ramsay, Andrew R; Zhang, Shao-sen; Zhou, Xiao-nong; Cibulskis, Richard E

2014-12-04

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide.

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.

Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

PubMed Central

Beeson, James G.; Drew, Damien R.; Boyle, Michelle J.; Feng, Gaoqian; Fowkes, Freya J.I.; Richards, Jack S.

2016-01-01

Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. PMID:26833236

Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria.

PubMed

Beeson, James G; Drew, Damien R; Boyle, Michelle J; Feng, Gaoqian; Fowkes, Freya J I; Richards, Jack S

2016-05-01

Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. © FEMS 2016.

The Internet and the Google Age: Prospects and Perils

ERIC Educational Resources Information Center

James, Jonathan D., Ed.

2014-01-01

"The Internet and the Google Age" commemorates the 25th Anniversary of the Internet in March 2014 and celebrates the achievements and benefits while also pointing out the limitations and perils of the Internet. It identifies the broad characteristics of the Internet age, and includes several studies that outline the educational benefits…

Assessing Causal Mechanistic Interactions: A Peril Ratio Index of Synergy Based on Multiplicativity

PubMed Central

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the ‘peril’. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the ‘peril ratio index of synergy based on multiplicativity’ (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of ‘relative excess risk due to interaction’. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms. PMID:23826299

Spatiotemporal Analysis of Malaria in Urban Ahmedabad (Gujarat), India: Identification of Hot Spots and Risk Factors for Targeted Intervention

PubMed Central

Parizo, Justin; Sturrock, Hugh J. W.; Dhiman, Ramesh C.; Greenhouse, Bryan

2016-01-01

The world population, especially in developing countries, has experienced a rapid progression of urbanization over the last half century. Urbanization has been accompanied by a rise in cases of urban infectious diseases, such as malaria. The complexity and heterogeneity of the urban environment has made study of specific urban centers vital for urban malaria control programs, whereas more generalizable risk factor identification also remains essential. Ahmedabad city, India, is a large urban center located in the state of Gujarat, which has experienced a significant Plasmodium vivax and Plasmodium falciparum disease burden. Therefore, a targeted analysis of malaria in Ahmedabad city was undertaken to identify spatiotemporal patterns of malaria, risk factors, and methods of predicting future malaria cases. Malaria incidence in Ahmedabad city was found to be spatially heterogeneous, but temporally stable, with high spatial correlation between species. Because of this stability, a prediction method utilizing historic cases from prior years and seasons was used successfully to predict which areas of Ahmedabad city would experience the highest malaria burden and could be used to prospectively target interventions. Finally, spatial analysis showed that normalized difference vegetation index, proximity to water sources, and location within Ahmedabad city relative to the dense urban core were the best predictors of malaria incidence. Because of the heterogeneity of urban environments and urban malaria itself, the study of specific large urban centers is vital to assist in allocating resources and informing future urban planning. PMID:27382081

Recent Progress in the Development of Diagnostic Tests for Malaria.

PubMed

Krampa, Francis D; Aniweh, Yaw; Awandare, Gordon A; Kanyong, Prosper

2017-09-19

The impact of malaria on global health has continually prompted the need to develop effective diagnostic strategies. In malaria endemic regions, routine diagnosis is hampered by technical and infrastructural challenges to laboratories. These laboratories lack standard facilities, expertise or diagnostic supplies; thus, therapy is administered based on clinical or self-diagnosis. There is the need for accurate diagnosis of malaria due to the continuous increase in the cost of medication, and the emergence and spread of drug resistant strains. However, the widely utilized Giemsa-stained microscopy and immunochromatographic tests for malaria are liable to several drawbacks, including inadequate sensitivity and false-positive outcomes. Alternative methods that offer improvements in performance are either expensive, have longer turnaround time or require a level of expertise that makes them unsuitable for point-of-care (POC) applications. These gaps necessitate exploration of more efficient detection techniques with the potential of POC applications, especially in resource-limited settings. This minireview discusses some of the recent trends and new approaches that are seeking to improve the clinical diagnosis of malaria.

[Epidemiology and control of malaria in the Federal Islamic Republic of Comoros].

PubMed

Ouledi, A

1995-01-01

Malaria constitutes a major public health problem in the Federal Islamic Republic of Comoros. This problem is relatively recent from the historical point of view of the archipelago. It represents 15 to 30% of the hospitalization cases and 15 to 20% of the registered deaths in the pediatric services. The epidemiological data collected show that the characteristics of malaria transmission continue for the stable type; however, the epidemiological situation varies from one island to another. The principal vectors of malaria are Anopheles gambiae s.l. and A. funestus. Of the four parasitic species, P. falciparum remains the most dominant, as it is responsible for 95% of the paludal attacks. Important progress has been accomplished during the last several years in the fight against malaria in the Federal Islamic Republic of Comoros, with the elaboration of national politics (October 1992), a national strategy for an antivectorial fight (August 1993) and a practical guide for the treatment and prevention of malaria and filariasis (October 1993). These important achievements allow the establishment of more vigorous and better targeted future actions.

Epidemiology and control of malaria in Colombia

PubMed Central

Rodríguez, Julio Cesar Padilla; Uribe, Gilberto Álvarez; Araújo, Roberto Montoya; Narváez, Pablo Chaparro; Valencia, Sócrates Herrera

2016-01-01

Malaria is currently one of the most serious public health problems in Colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. Plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to Plasmodium falciparum. A limited number of severe and complicated cases have resulted in mortality, which is a downward trend that has been maintained over the last few years. More than 90% of the malaria cases in Colombia are confined to 70 municipalities (about 7% of the total municipalities of Colombia), with high predominance (85%) in rural areas. The purpose of this paper is to review the progress of malaria-eradication activities and control measures over the past century within the eco-epidemiologic context of malaria transmission together with official consolidated morbidity and mortality reports. This review may contribute to the formulation of new antimalarial strategies and policies intended to achieve malaria elimination/eradication in Colombia and in the region. PMID:21881765

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.

Targeting imported malaria through social networks: a potential strategy for malaria elimination in Swaziland.

PubMed

Koita, Kadiatou; Novotny, Joseph; Kunene, Simon; Zulu, Zulizile; Ntshalintshali, Nyasatu; Gandhi, Monica; Gosling, Roland

2013-06-27

Swaziland has made great progress towards its goal of malaria elimination by 2015. However, malaria importation from neighbouring high-endemic Mozambique through Swaziland's eastern border remains a major factor that could prevent elimination from being achieved. In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs. A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks. Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25). Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique. The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business. Social networks of imported cases with similar travel patterns were identified through these interviews. Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed. Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria. This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns. This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to identify and treat additional malaria cases. Implementation of a proactive screening programme of importation networks may help Swaziland halt transmission and achieve malaria elimination by 2015.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

PubMed

Korenromp, Eline; Hamilton, Matthew; Sanders, Rachel; Mahiané, Guy; Briët, Olivier J T; Smith, Thomas; Winfrey, William; Walker, Neff; Stover, John

2017-11-07

In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Malaria Vector Control Still Matters despite Insecticide Resistance.

PubMed

Alout, Haoues; Labbé, Pierrick; Chandre, Fabrice; Cohuet, Anna

2017-08-01

Mosquito vectors' resistance to insecticides is usually considered a major threat to the recent progresses in malaria control. However, studies measuring the impact of interventions and insecticide resistance reveal inconsistencies when using entomological versus epidemiological indices. First, evaluation tests that do not reflect the susceptibility of mosquitoes when they are infectious may underestimate insecticide efficacy. Moreover, interactions between insecticide resistance and vectorial capacity reveal nonintuitive outcomes of interventions. Therefore, considering ecological interactions between vector, parasite, and environment highlights that the impact of insecticide resistance on the malaria burden is not straightforward and we suggest that vector control still matters despite insecticide resistance. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Promise and Perils of Thought Experiments

ERIC Educational Resources Information Center

Brown, James Robert

2006-01-01

A number of thought experiments are cited, some well-known, some not. These illustrate the power of thought experiments. Other examples are given that show some of the dangers. As well as examples from the science, some examples of visual reasoning from mathematics are also presented, again with an eye to illustrating their promise and perils.…

Writing In and Writing Out: Some Reflections on the Researcher's Dual Role in Ethnographic Research.

ERIC Educational Resources Information Center

Wu, Ruoyi

Novice researchers often face more peril than pleasures in the researching process, which can become even more perilous as bicultural backgrounds locate them in ambiguous and fluid positions in relation to the "native" and the research community. Such ambiguity problematizes the techniques of participant observation, revealing it as a…

The Perilous Legitimacy of the Foreign-Born Spanish Instructor in the U.S.

ERIC Educational Resources Information Center

Barahona, Byron A.

2014-01-01

This article discusses the perilous legitimacy and professional vulnerability of the foreign-born Spanish instructor in the U.S. First, it examines the academic goals of language and in particular Spanish departments regarding the development of language proficiency, the study of cultural values of the Spanish-speaking world, and the place of…

Give Earth a Chance Series, Dirty Air, Trash Is Taking Over, Sounds and Silence, Pesticides Are Perilous, Tragedy in the Laundromat, Troublesome Tail Pipes.

ERIC Educational Resources Information Center

Minneapolis Independent School District 275, Minn.

These six booklets in the "Give Earth a Chance Series" are titled, "Dirty Air,""Trash is Taking Over,""Sounds and Silence,""Pesticides are Perilous,""Tragedy in the Laundromat," and "Troublesome Tail Pipes." The booklets are suitable for elementary use, and are intended to…

Malaria burden among pregnant women living in the rural district of Boromo, Burkina Faso.

PubMed

Coulibaly, Sheick Oumar; Gies, Sabine; D'Alessandro, Umberto

2007-12-01

In two cross-sectional surveys carried out in the rural health district of Boromo, Burkina Faso, malaria infection was evaluated in 295 pregnant women in May 2003 and 288 pregnant women in December 2003. Malaria prevalence, all P. falciparum infection, was higher in December (32.2%) than in May (11.9%) (P < 0.0001). In both surveys primigravidae had a significantly higher risk of infection than multigravidae (P < 0.0001). Such risk decreased significantly and progressively with gestational age, the highest risk being during the first trimester. Women who had not attended the antenatal clinic had also a significantly higher risk of malaria infection. Despite the high antenatal clinic attendance and the use (or misuse) of chloroquine chemoprophylaxis, malaria remains an important problem for pregnant women living in the rural district of Boromo. This requires a major effort by the health authorities to guarantee all pregnant women have access to and use preventive measures.

[Plan to improve malaria control towards its elimination in Mesoamerica].

PubMed

Rodríguez, Mario Henry; Betanzos-Reyes, Angel Francisco

2011-01-01

To develop a plan to strengthen the control of malaria towards its elimination. In 2009, under the coordination of the National Public HealthInstitute ofMexico, atransdisciplinary equipment of technical and operative experts was conformed to carry out a situational analysis of malaria and control programs and for the selection of effective practices of intervention that would be incorporated to the plan, within the framework of an exercise in Theory of Change. Criteria for thestratificationof thelocalities, based ontheirtransmission characteristics were established. The structural and operative limitations of the control programs were identified. A plan of interventions was elaborated to improve the coverage of epidemiological surveillance, anti-malaria interventions and opportune diagnosis and treatment of cases. The plan delineates progressive phases of implementation: reorganization, intensification of interventions and evaluation of elimination feasibility. The adoption of a regional strategic plan will provide guidance and administrative elements to conform a system that coordinates the activities of the national control programs and facilitate the elimination of malaria in the region.

Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

PubMed Central

2011-01-01

Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. Conclusions While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti-malarials. PMID:22039922

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.

Hidden reservoir of resistant parasites: the missing link in the elimination of falciparum malaria.

PubMed

Abdul-Ghani, Rashad; Mahdy, Mohammed A K; Beier, John C; Basco, Leonardo K

2017-02-06

To successfully eliminate malaria, an integrated system that includes a number of approaches and interventions-aimed at overcoming the threat of antimalarial drug resistance-is required. Significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. To consolidate these gains, attention should be paid to the missing links in the elimination of malaria. One of these gaps is the residual reservoir of submicroscopic resistant parasites, which remains after case management or other control measures have been carried out. Therefore, the present opinion piece highlights the importance of exploring the role that submicroscopic resistant parasites could play in hindering malaria elimination by allowing the persistence of transmission, particularly in areas of low transmission or in the pre-elimination and/or elimination phase. If malaria elimination interventions are to be effective, the relative role of the hidden reservoir of resistant parasites needs to be assessed, particularly in regions that are low-transmission settings and/or in pre-elimination and/or elimination phases. Various ongoing studies are focusing on the role of submicroscopic malaria infections in malaria transmission but overlook the possible build-up of resistance to antimalarial drugs among submicroscopic parasite populations. This is an important factor as it may eventually limit the effectiveness of malaria elimination strategies. An evidence-based estimation of the "true" reservoir of resistant parasites can help target the existing and emerging foci of resistant parasites before they spread. Emergence and spread of artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia underline the need to contain drug resistance.

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

Interaction of Salicylate and a Terpenoid Plant Extract with Model Membranes: Reconciling Experiments and Simulations

PubMed Central

Khandelia, Himanshu; Witzke, Sarah; Mouritsen, Ole G.

2010-01-01

We investigate the effects of two structurally similar small cyclic molecules: salicylic acid and perillic acid on a zwitterionic model lipid bilayer, and show that both molecules might have biological activity related to membrane thinning. Salicylic acid is a nonsteroidal antiinflammatory drug, some of the pharmacological properties of which arise from its interaction with the lipid bilayer component of the plasma membrane. Prior simulations show that salicylate orders zwitterionic lipid membranes. However, this is in conflict with Raman scattering and vesicle fluctuation analysis data, which suggest the opposite. We show using extensive molecular dynamics simulations, cumulatively >2.5 μs, that salicylic acid indeed disorders membranes with concomitant membrane thinning and that the conflict arose because prior simulations suffered from artifacts related to the sodium-ion induced condensation of zwitterionic lipids modeled by the Berger force field. Perillic acid is a terpenoid plant extract that has antiinfective and anticancer properties, and is extensively used in eastern medicine. We found that perillic acid causes large-scale membrane thinning and could therefore exert its antimicrobial properties via a membrane-lytic mechanism reminiscent of antimicrobial peptides. Being more amphipathic, perillic acid is more potent in disrupting lipid headgroup packing, and significantly modifies headgroup dipole orientation. Like salicylate, the membrane thinning effect of perillic acid is masked by the presence of sodium ions. As an alternative to sodium cations, we advocate the straightforward solution of using larger countercations like potassium or tetra-methyl-ammonium that will maintain electroneutrality but not interact strongly with, and thus not condense, the lipid bilayer. PMID:21156130

Puzzling and ambivalent roles of malarial infections in cancer development and progression.

PubMed

Faure, Eric

2016-12-01

Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

Evaluation of direct and indirect effects of seasonal malaria chemoprevention in Mali.

PubMed

Druetz, Thomas

2018-05-25

Randomized controlled trials have established that seasonal malaria chemoprevention (SMC) in children is a promising strategy to reduce malaria transmission in Sahelian West Africa. This strategy was recently introduced in a dozen countries, and about 12 million children received SMC in 2016. However, evidence on SMC effectiveness under routine programme conditions is sparse. We aim to measure the effects of the nationwide SMC programme in Mali on the prevalence of malaria and anemia in children 6-59 months. We used data from the 2015 nationally representative malaria indicator survey. A post-test only with non-randomized control group study was designed. We fitted a generalized structural equation model that controlled for potential bias on observed and non-observed variables (endogenous treatment effect model). Having received SMC reduced by 44% (95% CI [0.39-0.49]) the risk of having a positive rapid diagnostic test for malaria. In addition, the programme indirectly reduced by 18% the risk of moderate-to-severe anemia (95% CI [0.15-0.21]). SMC in Mali has substantial protective effects under routine nationwide programme conditions. Endogenous treatment effects analyses can contribute to rigorously measuring the effectiveness of health programmes and to bridging a widening gap in evaluation methods to measure progress towards achieving malaria elimination.

Commentary: Cause for Alarm? Youth and Internet Risk Research--A Commentary on Livingstone and Smith (2014)

ERIC Educational Resources Information Center

Finkelhor, David

2014-01-01

This commentary on Livingstone and Smith (2014) suggests that more attention should be paid to a set of hypotheses about technology that contrasts with those that have animated much of the current research interest: (a) That the digital environment is no more perilous and perhaps less perilous than other offline environments youth inhabit; (b)…

Changing Malaria Prevalence on the Kenyan Coast since 1974: Climate, Drugs and Vector Control

PubMed Central

Snow, Robert W.; Kibuchi, Eliud; Karuri, Stella W.; Sang, Gilbert; Gitonga, Caroline W.; Mwandawiro, Charles; Bejon, Philip; Noor, Abdisalan M.

2015-01-01

Background Progress toward reducing the malaria burden in Africa has been measured, or modeled, using datasets with relatively short time-windows. These restricted temporal analyses may miss the wider context of longer-term cycles of malaria risk and hence may lead to incorrect inferences regarding the impact of intervention. Methods 1147 age-corrected Plasmodium falciparum parasite prevalence (PfPR2-10) surveys among rural communities along the Kenyan coast were assembled from 1974 to 2014. A Bayesian conditional autoregressive generalized linear mixed model was used to interpolate to 279 small areas for each of the 41 years since 1974. Best-fit polynomial splined curves of changing PfPR2-10 were compared to a sequence of plausible explanatory variables related to rainfall, drug resistance and insecticide-treated bed net (ITN) use. Results P. falciparum parasite prevalence initially rose from 1974 to 1987, dipped in 1991–92 but remained high until 1998. From 1998 onwards prevalence began to decline until 2011, then began to rise through to 2014. This major decline occurred before ITNs were widely distributed and variation in rainfall coincided with some, but not all, short-term transmission cycles. Emerging resistance to chloroquine and introduction of sulfadoxine/pyrimethamine provided plausible explanations for the rise and fall of malaria transmission along the Kenyan coast. Conclusions Progress towards elimination might not be as predictable as we would like, where natural and extrinsic cycles of transmission confound evaluations of the effect of interventions. Deciding where a country lies on an elimination pathway requires careful empiric observation of the long-term epidemiology of malaria transmission. PMID:26107772

malERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication

PubMed Central

2017-01-01

This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. Since 2011, progress has been made in a number of areas. The extent of submicroscopic and asymptomatic infections is better understood, as are the biological parameters governing transmission of sexual stage parasites. Limitations of existing transmission measures have been documented, and proof-of-concept has been established for new innovative serological and molecular methods to better characterise transmission. Finally, there now exists a concerted effort towards the use of ensemble datasets across the spectrum of metrics, from passive and active sources, to develop more accurate risk maps of transmission. These can be used to better target interventions and effectively monitor progress toward elimination. The success of interventions depends not only on the level of endemicity but also on how rapidly or recently an area has undergone changes in transmission. Improved understanding of the biology of mosquito–human and human–mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission. PMID:29190279

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.

The application of the haemagglutination test to a study of the immunity to malaria in protected and unprotected population groups in Australian New Guinea*

PubMed Central

Desowitz, R. S.; Saave, J. J.

1965-01-01

The formolized tanned sheep erythrocyte haemagglutination test has been applied to an immuno-malariometric study in Australian New Guinea to determine whether the haemagglutination titre reflects a subject's immune state and to measure the effect of malaria control operations on a population's immunity. Two population groups were studied—one (unprotected) living in holoendemic malaria conditions, the other (protected) living in an area subject to malaria control measures for four years. An increase in both serological positivity rates and geometric mean titres among the unprotected group with increasing age suggests that the test does serve to assess the state of immunity; the corresponding rates were much lower in the protected population, particularly among the children. The authors foresee the possible use of the haemagglutination test as a supplement to other procedures in assessing the progress of a malaria campaign. They, note, however, that more immuno-malariometric studies on populations subject to different degrees of malaria endemicity will need to be carried out before the relationship between the immune state and serological results can be clearly established. PMID:14310901

Recent advances in malaria drug discovery

PubMed Central

Biamonte, Marco A.; Wanner, Jutta; Le Roch, Karine G.

2013-01-01

This digest covers some of the most relevant progress in malaria drug disco very published betwe en 2010 and 2012. There is an urgent need to develop new antimalarial drugs. Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans. The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard. Drug disco very efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria. PMID:23587422

Malaria investigation and treatment of children admitted to county hospitals in western Kenya.

PubMed

Amboko, Beatrice I; Ayieko, Philip; Ogero, Morris; Julius, Thomas; Irimu, Grace; English, Mike

2016-10-18

Up to 90 % of the global burden of malaria morbidity and mortality occurs in sub-Saharan Africa and children under-five bear a disproportionately high malaria burden. Effective inpatient case management can reduce severe malaria mortality and morbidity, but there are few reports of how successfully international and national recommendations are adopted in management of inpatient childhood malaria. A descriptive cross-sectional study of inpatient malaria case management practices was conducted using data collected over 24 months in five hospitals from high malaria risk areas participating in the Clinical Information Network (CIN) in Kenya. This study describes documented clinical features, laboratory investigations and treatment of malaria in children (2-59 months) and adherence to national guidelines. A total of 13,014 children had a malaria diagnosis on admission to the five hospitals between March, 2014 and February, 2016. Their median age was 24 months (IQR 12-36 months). The proportion with a diagnostic test for malaria requested was 11,981 (92.1 %). Of 10,388 patients with malaria test results documented, 8050 (77.5 %) were positive and anti-malarials were prescribed in 6745 (83.8 %). Malaria treatment was prescribed in 1613/2338 (69.0 %) children with a negative malaria result out of which only 52 (3.2 %) had a repeat malaria test done as recommended in national guidelines. Documentation of clinical features was good across all hospitals, but quinine remained the most prescribed malaria drug (47.2 % of positive cases) although a transition to artesunate (46.1 %) was observed. Although documented clinical features suggested approximately half of positive malaria patients were not severe cases artemether-lumefantrine was prescribed on admission in only 3.7 % cases. Despite improvements in inpatient malaria care, high rates of presumptive treatment for test negative children and likely over-use of injectable anti-malarial drugs were observed. Three years after national policy change, there is a gradual transition to artesunate. Continued efforts to support improved routine inpatient malaria care through dissemination and implementation of guidelines, and access to recommended drugs are needed together with improved capacity of hospitals to investigate other causes of severe illness in children. Efforts to improve clinical information could help track progress.

Low perception of malaria risk among the Ra-glai ethnic minority in south-central Vietnam: implications for forest malaria control.

PubMed

Peeters Grietens, Koen; Xuan, Xa Nguyen; Van Bortel, Wim; Duc, Thang Ngo; Ribera, Joan Muela; Ba Nhat, Truong; Van, Ky Pham; Le Xuan, Hung; D'Alessandro, Umberto; Erhart, Annette

2010-01-20

Despite Vietnam's success in reducing malaria mortality and morbidity over the last decade, malaria persists in the forested and mountainous areas of the central and southern provinces, where more than 50% of the clinical cases and 90% of severe cases and malaria deaths occur. Between July 2005 and September 2006, a multi-method study, triangulating a malariometric cross-sectional survey and qualitative data from focused ethnography, was carried out among the Ra-glai ethnic minority in the hilly forested areas of south-central Vietnam. Despite the relatively high malaria burden among the Ra-glai and their general awareness that mosquitoes can transmit an unspecific kind of fever (84.2%), the use of bed nets, distributed free of charge by the national malaria control programme, remains low at the farmers' forest fields where the malaria risk is the highest. However, to meet work requirements during the labour intensive malaria transmission and rainy season, Ra-glai farmers combine living in government supported villages along the road with a second home or shelter at their slash and burn fields located in the forest. Bed net use was 84.6% in the villages but only 52.9% at the forest fields; 20.6% of the respondents slept unprotected in both places. Such low use may be explained by the low perception of the risk for malaria, decreasing the perceived need to sleep protected. Several reasons may account for this: (1) only 15.6% acknowledged the higher risk of contracting malaria in the forest than in the village; (2) perceived mosquito biting times only partially coincided with Anopheles dirus ss and Anopheles minimus A true biting times; (3) the disease locally identified as 'malaria' was hardly perceived as having an impact on forest farmers' daily lives as they were unaware of the specific kind of fevers from which they had suffered even after being diagnosed with malaria at the health centre (20.9%). The progressive confinement of malaria to minority groups and settings in the Greater Mekong sub-region implies that further success in malaria control will be linked to research into these specific socio-cultural contexts. Findings highlight the need for context sensitive malaria control policies; not only to reduce the local malaria burden but also to minimize the risk of malaria spreading to other areas where transmission has virtually ceased.

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

Progress towards malaria elimination in Sabang Municipality, Aceh, Indonesia

PubMed Central

2013-01-01

Background Indonesia has set 2030 as its deadline for elimination of malaria transmission in the archipelago, with regional deadlines established according to present levels of malaria endemicity and strength of health infrastructure. The Municipality of Sabang which historically had one of the highest levels of malaria in Aceh province aims to achieve elimination by the end of 2013. Method From 2008 to 2010, baseline surveys of malaria interventions, mapping of all confirmed malaria cases, categorization of residual foci of malaria transmission and vector surveys were conducted in Sabang, Aceh, a pilot district for malaria elimination in Indonesia. To inform future elimination efforts, mass screening from the focal areas to measure prevalence of malaria with both microscopy and PCR was conducted. G6PD deficiency prevalence was also measured. Result Despite its small size, a diverse mixture of potential malaria vectors were documented in Sabang, including Anopheles sundaicus, Anopheles minimus, Anopheles aconitus and Anopheles dirus. Over a two-year span, the number of sub-villages with ongoing malaria transmission reduced from 61 to 43. Coverage of malaria diagnosis and treatment, IRS, and LLINs was over 80%. Screening of 16,229 residents detected 19 positive people, for a point prevalence of 0.12%. Of the 19 positive cases, three symptomatic infections and five asymptomatic infections were detected with microscopy and 11 asymptomatic infections were detected with PCR. Of the 19 cases, seven were infected with Plasmodium falciparum, 11 were infected with Plasmodium vivax, and one subject was infected with both species. Analysis of the 937 blood samples for G6PD deficiency revealed two subjects (0.2%) with deficient G6PD. Discussion The interventions carried out by the government of Sabang have dramatically reduced the burden of malaria over the past seven years. The first phase, carried out between 2005 and 2007, included improved malaria diagnosis, introduction of ACT for treatment, and scale-up of coverage of IRS and LLINs. The second phase, from 2008 to 2010, initiated to eliminate the persistent residual transmission of malaria, consisted of development of a malaria database to ensure rapid case reporting and investigation, stratification of malaria foci to guide interventions, and active case detection to hunt symptomatic and asymptomatic malaria carriers. PMID:23363768

The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

PubMed Central

Breman, Joel G.; de Quadros, Ciro A.; Dowdle, Walter R.; Foege, William H.; Henderson, Donald A.; John, T. Jacob; Levine, Myron M.

2011-01-01

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases—smallpox, poliomyelitis, and measles—we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios. PMID:21311582

Creation of first malaria vaccine raises troubling questions about "intellectual racism". Interview by Kirsteen MacLeod.

PubMed Central

Patarroyo, M

1995-01-01

Some of the problems caused by malaria, which places a huge roadblock in front of economic progress in the Third World, may be solved by a new vaccine created by Dr. Manuel Patarroyo, a Columbian physician and researcher. "Imagine how things would be if Canadians had malaria," he says. "Episodes last 10 days, then there are 10 days of recovering. This leaves only 10 days each month in which to do some productive work. Then imagine killing the population of Toronto each year, and you can see the huge toll in terms of the number of yearly deaths globally from malaria." His discovery also raises the issue of "intellectual racism" because of criticism of Patarroyo's methods by Western scientists. Patarroyo, meanwhile, turned down a $60-million offer for his vaccine, and instead donated the patent to the World Health Organization. Images p1320-a PMID:7497394

Early life exposure to malaria and cognition in adulthood: evidence from Mexico.

PubMed

Venkataramani, Atheendar S

2012-09-01

This study examines the impact of early life malaria exposure on cognition in sample of Mexican adults, using the nationwide introduction of malaria eradication efforts to identify causal impacts. The core findings are that birth year exposure to malaria eradication was associated with increases in Raven Progressive Matrices test scores and consumption expenditures, but not schooling. Additionally, cohorts born after eradication both entered and exited school earlier than their pre-eradication counterparts. These effects were only seen for men and explanations for this are assessed. Collectively, these findings suggest that improvements in infant health help explain secular increases in cognitive test scores, that better cognition may link early life health to adulthood earnings, and that human capital investments through childhood and young adulthood respond sensitively to market returns to early life endowment shocks. Copyright © 2012 Elsevier B.V. All rights reserved.

Sustaining control: lessons from the Lubombo spatial development initiative in southern Africa.

PubMed

Maharaj, Rajendra; Moonasar, Devanand; Baltazar, Candrinho; Kunene, Simon; Morris, Natashia

2016-08-12

The Lubombo Spatial Development Initiative (LSDI) was a tri-country project between South Africa, Swaziland and Mozambique with the aim of accelerating socio-economic development in the region. The malaria component of the project was introduced to decrease the transmission of malaria in the region. This goal was met but with termination of this project resulted in an upsurge of malaria cases in the sub-region mainly as a result of migration from high transmission areas to low transmission ones. The movement of people across borders in southern Africa remains a challenge in sustaining malaria control and elimination. Malaria case data for Swaziland and South Africa were obtained from their respective national Malaria Information Systems. Data for Mozambique was obtained from the Mozambican Ministry of Health. Data obtained during the course of the LSDI project was compared to the case data post the termination of the LSDI. The 12-year period of the LSDI showed a substantial decrease in disease burden amongst the three countries involved when compared to the baseline year of 2000. The decrease in malaria cases was 99 % in South Africa and 98 % in Swaziland. Malaria prevalence in Mozambique decreased by 85 % over the same period. However, after the LSDI ended, between 2012 and 2014, there was an upward trend in case data that was counter to the goal of elimination. South Africa and Swaziland benefitted from the LSDI and were able to sustain malaria control and progress to the stage of elimination. Mozambique could not sustain the gains made during the LSDI and case numbers increased. Technical and financial resources are key challenges for malaria control and elimination interventions.

Spatiotemporal Clustering Analysis of Malaria Infection in Pakistan.

PubMed

Umer, Muhammad Farooq; Zofeen, Shumaila; Majeed, Abdul; Hu, Wenbiao; Qi, Xin; Zhuang, Guihua

2018-06-07

Despite tremendous progress, malaria remains a serious public health problem in Pakistan. Very few studies have been done on spatiotemporal evaluation of malaria infection in Pakistan. The study aimed to detect the spatiotemporal pattern of malaria infection at the district level in Pakistan, and to identify the clusters of high-risk disease areas in the country. Annual data on malaria for two dominant species ( Plasmodium falciparum , Plasmodium vivax ) and mixed infections from 2011 to 2016 were obtained from the Directorate of Malaria Control Program, Pakistan. Population data were collected from the Pakistan Bureau of Statistics. A geographical information system was used to display the spatial distribution of malaria at the district level throughout Pakistan. Purely spatiotemporal clustering analysis was performed to identify the high-risk areas of malaria infection in Pakistan. A total of 1,593,409 positive cases were included in this study over a period of 6 years (2011⁻2016). The maximum number of P . vivax cases (474,478) were reported in Khyber Pakhtunkhwa (KPK). The highest burden of P . falciparum (145,445) was in Balochistan, while the highest counts of mixed Plasmodium cases were reported in Sindh (22,421) and Balochistan (22,229), respectively. In Balochistan, incidence of all three types of malaria was very high. Cluster analysis showed that primary clusters of P . vivax malaria were in the same districts in 2014, 2015 and 2016 (total 24 districts, 12 in Federally Administered Tribal Areas (FATA), 9 in KPK, 2 in Punjab and 1 in Balochistan); those of P . falciparum malaria were unchanged in 2012 and 2013 (total 18 districts, all in Balochistan), and mixed infections remained the same in 2014 and 2015 (total 7 districts, 6 in Balochistan and 1 in FATA). This study indicated that the transmission cycles of malaria infection vary in different spatiotemporal settings in Pakistan. Efforts in controlling P . vivax malaria in particular need to be enhanced in high-risk areas. Based on these findings, further research is needed to investigate the impact of risk factors on transmission of malaria in Pakistan.

Earth Observation, Geographic Information Systems and Plasmodium falciparum Malaria in Sub-Saharan Africa

PubMed Central

Hay, S.I.; Omumbo, J.A.; Craig, M.H.; Snow, R. W.

2011-01-01

This review highlights the progress and current status of remote sensing (RS) and geographical information systems (GIS) as currently applied to the problem of Plasmodium falciparum malaria in sub-Saharan Africa (SSA). The burden of P. falciparum malaria in SSA is first summarized and then contrasted with the paucity of accurate and recent information on the nature and extent of the disease. This provides perspective on both the global importance of the pathogen and the potential for contribution of RS and GIS techniques. The ecology of P. falciparum malaria and its major anopheline vectors in SSA is then outlined, to provide the epidemiological background for considering disease transmission processes and their environmental correlates. Because RS and GIS are recent techniques in epidemiology, all mosquito-borne diseases are considered in this review in order to convey the range of ideas, insights and innovation provided. To conclude, the impact of these initial studies is assessed and suggestions provided on how these advances could be best used for malaria control in an appropriate and sustainable manner, with key areas for future research highlighted. PMID:10997207

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

Phase II trial in China of a new, rapidly-acting and effective oral antimalarial, CGP 56697, for the treatment of Plasmodium falciparum malaria.

PubMed

Jiao, X; Liu, G Y; Shan, C O; Zhao, X; Li, X W; Gathmann, I; Royce, C

1997-09-01

One hundred and two Chinese out-patients with naturally acquired, previously untreated, falciparum malaria were selected to evaluate the efficacy of a new combination anti-malaria therapy, CGP 56697 (artemether plus benflumetol). In this open non-comparative trial each patient received a combination of 80 mg artemether and 480 mg benflumetol given orally at 0, 8, 24 and 48 hours (total: 320 mg artemether, 1,920 mg benflumetol). Patients were kept for 28 days in a transmission-free hospital in an area with chloroquine resistant falciparum malaria to prevent reinfection and to aid diagnosis of recrudescence. Progress and possible adverse effects were monitored by blood film parasitology, blood biochemistry assays, urinalysis, ECG and X-ray. Ninety-eight of the 102 patients were shown to be free of infection at 28 days, a 96.1% cure rate. Parasite reduction at 24 hours was 99.4%. Time to effect complete parasite clearance ranged from 24 to 54 hours (median 30 hours). Time for fever clearance ranged from 6 to 78 hours (median 18 hours). Recrudescence was low (3.9%). No significant adverse side-effects were encountered. It is concluded that CGP 56697, a combination anti-malaria therapy of artemether with benflumetol, offered a rapid and highly effective treatment for acute uncomplicated falciparum malaria in an area of chloroquine-resistant malaria in China.

PubMed Central

Raccurt, C. P.; Le Bras, M.; Ripert, C.; Cuisinier-Raynal, J. C.; Carteron, B.; Buestel, M. L.

1991-01-01

This study of imported cases of malaria, which was carried out in Bordeaux (France) in 1987-89, emphasizes the major part played by Plasmodium falciparum, especially in areas lying south of the Sahara in Africa, from where falciparum malaria is mainly imported to other countries. The study of these imported cases is strengthening our understanding of the epidemiology of malaria in relation to the country or area, whether the transmission occurs without interruptions or seasonally. The number of cases of P. falciparum per 1000 travellers (seen for vaccination against yellow fever at Bordeaux) gives an index for evaluating the risk of malaria. This risk changes with the epidemiological profile of falciparum malaria in the three major African ecosystems (rain forest, savannah, and sahelian belts), and is related to the progression of chloroquine resistance in Africa and influenced by the type of chemoprophylaxis proposed to travellers. The use of mefloquine for stays shorter than one month in Central Africa reduced the risk of malaria in 1988 and 1989, compared to 1987. [Editorial note. Recent data indicate some undesirable side-effects of mefloquine, e.g., its use during early pregnancy could lead to congenital defects.] Appropriate chemoprophylaxis and advice to travellers to areas lying south of the Sahara are therefore more and more necessary in order to arrest the increase in the number of imported falciparum malaria cases and reduce the number of serious cases, which are costly in terms of public health. PMID:2054924

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

Preventing malaria in the Peruvian Amazon: a qualitative study in Iquitos, Peru.

PubMed

Newell, Ian; Wiskin, Connie; Anthoney, James; Meza, Graciela; de Wildt, Gilles

2018-01-16

In Peru, despite decades of concerted control efforts, malaria remains a significant public health burden. Peru has recently exhibited a dramatic rise in malaria incidence, impeding South America's progress towards malaria elimination. The Amazon basin, in particular the Loreto region of Peru, has been identified as a target for the implementation of intensified control strategies, aiming for elimination. No research has addressed why vector control strategies in Loreto have had limited impact in the past, despite vector control elsewhere being highly effective in reducing malaria transmission. This study employed qualitative methods to explore factors limiting the success of vector control strategies in the region. Twenty semi-structured interviews were conducted among adults attending a primary care centre in Iquitos, Peru, together with 3 interviews with key informants (health care professionals). The interviews focussed on how local knowledge, together with social and cultural attitudes, determined the use of vector control methods. Five themes emerged. (a) Participants believed malaria to be embedded within their culture, and commonly blamed this for a lack of regard for prevention. (b) They perceived a shift in mosquito biting times to early evening, rendering night-time use of bed nets less effective. (c) Poor preventive practices were compounded by a consensus that malaria prevention was the government's responsibility, and that this reduced motivation for personal prevention. (d) Participants confused the purpose of space-spraying. (e) Participants' responses also exposed persisting misconceptions, mainly concerning the cause of malaria and best practices for its prevention. To eliminate malaria from the Americas, region-specific strategies need to be developed that take into account the local social and cultural contexts. In Loreto, further research is needed to explore the potential shift in biting behaviour of Anopheles darlingi, and how this interacts with the population's social behaviours and current use of preventive measures. Attitudes concerning personal responsibility for malaria prevention and long-standing misconceptions as to the cause of malaria and best preventive practices also need to be addressed.

Low perception of malaria risk among the Ra-glai ethnic minority in south-central Vietnam: implications for forest malaria control

PubMed Central

2010-01-01

Background Despite Vietnam's success in reducing malaria mortality and morbidity over the last decade, malaria persists in the forested and mountainous areas of the central and southern provinces, where more than 50% of the clinical cases and 90% of severe cases and malaria deaths occur. Methods Between July 2005 and September 2006, a multi-method study, triangulating a malariometric cross-sectional survey and qualitative data from focused ethnography, was carried out among the Ra-glai ethnic minority in the hilly forested areas of south-central Vietnam. Results Despite the relatively high malaria burden among the Ra-glai and their general awareness that mosquitoes can transmit an unspecific kind of fever (84.2%), the use of bed nets, distributed free of charge by the national malaria control programme, remains low at the farmers' forest fields where the malaria risk is the highest. However, to meet work requirements during the labour intensive malaria transmission and rainy season, Ra-glai farmers combine living in government supported villages along the road with a second home or shelter at their slash and burn fields located in the forest. Bed net use was 84.6% in the villages but only 52.9% at the forest fields; 20.6% of the respondents slept unprotected in both places. Such low use may be explained by the low perception of the risk for malaria, decreasing the perceived need to sleep protected. Several reasons may account for this: (1) only 15.6% acknowledged the higher risk of contracting malaria in the forest than in the village; (2) perceived mosquito biting times only partially coincided with Anopheles dirus ss and Anopheles minimus A true biting times; (3) the disease locally identified as 'malaria' was hardly perceived as having an impact on forest farmers' daily lives as they were unaware of the specific kind of fevers from which they had suffered even after being diagnosed with malaria at the health centre (20.9%). Conclusions The progressive confinement of malaria to minority groups and settings in the Greater Mekong sub-region implies that further success in malaria control will be linked to research into these specific socio-cultural contexts. Findings highlight the need for context sensitive malaria control policies; not only to reduce the local malaria burden but also to minimize the risk of malaria spreading to other areas where transmission has virtually ceased. PMID:20089152

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.

Plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites.

PubMed

Andrabi, Syed Bilal Ahmad; Tahara, Michiru; Matsubara, Ryuma; Toyama, Tomoko; Aonuma, Hiroka; Sakakibara, Hitoshi; Suematsu, Makoto; Tanabe, Kazuyuki; Nozaki, Tomoyoshi; Nagamune, Kisaburo

2018-02-01

Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression. Immunofluorescence microscopy and quantitative PCR analysis showed that t-zeatin increased the genome-copy number of apicoplast, which are non-photosynthetic plastid, in the parasite, while thidiazuron led to their disappearance. Thidiazuron inhibited growth of T. gondii and Plasmodium falciparum, a human malaria parasite, suggesting that thidiazuron has therapeutic potential as an inhibitor of apicomplexan parasites. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Battling Malaria in Rural Zambia with Modern Technology: A Qualitative Study on the Value of Cell Phones, Geographical Information Systems, Asymptomatic Carriers and Rapid Diagnostic Tests to Identify, Treat and Control Malaria.

PubMed

Nygren, David; Isaksson, Arvid Lissel

2014-02-04

During the last decade much progress has been made in reducing malaria transmission in Macha, Southern Province, Zambia. Introduction of artemisinin combination therapies as well as mass screenings of asymptomatic carriers is believed to have contributed the most. When an endemic malaria situation is moving towards a non-endemic situation the resident population loses acquired immunity and therefore active case detection and efficient surveillance is crucial to prevent epidemic outbreaks. Our purpose was to evaluate the impact of cell phone surveillance and geographical information systems on malaria control in Macha. Furthermore, it evaluates what screening and treatment of asymptomatic carriers and implementation of rapid diagnostic tests in rural health care has led to. Ten in-depth semi-structured interviews, field observations and data collection were performed at the Macha Research Trust and at surrounding rural health centers. This qualitative method was inspired by rapid assessment procedure. The cell phone surveillance has been easily integrated in health care, and its integration with Geographical Information Systems has provided the ability to follow malaria transmission on a weekly basis. In addition, active case detection of asymptomatic carriers has been fruitful, which is reflected in it soon being applied nationwide. Furthermore, rapid diagnostic tests have provided rural health centers with reliable malaria diagnostics, thereby decreasing excessive malaria treatments and selection for drug resistance. This report reflects the importance of asymptomatic carriers in targeting malaria elimination, as well as development of effective surveillance systems when transmission decreases. Such an approach would be cost-efficient in the long run through positive effects in reduced child mortality and relief in health care.

Perils and potentials in qualitative psychology.

PubMed

Brinkmann, Svend

2015-06-01

Famously, Ebbinghaus declared that psychology has a long past, but only a short history. Psychology, as something implicit to human conduct, is as old as the human race, but the science, as an explicit investigative reflection upon that conduct, is a recent invention. Within the short history of psychology, we find an even shorter history of qualitative psychology specifically. Although most founding fathers (Freud, Piaget, Bartlett etc.) worked as "qualitative psychologists", they found no need to thematize their methods of inquiry in this manner. Since around 1980, however, a field has established itself that can be called qualitative psychology. In this paper, I discuss how this field can move sensibly into the future, and I highlight two perils and two potentials. The perils stem from neo-positivism and a threatening "McDonaldization" of qualitative research, while the potentials are related to proliferation of new forms of inquiry and a transcending of disciplinary boundaries.

Micro-spatial distribution of malaria cases and control strategies at ward level in Gwanda district, Matabeleland South, Zimbabwe.

PubMed

Manyangadze, Tawanda; Chimbari, Moses J; Macherera, Margaret; Mukaratirwa, Samson

2017-11-21

Although there has been a decline in the number of malaria cases in Zimbabwe since 2010, the disease remains the biggest public health threat in the country. Gwanda district, located in Matabeleland South Province of Zimbabwe has progressed to the malaria pre-elimination phase. The aim of this study was to determine the spatial distribution of malaria incidence at ward level for improving the planning and implementation of malaria elimination in the district. The Poisson purely spatial model was used to detect malaria clusters and their properties, including relative risk and significance levels at ward level. The geographically weighted Poisson regression (GWPR) model was used to explore the potential role and significance of environmental variables [rainfall, minimum and maximum temperature, altitude, Enhanced Vegetation Index (EVI), Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), rural/urban] and malaria control strategies [indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs)] on the spatial patterns of malaria incidence at ward level. Two significant clusters (p < 0.05) of malaria cases were identified: (1) ward 24 south of Gwanda district and (2) ward 9 in the urban municipality, with relative risks of 5.583 and 4.316, respectively. The semiparametric-GWPR model with both local and global variables had higher performance based on AICc (70.882) compared to global regression (74.390) and GWPR which assumed that all variables varied locally (73.364). The semiparametric-GWPR captured the spatially non-stationary relationship between malaria cases and minimum temperature, NDVI, NDWI, and altitude at the ward level. The influence of LLINs, IRS and rural or urban did not vary and remained in the model as global terms. NDWI (positive coefficients) and NDVI (range from negative to positive coefficients) showed significant association with malaria cases in some of the wards. The IRS had a protection effect on malaria incidence as expected. Malaria incidence is heterogeneous even in low-transmission zones including those in pre-elimination phase. The relationship between malaria cases and NDWI, NDVI, altitude, and minimum temperature may vary at local level. The results of this study can be used in planning and implementation of malaria control strategies at district and ward levels.

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.

Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

PubMed

Brentlinger, Paula E; Behrens, Christopher B; Micek, Mark A

2006-02-01

Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.

Methodological Considerations for Use of Routine Health Information System Data to Evaluate Malaria Program Impact in an Era of Declining Malaria Transmission

PubMed Central

Ashton, Ruth A.; Bennett, Adam; Yukich, Joshua; Bhattarai, Achuyt; Keating, Joseph; Eisele, Thomas P.

2017-01-01

Abstract. Coverage of malaria control interventions is increasing dramatically across endemic countries. Evaluating the impact of malaria control programs and specific interventions on health indicators is essential to enable countries to select the most effective and appropriate combination of tools to accelerate progress or proceed toward malaria elimination. When key malaria interventions have been proven effective under controlled settings, further evaluations of the impact of the intervention using randomized approaches may not be appropriate or ethical. Alternatives to randomized controlled trials are therefore required for rigorous evaluation under conditions of routine program delivery. Routine health management information system (HMIS) data are a potentially rich source of data for impact evaluation, but have been underused in impact evaluation due to concerns over internal validity, completeness, and potential bias in estimates of program or intervention impact. A range of methodologies were identified that have been used for impact evaluations with malaria outcome indicators generated from HMIS data. Methods used to maximize internal validity of HMIS data are presented, together with recommendations on reducing bias in impact estimates. Interrupted time series and dose-response analyses are proposed as the strongest quasi-experimental impact evaluation designs for analysis of malaria outcome indicators from routine HMIS data. Interrupted time series analysis compares the outcome trend and level before and after the introduction of an intervention, set of interventions or program. The dose-response national platform approach explores associations between intervention coverage or program intensity and the outcome at a subnational (district or health facility catchment) level. PMID:28990915

Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

PubMed

Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

2017-04-01

Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

The impact of insecticides management linked with resistance expression in Anopheles spp. populations.

PubMed

Silva, Guilherme Liberato da; Pereira, Thiago Nunes; Ferla, Noeli Juarez; Silva, Onilda Santos da

2016-06-01

The resistance of some species of Anopheles to chemical insecticides is spreading quickly throughout the world and has hindered the actions of prevention and control of malaria. The main mechanism responsible for resistance in these insects appears to be the target site known as knock-down resistance (kdr), which causes mutations in the sodium channel. Even so, many countries have made significant progress in the prevention of malaria, focusing largely on vector control through long-lasting insecticide nets (LLINs), indoor residual spraying and (IRS) of insecticides. The objective of this review is to contribute with information on the more applied insecticides for the control of the main vectors of malaria, its effects, and the different mechanisms of resistance. Currently it is necessary to look for others alternatives, e.g. biological control and products derived from plants and fungi, by using other organisms as a possible regulator of the populations of malaria vectors in critical outbreaks.

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response

PubMed Central

Rinchai, Darawan; Presnell, Scott; Vidal, Marta; Dutta, Sheetij; Chauhan, Virander; Cavanagh, David; Moncunill, Gemma; Dobaño, Carlota; Chaussabel, Damien

2017-01-01

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection. PMID:28883910

Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control.

PubMed

Keiser, J; Utzinger, J; Premji, Z; Yamagata, Y; Singer, B H

2002-10-01

One hundred years ago, Giemsa's stain was employed for the first time for malaria diagnosis. Giemsa staining continues to be the method of choice in most malarious countries, although, in the recent past, several alternatives have been developed that exhibit some advantages. Considerable progress has been made with fluorescent dyes, particularly with Acridine Orange (AO). The literature on the discovery, development and validation of the AO method for malaria diagnosis is reviewed here. Compared with conventional Giemsa staining, AO shows a good diagnostic performance, with sensitivities of 81.3%-100% and specificities of 86.4%-100%. However, sensitivities decrease with lower parasite densities, and species differentiation may occasionally be difficult. The most notable advantage of the AO method over Giemsa staining is its promptness; results are readily available within 3-10 min, whereas Giemsa staining may take 45 min or even longer. This is an important advantage for the organization of health services and the provision of effective treatment of malaria cases. The national malaria control programme of Tanzania, together with the Japan International Co-operation Agency, began to introduce the AO method in Tanzania in 1994. So far, AO staining has been introduced in 70 regional and district hospitals, and 400 laboratory technicians have been trained to use the method. The results of this introduction, which are reviewed here and have several important implications, indicate that AO is a viable alternative technique for the laboratory diagnosis of malaria in highly endemic countries.

Spatiotemporal Modeling for Fine-Scale Maps of Regional Malaria Endemicity and Its Implications for Transitional Complexities in a Routine Surveillance Network in Western Cambodia

PubMed Central

Okami, Suguru; Kohtake, Naohiko

2017-01-01

Due to the associated and substantial efforts of many stakeholders involved in malaria containment, the disease burden of malaria has dramatically decreased in many malaria-endemic countries in recent years. Some decades after the past efforts of the global malaria eradication program, malaria elimination has again featured on the global health agenda. While risk distribution modeling and a mapping approach are effective tools to assist with the efficient allocation of limited health-care resources, these methods need some adjustment and reexamination in accordance with changes occurring in relation to malaria elimination. Limited available data, fine-scale data inaccessibility (for example, household or individual case data), and the lack of reliable data due to inefficiencies within the routine surveillance system, make it difficult to create reliable risk maps for decision-makers or health-care practitioners in the field. Furthermore, the risk of malaria may dynamically change due to various factors such as the progress of containment interventions and environmental changes. To address the complex and dynamic nature of situations in low-to-moderate malaria transmission settings, we built a spatiotemporal model of a standardized morbidity ratio (SMR) of malaria incidence, calculated through annual parasite incidence, using routinely reported surveillance data in combination with environmental indices such as remote sensing data, and the non-environmental regional containment status, to create fine-scale risk maps. A hierarchical Bayesian frame was employed to fit the transitioning malaria risk data onto the map. The model was set to estimate the SMRs of every study location at specific time intervals within its uncertainty range. Using the spatial interpolation of estimated SMRs at village level, we created fine-scale maps of two provinces in western Cambodia at specific time intervals. The maps presented different patterns of malaria risk distribution at specific time intervals. Moreover, the visualized weights estimated using the risk model, and the structure of the routine surveillance network, represent the transitional complexities emerging from ever-changing regional endemic situations. PMID:29034229

The central role of national programme management for the achievement of malaria elimination: a cross case-study analysis of nine malaria programmes.

PubMed

Smith Gueye, Cara; Newby, Gretchen; Tulloch, Jim; Slutsker, Laurence; Tanner, Marcel; Gosling, Roland D

2016-09-22

A malaria eradication goal has been proposed, at the same time as a new global strategy and implementation framework. Countries are considering the strategies and tools that will enable progress towards malaria goals. The eliminating malaria case-study series reports were reviewed to identify successful programme management components using a cross-case study analytic approach. Nine out of ten case-study reports were included in the analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan). A conceptual framework for malaria elimination programme management was developed and data were extracted and synthesized. Findings were reviewed at a consultative workshop, which led to a revision of the framework and further data extraction and synthesis. Success factors of implementation, programme choices and changes, and enabling factors were distilled. Decentralized programmes enhanced engagement in malaria elimination by sub-national units and communities. Integration of the malaria programme into other health services was also common. Decentralization and integration were often challenging due to the skill and experience levels of newly tasked staff. Accountability for programme impact was not clarified for most programmes. Motivation of work force was a key factor in maintaining programme quality but there were few clear, detailed strategies provided. Different incentive schemes targeted various stakeholders. Training and supervision, although not well described, were prioritized by most programmes. Multi-sectoral collaboration helped some programmes share information, build strategies and interventions and achieve a higher quality of implementation. In most cases programme action was spurred by malaria outbreaks or a new elimination goal with strong leadership. Some programmes showed high capacity for flexibility through introduction of new strategies and tools. Several case-studies described methods for monitoring implementation quality and coverage; however analysis and feedback to those implementing malaria elimination in the periphery was not well described. Political commitment and sustained financing contributed to malaria programme success. Consistency of malaria programmes depends on political commitment, human and financial resources, and leadership. Operational capacity of the programme and the overall health system structure and strength are also important aspects. Malaria eradication will require adaptive, well-managed malaria programmes that are able to tailor implementation of evidence-based strategies, founded upon strong sub-national surveillance and response, with adequate funding and human resources.

Using remote sensing and modeling techniques to investigate the annual parasite incidence of malaria in Loreto, Peru

NASA Astrophysics Data System (ADS)

Mousam, Aneela; Maggioni, Viviana; Delamater, Paul L.; Quispe, Antonio M.

2017-10-01

Between 2001 and 2010 significant progress was made towards reducing the number of malaria cases in Peru; however, the country saw an increase between 2011 and 2015. This work attempts to uncover the associations among various climatic and environmental variables and the annual malaria parasite incidence in the Peruvian region of Loreto. A Multilevel Mixed-effects Poisson Regression model is employed, focusing on the 2009-2013 period, when trends in malaria incidence shifted from decreasing to increasing. The results indicate that variations in elevation (β = 0.78; 95% confidence interval (CI), 0.75-0.81), soil moisture (β = 0.0021; 95% CI, 0.0019-0.0022), rainfall (β = 0.59; 95% CI, 0.56-0.61), and normalized difference vegetation index (β = 2.13; 95% CI, 1.83-2.43) is associated with higher annual parasite incidence, whereas an increase in temperature (β = -0.0043; 95% CI, - 0.0044- 0.0041) is associated with a lower annual parasite incidence. The results from this study are particularly useful for healthcare workers in Loreto and have the potential of being integrated within malaria elimination plans.

Plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis.

PubMed

Brock, P M; Fornace, K M; Parmiter, M; Cox, J; Drakeley, C J; Ferguson, H M; Kao, R R

2016-04-01

The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.

Malaria determining risk factors at the household level in two rural villages of mainland Equatorial Guinea.

PubMed

Guerra, Mónica; de Sousa, Bruno; Ndong-Mabale, Nicolas; Berzosa, Pedro; Arez, Ana Paula

2018-05-18

After the introduction of an artemisinin-based combination therapy, the reduction of prevalence of malaria infections has shown a remarkable progress during the last decade. However due to the lack of a consistent malaria control programme and socioeconomic inequalities, Plasmodium infection is still one of the major cause of disease in Equatorial Guinea, namely in the rural communities. This study explored the associated risk factors of malaria transmission at the microeconomic level (households) in two rural villages of mainland Equatorial Guinea. This survey involved 232 individuals living in 69 households located in two rural villages, Ngonamanga and Miyobo, of coastal and interior of Equatorial Guinea, respectively. Malaria prevalence was measured by PCR and parasitaemia level by optical microscopy; household socioeconomic status (SES) was measured based on house characteristics using a 2-step cluster analysis. Logistic regression analysis was performed to investigate the relationship of a diverse set of independent variables on being diagnosed with malaria and on showing high levels of parasitaemia. The prevalence of Plasmodium spp. infection was 69%, with 80% of households having at least one parasitaemic member. The majority of houses have eaves (80%), walls of clay/wood (90%) and zinc roof (99%) and only 10% of them have basic sanitation facilities. The studied areas showed reduced rates of indoor residual spraying coverage (9%), and long-lasting insecticide-treated net ownership (35%), with none of these preventive tools showing any significant effects on malaria risk in these areas. Neither the risk of malaria infection (PCR positive result) or the development of high parasitaemia did show association with SES. This study has contributed to reinforce the importance of living conditions associated to a high risk of malaria infection and vulnerability to develop high parasitaemia. This study also contributes to future malaria control interventions to be implemented in mainland Equatorial Guinea or in other countries with similar environmental conditions.

A cross-sectional study of malaria endemicity and health system readiness to deliver services in Kenya, Namibia and Senegal.

PubMed

Lee, Elizabeth H; Olsen, Cara H; Koehlmoos, Tracey; Masuoka, Penny; Stewart, Ann; Bennett, Jason W; Mancuso, James

2017-11-01

Despite good progress towards elimination, malaria continues to contribute substantially to the sub-Saharan African disease burden. Sustaining previous gains requires continued readiness to deliver malaria services in response to actual disease burden, which in turn contributes to health systems strengthening. This study investigates a health system innovation. We examined whether malaria prevalence, or endemicity, is a driver of health facility readiness to deliver malaria services. To estimate this association, we geo-linked cross-sectional facility survey data to endemicity data for Kenya, Namibia and Senegal. We tested the validity and reliability of the primary study outcome, the malaria service readiness index and mapped service readiness components in a geographic information system. We conducted a weighted multivariable linear regression analysis of the relationship between endemicity and malaria service readiness, stratified for urban or rural facility location. As endemicity increased in rural areas, there was a concurrent, modest increase in service readiness at the facility level [β: 0.028; (95% CI 0.008, 0.047)], whereas no relationship existed in urban settings. Private-for-profit facilities were generally less prepared than public [β: -0.102; (95% CI - 0.154, -0.050)]. Most facilities had the necessary supplies to diagnose malaria, yet availability of malaria guidelines and adequately trained staff as well as medicines and commodities varied. Findings require cautious interpretation outside the study sample, which was a more limited subset of the original surveys' sampling schemes. Our approach and findings may be used by national malaria programs to identify low performing facilities in malarious areas for targeted service delivery interventions. This study demonstrates use of existing data sources to evaluate health system performance and to identify within- and cross-country variations for targeted interventions. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine 2017. This work is written by US Government employees and is in the public domain in the US.

Malaria early warning tool: linking inter-annual climate and malaria variability in northern Guadalcanal, Solomon Islands.

PubMed

Smith, Jason; Tahani, Lloyd; Bobogare, Albino; Bugoro, Hugo; Otto, Francis; Fafale, George; Hiriasa, David; Kazazic, Adna; Beard, Grant; Amjadali, Amanda; Jeanne, Isabelle

2017-11-21

Malaria control remains a significant challenge in the Solomon Islands. Despite progress made by local malaria control agencies over the past decade, case rates remain high in some areas of the country. Studies from around the world have confirmed important links between climate and malaria transmission. This study focuses on understanding the links between malaria and climate in Guadalcanal, Solomon Islands, with a view towards developing a climate-based monitoring and early warning for periods of enhanced malaria transmission. Climate records were sourced from the Solomon Islands meteorological service (SIMS) and historical malaria case records were sourced from the National Vector-Borne Disease Control Programme (NVBDCP). A declining trend in malaria cases over the last decade associated with improved malaria control was adjusted for. A stepwise regression was performed between climate variables and climate-associated malaria transmission (CMT) at different lag intervals to determine where significant relationships existed. The suitability of these results for use in a three-tiered categorical warning system was then assessed using a Mann-Whitney U test. Of the climate variables considered, only rainfall had a consistently significant relationship with malaria in North Guadalcanal. Optimal lag intervals were determined for prediction using R 2 skill scores. A highly significant negative correlation (R = - 0.86, R 2  = 0.74, p < 0.05, n = 14) was found between October and December rainfall at Honiara and CMT in northern Guadalcanal for the subsequent January-June. This indicates that drier October-December periods are followed by higher malaria transmission periods in January-June. Cross-validation emphasized the suitability of this relationship for forecasting purposes [Formula: see text]  as did Mann-Whitney U test results showing that rainfall below or above specific thresholds was significantly associated with above or below normal malaria transmission, respectively. This study demonstrated that rainfall provides the best predictor of malaria transmission in North Guadalcanal. This relationship is thought to be underpinned by the unique hydrological conditions in northern Guadalcanal which allow sandbars to form across the mouths of estuaries which act to develop or increase stagnant brackish marshes in low rainfall periods. These are ideal habitats for the main mosquito vector, Anopheles farauti. High rainfall accumulations result in the flushing of these habitats, reducing their viability. The results of this study are now being used as the basis of a malaria early warning system which has been jointly implemented by the SIMS, NVBDCP and the Australian Bureau of Meteorology.

What is surgery?

PubMed

Krummel, Thomas M

2006-11-01

Progress in surgical science has been characterized by a continuous cycle of innovation from bedside to bench to bedside. Beginning 30,000 years ago with the first bone needles to surgical lasers and robotics of today, each quantum leap has resulted from the convergence of technical advances and creative surgeons, but always defined by an attitude of care toward the sick. One of the most innovative pediatric surgeons, Dr. Mark Ravitch, elucidated some simple yet profound principles in the precise answer to the question "What is Surgery?" This section outlines some simple concepts summarized as "Ravitch's Rules," which provide a useful framework for clarity in understanding the past and illuminating the road ahead. Surgeons must be thoughtful in how they define themselves and their craft, ignoring technological advances at their own peril.

Implementation of G6PD testing and primaquine for P. vivax radical cure: Operational perspectives from Thailand and Cambodia.

PubMed

Kitchakarn, Suravadee; Lek, Dysoley; Thol, Sea; Hok, Chantheasy; Saejeng, Aungkana; Huy, Rekol; Chinanonwait, Nipon; Thimasarn, Krongthong; Wongsrichanalai, Chansuda

2017-09-01

Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection. Primaquine is the only anti-hypnozoite drug against P. vivax relapse currently available, with tafenoquine in the pipeline. However, both drugs may cause severe haemolysis in individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), a hereditary defect. The overall incidence of malaria has significantly declined in both Thailand and Cambodia over the last 15 years. However, P. vivax has replaced P. falciparum as the dominant species in large parts of both countries. This paper presents the experience of the national malaria control programmes of the two countries, in their efforts to implement safe primaquine therapy for the radical cure, i.e. relapse prevention, of P. vivax malaria by introducing a rapid, point-of-care test to screen for G6PD deficiency.

Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

PubMed Central

Arévalo-Herrera, Myriam; Solarte, Yezid; Marin, Catherin; Santos, Mariana; Castellanos, Jenniffer; Beier, John C; Valencia, Sócrates Herrera

2016-01-01

Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America. PMID:21881775

Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination.

PubMed

Ouji, Manel; Augereau, Jean-Michel; Paloque, Lucie; Benoit-Vical, Françoise

2018-01-01

The use of artemisinin-based combination therapies (ACTs), which combine an artemisinin derivative with a partner drug, in the treatment of uncomplicated malaria has largely been responsible for the significant reduction in malaria-related mortality in tropical and subtropical regions. ACTs have also played a significant role in the 18% decline in the incidence of malaria cases from 2010 to 2016. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterised by delayed parasitic clearance and a high rate of recrudescence, as reported in 2008 in Western Cambodia. Resistance to artemisinins has already spread to several countries in Southeast Asia. Furthermore, resistance to partner drugs has been shown in some instances to be facilitated by pre-existing decreased susceptibility to the artemisinin component of the ACT. A major concern is not only the spread of these multidrug-resistant parasites to the rest of Asia but also their possible appearance in Sub-Saharan Africa, the continent most affected by malaria, as has been the case in the past with parasite resistance to other antimalarial treatments. It is therefore essential to understand the acquisition of resistance to artemisinins by Plasmodium falciparum to adapt malaria treatment policies and to propose new therapeutic solutions. © M. Ouji et al., published by EDP Sciences, 2018.

Balancing the Pendulum of Freedom

DTIC Science & Technology

2008-03-25

16 Geoffrey R. Stone, “Perilous Times; Free Speech in Wartime from the Sedition Act of 1798 to the War on Terrorism,” linked from the Woodrow...the Sedition Act of 1798 to the War on Terrorism.” 20 “Eugene V. Debs.” 21 Stone, “Perilous Times; Free Speech in Wartime from the Sedition Act...deemed a violation of the Fourth Amendment… No federal official is authorized to commit a crime on behalf of the government.”8 The Supreme Court has

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.

The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in northwestern Brazil.

PubMed

Pincelli, Anaclara; Neves, Paulo A R; Lourenço, Barbara H; Corder, Rodrigo M; Malta, Maíra B; Sampaio-Silva, Juliana; de Souza, Rodrigo M; Cardoso, Marly A; Castro, Marcia C; Ferreira, Marcelo U; For The Mina Brazil Working Group

2018-05-07

We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax , were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z -scores of 0.35 (95% confidence interval [CI] = 0.14-0.57) and in birth length z -scores of 0.31 (95% CI = 0.08-0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05-0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite's DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.

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

The Curious Case of the OZ439 Mesylate Salt: An Amphiphilic Antimalarial Drug with Diverse Solution and Solid State Structures.

PubMed

Clulow, Andrew J; Salim, Malinda; Hawley, Adrian; Gilbert, Elliot P; Boyd, Ben J

2018-05-07

Efforts to develop orally administered drugs tend to place an exceptional focus on aqueous solubility as this is an essential criterion for their absorption in the gastrointestinal tract. In this work we examine the solid state behavior and solubility of OZ439, a promising single-dose cure for malaria being developed as the highly water-soluble mesylate salt. The aqueous phase behavior of the OZ439 mesylate salt was determined using a combination of small angle neutron and X-ray scattering (SANS and SAXS, respectively). It was found that this salt has low solubility at low concentrations with the drug largely precipitated in free base aggregates. However, with increasing concentration these crystalline aggregates were observed to dissociate into cationic micelles and lamellar phases, effectively increasing the dissolved drug concentration. It was also found that the dissolved OZ439 spontaneously precipitated in the presence of biologically relevant anions, which we attribute to the high lattice energies of most of the salt forms of the drug. These findings show that aqueous solubility is not always what it seems in the context of amphiphilic drug molecules and highlights that its use as the principal metric in selecting drug candidates for development can be perilous.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

PubMed

Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

2010-04-20

The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that capacity development in clinical trials is best carried out in the context of preparation for specific trials. In this regard MCTA centres involved in the phase III malaria vaccine trial were, on average, more successful at consolidating the training and infrastructure support than those centres focussing only on drug trials.

Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific.

PubMed

Wen, Shawn; Harvard, Kelly E; Gueye, Cara Smith; Canavati, Sara E; Chancellor, Arna; Ahmed, Be-Nazir; Leaburi, John; Lek, Dysoley; Namgay, Rinzin; Surya, Asik; Thakur, Garib D; Whittaker, Maxine Anne; Gosling, Roly D

2016-05-10

Significant progress has been made in reducing the malaria burden in the Asia Pacific region, which is aggressively pursuing a 2030 regional elimination goal. Moving from malaria control to elimination requires National Malaria Control Programmes (NMCPs) to target interventions at populations at higher risk, who are often not reached by health services, highly mobile and difficult to test, treat, and track with routine measures, and if undiagnosed, can maintain parasite reservoirs and contribute to ongoing transmission. A qualitative, free-text questionnaire was developed and disseminated among 17 of the 18 partner countries of the Asia Pacific Malaria Elimination Network (APMEN). All 14 countries that responded to the survey identified key populations at higher risk of malaria in their respective countries. Thirteen countries engage in the dissemination of malaria-related Information, Education, and Communication (IEC) materials. Eight countries engage in diagnostic screening, including of mobile and migrant workers, military staff, and/or overseas workers. Ten countries reported distributing or recommending the use of long-lasting insecticide-treated nets (LLINs) among populations at higher risk with fewer countries engaging in other prevention measures such as indoor residual spraying (IRS) (two countries), spatial repellents (four countries), chemoprophylaxis (five countries), and mass drug administration (MDA) (three countries). Though not specifically tailored to populations at higher risk, 11 countries reported using mass blood surveys as a surveillance tool and ten countries map case data. Most NMCPs lack a monitoring and evaluation structure. Countries in the Asia Pacific have identified populations at higher risk and targeted interventions to these groups but there is limited information on the effectiveness of these interventions. Platforms like APMEN offer the opportunity for the sharing of protocols and lessons learned related to finding, targeting and successfully clearing malaria from populations at higher risk. The sharing of programme data across borders may further strengthen national and regional efforts to eliminate malaria. This exchange of real-life experience is invaluable to NMCPs when scarce scientific evidence on the topic exists to aid decision-making and can further support NMCPs to develop strategies that will deliver a malaria-free Asia Pacific by 2030.

Strengthening individual capacity in monitoring and evaluation of malaria control programmes to streamline M&E systems and enhance information use in malaria endemic countries.

PubMed

Garley, Ashley; Eckert, Erin; Sie, Ali; Ye, Maurice; Malm, Keziah; Afari, Edwin A; Sawadogo, Mamadou; Herrera, Samantha; Ivanovich, Elizabeth; Ye, Yazoume

2016-05-28

Malaria control interventions in most endemic countries have intensified in recent years and so there is a need for a robust monitoring and evaluation (M&E) system to measure progress and achievements. Providing programme and M&E officers with the appropriate skills is a way to strengthen malaria's M&E systems and enhance information use for programmes' implementation. This paper describes a recent effort in capacity strengthening for malaria M&E in sub-Saharan Africa (SSA). From 2010 to 2014, capacity-strengthening efforts consisted of organizing regional in-person workshops for M&E of malaria programmes for Anglophone and Francophone countries in SSA in collaboration with partners from Ghana and Burkina Faso. Open-sourced online courses were also available in English. A post-workshop assessment was conducted after 5 years to assess the effects of these regional workshops and identify gaps in capacity. The regional workshops trained 181 participants from 28 countries from 2010 to 2014. Trained participants were from ministries of health, national malaria control and elimination programmes, non-governmental organizations, and development partners. The average score (%) for participants' knowledge tests increased from pretest to posttest for Anglophone workshops (2011: 59 vs. 76, 2012: 41 vs. 63, 2013: 51 vs. 73; 2014: 50 vs. 74). Similarly, Francophone workshop posttest scores increased, but were lower than Anglophone due to higher scores at pretest. (2011: 70 vs. 76, 2012: 74 vs. 79, 2013: 61 vs. 68; 2014: 64 vs. 75). Results of the post-workshop assessment revealed that participants retained practical M&E knowledge and skills for malaria programs, but there is a need for a module on malaria surveillance adapted to the pre-elimination context. The workshops were successful because of the curriculum content, facilitation quality, and the engagement of partner institutions with training expertise. Results from the post-workshop assessment will guide the curriculum's development and restructuring for the next phase of workshops. Country-specific malaria M&E capacity needs assessments may also inform this process as countries reduce malaria burden.

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

PubMed Central

Smithson, Paul; Florey, Lia; Salgado, S. Rene; Hershey, Christine L.; Masanja, Honorati; Bhattarai, Achuyt; Mwita, Alex; McElroy, Peter D.

2015-01-01

Background Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period. Methods Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM. Results Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains. Conclusion Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival. PMID:26536354

Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

PubMed Central

2010-01-01

Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that capacity development in clinical trials is best carried out in the context of preparation for specific trials. In this regard MCTA centres involved in the phase III malaria vaccine trial were, on average, more successful at consolidating the training and infrastructure support than those centres focussing only on drug trials. PMID:20406478

Challenges in and lessons learned during the implementation of the 1-3-7 malaria surveillance and response strategy in China: a qualitative study.

PubMed

Lu, Guangyu; Liu, Yaobao; Beiersmann, Claudia; Feng, Yu; Cao, Jun; Müller, Olaf

2016-10-05

China has made great progress in malaria control over the last century and now aims to eliminate malaria by 2020. In 2012, the country launched its 1-3-7 surveillance and response strategy for malaria elimination. The strategy involves to case reporting within 1 day, case investigation within 3 days, and focus investigation and public health actions within 7 days. The aim of this study was to evaluate the challenges in and lessons learned during the implementation of the 1-3-7 strategy in China so far. This qualitative study was conducted in two provinces in China: Gansu province (northwestern China) and Jiangsu province (southeastern China) in 2014. Key informant interviews (n = 6) and in-depth interviews (n = 36) about the implementation aspects of the 1-3-7 strategy were conducted with malaria experts, health staff, laboratory practitioners, and village doctors at the provincial, city, county, township, and village levels. Broad themes related to the challenges in and lessons learned during the implementation of the 1-3-7 strategy were identified according to: case reporting within 1 day, case investigation within 3 days, focus investigation within 7 days, and the overall strategy. The major challenges outlined were related to respecting the timeline of surveillance procedures, the absence of or difficulties in following guidelines on conducting focus investigations, diagnostics, and the increasing number of returning migrant workers from malaria-endemic countries. Important lessons learned revolve around the importance of continuous capacity building, supervision and motivation, quality control, information technology support, applied research, governmental commitment, and intersectoral collaboration. Surveillance is a key intervention in malaria elimination programs. The Chinese 1-3-7 strategy has already proven to be successful but still needs to be improved. In particular, dealing appropriately with imported malaria cases through the screening of migrant workers from malaria-endemic countries is essential for achieving and sustaining malaria elimination in China. China has perfect preconditions for successful malaria elimination provided political commitment and financial investment are guaranteed. The 1-3-7 strategy may also be considered as a model for other countries.

The perils of the imperfect expectation of the perfect baby.

PubMed

Chervenak, Frank A; McCullough, Laurence B; Brent, Robert L

2010-08-01

Advances in modern medicine invite the assumption that medicine can control human biology. There is a perilous logic that leads from expectations of medicine's control over reproductive biology to the expectation of having a perfect baby. This article proposes that obstetricians should take a preventive ethics approach to the care of pregnant women with expectations for a perfect baby. We use Nathaniel Hawthorne's classic short story, "The Birthmark," to illustrate the perils of the logic of control and perfection through science and then identify possible contemporary sources of the expectation of the perfect baby. We propose that the informed consent process should be used as a preventive ethics tool throughout the course of pregnancy to educate pregnant women about the inherent errors of human reproduction, the highly variable clinical outcomes of these errors, the limited capacity of medicine to detect these errors, and the even more limited capacity to correct them. Copyright (c) 2010 Mosby, Inc. All rights reserved.

In vivo photoacoustic flow cytometry for early malaria diagnosis.

PubMed

Cai, Chengzhong; Carey, Kai A; Nedosekin, Dmitry A; Menyaev, Yulian A; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I; Stumhofer, Jason S; Zharov, Vladimir P

2016-06-01

In vivo photoacoustic (PA) flow cytometry (PAFC) has already demonstrated a great potential for the diagnosis of deadly diseases through ultrasensitive detection of rare disease-associated circulating markers in whole blood volume. Here, we demonstrate the first application of this powerful technique for early diagnosis of malaria through label-free detection of malaria parasite-produced hemozoin in infected red blood cells (iRBCs) as high-contrast PA agent. The existing malaria tests using blood smears can detect the disease at 0.001-0.1% of parasitemia. On the contrary, linear PAFC showed a potential for noninvasive malaria diagnosis at an extremely low level of parasitemia of 0.0000001%, which is ∼10(3) times better than the existing tests. Multicolor time-of-flight PAFC with high-pulse repetition rate lasers at wavelengths of 532, 671, and 820 nm demonstrated rapid spectral and spatial identification and quantitative enumeration of individual iRBCs. Integration of PAFC with fluorescence flow cytometry (FFC) provided real-time simultaneous detection of single iRBCs and parasites expressing green fluorescence proteins, respectively. A combination of linear and nonlinear nanobubble-based multicolor PAFC showed capability to real-time control therapy efficiency by counting of iRBCs before, during, and after treatment. Our results suggest that high-sensitivity, high-resolution ultrafast PAFC-FFC platform represents a powerful research tool to provide the insight on malaria progression through dynamic study of parasite-cell interactions directly in bloodstream, whereas portable hand-worn PAFC device could be broadly used in humans for early malaria diagnosis. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

Impact of climate change upon vector born diseases in Europe and Africa using ENSEMBLES Regional Climate Models

NASA Astrophysics Data System (ADS)

Caminade, Cyril; Morse, Andy

2010-05-01

Climate variability is an important component in determining the incidence of a number of diseases with significant human/animal health and socioeconomic impacts. The most important diseases affecting health are vector-borne, such as malaria, Rift Valley Fever and including those that are tick borne, with over 3 billion of the world population at risk. Malaria alone is responsible for at least one million deaths annually, with 80% of malaria deaths occurring in sub-Saharan Africa. The climate has a large impact upon the incidence of vector-borne diseases; directly via the development rates and survival of both the pathogen and the vector, and indirectly through changes in the environmental conditions. A large ensemble of regional climate model simulations has been produced within the ENSEMBLES project framework for both the European and African continent. This work will present recent progress in human and animal disease modelling, based on high resolution climate observations and regional climate simulations. Preliminary results will be given as an illustration, including the impact of climate change upon bluetongue (disease affecting the cattle) over Europe and upon malaria and Rift Valley Fever over Africa. Malaria scenarios based on RCM ensemble simulations have been produced for West Africa. These simulations have been carried out using the Liverpool Malaria Model. Future projections highlight that the malaria incidence decreases at the northern edge of the Sahel and that the epidemic belt is shifted southward in autumn. This could lead to significant public health problems in the future as the demography is expected to dramatically rise over Africa for the 21st century.

Using Nano-mechanics and Surface Acoustic Wave (SAW) for Disease Monitoring and Diagnostics at a Cellular Level in Red Blood Cells

NASA Astrophysics Data System (ADS)

Sivanantha, Ninnuja; Ma, Charles; Collins, David J.; Sesen, Muhsincan; Brenker, Jason; Coppel, Ross L.; Neild, Adrian; Alan, Tuncay

A popular approach to monitoring diseases and their diagnosis is through biological, pathological or immunological characterization. However, at a cellular level progression of certain diseases manifests itself through mechanical effects as well. Here, we present a method which exploits localised flow; surface acoustic wave (SAW) induced acoustic streaming in a 9 μL droplet to characterize the adhesive properties of red blood cells (healthy, gluteraldehyde treated and malaria infected) in approximately 50 seconds. Our results show a 79% difference in cell mobilization between healthy malaria infected RBCs (and a 39% difference between healthy and treated ones), indicating that the method can serve as a platform for rapid clinical diagnosis; where separation of two or more different cell populations in a mixed solution is desirable. It can also act as a key biomarker for monitoring some diseases offering quantitative measures of disease progression and response to therapy.

A systematic review of knowledge, attitudes and beliefs about malaria among the South Asian population

PubMed Central

Regmi, Krishna; Kunwar, Anju; Ortega, Leonard

2016-01-01

Background Malaria is one of the deadliest mosquito-borne diseases in the world. More than 80% of the total populations are at risk of malaria in the 22 countries in Asia and the Pacific. South Asia alone is home to an estimated 1.4 billion people at risk of contracting malaria. Despite the remarkable progress in reducing the burden of malaria, evidence of the disease based on knowledge of the social and cultural contexts from a South Asian perspective is limited. Our objective was to understand the knowledge, attitudes and beliefs about malaria in South Asian communities. Methodology We conducted a systematic literature review, searching six databases, between 1990 and 2015, focusing on knowledge, attitudes and beliefs about malaria in South Asia. Databases were searched using both ‘free terms’ and ‘index terms’ funnelled using Boolean operators and truncations. Inclusion and exclusion criteria were set, and included papers were scrutinised, employing a critical appraisal tool to find the best available evidences to support the study purpose. Results and discussion Evidence from 32 articles (26 quantitative, four qualitative and two mixed methods). General knowledge and awareness of the disease, its transmission, and control and preventative measures were generally found to be lacking amongst both the general public and healthcare professionals. In addition, the study shows that poor socio-economic factors – including limited access to services due to poor/limited availability – and issues of affordability are considered as major risk factors. Conclusion This review suggests the importance of increasing health awareness, mobilising the local or community healthcare professionals, for prevention as well as early detection and effective treatment of malaria among people who are at risk. Malaria is also a disease associated with poverty and socio-cultural factors; therefore, strong political will, wider partnerships between health and non-health sectors, and strengthening health systems’ technical and managerial capabilities at all level of primary healthcare systems, is inevitable. PMID:27141987

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

Increasing malaria hospital admissions in Uganda between 1999 and 2009

PubMed Central

2011-01-01

Background Some areas of Africa are witnessing a malaria transition, in part due to escalated international donor support and intervention coverage. Areas where declining malaria rates have been observed are largely characterized by relatively low baseline transmission intensity and rapid scaling of interventions. Less well described are changing patterns of malaria burden in areas of high parasite transmission and slower increases in control and treatment access. Methods Uganda is a country predominantly characterized by intense, perennial malaria transmission. Monthly pediatric admission data from five Ugandan hospitals and their catchments have been assembled retrospectively across 11 years from January 1999 to December 2009. Malaria admission rates adjusted for changes in population density within defined catchment areas were computed across three time periods that correspond to periods where intervention coverage data exist and different treatment and prevention policies were operational. Time series models were developed adjusting for variations in rainfall and hospital use to examine changes in malaria hospitalization over 132 months. The temporal changes in factors that might explain changes in disease incidence were qualitatively examined sequentially for each hospital setting and compared between hospital settings Results In four out of five sites there was a significant increase in malaria admission rates. Results from time series models indicate a significant month-to-month increase in the mean malaria admission rates at four hospitals (trend P < 0.001). At all hospitals malaria admissions had increased from 1999 by 47% to 350%. Observed changes in intervention coverage within the catchments of each hospital showed a change in insecticide-treated net coverage from <1% in 2000 to 33% by 2009 but accompanied by increases in access to nationally recommended drugs at only two of the five hospital areas studied. Conclusions The declining malaria disease burden in some parts of Africa is not a universal phenomena across the continent. Despite moderate increases in the coverage of measures to reduce infection and disease without significant coincidental increasing access to effective medicines to treat disease may not lead to severe disease burden reductions in high transmission areas of Africa. More data is needed from a wider range of malaria settings to provide an honest tracking progress of the impact of scaled intervention coverage in Africa. PMID:21486498

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.

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

PubMed Central

2012-01-01

Background Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. Methods The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Juruá valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. Results The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 – 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 – 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 – 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. Conclusions In the remote region of the Juruá valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria. PMID:22905900

Drug use in the management of uncomplicated malaria in public health facilities in the Democratic Republic of the Congo.

PubMed

Ntamabyaliro, Nsengi Y; Burri, Christian; Nzolo, Didier B; Engo, Aline B; Lula, Yves N; Mampunza, Samuel M; Nsibu, Célestin N; Mesia, Gauthier K; Kayembe, Jean-Marie N; Likwela, Joris L; Kintaudi, Leon M; Tona, Gaston L

2018-05-03

Malaria the first causes of death from parasitic infection worldwide. Interventions to reduce the burden of malaria have produced a tremendous drop in malaria morbidity and mortality. However, progress is slower in DRC, which shares with Nigeria 39% of deaths related to malaria globally. Inappropriate use of drugs may be one of the factors of this below-average performance. The aim of this study was to describe the use of drugs in the management of uncomplicated malaria in public health facilities in DRC. A drug use study was carried out in DRC from January to March 2014. In each of the former 11 provinces of DRC, one Rural Health Centre, one Urban Health Centre and one General Hospital were selected. In each of them, 100 patient's files containing prescription of anti-malarials from January to December 2013 were randomly selected. Among them, all of the files with diagnosis of uncomplicated malaria were included in this study. Prescribed anti-malarials, co-prescribed drugs and their indications were collected. Descriptive analyses were performed. A total of 2300 files out of 3300 (69.7%) concerned uncomplicated malaria and were included in analysis. Malaria treatment was initiated after a positive RDT or microscopy in 51.5% of cases, upon suspicion without requesting biological confirmation in 37% and despite negative results in 11%. Twenty-nine (29) different treatment regimens were used. The drugs recommended by the National Malaria Control Programme were used in 54.3% of cases (artesunate-amodiaquine 37.4% or artemether-lumefantrine 16.9%). The second most used anti-malarial was quinine (32.4%). Apart from anti-malarials, an average of 3.1 drugs per patient were prescribed, among which antibiotics (67.9%), analgesics and non-steroidal anti-inflammatory (NSAIDs) (all abbreviations to be explicated on first use) (70.6%), vitamins (29.1%), anaemia drugs, including blood transfusion (9.1%) and corticosteroids (5.7%), In 51.4% of cases there was no indication for the concomitant medication. Management of uncomplicated malaria in DRC is characterized by a low adherence to treatment policy, numerous treatment regimens, and abundant concomitant medication potentially harmful to the patient. This may contribute to the low performance of DRC in malaria control. Determinant of this irrational use of drugs need to be assessed in order to formulate and implement efficient corrective measures.

Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

NASA Astrophysics Data System (ADS)

Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

2016-03-01

Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation.

The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology

PubMed Central

Safeukui, Innocent; Deplaine, Guillaume; Brousse, Valentine; Prendki, Virginie; Thellier, Marc; Turner, Gareth D.; Mercereau-Puijalon, Odile

2011-01-01

Clinical manifestations of Plasmodium falciparum infection are induced by the asexual stages of the parasite that develop inside red blood cells (RBCs). Because splenic microcirculatory beds filter out altered RBCs, the spleen can innately clear subpopulations of infected or uninfected RBC modified during falciparum malaria. The spleen appears more protective against severe manifestations of malaria in naïve than in immune subjects. The spleen-specific pitting function accounts for a large fraction of parasite clearance in artemisinin-treated patients. RBC loss contributes to malarial anemia, a clinical form associated with subacute progression, frequent splenomegaly, and relatively low parasitemia. Stringent splenic clearance of ring-infected RBCs and uninfected, but parasite-altered, RBCs, may altogether exacerbate anemia and reduce the risks of severe complications associated with high parasite loads, such as cerebral malaria. The age of the patient directly influences the risk of severe manifestations. We hypothesize that coevolution resulting in increased splenic clearance of P. falciparum–altered RBCs in children favors the survival of the host and, ultimately, sustained parasite transmission. This analysis of the RBC–spleen dynamic interactions during P falciparum infection reflects both data and hypotheses, and provides a framework on which a more complete immunologic understanding of malaria pathogenesis may be elaborated. PMID:20852127

Image classification of unlabeled malaria parasites in red blood cells.

PubMed

Zheng Zhang; Ong, L L Sharon; Kong Fang; Matthew, Athul; Dauwels, Justin; Ming Dao; Asada, Harry

2016-08-01

This paper presents a method to detect unlabeled malaria parasites in red blood cells. The current "gold standard" for malaria diagnosis is microscopic examination of thick blood smear, a time consuming process requiring extensive training. Our goal is to develop an automate process to identify malaria infected red blood cells. Major issues in automated analysis of microscopy images of unstained blood smears include overlapping cells and oddly shaped cells. Our approach creates robust templates to detect infected and uninfected red cells. Histogram of Oriented Gradients (HOGs) features are extracted from templates and used to train a classifier offline. Next, the ViolaJones object detection framework is applied to detect infected and uninfected red cells and the image background. Results show our approach out-performs classification approaches with PCA features by 50% and cell detection algorithms applying Hough transforms by 24%. Majority of related work are designed to automatically detect stained parasites in blood smears where the cells are fixed. Although it is more challenging to design algorithms for unstained parasites, our methods will allow analysis of parasite progression in live cells under different drug treatments.

Worldwide Emerging Environmental Issues Affecting the U.S. Military. November 2007 Report

DTIC Science & Technology

2007-11-01

Economist.com, Nov 19th 2007, DELHI http://www.economist.com/daily/news/displaystory.cfm?story_id=10163828&top_story=1 Andes water supply in peril...Economist.com, Nov 19th 2007, DELHI http://www.economist.com/daily/news/displaystory.cfm?story_id=10163828&top_story=1 Andes water supply in peril, scientists...Committee………………………………...3 Item 6. Reducing Military Footprint with Solar Energy at 30 Cents per Watt……………...4 Item 7. Updates on Previously Identified

BDA-410: a novel synthetic calpain inhibitor active against blood stage malaria.

PubMed

Li, Xuerong; Chen, Huiqing; Jeong, Jong-Jin; Chishti, Athar H

2007-09-01

Falcipains, the papain-family cysteine proteases of the Plasmodium falciparum, are potential drug targets for malaria parasite. Pharmacological inhibition of falcipains can block the hydrolysis of hemoglobin, parasite development, and egress, suggesting that falcipains play a key role at the blood stage of parasite life cycle. In the present study, we evaluated the anti-malarial effects of BDA-410, a novel cysteine protease inhibitor as a potential anti-malarial drug. Recombinant falcipain (MBP-FP-2B) and P. falciparum trophozoite extract containing native falcipains were used for enzyme inhibition studies in vitro. The effect of BDA-410 on the malaria parasite development in vitro as well as its anti-malarial activity in vivo was evaluated using the Plasmodium chabaudi infection rodent model. The 50% inhibitory concentrations of BDA-410 were determined to be 628 and 534nM for recombinant falcipain-2B and parasite extract, respectively. BDA-410 inhibited the malaria parasite growth in vitro with an IC(50) value of 173nM causing irreversible damage to the intracellular parasite. In vivo, the BDA-410 delayed the progression of malaria infection significantly using a mouse model of malaria pathogenesis. The characterization of BDA-410 as a potent inhibitor of P. falciparum cysteine proteases, and the demonstration of its efficacy in blocking parasite growth both in vitro and in vivo assays identifies BDA-410 is an important lead compound for the development of novel anti-malarial drugs.

BDA-410: A novel synthetic calpain inhibitor active against blood stage malaria

PubMed Central

Li, Xuerong; Chen, Huiqing; Jeong, Jong-Jin; Chishti, Athar H.

2007-01-01

Falcipains, the papain-family cysteine proteases of the Plasmodium falciparum, are potential drug targets for malaria parasite. Pharmacological inhibition of falcipains can block the hydrolysis of hemoglobin, parasite development, and egress, suggesting that falcipains play a key role at the blood stage of parasite life cycle. In the present study, we evaluated the anti-malarial effects of BDA-410, a novel cysteine protease inhibitor as a potential antimalarial drug. Recombinant falcipain (MBP-FP-2B) and Plasmodium falciparum trophozoite extract containing native falcipains were used for enzyme inhibition studies in vitro. The effect of BDA-410 on the malaria parasite development in vitro as well as its anti-malarial activity in vivo was evaluated using the Plasmodium chabaudi infection rodent model. The 50% inhibitory concentrations of BDA-410 were determined to be 628 nM and 534 nM for recombinant falcipain-2B and parasite extract, respectively. BDA-410 inhibited the malaria parasite growth in vitro with an IC50 value of 173 nM causing irreversible damage to the intracellular parasite. In vivo, the BDA-410 delayed the progression of malaria infection significantly using a mouse model of malaria pathogenesis. The characterization of BDA-410 as a potent inhibitor of Plasmodium falciparum cysteine proteases, and the demonstration of its efficacy in blocking parasite growth both in vitro and in vivo assays identifies BDA-410 is an important lead compound for the development of novel anti-malarial drugs. PMID:17583361

Artemisinin resistance--modelling the potential human and economic costs.

PubMed

Lubell, Yoel; Dondorp, Arjen; Guérin, Philippe J; Drake, Tom; Meek, Sylvia; Ashley, Elizabeth; Day, Nicholas P J; White, Nicholas J; White, Lisa J

2014-11-23

Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. This analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool. Using conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment. These 'ballpark' figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world.

Evidence on anti-malarial and diagnostic markets in Cambodia to guide malaria elimination strategies and policies.

PubMed

Phok, Sochea; Lek, Dysoley

2017-04-25

Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities. From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was conducted among 180 communes. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. A total of 26,664 outlets were screened, and 1303 outlets were eligible and interviewed. Among all screened outlets in the public sector, 75.9% of public health facilities and 67.7% of community health workers stocked both malaria diagnostic testing and a first-line artemisinin-based combination therapy (ACT). Among anti-malarial-stocking private sector outlets, 64.7% had malaria blood testing available, and 70.9% were stocking a first-line ACT. Market share data illustrate that most of the anti-malarials were sold or distributed through the private sector (58.4%), including itinerant drug vendors (23.4%). First-line ACT accounted for the majority of the market share across the public and private sectors (90.3%). Among private sector outlets stocking any anti-malarial, the proportion of outlets with a first-line ACT or RDT was higher among outlets that had reportedly received one or more forms of 'support' (e.g. reportedly received training in the previous year on malaria diagnosis [RDT and/or microscopy] and/or the national treatment guidelines for malaria) compared to outlets that did not report receiving any support (ACT: 82.1 and 60.6%, respectively; RDT: 78.2 and 64.0%, respectively). The results point to high availability and distribution of first-line ACT and widespread availability of malaria diagnosis, especially in the public sector. This suggests that there is a strong foundation for achieving elimination goals in Cambodia. However, key gaps in terms of availability of malaria commodities for case management must be addressed, particularly in the private sector where most people seek treatment. Continued engagement with the private sector will be important to ensure accelerated progress towards malaria elimination.

Development of malaria transmission-blocking vaccines: from concept to product.

PubMed

Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi

2015-06-01

Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward the development of effective transmission-blocking vaccines for malaria.

PubMed

Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

2015-05-01

The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa.

PubMed

Parpia, Alyssa S; Ndeffo-Mbah, Martial L; Wenzel, Natasha S; Galvani, Alison P

2016-03-01

Response to the 2014-2015 Ebola outbreak in West Africa overwhelmed the healthcare systems of Guinea, Liberia, and Sierra Leone, reducing access to health services for diagnosis and treatment for the major diseases that are endemic to the region: malaria, HIV/AIDS, and tuberculosis. To estimate the repercussions of the Ebola outbreak on the populations at risk for these diseases, we developed computational models for disease transmission and infection progression. We estimated that a 50% reduction in access to healthcare services during the Ebola outbreak exacerbated malaria, HIV/AIDS, and tuberculosis mortality rates by additional death counts of 6,269 (2,564-12,407) in Guinea; 1,535 (522-2,8780) in Liberia; and 2,819 (844-4,844) in Sierra Leone. The 2014-2015 Ebola outbreak was catastrophic in these countries, and its indirect impact of increasing the mortality rates of other diseases was also substantial.

A 2020 vision for vaccines against HIV, tuberculosis and malaria.

PubMed

Rappuoli, Rino; Aderem, Alan

2011-05-26

Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.

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.

Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

PubMed Central

Kenthirapalan, Sanketha; Waters, Andrew P.; Matuschewski, Kai; Kooij, Taco W. A.

2016-01-01

Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria. PMID:26796412

[Analysis on the performance evaluation of the Global Fund Malaria Programme in China from 2003 to 2013].

PubMed

Zhang, Q F; Wang, R B; Zheng, B; Xia, Z G; Zhou, S S

2017-05-06

Objective: To analyze the performance of the 5 Global Fund Malaria Programmes in China from 2003 to 2013. Methods: All of the proposals, summaries, progress reports, survey reports, Monitoring& Evaluation reports, and performance rating reports of the 5 Global Fund Malaria Programmes in China and the epidemic data of program areas were collected for statistical analysis from 2012 to 2014. Symposiums were held with relevant experts from national and provincial Centers for Disease Control and Prevention, program managers and staffs from national and provincial Global Fund Malaria Programme offices. The completion of the relevant programme indicators (including the general grant information such as program areas, beneficiaries and funding; the implementation of malaria control measures; the performance of malaria control measures; the malaria incidence in the program areas; the prevalence of malaria parasites; and program management and performance evaluation) were analyzed, and the results: of the symposiums were summarized. Results The implementation period of the 5 Global Fund Malaria Programs were as follows: Round 1 from 2003 to 2008, Round 5 from 2006 to 2010, Round 6 from 2007 to 2012, Round 10 from 2012 to 2013, and National Strategy Application (NSA) from 2010 to 2012. Under the support of all the Global Fund Malaria Programs, a total of 11 936 726 fever cases received microscopic tests, 1 485 915 confirmed and suspected malaria cases were treated, 1 579 773 Long Lasting Insecticide-treated Nets were distributed, 3 414 633 regular nets were treated by insecticide, 40 298 284 primary and middle school students received health education on malaria control. Compared with the baseline value, the completion rates of each indicator increased after the implementation of the programs. The growth value ranged from 12.83% to 83.11%, among which the biggest growth was the value of the indicator'Percentage of households with at least one LLIN/ITN in target areas', and it increased from 9.2% (baseline value of 2006) to 92.31% (value of 2012). The malaria incidence in program areas has dropped significantly year by year, the annual reported malaria incidence in Yunnan and Hainan provinces decreased from 1 950/100 000, 3 850/100 000 in 2002 to 3.31/100 000, 0.15/100 000 in 2012, the P. falciparum malaria incidence in target counties in Hainan province decreased from 90.6/100 000 in 2002 to 0/100 000 in 2012. As from the implementation of NSA grant in 2010 to 2012, the annual reported malaria incidence in 92% of the 75 Type 1 counties was less than 1 per 10 000, 60.00% of Type 1 counties and 98.69% of the 687 Type 2 counties reported zero locally transmitted malaria cases. The Global Fund Secretariat had conducted a total of 37 performance evaluations, of which 9 have been rated as A1, 4 rated as A2, 19 rated as B1 and 5 rated as B1. Conclusions: The Global Fund Malaria Program in China has been closely integrated with the goal and task of National Malaria Control Program, reducing malaria burden in target areas, and pushing Chinese malaria control efforts to move from control to elimination.

The Promise and Potential Perils of Big Data for Advancing Symptom Management Research in Populations at Risk for Health Disparities.

PubMed

Bakken, Suzanne; Reame, Nancy

2016-01-01

Symptom management research is a core area of nursing science and one of the priorities for the National Institute of Nursing Research, which specifically focuses on understanding the biological and behavioral aspects of symptoms such as pain and fatigue, with the goal of developing new knowledge and new strategies for improving patient health and quality of life. The types and volume of data related to the symptom experience, symptom management strategies, and outcomes are increasingly accessible for research. Traditional data streams are now complemented by consumer-generated (i.e., quantified self) and "omic" data streams. Thus, the data available for symptom science can be considered big data. The purposes of this chapter are to (a) briefly summarize the current drivers for the use of big data in research; (b) describe the promise of big data and associated data science methods for advancing symptom management research; (c) explicate the potential perils of big data and data science from the perspective of the ethical principles of autonomy, beneficence, and justice; and (d) illustrate strategies for balancing the promise and the perils of big data through a case study of a community at high risk for health disparities. Big data and associated data science methods offer the promise of multidimensional data sources and new methods to address significant research gaps in symptom management. If nurse scientists wish to apply big data and data science methods to advance symptom management research and promote health equity, they must carefully consider both the promise and perils.

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.

A systematic review and synthesis of the strengths and limitations of measuring malaria mortality through verbal autopsy.

PubMed

Herrera, Samantha; Enuameh, Yeetey; Adjei, George; Ae-Ngibise, Kenneth Ayuurebobi; Asante, Kwaku Poku; Sankoh, Osman; Owusu-Agyei, Seth; Yé, Yazoume

2017-10-23

Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method was developed to ascertain cause of death at the population level. Despite the adoption and wide use of VA, there are many recognized limitations of VA tools and methods, especially for measuring malaria mortality. This study synthesizes the strengths and limitations of existing VA tools and methods for measuring malaria mortality (MM) in low- and middle-income countries through a systematic literature review. The authors searched PubMed, Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and Demographic Surveillance System sites' websites from 1 January 1990 to 15 January 2016 for articles and reports on MM measurement through VA. article presented results from a VA study where malaria was a cause of death; article discussed limitations/challenges related to measurement of MM through VA. Two authors independently searched the databases and websites and conducted a synthesis of articles using a standard matrix. The authors identified 828 publications; 88 were included in the final review. Most publications were VA studies; others were systematic reviews discussing VA tools or methods; editorials or commentaries; and studies using VA data to develop MM estimates. The main limitation were low sensitivity and specificity of VA tools for measuring MM. Other limitations included lack of standardized VA tools and methods, lack of a 'true' gold standard to assess accuracy of VA malaria mortality. Existing VA tools and methods for measuring MM have limitations. Given the need for data to measure progress toward the World Health Organization's Global Technical Strategy for Malaria 2016-2030 goals, the malaria community should define strategies for improving MM estimates, including exploring whether VA tools and methods could be further improved. Longer term strategies should focus on improving countries' vital registration systems for more robust and timely cause of death data.

Measuring Coverage in MNCH: Accuracy of Measuring Diagnosis and Treatment of Childhood Malaria from Household Surveys in Zambia

PubMed Central

Eisele, Thomas P.; Silumbe, Kafula; Yukich, Josh; Hamainza, Busiku; Keating, Joseph; Bennett, Adam; Miller, John M.

2013-01-01

Background To assess progress in the scale-up of rapid diagnostic tests and artemisinin-based combination therapies (ACTs) across Africa, malaria control programs have increasingly relied on standardized national household surveys to determine the proportion of children with a fever in the past 2 wk who received an effective antimalarial within 1–2 d of the onset of fever. Here, the validity of caregiver recall for measuring the primary coverage indicators for malaria diagnosis and treatment of children <5 y old is assessed. Methods and Findings A cross-sectional study was conducted in five public clinics in Kaoma District, Western Provence, Zambia, to estimate the sensitivity, specificity, and accuracy of caregivers' recall of malaria testing, diagnosis, and treatment, compared to a gold standard of direct observation at the health clinics. Compared to the gold standard of clinic observation, for recall for children with fever in the past 2 wk, the sensitivity for recalling that a finger/heel stick was done was 61.9%, with a specificity of 90.0%. The sensitivity and specificity of caregivers' recalling a positive malaria test result were 62.4% and 90.7%, respectively. The sensitivity and specificity of recalling that the child was given a malaria diagnosis, irrespective of whether a laboratory test was actually done, were 76.8% and 75.9%, respectively. The sensitivity and specificity for recalling that an ACT was given were 81.0% and 91.5%, respectively. Conclusions Based on these findings, results from household surveys should continue to be used for ascertaining the coverage of children with a fever in the past 2 wk that received an ACT. However, as recall of a malaria diagnosis remains suboptimal, its use in defining malaria treatment coverage is not recommended. Please see later in the article for the Editors' Summary PMID:23667337

Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil

PubMed Central

2012-01-01

Background Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions. Methods An observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence. Results Twenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses. Conclusions A known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines. PMID:22839416

Epidemiology of disappearing Plasmodium vivax malaria: a case study in rural Amazonia.

PubMed

Barbosa, Susana; Gozze, Amanda B; Lima, Nathália F; Batista, Camilla L; Bastos, Melissa da Silva; Nicolete, Vanessa C; Fontoura, Pablo S; Gonçalves, Raquel M; Viana, Susana Ariane S; Menezes, Maria José; Scopel, Kézia Katiani G; Cavasini, Carlos E; Malafronte, Rosely dos Santos; da Silva-Nunes, Mônica; Vinetz, Joseph M; Castro, Márcia C; Ferreira, Marcelo U

2014-08-01

New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. P. vivax prevalence decreased from 23.8% (March-April 2010) to 3.0% (April-May 2013), with no P. falciparum infections diagnosed after March-April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2-3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

PubMed Central

Lima, Nathália F.; Batista, Camilla L.; Bastos, Melissa da Silva; Nicolete, Vanessa C.; Fontoura, Pablo S.; Gonçalves, Raquel M.; Viana, Susana Ariane S.; Menezes, Maria José; Scopel, Kézia Katiani G.; Cavasini, Carlos E.; Malafronte, Rosely dos Santos; da Silva-Nunes, Mônica; Vinetz, Joseph M.; Castro, Márcia C.; Ferreira, Marcelo U.

2014-01-01

Background New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance. PMID:25166263

Distribution of Plasmodium spp. infection in asymptomatic carriers in perennial and low seasonal malaria transmission settings in West Africa.

PubMed

Gbalégba, Constant G N; Ba, Hampâté; Silué, Kigbafori D; Ba, Ousmane; Tia, Emmanuel; Chouaibou, Mouhamadou; Tian-Bi, Nathan T Y; Yapi, Grégoire Y; Koné, Brama; Utzinger, Jürg; Koudou, Benjamin G

2018-04-25

Since 2000, substantial progress has been made in reducing malaria worldwide. However, some countries in West Africa remain a hotspot for malaria with all age groups at risk. Asymptomatic carriers of Plasmodium spp. are important sources of infections for malaria vectors and thus contribute to the anchoring of the disease in favourable eco-epidemiological settings. The objective of this study was to assess the asymptomatic malaria case rates in Korhogo and Kaedi, two urban areas in northern Côte d'Ivoire and southern Mauritania, respectively. Cross-sectional surveys were carried out during the rainy season in 2014 and the dry season in 2015 in both settings. During each season, 728 households were randomly selected and a household-based questionnaire was implemented to collect demographic and epidemiological data, including of malaria preventive methods used in communities. Finger-prick blood samples were obtained for biological examination using microscopy and rapid diagnostic tests (RDTs). Overall, 2672 households and 15 858 consenting participants were surveyed. Plasmodium spp. infection was confirmed in 12.4% (n = 832) and 0.3% (n = 22) of the assessed individuals in Korhogo and Kaedi, respectively. In Korhogo, the prevalence of asymptomatic malaria was 10.5% (95% CI: 9.7-11.2) as determined by microscopy and 9.3% (95% CI: 8.6-10.0%) when assessed by RDT. In Kaedi, asymptomatic malaria prevalence was 0.2% (95% CI: 0.1-0.4%) according to microscopy, while all RDTs performed were negative (n = 8372). In Korhogo, asymptomatic malaria infection was significantly associated with age and season, with higher risk within the 5-14 years-old, and during the rainy season. In Kaedi, the risk of asymptomatic malaria infection was associated with season only (higher during the dry season; crude OR (cOR): 6.37, 95% CI: 1.87-21.63). P. falciparum was the predominant species identified in both study sites representing 99.2% (n = 825) in Korhogo and 59.1% (n = 13) in Kaedi. Gametocytes were observed only in Korhogo and only during the rainy season at 1.3% (95% CI: 0.7-2.4%). Our findings show a low prevalence of clinical malaria episodes with a significant proportion of asymptomatic carriers in both urban areas. National policies for malaria infections are focused on treatment of symptomatic cases. Malaria control strategies should be designed for monitoring and managing malaria infections in asymptomatic carriers. Additional measures, including indoor residual spraying, effective use of long-lasting insecticidal nets is strongly needed to reduce the number of Plasmodium spp. infections in Korhogo and Kaedi.

Cultural Diversity in Nursing Education: Perils, Pitfalls, and Pearls

PubMed Central

Bednarz, Hedi; Schim, Stephanie; Doorenbos, Ardith

2010-01-01

Increasing diversity in the classroom challenges nursing educators to identify issues that complicate teaching (perils), analyze barriers for themselves and their students (pitfalls), and select new strategies for working with nontraditional students (pearls). This article identifies concerns arising from attitudes and values within nursing and common approaches to diversity education, and then discusses key issues in nursing education that relate to human nature, culture, faculty workload, and student demographics. Finally, some strategies are proposed for increasing the effectiveness of professional preparation with diverse students through a focus on culturally congruent education and development of faculty cultural competence. PMID:20143759

Cultural diversity in nursing education: perils, pitfalls, and pearls.

PubMed

Bednarz, Hedi; Schim, Stephanie; Doorenbos, Ardith

2010-05-01

Increasing diversity in the classroom challenges nursing educators to identify issues that complicate teaching (perils), analyze barriers for themselves and their students (pitfalls), and select new strategies for working with nontraditional students (pearls). This article identifies concerns arising from attitudes and values within nursing and common approaches to diversity education, and then discusses key issues in nursing education that relate to human nature, culture, faculty workload, and student demographics. Finally, some strategies are proposed for increasing the effectiveness of professional preparation with diverse students through a focus on culturally congruent education and development of faculty cultural competence.

Identification and Optimization of New Leads for Malaria Vector Control.

PubMed

Hueter, Ottmar F; Hoppé, Mark; Wege, Philip; Maienfisch, Peter

2016-10-01

A significant proportion of the world's population remains at risk from malaria, and whilst great progress has been made in reducing the number of malaria cases globally through the use of vector control insecticides, these gains are under threat from the emergence of insecticide resistance. The spread of resistance in the vector populations, principally to pyrethroids, is driving the need for the development of new tools for malaria vector control. In order to identify new leads 30,000 compounds from the Syngenta corporate chemical collection were tested in a newly developed screening platform. More than 3000 compounds (10%) showed activity at ≤200 mg active ingredient (AI) litre -1 against Anopheles stephensi. Further evaluation resulted in the identification of 12 viable leads for the control of adult mosquitoes, most originating from current or former insecticide projects. Surprisingly, one of these leads emerged from a former PPO herbicide project and one from a former complex III fungicide project. This indicates that representatives of certain herbicide and fungicide projects and modes of action can also represent a valuable source of leads for malaria vector control. Optimization of the diphenyl ether lead 1 resulted in the identification of the cyano-pyridyl compound 31. This compound 31 exhibits good activity against mosquito species including rdl resistant Anopheles. It is only slightly weaker than permethrin and does not show relevant levels of cross-resistance to the organochlorine insecticide dieldrin.

Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase.

PubMed

Yong, Kok Pin; Tan, Ban Hock; Low, Chian Yong

2012-12-20

Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK). A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus. In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

Recent advances in recombinant protein-based malaria vaccines

PubMed Central

Draper, Simon J.; Angov, Evelina; Horii, Toshihiro; Miller, Louis H.; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-01-01

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. PMID:26458807

[French language training course: malaria workshop organized by Institut Pasteur de Madagascar].

PubMed

Domarle, O; Randrianarivelojosia, M; Duchemin, J B; Robert, V; Ariey, F; Hommel, M

2007-10-01

The Malaria Workshop organized by Institut Pasteur de Madagascar is an original course that applies innovative concepts to training of health professionals involved in malaria control in endemic countries. Course objectives are to enhance the skills needed to fight malaria (transversal competencies, critical approach, and position statement), to reinforce project cycle management proficiency, and to demonstrate how the Internet can be used as a source of documentation to compensate for geographical isolation. The Malaria Workshop is a six-consecutive-week full-day course that has been presented once a year since 2003. Seventy-six researchers, physicians or health ministry officials have already benefited from this training. Teaching methods emphasize andragogy that facilitates a learner/mentor relationship promoting exchange rather than transmission of knowledge and problem-based learning that engages learners to take an active part in gathering information. These methods in combination with the diverse backgrounds and experience of course participants foster a positive dynamic environment for learning that is monitored by weekly progress evaluation. Follow-up surveys have confirmed the positive effect of this training on the professional performance of former participants who become more involved in program development and fund-raising efforts. A professional network is growing and learners are starting to their experience. In this report workshop organizers describe the course's origins and concepts and present the conclusions drawn based on the first five yearly sessions.

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

Factors influencing dropout rate of intermittent preventive treatment of malaria during pregnancy.

PubMed

Doku, David Teye; Zankawah, Mumuni Mukaila; Adu-Gyamfi, Addae Boateng

2016-10-10

The burden of malaria in terms of morbidity and mortality is huge is Sub-Saharan Africa, particularly among pregnant women. Among the measures to curb down this burden include intermittent preventive treatment (IPT) and effective case management. These strategies were adopted by Ghana and implemented since 2003; however, there is still high dropout rate in IPT coverage. This study sought to investigate factors contributing to high dropout rate between IPT1 and IPT3 in the Tamale Metropolis, one of the health facilities with the highest IPT dropout rates in Ghana. Survey, in-depth interviews and short ethnographic techniques were conducted among pregnant women, antenatal care (ANC) health workers and heads of health facilities to investigate factors which account for dropout rate of intermittent treatment of malaria. Shortage of sulphadoxine pyrimethamine (SP), inadequate supply of portable water for administration of SP, unavailability of IPT during outreach services, lack of knowledge by ANC staff about the dropout rate in their area of jurisdiction and poor attitude of some health workers were identified as barriers to achieving high IPT3 coverage. Late ANC visit, provider and logistical barriers account for the women's missed opportunities to prevent malaria in pregnancy through IPT. Addressing the above barriers will contribute to saving lives and ensuring progress towards the goal of combating malaria as well as reducing maternal, neonatal and child mortalities.

Antiplasmodial and antimalarial activities of quinolone derivatives: An overview.

PubMed

Fan, Yi-Lei; Cheng, Xiang-Wei; Wu, Jian-Bing; Liu, Min; Zhang, Feng-Zhi; Xu, Zhi; Feng, Lian-Shun

2018-02-25

Malaria remains one of the most deadly infectious diseases globally. Considering the growing spread of resistance, development of new and effective antimalarials remains an urgent priority. Quinolones, which are emerged as one of the most important class of antibiotics in the treatment of various bacterial infections, showed potential in vitro antiplasmodial and in vivo antimalarial activities, making them promising candidates for the chemoprophylaxis and treatment of malaria. This review presents the current progresses and applications of quinolone-based derivatives as potential antimalarials to pave the way for the development of new antimalarials. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Killing the hypnozoite – drug discovery approaches to prevent relapse in Plasmodium vivax

PubMed Central

Campo, Brice; Vandal, Omar; Wesche, David L.; Burrows, Jeremy N.

2015-01-01

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse. PMID:25891812

Killing the hypnozoite--drug discovery approaches to prevent relapse in Plasmodium vivax.

PubMed

Campo, Brice; Vandal, Omar; Wesche, David L; Burrows, Jeremy N

2015-05-01

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.

Performance and user acceptance of the Bhutan febrile and malaria information system: report from a pilot study.

PubMed

Tobgay, Tashi; Samdrup, Pema; Jamtsho, Thinley; Mannion, Kylie; Ortega, Leonard; Khamsiriwatchara, Amnat; Price, Ric N; Thriemer, Kamala; Kaewkungwal, Jaranit

2016-01-29

Over the last decade, Bhutan has made substantial progress in controlling malaria. The country is now in an elimination phase, aiming to achieve no locally transmitted malaria by 2018. However, challenges remain and innovative control strategies are needed to overcome these. The evaluation and user acceptance of a robust surveillance tool applicable for informing malaria elimination activities is reported here. The Bhutan Febrile and Malaria Information System (BFMIS) is a combination of web-based and mobile technology that captures malariometric surveillance data and generates real time reports. The system was rolled out at six sites and data uploaded regularly for analysis. Data completeness, accuracy and data turnaround time were accessed by comparison to traditional paper based surveillance records. User acceptance and willingness for further roll out was assessed using qualitative and quantitative data. Data completeness was nearly 10 % higher using the electronic system than the paper logs, and accuracy and validity of both approaches was comparable (up to 0.05 % in valid data and up to 3.06 % inaccurate data). Data turnaround time was faster using the BFMIS. General user satisfaction with the BFMIS was high, with high willingness of health facilities to adopt the system. Qualitative interviews revealed several areas for improvement before scale up. The BFMIS had numerous advantages over the paper-based system and based on the findings of the survey the Vector-Borne Disease Control Programme has taken the decision to incorporate the BMFIS and expand its use throughout all areas at risk for malaria as a key surveillance tool.

Scientific authorship and collaboration network analysis on malaria research in Benin: papers indexed in the web of science (1996-2016).

PubMed

Azondekon, Roseric; Harper, Zachary James; Agossa, Fiacre Rodrigue; Welzig, Charles Michael; McRoy, Susan

2018-01-01

To sustain the critical progress made, prioritization and a multidisciplinary approach to malaria research remain important to the national malaria control program in Benin. To document the structure of the malaria collaborative research in Benin, we analyze authorship of the scientific documents published on malaria from Benin. We collected bibliographic data from the Web Of Science on malaria research in Benin from January 1996 to December 2016. From the collected data, a mulitigraph co-authorship network with authors representing vertices was generated. An edge was drawn between two authors when they co-author a paper. We computed vertex degree, betweenness, closeness, and eigenvectors among others to identify prolific authors. We further assess the weak points and how information flow in the network. Finally, we perform a hierarchical clustering analysis, and Monte-Carlo simulations. Overall, 427 publications were included in this study. The generated network contained 1792 authors and 116,388 parallel edges which converted in a weighted graph of 1792 vertices and 95,787 edges. Our results suggested that prolific authors with higher degrees tend to collaborate more. The hierarchical clustering revealed 23 clusters, seven of which form a giant component containing 94% of all the vertices in the network. This giant component has all the characteristics of a small-world network with a small shortest path distance between pairs of three, a diameter of 10 and a high clustering coefficient of 0.964. However, Monte-Carlo simulations suggested our observed network is an unusual type of small-world network. Sixteen vertices were identified as weak articulation points within the network. The malaria research collaboration network in Benin is a complex network that seems to display the characteristics of a small-world network. This research reveals the presence of closed research groups where collaborative research likely happens only between members. Interdisciplinary collaboration tends to occur at higher levels between prolific researchers. Continuously supporting, stabilizing the identified key brokers and most productive authors in the Malaria research collaborative network is an urgent need in Benin. It will foster the malaria research network and ensure the promotion of junior scientists in the field.

Progress towards implementation of ACT malaria case-management in public health facilities in the Republic of Sudan: a cluster-sample survey

PubMed Central

2012-01-01

Background Effective malaria case-management based on artemisinin-based combination therapy (ACT) and parasitological diagnosis is a major pillar within the 2007-2012 National Malaria Strategic Plan in the Sudan. Three years after the launch of the strategy a health facility survey was undertaken to evaluate case-management practices and readiness of the health facilities and health workers to implement a new malaria case-management strategy. Methods A cross-sectional, cluster sample survey was undertaken at public health facilities in 15 states of Sudan. Data were collected using quality-of-care assessment methods. The main outcomes were the proportions of facilities with ACTs and malaria diagnostics; proportions of health workers exposed to malaria related health systems support activities; and composite and individual indicators of case-management practices for febrile outpatients stratified by age, availability of ACTs and diagnostics, use of malaria diagnostics, and test result. Results We evaluated 244 facilities, 294 health workers and 1,643 consultations for febrile outpatients (425 < 5 years and 1,218 ≥ 5 years). Health facility and health worker readiness was variable: chloroquine was available at only 5% of facilities, 73% stocked recommended artesunate and sulfadoxine/pyrimethamine (AS+SP), 51% had the capacity to perform parasitological diagnosis, 53% of health workers had received in-service training on ACTs, 24% were trained in the use of malaria Rapid Diagnostic Tests, and 19% had received a supervisory visit including malaria case-management. At all health facilities 46% of febrile patients were parasitologically tested and 35% of patients were both, tested and treated according to test result. At facilities where AS+SP and malaria diagnostics were available 66% of febrile patients were tested and 51% were both, tested and treated according to test result. Among test positive patients 64% were treated with AS+SP but 24% were treated with artemether monotherapy. Among test negative patients only 17% of patients were treated for malaria. The majority of ACT dispensing and counseling practices were suboptimal. Conclusions Five years following change of the policy from chloroquine to ACTs and 3 years before the end of the new malaria strategic plan chloroquine was successfully phased out from public facilities in Sudan, however, an important gap remained in the availability of ACTs, diagnostic capacities and coverage with malaria case-management activities. The national scale-up of diagnostics, using the findings of this survey as well as future qualitative research, should present an opportunity not only to expand existing testing capacities but also to implement effective support interventions to bridge the health systems gaps and support corrective case-management measures, including the discontinuation of artemether monotherapy treatment. PMID:22221821

Access to Medicines in Resource-limited Settings: The End of a Golden Decade?

PubMed Central

Ford, Nathan; Arkinstall, James

2012-01-01

Strong international mobilization and political will drove a golden decade for global health. Key initiatives over the last decade include setting of health-related Millennium Development Goals; the Commission on Macroeconomics and Health; the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria; the Doha Declaration on the TRIPS Agreement and Public Health affirming countries' rights to protect public health when implementing patent rules; and the creation of product development partnerships to address neglected areas of research and development. Significant progress was made in reducing the incidence of and morbidity and mortality from human immunodeficiency virus (HIV), tuberculosis (TB), and malaria, with a major impact made through increased access to medicines. Antiretroviral treatment for HIV was expanded to 6.6 million people, and medication prices were reduced significantly through generic competition. However, donor support has started to decline at a time when many patients still wait for treatment and the prices of needed newer medicines are on the increase due to patent protection. TB incidence has started to decrease, but progress in diagnosis and treatment of multi-drug-resistant TB has been slow due to complexity of treatment and high drug costs. Promising new TB drugs in development need to be introduced rapidly and appropriately while treatment is being expanded. The introduction of more affordable artemisinin combination therapies for malaria contributed to significantly reducing malaria incidence and mortality, but challenges remain in ensuring that the latest recommendations for treating severe malaria are implemented. Looking to the next decade, there is a worrisome mismatch between additional health priorities accompanied by shifting burdens of disease that need to be addressed and dwindling political attention and financial support. Difficulties in producing and guaranteeing access to affordable medicines are expected from a changing pharmaceutical market where an appropriate balance between trade and health has not been found. Systematic changes through a global framework for research and development and access are needed to support increased innovation and access to the health tools of the next decade.

The malaria testing and treatment landscape in the southern Lao People's Democratic Republic (PDR).

PubMed

Phanalasy, Saysana

2017-04-25

In the context of national and regional goals to eliminate malaria by 2030, the Center for Malaria Parasitology and Entomology in the Lao PDR is implementing strategies to ensure all malaria cases are detected and appropriately treated with first-line artemisinin combination therapy, artemether-lumefantrine (AL). Timely and relevant evidence to inform policies and strategies is needed to ensure the most effective and efficient use of resources, and to accelerate progress towards elimination goals. A 2015 outlet survey conducted in five provinces of the southern Lao PDR was the first of its kind to study the total market for malaria treatments and diagnostics. The sub-national outlet survey was designed to describe the market and to assess public and private sector readiness and performance for malaria case management. Additionally, key indicators were estimated among private outlets within districts with and without a Public Private Mix (PPM) programme. Over half of anti-malarial stockists were public sector (65.1%). In the private sector, pharmacies most commonly stocked anti-malarials, although anti-malarials were also found in private health facilities, drug stores, general retailers, and itinerant drug vendors. Nearly all anti-malarial stocking public health facilities had AL (99.5%) and 90.8% had confirmatory testing. Fewer than half of anti-malarial stocking private outlets stocked AL (40.8%) and malaria testing (43.5%). Chloroquine has not been a first-line treatment for Plasmodium falciparum malaria since 2005 and Plasmodium vivax since 2011 yet private sector availability was 77.6% and chloroquine accounted for 62.2% of the total anti-malarial market share. AL and confirmatory testing availability were higher in private outlets in PPM (68.1, 72.6%) versus non-PPM districts (2.5, 12.1%). Chloroquine was available in 63.6% of PPM and 96.7% of non-PPM-district outlets, and was the most commonly distributed anti-malarial among private outlets in both PPM (61.7%) and non-PPM districts (99.1%). Public sector outlets in the southern Lao PDR are typically equipped to test and appropriately treat malaria. There is need to address widespread private sector availability and distribution of chloroquine. The PPM programme has improved private provider readiness to manage malaria according to national guidelines. However, supporting interventions to address provider and consumer behaviours are needed to further drive uptake.

Determinants of delay in malaria care-seeking behaviour for children 15 years and under in Bata district, Equatorial Guinea.

PubMed

Romay-Barja, Maria; Cano, Jorge; Ncogo, Policarpo; Nseng, Gloria; Santana-Morales, Maria A; Valladares, Basilio; Riloha, Matilde; Benito, Agustin

2016-03-31

Malaria remains a major cause of morbidity and mortality in children under 5 years of age in Equatorial Guinea. Early appropriate treatment can reduce progression of the illness to severe stages, thus reducing of mortality, morbidity and onward transmission. The factors that contribute to malaria treatment delay have not been studied previously in Equatorial Guinea. The objective of this study was to assess the determinants of delay in seeking malaria treatment for children in the Bata district, in mainland Equatorial Guinea. A cross-sectional study was conducted in Bata district, in 2013, which involved 428 houses in 18 rural villages and 26 urban neighbourhoods. Household caregivers were identified in each house and asked about their knowledge of malaria and about the management of the last reported malaria episode in a child 15 years and younger under their care. Bivariate and multivariate statistical analyses were conducted to determine the relevance of socio-economic, geographical and behavioural factors on delays in care-seeking behaviour. Nearly half of the children sought treatment at least 24 h after the onset of the symptoms. The median delay in seeking care was 2.8 days. Children from households with the highest socio-economic status were less likely to be delayed in seeking care than those from households with the lowest socio-economic status (OR 0.37, 95% CI 0.19-0.72). Children that first received treatment at home, mainly paracetamol, were more than twice more likely to be delayed for seeking care, than children who did not first receive treatment at home (OR 2.36, 95% CI 1.45-3.83). Children living in a distance >3 km from the nearest health facility were almost two times more likely to be delayed in seeking care than those living closer to a facility but with non significant association once adjusted for other variables (OR 1.75, 95% CI 0.88-3.47). To decrease malaria morbidity and mortality in Bata district, efforts should be addressed to reduce household delays in seeking care. It is necessary to provide free access to effective malaria diagnosis and treatment, to reinforce malaria management at community level through community health workers and drug sellers and to increase awareness on the severity of malaria, the importance of early diagnosis and appropriate treatment.

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.

Temporal and spatial patterns of serologic responses to Plasmodium falciparum antigens in a region of declining malaria transmission in southern Zambia.

PubMed

Kobayashi, Tamaki; Chishimba, Sandra; Shields, Timothy; Hamapumbu, Harry; Mharakurwa, Sungano; Thuma, Philip E; Glass, Gregory; Moss, William J

2012-12-31

Critical to sustaining progress in malaria control is comprehensive surveillance to identify outbreaks and prevent resurgence. Serologic responses to Plasmodium falciparum antigens can serve as a marker of recent transmission and serosurveillance may be feasible on a large scale. Satellite images were used to construct a sampling frame for the random selection of households enrolled in prospective longitudinal and cross-sectional surveys in two study areas in Southern Province, Zambia, one in 2007 and the other in 2008 and 2009. Blood was collected and stored as dried spots from participating household members. A malaria rapid diagnostic test (RDT) was used to diagnose malaria. An enzyme immunoassay (EIA) was used to detect IgG antibodies to asexual stage P. falciparum whole parasite lysate using serum eluted from dried blood spots. The expected mean annual increase in optical density (OD) value for individuals with a documented prior history of recent malaria was determined using mixed models. SatScan was used to determine the spatial clustering of households with individuals with serological evidence of recent malaria, and these households were plotted on a malaria risk map. RDT positivity differed markedly between the study areas and years: 28% of participants for whom serologic data were available were RDT positive in the 2007 study area, compared to 8.1% and 1.4% in the 2008 and 2009 study area, respectively. Baseline antibody levels were measured in 234 participants between April and July 2007, 435 participants between February and December 2008, and 855 participants between January and December 2009. As expected, the proportion of seropositive individuals increased with age in each year. In a subset of participants followed longitudinally, RDT positivity at the prior visit was positively correlated with an increase in EIA OD values after adjusting for age in 2007 (0.261, p = 0.003) and in 2008 (0.116, p = 0.03). RDT positivity at the concurrent visit also was associated with an increase in EIA OD value in 2007 (mean increase 0.177, p = 0.002) but not in 2008 (-0.063, p =0.50). Households comprised of individuals with serologic evidence of recent malaria overlapped areas of high malaria risk for serologic data from 2009, when parasite prevalence was lowest. Serological surveys to whole asexual P. falciparum antigens using blood collected as dried blood spots can be used to detect temporal and spatial patterns of malaria transmission in a region of declining malaria burden, and have the potential to identify focal areas of recent transmission.

Malaria in Brazil: an overview

PubMed Central

2010-01-01

Malaria is still a major public health problem in Brazil, with approximately 306 000 registered cases in 2009, but it is estimated that in the early 1940s, around six million cases of malaria occurred each year. As a result of the fight against the disease, the number of malaria cases decreased over the years and the smallest numbers of cases to-date were recorded in the 1960s. From the mid-1960s onwards, Brazil underwent a rapid and disorganized settlement process in the Amazon and this migratory movement led to a progressive increase in the number of reported cases. Although the main mosquito vector (Anopheles darlingi) is present in about 80% of the country, currently the incidence of malaria in Brazil is almost exclusively (99,8% of the cases) restricted to the region of the Amazon Basin, where a number of combined factors favors disease transmission and impair the use of standard control procedures. Plasmodium vivax accounts for 83,7% of registered cases, while Plasmodium falciparum is responsible for 16,3% and Plasmodium malariae is seldom observed. Although vivax malaria is thought to cause little mortality, compared to falciparum malaria, it accounts for much of the morbidity and for huge burdens on the prosperity of endemic communities. However, in the last few years a pattern of unusual clinical complications with fatal cases associated with P. vivax have been reported in Brazil and this is a matter of concern for Brazilian malariologists. In addition, the emergence of P. vivax strains resistant to chloroquine in some reports needs to be further investigated. In contrast, asymptomatic infection by P. falciparum and P. vivax has been detected in epidemiological studies in the states of Rondonia and Amazonas, indicating probably a pattern of clinical immunity in both autochthonous and migrant populations. Seropidemiological studies investigating the type of immune responses elicited in naturally-exposed populations to several malaria vaccine candidates in Brazilian populations have also been providing important information on whether immune responses specific to these antigens are generated in natural infections and their immunogenic potential as vaccine candidates. The present difficulties in reducing economic and social risk factors that determine the incidence of malaria in the Amazon Region render impracticable its elimination in the region. As a result, a malaria-integrated control effort - as a joint action on the part of the government and the population - directed towards the elimination or reduction of the risks of death or illness, is the direction adopted by the Brazilian government in the fight against the disease. PMID:20433744

Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings.

PubMed

Britton, Sumudu; Cheng, Qin; McCarthy, James S

2016-02-16

As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK

PubMed Central

Badr, Gamal; Sayed, Ayat; Abdel-Maksoud, Mostafa A.; Mohamed, Amany O.; El-Amir, Azza; Abdel-Ghaffar, Fathy A.; Al-Quraishy, Saleh; Mahmoud, Mohamed H.

2015-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-β, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity. PMID:25909640

Fine-Scale Mapping by Spatial Risk Distribution Modeling for Regional Malaria Endemicity and Its Implications under the Low-to-Moderate Transmission Setting in Western Cambodia

PubMed Central

Okami, Suguru; Kohtake, Naohiko

2016-01-01

The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman’s rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414–0.827 and 0.368–0.813, respectively), Welch’s t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity. PMID:27415623

Infection of Female BWF1 Lupus Mice with Malaria Parasite Attenuates B Cell Autoreactivity by Modulating the CXCL12/CXCR4 Axis and Its Downstream Signals PI3K/AKT, NFκB and ERK.

PubMed

Badr, Gamal; Sayed, Ayat; Abdel-Maksoud, Mostafa A; Mohamed, Amany O; El-Amir, Azza; Abdel-Ghaffar, Fathy A; Al-Quraishy, Saleh; Mahmoud, Mohamed H

2015-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by abnormal autoreactivity in B cells. Lymphocytes and their soluble mediators contribute to the disease pathogenesis. We recently demonstrated that infecting lupus mice with malaria confers protection against lupus nephritis by attenuating oxidative stress in both liver and kidney tissues. In the current study, we further investigated B cell autoreactivity in female BWF1 lupus mice after infection with either live or gamma-irradiated malaria, using ELISA, flow cytometry and Western blot analysis. The lupus mice exhibited a significant elevation in plasma levels of IL-4, IL-6, IL-7, IL-12, IL-17, IFN-α, IFN-γ, TGF-β, BAFF and APRIL and a marked elevation of IgG2a, IgG3 and ant-dsDNA autoantibodies compared with normal healthy mice. Infecting lupus mice with live but not gamma-irradiated malaria parasite partially and significantly restored the levels of the soluble mediators that contribute to the progression of lupus. Furthermore, the B cells of lupus mice exhibited an increased proliferative capacity; aberrant overexpression of the chemokine receptor CXCR4; and a marked elevation in responsiveness to their cognate ligand (CXCL12) via aberrant activation of the PI3K/AKT, NFκB and ERK signaling pathways. Interestingly, infecting lupus mice with live but not gamma-irradiated malaria parasite restored a normal proliferative capacity, surface expression of CXCR4 and B cell response to CXCL-12. Taken together, our data present interesting findings that clarify, for the first time, the molecular mechanisms of how infection of lupus mice with malaria parasite controls B cell autoreactivity and thus confers protection against lupus severity.

Health laboratories in the Tanga region of Tanzania: the quality of diagnostic services for malaria and other communicable diseases.

PubMed

Ishengoma, D R S; Rwegoshora, R T; Mdira, K Y; Kamugisha, M L; Anga, E O; Bygbjerg, I C; Rønn, A M; Magesa, S M

2009-07-01

Although critical for good case management and the monitoring of health interventions, the health-laboratory services in sub-Saharan Africa are grossly compromised by poor infrastructures and a lack of trained personnel, essential reagents and other supplies. The availability and quality of diagnostic services in 37 health laboratories in three districts of the Tanga region of Tanzania have recently been assessed. The results of the survey, which involved interviews with health workers, observations and a documentary review, revealed that malaria accounted for >50% of admissions and out-patient visits. Most (92%) of the laboratories were carrying out malaria diagnosis and 89% were measuring haemoglobin concentrations but only one (3%) was conducting culture and sensitivity tests, and those only on urine and pus samples. Only 14 (17%) of the 84 people found working in the visited laboratories were laboratory technologists with a diploma certificate or higher qualification. Sixteen (43%) of the study laboratories each had five or fewer types of equipment and only seven (19%) had more than 11 types each. Although 11 (30%) of the laboratories reported that they conducted internal quality control, none had standard operating procedures (SOP) on display or evidence of such quality assurance. Although malaria was the main health problem, diagnostic services for malaria and other diseases were inadequate and of poor quality because of the limited human resources, poor equipment and shortage of supplies. If the health services in Tanga are not to be overwhelmed by the progressively increasing burden of HIV/AIDS, malaria, tuberculosis and other emerging and re-emerging diseases, more funding and appropriate policies to improve the availability and quality of the area's diagnostic services will clearly be required.

The Global Fund to Fight AIDS, Tuberculosis, and Malaria: Progress Report and Issues for Congress

DTIC Science & Technology

2006-04-25

artemisinin -based combination drug treatments (ACT). Artemisinin -based treatments have been found to be effective in dealing with drug-resistant...and have no observable resistance are considerably more expensive. The new drugs called, “ artemisinin -based combination therapies” (ACTs) cost about

Managing intellectual property to develop medicines for the world's poorest.

PubMed

Fonteilles-Drabek, Sylvie; Reddy, David; Wells, Timothy N C

2017-04-01

It has been argued that patents impede the development and access of medicines for tropical diseases such as malaria. However, we believe that intellectual property can be a key tool to enable timely progression of drug development projects involving multiple partners and to ensure equitable access to successful products.

Recent advances in recombinant protein-based malaria vaccines.

PubMed

Draper, Simon J; Angov, Evelina; Horii, Toshihiro; Miller, Louis H; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-12-22

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

malERA: An updated research agenda for combination interventions and modelling in malaria elimination and eradication

PubMed Central

2017-01-01

This paper summarises key advances and priorities since the 2011 presentation of the Malaria Eradication Research Agenda (malERA), with a focus on the combinations of intervention tools and strategies for elimination and their evaluation using modelling approaches. With an increasing number of countries embarking on malaria elimination programmes, national and local decisions to select combinations of tools and deployment strategies directed at malaria elimination must address rapidly changing transmission patterns across diverse geographic areas. However, not all of these approaches can be systematically evaluated in the field. Thus, there is potential for modelling to investigate appropriate ‘packages’ of combined interventions that include various forms of vector control, case management, surveillance, and population-based approaches for different settings, particularly at lower transmission levels. Modelling can help prioritise which intervention packages should be tested in field studies, suggest which intervention package should be used at a particular level or stratum of transmission intensity, estimate the risk of resurgence when scaling down specific interventions after local transmission is interrupted, and evaluate the risk and impact of parasite drug resistance and vector insecticide resistance. However, modelling intervention package deployment against a heterogeneous transmission background is a challenge. Further validation of malaria models should be pursued through an iterative process, whereby field data collected with the deployment of intervention packages is used to refine models and make them progressively more relevant for assessing and predicting elimination outcomes. PMID:29190295

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

Spatio-temporal mapping of Madagascar's Malaria Indicator Survey results to assess Plasmodium falciparum endemicity trends between 2011 and 2016.

PubMed

Kang, Su Yun; Battle, Katherine E; Gibson, Harry S; Ratsimbasoa, Arsène; Randrianarivelojosia, Milijaona; Ramboarina, Stéphanie; Zimmerman, Peter A; Weiss, Daniel J; Cameron, Ewan; Gething, Peter W; Howes, Rosalind E

2018-05-23

Reliable measures of disease burden over time are necessary to evaluate the impact of interventions and assess sub-national trends in the distribution of infection. Three Malaria Indicator Surveys (MISs) have been conducted in Madagascar since 2011. They provide a valuable resource to assess changes in burden that is complementary to the country's routine case reporting system. A Bayesian geostatistical spatio-temporal model was developed in an integrated nested Laplace approximation framework to map the prevalence of Plasmodium falciparum malaria infection among children from 6 to 59 months in age across Madagascar for 2011, 2013 and 2016 based on the MIS datasets. The model was informed by a suite of environmental and socio-demographic covariates known to influence infection prevalence. Spatio-temporal trends were quantified across the country. Despite a relatively small decrease between 2013 and 2016, the prevalence of malaria infection has increased substantially in all areas of Madagascar since 2011. In 2011, almost half (42.3%) of the country's population lived in areas of very low malaria risk (<1% parasite prevalence), but by 2016, this had dropped to only 26.7% of the population. Meanwhile, the population in high transmission areas (prevalence >20%) increased from only 2.2% in 2011 to 9.2% in 2016. A comparison of the model-based estimates with the raw MIS results indicates there was an underestimation of the situation in 2016, since the raw figures likely associated with survey timings were delayed until after the peak transmission season. Malaria remains an important health problem in Madagascar. The monthly and annual prevalence maps developed here provide a way to evaluate the magnitude of change over time, taking into account variability in survey input data. These methods can contribute to monitoring sub-national trends of malaria prevalence in Madagascar as the country aims for geographically progressive elimination.

A World Malaria Map: Plasmodium falciparum Endemicity in 2007

PubMed Central

Hay, Simon I; Guerra, Carlos A; Gething, Peter W; Patil, Anand P; Tatem, Andrew J; Noor, Abdisalan M; Kabaria, Caroline W; Manh, Bui H; Elyazar, Iqbal R. F; Brooker, Simon; Smith, David L; Moyeed, Rana A; Snow, Robert W

2009-01-01

Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the Africa+ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. Conclusions High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process. PMID:19323591

Effect of anti-malarial interventions on trends of malaria cases, hospital admissions and deaths, 2005-2015, Ghana.

PubMed

Aregawi, Maru; Malm, Keziah L; Wahjib, Mohammed; Kofi, Osae; Allotey, Naa-Korkor; Yaw, Peprah Nana; Abba-Baffoe, Wilmot; Segbaya, Sylvester; Owusu-Antwi, Felicia; Kharchi, Abderahmane T; Williams, Ryan O; Saalfeld, Mark; Workneh, Nibretie; Shargie, Estifanos Biru; Noor, Abdisalan M; Bart-Plange, Constance

2017-04-26

Since 2005, the Government of Ghana and its partners, in concerted efforts to control malaria, scaled up the use of artemisinin-based combination therapy (ACT) and insecticide-treated nets (ITNs). Beginning in 2011, a mass campaign of long-lasting insecticidal nets (LLINs) was implemented, targeting all the population. The impact of these interventions on malaria cases, admissions and deaths was assessed using data from district hospitals. Records of malaria cases and deaths and availability of ACT in 88 hospitals, as well as at district level, ITN distribution, and indoor residual spraying were reviewed. Annual proportion of the population potentially protected by ITNs was estimated with the assumption that each LLIN covered 1.8 persons for 3 years. Changes in trends of cases and deaths in 2015 were estimated by segmented log-linear regression, comparing trends in post-scale-up (2011-2015) with that of pre-scale-up (2005-2010) period. Trends of mortality in children under 5 years old from population-based household surveys were also compared with the trends observed in hospitals for the same time period. Among all ages, the number of outpatient malaria cases (confirmed and presumed) declined by 57% (95% confidence interval [CI], 47-66%) by first half of 2015 (during the post-scale-up) compared to the pre-scale-up (2005-2010) period. The number of microscopically confirmed cases decreased by 53% (28-69%) while microscopic testing was stable. Test positivity rate (TPR) decreased by 41% (19-57%). The change in malaria admissions was insignificant while malaria deaths fell significantly by 65% (52-75%). In children under 5 years old, total malaria outpatient cases, admissions and deaths decreased by 50% (32-63%), 46% (19-75%) and 70% (49-82%), respectively. The proportion of outpatient malaria cases, admissions and deaths of all-cause conditions in both all ages and children under five also fell significantly by >30%. Similar decreases in the main malaria indicators were observed in the three epidemiological strata (coastal, forest, savannah). All-cause admissions increased significantly in patients covered by the National Health Insurance Scheme (NHIS) compared to the non-insured. The non-malaria cases and non-malaria deaths increased or remained unchanged during the same period. All-cause mortality for children under 5 years old in household surveys, similar to those observed in the hospitals, declined by 43% between 2008 and 2014. The data provide compelling evidence of impact following LLIN mass campaigns targeting all ages since 2011, while maintaining other anti-malarial interventions. Malaria cases and deaths decreased by over 50 and 65%, respectively. The declines were stronger in children under five. Test positivity rate in all ages decreased by >40%. The decrease in malaria deaths was against a backdrop of increased admissions owing to free access to hospitalization through the NHIS. The study demonstrated that retrospective health facility-based data minimize reporting biases to assess effect of interventions. Malaria control in Ghana is dependent on sustained coverage of effective interventions and strengthened surveillance is vital to monitor progress of these investments.

Caregivers' perception of malaria and treatment-seeking behaviour for under five children in Mandura District, West Ethiopia: a cross-sectional study.

PubMed

Mitiku, Israel; Assefa, Adane

2017-04-08

Early diagnosis and prompt malaria treatment is essential to reduce progression of the illness to severe disease and, therefore, decrease mortality particularly among children under 5 years of age. This study assessed perception of malaria and treatment-seeking behaviour for children under five with fever in the last 2 weeks in Mandura District, West Ethiopia. A community based cross-sectional study was conducted among 491 caregivers of children under five in Mandura District, West Ethiopia in December 2014. Data were collected using interviewer-administered questionnaires. Data were entered into Epi Info version 7 and analysed using SPSS version 20. Multiple logistic regression analyses were conducted to identify the determinants of caregivers' treatment-seeking behaviour. Overall, 94.1% of the respondents perceived that fever is the most common symptom and 70% associated mosquito bite with the occurrence of malaria. Of 197 caregivers with under five children with fever in the last 2 weeks preceding the study 87.8% sought treatment. However, only 38.7% received treatment within 24 h of onset of fever. Determinants of treatment-seeking include place of residence (rural/urban) (AOR 2.80, 95% CI 1.01-7.70), caregivers age (AOR 3.40, 95% CI 1.27-9.10), knowledge of malaria (AOR 4.65, 95% CI 1.38-15.64), perceived susceptibility to malaria (AOR 3.63, 95% CI 1.21-10.88), and perceived barrier to seek treatment (AOR 0.18, 95% CI 0.06-0.52). Majority of the respondents of this study sought treatment for their under five children. However, a considerable number of caregivers first consulted traditional healers and tried home treatment, thus, sought treatment late. Living in rural village, caregivers' age, malaria knowledge, perceived susceptibility to malaria and perceived barrier to seek treatment were important factors in seeking health care. There is a need to focus on targeted interventions, promote awareness and prevention, and address misconceptions about childhood febrile illness.

Malaria elimination in Botswana, 2012-2014: achievements and challenges.

PubMed

Chihanga, Simon; Haque, Ubydul; Chanda, Emmanuel; Mosweunyane, Tjantilili; Moakofhi, Kense; Jibril, Haruna Baba; Motlaleng, Mpho; Zhang, Wenyi; Glass, Gregory E

2016-02-24

Botswana significantly reduced its malaria burden between 2000 and 2012. Incidence dropped from 0.99 to 0.01 % and deaths attributed to malaria declined from 12 to 3. The country initiated elimination strategies in October 2012. We examine the progress and challenges during implementation and identify future needs for a successful program in Botswana. A national, rapid notification and response strategy was developed. Cases detected through the routine passive surveillance system at health facilities were intended to initiate screening of contacts around a positive case during follow up. Positive cases were reported to district health management teams to activate district rapid response teams (DRRT). The health facility and the DRRT were to investigate the cases, and screen household members within 100 m of case households within 48 h of notification using rapid diagnostic tests (RDT) and microscopy. Positive malaria cases detected in health facilities were used for spatial analysis. There were 1808 malaria cases recorded in Botswana during 26 months from October, 2012 to December, 2014. Males were more frequently infected (59%) than females. Most cases (60%) were reported from Okavango district which experienced an outbreak in 2013 and 2014. Among the factors creating challenges for malaria eradication, only 1148 cases (63.5%) were captured by the required standardized notification forms. In total, 1080 notified cases were diagnosed by RDT. Of the positive malaria cases, only 227 (12.6%) were monitored at the household level. One hundred (8.7%) cases were associated with national or transnational movement of patients. Local movements of infected individuals within Botswana accounted for 31 cases while 69 (6.01%) cases were imported from other countries. Screening individuals in and around index households identified 37 additional, asymptomatic infections. Oscillating, sporadic and new malaria hot-spots were detected in Botswana during the study period. Botswana's experience shows some of the practical challenges of elimination efforts. Among them are the substantial movements of human infections within and among countries, and the persistence of asymptomatic reservoir infections. Programmatically, challenges include improving the speed of communicating and improving the thoroughness when responding to newly identified cases. The country needs further sustainable interventions to target infections if it is to successfully achieve its elimination goal.

Progress with viral vectored malaria vaccines: A multi-stage approach involving "unnatural immunity".

PubMed

Ewer, Katie J; Sierra-Davidson, Kailan; Salman, Ahmed M; Illingworth, Joseph J; Draper, Simon J; Biswas, Sumi; Hill, Adrian V S

2015-12-22

Viral vectors used in heterologous prime-boost regimens are one of very few vaccination approaches that have yielded significant protection against controlled human malaria infections. Recently, protection induced by chimpanzee adenovirus priming and modified vaccinia Ankara boosting using the ME-TRAP insert has been correlated with the induction of potent CD8(+) T cell responses. This regimen has progressed to field studies where efficacy against infection has now been reported. The same vectors have been used pre-clinically to identify preferred protective antigens for use in vaccines against the pre-erythrocytic, blood-stage and mosquito stages of malaria and this work is reviewed here for the first time. Such antigen screening has led to the prioritization of the PfRH5 blood-stage antigen, which showed efficacy against heterologous strain challenge in non-human primates, and vectors encoding this antigen are in clinical trials. This, along with the high transmission-blocking activity of some sexual-stage antigens, illustrates well the capacity of such vectors to induce high titre protective antibodies in addition to potent T cell responses. All of the protective responses induced by these vectors exceed the levels of the same immune responses induced by natural exposure supporting the view that, for subunit vaccines to achieve even partial efficacy in humans, "unnatural immunity" comprising immune responses of very high magnitude will need to be induced. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes

PubMed Central

Gonçalves, Lígia Antunes; Rodo, Joana; Rodrigues-Duarte, Lurdes; de Moraes, Luciana Vieira; Penha-Gonçalves, Carlos

2017-01-01

Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite. PMID:28220125

HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes.

PubMed

Gonçalves, Lígia Antunes; Rodo, Joana; Rodrigues-Duarte, Lurdes; de Moraes, Luciana Vieira; Penha-Gonçalves, Carlos

2017-01-01

Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium -infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite.

A Cas9 transgenic Plasmodium yoelii parasite for efficient gene editing.

PubMed

Qian, Pengge; Wang, Xu; Yang, Zhenke; Li, Zhenkui; Gao, Han; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

2018-06-01

The RNA-guided endonuclease Cas9 has applied as an efficient gene-editing method in malaria parasite Plasmodium. However, the size (4.2 kb) of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for genome editing in the parasites only introduced with cas9 plasmid. To establish the endogenous and constitutive expression of Cas9 protein in the rodent malaria parasite P. yoelii, we replaced the coding region of an endogenous gene sera1 with the intact SpCas9 coding sequence using the CRISPR/Cas9-mediated genome editing method, generating the cas9-knockin parasite (PyCas9ki) of the rodent malaria parasite P. yoelii. The resulted PyCas9ki parasite displays normal progression during the whole life cycle and possesses the Cas9 protein expression in asexual blood stage. By introducing the plasmid (pYCs) containing only sgRNA and homologous template elements, we successfully achieved both deletion and tagging modifications for different endogenous genes in the genome of PyCas9ki parasite. This cas9-knockin PyCas9ki parasite provides a new platform facilitating gene functions study in the rodent malaria parasite P. yoelii. Copyright © 2018 Elsevier B.V. All rights reserved.

[Determination of prevalence and etiology of anemia during pregnancy in southern Benin, in conjunction with revision of national management policy].

PubMed

Koura, K G; Briand, V; Massougbodji, A; Chippaux, J P; Cot, M; Garcia, A

2011-02-01

Anemia during pregnancy is a serious public health problem. Control requires identification of the underlying etiology. The objective of this study carried out in conjunction with revision of the national policy for the protection of pregnant women in Benin was to determine the prevalence and etiology of anemia. From October 2006 to April 2007, 300 pregnant women were examined at two maternities in Ouidah, Benin. Sociodemographic and environmental characteristics, dietary data, behavioral practices, and history of malaria infection during pregnancy were collected. Blood and stool samples were tested for the presence of malaria parasites and intestinal worms respectively. Hemoglobin and ferritinemia levels were also determined. The prevalence of anemia (Hb < 11 g/dL) was 65.7% while that of malaria and intestinal worms was 4.3% and 8% respectively. Iron deficiency was not found. A borderline significant correlation was found between helminthiasis and anemia. No correlation was found between anemia and malaria. These findings indicate that kits progressively introduced by the health system during the study period provided relatively effective care. This study demonstrates a high prevalence of moderate anemia during pregnancy and suggests that it is mainly due to intestinal helminthiasis. These findings underline the importance of preventive antihelminthic treatment during pregnancy.

Antimalarial compounds in Phase II clinical development.

PubMed

Held, Jana; Jeyaraj, Sankarganesh; Kreidenweiss, Andrea

2015-03-01

Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development. Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations. Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.

Impact of home-based management of malaria on health outcomes in Africa: a systematic review of the evidence.

PubMed

Hopkins, Heidi; Talisuna, Ambrose; Whitty, Christopher Jm; Staedke, Sarah G

2007-10-08

Home-based management of malaria (HMM) is promoted as a major strategy to improve prompt delivery of effective malaria treatment in Africa. HMM involves presumptively treating febrile children with pre-packaged antimalarial drugs distributed by members of the community. HMM has been implemented in several African countries, and artemisinin-based combination therapies (ACTs) will likely be introduced into these programmes on a wide scale. The published literature was searched for studies that evaluated the health impact of community- and home-based treatment for malaria in Africa. Criteria for inclusion were: 1) the intervention consisted of antimalarial treatment administered presumptively for febrile illness; 2) the treatment was administered by local community members who had no formal education in health care; 3) measured outcomes included specific health indicators such as malaria morbidity (incidence, severity, parasite rates) and/or mortality; and 4) the study was conducted in Africa. Of 1,069 potentially relevant publications identified, only six studies, carried out over 18 years, were identified as meeting inclusion criteria. Heterogeneity of the evaluations, including variability in study design, precluded meta-analysis. All trials evaluated presumptive treatment with chloroquine and were conducted in rural areas, and most were done in settings with seasonal malaria transmission. Conclusions regarding the impact of HMM on morbidity and mortality endpoints were mixed. Two studies showed no health impact, while another showed a decrease in malaria prevalence and incidence, but no impact on mortality. One study in Burkina Faso suggested that HMM decreased the proportion of severe malaria cases, while another study from the same country showed a decrease in the risk of progression to severe malaria. Of the four studies with mortality endpoints only one from Ethiopia showed a positive impact, with a reduction in the under-5 mortality rate of 40.6% (95% CI 29.2 - 50.6). Currently the evidence base for HMM in Africa, particularly regarding use of ACTs, is narrow and priorities for further research are discussed. To optimize treatment and maximize health benefits, drug regimens and delivery strategies in HMM programmes may need to be tailored to local conditions. Additional research could help guide programme development, policy decision-making, and implementation.

Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study.

PubMed

Bisoffi, Zeno; Leoni, Stefania; Buonfrate, Dora; Lodesani, Claudia; Eseme, Franklin Esoka; Monteiro, Geraldo Badona; Marocco, Stefania; Guerriero, Massimo

2015-12-02

The hyperreactive malarial splenomegaly (HMS) represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly (e-HMS). The main research questions was: does "e-HMS" tend to evolve to the full-blown syndrome? And if so, what are the main factors influencing this evolution? Retrospective, longitudinal study. The patient database was searched to retrieve all potentially eligible patients. e-HMS was defined by splenomegaly of any size (with or without raised IgM), high anti-malarial antibody titre and exclusion of other causes of splenomegaly. The clinical outcome at following visits was analysed in relation to re-exposure to malaria, and to treatment (only part of the patients with e-HMS were treated with a single anti-malarial treatment and advised to follow an effective anti-malarial prophylaxis, if re-exposed). The association of the outcome with the main independent variables was first assessed with univariate analysis. A stepwise logistic regression model was then performed to study the association of the outcome with the main independent variables. One hundred and twenty-six subjects with e-HMS were retrieved. Eighty-one had at least one follow-up visit. Of 46 re-exposed to malaria for a variable period, 21 (46 %) had progressed, including 10/46 (22 %) evolving to full-blown HMS, while of 29 patients not re-exposed, 24 (93 %) had improved or cured and five (7 %) progressed (p < 0.001). At logistic regression re-exposure was confirmed as a major risk factor of progression (OR 9.458, CI 1.767-50.616) while treatment at initial visit was protective (OR 0.187, CI 0.054-0.650). e-HMS should be regarded as a clinical condition predisposing to HMS. Although the case definition may include false positives, e-HMS should be treated just as the full-blown syndrome. A single anti-malarial treatment is probably adequate, followed by effective prophylaxis for patients exposed again to malaria transmission.

Perils of the new labor management guidelines.

PubMed

Cohen, Wayne R; Friedman, Emanuel A

2015-04-01

Recent guidelines issued jointly by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine for assessing labor progress differ substantially from those described initially by Friedman, which have guided clinical practice for decades. The guidelines are based on results obtained from new and untested methods of analyzing patterns of cervical dilatation and fetal descent. Before these new guidelines are adopted into clinical practice, the results obtained by these unconventional analytic approaches should be validated and shown to be superior, or at least equivalent, to currently accepted standards. The new guidelines indicate the patterns of labor originally described by Friedman are incorrect and, further, are inapplicable to modern obstetric practice. We contend that the original descriptions of normal and abnormal labor progress, which were based on direct clinical observations, accurately describe progress in dilatation and descent, and that the differences reported more recently are likely attributable to patient selection and the potential inaccuracy of very high-order polynomial curve-fitting methods. The clinical evaluation of labor is a process of serially estimating the likelihood of a safe vaginal delivery. Because many factors contribute to that likelihood, such as cranial molding, head position and attitude, and the bony architecture and capacity of the pelvis, graphic labor patterns should never be used in isolation. The new guidelines are based heavily on unvalidated notions of labor progress and ignore clinical parameters that should remain cornerstones of intrapartum decision-making. Copyright © 2015. Published by Elsevier Inc.

Real-time flood forecasting

USGS Publications Warehouse

Lai, C.; Tsay, T.-K.; Chien, C.-H.; Wu, I.-L.

2009-01-01

Researchers at the Hydroinformatic Research and Development Team (HIRDT) of the National Taiwan University undertook a project to create a real time flood forecasting model, with an aim to predict the current in the Tamsui River Basin. The model was designed based on deterministic approach with mathematic modeling of complex phenomenon, and specific parameter values operated to produce a discrete result. The project also devised a rainfall-stage model that relates the rate of rainfall upland directly to the change of the state of river, and is further related to another typhoon-rainfall model. The geographic information system (GIS) data, based on precise contour model of the terrain, estimate the regions that were perilous to flooding. The HIRDT, in response to the project's progress, also devoted their application of a deterministic model to unsteady flow of thermodynamics to help predict river authorities issue timely warnings and take other emergency measures.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm.

PubMed

Dinerstein, Eric; Olson, David; Joshi, Anup; Vynne, Carly; Burgess, Neil D; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E M; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C; Llewellyn, Othman A; Miller, Anthony G; Patzelt, Annette; Ghazanfar, Shahina A; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F; Saleem, Muhammad

2017-06-01

We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature-a companion to the Paris Climate Deal-to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods.

An Ecoregion-Based Approach to Protecting Half the Terrestrial Realm

PubMed Central

Olson, David; Joshi, Anup; Burgess, Neil D.; Wikramanayake, Eric; Hahn, Nathan; Palminteri, Suzanne; Hedao, Prashant; Noss, Reed; Hansen, Matt; Locke, Harvey; Ellis, Erle C; Jones, Benjamin; Barber, Charles Victor; Hayes, Randy; Kormos, Cyril; Martin, Vance; Crist, Eileen; Sechrest, Wes; Price, Lori; Baillie, Jonathan E. M.; Weeden, Don; Suckling, Kierán; Davis, Crystal; Sizer, Nigel; Moore, Rebecca; Thau, David; Birch, Tanya; Potapov, Peter; Turubanova, Svetlana; Tyukavina, Alexandra; de Souza, Nadia; Pintea, Lilian; Brito, José C.; Llewellyn, Othman A.; Miller, Anthony G.; Patzelt, Annette; Ghazanfar, Shahina A.; Timberlake, Jonathan; Klöser, Heinz; Shennan-Farpón, Yara; Kindt, Roeland; Lillesø, Jens-Peter Barnekow; van Breugel, Paulo; Graudal, Lars; Voge, Maianna; Al-Shammari, Khalaf F.; Saleem, Muhammad

2017-01-01

Abstract We assess progress toward the protection of 50% of the terrestrial biosphere to address the species-extinction crisis and conserve a global ecological heritage for future generations. Using a map of Earth's 846 terrestrial ecoregions, we show that 98 ecoregions (12%) exceed Half Protected; 313 ecoregions (37%) fall short of Half Protected but have sufficient unaltered habitat remaining to reach the target; and 207 ecoregions (24%) are in peril, where an average of only 4% of natural habitat remains. We propose a Global Deal for Nature—a companion to the Paris Climate Deal—to promote increased habitat protection and restoration, national- and ecoregion-scale conservation strategies, and the empowerment of indigenous peoples to protect their sovereign lands. The goal of such an accord would be to protect half the terrestrial realm by 2050 to halt the extinction crisis while sustaining human livelihoods. PMID:28608869

Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates.

PubMed

Essone, Jean Claude Biteghe Bi; N'Dilimabaka, Nadine; Ondzaga, Julien; Lekana-Douki, Jean Bernard; Mba, Dieudonné Nkoghe; Deloron, Philippe; Mazier, Dominique; Gay, Frédrérick; Touré Ndouo, Fousseyni S

2017-06-27

Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive. The cerebral microvascular endothelial cells-D3 and lung endothelial cells both from human were cultured separately and challenged with P. falciparum field isolates taken directly from malaria patients or 3D7 strain (in vitro maintained culture). The capacity of these P. falciparum isolates to induce endothelial cell apoptosis via cytoadherence or not was then assessed. Overall, 27 P. falciparum isolates were collected from patients with uncomplicated malaria (n = 25) or severe malaria (n = 2). About half the isolates (n = 17) were able to bind brain endothelial cells (12 isolates, 44%) or lung endothelial cells (17 isolates, 63%) or both (12 isolates, 44%). Sixteen (59%) of the 27 isolates were apoptogenic for brain and/or lung endothelial cells. The apoptosis stimulus could be cytoadherence, direct cell-cell contact without cytoadherence, or diffusible soluble factors. While some of the apoptogenic isolates used two stimuli (direct contact with or without cytoadherence, plus soluble factors) to induce apoptosis, others used only one. Among the 16 apoptogenic isolates, eight specifically targeted brain endothelial cells, one lung endothelial cells, and seven both. These results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction.

Drugs in Development for Malaria.

PubMed

Ashley, Elizabeth A; Phyo, Aung Pyae

2018-05-25

The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical development. Most of these are blood schizonticides for the treatment of uncomplicated falciparum malaria, under evaluation either singly or as part of two-drug combinations. Leading candidates progressing through the pipeline are artefenomel-ferroquine and lumefantrine-KAF156, both in Phase 2b. Treatment of severe malaria continues to rely on two parenteral drugs with ancient forebears: artesunate and quinine, with sevuparin being evaluated as an adjuvant therapy. Tafenoquine is under review by stringent regulatory authorities for approval as a single-dose treatment for Plasmodium vivax relapse prevention. This represents an advance over standard 14-day primaquine regimens; however, the risk of acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency remains. For disease prevention, several of the newer agents show potential but are unlikely to be recommended for use in the main target groups of pregnant women and young children for some years. Latest predictions are that the malaria burden will continue to be high in the coming decades. This fact, coupled with the repeated loss of antimalarials to resistance, indicates that new antimalarials will be needed for years to come. Failure of the artemisinin-based combinations in Southeast Asia has stimulated a reappraisal of current approaches to combination therapy for malaria with incorporation of three or more drugs in a single treatment under consideration.

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.

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.

Negotiating Peril: The Lived Experience of Rural, Low-Income Women Exposed to IPV During Pregnancy and Postpartum.

PubMed

Burnett, Camille; Schminkey, Donna; Milburn, Juliane; Kastello, Jennifer; Bullock, Linda; Campbell, Jacquelyn; Sharps, Phyllis

2016-07-01

This qualitative study of 10 rural women examines their lived experience of intimate partner violence during pregnancy and the first 2 postpartum years. In-depth interviews occurred during pregnancy and 4 times postpartum. A Heideggerian approach revealed "negotiating peril" as the overarching theme; sub-themes were unstable environment, adaptive calibration, primacy of motherhood, and numb acceptance. Some incremental shifts in severity of abusive situations were observed. Results elucidate the ambivalence with which these women view institutions that are designed to help them. Findings highlight factors that may explain why interventions designed to help often do not appear efficacious in facilitating complete termination of an abusive situation. © The Author(s) 2015.

Extreme risk assessment based on normalized historic loss data

NASA Astrophysics Data System (ADS)

Eichner, Jan

2017-04-01

Natural hazard risk assessment and risk management focuses on the expected loss magnitudes of rare and extreme events. Such large-scale loss events typically comprise all aspects of compound events and accumulate losses from multiple sectors (including knock-on effects). Utilizing Munich Re's NatCatSERVICE direct economic loss data, we beriefly recap a novel methodology of peril-specific loss data normalization which improves the stationarity properties of highly non-stationary historic loss data (due to socio-economic growth of assets prone to destructive forces), and perform extreme value analysis (peaks-over-threshold method) to come up with return level estimates of e.g. 100-yr loss event scenarios for various types of perils, globally or per continent, and discuss uncertainty in the results.

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

Comparison of a PfHRP2-based rapid diagnostic test and PCR for malaria in a low prevalence setting in rural southern Zambia: implications for elimination.

PubMed

Laban, Natasha M; Kobayashi, Tamaki; Hamapumbu, Harry; Sullivan, David; Mharakurwa, Sungano; Thuma, Philip E; Shiff, Clive J; Moss, William J

2015-01-28

Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum. Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR. Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 x 10(3) copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of >99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion. Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination.

Impact of long-lasting, insecticidal nets on anaemia and prevalence of Plasmodium falciparum among children under five years in areas with highly resistant malaria vectors.

PubMed

Tokponnon, Filémon T; Ogouyémi, Aurore Hounto; Sissinto, Yolande; Sovi, Arthur; Gnanguenon, Virgile; Cornélie, Sylvie; Adéothy, Adicath Adéola; Ossè, Razaki; Wakpo, Abel; Gbénou, Dina; Oke, Mariam; Kinde-Gazard, Dorothée; Kleinschmidt, Immo; Akogbeto, Martin C; Massougbodji, Achille

2014-03-01

The widespread use of insecticide-treated nets (LLINs) leads to the development of vector resistance to insecticide. This resistance can reduce the effectiveness of LLIN-based interventions and perhaps reverse progress in reducing malaria morbidity. To prevent such difficulty, it is important to know the real impact of resistance in the effectiveness of mosquito nets. Therefore, an assessment of LLIN efficacy was conducted in malaria prevention among children in high and low resistance areas. The study was conducted in four rural districts and included 32 villages categorized as low or high resistance areas in Plateau Department, south-western Benin. Larvae collection was conducted to measure vector susceptibility to deltamethrin and knockdown resistance (kdr) frequency. In each resistance area, around 500 children were selected to measure the prevalence of malaria infection as well as the prevalence of anaemia associated with the use of LLINs. Observed mortalities of Anopheles gambiae s.s population exposed to deltamethrin ranged from 19 to 96%. Knockdown resistance frequency was between 38 and 84%. The prevalence of malaria infection in children under five years was 22.4% (19.9-25.1). This prevalence was 17.3% (14.2-20.9) in areas of high resistance and 27.1% (23.5-31.1) in areas of low resistance (p=0.04). Eight on ten children that were aged six - 30 months against seven on ten of those aged 31-59 months were anaemic. The anaemia observed in the six to 30-month old children was significantly higher than in the 31-59 month old children (p=0.00) but no difference associated with resistance areas was observed (p=0.35). The net use rate was 71%. The risk of having malaria was significantly reduced (p<0.05) with LLIN use in both low and high resistance areas. The preventive effect of LLINs in high resistance areas was 60% (95% CI: 40-70), and was significantly higher than that observed in low resistance areas (p<0.05). The results of this study showed that the resistance of malaria vectors seems to date not have affected the impact of LLINs and the use of LLINs was highly associated with reduced malaria prevalence irrespective of resistance.

Molecular Farming in Artemisia annua, a Promising Approach to Improve Anti-malarial Drug Production

PubMed Central

Pulice, Giuseppe; Pelaz, Soraya; Matías-Hernández, Luis

2016-01-01

Malaria is a parasite infection affecting millions of people worldwide. Even though progress has been made in prevention and treatment of the disease; an estimated 214 million cases of malaria occurred in 2015, resulting in 438,000 estimated deaths; most of them occurring in Africa among children under the age of five. This article aims to review the epidemiology, future risk factors and current treatments of malaria, with particular focus on the promising potential of molecular farming that uses metabolic engineering in plants as an effective anti-malarial solution. Malaria represents an example of how a health problem may, on one hand, influence the proper development of a country, due to its burden of the disease. On the other hand, it constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is proposed here as a sustainable, promising, alternative for the production, not only of natural herbal repellents for malaria prevention but also for the production of sustainable anti-malarial drugs, like artemisinin (AN), used for primary parasite infection treatments. AN, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua. However, the low concentration of AN in the plant makes this molecule relatively expensive and difficult to produce in order to meet the current worldwide demand of Artemisinin Combination Therapies (ACTs), especially for economically disadvantaged people in developing countries. The biosynthetic pathway of AN, a process that takes place only in glandular secretory trichomes of A. annua, is relatively well elucidated. Significant efforts have been made using plant genetic engineering to increase production of this compound. These include diverse genetic manipulation approaches, such as studies on diverse transcription factors which have been shown to regulate the AN genetic pathway and other biological processes. Results look promising; however, further efforts should be addressed toward optimization of the most cost-effective biofarming approaches for synthesis and production of medicines against the malaria parasite. PMID:27047510

Sickle cell protection from malaria.

PubMed

Eridani, Sandro

2011-10-19

A linkage between presence of Sickle Haemoglobin (HbS) and protection from malaria infection and clinical manifestations in certain areas was suspected from early observations and progressively elucidated by more recent studies. Research has confirmed the abovementioned connection, but also clarified how such protection may be abolished by coexistence of sickle cell trait (HbS trait) and alpha thalassemia, which may explain the relatively low incidence of HbS trait in the Mediterranean. The mechanisms of such protective effect are now being investigated: factors of genetic, molecular and immunological nature are prominent. As for genetic factors attention is given to the role of the red blood cell (RBC) membrane complement regulatory proteins as polymorphisms of these components seem to be associated with resistance to severe malaria; genetic ligands like the Duffy group blood antigen, necessary for erythrocytic invasion, and human protein CD36, a major receptor for P. falciparum-infected RBC's, are also under scrutiny: attention is focused also on plasmodium erythrocyte-binding antigens, which bind to RBC surface components. Genome-wide linkage and association studies are now carried out too, in order to identify genes associated with malaria resistance. Only a minor role is attributed to intravascular sickling, phagocytosis and haemolysis, while specific molecular mechanisms are the object of intensive research: among these a decisive role is played by a biochemical sequence, involving activation of haeme oxygenase (HMO-1), whose effect appears mediated by carbon monoxide (CO). A central role in protection from malaria is also played by immunological factors, which may stimulate antibody production to plasmodium antigens in the early years of life; the role of agents like pathogenic CD8 T-cells has been suggested while the effects of molecular actions on the immunity mechanism are presently investigated. It thus appears that protection from malaria can be explained by interaction of different factors: the elucidation of such mechanisms may prove valuable for the prevention and treatment strategy of a disease which still affects large parts of the world.

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.

Modelling climate change and malaria transmission.

PubMed

Parham, Paul E; Michael, Edwin

2010-01-01

The impact of climate change on human health has received increasing attention in recent years, with potential impacts due to vector-borne diseases only now beginning to be understood. As the most severe vector-borne disease, with one million deaths globally in 2006, malaria is thought most likely to be affected by changes in climate variables due to the sensitivity of its transmission dynamics to environmental conditions. While considerable research has been carried out using statistical models to better assess the relationship between changes in environmental variables and malaria incidence, less progress has been made on developing process-based climate-driven mathematical models with greater explanatory power. Here, we develop a simple model of malaria transmission linked to climate which permits useful insights into the sensitivity of disease transmission to changes in rainfall and temperature variables. Both the impact of changes in the mean values of these key external variables and importantly temporal variation in these values are explored. We show that the development and analysis of such dynamic climate-driven transmission models will be crucial to understanding the rate at which P. falciparum and P. vivax may either infect, expand into or go extinct in populations as local environmental conditions change. Malaria becomes endemic in a population when the basic reproduction number R0 is greater than unity and we identify an optimum climate-driven transmission window for the disease, thus providing a useful indicator for determing how transmission risk may change as climate changes. Overall, our results indicate that considerable work is required to better understand ways in which global malaria incidence and distribution may alter with climate change. In particular, we show that the roles of seasonality, stochasticity and variability in environmental variables, as well as ultimately anthropogenic effects, require further study. The work presented here offers a theoretical framework upon which this future research may be developed.

The role of vector control in stopping the transmission of malaria: threats and opportunities.

PubMed

Hemingway, Janet

2014-01-01

Malaria control, and that of other insect borne diseases such as dengue, is heavily dependent on our ability to control the mosquito populations that transmit these diseases. The major push over the last decade to reduce the global burden of malaria has been driven by the distribution of pyrethroid insecticide-treated bednets and an increase in coverage of indoor residual spraying (IRS). This has reduced malaria deaths by a third. Progress towards the goal of reducing this further is threatened by lack of funding and the selection of drug and insecticide resistance. When malaria control was initially scaled up, there was little pyrethroid resistance in the major vectors, today there is no country in Africa where the vectors remain fully susceptible to pyrethroids. The first pyrethroid resistance mechanisms to be selected produced low-level resistance which had little or no operational significance. More recently, metabolically based resistance has been selected, primarily in West Africa, which in some mosquito populations produces more than 1000-fold resistance. As this spreads the effectiveness of pyrethroid-based bednets and IRS will be compromised. New public health insecticides are not readily available. The pipeline of agrochemical insecticides that can be re-purposed for public health dried up 30 years ago when the target product profile for agricultural insecticides shifted from broad spectrum, stable, contact-acting insecticides to narrow spectrum stomach poisons that could be delivered through the plant. A public-private partnership, the Innovative Vector Control Consortium, was established in 2005 to stimulate the development of new public health pesticides. Nine potential new classes of chemistry are in the pipeline, with the intention of developing three into new insecticides. While this has been successfully achieved, it will still take 6-9 years for new insecticides to reach the market. Careful management of the resistance situation in the interim will be needed if current gains in malaria control are not to be reversed.

The role of vector control in stopping the transmission of malaria: threats and opportunities

PubMed Central

Hemingway, Janet

2014-01-01

Malaria control, and that of other insect borne diseases such as dengue, is heavily dependent on our ability to control the mosquito populations that transmit these diseases. The major push over the last decade to reduce the global burden of malaria has been driven by the distribution of pyrethroid insecticide-treated bednets and an increase in coverage of indoor residual spraying (IRS). This has reduced malaria deaths by a third. Progress towards the goal of reducing this further is threatened by lack of funding and the selection of drug and insecticide resistance. When malaria control was initially scaled up, there was little pyrethroid resistance in the major vectors, today there is no country in Africa where the vectors remain fully susceptible to pyrethroids. The first pyrethroid resistance mechanisms to be selected produced low-level resistance which had little or no operational significance. More recently, metabolically based resistance has been selected, primarily in West Africa, which in some mosquito populations produces more than 1000-fold resistance. As this spreads the effectiveness of pyrethroid-based bednets and IRS will be compromised. New public health insecticides are not readily available. The pipeline of agrochemical insecticides that can be re-purposed for public health dried up 30 years ago when the target product profile for agricultural insecticides shifted from broad spectrum, stable, contact-acting insecticides to narrow spectrum stomach poisons that could be delivered through the plant. A public–private partnership, the Innovative Vector Control Consortium, was established in 2005 to stimulate the development of new public health pesticides. Nine potential new classes of chemistry are in the pipeline, with the intention of developing three into new insecticides. While this has been successfully achieved, it will still take 6–9 years for new insecticides to reach the market. Careful management of the resistance situation in the interim will be needed if current gains in malaria control are not to be reversed. PMID:24821917

Chemopreventive and remediation effect of Adansonia digitata L. Baobab (Bombacaceae) stem bark extracts in mouse model malaria.

PubMed

Adeoye, A O; Bewaji, C O

2018-01-10

Adansonia digitata L. Baobab (Bombacaceae) solvent extracts have been reported to possess medicinal properties and are currently been used traditionally for the treatment of malaria and several other diseases and infection; however few reports exist in literature that provides supportive scientific evidence in favour of its medicinal use. This study investigated the efficacy of Adansonia digitata stem bark extract in offering protection against experimental malaria and also examined its remediation effect when administered after established infection. Weanling albino mice were used in the study. The mice were transfected intraperitonially with an inoculums size of 1× 10 7 of chloroquine susceptible strain of plasmodium berghei infected erythrocytes. Mechanisms of action of the extract were investigated by measuring the degree of tissue peroxidation and tissue antioxidant status. Severity of malaria was determined by measuring the serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and serum and tissue Alkaline phosphatase (ALP) activity. There was a significant increase in serum CRP, TNF-α concentrations and serum and tissue ALP activity in the control mice following Plasmodium berghei infection. All the treatment had effect on the growth of Plasmodium berghei parasites in mice. The extracts showed a significant dose dependent increase packed cell volume (PCV), percentage chemosupression/clearance and a significant decrease in percentage parasitemia at the two doses when administered after established infection. Methanolic extract (MEAD) at 400mg/kg exhibited the highest chemosupressive activity. The extract significantly reduced the degree of tissue peroxidation, increased the level of reduced glutathione (GSH), catalase and superoxide dismutase activity. Administration of the extract after established infection reduced serum CRP and TNF-α concentrations and serum and tissue ALP activity. Our study suggests that Adansonia digitata protects against Plasmodium berghei induced-malaria, and that administration of the extract after established infection reduced malaria progression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Determinants of malaria infection in Dembia district, Northwest Ethiopia: a case-control study.

PubMed

Agegnehu, Fisseha; Shimeka, Alemayehu; Berihun, Firnus; Tamir, Melkamu

2018-04-11

Despite the progress in reducing malaria infections and related deaths, the disease remains a major global public health problem. The problem is among the top five leading causes of outpatient visits in Dembia district of the northwest Ethiopia. Therefore, this study aimed to assess the determinants of malaria infections in the district. An institution-based case-control study was conducted in Dembia district from October to November 2016. Out of the ten health centers in the district, four were randomly selected for the study in which 370 participants (185 cases and 185 controls) were enrolled. Data were collected using a pretested structured questionnaire. Factors associated with malaria infections were determined using logistic regression analysis. Odds ratio with 95% CI was used as a measure of association, and variables with a p-value of ≤0.05 were considered as statistically significant. The median age of all participants was 26 years, while that of cases and controls was 22 and 30 with a range of 1 to 80 and 2 to 71, respectively. In the multivariable logistic regression, over 15 years of age adjusted odds ratio(AOR) and confidence interval (CI) of (AOR = 18; 95% CI: 2.1, 161.5), being male (AOR = 2.2; 95% CI: 1.2, 3.9), outdoor activities at night (AOR = 5.7; 95% CI: 2.5, 12.7), bed net sharing (AOR = 3.9; 95% CI: 2.0, 7.7), and proximity to stagnant water sources (AOR = 2.7; 95% CI: 1.3, 5.4) were independent predictors. Being in over 15 years of age group, male gender, night time activity, bed net sharing and proximity to stagnant water sources were determinant factors of malaria infection in Dembia district. Additional interventions and strategies which focus on men, outdoor work at night, household net utilization, and nearby stagnant water sources are essential to reduce malaria infections in the area.

Malaria Surveillance - United States, 2014.

PubMed

Mace, Kimberly E; Arguin, Paul M

2017-05-26

Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. This report summarizes cases in persons with onset of illness in 2014 and trends during previous years. Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducts antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. Data from these reporting systems serve as the basis for this report. CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases, with onset of symptoms in 2014 among persons in the United States. The number of confirmed cases in 2014 is consistent with the number of confirmed cases reported in 2013 (n = 1,741; this number has been updated from a previous publication to account for delayed reporting for persons with symptom onset occurring in late 2013). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively. Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (<1.0%) with atovaquone resistance, and two (1.4%) with artemisinin resistance. The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2014 is the fourth highest annual total since then. Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate. Completion of data elements on the malaria case report form increased slightly in 2014 compared with 2013, but still remains unacceptably low. In 2014, at least one essential element (i.e., species, travel history, or resident status) was missing in 21.3% of case report forms. Incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFR travelers continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the number of imported malaria cases in the United States. Fewer U.S. resident patients reported taking chemoprophylaxis in 2014 (27.2%) compared with 2013 (28.6%), and adherence was poor among those who did take chemoprophylaxis. Proper use of malaria chemoprophylaxis will prevent the majority of malaria illnesses and reduce risk for severe disease (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC Guidelines for Treatment of Malaria in the United States and contact the CDC Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online at https://www.cdc.gov/malaria/diagnosis_treatment/ or by calling the Malaria Hotline at 770-488-7788 or toll-free at 855-856-4713.

Malaria Surveillance — United States, 2014

PubMed Central

Arguin, Paul M.

2017-01-01

Problem/Condition Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. Period Covered This report summarizes cases in persons with onset of illness in 2014 and trends during previous years. Description of System Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducts antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. Data from these reporting systems serve as the basis for this report. Results CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases, with onset of symptoms in 2014 among persons in the United States. The number of confirmed cases in 2014 is consistent with the number of confirmed cases reported in 2013 (n = 1,741; this number has been updated from a previous publication to account for delayed reporting for persons with symptom onset occurring in late 2013). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively. Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (<1.0%) with atovaquone resistance, and two (1.4%) with artemisinin resistance. Interpretation The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2014 is the fourth highest annual total since then. Despite progress in reducing global prevalence of malaria, the disease remains endemic in many regions and use of appropriate prevention measures by travelers is still inadequate. Public Health Action Completion of data elements on the malaria case report form increased slightly in 2014 compared with 2013, but still remains unacceptably low. In 2014, at least one essential element (i.e., species, travel history, or resident status) was missing in 21.3% of case report forms. Incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFR travelers continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFR travelers need to be developed and implemented to have a substantial impact on the number of imported malaria cases in the United States. Fewer U.S. resident patients reported taking chemoprophylaxis in 2014 (27.2%) compared with 2013 (28.6%), and adherence was poor among those who did take chemoprophylaxis. Proper use of malaria chemoprophylaxis will prevent the majority of malaria illnesses and reduce risk for severe disease (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC Guidelines for Treatment of Malaria in the United States and contact the CDC Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online at https://www.cdc.gov/malaria/diagnosis_treatment/ or by calling the Malaria Hotline at 770-488-7788 or toll-free at 855-856-4713. PMID:28542123

7 CFR 1436.5 - Eligible borrowers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... with any applicable local zoning, land use, and building codes for the applicable farm storage facility... has all peril structural insurance; (10) Demonstrates compliance with the National Environmental...

A qualitative study to identify community structures for management of severe malaria: a basis for introducing rectal artesunate in the under five years children in Nakonde District of Zambia.

PubMed

Kaona, Frederick A D; Tuba, Mary

2005-03-25

Malaria is a serious illness among children aged 5 years and below in Zambia, which carries with it many adverse effects including anemia and high parasites exposure that lead to infant and childhood mortality. Due to poor accessibility to modern health facilities, malaria is normally managed at home using indigenous and cosmopolitan medicines. In view of problems and implications associated with management of severe malaria at home, rectal artesunate is being proposed as a first aid drug to slow down multiplication of parasites in children before accessing appropriate treatment. A qualitative study using standardised in-depth and Focus Group Discussions (FGDs) guides to collect information from four (4) villages in Nakonde district, was conducted between February and March 2004. The guides were administered on 29 key informants living in the community and those whose children were admitted in the health facility. Participants in the 12 FGDs came from the 4 participating villages. Participants and key informants were fathers, younger and older mothers including grandmothers and other influential people at household level. Others were traditional healers, headmen, village secretaries, traditional birth attendants, church leaders and blacksmiths. FGDs and interview transcriptions were coded to identify common themes that were related to recognition, classification and naming of malaria illness, care-seeking behaviour and community treatment practices for severe malaria. Parental prior knowledge of the disease was important as the majority of informants (23 out of 29) and participants (69 out of 97) mentioned four combined symptoms that were used to recognise severe malaria. The symptoms were excessive body hotness, convulsions, vomiting yellow things and bulging of the fontanelle. On the other hand, all informants mentioned two or more of symptoms associated with severe malaria. In all 12 FGDs, participants reported that treatment of severe malaria commenced with the family and moved into the community as the illness progressed. Although treatment of severe diarrheal effects, were common among the Winamwanga, no rectal medicines to treat severe malaria were identified. Apart from the anti-malarial fansidar, which was mentioned by 23 in IDIs and 40 in FGDs, participants and informants also frequently mentioned indigenous medicines provided by healers and other respectable herbalists for repelling evil spirits, once a child had severe malaria. Mothers were the important arms for administration of ant-malarial drugs in the villages. Referrals began with healers to CHWs, where no CHWs existed healers directly referred sick children to the health facility. Our findings showed that there is a precedent for rectal application of traditional medicine for childhood illness. Therefore rectal artesunate may be a well-received intervention in Nakonde District, provided effective sensitisation, to mothers and CHWs is given which will strengthen the health care delivery system at community level.

Hit and lead criteria in drug discovery for infectious diseases of the developing world.

PubMed

Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

2015-11-01

Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

Utilizing direct skin feeding assays for development of vaccines that interrupt malaria transmission: A systematic review of methods and case study.

PubMed

Brickley, Elizabeth B; Coulibaly, Mamadou; Gabriel, Erin E; Healy, Sara A; Hume, Jen C C; Sagara, Issaka; Traore, Sekou F; Doumbo, Ogobara; Duffy, Patrick E

2016-11-21

Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay's use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel® vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the "effective sample size" (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays. Published by Elsevier Ltd.

Malaria Surveillance - United States, 2015.

PubMed

Mace, Kimberly E; Arguin, Paul M; Tan, Kathrine R

2018-05-04

Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000-2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC's Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.

Malaria Surveillance — United States, 2015

PubMed Central

Arguin, Paul M.; Tan, Kathrine R.

2018-01-01

Problem/Condition Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. Period Covered This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Description of System Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. Results CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000–2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). Interpretation The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. Public Health Actions The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC’s Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States. PMID:29723168

A School and Its Money...Soon Parted.

ERIC Educational Resources Information Center

Szabo, Joan

1995-01-01

Describes the potential perils of corporate tax incentives for communities. Discusses practices that drain funding from public schools--tax abatements, tax-increment financing, and industrial bonds. Three sidebars are included. (LMI)

Citizen Science in the Classroom: Perils and Promise of the New Web

NASA Astrophysics Data System (ADS)

Loughran, T.; Dirksen, R.

2010-12-01

Classroom citizen science projects invite students to generate, curate, post, query, and analyze data, publishing and discussing results in potentially large collaborative contexts. The new web offers a rich palette of such projects for any STEM educator to select from or create. This easy access to citizen science in the classroom is full of both promise and peril for science education. By offering examples of classroom citizen science projects in particle physics, earth and environmental sciences, each supported by a common mashup of technologies available to ordinary users, we will illustrate something of the promise of these projects for science education, and point to some of the challenges and failure modes--the peril--raised by easy access and particularly easy publication of data. How one sensibly responds to this promise and peril depends on how one views the goals of science (or more broadly, STEM) education: either as the equipping of individual students with STEM knowledge and skills so as to empower them for future options, or as the issuing of effective invitations into STEM communities. Building on the claim that these are complementary perspectives, both of value, we will provide an example of a classroom citizen science project analyzed from both perspectives. The BOSCO classroom-to-classroom water source mapping project provides students both in Northern Uganda and in South Dakota a collaborative platform for analyzing and responding to local water quality concerns. Students gather water quality data, use Google Forms embedded in a project wiki to enter data in a spreadsheet, which then automatically (through Mapalist, a free web service) gets posted to a Google Map, itself embedded in the project wiki. Using these technologies, data is thus collected and posted for analysis in a collaborative environment: the stage is set for classroom citizen science. In the context of this project we will address the question of how teachers can take advantage of the new web to encourage students to become creative problem-solvers in online collaborative contexts without looking past the foundation of careful preparation and the standards of reliability associated with publication in the STEM disciplines.

[The progress of malaria in sahelian eastern Niger. An ecological disaster zone].

PubMed

Julvez, J; Mouchet, J; Michault, A; Fouta, A; Hamidine, M

1997-01-01

The south eastern part of the Republic of Niger was ecologically damaged by the dryness since 1971. Rainfall decreased by 30 to 40% as compared to 1961-70 and lake Chad retreated 100 km to the south. Now it does not reach any more the Republic of Niger. Malaria studies have been carried out in urban and suburban places in Zinder and in the Diffa area at the extreme east. In Zinder parasitic indexes (PI) after the rainy season were around 30% to 10% according to the situation of the corner in respect with surface waters during the rains. In dry season the index fell to 3%. In Diffa in a part of the city at high risk because lining the Komadougou river, PI was only 6.7% in October after the rains. Before 1970 PI recorded in Niamey were up to 50%. In Diffa area they were of 49% in N'Guigmi and 32% in Bosso, ecologically similar to Diffa. Obviously there was a sharp decrease of malaria which could be due to the disappearance of An. funestus after 1970. It was one of the main malaria vectors. Its larvae were developing in pools remaining after the rains with heavy standing vegetation. These breeding sites have been destroyed by both dryness and human activities. Now the area has became hypoendemic and is suitable for epidemic because population has not much immunity. A surveillance system for epidemic control should be settle.

[Malaria research for developing countries: the PAL+ program].

PubMed

Agid, F

2003-01-01

Despite extensive national and international intervention, little progress has been made in controlling, malaria and other communicable diseases afflicting many developing countries in the world. In response to the need to pursue and enhance investigation, the French Ministry of Research launched the PAL+ program in 1999 with the purpose of promoting concerted "research on malaria and other communicable diseases afflicting developing countries". The program is focused on developing methods of prevention and treatment for countries in Sub-Saharan Africa, Southeast Asia, and Latin America. Advancement of these scientific goals is further by a determined efforts (i) to provide means for national coordination and scientific organization of malaria research in France and (ii) to revive the spirit and mechanisms that characterized previous operations of cooperation between France and countries in the southern hemisphere. This new vision of cooperation is based on two organizational approaches. The first involves integrated programs in which training and transfer of knowledge are essential. The second involves joint projects in which networks maintained by a continuous exchange in operational seminars contribute to establishing a permanent dialogue between the North and South. Priority research areas have been encouraged to respond to specific public health issues with emphasis on establishing a balance between work in the field and development of knowledge. The priority areas include (i) responding to the increasing incidence of drug resistance by identifying of new antimalarial drugs and defining new therapeutic strategies; (ii) understanding the implications of the pathophysiology and physiopathology mechanisms underlying severe malaria manifestations for development of a malaria vaccine; (iii) finding new opportunities for prevention of malaria based on more effective vector control; (iv) using social anthropology to factor population behaviour and habits into the design of effective malaria control measures. The PAL+ program was founded on a commitment to provide participating countries with the means necessary to improve their research capability and to coordinate and structure scientific research by creating enduring partnerships between investigators in France and southern hemisphere countries. For this purpose the PAL+ workshop program involving regular encounters between northern and southern hemisphere researchers has been set up to encourage discussion, interaction, and multidisciplinary projects. The exceptionally instructive impact of these workshops has proven to be an essential element in the overall PAL+ program that has greatly stimulated malaria research. This program has been successful in creating a new spirit of intervention and has provided a rarely equalled vehicle for collaboration. By bringing the whole research community together over the major research programs now under way in the North/South networks, the PAL+ program represents a new and decisive step in achieving the long-sought goal of meaningful scientific cooperation between northern and southern hemisphere countries in the domain of public health.

Impact of insecticide-treated bed nets on malaria transmission indices on the south coast of Kenya

PubMed Central

2011-01-01

Background Besides significantly reducing malaria vector densities, prolonged usage of bed nets has been linked to decline of Anopheles gambiae s.s. relative to Anopheles arabiensis, changes in host feeding preference of malaria vectors, and behavioural shifts to exophagy (outdoor biting) for the two important malaria vectors in Africa, An. gambiae s.l. and Anopheles funestus. In southern coastal Kenya, bed net use was negligible in 1997-1998 when Anopheles funestus and An. gambiae s.s. were the primary malaria vectors, with An. arabiensis and Anopheles merus playing a secondary role. Since 2001, bed net use has increased progressively and reached high levels by 2009-2010 with corresponding decline in malaria transmission. Methods To evaluate the impact of the substantial increase in household bed net use within this area on vector density, vector composition, and human-vector contact, indoor and outdoor resting mosquitoes were collected in the same region during 2009-2010 using pyrethrum spray catches and clay pots for indoor and outdoor collections respectively. Information on bed net use per sleeping spaces and factors influencing mosquito density were determined in the same houses using Poisson regression analysis. Species distribution was determined, and number of mosquitoes per house, human-biting rates (HBR), and entomological inoculation rate (EIR) were compared to those reported for the same area during 1997-1998, when bed net coverage had been minimal. Results Compared to 1997-1998, a significant decline in the relative proportion of An. gambiae s.s. among collected mosquitoes was noted, coupled with a proportionate increase of An. arabiensis. Following > 5 years of 60-86% coverage with bed nets, the density, human biting rate and EIR of indoor resting mosquitoes were reduced by more than 92% for An. funestus and by 75% for An. gambiae s.l. In addition, the host feeding choice of both vectors shifted more toward non-human vertebrates. Besides bed net use, malaria vector abundance was also influenced by type of house construction and according to whether one sleeps on a bed or a mat (both of these are associated with household wealth). Mosquito density was positively associated with presence of domestic animals. Conclusions These entomological indices indicate a much reduced human biting rate and a diminishing role of An. gambiae s.s. in malaria transmission following high bed net coverage. While increasing bed net coverage beyond the current levels may not significantly reduce the transmission potential of An. arabiensis, it is anticipated that increasing or at least sustaining high bed net coverage will result in a diminished role for An. funestus in malaria transmission. PMID:22165904

Watson, Swellengrebel and species sanitation: environmental and ecological aspects.

PubMed

Bradley, D J

1994-08-01

Following the discovery of mosquito transmission of malaria, the theory and practice of malaria control by general and selective removal of specific vector populations resulted particularly from Malcolm Watson's empirical work in peninsular Malaysia, first in the urban and peri-urban areas of Klang and Port Swettenham and subsequently in the rural rubber plantations, and from the work of N.H. Swellengrebel in nearby Indonesia on the taxonomy, ecology and control of anophelines. They developed the concept of species sanitation: the selective modification of the environment to render a particular anopheline of no importance as a vector in a particular situation. The lack of progress along these lines in India at that time is contrasted with that in south-east Asia. The extension of species sanitation and related concepts to other geographical areas and to other vector-borne disease situations is outlined.

Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

DTIC Science & Technology

2009-01-01

CBC, reticulocyte count, G-6-PD determination, Duffy phenotype, ABO and Rh group typing, hemoglobin electrophoresis and erythrocyte sedimentation ... rates and APTT† Cardiovascular disease Hepatic or renal abnormalities Cardiovascular function Immunodeficiency Electrocardiogram Autoimmune...malaria vaccine. Progress has been achieved in the development of P. vivax pre- erythrocytic subunit vaccines such as the circumsporo- zoite (CS) and

Parasites and vectors carry no passport: how to fund cross-border and regional efforts to achieve malaria elimination

PubMed Central

2012-01-01

Background Tremendous progress has been made in the last ten years in reducing morbidity and mortality caused by malaria, in part because of increases in global funding for malaria control and elimination. Today, many countries are striving for malaria elimination. However, a major challenge is the neglect of cross-border and regional initiatives in malaria control and elimination. This paper seeks to better understand Global Fund support for multi-country initiatives. Methods Documents and proposals were extracted and reviewed from two main sources, the Global Fund website and Aidspan.org. Documents and reports from the Global Fund Technical Review Panel, Board, and Secretariat documents such as guidelines and proposal templates were reviewed to establish the type of policies enacted and guidance provided from the Global Fund on multi-country initiatives and applications. From reviewing this information, the researchers created 29 variables according to eight dimensions to use in a review of Round 10 applications. All Round 10 multi-country applications (for HIV, malaria and tuberculosis) and all malaria multi-country applications (6) from Rounds 1 – 10 were extracted from the Global Fund website. A blind review was conducted of Round 10 applications using the 29 variables as a framework, followed by a review of four of the six successful malaria multi-country grant applications from Rounds 1 – 10. Findings During Rounds 3 – 10 of the Global Fund, only 5.8% of grants submitted were for multi-country initiatives. Out of 83 multi-country proposals submitted, 25.3% were approved by the Technical Review Panel (TRP) for funding, compared to 44.9% of single-country applications. The majority of approved multi-country applications were for HIV (76.2%), followed by malaria (19.0%), then tuberculosis (4.8%). TRP recommendations resulted in improvements to application forms, although guidance was generally vague. The in-depth review of Round 10 multi-country proposals showed that applicants described their projects in one of two ways: a regional ‘network approach’ by which benefits are derived from economies of scale or from enhanced opportunities for mutual support and learning or the development of common policies and approaches; or a ‘cross-border’ approach for enabling activities to be more effectively delivered towards border-crossing populations or vectors. In Round 10, only those with a ‘network approach’ were recommended for funding. The Global Fund has only ever approved six malaria multi-country applications. Four approved applications stated strong arguments for a multi-country initiative, combining both ‘cross-border’ and ‘network’ approaches. Conclusion With the cancellation of Round 11 and the proposal that the Global Fund adopt a more targeted and strategic approach to funding, the time is opportune for the Global Fund to develop a clear consensus about the key factors and criteria for funding malaria specific multi-country initiatives. This study found that currently there was a lack of guidance on the key features that a successful multi-country proposal needs to be approved and that applications directed towards the ‘network’ approach were most successful in Round 10. This type of multi-country proposal may favour other diseases such as HIV, whereas the need for malaria control and elimination is different, focusing on cross-border coordination and delivery of interventions to specific groups. The Global Fund should seek to address these issues and give better guidance to countries and regions and investigate disease-specific calls for multi-country and regional applications. PMID:23057734

Field assessment of a novel spatial repellent for malaria control: a feasibility and acceptability study in Mondulkiri, Cambodia.

PubMed

Liverani, Marco; Charlwood, Jacques Derek; Lawford, Harriet; Yeung, Shunmay

2017-10-13

Large-scale use of insecticide-treated nets and indoor residual spraying have contributed to a significant decrease in malaria transmission worldwide. Further reduction and progress towards elimination, however, require complementary control measures which can address the remaining gaps in protection from mosquito bites. Following the development of novel pyrethroids with high knockdown effects on malaria vectors, programmatic use of spatial repellents has been suggested as one potential strategy to fill the gaps. This report explores social and contextual factors that may influence the relevance, uptake and sustainable use of a spatial repellent in two remote villages in Mondulkiri province, Cambodia, with endemic malaria transmission. The repellent consisted of polyethylene emanators, held in an open plastic frame and impregnated with 10% metofluthrin. In a baseline survey, 90.9% of households in Ou Chra (n = 30/33) and 96.6% in Pu Cha (n = 57/59) were interviewed. Behavioural data were collected for all household occupants (n = 448). In both villages, there were times and places in which people remained exposed to mosquito bites. Prior to the installation of the repellent, 50.6 and 59.5% of respondents noted that bites occurred "very often" inside the house and in the outdoor area surrounding the house, respectively. Indoor biting was reported to occur more frequently in the evening, followed by at night, while outdoor biting occurred more frequently in the early morning. In a follow-up survey, spatial repellents were well received in both villages, although 63.2% of respondents would not replace bed nets with repellents. Most participants (96.6%) were willing to use the product again; the mean willingness to pay was US$ 0.3 per unit. A preference for local procurement methods emerged. Widespread use of spatial repellents would not fill all protective gaps, but, if their entomological efficacy can be ascertained, outdoor application has the potential to enhance vector control strategies in Cambodia. Successful implementation would require subsidisation and integration with the existing national malaria control strategy. It is hoped that this study, while contributing to a better understanding of the social contexts of residual malaria transmission, will generate further interest in the evaluation of spatial repellents for malaria control.

7 CFR 457.151 - Forage seeding crop insurance provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... insufficient or improper application of disease control measures; (e) Wildlife; (f) Earthquake; (g) Volcanic eruption; or (h) Failure of the irrigation water supply, if caused by an insured peril that occurs during...

7 CFR 457.151 - Forage seeding crop insurance provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... insufficient or improper application of disease control measures; (e) Wildlife; (f) Earthquake; (g) Volcanic eruption; or (h) Failure of the irrigation water supply, if caused by an insured peril that occurs during...

7 CFR 457.151 - Forage seeding crop insurance provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... insufficient or improper application of disease control measures; (e) Wildlife; (f) Earthquake; (g) Volcanic eruption; or (h) Failure of the irrigation water supply, if caused by an insured peril that occurs during...

The perilous effects of racism on blacks.

PubMed

Clark, V R

2001-01-01

This paper focuses on understanding the perilous effects of interpersonal and institutional racism on the psychological and physiological well-being of Blacks. Interpersonal racism refers to prejudice and discriminatory behaviors directed toward individuals because of their race or ethnicity, and institutional racism refers to formal and informal policies and practices that deny equitable treatment to individuals because of their race or ethnic group affiliation. Racism can psychologically affect Blacks by allowing society to deny their value as individuals, and by compelling them to internalize the racist conceptions of them held by their oppressors. Racist stressors may also lead to increased physiological reactivity which, when sustained for a period of time, can lead to cardiovascular disorders and diseases. To eliminate the effects of racism, it is imperative that further research seek better ways to shield Blacks from these menacing stressors.

The Public Stigma of Problem Gambling: Its Nature and Relative Intensity Compared to Other Health Conditions.

PubMed

Hing, Nerilee; Russell, Alex M T; Gainsbury, Sally M; Nuske, Elaine

2016-09-01

Problem gambling attracts considerable public stigma, with deleterious effects on mental health and use of healthcare services amongst those affected. However, no research has examined the extent of stigma towards problem gambling within the general population. This study aimed to examine the stigma-related dimensions of problem gambling as perceived by the general public compared to other health conditions, and determine whether the publicly perceived dimensions of problem gambling predict its stigmatisation. A sample of 2000 Australian adults was surveyed, weighted to be representative of the state population by gender, age and location. Based on vignettes, the online survey measured perceived origin, peril, concealability, course and disruptiveness of problem gambling and four other health conditions, and desired social distance from each. Problem gambling was perceived as caused mainly by stressful life circumstances, and highly disruptive, recoverable and noticeable, but not particularly perilous. Respondents stigmatised problem gambling more than sub-clinical distress and recreational gambling, but less than alcohol use disorder and schizophrenia. Predictors of stronger stigma towards problem gambling were perceptions it is caused by bad character, is perilous, non-recoverable, disruptive and noticeable, but not due to stressful life circumstances, genetic/inherited problem, or chemical imbalance in the brain. This new foundational knowledge can advance understanding and reduction of problem gambling stigma through countering inaccurate perceptions that problem gambling is caused by bad character, that people with gambling problems are likely to be violent to other people, and that people cannot recover from problem gambling.

Gestalt theory reconfigured: Max Wertheimer's anticipation of recent developments in visual neuroscience.

PubMed

Westheimer, G

1999-01-01

In the 1920s Max Wertheimer enunciated a credo of Gestalt theory: the properties of any of the parts are governed by the structural laws of the whole. Intense efforts at the time to discover these laws had only very limited success. Psychology was in the grips of the Fechnerian tradition to seek exact relationships between the material and the mental and, because the Gestalt movement could not deliver these, it never attained a major standing among students of perception. However, as neurophysiological research into cortical processing of visual stimuli progresses the need for organizing principles is increasingly making itself felt. Concepts like contour salience and figure segregation, once the province of Gestalt psychology, are now taking on renewed significance as investigators combine neural modeling and psychophysical approaches with electrophysiological ones to characterize neural mechanisms of cognition. But it would be perilous not to take heed of some of the lessons that the history of the Gestalt movement teaches.

Plasmodium Sporozoite Biology.

PubMed

Frischknecht, Friedrich; Matuschewski, Kai

2017-05-01

Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Coordination of Wind and Flood Perils Act of 2010

THOMAS, 111th Congress

Sen. Wicker, Roger F. [R-MS

2010-07-29

Senate - 07/29/2010 Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Reflections on Governance.

ERIC Educational Resources Information Center

Tyler, Gus

1982-01-01

Governance is described as an inherent, instinctive impulse to make society an orderly, coherent organism. It helps cope with the perils of the physical world, the conflicts within the human world, and the internal anguish of man himself. (MLW)

33 CFR 13.01-20 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... bodies of water such as lakes, bays, sounds and rivers; whenever, wherever and in whatever way human life...” includes an incident threatening persons whose lives are endangered by perils of the water as well as those...

Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

NASA Astrophysics Data System (ADS)

Edward, Kert; Farahi, Faramarz

2014-05-01

Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.

Chloroquine: novel uses & manifestations.

PubMed

Cooper, R G; Magwere, T

2008-04-01

Chloroquine (CHQ) is a cheap, relatively well tolerated drug initially developed for the treatment of malaria in the 1930s. CHQ has, however, since accrued a plethora of uses in the treatment and amelioration of several other diseases and conditions because of its lysosomotropic properties. It also has characteristic physiological and systemic effects. This review gives an overview of the history and pharmacology of CHQ, and progresses to consider some of the mechanisms that may underlie its biochemical and physiological effects. Additionally, an overview of some of the novel uses of CHQ in the treatment of viral infections and cancer are presented. The antimalarial mechanisms of CHQ were not discussed in this review. The message is that CHQ, despite its welldocumented toxicity and adverse side effects may have important future uses that are associated with its lysosomotropic and immunomodulatory mechanisms. The possibility exists therefore that CHQ might be re-introduced into regular malaria treatment.

Surface antigens of Plasmodium falciparum gametocytes--a new class of transmission-blocking vaccine targets?

PubMed

Sutherland, Colin J

2009-08-01

The re-establishment of elimination and eradication on the malaria control agenda has led to calls for renewed effort in the development of parasite transmission-blocking interventions. Vaccines are ideally suited to this task, but progress towards an anti-gamete transmission-blocking vaccine, designed to act on parasites in blood-fed mosquitoes, has been slow. Recent work has confirmed that the surface of the gametocyte-infected erythrocyte presents antigens to the host immune system, and elicits specific humoral immune responses to these antigens, termed gametocyte surface antigens (GSAs). Likely candidate molecules, including antigens encoded by sub-telomeric multi-gene families, are discussed, and a hypothetical group of parasite molecules involved in spatial and temporal signal transduction in the human host is proposed, the tropins and circadins. The next steps for development of anti-gametocyte transmission-blocking vaccines for P. falciparum and the other human malaria species are considered.

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

PubMed Central

2011-01-01

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed. PMID:21676209

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa.

PubMed

Slavic, Ksenija; Krishna, Sanjeev; Derbyshire, Elvira T; Staines, Henry M

2011-06-15

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed.

Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities.

PubMed

Birkett, Ashley J; Moorthy, Vasee S; Loucq, Christian; Chitnis, Chetan E; Kaslow, David C

2013-04-18

While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anaemia in Ugandan preschool-aged children: the relative contribution of intestinal parasites and malaria.

PubMed

Green, Helen K; Sousa-Figueiredo, Jose C; Basáñez, Maria-Gloria; Betson, Martha; Kabatereine, Narcis B; Fenwick, Alan; Stothard, J Russell

2011-10-01

Anaemia is a severe public health issue among African preschool-aged children, yet little effective progress has been made towards its amelioration, in part due to difficulties in unravelling its complex, multifactorial aetiology. To determine the current anaemia situation and assess the relative contribution of malaria, intestinal schistosomiasis and infection with soil-transmitted helminths, two separate cross-sectional epidemiological surveys were carried out in Uganda including 573 and 455 preschool-aged children (≤6 years) living along the shores of Lake Albert and on the islands in Lake Victoria, respectively. Anaemia was found to be a severe public health problem in Lake Albert, affecting 68·9% of children (ninety-five percent confidence intervals (95% CI) 64·9-72·7%), a statistically significant higher prevalence relative to the 27·3% detected in Lake Victoria (95% CI: 23·3-31·7%). After multivariate analysis (controlling for sex and age of the child), the only factor found to be significantly associated with increased odds of anaemia in both lake systems was malaria (Lake Albert, odds ratio (OR)=2·1, 95% CI: 1·4-3·2; Lake Victoria, OR=1·9, 95% CI: 1·2-2·9). Thus intervention strategies primarily focusing on very young children and combating malaria appear to represent the most appropriate use of human and financial resources for the prevention of anaemia in this age group and area. Looking to the future, these activities could be further emphasised within the National Child Health Days(PLUS) agenda.

Travel patterns and demographic characteristics of malaria cases in Swaziland, 2010-2014.

PubMed

Tejedor-Garavito, Natalia; Dlamini, Nomcebo; Pindolia, Deepa; Soble, Adam; Ruktanonchai, Nick W; Alegana, Victor; Le Menach, Arnaud; Ntshalintshali, Nyasatu; Dlamini, Bongani; Smith, David L; Tatem, Andrew J; Kunene, Simon

2017-09-08

As Swaziland progresses towards national malaria elimination, the importation of parasites into receptive areas becomes increasingly important. Imported infections have the potential to instigate local transmission and sustain local parasite reservoirs. Travel histories from Swaziland's routine surveillance data from January 2010 to June 2014 were extracted and analysed. The travel patterns and demographics of rapid diagnostic test (RDT)-confirmed positive cases identified through passive and reactive case detection (RACD) were analysed and compared to those found to be negative through RACD. Of 1517 confirmed cases identified through passive surveillance, 67% reported travel history. A large proportion of positive cases reported domestic or international travel history (65%) compared to negative cases (10%). The primary risk factor for malaria infection in Swaziland was shown to be travel, more specifically international travel to Mozambique by 25- to 44-year old males, who spent on average 28 nights away. Maputo City, Inhambane and Gaza districts were the most likely travel destinations in Mozambique, and 96% of RDT-positive international travellers were either Swazi (52%) or Mozambican (44%) nationals, with Swazis being more likely to test negative. All international travellers were unlikely to have a bed net at home or use protection of any type while travelling. Additionally, paths of transmission, important border crossings and means of transport were identified. Results from this analysis can be used to direct national and well as cross-border targeting of interventions, over space, time and by sub-population. The results also highlight that collaboration between neighbouring countries is needed to tackle the importation of malaria at the regional level.

Cell based assays for anti-Plasmodium activity evaluation.

PubMed

Mokgethi-Morule, Thabang; N'Da, David D

2016-03-10

Malaria remains one of the most common and deadly infectious diseases worldwide. The severity of this global public health challenge is reflected by the approximately 198 million people, who were reportedly infected in 2013 and by the more than 584,000 related deaths in that same year. The rising emergence of drug resistance towards the once effective artemisinin combination therapies (ACTs) has become a serious concern and warrants more robust drug development strategies, with the objective of eradicating malaria infections. The intricate biology and life cycle of Plasmodium parasites complicate the understanding of the disease in such a way that would enhance the development of more effective chemotherapies that would achieve radical clinical cure and that would prevent disease relapse. Phenotypic cell based assays have for long been a valuable approach and involve the screening and analysis of diverse compounds with regards to their activities towards whole Plasmodium parasites in vitro. To achieve the Millennium Development Goal (MDG) of malaria eradication by 2020, new generation drugs that are active against all parasite stages (erythrocytic (blood), exo-erythrocytic (liver stages and gametocytes)) are needed. Significant advances are being made in assay development to overcome some of the practical challenges of assessing drug efficacy, particularly in the liver and transmission stage Plasmodium models. This review discusses primary screening models and the fundamental progress being made in whole cell based efficacy screens of anti-malarial activity. Ongoing challenges and some opportunities for improvements in assay development that would assist in the discovery of effective, safe and affordable drugs for malaria treatments are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Verbicide: The Perilously Leaning Tower of Babble.

ERIC Educational Resources Information Center

Pindell, Richard

1983-01-01

Points out that language abuses--whether jargon, euphemism, or malapropism--blur the distinction between words. Stresses the need for English instructors that can teach students the grammatical rules and inspire them with a love of language. (MM)

7 CFR 457.109 - Sugar Beet Crop Insurance Provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Interplanted with another crop; (ii) Planted into an established grass or legume; or (iii) Planted prior to... eruption; or (h) Failure of the irrigation water supply, if caused by an insured peril that occurs during...

7 CFR 457.109 - Sugar Beet Crop Insurance Provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Interplanted with another crop; (ii) Planted into an established grass or legume; or (iii) Planted prior to... eruption; or (h) Failure of the irrigation water supply, if caused by an insured peril that occurs during...

With God on our side: Religious primes reduce the envisioned physical formidability of a menacing adversary.

PubMed

Holbrook, Colin; Fessler, Daniel M T; Pollack, Jeremy

2016-01-01

The imagined support of benevolent supernatural agents attenuates anxiety and risk perception. Here, we extend these findings to judgments of the threat posed by a potentially violent adversary. Conceptual representations of bodily size and strength summarize factors that determine the relative threat posed by foes. The proximity of allies moderates the envisioned physical formidability of adversaries, suggesting that cues of access to supernatural allies will reduce the envisioned physical formidability of a threatening target. Across two studies, subtle cues of both supernatural and earthly social support reduced the envisioned physical formidability of a violent criminal. These manipulations had no effect on the perceived likelihood of encountering non-conflictual physical danger, raising the possibility that imagined supernatural support leads participants to view themselves not as shielded from encountering perilous situations, but as protected should perils arise. Copyright © 2015 Elsevier B.V. All rights reserved.

Managing a perilous stigma: Ex-offenders' use of reparative impression management tactics in hiring contexts.

PubMed

Ali, Abdifatah A; Lyons, Brent J; Ryan, Ann Marie

2017-09-01

Individuals with a criminal record face employment challenges because of the nature of their stigma. In this study, we examined the efficacy of using reparative impression management tactics to mitigate integrity concerns associated with a perilous stigma. Drawing on affect control theory, we proposed that the use of 3 impression management tactics-apology, justification, excuse-would differentially affect hiring evaluations through their influence on perceived remorse and anticipated workplace deviance. Across 3 studies, we found support for our proposed model. Our results revealed the use of an apology or justification tactic when explaining a previous criminal offense had a positive indirect effect on hiring evaluations, whereas the use of an excuse tactic had a negative indirect effect. These findings suggest applicants may benefit from using impression management tactics that communicate remorse when discussing events or associations that violate integrity expectations. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Promise and Peril: Dissemination of Findings from Studies of Drugs Used in Pregnancy and Their Association with Birth Defects

PubMed Central

Patrick, Stephen W.; Cooper, William O.

2015-01-01

When and how to publish birth defects research can be complex, especially in the context of drugs used in pregnancy. Such research frequently involves multiple stakeholders, including regulatory agencies. Researchers must balance the potential peril of an unnecessarily panicked populace versus the benefit of protecting the public's health. We use a case presentation and contemporary literature to highlight the potential tradeoffs that researchers must consider. We highlight important considerations including the public health impact, examining the likelihood of causality, understanding common considerations when using large data sources, the role of peer review and working in partnership with regulatory agencies. We suggest that plans for analyses, dissemination and risk communication are done best a priori and not post hoc. Rigorous research evaluating the impact of drugs used in pregnancy, coupled with effective dissemination strategies, has the potential improve outcomes for mothers and their infants for generations. PMID:26153150

Moving malaria in pregnancy programs from neglect to priority: experience from Malawi, Senegal, and Zambia.

PubMed

Roman, Elaine; Wallon, Michelle; Brieger, William; Dickerson, Aimee; Rawlins, Barbara; Agarwal, Koki

2014-02-01

Pregnant women and infants are particularly vulnerable to malaria. National malaria in pregnancy (MIP) programs in Malawi, Senegal, and Zambia were reviewed to identify promising strategies that have helped these countries achieve relatively high coverage of MIP interventions as well as ongoing challenges that have inhibited further progress. We used a systematic case study methodology to assess health system strengths and challenges in the 3 countries, including desk reviews of available reports and literature and key informant interviews with national stakeholders. Data were collected between 2009 and 2011 and analyzed across 8 MIP health systems components: (1) integration of programs and services, (2) policy, (3) commodities, (4) quality assurance, (5) capacity building, (6) community involvement, (7) monitoring and evaluation, and (8) financing. Within each program area, we ranked degree of scale up across 4 stages and synthesized the findings in a MIP table of analysis to reveal common themes related to better practices, remaining bottlenecks, and opportunities to accelerate MIP coverage, strengthen MIP programs, and improve results. Each of the 3 countries has malaria policies in place that reflect current MIP guidance from the World Health Organization. The 3 countries successfully integrated MIP interventions into a platform of antenatal care services, but coordination at the national level was disjointed. All 3 countries recognized the importance of having a MIP focal person to ensure collaboration and planning at the national level, but only Malawi had appointed one. Commodity stockouts were frequent due to problems at all levels of the logistics system, from quantification to distribution. Lack of support for quality assurance and weak monitoring and evaluation mechanisms across all 3 countries affected optimal coverage. MIP programs should address all 8 interconnected MIP health systems areas holistically, in the context of a health systems approach to building successful programs. The MIP table of analysis can be a useful tool for other malaria-endemic countries to review their programs and improve MIP outcomes.

Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

PubMed Central

Baer, Kerstin; Mikolajczak, Sebastian A.; Kappe, Stefan H. I.; Frevert, Ute

2012-01-01

Plasmodium falciparum malaria is responsible for nearly one million annual deaths worldwide. Because of the difficulty in monitoring the pathogenesis of cerebral malaria in humans, we conducted a study in various mouse models to better understand disease progression in experimental cerebral malaria (ECM). We compared the effect on the integrity of the blood brain barrier (BBB) and the histopathology of the brain of P. berghei ANKA, a known ECM model, P. berghei NK65, generally thought not to induce ECM, P. yoelii 17XL, originally reported to induce human cerebral malaria-like histopathology, and P. yoelii YM. As expected, P. berghei ANKA infection caused neurological signs, cerebral hemorrhages, and BBB dysfunction in CBA/CaJ and Swiss Webster mice, while Balb/c and A/J mice were resistant. Surprisingly, PbNK induced ECM in CBA/CaJ mice, while all other mice were resistant. P. yoelii 17XL and P. yoelii YM caused lethal hyperparasitemia in all mouse strains; histopathological alterations, BBB dysfunction, or neurological signs were not observed. Intravital imaging revealed that infected erythrocytes containing mature parasites passed slowly through capillaries making intimate contact with the endothelium, but did not arrest. Except for relatively rare microhemorrhages, mice with ECM presented no obvious histopathological alterations that would explain the widespread disruption of the BBB. Intravital imaging did reveal, however, that postcapillary venules, but not capillaries or arterioles, from mice with ECM, but not hyperparasitemia, exhibit platelet marginalization, extravascular fibrin deposition, CD14 expression, and extensive vascular leakage. Blockage of LFA-1 mediated cellular interactions prevented leukocyte adhesion, vascular leakage, neurological signs, and death from ECM. The endothelial barrier-stabilizing mediators imatinib and FTY720 inhibited vascular leakage and neurological signs and prolonged survival to ECM. Thus, it appears that neurological signs and coma in ECM are due to regulated opening of paracellular-junctional and transcellular-vesicular fluid transport pathways at the neuroimmunological BBB. PMID:23133375

The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites

PubMed Central

Moreira, Cristina K.; Naissant, Bernina; Coppi, Alida; Bennett, Brandy L.; Aime, Elena; Franke-Fayard, Blandine; Janse, Chris J.; Coppens, Isabelle; Sinnis, Photini; Templeton, Thomas J.

2016-01-01

The phist gene family has members identified across the Plasmodium genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in P. falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are predominant in schizonts, whereas in P. falciparum transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of P. berghei phist genes in order to characterize a simplistic model for the expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt P. berghei PBANKA_114540 suggest that this phist gene is essential, while knockout of phist PBANKA_122900 shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of P. falciparum and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites. PMID:27022937

Insights from agriculture for the management of insecticide resistance in disease vectors.

PubMed

Sternberg, Eleanore D; Thomas, Matthew B

2018-04-01

Key to contemporary management of diseases such as malaria, dengue, and filariasis is control of the insect vectors responsible for transmission. Insecticide-based interventions have contributed to declines in disease burdens in many areas, but this progress could be threatened by the emergence of insecticide resistance in vector populations. Insecticide resistance is likewise a major concern in agriculture, where insect pests can cause substantial yield losses. Here, we explore overlaps between understanding and managing insecticide resistance in agriculture and in public health. We have used the Global Plan for Insecticide Resistance Management in malaria vectors, developed under the auspices of the World Health Organization Global Malaria Program, as a framework for this exploration because it serves as one of the few cohesive documents for managing a global insecticide resistance crisis. Generally, this comparison highlights some fundamental differences between insect control in agriculture and in public health. Moreover, we emphasize that the success of insecticide resistance management strategies is strongly dependent on the biological specifics of each system. We suggest that the biological, operational, and regulatory differences between agriculture and public health limit the wholesale transfer of knowledge and practices from one system to the other. Nonetheless, there are some valuable insights from agriculture that could assist in advancing the existing Global Plan for Insecticide Resistance Management framework.

Spatio-temporal analysis of the genetic diversity and complexity of Plasmodium falciparum infections in Kedougou, southeastern Senegal.

PubMed

Niang, Makhtar; Thiam, Laty G; Loucoubar, Cheikh; Sow, Abdourahmane; Sadio, Bacary D; Diallo, Mawlouth; Sall, Amadou A; Toure-Balde, Aissatou

2017-01-19

Genetic analyses of the malaria parasite population and its temporal and spatial dynamics could provide an assessment of the effectiveness of disease control strategies. The genetic diversity of Plasmodium falciparum has been poorly documented in Senegal, and limited data are available from the Kedougou Region. This study examines the spatial and temporal variation of the genetic diversity and complexity of P. falciparum infections in acute febrile patients in Kedougou, southeastern Senegal. A total of 263 sera from patients presenting with acute febrile illness and attending Kedougou health facilities between July 2009 and July 2013 were obtained from a collection established as part of arbovirus surveillance in Kedougou. Samples identified as P. falciparum by nested PCR were characterized for their genetic diversity and complexity using msp-1 and msp-2 polymorphic markers. Samples containing only P. falciparum accounted for 60.83% (160/263) of the examined samples. All three msp-1 allelic families (K1, MAD20 and RO33) and two msp-2 allelic families (FC27 and 3D7) were detected in all villages investigated over the 5-year collection period. The average genotype per allelic family was comparable between villages. Frequencies of msp-1 and msp-2 allelic types showed no correlation with age (Fisher's exact test, P = 0.59) or gender (Fisher's exact test, P = 0.973), and were similarly distributed throughout the 5-year sampling period (Fisher's exact test, P = 0.412) and across villages (Fisher's exact test, P = 0.866). Mean multiplicity of infection (MOI) for both msp-1 and msp-2 was highest in Kedougou village (2.25 and 2.21, respectively) and among younger patients aged ≤ 15 years (2.12 and 2.00, respectively). The mean MOI was highest in 2009 and decreased progressively onward. Characterization of the genetic diversity and complexity of P. falciparum infections in Kedougou revealed no spatio-temporal variation in the genetic diversity of P. falciparum isolates. However, mean MOI varied with time of sera collection and decreased over the course of the study (July 2009 to July 2013). This suggests a slow progressive decrease of malaria transmission intensity in Kedougou Region despite the limited impact of preventive and control measures implemented by the National Malaria Control Programme on malaria morbidity and mortality.

Perils in the adaptation of fire management to a changing world

Treesearch

Armando González-Cabán; M.M. Fernández-Ramiro; Claudio Conese; Francesco Bosello; Jorge Núñez; Victor Otrachshenko; B.J. Orr

2014-01-01

Increased fire load and costs are anticipated under future scenarios of climate and other global changes. This requires increased efficiency in investments in wildfire management operations, and resolving the disconnect problem between science, policy and management.

The Perils of Knitting New Life

ERIC Educational Resources Information Center

Lappe, Marc

1977-01-01

Reviews history of "recombinant DNA" research, including early experiments and origins of bioethical debates between concerned scientists. Discusses National Institutes of Health (NIH) guidelines and accompanying Environmental Impact statement regarding recombinant DNA research and possibilities of human error covered by neither…

Publish or Perish: The Secret Life of a Textbook Writer.

ERIC Educational Resources Information Center

Richards, Jack

1988-01-01

The rewards and perils of making the transition from classroom language teacher to developer of English-as-a-Second-Language textbooks are discussed. Issues include national and international marketing as well as the production process. (LB)

Retroperitoneal Necrotizing Fasciitis Masquerading as Perianal Abscess - Rare and Perilous.

PubMed

Amaranathan, Anandhi; Sahoo, Ashok Kumar; Barathi, Deepak; Shankar, Gomathi; Sistla, Sarath Chandra

2017-01-17

Necrotizing fasciitis is one of the uncommon presentations of a rapidly spreading subcutaneous tissue infection. Although the actual cause is unclear in many cases, most of them are due to the rapid proliferation of microorganisms. Retroperitoneal necrotizing fasciitis is extremely rare. It is a potentially lethal infection that requires immediate and aggressive surgical care. Early diagnosis is the key to a better prognosis. The possibility of retroperitoneal necrotizing fasciitis should be suspected in patients with symptoms of sepsis that are disproportionate to clinical findings. The rapid deterioration of the patient also gives a clue towards the diagnosis. We report a 35-year-old male with perianal abscess who had been progressed to retroperitoneal necrotizing fasciitis. The patient was managed successfully with aggressive debridement and drainage after laparotomy. Appropriate antibiotics were used to combat the sepsis. The patient recovered well at follow up, three months after discharge. Another patient, a 45-year-old male with a retroperitoneal abscess, progressed to retroperitoneal necrotizing fasciitis, and extra peritoneal drainage and debridement was done. Antibiotics depending upon the culture and sensitivity were used to control sepsis. But the patient succumbed to death 45 days after surgery due to uncontrolled sepsis. Necrotizing fasciitis of any anatomical site needs aggressive surgical care with early intervention. But retroperitoneal necrotizing fasciitis needs an extra effort for diagnosis. After diagnosis, it needs timely surgical intervention and appropriate antibiotic therapy for the recovery of the patients.

3 CFR 8882 - Proclamation 8882 of October 5, 2012. Columbus Day, 2012

Code of Federal Regulations, 2013 CFR

2013-01-01

... broke over the Atlantic on October 12, 1492, a perilous 10-week journey across an ocean gave way to... scientists, explorers of the physical world and chroniclers of the human spirit—all have worked to broaden...

32 CFR 842.51 - Applicable law.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., assumption of risk, res ipsa loquitur, last clear chance, discovered peril, and comparative and contributory... the legal effect of contributory or comparative negligence by the claimant will be applied in... contributory or comparative negligence does not exist, use traditional rules of contributory negligence...

32 CFR 842.111 - Applicable law.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., discovered peril, and comparative and contributory negligence are considered. Absolute liability is never... act or omission occurs governs the effect of the claimant's comparative or contributory negligence... apportioned if local law applies comparative negligence. (3) Proceeds from private insurance policies are not...

32 CFR 842.111 - Applicable law.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., discovered peril, and comparative and contributory negligence are considered. Absolute liability is never... act or omission occurs governs the effect of the claimant's comparative or contributory negligence... apportioned if local law applies comparative negligence. (3) Proceeds from private insurance policies are not...

32 CFR 842.51 - Applicable law.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., assumption of risk, res ipsa loquitur, last clear chance, discovered peril, and comparative and contributory... the legal effect of contributory or comparative negligence by the claimant will be applied in... contributory or comparative negligence does not exist, use traditional rules of contributory negligence...

32 CFR 842.51 - Applicable law.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., assumption of risk, res ipsa loquitur, last clear chance, discovered peril, and comparative and contributory... the legal effect of contributory or comparative negligence by the claimant will be applied in... contributory or comparative negligence does not exist, use traditional rules of contributory negligence...

32 CFR 842.111 - Applicable law.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., discovered peril, and comparative and contributory negligence are considered. Absolute liability is never... act or omission occurs governs the effect of the claimant's comparative or contributory negligence... apportioned if local law applies comparative negligence. (3) Proceeds from private insurance policies are not...

32 CFR 842.51 - Applicable law.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., assumption of risk, res ipsa loquitur, last clear chance, discovered peril, and comparative and contributory... the legal effect of contributory or comparative negligence by the claimant will be applied in... contributory or comparative negligence does not exist, use traditional rules of contributory negligence...

32 CFR 842.111 - Applicable law.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., discovered peril, and comparative and contributory negligence are considered. Absolute liability is never... act or omission occurs governs the effect of the claimant's comparative or contributory negligence... apportioned if local law applies comparative negligence. (3) Proceeds from private insurance policies are not...

32 CFR 842.111 - Applicable law.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., discovered peril, and comparative and contributory negligence are considered. Absolute liability is never... act or omission occurs governs the effect of the claimant's comparative or contributory negligence... apportioned if local law applies comparative negligence. (3) Proceeds from private insurance policies are not...

32 CFR 842.51 - Applicable law.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., assumption of risk, res ipsa loquitur, last clear chance, discovered peril, and comparative and contributory... the legal effect of contributory or comparative negligence by the claimant will be applied in... contributory or comparative negligence does not exist, use traditional rules of contributory negligence...

Network-Based Mitigation of Illegal Immigration in Aegean Sea (Greece)

DTIC Science & Technology

2010-09-01

From Google- Images ) ...........................................1 Figure 2. The perilous trip (From Google- Images ...2 Figure 3. EU countries (From Google- Images ).................................................................3 Figure 4...Eastern Aegen Sea and territorial water line (From Google- Images )................4 Figure 5. Cross-border zone

Japanese Americans, Pluralism, and the Model Minority Myth.

ERIC Educational Resources Information Center

Endo, George T.; Della-Piana, Connie Kubo

1981-01-01

The current belief is that Japanese Americans are passive, industrious, respectful, patient, and intelligent. They have been transformed from the "yellow peril" into the "model minority". Education featuring respect for and awareness of various ethnicities will eliminate much prejudice. (JN)

Titan is to Earth's Hydrological Cycle what Venus is to its Greenhouse Effect

NASA Astrophysics Data System (ADS)

Lorenz, R. D.

2012-06-01

Titan serves as an extreme extrapolation of Earth's possible present trend toward more violent rainstorms interspersed by long droughts, much as Venus has acted as a bogeyman to illustrate the perils of enhanced greenhouse warming.

30 CFR 701.5 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., animal stocking requirements, scheduling of activities and design of sedimentation ponds in accordance... practice giving rise to the peril, would avoid exposure to the danger during the time necessary for... establishments. (g) Recreation. Land used for public or private leisure-time activities, including developed...

30 CFR 701.5 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., animal stocking requirements, scheduling of activities and design of sedimentation ponds in accordance... practice giving rise to the peril, would avoid exposure to the danger during the time necessary for... establishments. (g) Recreation. Land used for public or private leisure-time activities, including developed...

30 CFR 701.5 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., animal stocking requirements, scheduling of activities and design of sedimentation ponds in accordance... practice giving rise to the peril, would avoid exposure to the danger during the time necessary for... establishments. (g) Recreation. Land used for public or private leisure-time activities, including developed...

30 CFR 701.5 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., animal stocking requirements, scheduling of activities and design of sedimentation ponds in accordance... practice giving rise to the peril, would avoid exposure to the danger during the time necessary for... establishments. (g) Recreation. Land used for public or private leisure-time activities, including developed...

30 CFR 701.5 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., animal stocking requirements, scheduling of activities and design of sedimentation ponds in accordance... practice giving rise to the peril, would avoid exposure to the danger during the time necessary for... establishments. (g) Recreation. Land used for public or private leisure-time activities, including developed...

Moving freight in the new economy : payoffs, perils and paradoxes.

DOT National Transportation Integrated Search

2000-09-26

The infusion of information technology in all industrial processes has elevated the performance of the U.S. economy to new heights. Yet our transportation system is still guided by many of the obsolete infrastructure investment and pricing paradigms ...

Disease and Stigma: A Review of Literature

ERIC Educational Resources Information Center

Pettit, Michele L.

2008-01-01

This article presents a review of literature pertaining to disease and stigma. Specifically, a definition of stigma is provided along with an historical overview of disease and stigma and research trends related to three public health perils-AIDS, mental illness, and obesity.

Achieving development goals for HIV, tuberculosis and malaria in sub-Saharan Africa through integrated antenatal care: barriers and challenges.

PubMed

Fowkes, Freya J I; Draper, Bridget L; Hellard, Margaret; Stoové, Mark

2016-12-12

The global health community is currently transitioning from the Millennium Development Goals (MDGs) to the Sustainable Development Goals (SDGs). Unfortunately, progress towards maternal, newborn and infant health MDGs has lagged significantly behind other key health goals, demanding a renewed global effort in this key health area. The World Health Organization and other institutions heralded integrated antenatal care (ANC) as the best way to address the inter-related health issues of HIV, tuberculosis (TB) and malaria in the high risk groups of pregnant women and infants; integrated ANC services also offer a mechanism to address slow progress towards improved maternal health. There is remarkably limited evidence on best practice approaches of program implementation, acceptability and effectiveness for integrated ANC models targeting multiple diseases. Here, we discuss current integrated ANC global guidelines and the limited literature describing integrated ANC implementation and evidence for their role in addressing HIV, malaria and TB during pregnancy in sub-Saharan Africa. We highlight the paucity of data on the effectiveness of integrated ANC models and identify significant structural barriers in the health system (funding, infrastructure, distribution, human resources), the adoption system (limited buy-in from implementers, leadership, governance) and, in the broader context, patient-centred barriers (fear, stigma, personal burdens) and barriers in funding structures. We highlight recommendations for action and discuss avenues for the global health community to develop systems to integrate multiple disease programs into ANC models of care that better address these three priority infectious diseases. With the current transition to the SDGs and concerns regarding the failure to meet maternal health MDGs, the global health community, researchers, implementers and funding bodies must work together to ensure the establishment of quality operational and implementation research to inform integrated ANC models. It is imperative that the global health community engages in a timely discussion about such implementation innovations and instigates appropriate actions to ensure advances in maternal health are sufficient to meet applicable SDGs.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†.

PubMed

James, Stephanie; Collins, Frank H; Welkhoff, Philip A; Emerson, Claudia; Godfray, H Charles J; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W; Mbogo, Charles M; Okumu, Fredros O; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A; Tountas, Karen H; Touré, Yeya T

2018-06-01

Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes , focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.

Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province, Solomon Islands

PubMed Central

2013-01-01

Background Temotu Province, Solomon Islands is progressing toward malaria elimination. A baseline survey conducted in 2008 showed that most Plasmodium infections in the province were of low parasite density and asymptomatic infections. To better understand mechanisms underlying these malaria transmission characteristics genetic diversity and relationships among Plasmodium falciparum and Plasmodium vivax populations in the province were examined. Methods Forty-five P. falciparum and 67 P. vivax samples collected in the 2008 baseline survey were successfully genotyped using eight P. falciparum and seven P. vivax microsatellite markers. Genetic diversity, relationships and distribution of both P. falciparum and P. vivax populations were analysed. Results Plasmodium falciparum population exhibited low diversity with 19 haplotypes identified and had closely related clusters indicating clonal expansion. Interestingly, a dominant haplotype was significantly associated with fever and high parasite density. In contrast, the P. vivax population was highly diverse with 58 haplotypes identified that were not closely related. Parasite populations between different islands in the province showed low genetic differentiation. Conclusion The low diversity and clonal population of P. falciparum population may partially account for clinical immunity developed against illness. However, it is possible that importation of a new P. falciparum strain was the major cause of illness. High diversity in P. vivax population and low relatedness between strains suggested clinical immunity to P. vivax may be maintained by different mechanisms. The genetic diversity, population structure and distribution of strains indicate that transmission of P. falciparum was low, but that of P. vivax was still high in 2008. These data will be useful for assessing changes in malaria transmission resulting from interventions. PMID:24261646

Malaria prevalence metrics in low- and middle-income countries: an assessment of precision in nationally-representative surveys.

PubMed

Alegana, Victor A; Wright, Jim; Bosco, Claudio; Okiro, Emelda A; Atkinson, Peter M; Snow, Robert W; Tatem, Andrew J; Noor, Abdisalan M

2017-11-21

One pillar to monitoring progress towards the Sustainable Development Goals is the investment in high quality data to strengthen the scientific basis for decision-making. At present, nationally-representative surveys are the main source of data for establishing a scientific evidence base, monitoring, and evaluation of health metrics. However, little is known about the optimal precisions of various population-level health and development indicators that remains unquantified in nationally-representative household surveys. Here, a retrospective analysis of the precision of prevalence from these surveys was conducted. Using malaria indicators, data were assembled in nine sub-Saharan African countries with at least two nationally-representative surveys. A Bayesian statistical model was used to estimate between- and within-cluster variability for fever and malaria prevalence, and insecticide-treated bed nets (ITNs) use in children under the age of 5 years. The intra-class correlation coefficient was estimated along with the optimal sample size for each indicator with associated uncertainty. Results suggest that the estimated sample sizes for the current nationally-representative surveys increases with declining malaria prevalence. Comparison between the actual sample size and the modelled estimate showed a requirement to increase the sample size for parasite prevalence by up to 77.7% (95% Bayesian credible intervals 74.7-79.4) for the 2015 Kenya MIS (estimated sample size of children 0-4 years 7218 [7099-7288]), and 54.1% [50.1-56.5] for the 2014-2015 Rwanda DHS (12,220 [11,950-12,410]). This study highlights the importance of defining indicator-relevant sample sizes to achieve the required precision in the current national surveys. While expanding the current surveys would need additional investment, the study highlights the need for improved approaches to cost effective sampling.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†

PubMed Central

James, Stephanie; Collins, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, Yeya T.

2018-01-01

Abstract. Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes. PMID:29882508

Modeling the public health impact of malaria vaccines for developers and policymakers

PubMed Central

2013-01-01

Background Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model’s functionality is demonstrated through a hypothetical vaccine. Methods The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. Results The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. Conclusions The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions. PMID:23815273

Cost-effectiveness analysis of vaccinating children in Malawi with RTS,S vaccines in comparison with long-lasting insecticide-treated nets.

PubMed

Seo, Mikyung Kelly; Baker, Peter; Ngo, Karen Ngoc-Lan

2014-02-24

New RTS,S malaria vaccines may soon be licensed, yet its cost-effectiveness is unknown. Before the widespread introduction of RTS,S vaccines, cost-effectiveness studies are needed to help inform governments in resource-poor settings about how best to prioritize between the new vaccine and existing malaria interventions. A Markov model simulated malaria progression in a hypothetical Malawian birth cohort. Parameters were based on published data. Three strategies were compared: no intervention, vaccination at one year, and long-lasting, insecticide-treated nets (LLINs) at birth. Both health service and societal perspectives were explored. Health outcomes were measured in disability-adjusted life years (DALYs) averted and costed in 2012 US$. Incremental cost-effectiveness ratios (ICERs) were calculated and extensive sensitivity analyses were conducted. Three times GDP per capita ($1,095) per DALY averted was used for a cost-effectiveness threshold, whilst one times GDP ($365) was considered 'very cost-effective'. From a societal perspective the vaccine strategy was dominant. It averted 0.11 more DALYs than LLINs and 0.372 more DALYs than the no intervention strategy per person, while costing $10.04 less than LLINs and $59.74 less than no intervention. From a health service perspective the vaccine's ICER was $145.03 per DALY averted, and thus can be considered very cost-effective. The results were robust to changes in all variables except the vaccine and LLINs' duration of efficacy. Vaccines remained cost-effective even at the lowest assumed efficacy levels of 49.6% (mild malaria) and 14.2% (severe malaria), and the highest price of $15. However, from a societal perspective, if the vaccine duration efficacy was set below 2.69 years or the LLIN duration of efficacy was greater than 4.24 years then LLINs became the more cost-effective strategy. The results showed that vaccinating Malawian children with RTS,S vaccines was very cost-effective from both a societal and a health service perspective. This result was robust to changes in most variables, including vaccine price and vaccine efficacy, but was sensitive to the duration of efficacy of the vaccine and LLINs. Given the best evidence currently available, vaccines can be considered as a very cost-effective component of Malawi's future malaria control programmes. However, long-term follow-up studies on both interventions are needed.

Modeling the public health impact of malaria vaccines for developers and policymakers.

PubMed

Nunes, Julia K; Cárdenas, Vicky; Loucq, Christian; Maire, Nicolas; Smith, Thomas; Shaffer, Craig; Måseide, Kårstein; Brooks, Alan

2013-07-01

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine. The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions.

Mapping transmission foci to eliminate malaria in the People's Republic of China, 2010-2015: a retrospective analysis.

PubMed

Feng, Jun; Tu, Hong; Zhang, Li; Zhang, Shaosen; Jiang, Shan; Xia, Zhigui; Zhou, Shuisen

2018-03-07

China has initiated the National Malaria Elimination Action Plan, which aims to eliminate malaria by 2020. However, the transmission of malaria occurs sporadically or in distinct foci, which greatly hampers progress toward elimination in China and other countries. The object of this study was to foci categorization and evaluates whether the response met the requirements issued by the nation or WHO. Residual transmissions were investigated and located with fine spatial resolution mapping from parasitological confirmed malaria cases by use of routine national surveillance data. The "1-3-7" timeframes were monitored for each focus between 2012 and 2015. Each focus was identified, and the application of appropriate measures was evaluated. A total of 5996 indigenous cases were recorded between 2010 and 2015; during this period, the number of cases declined by 99.1% (2010, n = 4262; 2015, n = 39). Most indigenous cases (92.5%) were reported in Anhui (n = 2326), Yunnan (n = 1373), Henan (n = 930), Hubei (n = 459), and Guizhou (n = 458). The temporal distribution showed that the indigenous malaria cases were clustered during the period of May to August. A total of 320 foci were carefully investigated and analyzed: 24 were active foci; 72, residual non-active foci; and 224 cleared-up foci. For the foci response evaluation, all the active foci were investigated within 7 days, while 80.2% of the residual non-active foci were responded within 7 days. In addition, reactive case detection (RACD) was carried out with 92.9% of the active foci and vector investigation carried out with 75%. For residual non-active foci, RACD was carried out with 83.2% and vector investigation with 78.2% of the foci. This study used nationwide data to categorize foci in China and evaluate the response of these areas during the control and elimination phases. Our approach stratifies future control responses by identifying those locations where the elimination of endemic transmission is needed, such as in the counties at the China-Myanmar border and in Tibet. In addition, this study will help local CDC staff to reassess their needs and responses against different types of foci during the elimination and post-elimination phases.

7 CFR 400.402 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... FCIC or the insurance provider. Retrieval of records. Retrieval of a person's records by that person's... and State, applicable policy numbers, and other information related to multiple peril crop insurance policies as required by FCIC, from which information is retrieved by a personal identifier including, but...

7 CFR 400.402 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... FCIC or the insurance provider. Retrieval of records. Retrieval of a person's records by that person's... and State, applicable policy numbers, and other information related to multiple peril crop insurance policies as required by FCIC, from which information is retrieved by a personal identifier including, but...

7 CFR 400.402 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... FCIC or the insurance provider. Retrieval of records. Retrieval of a person's records by that person's... and State, applicable policy numbers, and other information related to multiple peril crop insurance policies as required by FCIC, from which information is retrieved by a personal identifier including, but...

The Perils of Prototyping.

ERIC Educational Resources Information Center

Lowry, Christina; Little, Robert

1985-01-01

The benefits of prototyping as a basis for system design include better specifications, earlier discovery of omissions and extensions, and the likelihood of salvaging much of the effort expended on the prototype. Risks and methods of prototyping during rapid systems development are also noted. (Author/MLW)

Easing the Perils of the Postdoctoral Years: A Call for Institutional Attention.

ERIC Educational Resources Information Center

Lorden, Joan F.; Matalon, Sadis

2002-01-01

Describes the University of Alabama at Birmingham's experience grappling with the many issues surrounding postdoctoral education in order to ensure that postdoctoral researchers are treated as more than cheap skilled labor and given benefits or opportunities for advancement. (EV)

Profits and Perils in Real Estate.

ERIC Educational Resources Information Center

McMillen, Liz; Mangan, Katherine S.

1989-01-01

In an effort to diversify their investments, colleges are pouring money into hotels, shopping centers, research parks, and apartment buildings. Institutional involvement in real estate takes a variety of forms, some considered risky, and has resulted in both profit and public-relations problems. (MSE)

The Promise & The Peril.

ERIC Educational Resources Information Center

Roach, Ronald

1997-01-01

Experiences of three historically black universities illustrate advantages and problems of college ownership of hotels and conference centers. Tuskegee University (Alabama) hopes its city, university, and conference facility will draw African American groups. Clark Atlanta University (Georgia) has purchased and renovated a hotel and restaurant.…

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

PubMed

Murray, Christopher J L; Ortblad, Katrina F; Guinovart, Caterina; Lim, Stephen S; Wolock, Timothy M; Roberts, D Allen; Dansereau, Emily A; Graetz, Nicholas; Barber, Ryan M; Brown, Jonathan C; Wang, Haidong; Duber, Herbert C; Naghavi, Mohsen; Dicker, Daniel; Dandona, Lalit; Salomon, Joshua A; Heuton, Kyle R; Foreman, Kyle; Phillips, David E; Fleming, Thomas D; Flaxman, Abraham D; Phillips, Bryan K; Johnson, Elizabeth K; Coggeshall, Megan S; Abd-Allah, Foad; Abera, Semaw Ferede; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen Me; Achoki, Tom; Adeyemo, Austine Olufemi; Adou, Arsène Kouablan; Adsuar, José C; Agardh, Emilie Elisabet; Akena, Dickens; Al Kahbouri, Mazin J; Alasfoor, Deena; Albittar, Mohammed I; Alcalá-Cerra, Gabriel; Alegretti, Miguel Angel; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, Francois; Allen, Peter J; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Amini, Hassan; Ammar, Walid; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Arnlöv, Johan; Arsenijevic, Valentina S Arsic; Artaman, Ali; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Badawi, Alaa; Balakrishnan, Kalpana; Banerjee, Amitava; Basu, Sanjay; Beardsley, Justin; Bekele, Tolesa; Bell, Michelle L; Bernabe, Eduardo; Beyene, Tariku Jibat; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Abdulhak, Aref Bin; Binagwaho, Agnes; Blore, Jed D; Basara, Berrak Bora; Bose, Dipan; Brainin, Michael; Breitborde, Nicholas; Castañeda-Orjuela, Carlos A; Catalá-López, Ferrán; Chadha, Vineet K; Chang, Jung-Chen; Chiang, Peggy Pei-Chia; Chuang, Ting-Wu; Colomar, Mercedes; Cooper, Leslie Trumbull; Cooper, Cyrus; Courville, Karen J; Cowie, Benjamin C; Criqui, Michael H; Dandona, Rakhi; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Deribe, Kebede; Des Jarlais, Don C; Dessalegn, Muluken; Dharmaratne, Samath D; Dilmen, Uğur; Ding, Eric L; Driscoll, Tim R; Durrani, Adnan M; Ellenbogen, Richard G; Ermakov, Sergey Petrovich; Esteghamati, Alireza; Faraon, Emerito Jose A; Farzadfar, Farshad; Fereshtehnejad, Seyed-Mohammad; Fijabi, Daniel Obadare; Forouzanfar, Mohammad H; Fra Paleo, Urbano; Gaffikin, Lynne; Gamkrelidze, Amiran; Gankpé, Fortuné Gbètoho; Geleijnse, Johanna M; Gessner, Bradford D; Gibney, Katherine B; Ginawi, Ibrahim Abdelmageem Mohamed; Glaser, Elizabeth L; Gona, Philimon; Goto, Atsushi; Gouda, Hebe N; Gugnani, Harish Chander; Gupta, Rajeev; Gupta, Rahul; Hafezi-Nejad, Nima; Hamadeh, Randah Ribhi; Hammami, Mouhanad; Hankey, Graeme J; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hedayati, Mohammad T; Pi, Ileana B Heredia; Hoek, Hans W; Hornberger, John C; Hosgood, H Dean; Hotez, Peter J; Hoy, Damian G; Huang, John J; Iburg, Kim M; Idrisov, Bulat T; Innos, Kaire; Jacobsen, Kathryn H; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jonas, Jost B; Juel, Knud; Kan, Haidong; Kankindi, Ida; Karam, Nadim E; Karch, André; Karema, Corine Kakizi; Kaul, Anil; Kawakami, Norito; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khang, Young-Ho; Khonelidze, Irma; Kinfu, Yohannes; Kinge, Jonas M; Knibbs, Luke; Kokubo, Yoshihiro; Kosen, S; Defo, Barthelemy Kuate; Kulkarni, Veena S; Kulkarni, Chanda; Kumar, Kaushalendra; Kumar, Ravi B; Kumar, G Anil; Kwan, Gene F; Lai, Taavi; Balaji, Arjun Lakshmana; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larson, Heidi J; Larsson, Anders; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Li, Yichong; Li, Yongmei; De Lima, Graça Maria Ferreira; Lin, Hsien-Ho; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lotufo, Paulo A; Machado, Vasco Manuel Pedro; Maclachlan, Jennifer H; Magis-Rodriguez, Carlos; Majdan, Marek; Mapoma, Christopher Chabila; Marcenes, Wagner; Marzan, Melvin Barrientos; Masci, Joseph R; Mashal, Mohammad Taufiq; Mason-Jones, Amanda J; Mayosi, Bongani M; Mazorodze, Tasara T; Mckay, Abigail Cecilia; Meaney, Peter A; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Melaku, Yohannes Adama; Memish, Ziad A; Mendoza, Walter; Miller, Ted R; Mills, Edward J; Mohammad, Karzan Abdulmuhsin; Mokdad, Ali H; Mola, Glen Liddell; Monasta, Lorenzo; Montico, Marcella; Moore, Ami R; Mori, Rintaro; Moturi, Wilkister Nyaora; Mukaigawara, Mitsuru; Murthy, Kinnari S; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nangia, Vinay; Narayan, K M Venkat; Nash, Denis; Nejjari, Chakib; Nelson, Robert G; Neupane, Sudan Prasad; Newton, Charles R; Ng, Marie; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F; Nowaseb, Vincent; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orisakwe, Orish Ebere; Pandian, Jeyaraj D; Papachristou, Christina; Caicedo, Angel J Paternina; Patten, Scott B; Paul, Vinod K; Pavlin, Boris Igor; Pearce, Neil; Pereira, David M; Pervaiz, Aslam; Pesudovs, Konrad; Petzold, Max; Pourmalek, Farshad; Qato, Dima; Quezada, Amado D; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Ur Rahman, Sajjad; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reilly, Robert Quentin; Remuzzi, Giuseppe; Richardus, Jan Hendrik; Ronfani, Luca; Roy, Nobhojit; Sabin, Nsanzimana; Saeedi, Mohammad Yahya; Sahraian, Mohammad Ali; Samonte, Genesis May J; Sawhney, Monika; Schneider, Ione J C; Schwebel, David C; Seedat, Soraya; Sepanlou, Sadaf G; Servan-Mori, Edson E; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin Hyun; Shiue, Ivy; Shivakoti, Rupak; Sigfusdottir, Inga Dora; Silberberg, Donald H; Silva, Andrea P; Simard, Edgar P; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soneji, Samir; Soshnikov, Sergey S; Sreeramareddy, Chandrashekhar T; Stathopoulou, Vasiliki Kalliopi; Stroumpoulis, Konstantinos; Swaminathan, Soumya; Sykes, Bryan L; Tabb, Karen M; Talongwa, Roberto Tchio; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thomson, Alan J; Thorne-Lyman, Andrew L; Towbin, Jeffrey A; Traebert, Jefferson; Tran, Bach X; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Uchendu, Uche S; Ukwaja, Kingsley N; Uzun, Selen Begüm; Vallely, Andrew J; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vollset, Stein Emil; Waller, Stephen; Wallin, Mitchell T; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Westerman, Ronny; White, Richard A; Wilkinson, James D; Williams, Thomas Neil; Woldeyohannes, Solomon Meseret; Wong, John Q; Xu, Gelin; Yang, Yang C; Yano, Yuichiro; Yentur, Gokalp Kadri; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa; Yu, Chuanhua; Jin, Kim Yun; El Sayed Zaki, Maysaa; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zou, Xiao Nong; Lopez, Alan D; Vos, Theo

2014-09-13

The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

PubMed Central

Ortblad, Katrina F; Guinovart, Caterina; Lim, Stephen S; Wolock, Timothy M; Roberts, D Allen; Dansereau, Emily A; Graetz, Nicholas; Barber, Ryan M; Brown, Jonathan C; Wang, Haidong; Duber, Herbert C; Naghavi, Mohsen; Dicker, Daniel; Dandona, Lalit; Salomon, Joshua A; Heuton, Kyle R; Foreman, Kyle; Phillips, David E; Fleming, Thomas D; Flaxman, Abraham D; Phillips, Bryan K; Johnson, Elizabeth K; Coggeshall, Megan S; Abd-Allah, Foad; Ferede, Semaw; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen Me; Achoki, Tom; Adeyemo, Austine Olufemi; Adou, Arsène Kouablan; Adsuar, José C; Agardh, Emilie Elisabet; Akena, Dickens; Al Kahbouri, Mazin J; Alasfoor, Deena; Albittar, Mohammed I; Alcalá-Cerra, Gabriel; Alegretti, Miguel Angel; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, Francois; Allen, Peter J; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Amini, Hassan; Ammar, Walid; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Ärnlöv, Johan; Arsenijevic, Valentina S Arsic; Artaman, Ali; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Badawi, Alaa; Balakrishnan, Kalpana; Banerjee, Amitava; Basu, Sanjay; Beardsley, Justin; Bekele, Tolesa; Bell, Michelle L; Bernabe, Eduardo; Beyene, Tariku Jibat; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Abdulhak, Aref Bin; Binagwaho, Agnes; Blore, Jed D; Basara, Berrak Bora; Bose, Dipan; Brainin, Michael; Breitborde, Nicholas; Castañeda-Orjuela, Carlos A; Catalá-López, Ferrán; Chadha, Vineet K; Chang, Jung-Chen; Chiang, Peggy Pei-Chia; Chuang, Ting-Wu; Colomar, Mercedes; Cooper, Leslie Trumbull; Cooper, Cyrus; Courville, Karen J; Cowie, Benjamin C; Criqui, Michael H; Dandona, Rakhi; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Deribe, Kebede; Jarlais, Don C Des; Dessalegn, Muluken; Dharmaratne, Samath D; Dilmen, Uğur; Ding, Eric L; Driscoll, Tim R; Durrani, Adnan M; Ellenbogen, Richard G; Ermakov, Sergey Petrovich; Esteghamati, Alireza; Faraon, Emerito Jose A; Farzadfar, Farshad; Fereshtehnejad, Seyed-Mohammad; Fijabi, Daniel Obadare; Forouzanfar, Mohammad H; Paleo, Urbano Fra.; Gaffikin, Lynne; Gamkrelidze, Amiran; Gankpé, Fortuné Gbètoho; Geleijnse, Johanna M; Gessner, Bradford D; Gibney, Katherine B; Ginawi, Ibrahim Abdelmageem Mohamed; Glaser, Elizabeth L; Gona, Philimon; Goto, Atsushi; Gouda, Hebe N; Gugnani, Harish Chander; Gupta, Rajeev; Gupta, Rahul; Hafezi-Nejad, Nima; Hamadeh, Randah Ribhi; Hammami, Mouhanad; Hankey, Graeme J; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hedayati, Mohammad T; Pi, Ileana B Heredia; Hoek, Hans W; Hornberger, John C; Hosgood, H Dean; Hotez, Peter J; Hoy, Damian G; Huang, John J; Iburg, Kim M; Idrisov, Bulat T; Innos, Kaire; Jacobsen, Kathryn H; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jonas, Jost B; Juel, Knud; Kan, Haidong; Kankindi, Ida; Karam, Nadim E; Karch, André; Karema, Corine Kakizi; Kaul, Anil; Kawakami, Norito; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khang, Young-Ho; Khonelidze, Irma; Kinfu, Yohannes; Kinge, Jonas M; Knibbs, Luke; Kokubo, Yoshihiro; Kosen, S; Defo, Barthelemy Kuate; Kulkarni, Veena S; Kulkarni, Chanda; Kumar, Kaushalendra; Kumar, Ravi B; Kumar, G Anil; Kwan, Gene F; Lai, Taavi; Balaji, Arjun Lakshmana; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larson, Heidi J; Larsson, Anders; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Li, Yichong; Li, Yongmei; De Lima, Graça Maria Ferreira; Lin, Hsien-Ho; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lotufo, Paulo A; Machado, Vasco Manuel Pedro; Maclachlan, Jennifer H; Magis-Rodriguez, Carlos; Majdan, Marek; Mapoma, Christopher Chabila; Marcenes, Wagner; Marzan, Melvin Barrientos; Masci, Joseph R; Mashal, Mohammad Taufiq; Mason-Jones, Amanda J; Mayosi, Bongani M; Mazorodze, Tasara T; Mckay, Abigail Cecilia; Meaney, Peter A; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Melaku, Yohannes Adama; Memish, Ziad A; Mendoza, Walter; Miller, Ted R; Mills, Edward J; Mohammad, Karzan Abdulmuhsin; Mokdad, Ali H; Mola, Glen Liddell; Monasta, Lorenzo; Montico, Marcella; Moore, Ami R; Mori, Rintaro; Moturi, Wilkister Nyaora; Mukaigawara, Mitsuru; Murthy, Kinnari S; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nangia, Vinay; Narayan, K M Venkat; Nash, Denis; Nejjari, Chakib; Nelson, Robert G; Neupane, Sudan Prasad; Newton, Charles R; Ng, Marie; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F; Nowaseb, Vincent; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orisakwe, Orish Ebere; Pandian, Jeyaraj D; Papachristou, Christina; Caicedo, Angel J Paternina; Patten, Scott B; Paul, Vinod K; Pavlin, Boris Igor; Pearce, Neil; Pereira, David M; Pervaiz, Aslam; Pesudovs, Konrad; Petzold, Max; Pourmalek, Farshad; Qato, Dima; Quezada, Amado D; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Sajjad Ur; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reilly, Robert Quentin; Remuzzi, Giuseppe; Richardus, Jan Hendrik; Ronfani, Luca; Roy, Nobhojit; Sabin, Nsanzimana; Saeedi, Mohammad Yahya; Sahraian, Mohammad Ali; Samonte, Genesis May J; Sawhney, Monika; Schneider, Ione J C; Schwebel, David C; Seedat, Soraya; Sepanlou, Sadaf G; Servan-Mori, Edson E; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin Hyun; Shiue, Ivy; Shivakoti, Rupak; Sigfusdottir, Inga Dora; Silberberg, Donald H; Silva, Andrea P; Simard, Edgar P; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soneji, Samir; Soshnikov, Sergey S; Sreeramareddy, Chandrashekhar T; Stathopoulou, Vasiliki Kalliopi; Stroumpoulis, Konstantinos; Swaminathan, Soumya; Sykes, Bryan L; Tabb, Karen M; Talongwa, Roberto Tchio; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thomson, Alan J; Thorne-Lyman, Andrew L; Towbin, Jeffrey A; Traebert, Jefferson; Tran, Bach X; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Uchendu, Uche S; Ukwaja, Kingsley N; Uzun, Selen Begüm; Vallely, Andrew J; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vollset, Stein Emil; Waller, Stephen; Wallin, Mitchell T; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Westerman, Ronny; White, Richard A; Wilkinson, James D; Williams, Thomas Neil; Woldeyohannes, Solomon Meseret; Wong, John Q; Xu, Gelin; Yang, Yang C; Yano, Yuichiro; Yentur, Gokalp Kadri; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa; Yu, Chuanhua; Jin, Kim Yun; El Sayed Zaki, Maysaa; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zou, Xiao Nong; Lopez, Alan D; Vos, Theo

2014-01-01

Summary Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occurred since the Millennium Declaration. Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets. Findings Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. Interpretation Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS’s estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. Funding Bill & Melinda Gates Foundation. PMID:25059949

[Establishment of malaria early warning system in Jiangsu Province II application of digital earth system in malaria epidemic management and surveillance].

PubMed

Wang, Wei-Ming; Zhou, Hua-Yun; Liu, Yao-Bao; Li, Ju-Lin; Cao, Yuan-Yuan; Cao, Jun

2013-04-01

To explore a new mode of malaria elimination through the application of digital earth system in malaria epidemic management and surveillance. While we investigated the malaria cases and deal with the epidemic areas in Jiangsu Province in 2011, we used JISIBAO UniStrong G330 GIS data acquisition unit (GPS) to collect the latitude and longitude of the cases located, and then established a landmark library about early-warning areas and an image management system by using Google Earth Free 6.2 and its image processing software. A total of 374 malaria cases were reported in Jiangsu Province in 2011. Among them, there were 13 local vivax malaria cases, 11 imported vivax malaria cases from other provinces, 20 abroad imported vivax malaria cases, 309 abroad imported falciparum malaria cases, 7 abroad imported quartan malaria cases (Plasmodium malaria infection), and 14 abroad imported ovale malaria cases (P. ovale infection). Through the analysis of Google Earth Mapping system, these malaria cases showed a certain degree of aggregation except the abroad imported quartan malaria cases which were highly sporadic. The local vivax malaria cases mainly concentrated in Sihong County, the imported vivax malaria cases from other provinces mainly concentrated in Suzhou City and Wuxi City, the abroad imported vivax malaria cases concentrated in Nanjing City, the abroad imported falciparum malaria cases clustered in the middle parts of Jiangsu Province, and the abroad imported ovale malaria cases clustered in Liyang City. The operation of Google Earth Free 6.2 is simple, convenient and quick, which could help the public health authority to make the decision of malaria prevention and control, including the use of funds and other health resources.

Performance of Rapid Diagnostic Tests for Plasmodium ovale Malaria in Japanese Travellers

PubMed Central

Tanizaki, Ryutaro; Kato, Yasuyuki; Iwagami, Moritoshi; Kutsuna, Satoshi; Ujiie, Mugen; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Kano, Shigeyuki; Ohmagari, Norio

2014-01-01

Background: Rapid diagnostic tests (RDTs) are used widely in the diagnosis of malaria. Although the effectiveness of RDTs for malaria has been described in many previous studies, the low performance of RDT particularly for Plasmodium ovale malaria in traveller has rarely been reported. Methods: This was a retrospective cohort study conducted on Japanese travellers diagnosed with malaria at the National Center for Global Health and Medicine between January 2004 and June 2013. The diagnosis of malaria was confirmed by microscopic examination, RDT, and polymerase chain reaction in all patients. The RDTs used in our study were Binax NOW Malaria (Binax Inc., Scarborough, Maine, USA) (BN) and SD Malaria Antigen Pf/Pan (Standard Diagnostics Inc., Korea) (SDMA). We compared the sensitivity of the RDTs to P. ovale malaria and Plasmodium vivax malaria. Results: A total of 153 cases of malaria were observed, 113 of which were found among Japanese travellers. Nine patients with P. ovale malaria and 17 patients with P. vivax malaria undergoing RDTs were evaluated. The overall sensitivity of RDTs for P. ovale malaria and P. vivax malaria was 22.2% and 94.1%, respectively (P < 0.001). The sensitivity of SDMA for P. ovale malaria and P. vivax malaria was 50% and 100%, respectively. The sensitivity of BN for P. vivax malaria was 90.0%, but it was ineffective in detecting the cases of P. ovale malaria. Conclusions: The sensitivity of RDTs was not high enough to diagnose P. ovale malaria in our study. In order not to overlook P. ovale malaria, therefore, microscopic examination is indispensable. PMID:25473374

[Morphology, biology and life-cycle of Plasmodium parasites].

PubMed

Hommel, Marcel

2007-10-01

Laveran first discovered that an infectious agent was responsible for malaria by using a simple microscope, without the assistance of specific stains. Our knowledge of the Plasmodium life cycle and cellular biology has progressed with each technological advance, from Romanovsky staining and histology to electron microscopy, immunocytochemistry, molecular methods and modern imaging techniques. The use of bird, primate and rodent models also made a major contribution, notably in the development of antimalarial drugs that are still in use today.

Placental malaria and the risk of malaria in infants in a high malaria transmission area in ghana: a prospective cohort study.

PubMed

Asante, Kwaku Poku; Owusu-Agyei, Seth; Cairns, Matthew; Dodoo, Daniel; Boamah, Ellen Abrafi; Gyasi, Richard; Adjei, George; Gyan, Ben; Agyeman-Budu, Akua; Dodoo, Theophilus; Mahama, Emmanuel; Amoako, Nicholas; Dosoo, David Kwame; Koram, Kwadwo; Greenwood, Brian; Chandramohan, Daniel

2013-11-01

Whether the risk of malaria is increased in infants born to mothers who experience malaria during pregnancy is uncertain.  We investigated malaria incidence among an infant cohort born to 355 primigravidae and 1500 multigravidae with or without placental malaria (PM) in a high malaria transmission area of Ghana. PM was assessed using placental histology. The incidence of all episodes of malaria parasitemia or clinical malaria was very similar among 3 groups of infants: those born to multigravidae without PM, multigravidae with PM, and primigravidae with PM. Infants born to primigravidae without PM experienced a lower incidence of malaria parasitemia or clinical malaria than the other 3 groups: adjusted hazard ratio, 0.64 (95% confidence interval [CI], .48-.86, P < .01) and 0.60 (95% CI, .43-.84, P < .01), respectively. The incidence of malaria parasitemia or clinical malaria was about 2 times higher in most poor infants compared to least poor infants. There was no suggestion that exposure to PM directly increased incidence of malaria among infants of multigravidae. In our study area, absence of placental malaria in primigravidae is a marker of low exposure, and this probably explains the lower incidence of malaria-related outcomes among infants of PM-negative primigravidae.

Structure and needs of global loss databases about natural disaster

NASA Astrophysics Data System (ADS)

Steuer, Markus

2010-05-01

Global loss databases are used for trend analyses and statistics in scientific projects, studies for governmental and nongovernmental organizations and for the insurance and finance industry as well. At the moment three global data sets are established: EM-DAT (CRED), Sigma (Swiss Re) and NatCatSERVICE (Munich Re). Together with the Asian Disaster Reduction Center (ADRC) and United Nations Development Program (UNDP) started a collaborative initiative in 2007 with the aim to agreed on and implemented a common "Disaster Category Classification and Peril Terminology for Operational Databases". This common classification has been established through several technical meetings and working groups and represents a first and important step in the development of a standardized international classification of disasters and terminology of perils. This means concrete to set up a common hierarchy and terminology for all global and regional databases on natural disasters and establish a common and agreed definition of disaster groups, main types and sub-types of events. Also the theme of georeferencing, temporal aspects, methodology and sourcing were other issues that have been identified and will be discussed. The implementation of the new and defined structure for global loss databases is already set up for Munich Re NatCatSERVICE. In the following oral session we will show the structure of the global databases as defined and in addition to give more transparency of the data sets behind published statistics and analyses. The special focus will be on the catastrophe classification from a moderate loss event up to a great natural catastrophe, also to show the quality of sources and give inside information about the assessment of overall and insured losses. Keywords: disaster category classification, peril terminology, overall and insured losses, definition

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.

The Adam and Eve story as exemplar of an early-life variant of the oedipus complex.

PubMed

Osman, M P

2000-01-01

The Adam and Eve story is construed as having an organizing function that facilitates the analytic understanding of certain patients. In this interpretation, the story epitomizes a psychodynamic in which progressive growth, with separation and individuation, of the young is experienced as perilous--not only to them, but also correspondingly to their procreators. In the myth, the increasing psychic and physical maturation of Adam and Eve produced a crisis. Not only was divine authority flouted, but also apprehensions were aroused that God might be humbled or diminished. This threatened him, evoking his wrath and leading to the punishment by abandonment of his youthful wards. It is suggested that the story depicts an emotional complex of widespread application and is an archaic version of the oedipus complex, continuous with the oedipus complex proper, but from an earlier stage of development. This archaic complex is delineated with clinical vignettes, and a clinical explication of its various components is provided. Clinical management is considered, particularly with reference to the challenge that a closed-system perspective (Fairbairn 1958) presents to a patient's development.

Ties That Bind

ERIC Educational Resources Information Center

Perkins, Thomas

2012-01-01

These are perilous times for community colleges. State and federal departments of education are pressing the nation's two-year career and technical colleges to be accountable while the colleges experience reductions in state funding and try to streamline services. That pressure is intensified by a growing national expectation that community…

The Miserable Truth.

ERIC Educational Resources Information Center

Shaughnessy, Mina

1998-01-01

Presents Mina Shaughnessy's 1976 speech, given at a time when great financial crisis threatened to result in the wholesale disestablishment of basic writing programs. Notes grave perils, and outlines some of the truths uncovered through the experience of Open Admissions in higher education, truths that are indestructible despite retrenchments and…

7 CFR 400.402 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... insurance provider. Retrieval of records—Retrieval of a person's records by that person's SSN or EIN, or..., applicable policy numbers, and other information related to multiple peril crop insurance policies as required by FCIC, from which information is retrieved by a personal identifier including, but not limited...

7 CFR 400.402 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... insurance provider. Retrieval of records—Retrieval of a person's records by that person's SSN or EIN, or..., applicable policy numbers, and other information related to multiple peril crop insurance policies as required by FCIC, from which information is retrieved by a personal identifier including, but not limited...

"Write Every Day!": A Mantra Dismantled

ERIC Educational Resources Information Center

Sword, Helen

2016-01-01

Numerous books, blogs, and articles on research productivity exhort academics to "write every day" even during the busiest of teaching times. Ironically, however, this research-boosting advice hangs from a perilously thin research thread. This article scrutinises the key findings of Robert Boice, whose pioneering studies of…

48 CFR 28.301 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 416, are required by law and this regulation to provide insurance for certain types of perils (e.g., workers' compensation). Insurance is mandatory also when commingling of property, type of operation... property. (2) The Government reserves the right to disapprove the purchase of any insurance coverage not in...

48 CFR 28.301 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 416, are required by law and this regulation to provide insurance for certain types of perils (e.g., workers' compensation). Insurance is mandatory also when commingling of property, type of operation... property. (2) The Government reserves the right to disapprove the purchase of any insurance coverage not in...

48 CFR 28.301 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 416, are required by law and this regulation to provide insurance for certain types of perils (e.g., workers' compensation). Insurance is mandatory also when commingling of property, type of operation... property. (2) The Government reserves the right to disapprove the purchase of any insurance coverage not in...

48 CFR 28.301 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 416, are required by law and this regulation to provide insurance for certain types of perils (e.g., workers' compensation). Insurance is mandatory also when commingling of property, type of operation... property. (2) The Government reserves the right to disapprove the purchase of any insurance coverage not in...

48 CFR 28.301 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 416, are required by law and this regulation to provide insurance for certain types of perils (e.g., workers' compensation). Insurance is mandatory also when commingling of property, type of operation... property. (2) The Government reserves the right to disapprove the purchase of any insurance coverage not in...

Crossing the Rubric-Con

ERIC Educational Resources Information Center

Bailey, James R.

2014-01-01

This essay engages the prospect and peril of employing rubrics in America. It discusses how institutional independence affects the enterprise, and addresses whether rubrics will be received as salvation or subservience by educational agents. It asks how rubrics can benefit stakeholders while examining their unintended consequences. It concludes by…

Reconstruction of Social Studies

ERIC Educational Resources Information Center

Gaudelli, William; Laverty, Megan J.

2018-01-01

As the world grows increasingly contentious, education for citizenship demands greater attention. Yet at this perilous juncture, social studies has neglected to take up the task of preparing citizens in a democratic and global society. Social studies has become increasingly fragmented and isolated by disciplinary foci that fetishize academic…

The Perils and Promises of Praise

ERIC Educational Resources Information Center

Dweck, Carol S.

2007-01-01

Educators commonly believe that praising students' intelligence builds their confidence and motivation to learn and that students' inherent intelligence is the major cause of their school achievement. The author's research shows that, on the contrary, praising students' intelligence can be problematic. Praise is intricately connected to how…

22 CFR 211.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... assistance a vessel or its cargo has been saved from impending peril or recovered from actual loss. (o... monitoring. (p) Nonprofit means that the residue of income over operating expenses accruing in any activity... monetized proceeds, revenue from income generating activities, funds accruing from the sale of containers...

22 CFR 211.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... assistance a vessel or its cargo has been saved from impending peril or recovered from actual loss. (o... monitoring. (p) Nonprofit means that the residue of income over operating expenses accruing in any activity... monetized proceeds, revenue from income generating activities, funds accruing from the sale of containers...

22 CFR 211.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... assistance a vessel or its cargo has been saved from impending peril or recovered from actual loss. (o... monitoring. (p) Nonprofit means that the residue of income over operating expenses accruing in any activity... monetized proceeds, revenue from income generating activities, funds accruing from the sale of containers...

22 CFR 211.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... assistance a vessel or its cargo has been saved from impending peril or recovered from actual loss. (o... monitoring. (p) Nonprofit means that the residue of income over operating expenses accruing in any activity... monetized proceeds, revenue from income generating activities, funds accruing from the sale of containers...

22 CFR 211.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... assistance a vessel or its cargo has been saved from impending peril or recovered from actual loss. (o... monitoring. (p) Nonprofit means that the residue of income over operating expenses accruing in any activity... monetized proceeds, revenue from income generating activities, funds accruing from the sale of containers...

Perilous plastics - are phthalate esters a risk for human reproductive health?

EPA Science Inventory

Phthalate diesters are high-production volume chemicals used to impart flexibility to polyvinyl chloride plastic (e.g. children’s toys and medical tubing) and are also found in other products (e.g. health and beauty products). Certain phthalate esters inhibit reproductive develop...

12 CFR 618.8040 - Authorized insurance services.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 618.8040 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM GENERAL PROVISIONS Member Insurance § 618.8040 Authorized insurance services. (a) Farm Credit System banks (excluding banks for... member's or borrower's farm or aquatic unit is permitted, but limited to hail and multiple-peril crop...

12 CFR 618.8040 - Authorized insurance services.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 618.8040 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM GENERAL PROVISIONS Member Insurance § 618.8040 Authorized insurance services. (a) Farm Credit System banks (excluding banks for... member's or borrower's farm or aquatic unit is permitted, but limited to hail and multiple-peril crop...

12 CFR 618.8040 - Authorized insurance services.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 618.8040 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM GENERAL PROVISIONS Member Insurance § 618.8040 Authorized insurance services. (a) Farm Credit System banks (excluding banks for... member's or borrower's farm or aquatic unit is permitted, but limited to hail and multiple-peril crop...

Perilous plasticizers - are phthalate esters a risk for human reproductive health?

EPA Science Inventory

Phthalate diesters are high-production volume chemicals used to impart flexibility to polyvinyl chloride plastic (e.g. children’s toys and medical tubing) as well as other products (e.g. health and beauty products). Certain phthalate esters inhibit reproductive development in la...

Case Series in Cognitive Neuropsychology: Promise, Perils and Proper Perspective

PubMed Central

Rapp, Brenda

2012-01-01

Schwartz & Dell (2010) advocated for a major role for case series investigations in cognitive neuropsychology. They defined the key features of this approach and presented a number of arguments and examples illustrating the benefits of case series studies and their contribution to computational cognitive neuropsychology. In the Special Issue on “Case Series in Cognitive Neuropsychology” there are six commentaries on Schwartz and Dell (2010) as well as a response to the six commentaries by Dell and Schwartz. In this paper, I provide a brief summary of the key points made in Schwartz and Dell (2010) and I review the promise and perils of case series design as revealed by the six commentaries. I conclude by placing the set of papers within a broader perspective, providing some clarification of the historical record on case series and single case approaches, raising some cautionary notes for case series studies and situating both case series and single case approaches within the larger context of theory development in the cognitive sciences. PMID:22746685

The perils and promises of microbial abundance: novel natures and model ecosystems, from artisanal cheese to alien seas.

PubMed

Paxson, Heather; Helmreich, Stefan

2014-04-01

Microbial life has been much in the news. From outbreaks of Escherichia coli to discussions of the benefits of raw and fermented foods to recent reports of life forms capable of living in extreme environments, the modest microbe has become a figure for thinking through the presents and possible futures of nature, writ large as well as small. Noting that dominant representations of microbial life have shifted from an idiom of peril to one of promise, we argue that microbes--especially when thriving as microbial communities--are being upheld as model ecosystems in a prescriptive sense, as tokens of how organisms and human ecological relations with them could, should, or might be. We do so in reference to two case studies: the regulatory politics of artisanal cheese and the speculative research of astrobiology. To think of and with microbial communities as model ecosystems offers a corrective to the scientific determinisms we detect in some recent calls to attend to the materiality of scientific objects.

Promise and peril: Dissemination of findings from studies of drugs used in pregnancy and their association with birth defects.

PubMed

Patrick, Stephen W; Cooper, William O

2015-08-01

When and how to publish birth defects research can be complex, especially in the context of drugs used in pregnancy. Such research frequently involves multiple stakeholders, including regulatory agencies. Researchers must balance the potential peril of an unnecessarily panicked populace versus the benefit of protecting the public's health. We use a case presentation and contemporary literature to highlight the potential tradeoffs that researchers must consider. We highlight important considerations including the public health impact, examining the likelihood of causality, understanding common considerations when using large data sources, the role of peer review and working in partnership with regulatory agencies. We suggest that plans for analyses, dissemination and risk communication are done best a priori and not post hoc. Rigorous research evaluating the impact of drugs used in pregnancy, coupled with effective dissemination strategies, has the potential improve outcomes for mothers and their infants for generations. © 2015 Wiley Periodicals, Inc.

The comparison of detection methods of asymptomatic malaria in hypoendemic areas

NASA Astrophysics Data System (ADS)

Siahaan, L.; Panggabean, M.; Panggabean, Y. C.

2018-03-01

Malaria is still a problem that disrupts public health in North Sumatera. Late diagnosis will increase the chances of increased morbidity and mortality due to malaria. The early detection of asymptomatic malaria is one of the best efforts to reduce the transmission of the disease. Early detection is certainly must be done on suspect patients who have no malaria complaints. Passive Case Detection (PCD) methods seem hard to find asymptomatic malaria. This study was conducted to compare ACD (Active Case Detection) and PCD methods in asymptomatic malaria detection in the hypoendemic areas of malaria. ACD method is done by going to the sample based on secondary data. Meanwhile, PCD is done on samples that come to health services. Samples were taken randomly and diagnosis was confirmed by microscopic examination with 3% Giemsa staining, as gold standard of malaria diagnostics. There was a significant difference between ACD and PCD detection methods (p = 0.034), where ACD method was seen superior in detecting malaria patients in all categories, such as: clinical malaria (65.2%), asymptomatic malaria (65.1%) and submicroscopic malaria (58.5%). ACD detection methods are superior in detecting malaria sufferers, especially asymptomatic malaria sufferers.

Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein

PubMed Central

Oyen, David; Torres, Jonathan L.; Wille-Reece, Ulrike; Ockenhouse, Christian F.; Emerling, Daniel; Glanville, Jacob; Volkmuth, Wayne; Flores-Garcia, Yevel; Zavala, Fidel; Ward, Andrew B.; King, C. Richter; Wilson, Ian A.

2017-01-01

Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%. Crystal structures of antibody fragments (Fabs) 311 and 317 with an (NPNA)3 peptide illustrate their different binding modes. Notwithstanding, one and three of the three NPNA repeats adopt similar well-defined type I β-turns with Fab311 and Fab317, respectively. Furthermore, to explore antibody binding in the context of P. falciparum CSP, we used negative-stain electron microscopy on a recombinant shortened CSP (rsCSP) construct saturated with Fabs. Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP–Fab311 complex forming a highly organized helical structure. Together, these structural insights may aid in the design of a next-generation malaria vaccine. PMID:29138320

Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein

DOE PAGES

Oyen, David; Torres, Jonathan L.; Wille-Reece, Ulrike; ...

2017-11-14

Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here in this paper, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development inmore » vivo by at least 97%. Crystal structures of antibody fragments (Fabs) 311 and 317 with an (NPNA) 3 peptide illustrate their different binding modes. Notwithstanding, one and three of the three NPNA repeats adopt similar well-defined type I β-turns with Fab311 and Fab317, respectively. Furthermore, to explore antibody binding in the context of P. falciparum CSP, we used negative-stain electron microscopy on a recombinant shortened CSP (rsCSP) construct saturated with Fabs. Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP–Fab311 complex forming a highly organized helical structure. Lastly, together, these structural insights may aid in the design of a next-generation malaria vaccine.« less

Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oyen, David; Torres, Jonathan L.; Wille-Reece, Ulrike

Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here in this paper, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development inmore » vivo by at least 97%. Crystal structures of antibody fragments (Fabs) 311 and 317 with an (NPNA) 3 peptide illustrate their different binding modes. Notwithstanding, one and three of the three NPNA repeats adopt similar well-defined type I β-turns with Fab311 and Fab317, respectively. Furthermore, to explore antibody binding in the context of P. falciparum CSP, we used negative-stain electron microscopy on a recombinant shortened CSP (rsCSP) construct saturated with Fabs. Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP–Fab311 complex forming a highly organized helical structure. Lastly, together, these structural insights may aid in the design of a next-generation malaria vaccine.« less

Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

PubMed Central

Salman, Ahmed M.; Montoya-Díaz, Eduardo; West, Heather; Lall, Amar; Atcheson, Erwan; Lopez-Camacho, Cesar; Ramesar, Jai; Bauza, Karolis; Collins, Katharine A.; Brod, Florian; Reis, Fernando; Pappas, Leontios; González-Cerón, Lilia; Janse, Chris J.; Hill, Adrian V. S.; Khan, Shahid M.; Reyes-Sandoval, Arturo

2017-01-01

Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. PMID:28417968

Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

PubMed Central

Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

2013-01-01

Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

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.

Global Epidemiology of Plasmodium vivax

PubMed Central

Howes, Rosalind E.; Battle, Katherine E.; Mendis, Kamini N.; Smith, David L.; Cibulskis, Richard E.; Baird, J. Kevin; Hay, Simon I.

2016-01-01

Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection. Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum. Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses. These traits affect both its geographic distribution and transmission patterns. Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review. Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign. Plasmodium vivax can be associated with severe and even fatal illness. Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year. Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded. PMID:27402513

Economic and practical challenges to the formulation of vaccines against endemic infectious diseases such as malaria.

PubMed

Plebanski, Magdalena; Lopez, Ester; Proudfoot, Owen; Cooke, Brian M; Itzstein, Mark von; Coppel, Ross L

2006-09-01

Herein, we analyze in general the current vaccine market and identify potential factors driving and modulating supply and demand for vaccines. An emphasis is placed on changes in regulation in the last 20 years which have led to increased indirect costs of production, and which can create a barrier against the timely use of technological advances to reduce direct costs. Other defining industry characteristics, such as firm numbers and sizes, cost and pricing strategies, nature extent and impact of Government involvement and international regulation are noted. These considerations, far from being removed from basic vaccine research, influence its ability to achieve aims that can be then progressed into effective vaccine products. We discuss specifically the development of particulate vaccines against malaria, a major lethal disease and health problem prevalent in Africa, including some key economic and methodological challenges and opportunities. We note some practical issues blocking the development of effective particulate vaccines for the Third World, mainly driven by the regulatory spiral noted above.

Targeting channels and transporters in protozoan parasite infections

NASA Astrophysics Data System (ADS)

Meier, Anna; Erler, Holger; Beitz, Eric

2018-03-01

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

Prevalence of gestational, placental and congenital malaria in north-west Colombia

PubMed Central

2013-01-01

Background The frequency of pregnancy-associated malaria is increasingly being documented in American countries. In Colombia, with higher frequency of Plasmodium vivax over Plasmodium falciparum infection, recent reports confirmed gestational malaria as a serious public health problem. Thick smear examination is the gold standard to diagnose malaria in endemic settings, but in recent years, molecular diagnostic methods have contributed to elucidate the dimension of the problem of gestational malaria. The study was aimed at exploring the prevalence of gestational, placental and congenital malaria in women who delivered at the local hospitals of north-west Colombia, between June 2008 and April 2011. Methods A group of 129 parturient women was selected to explore the prevalence of gestational, placental and congenital malaria in a descriptive, prospective and transversal (prevalence) design. Diagnosis was based on the simultaneous application of two independent diagnostic tests: microscopy of thick blood smears and a polymerase chain reaction assay (PCR). Results The prevalence of gestational malaria (thick smear /PCR) was 9.1%/14.0%; placental malaria was 3.3%/16.5% and congenital malaria was absent. A history of gestational malaria during the current pregnancy was significantly associated with gestational malaria at delivery. Plasmodium vivax caused 65% of cases of gestational malaria, whereas P. falciparum caused most cases of placental malaria. Conclusions Gestational and placental malaria are a serious problem in the region, but the risk of congenital malaria is low. A history of malaria during pregnancy may be a practical indicator of infection at delivery. PMID:24053184

Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa

PubMed Central

2010-01-01

Background The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement. Methods This study is a cost-effectiveness analysis based on malaria cases imported from West Africa to Switzerland from the perspective of the Swiss health system. We used a decision tree model and made a literature research on the components of travel related malaria. The main outcome measure was the cost effectiveness of malaria chemoprophylaxis reimbursement based on malaria and deaths averted. Results Using a program where travellers would be reimbursed for 80% of the cost of the cheapest malaria chemoprophylaxis is dominant (i.e. cost saving and more effective than the current situation) using the assumption that currently 68.7% of travellers to West Africa use malaria chemoprophylaxis. If the current usage of malaria chemoprophylaxis would be higher, 82.4%, the incremental cost per malaria case averted is € 2'302. The incremental cost of malaria death averted is € 191'833. The most important factors influencing the model were: the proportion of travellers using malaria chemoprophylaxis, the probability of contracting malaria without malaria chemoprophylaxis, the cost of the mefloquine regimen, the decrease in the number of travellers without malaria chemoprophylaxis in the reimbursement strategy. Conclusions This study suggests that a reimbursement of 80% of the cost of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers from Switzerland to West Africa is highly effective in terms of malaria cases averted and is cost effective to the Swiss health system. These data are relevant to discussions about the cost effectiveness of malaria chemoprophylaxis reimbursement for vulnerable groups such as those visiting friends and relatives who have the highest risk of malaria, who are least likely to use chemoprophylaxis. PMID:20860809

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 ...

Spatial heterogeneity and temporal evolution of malaria transmission risk in Dakar, Senegal, according to remotely sensed environmental data.

PubMed

Machault, Vanessa; Vignolles, Cécile; Pagès, Frédéric; Gadiaga, Libasse; Gaye, Abdoulaye; Sokhna, Cheikh; Trape, Jean-François; Lacaux, Jean-Pierre; Rogier, Christophe

2010-09-03

The United Nations forecasts that by 2050, more than 60% of the African population will live in cities. Thus, urban malaria is considered an important emerging health problem in that continent. Remote sensing (RS) and geographic information systems (GIS) are useful tools for addressing the challenge of assessing, understanding and spatially focusing malaria control activities. The objectives of the present study were to use high spatial resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to identify some urban environmental factors in Dakar associated with Anopheles arabiensis densities, to assess the persistence of these associations and to describe spatial changes in at-risk environments using a decadal time scale. Two SPOT images from the 1996 and 2007 rainy seasons in Dakar were processed to extract environmental factors, using supervised classification of land use and land cover, and a calculation of NDVI (Normalized Difference Vegetation Index) and distance to vegetation. Linear regressions were fitted to identify the ecological factors associated with An. arabiensis aggressiveness measured in 1994-97 in the South and centre districts of Dakar. Risk maps for populated areas were computed and compared for 1996 and 2007 using the results of the statistical models. Almost 60% of the variability in anopheline aggressiveness measured in 1994-97 was explained with only one variable: the built-up area in a 300-m radius buffer around the catching points. This association remained stable between 1996 and 2007. Risk maps were drawn by inverting the statistical association. The total increase of the built-up areas in Dakar was about 30% between 1996 and 2007. In proportion to the total population of the city, the population at high risk for malaria fell from 32% to 20%, whereas the low-risk population rose from 29 to 41%. Environmental data retrieved from high spatial resolution SPOT satellite images were associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed.

Repellent Plants Provide Affordable Natural Screening to Prevent Mosquito House Entry in Tropical Rural Settings—Results from a Pilot Efficacy Study

PubMed Central

Mng'ong'o, Frank C.; Sambali, Joseph J.; Sabas, Eustachkius; Rubanga, Justine; Magoma, Jaka; Ntamatungiro, Alex J.; Turner, Elizabeth L.; Nyogea, Daniel; Ensink, Jeroen H. J.; Moore, Sarah J.

2011-01-01

Sustained malaria control is underway using a combination of vector control, prompt diagnosis and treatment of malaria cases. Progress is excellent, but for long-term control, low-cost, sustainable tools that supplement existing control programs are needed. Conventional vector control tools such as indoor residual spraying and house screening are highly effective, but difficult to deliver in rural areas. Therefore, an additional means of reducing mosquito house entry was evaluated: the screening of mosquito house entry points by planting the tall and densely foliated repellent plant Lantana camara L. around houses. A pilot efficacy study was performed in Kagera Region, Tanzania in an area of high seasonal malaria transmission, where consenting families within the study village planted L. camara (Lantana) around their homes and were responsible for maintaining the plants. Questionnaire data on house design, socioeconomic status, malaria prevention knowledge, attitude and practices was collected from 231 houses with Lantana planted around them 90 houses without repellent plants. Mosquitoes were collected using CDC Light Traps between September 2008 and July 2009. Data were analysed with generalised negative binomial regression, controlling for the effect of sampling period. Indoor catches of mosquitoes in houses with Lantana were compared using the Incidence Rate Ratio (IRR) relative to houses without plants in an adjusted analysis. There were 56% fewer Anopheles gambiae s.s. (IRR 0.44, 95% CI 0.28–0.68, p<0.0001); 83% fewer Anopheles funestus s.s. (IRR 0.17, 95% CI 0.09–0.32, p<0.0001), and 50% fewer mosquitoes of any kind (IRR 0.50, 95% CI 0.38–0.67, p<0.0001) in houses with Lantana relative to controls. House screening using Lantana reduced indoor densities of malaria vectors and nuisance mosquitoes with broad community acceptance. Providing sufficient plants for one home costs US $1.50 including maintenance and labour costs, (30 cents per person). L. camara mode of action and suitability for mosquito control is discussed. PMID:22022471

Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy.

PubMed

Ouédraogo, Smaïla; Bodeau-Livinec, Florence; Briand, Valérie; Huynh, Bich-Tram; Koura, Ghislain K; Accrombessi, Manfred M K; Fievet, Nadine; Massougbodji, Achille; Deloron, Philippe; Cot, Michel

2012-10-22

Primigravidity is one of the main risk factors for both malaria and anaemia. Since the implementation of intermittent preventive treatment (IPTp) in sub-Saharan Africa, the relationship between anaemia and gravidity and its evolution during pregnancy has been little explored. This study aimed to evaluate the impact of gravidity on the variation of haemoglobin during pregnancy according to the timing of gestation. Data from three studies carried out in nearby areas in south Benin (Ouidah, Comé, Allada) between 2005 and 2012 were analysed. At inclusion (first antenatal visit, ANV1) women's age, area of residence, schooling, gravidity, gestational age, weight and height were recorded. Thick blood smears were performed on ANV1, second visit (ANV2) and at delivery. In Allada, women's serum ferritin and CRP concentrations were also assessed. The impact of gravidity on maternal haemoglobin (Hb) was analysed using a logistic or linear regression depending on the outcome. The statistical significance was set to P < 0.05. In total, data from 3,591 pregnant women were analysed. Both univariate and multivariate analyses showed a constant association between Hb concentrations and gravidity in the three periods of Hb assessment (ANV1, ANV2 and delivery). Mean Hb concentration was significantly lower in primigravidae than in multigravidae at ANV1 (mean difference = -2.4 g/L, CI 95%: [-3.4, -1.4], P < 0.001). Afterwards, there was a significant increase in primigravidae only, with a tendency to reversal between primigravidae and multigravidae, which was confirmed at delivery (mean difference = 2.8 g/L, CI 95%: [1.3, 4.2], P < 0.001). The prevalence of malaria infection was halved between ANV1 and delivery in primigravidae while it decreased by only 38% among multigravidae, who were less prone to malaria infection (prevalence at ANV1, 20% and 10% respectively). Iron deficiency was more common in multigravidae, and it decreased slightly in this group between ANV1 and delivery. In a context of IPTp, Hb levels improved progressively throughout pregnancy in primigravidae, likely as a result of reduction in malaria infection. In multigravidae, the improvement was less perceptible and anaemia was mainly due to iron deficiency.

Repellent plants provide affordable natural screening to prevent mosquito house entry in tropical rural settings--results from a pilot efficacy study.

PubMed

Mng'ong'o, Frank C; Sambali, Joseph J; Sabas, Eustachkius; Rubanga, Justine; Magoma, Jaka; Ntamatungiro, Alex J; Turner, Elizabeth L; Nyogea, Daniel; Ensink, Jeroen H J; Moore, Sarah J

2011-01-01

Sustained malaria control is underway using a combination of vector control, prompt diagnosis and treatment of malaria cases. Progress is excellent, but for long-term control, low-cost, sustainable tools that supplement existing control programs are needed. Conventional vector control tools such as indoor residual spraying and house screening are highly effective, but difficult to deliver in rural areas. Therefore, an additional means of reducing mosquito house entry was evaluated: the screening of mosquito house entry points by planting the tall and densely foliated repellent plant Lantana camara L. around houses. A pilot efficacy study was performed in Kagera Region, Tanzania in an area of high seasonal malaria transmission, where consenting families within the study village planted L. camara (Lantana) around their homes and were responsible for maintaining the plants. Questionnaire data on house design, socioeconomic status, malaria prevention knowledge, attitude and practices was collected from 231 houses with Lantana planted around them 90 houses without repellent plants. Mosquitoes were collected using CDC Light Traps between September 2008 and July 2009. Data were analysed with generalised negative binomial regression, controlling for the effect of sampling period. Indoor catches of mosquitoes in houses with Lantana were compared using the Incidence Rate Ratio (IRR) relative to houses without plants in an adjusted analysis. There were 56% fewer Anopheles gambiae s.s. (IRR 0.44, 95% CI 0.28-0.68, p<0.0001); 83% fewer Anopheles funestus s.s. (IRR 0.17, 95% CI 0.09-0.32, p<0.0001), and 50% fewer mosquitoes of any kind (IRR 0.50, 95% CI 0.38-0.67, p<0.0001) in houses with Lantana relative to controls. House screening using Lantana reduced indoor densities of malaria vectors and nuisance mosquitoes with broad community acceptance. Providing sufficient plants for one home costs US $1.50 including maintenance and labour costs, (30 cents per person). L. camara mode of action and suitability for mosquito control is discussed.

Symptomatic malaria diagnosis overestimate malaria prevalence, but underestimate anaemia burdens in children: results of a follow up study in Kenya.

PubMed

Choge, Joseph K; Magak, Ng'wena G; Akhwale, Willis; Koech, Julius; Ngeiywa, Moses M; Oyoo-Okoth, Elijah; Esamai, Fabian; Osano, Odipo; Khayeka-Wandabwa, Christopher; Kweka, Eliningaya J

2014-04-09

The commonly accepted gold standard diagnostic method for detecting malaria is a microscopic reading of Giemsa-stained blood films. However, symptomatic diagnosis remains the basis of therapeutic care for the majority of febrile patients in malaria endemic areas. This study aims to compare the discrepancy in malaria and anaemia burdens between symptomatic diagnosed patients with those diagnosed through the laboratory. Data were collected from Western Kenya during a follow-up study of 887 children with suspected cases of malaria visiting the health facilities. In the laboratory, blood samples were analysed for malaria parasite and haemoglobin levels. Differences in malaria prevalence between symptomatic diagnosis and laboratory diagnosis were analysed by Chi-square test. Bayesian probabilities were used for the approximation of the malaria and anaemia burdens. Regression analysis was applied to: (1) determine the relationships between haemoglobin levels, and malaria parasite density and (2) relate the prevalence of anaemia and the prevalence of malaria. The prevalence of malaria and anaemia ranged from 10% to 34%, being highest during the rainy seasons. The predominant malaria parasite was P. falciparum (92.3%), which occurred in higher density in children aged 2‒5 years. Fever, high temperature, sweating, shivering, vomiting and severe headache symptoms were associated with malaria during presumptive diagnosis. After conducting laboratory diagnosis, lower malaria prevalence was reported among the presumptively diagnosed patients. Surprisingly, there were no attempts to detect anaemia in the same cohort. There was a significant negative correlation between Hb levels and parasite density. We also found a positive correlation between the prevalence of anaemia and the prevalence of malaria after laboratory diagnosis indicating possible co-occurrence of malaria and anaemia. Symptomatic diagnosis of malaria overestimates malaria prevalence, but underestimates the anaemia burden in children. Good clinical practice dictates that a laboratory should confirm the presence of parasites for all suspected cases of malaria.

Economic cost analysis of malaria case management at the household level during the malaria elimination phase in The People's Republic of China.

PubMed

Xia, Shang; Ma, Jin-Xiang; Wang, Duo-Quan; Li, Shi-Zhu; Rollinson, David; Zhou, Shui-Sen; Zhou, Xiao-Nong

2016-06-03

In China, malaria has been posing a significant economic burden on households. To evaluate malaria economic burden in terms of both direct and indirect costs has its meaning in improving the effectiveness of malaria elimination program in China. A number of study sites (eight counties in five provinces) were selected from the malaria endemic area in China, representing the different levels of malaria incidence, risk classification, economic development. A number of households with malaria cases (n = 923) were surveyed during the May to December in 2012 to collect information on malaria economic burden. Descriptive statistics were used to characterize the basic profiles of selected malaria cases in terms of their gender, age group, occupation and malaria type. The malaria economic costs were evaluated by direct and indirect costs. Comparisons were carried out by using the chi-square test (or Z-test) and the Mann-Whitney U test among malaria cases with reference to local/imported malaria patients, hospitalized/out patients, and treatment hospitals. The average cost of malaria per case was 1 691.23 CNY (direct cost was 735.41 CNY and indirect cost was 955.82 CNY), which accounted for 11.1 % of a household's total income. The average costs per case for local and imported malaria were 1 087.58 CNY and 4271.93 CNY, respectively. The average cost of a malaria patient being diagnosed and treated in a hospital at the county level or above (3 975.43 CNY) was 4.23 times higher than that of malaria patient being diagnosed and treated at a village or township hospital (938.80 CNY). This study found that malaria has been posing a significant economic burden on households in terms of direct and indirect costs. There is a need to improve the effectiveness of interventions in order to reduce the impact costs of malaria, especially of imported infections, in order to eliminate the disease in China.

Comparison of Malaria Simulations Driven by Meteorological Observations and Reanalysis Products in Senegal.

PubMed

Diouf, Ibrahima; Rodriguez-Fonseca, Belen; Deme, Abdoulaye; Caminade, Cyril; Morse, Andrew P; Cisse, Moustapha; Sy, Ibrahima; Dia, Ibrahima; Ermert, Volker; Ndione, Jacques-André; Gaye, Amadou Thierno

2017-09-25

The analysis of the spatial and temporal variability of climate parameters is crucial to study the impact of climate-sensitive vector-borne diseases such as malaria. The use of malaria models is an alternative way of producing potential malaria historical data for Senegal due to the lack of reliable observations for malaria outbreaks over a long time period. Consequently, here we use the Liverpool Malaria Model (LMM), driven by different climatic datasets, in order to study and validate simulated malaria parameters over Senegal. The findings confirm that the risk of malaria transmission is mainly linked to climate variables such as rainfall and temperature as well as specific landscape characteristics. For the whole of Senegal, a lag of two months is generally observed between the peak of rainfall in August and the maximum number of reported malaria cases in October. The malaria transmission season usually takes place from September to November, corresponding to the second peak of temperature occurring in October. Observed malaria data from the Programme National de Lutte contre le Paludisme (PNLP, National Malaria control Programme in Senegal) and outputs from the meteorological data used in this study were compared. The malaria model outputs present some consistencies with observed malaria dynamics over Senegal, and further allow the exploration of simulations performed with reanalysis data sets over a longer time period. The simulated malaria risk significantly decreased during the 1970s and 1980s over Senegal. This result is consistent with the observed decrease of malaria vectors and malaria cases reported by field entomologists and clinicians in the literature. The main differences between model outputs and observations regard amplitude, but can be related not only to reanalysis deficiencies but also to other environmental and socio-economic factors that are not included in this mechanistic malaria model framework. The present study can be considered as a validation of the reliability of reanalysis to be used as inputs for the calculation of malaria parameters in the Sahel using dynamical malaria models.

Workshop report: Malaria vaccine development in Europe--preparing for the future.

PubMed

Viebig, Nicola K; D'Alessio, Flavia; Draper, Simon J; Sim, B Kim Lee; Mordmüller, Benjamin; Bowyer, Paul W; Luty, Adrian J F; Jungbluth, Stefan; Chitnis, Chetan E; Hill, Adrian V S; Kremsner, Peter; Craig, Alister G; Kocken, Clemens H M; Leroy, Odile

2015-11-17

The deployment of a safe and effective malaria vaccine will be an important tool for the control of malaria and the reduction in malaria deaths. With the launch of the 2030 Malaria Vaccine Technology Roadmap, the malaria community has updated the goals and priorities for the development of such a vaccine and is now paving the way for a second phase of malaria vaccine development. During a workshop in Brussels in November 2014, hosted by the European Vaccine Initiative, key players from the European, North American and African malaria vaccine community discussed European strategies for future malaria vaccine development in the global context. The recommendations of the European malaria community should guide researchers, policy makers and funders of global health research and development in fulfilling the ambitious goals set in the updated Malaria Vaccine Technology Roadmap. Copyright © 2015.

Malaria's indirect contribution to all-cause mortality in the Andaman Islands during the colonial era.

PubMed

Shanks, G Dennis; Hay, Simon I; Bradley, David J

2008-09-01

Malaria has a substantial secondary effect on other causes of mortality. From the 19th century, malaria epidemics in the Andaman Islands' penal colony were initiated by the brackish swamp-breeding malaria vector Anopheles sundaicus and fuelled by the importation of new prisoners. Malaria was a major determinant of the highly variable all-cause mortality rate (correlation coefficient r(2)=0.60, n=68, p<0.0001) from 1872 to 1939. Directly attributed malaria mortality based on post-mortem examinations rarely exceeded one-fifth of total mortality. Infectious diseases such as pneumonia, tuberculosis, dysentery, and diarrhoea, which combined with malaria made up the majority of all-cause mortality, were positively correlated with malaria incidence over several decades. Deaths secondary to malaria (indirect malaria mortality) were at least as great as mortality directly attributed to malaria infections.

The promise and peril of chemical probes

PubMed Central

Arrowsmith, Cheryl H; Audia, James E; Austin, Christopher; Baell, Jonathan; Bennett, Jonathan; Blagg, Julian; Bountra, Chas; Brennan, Paul E; Brown, Peter J; Bunnage, Mark E; Buser-Doepner, Carolyn; Campbell, Robert M; Carter, Adrian J; Cohen, Philip; Copeland, Robert A; Cravatt, Ben; Dahlin, Jayme L; Dhanak, Dashyant; Frederiksen, Mathias; Frye, Stephen V; Gray, Nathanael; Grimshaw, Charles E; Hepworth, David; Howe, Trevor; Huber, Kilian V M; Jin, Jian; Knapp, Stefan; Kotz, Joanne D; Kruger, Ryan G; Lowe, Derek; Mader, Mary M; Marsden, Brian; Mueller-Fahrnow, Anke; Müller, Susanne; O'Hagan, Ronan C; Overington, John P; Owen, Dafydd R; Rosenberg, Saul H; Ross, Ruth; Roth, Bryan; Schapira, Matthieu; Schreiber, Stuart L; Shoichet, Brian; Sundström, Michael; Superti-Furga, Giulio; Taunton, Jack; Toledo-Sherman, Leticia; Walpole, Chris; Walters, Michael A; Willson, Timothy M; Workman, Paul; Young, Robert N; Zuercher, William J

2016-01-01

Chemical probes are powerful reagents with increasing impacts on biomedical research. However, probes of poor quality or that are used incorrectly generate misleading results. To help address these shortcomings, we will create a community-driven wiki resource to improve quality and convey current best practice. PMID:26196764

Environmental Education Research: To What Ends?

ERIC Educational Resources Information Center

Jickling, Bob

2009-01-01

This paper engages questions about ends in environmental education research. In doing so, I argue that such questions are essentially normative, and that normative questions are underrepresented in this field. After cautioning about perils of prescribing research agendas, I gently suggest that in environmental education key normative questions…

Unleashing the Kraken: The Perils of Ignoring Community Values.

ERIC Educational Resources Information Center

Carnes, William J.

1995-01-01

A Midwest superintendent describes some painful on-the-job experiences. To regain community acceptance and support, educators must understand and respect community history, apply classroom-inspired lessons to relationships with parents, involve the community meaningfully, recognize the failings of New Age terminology, understand families'…

The British Higher Education Funding Debate: The Perils of "Talking Economics"

ERIC Educational Resources Information Center

Dodds, Anneliese

2011-01-01

This article examines current debates surrounding British higher education funding from a political economy perspective, drawing on "positive" and "institutionalist" political economy. Adopting the lens of political economy enables a critical assessment of the use of terms drawn from economics by many higher education…

Automated Turn-Key Systems in the Library: Prospects and Perils

ERIC Educational Resources Information Center

Brownrigg, Edwin Blake; Bruer, J. Michael

1976-01-01

Problems, issues, and alternatives in designing individual, stand alone systems for servicing selected library operations, with emphasis on problems of integrating these with major automated systems, a new mode of operation called coupling, and strategies for dealing with large amounts of retrospective data. (Author/LS)

A Perfect Storm

ERIC Educational Resources Information Center

Jones, Bill

2009-01-01

The present state of adult education is perilous, as all readers of "Adults Learning" will know well. All sectors are damagingly affected by funding decisions, as witnessed by the large numbers of organisations and providers represented at the recent Parliamentary lobby by the Campaigning Alliance for Lifelong Learning (CALL). The damage…

Reconciliation through Communication in Intercultural Encounters: Potential or Peril?

ERIC Educational Resources Information Center

Gallois, Cindy

2003-01-01

Notes that in the aftermath of September 11th there is strong motivation to improve intercultural and international relations through communication. Explains that in many interethnic and intercultural contexts, participants are not motivated to communicate well. Concludes it is crucial to understand intercultural communications as simultaneously…

Adolescence: Guiding Youth through the Perilous Ordeal. First Edition.

ERIC Educational Resources Information Center

Newton, Miller

Adolescence is becoming an increasingly dangerous time of life, with increased violent deaths, juvenile delinquency, and sexual activity. Designed for therapists in psychology, social work, school psychology, family therapy, guidance counseling, and other areas, this book outlines current knowledge concerning adolescent development, along with the…

Virtual Reality: Directions in Research and Development.

ERIC Educational Resources Information Center

Stuart, Rory

1992-01-01

Discussion of virtual reality (VR) focuses on research and development being carried out at NYNEX to solve business problems. Component technologies are described; design decisions are considered, including interactivity, connectivity, and locus of control; potential perils of VR are discussed, including user dissociation; and areas of promise are…

Planning for the Perils of CD-ROM.

ERIC Educational Resources Information Center

Zink, Steven D.

1990-01-01

Argues that, because of its meteoric entrance into the library marketplace, too few institutions have reviewed the implications of CD-ROM before making their purchases. Issues that need to be considered are discussed, including funding, costs, equipment requirements, optimal locations for workstations, security and viruses, human resources, user…

The Pacific Age in World History.

ERIC Educational Resources Information Center

Korhonen, Pekka

1996-01-01

Tracks the intermittent appearances and variations of the historical concept of a "Pacific Age" from the 1890s to the present. Discusses the social, economic, and historical conditions that resulted in the term's heralding of either economic optimism or racist peril. Suggests these interpretations come in cycles. (MJP)

7 CFR 457.111 - Pear crop insurance provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... alternating or mixed pattern. Marketable. Pear production acceptable for processing or other human consumption... irrigation water supply, if caused by an insured peril that occurs during the insurance period. (b) In... provisions of the Basic Provisions are not applicable. 13. Pear Quality Adjustment Endorsement (a) This...

Pride and Peril: Historically Black Colleges and Universities

ERIC Educational Resources Information Center

Nealy, Michelle J.

2009-01-01

Once a beacon of hope for thousands of Black students denied access to higher education by predominantly White institutions, historically Black colleges and universities (HBCUs) have educated generations of Black scientists, doctors, lawyers, educators and social activists. But today, these institutions face serious challenges. Questions of…

Publishing in Peril

ERIC Educational Resources Information Center

Lum, Lydia

2009-01-01

University presses are more likely to give voice to stories that might not otherwise be told, such as those involving minority perspectives. But opportunities are shrinking. As extensions of their parent schools, academic presses rarely reap profits, experts say. Many rely on school subsidies to survive. Factor in substantial budget cuts to…

Glucose-6-phosphate dehydrogenase deficiency in people living in malaria endemic districts of Nepal.

PubMed

Ghimire, Prakash; Singh, Nihal; Ortega, Leonard; Rijal, Komal Raj; Adhikari, Bipin; Thakur, Garib Das; Marasini, Baburam

2017-05-23

Glucose-6-phosphate dehydrogenase (G6PD) is a rate limiting enzyme of the pentose phosphate pathway and is closely associated with the haemolytic disorders among patients receiving anti-malarial drugs, such as primaquine. G6PD deficiency (G6PDd) is an impending factor for radical treatment of malaria which affects the clearance of gametocytes from the blood and subsequent delay in the achievement of malaria elimination. The main objective of this study was to assess the prevalence of G6PD deficiency in six malaria endemic districts in Southern Nepal. A cross-sectional population based prevalence survey was conducted in six malaria endemic districts of Nepal, during April-Dec 2013. A total of 1341 blood samples were tested for G6PDd using two different rapid diagnostic test kits (Binax-Now ® and Care Start™). Equal proportions of participants from each district (n ≥ 200) were enrolled considering ethnic and demographic representation of the population groups. Out of total 1341 blood specimens collected from six districts, the overall prevalence of G6PDd was 97/1341; 7.23% on Binax Now and 81/1341; 6.0% on Care Start test. Higher prevalence was observed in male than females [Binax Now: male 10.2%; 53/521 versus female 5.4%; 44/820 (p = 0.003) and Care Start: male 8.4%; 44/521 versus female 4.5%; 37/820 (p = 0.003)]. G6PDd was higher in ethnic groups Rajbanshi (11.7%; 19/162) and Tharu (5.6%; 56/1005) (p = 0.006), major inhabitant of the endemic districts. Higher prevalence of G6PDd was found in Jhapa (22/224; 9.8%) and Morang districts (18/225; 8%) (p = 0.031). In a multivariate analysis, male were found at more risk for G6PDd than females, on Binax test (aOR = 1.97; CI 1.28-3.03; p = 0.002) and Care Start test (aOR = 1.86; CI 1.16-2.97; p = 0.009). The higher prevalence of G6PDd in certain ethnic group, gender and geographical region clearly demonstrates clustering of the cases and ascertained the risk groups within the population. This is the first study in Nepal which identified the vulnerable population groups for G6PDd in malaria endemic districts. The finding of this study warrants the need for G6PDd testing in vulnerable population groups in endemic districts, and also facilitates use of primaquine in mass supporting timely progress for malaria elimination.

Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity.

PubMed

Odorizzi, Pamela M; Feeney, Margaret E

2016-10-01

Pregnancy-associated malaria, including placental malaria, causes significant morbidity and mortality worldwide. Recently, it has been suggested that in utero exposure of the fetus to malaria antigens may negatively impact the developing immune system and result in tolerance to malaria. Here, we review our current knowledge of fetal immunity to malaria, focusing on the dynamic interactions between maternal malaria infection, placental development, and the fetal immune system. A better understanding of the long-term impact of in utero malaria exposure on the development of natural immunity to malaria, immune responses to other childhood pathogens, and vaccine immunogenicity is urgently needed. This may guide the implementation of novel chemoprevention strategies during pregnancy and facilitate the push toward malaria vaccines. Published by Elsevier Ltd.

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

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.

Long-term impact of childhood malaria infection on school performance among school children in a malaria endemic area along the Thai-Myanmar border.

PubMed

Vorasan, Nutchavadee; Pan-Ngum, Wirichada; Jittamala, Podjanee; Maneeboonyang, Wanchai; Rukmanee, Prasert; Lawpoolsri, Saranath

2015-10-09

Children represent a high-risk group for malaria worldwide. Among people in Thailand who have malaria during childhood, some may have multiple malaria attacks during their lifetime. Malaria may affect neurological cognition in children, resulting in short-term impairment of memory and language functions. However, little is known regarding the long-term effects of malaria infection on cognitive function. This study examines the long-term impact of malaria infection on school performance among school children living in a malaria-endemic area along the Thai-Myanmar border. A retrospective cohort study was conducted among school children aged 6-17 years in a primary-secondary school of a sub-district of Ratchaburi Province, Thailand. History of childhood malaria infection was obtained from the medical records of the sole malaria clinic in the area. School performance was assessed by using scores for the subjects Thai Language and Mathematics in 2014. Other variables, such as demographic characteristics, perinatal history, nutritional status, and emotional intelligence, were also documented. A total of 457 students were included, 135 (30 %) of whom had a history of uncomplicated malaria infection. About half of the malaria-infected children had suffered infection before the age of four years. The mean scores for both Mathematics and Thai Language decreased in relation to the increasing number of malaria attacks. Most students had their last malaria episode more than two years previously. The mean scores were not associated with duration since the last malaria attack. The association between malaria infection and school performance was not significant after adjusting for potential confounders, including gender, school absenteeism over a semester term, and emotional intelligence. This study characterizes the long-term consequences of uncomplicated malaria disease during childhood. School performance was not associated with a history of malaria infection, considering that most students had their last malaria infection more than two years previously. These findings indicate that the impact of uncomplicated malaria infection on school performance may not be prolonged.

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.

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

Prevalence of Malaria in Pregnant Women in Lagos, South-West Nigeria

PubMed Central

Agomo, Chimere O.; Anorlu, Rose I.; Agomo, Philip U.

2009-01-01

Prevalence rates reported for malaria in pregnancy in Nigeria vary considerably. The accuracy of results of malaria diagnosis is dependent on training, experience, and motivation of the microscopist as well as the laboratory facility available. Results of training programmes on malaria microscopy have shown low levels of sensitivity and specificity of those involved in malaria diagnosis routinely and for research. This study was done to ascertain the true prevalence of malaria in pregnancy in Lagos, South-West Nigeria. A total of 1,084 pregnant women were recruited into this study. Blood smears stained with Giemsa were used for malaria diagnosis by light microscopy. Malaria infection during pregnancy presents mostly as asymptomatic infection. The prevalence of malaria in this population was 7.7% (95% confidence interval; 6.2-9.4%). Factors identified to increase the risk of malaria infection include young maternal age (< 20 years), and gravidity (primigravida). In conclusion, this study exposes the over-diagnosis of malaria in pregnancy and the need for training and retraining of laboratory staffs as well as establishing the malaria diagnosis quality assurance programme to ensure the accuracy of malaria microscopy results at all levels. PMID:19488427

Prevalence of HIV and malaria: a cross-sectional study on Bioko Island, Equatorial Guinea.

PubMed

Zheng, Xiangbin; Lin, Min; Xie, Dong-De; Li, Jian; Chen, Jiang-Tao; Eyi, Urbano Monsuy; Monte-Nguba, Santiago-M; Ehapo, Juan Carlos Sala; Yang, Hui; Yang, Hui-Tian; Yang, Li-Ye

2017-03-01

Malaria and HIV are two of the most severe public health problems in Africa. However, epidemiological data on Bioko Island is scarce. To investigate the prevalence of malaria and HIV infections and assess association of malaria and HIV infections and possible confounding factors, we performed a cross-sectional survey of people of malaria-endemic Bioko Island, Equatorial Guinea. A cross-sectional study of 1 526 subjects was carried out to determine the prevalence of malaria and HIV infection in Malabo region hospital on Bioko Island. Questionnaires were administered and venous blood samples were drawn for malaria parasites and HIV detection. The prevalence of participants infected with malaria and HIV in this area were 13.8% and 6.6% respectively. The average prevalence of co-infection for malaria and HIV was 0.92%. HIV-infection was significantly associated with the age and gender. Malaria infections were significantly associated with the age. This study showed that the prevalence of HIV and malaria on Bioko Island was higher than expected, although the co-infection prevalence of malaria and HIV was low. The results also indicated that malaria and HIV infections lead to more public health risk to youngsters and women.

Commentary: The Perils of Seduction: Distracting Details or Incomprehensible Abstractions?

ERIC Educational Resources Information Center

Goetz, Ernest T.; Sadoski, Mark

1995-01-01

Reviews studies that have explicitly investigated the "seductive detail" effect (in which a reader's attention is diverted toward the interesting but unimportant seductive details and away from the uninteresting but important main ideas). Concludes that these studies do not provide convincing evidence for the existence of the effect.…

Minority Recruitment and Retention for Universities: Bilingual Special Education Faculty

ERIC Educational Resources Information Center

Brice, Alejandro E.

2012-01-01

Recruitment and retention of minority faculty in bilingual special education is a perilous task. Research has shown that minority faculty/teachers are able to provide emotional support, mentor students, serve as role models, create a positive climate, provide diverse views, increase collaboration among faculty and teachers, and work with…

The Shape of Work to Come: Perils.

ERIC Educational Resources Information Center

Raskin, A. H.

1979-01-01

Changes and problems in the economy and workplace, including the certainty of future struggles for good jobs, new management mood toward unions, automation, and fringe benefits, are examined. It is suggested that education for this future must inculcate moral values along with academic skills and seek to restore faith in institutions. (JMD)

Second Language Reading and Vocabulary Learning.

ERIC Educational Resources Information Center

Huckin, Thomas, Ed.; And Others

This book contains 14 essays on reading and vocabulary learning in second language acquisition. Chapters include: "Research on ESL/EFL Vocabulary Acquisition: Putting It in Context" (James Coady); "Implications for L2 Vocabulary Acquisition and Instruction From L1 Vocabulary Research" (Fredricka Stoller and William Grabe); "Patterns and Perils of…

Freedoms and Perils: Academy Schools in England

ERIC Educational Resources Information Center

Heilbronn, Ruth

2016-01-01

Can Dewey's Moral Principles in Education throw light on a contemporary policy issue in education, namely the privatisation of education through the establishment of academy schools in England? The article first considers what the policy entails, in terms of its conception of education as a market commodity. The next section suggests an…

Ritalin: Education's Fix-It Drug?

ERIC Educational Resources Information Center

Divoky, Diane

1989-01-01

Describes the case of Casey Jesson, a hyperactive child ordered by the state of Hew Hampshire to ingest Ritalin or forego a public education. Despite adverse side effects and the perils of drug dependency, there is greater parental and educator acceptance of Ritalin than ever before. Scientologists are sparking an anti-Ritalin campaign. Includes…

Beyond Cliche--Reclaiming the Concept of Sustainability

ERIC Educational Resources Information Center

Fuller, Robert J.

2010-01-01

In closing his 2008 Myer Lecture, the scientist and environmentalist Dr. Tim Flannery said that this century will be defined by the search for sustainability. How perilous therefore that nowadays there is so much overuse of the word "sustainability" that it has become a cliche. Today's tertiary students studying architecture and…

New Models in Transcultural Learning Institutions and Curricula

ERIC Educational Resources Information Center

Van Hook, Steven R.

2011-01-01

This research examines driving issues forcing change in international higher education, changes institutions might adopt to adapt to those drivers, new academic policies, and concludes with consideration of the promise and peril the future might hold. The interrelated issues of governance, funding, faculty, technologies, curriculum, and so on, are…

A New Script for Working with Parents

ERIC Educational Resources Information Center

Wischnowski, Michael W.; Cianca, Marie

2012-01-01

Parent/teacher relationships are fraught with potential for perilous misunderstandings amid what often are construed as conflicting interests. Perhaps that is nowhere more true than in parent/teacher relationships regarding children with disabilities. The authors report on a program at St. John Fisher College where teams of preservice teachers…

The Perils of Repressive Tolerance in Music Education Curriculum

ERIC Educational Resources Information Center

Perrine, William M.

2017-01-01

In recent years, philosophers of music education have called for a greater degree of political engagement by music education practitioners. Using Marcuse's discussion of "repressive tolerance" as a conceptual framework, I argue that a politicized curriculum in music education works against the liberal ideas of free speech and a free…

The Peril of Ignoring Middle School Student Speech Rights

ERIC Educational Resources Information Center

Hassenpflug, Ann

2016-01-01

Analysis of two recent federal court cases in which principals violated student speech rights offers guidance to middle school administrators as they attempt to address student expression. Characteristics of a successful school from the Association for Middle Level Education provide a framework for analyzing these cases in order to prevent…

Facebook: Perils, Perceptions and Precautions

ERIC Educational Resources Information Center

La Roche, Claire Reeves; Flanigan, Mary A.; La Roche, St. Clair Reeves

2009-01-01

Facebook is one of the fastest growing applications of the Internet. Social networking via Facebook provides a popular way for students and others to connect with a wide audience and expand their circle of friends. Facebook account holders have been denied admission to universities, not hired for jobs, lost scholarships, been disciplined by…

The Free Mind: Intellectual Freedom's Perils and Prospects

ERIC Educational Resources Information Center

Oboler, Eli

1976-01-01

It is more important to make available all possible shades of opinion and varieties of creative effort than to have the widest possible range of gadgets and gizmos connected by the fanciest and longest possible networks, but including only a restricted, censored, limited range of topics and their interpretations. (Author)

Chronicle of Higher Education. Volume 51, Number 20, January 21, 2005

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2005

2005-01-01

"Chronicle of Higher Education" presents an abundant source of news and information for college and university faculty members and administrators. This January 21, 2005 issue of "Chronicle of Higher Education" includes the following articles: (1) "The Perils of Pursuing Prestige" (Lovett, Clara M.); (2) "A…

Assessing the Science Knowledge of University Students: Perils, Pitfalls and Possibilities

ERIC Educational Resources Information Center

Jones, Susan M.

2014-01-01

Science content knowledge is internationally regarded as a fundamentally important learning outcome for graduates of bachelor level science degrees: the Science Threshold Learning Outcomes (TLOs) recently adopted in Australia as a nationally agreed framework include "Science Knowledge" as TLO 2. Science knowledge is commonly assessed…

Gaelic Singing and Oral Tradition

ERIC Educational Resources Information Center

Sheridan, Mark; MacDonald, Iona; Byrne, Charles G.

2011-01-01

A recent report by UNESCO placed Scots Gaelic on a list of 2500 endangered languages highlighting the perilous state of a key cornerstone of Scottish culture. Scottish Gaelic song, poems and stories have been carried through oral transmission for many centuries reflecting the power of indigenous peoples to preserve cultural heritage from…

The Promise and Peril of Video Cases: Reflections on Their Creation and Use.

ERIC Educational Resources Information Center

Liedtka, Jeanne

2001-01-01

Presents a rationale for video case studies: they are engaging and flexible, facilitate listening skills, and make the classroom a virtual world. Describes development challenges in terms of time, expense, editing, storytelling, and conveying content. Provides advice for teaching with video cases. (SK)

Validity for What? The Peril of Overclarifying

ERIC Educational Resources Information Center

Murphy, Kevin R.

2012-01-01

As Paul Newton so ably demonstrates, the concept of validity is both important and problematic. Over the last several decades, a consensus definition of validity has emerged; the current edition of "Standards for Educational and Psychological Testing" notes, "Validity refers to the degree to which evidence and theory support the interpretations of…

On Men Mentoring Women: Then and Now.

ERIC Educational Resources Information Center

Kronik, John W.

1990-01-01

Suggests that mentoring varies greatly in degree and nature of involvement, and can be perilous and abusive, particularly between male mentors and female subordinates. For the mentor system to work, the mentor/subordinate association must be based on mutual respect and allow for subtle and beneficial exercise of power. (GLR)

Competency Education Offers Promise and Peril for Students

ERIC Educational Resources Information Center

Ritterband, Vicki; Heller, Rafael

2015-01-01

Lindsay Unified School District (California) exemplifies the promise of competency education (or performance-based education, as it is called locally). Since beginning its transition to the model in 2009, discipline problems have sharply dropped, the school climate has dramatically improved (as measured by the California Healthy Kids Survey), and…

Theoretical, Methodological, and Ethical Challenges to the Study of Immigrants: Perils and Possibilities

ERIC Educational Resources Information Center

Mahalingam, Ramaswami; Rabelo, Verónica Caridad

2013-01-01

Research on immigrant communities has often been reductionist, stereotypical, and simplistic, and even the most well-intentioned researchers are susceptible to using cultural deficit models. This chapter critically evaluates some of the dominant tensions and problem areas with respect to researching immigrant communities. Specifically, we analyze…

Financial Perils in Higher Education--Good Grief!

ERIC Educational Resources Information Center

Shaw, Kenneth A.; Britton, Thomas C.

The premise that institutions pass through a grief process in adjusting to declining resources and radical changes, is proposed. In addition, strategies that administrators can use to respond to institutional grief are suggested. Elisabeth Kubler-Ross's paradigm of five grief stages/reactions to serious loss are described: denial, anger,…

Performance Funding in Higher Education: Panacea or Peril?

ERIC Educational Resources Information Center

Pickens, William H.

The use of performance funding, which provides institutions with income for educational results, was tested in Tennessee. Traditionally, the budget has been separated from performance evaluation, and state formulas have evolved from the need for funding to be objective, comparable, and predictable. The Performance Funding Project in Tennessee,…

The Potential Perils of Praise in a Democratic Interactive Classroom.

ERIC Educational Resources Information Center

Larrivee, Barbara

2002-01-01

Teacher praise can undermine the development of fundamental democratic values. This article presents styles of teacher talk in line with the principles and goals of democratic leadership and interactive teaching. Advocated discourse patterns encourage self-evaluation and self-reflection, enabling students to develop standards for judging their own…

The Research University in a Time of Discontent.

ERIC Educational Resources Information Center

Cole, Jonathan R., Ed.; And Others

This volume contains 19 papers on the current status of the research university particularly in light of diminished federal research support and of the opportunities and perils of the larger, international educational stage. The papers are: (1) "Balancing Acts: Dilemmas of Choice Facing Research Universities" (Jonathan R. Cole); (2)…

Adolescents Saying "No" to Sex.

ERIC Educational Resources Information Center

Valentine, Paul W.

1992-01-01

Students at a Baltimore, Maryland, middle school have been bombarded with lessons in self-esteem, career planning, and perils of early pregnancy. Directed equally at girls and boys, the Campaign for Our Children program is part of city's effort to curb its galloping teenage pregnancy. Through Governor's Council on Adolescent Pregnancy, campaign…

Planning for Quality: Perils and Possibilities.

ERIC Educational Resources Information Center

Schmidtlein, Frank A.

This paper reports selected findings from a study of formal, institution-wide planning in the United States undertaken by the National Center for Postsecondary Governance and Finance, located at the University of Maryland. The study included a review of higher education planning literature, a survey of administrators at 256 institutions, and…

Is There a Gray Peril?: Retirement Politics in Florida.

ERIC Educational Resources Information Center

Rosenbaum, Walter A.; Button, James W.

1989-01-01

Surveyed local government officials and obtained socioeconomic data about local government regarding 103 municipalities and 62 counties in Florida to test 3 hypotheses concerning political impact of retirement migration on the Sunbelt. Findings suggest that aging persons, although politically active, are seldom involved in organized advocacy or…

Managing Risk in Systems Development.

ERIC Educational Resources Information Center

DePaoli, Marilyn M.; And Others

Stanford University's use of a risk assessment methodology to improve the management of systems development projects is discussed. After examining the concepts of hazard, peril, and risk as they relate to the system development process, three ways to assess risk are covered: size, structure, and technology. The overall objective for Stanford…

Health Information Technology: Dos and Don'ts for Today and Tomorrow.

PubMed

Sidorov, Jaan; Randhar, Akash

2017-01-01

The challenges include not overburdening physicians and fitting into an increasingly complex, multilayered informatics ecosystem. Innovative health care entities that neglect health care's reliance on evidence-based medicine and go to market without the benefit of any peer review do so at their own peril.

Brazilian cuts put projects in peril

NASA Astrophysics Data System (ADS)

José Lopes, Reinaldo

2015-10-01

The soap opera surrounding Brazil's participation in the European Southern Observatory (ESO) has taken another twist after the Ministry of Science, Technology and Innovation said that the government is still “considering” what to do, even though physicist Sérgio Rezende - a former science minister - was behind the push for Brazilian membership.

Perilous Human Security in South Asia: Are There Ways Out?

DTIC Science & Technology

2011-03-21

threats directed against women and child . Most people derive security from their membership in a group – a family, a community, an organization, a...Strategic Environment, 10-11. 84 Aun Porn Moniroth, “Economic Integration in East Asia – Cambodia’s Experience” in East Asian Visions, ed. Indermit Gil

The Perils of "Adjustment Disorder" as a Diagnostic Category

ERIC Educational Resources Information Center

Daniels, John

2009-01-01

"Adjustment disorder" occupies a peculiar position in the diagnostic system of the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) straddling the boundary between normal and abnormal psychology. A more human-centered approach in counseling offers a defense of "normal" adjustment as…

Faith Partnerships and Public Schools in Philadelphia: Rewards and Perils.

ERIC Educational Resources Information Center

Mundell, Leah

In 1999, Philadelphia (Pennsylvania) school superintendent David Hornbeck introduced educators and religious leaders to his requirement that each public school in the city develop a relationship with a faith partner, a religious institution that could share facilities and resources with the school. Hornbeck saw religious institutions and schools…

Getting Your Message out (And Why It's Not Enough)

ERIC Educational Resources Information Center

Johnson, Jean

2015-01-01

Sometimes, education leaders are so intent on getting their message out that they neglect the other side of the equation--listening. In this article, Jean Johnson of Public Agenda describes the conditions that make "messaging" a perilous undertaking today. "These are skeptical times," she explains, in which Americans are…

Inside Public Television

ERIC Educational Resources Information Center

Wurtzel, Alan

1977-01-01

In the continuing saga of the perils of public television, the author, University of Georgia School of Journalism TV Coordinator, gives the viewer an inside look at the unwieldy structure of this non-commercial medium. Today's episode: Will high-quality programming survive? The players: 265 independent public TV stations, a decentralized public TV…

Voice of the Presidents: The Hidden Perils of Globalization.

ERIC Educational Resources Information Center

Robertson, Jamie

2001-01-01

A tribal college president describes how partnerships with international companies (such as one that changes slaughterhouse waste blood into protein additives for animal and human foods) may be lucrative but conflict with tribal traditions, culture, and integrity. States that globalization does not always serve the purposes of tribal colleges.…

New Perils for the Contract Ethnographer.

ERIC Educational Resources Information Center

Fetterman, David M.

1981-01-01

Conditions of contract research may lead some workers to ignore publication rights of colleagues whose reports are of limited circulation. The author presents a case example of how this process occurred with the use of his own work and argues for rigorous ethical standards in the publication of contract research results. (Author/GC)

Reflecting on Teaching Experiences in the Lab: Challenges with Classroom Design

ERIC Educational Resources Information Center

Cozza, Vanessa

2010-01-01

In Cynthia Selfe's "Technology and Literacy: A Story about the Perils of Not Paying Attention," she advises that composition teachers "have to pay attention to technology." Similar to Brittany B. Cottrill's discussion of issues of access, this reflective piece pays attention to another issue concerning technology, specifically…

Malaria and HIV among pediatric inpatients in two Tanzanian referral hospitals: A prospective study.

PubMed

Smart, Luke R; Orgenes, Neema; Mazigo, Humphrey D; Minde, Mercy; Hokororo, Adolfine; Shakir, Muhammad; Verweij, Jaco J; Downs, Jennifer A; Peck, Robert N

2016-07-01

Malaria remains common in sub-Saharan Africa, but it is frequently over-diagnosed and over-treated in hospitalized children. HIV is prevalent in many malaria endemic areas and may delay parasite clearance and increase mortality among children with malaria. This prospective cohort study enrolled children with suspected malaria between 3 months and 12 years of age hospitalized at two referral hospitals in Tanzania. Both a thick blood smear (BS) and a malaria rapid diagnostic test (mRDT) were performed. If discordant results were obtained, PCR was performed for Plasmodium falciparum. Malaria was confirmed if two out of three tests were positive. Malaria parasite densities were determined for two consecutive days after diagnosis and treatment of malaria. All participants were tested for HIV. Among 1492 hospitalized children, 400 (26.8%) were enrolled with suspected malaria infection. There were 196/400 (49.0%) males, and the median age was 18 [9-36] months. BS was positive in 95/400 (23.8%), and mRDT was positive in 70/400 (17.5%), with moderate agreement (Kappa=0.598). Concordant results excluded malaria in 291/400 (72.8%) and confirmed malaria in 56/400 (14.0%). PCR performed on 53 discordant results confirmed malaria in 1/39 of the BS-positive/mRDT-negative cases, and 6/14 of the BS-negative/mRDT-positive cases. The prevalence of confirmed malaria was 63/400 (15.8%). In multivariable logistic regression, malaria was associated with HIV (OR 3.45 [1.65-7.20], p=0.001). Current breastfeeding (OR 0.25 [0.11-0.56], p=0.001) and higher hemoglobin (OR 0.70 [0.60-0.81], p<0.001 per 1g/dL) were associated with decreased odds of malaria. Malaria parasite clearance was delayed in HIV-infected participants (p<0.001). Malaria is over-diagnosed even at referral centers in high transmission areas. Hospitalized HIV-infected children are more likely to have malaria and exhibit delayed clearance of parasites. Hospitals should consider using mRDTs as a first step for malaria testing among hospitalized children in sub-Saharan Africa. Copyright © 2016 Elsevier B.V. All rights reserved.