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Sample records for malaria genetic clues

  1. Parasite-host interaction in malaria: genetic clues and copy number variation

    PubMed Central

    2009-01-01

    In humans, infections contribute highly to mortality and morbidity rates worldwide. Malaria tropica is one of the major infectious diseases globally and is caused by the protozoan parasite Plasmodium falciparum. Plasmodia have accompanied human beings since the emergence of humankind. Due to its pathogenicity, malaria is a powerful selective force on the human genome. Genetic epidemiology approaches such as family and twin studies, candidate gene studies, and disease-association studies have identified a number of genes that mediate relative protection against the severest forms of the disease. New molecular approaches, including genome-wide association studies, have recently been performed to expand our knowledge on the functional effect of human variation in malaria. For the future, a systematic determination of gene-dosage effects and expression profiles of protective genes might unveil the functional impact of structural alterations in these genes on either side of the host-parasite interaction. PMID:19725943

  2. Scientists Spot Genetic Clues to Disfiguring 'Fish Scale' Disease

    MedlinePlus

    ... medlineplus.gov/news/fullstory_166145.html Scientists Spot Genetic Clues to Disfiguring 'Fish Scale' Disease People with ... June 1 in the American Journal of Human Genetics , adds to the list of genetic culprits. The ...

  3. Genetic Control Of Malaria Mosquitoes.

    PubMed

    McLean, Kyle Jarrod; Jacobs-Lorena, Marcelo

    2016-03-01

    Experiments demonstrating the feasibility of genetically modifying mosquito vectors to impair their ability to transmit the malaria parasite have been known for well over a decade. However, means to spread resistance or population control genes into wild mosquito populations remains an unsolved challenge. Two recent reports give hope that CRISPR technology may allow such challenge to be overcome.

  4. Behavioral phenotypes in genetic syndromes: genetic clues to human behavior.

    PubMed

    Cassidy, Suzanne B; Morris, Colleen A

    2002-01-01

    A behavioral phenotype is the characteristic cognitive, personality, behavioral, and psychiatric pattern that typifies a disorder. A number of genetic syndromes have been identified as having this type of distinctive and consistent behavior pattern. It may act as an important diagnostic sign, like a malformation or characteristic facial appearance. Such patterns are also useful for the physician's anticipatory guidance from an educational, rehabilitative, and parenting perspective. In addition, because they are the consequences of known genetic alterations, behavioral phenotypes can be potentially highly valuable clues to the identification of genes in the population that are important to determination of cognitive skills or deficits, personality determinants, behavioral abnormalities, or psychiatric disorders. The nature of a behavioral phenotype and its potential for genetic insight can be appreciated through the examples of Williams syndrome, Prader-Willi syndrome, and Angelman syndrome. The cognitive and behavioral characteristics of these disorders are distinctive. Williams syndrome is known for its association with remarkable conversational verbal abilities and excessive empathy, whereas Prader-Willi syndrome is known for temper tantrums and obsessive-compulsive features, and Angelman syndrome is associated with a constantly happy affect and hyperactivity. The genetic basis for each of these disorders is known, and the pathophysiology and genotype-phenotype correlations are beginning to provide insight into genes responsible for personality characteristics and behavioral abnormalities.

  5. Genetic polymorphisms linked to susceptibility to malaria.

    PubMed

    Driss, Adel; Hibbert, Jacqueline M; Wilson, Nana O; Iqbal, Shareen A; Adamkiewicz, Thomas V; Stiles, Jonathan K

    2011-09-19

    The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature.Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.

  6. Population genetics of malaria resistance in humans

    PubMed Central

    Hedrick, P W

    2011-01-01

    The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldane's initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deficiency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are ‘loss-of-function' mutants and appear to be recent polymorphisms from the last 5000–10 000 years or less. I discuss estimation of selection coefficients from case–control data and make predictions about the change for S, C and G6PD-deficiency variants. In addition, I consider the predicted joint changes when the two β-globin alleles S and C are both variable in the same population and when there is a variation for α-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants. PMID:21427751

  7. Malaria

    PubMed Central

    Suh, Kathryn N.; Kain, Kevin C.; Keystone, Jay S.

    2004-01-01

    Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research. PMID:15159369

  8. Molecular Genetic Analysis of Parasite Survival in P. falciparum Malaria

    DTIC Science & Technology

    1993-02-08

    AD-A279 410 GRANT NO: DAMN17-89-Z-9003 TITLE: MOLECULAR GENETIC ANALYSIS OF PARASITE SURVIVAL IN R. E&LEZjpAIM MALARIA PRINCIPAL INVESTIGATOR... Analysis of Parasite Survival Grant No. in P. Falciparum Malaria DAMDi 7-89- Z-9003 -6. AUTHOR(S) Jeffrey V. Ravetch, M.D., Ph.D. 7. PERFORMING...consequences of genetic variation for parasite survival. Genetic polymorphisms in PRfalciparum were initially detected by pulsed-field gel analysis of intact

  9. [A plasmodium alciparum malaria case originated from Mozambique: clues for the diagnosis and therapy].

    PubMed

    Ozkaya, Gülşen; Yildirim, Tolga; Aydin, Kadriye; Ergüven, Sibel; Unal, Serhat

    2006-10-01

    The aim of this report was the presentation of a falciparum malaria case originated from Mozambique and the evaluation of diagnostic and therapeutic approaches. Sixty years old Canadian male patient who has been working in Mozambique for 13 years was admitted to hospital with the complaints of high fever (39.6 degrees C), weakness, nausea and vomiting, when returned to Turkey. The patient was sleepiness and has undulating confusions with the laboratory findings of thrombocytopenia, hypoglycemia, hyperlactatemia, increased BUN/creatinine levels, increased LDH levels and hypocholesterolemia. The diagnosis was based on the detection of multiple ring formed trophozoites in the thick blood film and the presence of multiple ring forms inside the erythrocytes and the absence of trophozoite and shizont forms in the thin blood film. His medical history revealed that he experienced another falciparum malaria infection one year ago, although he has been using mefloquine prophylaxis during his stay in Mozambique. Since chloroquine resistance was thought to be high in this region, the patient was treated with quinine sulphate and doxycycline. Six days after the onset of therapy, the biochemical markers turned to normal and 14 days later the blood films were free of the parasite. The patient was given doxycycline prophylaxis since he would return to Mozambique. In conclusion, the followings should be taken into consideration for the diagnosis and therapy: (i) cyclic type of fever which is characteristic for malaria, might not be detected in falciparum malaria; (ii) some of the clinical symptoms might be blocked by partial immune response in case of recurrent infections; (iii) thrombocytopenia and hypocholesterolemia might indicate the presence of falciparum malaria; and when falciparum malaria is confirmed by parasitological examinations the patient should be treated as if he/she is accepted as resistant to chloroquine.

  10. ogaraK: a population genetics simulator for malaria.

    PubMed

    Antao, Tiago; Hastings, Ian M

    2011-05-01

    The evolution of resistance in Plasmodium falciparum malaria against most available treatments is a major global health threat. Population genetics approaches are commonly used to model the spread of drug resistance. Due to uncommon features in malaria biology, existing forward-time population genetics simulators cannot suitably model Plasmodium falciparum malaria. Here we present ogaraK, a population genetics simulator for modelling the spread of drug-resistant malaria. OgaraK is designed to make malaria simulation computationally tractable as it models infections, not individual parasites. OgaraK is also able to model the life cycle of the parasite which includes both haploid and diploid phases and sexual and asexual reproduction. We also allow for the simulation of different inbreeding levels, an important difference between high and low transmission areas and a fundamental factor influencing the outcome of strategies to control or eliminate malaria. OgaraK is available as free software (GPL) from the address http://popgen.eu/soft/ogaraK.

  11. 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 ...

  12. Eradication of malaria through genetic engineering: the current situation.

    PubMed

    Chong, Wing-Chui; Basir, Rusliza; Fei, Yam Mun

    2013-02-01

    Malaria is an intra-cellular parasitic protozoon responsible for millions of deaths annually. Host and parasite genetic factors are crucial in affecting susceptibility to malaria and progression of the disease. Recent increased deployment of vector controls and new artemisinin combination therapies have dramatically reduced the mortality and morbidity of malaria worldwide. However, the gradual emergence of parasite and mosquito resistance has raised alarm regarding the effectiveness of current artemisinin-based therapies. In this review, mechanisms of anti-malarial drug resistance in the Plasmodium parasite and new genetically engineered tools of research priorities are discussed. The complexity of the parasite lifecycle demands novel interventions to achieve global eradication. However, turning laboratory discovered transgenic interventions into functional products entails multiple experimental phases in addition to ethical and safety hurdles. Uncertainty over the regulatory status and public acceptance further discourage the implementation of genetically modified organisms. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. Seasonal genetic partitioning in the neotropical malaria vector, Anopheles darlingi

    PubMed Central

    2014-01-01

    Background Anopheles darlingi is the main malaria mosquito vector in the Amazonia region. In spite of being considered a riverine, forest-dwelling species, this mosquito is becoming more abundant in peri-urban areas, increasing malaria risk. This has been associated with human-driven environmental changes such as deforestation. Methods Microsatellites were used to characterize A. darlingi from seven localities along the Madeira River, Rondônia (Brazil), collected in the early and late periods of the rainy season. Results Two genetically distinct subpopulations were detected: one (subpopulation A) was associated with the late rainfall period and seems to be ecologically closer to the typical forest A. darlingi; the other (subpopulation B) was associated with the early rainfall period and is probably more adapted to drier conditions by exploiting permanent anthropogenic breeding sites. Results suggest also a pattern of asymmetric introgression, with more subpopulation A alleles introgressed into subpopulation B. Both subpopulations (and admixed mosquitoes) presented similar malaria infection rates, highlighting the potential for perennial malaria transmission in the region. Conclusions The co-occurrence of two genetically distinct subpopulations of A. darlingi adapted to different periods of rainfall may promote a more perennial transmission of malaria throughout the year. These findings, in a context of strong environmental impact due to deforestation and dam construction, have serious implications for malaria epidemiology and control in the Amazonian region. PMID:24885508

  14. Genetic engineering of attenuated malaria parasites for vaccination.

    PubMed

    Khan, Shahid M; Janse, Chris J; Kappe, Stefan H I; Mikolajczak, Sebastian A

    2012-12-01

    Vaccination with live-attenuated Plasmodium sporozoites that arrest in the liver can completely protect against a malaria infection both in animal models and in humans; this has provided the conceptual basis for the most promising, but also challenging, approach to develop an efficacious malaria vaccine. Advances in genetic manipulation of Plasmodium in conjunction with improved genomic and biological information has enabled new approaches to design genetically attenuated parasites (GAPs). In this review we discuss the principles in discovery and development of GAPs in preclinical models that are important in selecting GAP parasites for first-in-human clinical studies. Finally, we highlight the challenges in manufacture, formulation and delivery of a live-attenuated whole parasite malaria vaccine, as well as the further refinements that may be implemented in the next generation GAP vaccines.

  15. Contribution of inflammasome genetics in Plasmodium vivax malaria.

    PubMed

    Santos, Marina L S; Reis, Edione Cristina; Bricher, Pamela N; Sousa, Tais N; Brito, Cristiana F A; Lacerda, Marcus V G; Fontes, Cor J F; Carvalho, Luzia H; Pontillo, Alessandra

    2016-06-01

    Recent reports showed that, in mice, symptomatic Plasmodium infection triggers NLRP3/NLRP12-dependent inflammasome formation and caspase-1 activation in monocytes. In humans, few works demonstrated that inflammasome is activated in malaria. As Plasmodiumvivax is a potent inducer of inflammatory response we hypothesised that inflammasome genetics might affect P. vivax malaria clinical presentation. For this purpose, selected SNPs in inflammasome genes were analysed among patients with symptomatic P. vivax malaria. 157 Brazilian Amazon patients with P. vivax malaria were genotyped for 10 single nucleotide polymorphisms (SNPs) in inflammasome genes NLRP1, NLRP3, AIM2, CARD8, IL1B, IL18 and MEFV. Effect of SNPs on hematologic and clinical parameters was analysed by multivariate analysis. Our data suggested an important role of NLRP1 inflammasome receptor in shaping the clinical presentation of P. vivax malaria, in term of presence of fever, anaemia and thrombocytopenia. Moreover IL1B rs1143634 resulted significantly associated to patients' parasitaemia, while IL18 rs5744256 plays a protective role against the development of anaemia. Polymorphisms in inflammasome genes could affect one or other aspects of malaria pathogenesis. Moreover, these data reveal novel aspects of P.vivax/host interaction that involved NLRP1-inflammasome.

  16. Genetic expression outside the skin: clues to mechanisms of Genotype x Environment interaction.

    PubMed

    Reiss, David; Leve, Leslie D

    2007-01-01

    The rapidly moving study of Gene x Environment interaction (G x E) needs interim conceptual tools to track progress, integrate findings, and apply this knowledge to preventive intervention. We define two closely related concepts: the social mediation of the expression of genetic influences and the interaction between the entire genotype and the social environment (G x E). G x E, the primary focus of this report, assesses individual differences in the full genotype using twin, sibling, and adoption designs and, for the most part, employs fine-grained analyses of relational processes in the social environment. In comparison, studies of Allele x Environment interaction assess the influence on development of one or more measured polymorphisms as modified by environmental factors. G x E studies build on work showing how the social environment responds to genetic influences and how genetic influences shape the social environment. Recent G x E research has yielded new insight into variations in the sensitivity of the social environment to genotypic influences and provides clues to the specificity and timing of these environmental responses that can be leveraged to inform preventive interventions aimed at reducing genetic risk for problem behavior.

  17. Population genetic structure of malaria vector Anopheles stephensi Liston (Diptera: Culicidae).

    PubMed

    Gakhar, S K; Sharma, Richa; Sharma, Arvind

    2013-04-01

    Malaria is a complex disease that afflicts human today. Malaria epidemiology is associated with drug resistance in parasite and differential distribution and insecticide resistance in vector. Efforts are being made to eradicate malaria but burden of malaria is still increasing. Vector control is essential for malaria prevention strategies. Knowledge of population genetic structure is pre-requisite for determining prevention strategies particularly using transgenic mosquitoes. Population genetic study can predict level of gene flow between different populations. Anopheles stephensi Liston is urban vector of malaria in Indo-Pakistan subcontinent. About 12% of malaria cases of malaria in India are contributed by A. stephensi. Studies conducted on population genetics of A. stephensi using various markers in different parts of the world are discussed in this communication.

  18. Identifying permethrin resistance loci in malaria vectors by genetic mapping.

    PubMed

    Witzig, Claudia; Wondji, Charles S; Strode, Clare; Djouaka, Rousseau; Ranson, Hilary

    2013-10-01

    Identification of the major loci responsible for insecticide resistance in malaria vectors would aid the development and implementation of effective resistance management strategies, which are urgently needed to tackle the growing threat posed by resistance to the limited insecticides available for malaria control. Genome-wide association studies in the major malaria vector, Anopheles gambiae, have been hindered by the high degree of within-population structuring and very low levels of linkage disequilibrium hence we revisited the use of quantitative trait loci (QTL) mapping to study resistance phenotypes in this vector species. Earlier work, identified two major QTL associated with pyrethroid resistance in A. gambiae s.s. from East Africa using genetic crossing of laboratory-colonized resistant and susceptible strains. In this study, we report the results from genetic mapping of pyrethroid resistance in three isofemale pedigrees established from wild-caught female A. gambiae s.s. mosquitoes from Benin. We identified two QTL on chromosomes 2L and 3R in these field populations, in similar genomic locations to the QTL identified in laboratory strains. The relative merits of two alternative study designs are discussed and suggestions made for future genetic mapping studies of insecticide resistance in mosquitoes.

  19. Dissecting malaria biology and epidemiology using population genetics and genomics.

    PubMed

    Auburn, Sarah; Barry, Alyssa E

    2017-02-01

    Molecular approaches have an increasingly recognized utility in surveillance of malaria parasite populations, not only in defining prevalence and incidence with higher sensitivity than traditional methods, but also in monitoring local and regional parasite transmission patterns. In this review, we provide an overview of population genetic and genomic studies of human-infecting Plasmodium species, highlighting recent advances in the field. In accordance with the renewed impetus for malaria eradication, many studies are now using genetic and genomic epidemiology to support local evidence-based intervention strategies. Microsatellite genotyping remains a popular approach for both Plasmodium falciparum and Plasmodium vivax. However, with the increasing availability of whole genome sequencing data enabling effective single nucleotide polymorphism-based panels tailored to a given study question and setting, this approach is gaining popularity. The availability of new reference genomes for Plasmodium malariae and Plasmodium ovale should see a surge in similar molecular studies on these currently neglected species. Genomic studies are revealing new insights into important adaptive mechanisms of the parasite including antimalarial drug resistance. The advent of new methodologies such as selective whole genome amplification for dealing with extensive human DNA in low density field isolates should see genome-wide approaches becoming routine for parasite surveillance once the economic costs outweigh the current cost benefits of targeted approaches. Copyright © 2016. Published by Elsevier Ltd.

  20. The geography of malaria genetics in the Democratic Republic of Congo: A complex and fragmented landscape

    PubMed Central

    Carrel, Margaret; Patel, Jaymin; Taylor, Steve M.; Janko, Mark; Mwandagalirwa, Melchior Kashamuka; Tshefu, Antoinette K.; Escalante, Ananias A.; McCollum, Andrea; Alam, Md Tauqeer; Udhayakumar, Venkatachalam; Meshnick, Steven; Emch, Michael

    2014-01-01

    Understanding how malaria parasites move between populations is important, particularly given the potential for malaria to be reintroduced into areas where it was previously eliminated. We examine the distribution of malaria genetics across seven sites within the Democratic Republic of Congo (DRC) and two nearby countries, Ghana and Kenya, in order to understand how the relatedness of malaria parasites varies across space, and whether there are barriers to the flow of malaria parasites within the DRC or across borders. Parasite DNA was retrieved from dried blood spots from 7 Demographic and Health Survey sample clusters in the DRC. Malaria genetic characteristics of parasites from Ghana and Kenya were also obtained. For each of 9 geographic sites (7 DRC, 1 Ghana and 1 Kenya), a pair-wise RST statistic was calculated, indicating the genetic distance between malaria parasites found in those locations. Mapping genetics across the spatial extent of the study area indicates a complex genetic landscape, where relatedness between two proximal sites may be relatively high (RST > 0.64) or low (RST < 0.05), and where distal sites also exhibit both high and low genetic similarity. Mantel’s tests suggest that malaria genetics differ as geographic distances increase. Principal Coordinate Analysis suggests that genetically related samples are not co-located. Barrier analysis reveals no significant barriers to gene flow between locations. Malaria genetics in the DRC have a complex and fragmented landscape. Limited exchange of genes across space is reflected in greater genetic distance between malaria parasites isolated at greater geographic distances. There is, however, evidence for close genetic ties between distally located sample locations, indicating that movement of malaria parasites and flow of genes is being driven by factors other than distance decay. This research demonstrates the contributions that spatial disease ecology and landscape genetics can make to

  1. Genetic structure and evolved malaria resistance in Hawaiian honeycreepers

    USGS Publications Warehouse

    Foster, J.T.; Woodworth, B.L.; Eggert, L.E.; Hart, P.J.; Palmer, D.; Duffy, D.C.; Fleischer, R.C.

    2007-01-01

    Infectious diseases now threaten wildlife populations worldwide but population recovery following local extinction has rarely been observed. In such a case, do resistant individuals recolonize from a central remnant population, or do they spread from small, perhaps overlooked, populations of resistant individuals? Introduced avian malaria (Plasmodium relictum) has devastated low-elevation populations of native birds in Hawaii, but at least one species (Hawaii amakihi, Hemignathus virens) that was greatly reduced at elevations below about 1000 m tolerates malaria and has initiated a remarkable and rapid recovery. We assessed mitochondrial and nuclear DNA markers from amakihi and two other Hawaiian honeycreepers, apapane (Himatione sanguinea) and iiwi (Vestiaria coccinea), at nine primary study sites from 2001 to 2003 to determine the source of re-establishing birds. In addition, we obtained sequences from tissue from amakihi museum study skins (1898 and 1948-49) to assess temporal changes in allele distributions. We found that amakihi in lowland areas are, and have historically been, differentiated from birds at high elevations and had unique alleles retained through time; that is, their genetic signature was not a subset of the genetic variation at higher elevations. We suggest that high disease pressure rapidly selected for resistance to malaria at low elevation, leaving small pockets of resistant birds, and this resistance spread outward from the scattered remnant populations. Low-elevation amakihi are currently isolated from higher elevations (> 1000 m) where disease emergence and transmission rates appear to vary seasonally and annually. In contrast to results from amakihi, no genetic differentiation between elevations was found in apapane and iiwi, indicating that slight variation in genetic or life-history attributes can determine disease resistance and population recovery. Determining the conditions that allow for the development of resistance to disease is

  2. Parkinson disease, 10 years after its genetic revolution: multiple clues to a complex disorder.

    PubMed

    Klein, Christine; Schlossmacher, Michael G

    2007-11-27

    Over the last 10 years, an unprecedented number of scientific reports have been published that relate to the pathogenesis of parkinsonism. Since the discovery in 1997 of the first heritable form of parkinsonism that could be linked to a mutation in a single gene, SNCA, many more genetic leads have followed (Parkin, DJ-1, PINK1, LRRK2, to name a few); these have provided us with many molecular clues to better explore the etiology of parkinsonism and have led to the dismantling of many previously held dogmas about Parkinson disease (PD). Epidemiologic studies have delineated an array of environmental modulators of susceptibility to parkinsonism, which can now be examined in the context of gene expression. Furthermore, in vivo imaging data and postmortem results have generated concepts that greatly expanded our appreciation for the phenotypic spectrum of parkinsonism from its presymptomatic to advanced stages. With this plethora of new information emerged the picture of a complex syndrome that raises many questions: How many forms of classic parkinsonism/Parkinson disease(s) are there? Where does the disease begin? What causes late-onset, "idiopathic" PD? What are the caveats related to genetic testing? What is the role of Lewy bodies? What will be the best disease model to accommodate the now known genetic and environmental contributors to parkinsonism? What will be the ideal markers and targets for earlier diagnosis and cause-directed therapy? In the following article we highlight some of the burning issues surrounding the understanding of classic parkinsonism, a complex puzzle of genes, environment, and an aging host.

  3. Genetic approaches to interfere with malaria transmission by vector mosquitoes

    PubMed Central

    Wang, Sibao; Jacobs-Lorena, Marcelo

    2013-01-01

    Malaria remains one of the world’s most devastating diseases, causing over one million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications. PMID:23395485

  4. Genetic approaches to interfere with malaria transmission by vector mosquitoes.

    PubMed

    Wang, Sibao; Jacobs-Lorena, Marcelo

    2013-03-01

    Malaria remains one of the most devastating diseases worldwide, causing over 1 million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications.

  5. Genetics of chloroquine-resistant malaria: a haplotypic view

    PubMed Central

    Awasthi, Gauri; Das, Aparup

    2013-01-01

    The development and rapid spread of chloroquine resistance (CQR) in Plasmodium falciparum have triggered the identification of several genetic target(s) in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76), are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria. PMID:24402147

  6. [Malaria vectors: from the field to genetics. Research in Africa].

    PubMed

    Fontenille, D; Cohuet, A; Awono-Ambene, P; Kengne, P; Antonio-Nkondjio, C; Wondji, C; Simard, F

    2005-06-01

    Only about 60 Anopheline species transmit malaria among more than 3,000 mosquito species recorded in the world. In Africa, the major vectors are Anopheles gambiae,An. arabiensis, An. funestus, An. nili and An. moucheti. They all belong to species complexes or groups of closely related species that are very difficult to set apart on morphological grounds, but which may have highly variable behaviours and vectorial capacities. Understanding this complexity is of major importance in vector control programs or for implementing any public health intervention program such as drugs or vaccine trials. Among the seven species of the complex,Anopheles gambiaes.s. shows a huge chromosomal polymorphism related to adaptation to specific natural or anthropic environments, from equatorial forested Africa to dry sahelian areas. Recent studies conducted in West and Central Africa suggest an incipient speciation into 2 molecular forms provisionally called M and S. A similar evolutionary phenomenon is observed in An. funestus, in which sympatric populations carrying specific chromosomal paracentric inversions showed restricted gene flow. Distribution of species from An. nili group and An. moucheti complex is restricted to more humid regions of Africa. However in some areas these species play the major role in malaria transmission. Comprehensive knowledge of transmission cycles and of behavioural and underlying genetic heterogeneities that exist within and among natural vector populations will thus benefit the whole area of malaria control and epidemiology. Molecular and genetic studies, as well as in depth monitoring of vector biology, have been recently facilitated by advances in functional and comparative genomics, including recent publication of the nearly complete genome sequence of An. gambiae. Challenge for the next years is to answer to the very simple question: why is an insect a vector?

  7. Network-based gene prediction for Plasmodium falciparum malaria towards genetics-based drug discovery.

    PubMed

    Chen, Yang; Xu, Rong

    2015-01-01

    Malaria is the most deadly parasitic infectious disease. Existing drug treatments have limited efficacy in malaria elimination, and the complex pathogenesis of the disease is not fully understood. Detecting novel malaria-associated genes not only contributes in revealing the disease pathogenesis, but also facilitates discovering new targets for anti-malaria drugs. In this study, we developed a network-based approach to predict malaria-associated genes. We constructed a cross-species network to integrate human-human, parasite-parasite and human-parasite protein interactions. Then we extended the random walk algorithm on this network, and used known malaria genes as the seeds to find novel candidate genes for malaria. We validated our algorithms using 77 known malaria genes: 14 human genes and 63 parasite genes were ranked averagely within top 2% and top 4%, respectively among human and parasite genomes. We also evaluated our method for predicting novel malaria genes using a set of 27 genes with literature supporting evidence. Our approach ranked 12 genes within top 1% and 24 genes within top 5%. In addition, we demonstrated that top-ranked candied genes were enriched for drug targets, and identified commonalities underlying top-ranked malaria genes through pathway analysis. In summary, the candidate malaria-associated genes predicted by our data-driven approach have the potential to guide genetics-based anti-malaria drug discovery.

  8. Network-based gene prediction for Plasmodium falciparum malaria towards genetics-based drug discovery

    PubMed Central

    2015-01-01

    Background Malaria is the most deadly parasitic infectious disease. Existing drug treatments have limited efficacy in malaria elimination, and the complex pathogenesis of the disease is not fully understood. Detecting novel malaria-associated genes not only contributes in revealing the disease pathogenesis, but also facilitates discovering new targets for anti-malaria drugs. Methods In this study, we developed a network-based approach to predict malaria-associated genes. We constructed a cross-species network to integrate human-human, parasite-parasite and human-parasite protein interactions. Then we extended the random walk algorithm on this network, and used known malaria genes as the seeds to find novel candidate genes for malaria. Results We validated our algorithms using 77 known malaria genes: 14 human genes and 63 parasite genes were ranked averagely within top 2% and top 4%, respectively among human and parasite genomes. We also evaluated our method for predicting novel malaria genes using a set of 27 genes with literature supporting evidence. Our approach ranked 12 genes within top 1% and 24 genes within top 5%. In addition, we demonstrated that top-ranked candied genes were enriched for drug targets, and identified commonalities underlying top-ranked malaria genes through pathway analysis. In summary, the candidate malaria-associated genes predicted by our data-driven approach have the potential to guide genetics-based anti-malaria drug discovery. PMID:26099491

  9. Review of genetic diversity in malaria vectors (Culicidae: Anophelinae).

    PubMed

    Loaiza, J R; Bermingham, E; Sanjur, O I; Scott, M E; Bickersmith, S A; Conn, J E

    2012-01-01

    We review previous studies on the genetic diversity of malaria vectors to highlight the major trends in population structure and demographic history. In doing so, we outline key information about molecular markers, sampling strategies and approaches to investigate the causes of genetic structure in Anopheles mosquitoes. Restricted gene flow due to isolation by distance and physical barriers to dispersal may explain the spatial pattern of current genetic diversity in some Anopheles species. Nonetheless, there is noteworthy disagreement among studies, perhaps due to variation in sampling methodologies, choice of molecular markers, and/or analytical approaches. More refined genealogical methods of population analysis allowing for the inclusion of the temporal component of genetic diversity facilitated the evaluation of the contribution of historical demographic processes to genetic structure. A common pattern of past unstable demography (i.e., historical fluctuation in the effective population size) by several Anopheles species, regardless of methodology (DNA markers), mosquito ecology (anthropophilic vs zoophilic), vector status (primary vs secondary) and geographical distribution, suggests that Pleistocene environmental changes were major drivers of divergence at population and species levels worldwide.

  10. Malaria

    MedlinePlus

    ... common?Malaria is a health problem in many tropical and subtropical countries, including portions of Central and ... these countries. If you are traveling to a tropical area or to a country where malaria is ...

  11. [Malaria: from genetic and molecular biology to disease control].

    PubMed

    Ambroise-Thomas, Pierre

    2004-01-01

    The knowledge of the genomic structure of Plasmodium falciparum and of its main vector, Anopheles gambiae, may offer new perspectives for malaria therapy, vaccines or control of mosquito-borne transmission. New targets for future antimalarial drugs were identified, mainly apicoplast (a vestige of a vegetal structure incorporated by the parasite) and several enzymes, particularly proteases. The practical difficulty is now to select a few number of these "promising molecules", probably no more than 3 or 4, for a preclinical and clinical pharmaceutical development. Indeed, several other antimalarial drugs are already under development, and the industrial possibilities for developing new drugs are evidently limited. Many new vaccination targets and antigenic proteins were also identified. According to scientific and industrial limitations, a complete evaluation of these antigens is absolutely necessary to select a few of them for clinical development. For anti-malarial vaccinations, DNA vaccines may offer the most interesting perspectives, with the possibility of simultaneous immunisation against different Plasmodium stages and of an adjuvant effect by adding a gene encoding certain cytokines. In Anopheles gambiae genome, several genes encoding key-proteins (particularly odorant receptors necessary for blood feeding) were identified, as other genes encoding for proteins limiting the sexual development of Plasmodium inside its vector. From a theoretical viewpoint, genetically modified non biting or non transmitting mosquitoes offer new perspectives for the control of malaria transmission, but until now, the preliminary practical attempts gave rather poor results. On the whole, the genomic and proteomic of Plasmodium falciparum and Anopheles gambiae yielded exciting scientific results, but it is still too early and very speculative to imagine their practical applications for the control of malaria.

  12. Malaria.

    ERIC Educational Resources Information Center

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  13. Malaria

    DTIC Science & Technology

    2011-06-01

    appearance of dark urine after an acute attack of falciparum malaria. Other complications include gastroenteritis in children, pulmonary edema, severe...placental malaria on mothers and neonates from Zaire. Z Parasitenkd 1986;72:57-64. 12. Kean BH, Smith JA. Death due to estivo-autumnal malaria: a

  14. Malaria.

    ERIC Educational Resources Information Center

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  15. Malaria

    MedlinePlus

    Malaria is a serious disease caused by a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of death worldwide, but ... at risk. There are four different types of malaria caused by four related parasites. The most deadly ...

  16. Optimal control strategy of malaria vector using genetically modified mosquitoes.

    PubMed

    Rafikov, M; Bevilacqua, L; Wyse, A P P

    2009-06-07

    The development of transgenic mosquitoes that are resistant to diseases may provide a new and effective weapon of diseases control. Such an approach relies on transgenic mosquitoes being able to survive and compete with wild-type populations. These transgenic mosquitoes carry a specific code that inhibits the plasmodium evolution in its organism. It is said that this characteristic is hereditary and consequently the disease fades away after some time. Once transgenic mosquitoes are released, interactions between the two populations and inter-specific mating between the two types of mosquitoes take place. We present a mathematical model that considers the generation overlapping and variable environment factors. Based on this continuous model, the malaria vector control is formulated and solved as an optimal control problem, indicating how genetically modified mosquitoes should be introduced in the environment. Numerical simulations show the effectiveness of the proposed control.

  17. GENETIC ISOLATION WITHIN THE MALARIA MOSQUITO ANOPHELES MELAS

    PubMed Central

    Deitz, Kevin C; Athrey, Giri; Reddy, Michael R; Overgaard, Hans J; Matias, Abrahan; Jawara, Musa; della Torre, Alessandra; Petrarca, Vincenzo; Pinto, Joao; Kiszewski, Anthony; Kengne, Pierre; Costantini, Carlo; Caccone, Adalgisa; Slotman, Michel A

    2014-01-01

    Anopheles melas is a brackish water-breeding member of the An. gambiae complex that is distributed along the coast of West Africa and is a major malaria vector within its range. Because little is known about the population structure of this species, we analyzed 15 microsatellite markers and 1,161 bp of mtDNA in 11 An. melas populations collected throughout its range. Compared to its sibling species An. gambiae, An. melas populations have a high level of genetic differentiation between them, representing its patchy distribution due to its fragmented larval habitat which is associated with mangroves and salt marsh grass. Populations clustered into three distinct groups representing Western Africa, Southern Africa, and Bioko Island populations that appear to be mostly isolated. Fixed differences in the mtDNA are present between all three clusters, and a Bayesian clustering analysis of the microsatellite data found no evidence for migration from mainland to Bioko Island populations, and little migration was evident between the Southern to the Western cluster. Surprisingly, mtDNA divergence between the three An. melas clusters is on par with levels of divergence between other species of the An. gambiae complex, and no support for monophyly was observed in a maximum likelihood phylogenetic analysis. Finally, an Approximate Bayesian Analysis of microsatellite data indicates that Bioko Island An. melas populations were connected to the mainland populations in the past, but became isolated, presumably when sea levels rose after the last glaciation period (≥10,000-11,000 years ago). This study has exposed species level genetic divergence within An. melas, and also has implications for control of this malaria vector. PMID:22882458

  18. Environmental influence on the genetic basis of mosquito resistance to malaria parasites

    PubMed Central

    Lambrechts, Louis; Chavatte, Jean-Marc; Snounou, Georges; Koella, Jacob C

    2006-01-01

    The genetic basis of a host's resistance to parasites has important epidemiological and evolutionary consequences. Understanding this genetic basis can be complicated by non-genetic factors, such as environmental quality, which may influence the expression of genetic resistance and profoundly alter patterns of disease and the host's response to selection. In particular, understanding the environmental influence on the genetic resistance of mosquitoes to malaria gives valuable knowledge concerning the use of malaria-resistant transgenic mosquitoes as a measure of malaria control. We made a step towards this understanding by challenging eight isofemale lines of the malaria vector Anopheles stephensi with the rodent malaria parasite Plasmodium yoelii yoelii and by feeding the mosquitoes with different concentrations of glucose. The isofemale lines differed in infection loads (the numbers of oocysts), corroborating earlier studies showing a genetic basis of resistance. In contrast, the proportion of infected mosquitoes did not differ among lines, suggesting that the genetic component underlying infection load differs from the genetic component underlying infection rate. In addition, the mean infection load and, in particular, its heritable variation in mosquitoes depended on the concentration of glucose, which suggests that the environment affects the expression and the evolution of the mosquitoes' resistance in nature. We found no evidence of genotype-by-environment interactions, i.e. the lines responded similarly to environmental variation. Overall, these results indicate that environmental variation can significantly reduce the importance of genes in determining the resistance of mosquitoes to malaria infection. PMID:16777744

  19. Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth

    PubMed Central

    Commandeur, Arno E.; Styer, Aaron K.; Teixeira, Jose M.

    2015-01-01

    BACKGROUND Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. METHODS A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. RESULTS In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and

  20. Genetically engineered parasites: the solution to designing an effective malaria vaccine?

    PubMed

    Fitchett, Joseph R; Cooke, Mary K

    2010-07-01

    Genetic engineering provides an ingenious method of attenuating Plasmodium falciparum parasites for next generation vaccines. A novel approach stimulates new optimism in the struggle to eliminate the burden of malaria.

  1. Malaria.

    PubMed

    Phillips, Margaret A; Burrows, Jeremy N; Manyando, Christine; van Huijsduijnen, Rob Hooft; Van Voorhis, Wesley C; Wells, Timothy N C

    2017-08-03

    Malaria is caused in humans by five species of single-celled eukaryotic Plasmodium parasites (mainly Plasmodium falciparum and Plasmodium vivax) that are transmitted by the bite of Anopheles spp. mosquitoes. Malaria remains one of the most serious infectious diseases; it threatens nearly half of the world's population and led to hundreds of thousands of deaths in 2015, predominantly among children in Africa. Malaria is managed through a combination of vector control approaches (such as insecticide spraying and the use of insecticide-treated bed nets) and drugs for both treatment and prevention. The widespread use of artemisinin-based combination therapies has contributed to substantial declines in the number of malaria-related deaths; however, the emergence of drug resistance threatens to reverse this progress. Advances in our understanding of the underlying molecular basis of pathogenesis have fuelled the development of new diagnostics, drugs and insecticides. Several new combination therapies are in clinical development that have efficacy against drug-resistant parasites and the potential to be used in single-dose regimens to improve compliance. This ambitious programme to eliminate malaria also includes new approaches that could yield malaria vaccines or novel vector control strategies. However, despite these achievements, a well-coordinated global effort on multiple fronts is needed if malaria elimination is to be achieved.

  2. Population genetic structure of urban malaria vector Anopheles stephensi in India.

    PubMed

    Sharma, Richa; Sharma, Arvind; Kumar, Ashwani; Dube, Madhulika; Gakhar, S K

    2016-04-01

    Malaria is a major public health problem in India because climatic condition and geography of India provide an ideal environment for development of malaria vector. Anopheles stephensi is a major urban malaria vector in India and its control has been hampered by insecticide resistance. In present study population genetic structure of A. stephensi is analyzed at macro geographic level using 13 microsatellite markers. Significantly high genetic differentiation was found in all studied populations with differentiation values (FST) ranging from 0.0398 to 0.1808. The geographic distance was found to be playing a major role in genetic differentiation between different populations. Overall three genetic pools were observed and population of central India was found to be coexisting in two genetic pools. High effective population size (Ne) was found in all the studied populations.

  3. Advances in genetics and genomics: use and limitations in achieving malaria elimination goals

    PubMed Central

    Gunawardena, Sharmini; Karunaweera, Nadira D.

    2015-01-01

    Success of the global research agenda towards eradication of malaria will depend on the development of new tools, including drugs, vaccines, insecticides and diagnostics. Genetic and genomic information now available for the malaria parasites, their mosquito vectors and human host, can be harnessed to both develop these tools and monitor their effectiveness. Here we review and provide specific examples of current technological advances and how these genetic and genomic tools have increased our knowledge of host, parasite and vector biology in relation to malaria elimination and in turn enhanced the potential to reach that goal. We then discuss limitations of these tools and future prospects for the successful achievement of global malaria elimination goals. PMID:25943157

  4. Advances in genetics and genomics: use and limitations in achieving malaria elimination goals.

    PubMed

    Gunawardena, Sharmini; Karunaweera, Nadira D

    2015-05-01

    Success of the global research agenda towards eradication of malaria will depend on the development of new tools, including drugs, vaccines, insecticides and diagnostics. Genetic and genomic information now available for the malaria parasites, their mosquito vectors and human host, can be harnessed to both develop these tools and monitor their effectiveness. Here we review and provide specific examples of current technological advances and how these genetic and genomic tools have increased our knowledge of host, parasite and vector biology in relation to malaria elimination and in turn enhanced the potential to reach that goal. We then discuss limitations of these tools and future prospects for the successful achievement of global malaria elimination goals.

  5. Preventing the spread of malaria and dengue fever using genetically modified mosquitoes.

    PubMed

    James, Anthony A

    2007-01-01

    In this candid interview, Anthony A. James explains how mosquito genetics can be exploited to control malaria and dengue transmission. Population replacement strategy, the idea that transgenic mosquitoes can be released into the wild to control disease transmission, is introduced, as well as the concept of genetic drive and the design criterion for an effective genetic drive system. The ethical considerations of releasing genetically-modified organisms into the wild are also discussed.

  6. Preventing the Spread of Malaria and Dengue Fever Using Genetically Modified Mosquitoes

    PubMed Central

    James, Anthony A.

    2007-01-01

    In this candid interview, Anthony A. James explains how mosquito genetics can be exploited to control malaria and dengue transmission. Population replacement strategy, the idea that transgenic mosquitoes can be released into the wild to control disease transmission, is introduced, as well as the concept of genetic drive and the design criterion for an effective genetic drive system. The ethical considerations of releasing genetically-modified organisms into the wild are also discussed. PMID:18979028

  7. Bottlenecks and Multiple Introductions: Population Genetics of the Vector of Avian Malaria in Hawaii

    DTIC Science & Technology

    2000-01-01

    evolution of vector-mediated parasite-host interactions in general we studied the population genetics of Cx. quinquefasciatus in the Hawaiian Islands...there have been several introductions and to speculate on some processes that may be responsible for the current population genetics of vectors of avian malaria in Hawaii.

  8. Genetic surveillance detects both clonal and epidemic transmission of malaria following enhanced intervention in Senegal.

    PubMed

    Daniels, Rachel; Chang, Hsiao-Han; Séne, Papa Diogoye; Park, Danny C; Neafsey, Daniel E; Schaffner, Stephen F; Hamilton, Elizabeth J; Lukens, Amanda K; Van Tyne, Daria; Mboup, Souleymane; Sabeti, Pardis C; Ndiaye, Daouda; Wirth, Dyann F; Hartl, Daniel L; Volkman, Sarah K

    2013-01-01

    Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs), use of rapid diagnostic tests (RDTs) for malaria detection, and deployment of artemisinin combination therapy (ACT). Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign.

  9. Malaria life cycle intensifies both natural selection and random genetic drift.

    PubMed

    Chang, Hsiao-Han; Moss, Eli L; Park, Daniel J; Ndiaye, Daouda; Mboup, Souleymane; Volkman, Sarah K; Sabeti, Pardis C; Wirth, Dyann F; Neafsey, Daniel E; Hartl, Daniel L

    2013-12-10

    Analysis of genome sequences of 159 isolates of Plasmodium falciparum from Senegal yields an extraordinarily high proportion (26.85%) of protein-coding genes with the ratio of nonsynonymous to synonymous polymorphism greater than one. This proportion is much greater than observed in other organisms. Also unusual is that the site-frequency spectra of synonymous and nonsynonymous polymorphisms are virtually indistinguishable. We hypothesized that the complicated life cycle of malaria parasites might lead to qualitatively different population genetics from that predicted from the classical Wright-Fisher (WF) model, which assumes a single random-mating population with a finite and constant population size in an organism with nonoverlapping generations. This paper summarizes simulation studies of random genetic drift and selection in malaria parasites that take into account their unusual life history. Our results show that random genetic drift in the malaria life cycle is more pronounced than under the WF model. Paradoxically, the efficiency of purifying selection in the malaria life cycle is also greater than under WF, and the relative efficiency of positive selection varies according to conditions. Additionally, the site-frequency spectrum under neutrality is also more skewed toward low-frequency alleles than expected with WF. These results highlight the importance of considering the malaria life cycle when applying existing population genetic tools based on the WF model. The same caveat applies to other species with similarly complex life cycles.

  10. Genetic susceptibility to systemic lupus erythematosus protects against cerebral malaria in mice

    PubMed Central

    Waisberg, Michael; Tarasenko, Tatyana; Vickers, Brandi K.; Scott, Bethany L.; Willcocks, Lisa C.; Molina-Cruz, Alvaro; Pierce, Matthew A.; Huang, Chiung-yu; Torres-Velez, Fernando J.; Smith, Kenneth G. C.; Barillas-Mury, Carolina; Miller, Louis H.; Pierce, Susan K.; Bolland, Silvia

    2011-01-01

    Plasmodium falciparum has exerted tremendous selective pressure on genes that improve survival in severe malarial infections. Systemic lupus erythematosus (SLE) is an autoimmune disease that is six to eight times more prevalent in women of African descent than in women of European descent. Here we provide evidence that a genetic susceptibility to SLE protects against cerebral malaria. Mice that are prone to SLE because of a deficiency in FcγRIIB or overexpression of Toll-like receptor 7 are protected from death caused by cerebral malaria. Protection appears to be by immune mechanisms that allow SLE-prone mice better to control their overall inflammatory responses to parasite infections. These findings suggest that the high prevalence of SLE in women of African descent living outside of Africa may result from the inheritance of genes that are beneficial in the immune control of cerebral malaria but that, in the absence of malaria, contribute to autoimmune disease. PMID:21187399

  11. Malaria.

    PubMed

    Heck, J E

    1991-03-01

    Human malaria is caused by four species of the genus plasmodium. The sexual stage of the parasite occurs in the mosquito and asexual reproduction occurs in man. Symptoms of fever, chills, headache, and myalgia result from the invasion and rupture of erythrocytes. Merozoites are released from erythrocytes and invade other cells, thus propagating the infection. The most vulnerable hosts are nonimmune travelers, young children living in the tropics, and pregnant women. P. falciparum causes the most severe infections because it infects RBCs of all ages and has the propensity to develop resistance to antimalarials. Rapid diagnosis can be made with a malarial smear, and treatment should be initiated promptly. In some regions (Mexico, Central America except Panama, and North Africa) chloroquine phosphate is effective therapy. In subsaharan Africa, South America, and Southeast Asia, chloroquine resistance has become widespread, and other antimalarials are necessary. The primary care physician should have a high index of suspicion for malaria in the traveler returning from the tropics. Malaria should also be suspected in the febrile transfusion recipient and newborns of mothers with malaria.

  12. Longitudinal analysis of Plasmodium falciparum genetic variation in Turbo, Colombia: implications for malaria control and elimination.

    PubMed

    Chenet, Stella M; Taylor, Jesse E; Blair, Silvia; Zuluaga, Lina; Escalante, Ananias A

    2015-09-22

    Malaria programmes estimate changes in prevalence to evaluate their efficacy. In this study, parasite genetic data was used to explore how the demography of the parasite population can inform about the processes driving variation in prevalence. In particular, how changes in treatment and population movement have affected malaria prevalence in an area with seasonal malaria. Samples of Plasmodium falciparum collected over 8 years from a population in Turbo, Colombia were genotyped at nine microsatellite loci and three drug-resistance loci. These data were analysed using several population genetic methods to detect changes in parasite genetic diversity and population structure. In addition, a coalescent-based method was used to estimate substitution rates at the microsatellite loci. The estimated mean microsatellite substitution rates varied between 5.35 × 10(-3) and 3.77 × 10(-2) substitutions/locus/month. Cluster analysis identified six distinct parasite clusters, five of which persisted for the full duration of the study. However, the frequencies of the clusters varied significantly between years, consistent with a small effective population size. Malaria control programmes can detect re-introductions and changes in transmission using rapidly evolving microsatellite loci. In this population, the steadily decreasing diversity and the relatively constant effective population size suggest that an increase in malaria prevalence from 2004 to 2007 was primarily driven by local rather than imported cases.

  13. Genetic characterization of Plectorhinchus mediterraneus yields important clues about genome organization and evolution of multigene families

    PubMed Central

    2012-01-01

    markers have been obtained. Some of these results have not been described before in any other fish species. New clues about the genome organization and evolution of the multigene families are offered in this study. PMID:22545758

  14. Genetics of diabetic nephropathy: are there clues to the understanding of common kidney diseases?

    PubMed

    Conway, B R; Maxwell, A P

    2009-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.

  15. Childhood neuroendocrine tumours: a descriptive study revealing clues for genetic predisposition.

    PubMed

    Diets, I J; Nagtegaal, I D; Loeffen, J; de Blaauw, I; Waanders, E; Hoogerbrugge, N; Jongmans, M C J

    2017-01-17

    Neuroendocrine tumours (NETs) are rare in children and limited data are available. We aimed to specify tumour and patient characteristics and to investigate the role of genetic predisposition in the aetiology of paediatric NETs. Using the Dutch Pathology Registry PALGA, we collected patient- and tumour data of paediatric NETs in the Netherlands between 1991 and 2013 (N=483). The incidence of paediatric NETs in the Netherlands is 5.40 per one million per year. The majority of NETs were appendiceal tumours (N=441;91.3%). Additional surgery in appendiceal NETs was indicated in 89 patients, but performed in only 27 of these patients. Four out of five patients with pancreatic NETs were diagnosed with Von Hippel-Lindau disease (N=2) and Multiple Endocrine Neoplasia type 1 (N=2). In one patient with an appendiceal NET Familial Adenomatous Polyposis was diagnosed. On the basis of second primary tumours or other additional diagnoses, involvement of genetic predisposition was suggestive in several others. We identified a significant number of patients with a confirmed or suspected tumour predisposition syndrome and show that paediatric pancreatic NETs in particular are associated with genetic syndromes. In addition, we conclude that treatment guidelines for appendiceal paediatric NETs need revision and improved implementation.

  16. Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to Plasmodium falciparum.

    PubMed

    Gupta, Himanshu; Chaudhari, Sima; Rai, Ayushi; Bhat, Smitha; Sahu, Pratima K; Hande, Manjunath H; D'Souza, Sydney C; Shashikiran, Umakanth; Satyamoorthy, Kapaettu

    2017-01-01

    Multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to anti-malarial drugs in the population. ABCB1 is one of the well-studied membrane transporter genes that code for the P-glycoprotein (an efflux protein) and whose effect on malaria disease predisposition and susceptibility to drugs remains to be understood. We studied the association of single nucleotide variations in human ABCB1 that influences its function in subjects with uncomplicated and complicated malaria caused by Plasmodium falciparum (Pf). Global DNA methylation and ABCB1 DNA promoter methylation levels were performed along with transcriptional response and protein expression in subjects with malaria and healthy controls. The rs2032582 locus was significantly associated with complicated and combined malaria groups when compared to controls (p < 0.05). Significant DNA methylation difference was noticed between case and control (p < 0.05). In addition, global DNA methylation levels of the host DNA were inversely proportional to parasitemia in individuals with Pf infection. Our study also revealed the correlation between ABCB1 DNA promoter methylation with rs1128503 and rs2032582 polymorphisms in malaria and was related to increased expression of ABCB1 protein levels in complicated malaria group (p < 0.05) when compared to uncomplicated malaria and control groups. The study provides evidence for multiple mechanisms that may regulate the role of host ABCB1 function to mediate aetiology of malaria susceptibility, prognosis and drug response. These may have clinical implications and therapeutic application for various malarial conditions.

  17. Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe

    PubMed Central

    2011-01-01

    Background There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector, Anopheles atroparvus. Levels of population differentiation of An. atroparvus from southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission. Methods Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks. Results Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004 Genetic differentiation (0.202

  18. Standardization in generating and reporting genetically modified rodent malaria parasites: the RMgmDB database.

    PubMed

    Khan, Shahid M; Kroeze, Hans; Franke-Fayard, Blandine; Janse, Chris J

    2013-01-01

    Genetically modified Plasmodium parasites are central gene function reagents in malaria research. The Rodent Malaria genetically modified DataBase (RMgmDB) ( www.pberghei.eu ) is a manually curated Web - based repository that contains information on genetically modified rodent malaria parasites. It provides easy and rapid access to information on the genotype and phenotype of genetically modified mutant and reporter parasites. Here, we provide guidelines for generating and describing rodent malaria parasite mutants. Standardization in describing mutant genotypes and phenotypes is important not only to enhance publication quality but also to facilitate cross-linking and mining data from multiple sources, and should permit information derived from mutant parasites to be used in integrative system biology approaches. We also provide guidelines on how to submit information to RMgmDB on non-published mutants, mutants that do not exhibit a clear phenotype, as well as negative attempts to disrupt/mutate genes. Such information helps to prevent unnecessary duplication of experiments in different laboratories, and can provide indirect evidence that these genes are essential for blood-stage development.

  19. Genetic diversity and gene flow of humans, Plasmodium falciparum, and Anopheles farauti s.s. of Vanuatu: inferred malaria dispersal and implications for malaria control.

    PubMed

    Lum, J K; Kaneko, A; Taleo, G; Amos, M; Reiff, D M

    2007-08-01

    A comparison of the patterns of gene flow within and between islands and the genetic diversities of the three species required for malaria transmission (humans, Plasmodium falciparum, and Anopheles farauti s.s.) within the model island system of Vanuatu, shows that the active dispersal of An. farauti s.s. is responsible for within island movement of parasites. In contrast, since both P. falciparum and An. farauti s.s. populations are largely restricted to islands, movement of parasites between islands is likely due to human transport. Thus, control of vectors is crucial for controlling malaria within islands, while control of human movement is essential to control malaria transmission across the archipelago.

  20. Genetic diversity of Plasmodium falciparum in human malaria cases in Mali.

    PubMed

    Nabet, Cécile; Doumbo, Safiatou; Jeddi, Fakhri; Konaté, Salimata; Manciulli, Tommaso; Fofana, Bakary; L'Ollivier, Coralie; Camara, Aminata; Moore, Sandra; Ranque, Stéphane; Théra, Mahamadou A; Doumbo, Ogobara K; Piarroux, Renaud

    2016-07-11

    In Mali, Plasmodium falciparum malaria is highly endemic and remains stable despite the implementation of various malaria control measures. Understanding P. falciparum population structure variations across the country could provide new insights to guide malaria control programmes. In this study, P. falciparum genetic diversity and population structure in regions of varying patterns of malaria transmission in Mali were analysed. A total of 648 blood isolates adsorbed onto filter papers during population surveillance surveys (December 2012-March 2013, October 2013) in four distinct sites of Mali were screened for the presence of P. falciparum via quantitative PCR (qPCR). Multiple loci variable number of tandem repeats analysis (MLVA) using eight microsatellite markers was then performed on positive qPCR samples. Complete genotypes were then analysed for genetic diversity, genetic differentiation and linkage disequilibrium. Of 156 qPCR-positive samples, complete genotyping of 112 samples was achieved. The parasite populations displayed high genetic diversity (mean He = 0.77), which was consistent with a high level of malaria transmission in Mali. Genetic differentiation was low (FST < 0.02), even between sites located approximately 900 km apart, thereby illustrating marked gene flux amongst parasite populations. The lack of linkage disequilibrium further revealed an absence of local clonal expansion, which was corroborated by the genotype relationship results. In contrast to the stable genetic diversity level observed throughout the country, mean multiplicity of infection increased from north to south (from 1.4 to 2.06) and paralleled malaria transmission levels observed locally. In Mali, the high level of genetic diversity and the pronounced gene flux amongst P. falciparum populations may represent an obstacle to control malaria. Indeed, results suggest that parasite populations are polymorphic enough to adapt to their host and to counteract interventions, such

  1. The Unexplained Female Predominance of Systemic Lupus Erythematosus: Clues from Genetic and Cytokine Studies

    PubMed Central

    Weckerle, Corinna E.

    2010-01-01

    Despite recent progress in the understanding of systemic lupus erythematosus (SLE), the striking 9:1 female to male ratio of disease incidence remains largely unexplained. In addition, peak SLE incidence rates occur during the early reproductive years in women. Studies which illuminate potential causes underlying this sex difference and characteristic onset during the reproductive years have the potential to fundamentally advance our understanding of disease pathogenesis in SLE. Similarly, progress in this area will likely inform human reproductive immunology. Studies of sex hormone function in the immune system are of obvious importance; however, it seems likely that many other types of sex-related genetic and immunological differences will contribute to SLE. In this review, we will focus on recent work in sex-related differences in cytokine pathways and genetics of these pathways as they relate to SLE pathogenesis. It seems quite possible that many of these sex-related differences could be important to reproductive fitness, which may explain the conservation of these immune system features and the observed female predominance of SLE. PMID:20063186

  2. Genetic Continuity in the Franco-Cantabrian Region: New Clues from Autochthonous Mitogenomes

    PubMed Central

    Olivieri, Anna; Behar, Doron M.; Achilli, Alessandro; Torroni, Antonio

    2012-01-01

    Background The Late Glacial Maximum (LGM), ∼20 thousand years ago (kya), is thought to have forced the people inhabiting vast areas of northern and central Europe to retreat to southern regions characterized by milder climatic conditions. Archaeological records indicate that Franco-Cantabria might have been the major source for the re-peopling of Europe at the beginning of the Holocene (11.5 kya). However, genetic evidence is still scarce and has been the focus of an intense debate. Methods/Principal Findings Based on a survey of more than 345,000 partial control region sequences and the analysis of 53 mitochondrial DNA (mtDNA) genomes, we identified an mtDNA lineage, HV4a1a, which most likely arose in the Franco-Cantabrian area about 5.4 kya and remained confined to northern Iberia. Conclusions/Significance The HV4a1a lineage and several of its younger branches reveal for the first time genetic continuity in this region and long-term episodes of isolation. This, in turn, could at least in part explain the unique linguistic and cultural features of the Basque region. PMID:22442672

  3. [Novel approach toward infectious diseases--combating malaria by using genetically engineered mosquitoes].

    PubMed

    Yoshida, Shigeto; Shimada, Yohei; Watanabe, Hiroyuki

    2007-09-01

    Malaria is a devastating disease that kills millions of people every year, yet there has been little progress in controlling this disease. Mosquitoes are obligatory vectors for the disease and this part of the parasite cycle represents a potential weak link in transmission. Therefore, control of parasite development in the mosquito has considerable promise as a new approach in the fight against malaria. In recent year, methods for the genetic modification of mosquitoes have been developed, and effector genes whose products interfere with Plasmodium development in the mosquito are beginning to be identified. Here we review strategies to alter mosquito vector competence and consider issues related to translating this knowledge to field applications.

  4. Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control

    PubMed Central

    2010-01-01

    Background Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. Methods The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Results Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a

  5. Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control.

    PubMed

    Marshall, John M; Touré, Mahamoudou B; Traore, Mohamed M; Famenini, Shannon; Taylor, Charles E

    2010-05-14

    Genetically-modified (GM) mosquitoes have been proposed as part of an integrated vector control strategy for malaria control. Public acceptance is essential prior to field trials, particularly since mosquitoes are a vector of human disease and genetically modified organisms (GMOs) face strong scepticism in developed and developing nations. Despite this, in sub-Saharan Africa, where the GM mosquito effort is primarily directed, very little data is available on perspectives to GMOs. Here, results are presented of a qualitative survey of public attitudes to GM mosquitoes for malaria control in rural and urban areas of Mali, West Africa between the months of October 2008 and June 2009. The sample consisted of 80 individuals - 30 living in rural communities, 30 living in urban suburbs of Bamako, and 20 Western-trained and traditional health professionals working in Bamako and Bandiagara. Questions were asked about the cause of malaria, heredity and selective breeding. This led to questions about genetic alterations, and acceptable conditions for a release of pest-resistant GM corn and malaria-refractory GM mosquitoes. Finally, participants were asked about the decision-making process in their community. Interviews were transcribed and responses were categorized according to general themes. Most participants cited mosquitoes as one of several causes of malaria. The concept of the gene was not widely understood; however selective breeding was understood, allowing limited communication of the concept of genetic modification. Participants were open to a release of pest-resistant GM corn, often wanting to conduct a trial themselves. The concept of a trial was reapplied to GM mosquitoes, although less frequently. Participants wanted to see evidence that GM mosquitoes can reduce malaria prevalence without negative consequences for human health and the environment. For several participants, a mosquito control programme was preferred; however a transgenic release that satisfied

  6. Avian genetic resource banking: can fish embryos yield any clues for bird embryos?

    PubMed

    Hagedorn, M

    2006-02-01

    Cryopreservation of avian germplasm is becoming better understood and more commonly practiced. However, one area that would be of great benefit for genome resource banking is the preservation of avian embryos. Little is know about the cryobiology of avian embryos, and they have never been successfully cryopreserved. However, it is likely that they share many of the challenges of other yolk-filled multicompartmental embryos. For example, the fish embryo has 1) a large overall size, resulting in a low surface-to-volume ratio, which retards water and cryoprotectant efflux/influx; 2) large-sized cells, such as the yolk, which could increase the likelihood of membrane disruption by intracellular ice formation; 3) compartments, such as the blastoderm and yolk, with differing permeability properties; and 4) susceptibility to chilling injury. Both the avian and fish systems share many physical and anatomical properties, and it is predicted that some of the same permeability barriers would exist in both as well. Although the systems are similar, some of the goals, and thus the practices, to protect the genome may be quite different. One of these major goals in avian developmental biology is to produce chicken:chicken transgenic animals, especially those with germ line transmission. Producing efficient germ line transmissions and being able to cryopreserve these transmissions would be extremely beneficial to both basic and agricultural science. This could be accomplished through the cryopreservation of embryonic gonadal tissue followed by grafting into a host. The gonadal/tail-graft system would provide an advantage for cryopreservation because it is small (in comparison with the whole embryo), has fairly uniform tissue, and contains the essential primordial germ line cells capable of recreating the genetic line of interest. Moreover, because the chicken is such a robust model for most other avian species, the cryopreservation of the gonadal/tail-graft may potentially open

  7. Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia

    PubMed Central

    Mohd Abd Razak, Mohd Ridzuan; Sastu, Umi Rubiah; Norahmad, Nor Azrina; Abdul-Karim, Abass; Muhammad, Amirrudin; Muniandy, Prem Kumar; Jelip, Jenarun; Rundi, Christina; Imwong, Mallika; Mudin, Rose Nani; Abdullah, Noor Rain

    2016-01-01

    Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751–800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651–700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P. falciparum populations (0.601, p<0.01). High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0

  8. Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia.

    PubMed

    Mohd Abd Razak, Mohd Ridzuan; Sastu, Umi Rubiah; Norahmad, Nor Azrina; Abdul-Karim, Abass; Muhammad, Amirrudin; Muniandy, Prem Kumar; Jelip, Jenarun; Rundi, Christina; Imwong, Mallika; Mudin, Rose Nani; Abdullah, Noor Rain

    2016-01-01

    Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P. falciparum populations (0.601, p<0.01). High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0

  9. Using evolutionary costs to enhance the efficacy of malaria control via genetically manipulated mosquitoes.

    PubMed

    Koella, Jacob C; Zaghloul, Lamia

    2008-11-01

    An earlier mathematical model exploring the use of genetically manipulated mosquitoes for malaria control suggested that the prevalence of malaria is reduced significantly only if almost all mosquitoes become completely resistant to malaria. Central to the model was the 'cost of resistance': the reduction of a resistant mosquito's evolutionary fitness in comparison with a sensitive one's. Here, we consider the possibility of obtaining more optimistic outcomes by taking into account the epidemiological (in addition to the evolutionary) consequences of a cost of resistance that decreases the life-span of adult mosquitoes (the most relevant parameter for the parasite's epidemiology). There are two main results. First, if despite its cost, resistance is fixed in the population, increasing the cost of resistance decreases the intensity of transmission. However, this epidemiological effect is weak if resistance is effective enough to be considered relevant for control. Second, if the cost of resistance prevents its fixation, increasing it intensifies transmission. Thus, the epidemiological effect of the cost of resistance cannot compensate for the lower frequency of resistant mosquitoes in the population. Overall, our conclusion remains pessimistic: so that genetic manipulation can become a promising method of malaria control, we need techniques that enable almost all mosquitoes to be almost completely resistant to infection.

  10. Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children

    PubMed Central

    Schuldt, Kathrin; Ehmen, Christa; Sievertsen, Juergen; Evans, Jennifer; May, Juergen; Ansong, Daniel; Muntau, Birgit; Ruge, Gerd; Timmann, Christian; Agbenyega, Tsiri; Horstmann, Rolf D.; Thye, Thorsten

    2017-01-01

    In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease. PMID:28104671

  11. Merozoite surface protein-1 genetic diversity in Plasmodium malariae and Plasmodium brasilianum from Brazil.

    PubMed

    Guimarães, Lilian O; Wunderlich, Gerhard; Alves, João M P; Bueno, Marina G; Röhe, Fabio; Catão-Dias, José L; Neves, Amanda; Malafronte, Rosely S; Curado, Izilda; Domingues, Wilson; Kirchgatter, Karin

    2015-11-16

    The merozoite surface protein 1 (MSP1) gene encodes the major surface antigen of invasive forms of the Plasmodium erythrocytic stages and is considered a candidate vaccine antigen against malaria. Due to its polymorphisms, MSP1 is also useful for strain discrimination and consists of a good genetic marker. Sequence diversity in MSP1 has been analyzed in field isolates of three human parasites: P. falciparum, P. vivax, and P. ovale. However, the extent of variation in another human parasite, P. malariae, remains unknown. This parasite shows widespread, uneven distribution in tropical and subtropical regions throughout South America, Asia, and Africa. Interestingly, it is genetically indistinguishable from P. brasilianum, a parasite known to infect New World monkeys in Central and South America. Specific fragments (1 to 5) covering 60 % of the MSP1 gene (mainly the putatively polymorphic regions), were amplified by PCR in isolates of P. malariae and P. brasilianum from different geographic origin and hosts. Sequencing of the PCR-amplified products or cloned PCR fragments was performed and the sequences were used to construct a phylogenetic tree by the maximum likelihood method. Data were computed to give insights into the evolutionary and phylogenetic relationships of these parasites. Except for fragment 4, sequences from all other fragments consisted of unpublished sequences. The most polymorphic gene region was fragment 2, and in samples where this region lacks polymorphism, all other regions are also identical. The low variability of the P. malariae msp1 sequences of these isolates and the identification of the same haplotype in those collected many years apart at different locations is compatible with a low transmission rate. We also found greater diversity among P. brasilianum isolates compared with P. malariae ones. Lastly, the sequences were segregated according to their geographic origins and hosts, showing a strong genetic and geographic structure. Our data

  12. Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission.

    PubMed

    Rice, Benjamin L; Golden, Christopher D; Anjaranirina, Evelin Jean Gasta; Botelho, Carolina Mastella; Volkman, Sarah K; Hartl, Daniel L

    2016-12-20

    Encouraging advances in the control of Plasmodium falciparum malaria have been observed across much of Africa in the past decade. However, regions of high relative prevalence and transmission that remain unaddressed or unrecognized provide a threat to this progress. Difficulties in identifying such localized hotspots include inadequate surveillance, especially in remote regions, and the cost and labor needed to produce direct estimates of transmission. Genetic data can provide a much-needed alternative to such empirical estimates, as the pattern of genetic variation within malaria parasite populations is indicative of the level of local transmission. Here, genetic data were used to provide the first empirical estimates of P. falciparum malaria prevalence and transmission dynamics for the rural, remote Makira region of northeastern Madagascar. Longitudinal surveys of a cohort of 698 total individuals (both sexes, 0-74 years of age) were performed in two communities bordering the Makira Natural Park protected area. Rapid diagnostic tests, with confirmation by molecular methods, were used to estimate P. falciparum prevalence at three seasonal time points separated by 4-month intervals. Genomic loci in a panel of polymorphic, putatively neutral markers were genotyped for 94 P. falciparum infections and used to characterize genetic parameters known to correlate with transmission levels. Overall, 27.8% of individuals tested positive for P. falciparum over the 10-month course of the study, a rate approximately sevenfold higher than the countrywide average for Madagascar. Among those P. falciparum infections, a high level of genotypic diversity and a high frequency of polygenomic infections (68.1%) were observed, providing a pattern consistent with high and stable transmission. Prevalence and genetic diversity data indicate that the Makira region is a hotspot of P. falciparum transmission in Madagascar. This suggests that the area should be highlighted for future

  13. A model for the control of malaria using genetically modified vectors.

    PubMed

    Diaz, H; Ramirez, A A; Olarte, A; Clavijo, C

    2011-05-07

    Recent works have considered the problem of using transgenic mosquitoes to control a malaria epidemic. These insects have been genetically engineered to reduce their capacity to infect humans with malaria parasites. We analyze a model of the mosquito population dynamics when genetically modified individuals are introduced into a wild type population so that the effect of their introduction can be assessed. The model describes the dynamics of gene selection under sexual reproduction in a closed vector population. Our results show that the fitness of the resulting heterozygous population is the key parameter for the success of the invasion, independently of the fitness of homozygous vectors. The vector population dynamics model is then combined with an epidemiological model to study the feasibility of controlling a malaria epidemic. Basic reproductive numbers are calculated for both models, and conditions are obtained for preventing reappearance of the epidemic. Simulations on this model show that it may be possible to reduce or even eradicate the epidemic only if the heterozygous population is better adapted than the wild type. They also show that this can be achieved without completely eliminating the wild type mosquitoes.

  14. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes

    PubMed Central

    Moon, Robert W.; Hall, Joanna; Rangkuti, Farania; Ho, Yung Shwen; Almond, Neil; Mitchell, Graham H.; Pain, Arnab; Holder, Anthony A.; Blackman, Michael J.

    2013-01-01

    Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen. PMID:23267069

  15. Population genetic structure of the malaria vector Anopheles moucheti in south Cameroon forest region.

    PubMed

    Antonio-Nkondjio, Christophe; Ndo, Cyrille; Awono-Ambene, Parfait; Ngassam, Pierre; Fontenille, Didier; Simard, Frédéric

    2007-01-01

    We used recently developed microsatellite DNA markers to explore the population genetic structure of the malaria vector, Anopheles moucheti. Polymorphism at 10 loci was examined to assess level of genetic differentiation between four A. moucheti populations from South Cameroon situated 65-400 km apart. All microsatellite loci were highly polymorphic with a number of distinct alleles per locus ranging from 9 to 17. Fst estimates ranging from 0.0094 to 0.0275 (P < 0.001) were recorded. These results suggest a very low level of genetic differentiation between A. moucheti populations. The recently available microsatellite loci revealed useful markers to assess genetic differentiation between geographical populations of A. moucheti in Cameroon.

  16. Risk of Plasmodium vivax malaria reintroduction in Uzbekistan: genetic characterization of parasites and status of potential malaria vectors in the Surkhandarya region.

    PubMed

    Severini, Carlo; Menegon, Michela; Di Luca, Marco; Abdullaev, Iso; Majori, Giancarlo; Razakov, Shavkat A; Gradoni, Luigi

    2004-10-01

    Plasmodium vivax malaria was eradicated from Uzbekistan in 1961. Due to resurgence of the disease in neighbouring states and massive population migration, there has been an increase of P. vivax malaria, imported from Tajikistan, resulting in a number of indigenous cases being identified in areas bordering that country. A molecular study using the merozoite surface protein 1 (msp-1) gene as a marker was performed on 24 P. vivax genomic isolates from 12 indigenous and 10 imported malaria cases that occurred in the Surkhandarya region during the summer of 2002. Results have shown a significant difference in the frequency of msp-1 types between indigenous and imported isolates, the latter showing greater genetic heterogeneity. An entomological investigation in the area suggested that three Anopheles species, namely A. superpictus, A. pulcherrimus and A. hyrcanus may have a potential role in the endemic transmission of P. vivax.

  17. Alterations in Plasmodium falciparum genetic structure two years after increased malaria control efforts in western Kenya.

    PubMed

    Vardo-Zalik, Anne M; Zhou, Guofa; Zhong, Daibin; Afrane, Yaw A; Githeko, Andrew K; Yan, Guiyun

    2013-01-01

    The impact of malaria intervention measures (insecticide-treated net use and artemisinin combination therapy) on malaria genetics was investigated at two sites in western Kenya: an endemic lowland and an epidemic highland. The genetic structure of the parasite population was assessed by using microsatellites, and the prevalence of drug-resistant mutations was examined by using the polymerase chain reaction-restriction fragment length polymorphism method. Two years after intervention, genetic diversity remained high in both populations. A significant decrease in the prevalence of quintuple mutations conferring resistance to sulfadoxine-pyrimethamine was detected in both populations, but the mutation prevalence at codon 1246 of the Plasmodium falciparum multidrug resistance 1 gene had increased in the highland population. The decrease in sulfadoxine-pyrimethamine-resistant mutants is encouraging, but the increase in P. falciparum multidrug resistance 1 gene mutations is worrisome because these mutations are linked to resistance to other antimalarial drugs. In addition, the high level of genetic diversity observed after intervention suggests transmission is still high in each population.

  18. Genetic diversity of Plasmodium vivax population before elimination of malaria in Hainan Province, China.

    PubMed

    Li, Yu-Chun; Wang, Guang-Ze; Meng, Feng; Zeng, Wen; He, Chang-hua; Hu, Xi-Min; Wang, Shan-Qing

    2015-02-14

    Hainan Province is one of the most severe endemic regions with high transmission of Plasmodium falciparum and Plasmodium vivax in China. However, the incidence of P. falciparum and P. vivax has dropped dramatically since 2007 and a national elimination malaria programme (NEMP) was launched after 2010. To better understand the genetic information on P. vivax population before elimination of malaria in Hainan Province, the extent of genetic diversity of P. vivax isolates in Hainan Province was investigated using four polymorphic genetic markers, including P. vivax merozoite surface proteins 1, 3α, and 3β (pvmsp-1, pvmsp-3α, and pvmsp-3β) and circumsporozoite protein (pvcsp). Isolates of P. vivax (n = 27) from Hainan Province were collected from 2009 to 2010 and pvmsp-1 and pvcsp were analysed by DNA sequencing, respectively. Using polymerase chain reaction-restriction fragment length polymorphism were analysed in pvmsp-3α, and pvmsp-3β. The DNA sequencing analysis on pvmsp1 revealed that there were three allele types: Salvador-1 (Sal-1), Belem and recombinant (R) types. Among them, Sal-1 type was a dominant strain with eight variant subtypes (88.9%), whereas R- (3.7%) and Belem-type strains (7.4%) had one variant subtypes, respectively. All the isolates carried pvcsp with VK210 type accounting for 85.2% (23/27 isolates) and VK247 type accounting for 14.8% (4/27). Only type A and type B alleles were successfully amplified in pvmsp-3α gene, and a high level of polymorphism was observed in pvmsp-3α. Considering pvmsp-3β gene, type A was the predominant type in 17 isolates (63%), whereas type B was dominant in only ten isolates (37%). The present data indicate that there was high degree of genetic diversity among P. vivax population in Hainan Province of China during the pre-elimination stage of malaria, with 26 unique haplotypes observed among 27 samples.

  19. 'Tennessee' Clues

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This false-color image shows the area within 'Endurance Crater,' currently being investigated by the Mars Exploration Rover Opportunity. The rover is inspecting a hole it drilled into a flat rock (center) dubbed 'Tennessee,' which scientists believe may be made up of the same evaporite-rich materials as those found in 'Eagle Crater.'

    The overall geography inside Endurance is more complex than scientists anticipated, with at least three distinct bands of rock visible in front of the rover. Scientists hope to investigate the second and third layers of rock for more clues to Mars' history. This image was taken on sol 133 (June 8, 2004) with the rover's panoramic camera, using the 750-, 530- and 430-nanometer filters.

  20. 'Tennessee' Clues

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This false-color image shows the area within 'Endurance Crater,' currently being investigated by the Mars Exploration Rover Opportunity. The rover is inspecting a hole it drilled into a flat rock (center) dubbed 'Tennessee,' which scientists believe may be made up of the same evaporite-rich materials as those found in 'Eagle Crater.'

    The overall geography inside Endurance is more complex than scientists anticipated, with at least three distinct bands of rock visible in front of the rover. Scientists hope to investigate the second and third layers of rock for more clues to Mars' history. This image was taken on sol 133 (June 8, 2004) with the rover's panoramic camera, using the 750-, 530- and 430-nanometer filters.

  1. Environmental, pharmacological and genetic influences on the spread of drug-resistant malaria.

    PubMed

    Antao, Tiago; Hastings, Ian M

    2011-06-07

    Plasmodium falciparum malaria is subject to artificial selection from antimalarial drugs that select for drug-resistant parasites. We describe and apply a flexible new approach to investigate how epistasis, inbreeding, selection heterogeneity and multiple simultaneous drug deployments interact to influence the spread of drug-resistant malaria. This framework recognizes that different human 'environments' within which treatment may occur (such as semi- and non-immune humans taking full or partial drug courses) influence the genetic interactions between parasite loci involved in resistance. Our model provides an explanation for how the rate of spread varies according to different malaria transmission intensities, why resistance might stabilize at intermediate frequencies and also identifies several factors that influence the decline of resistance after a drug is removed. Results suggest that studies based on clinical outcomes might overestimate the spread of resistant parasites, especially in high-transmission areas. We show that when transmission decreases, prevalence might decrease without a corresponding change in frequency of resistance and that this relationship is heavily influenced by the extent of linkage disequilibrium between loci. This has important consequences on the interpretation of data from areas where control is being successful and suggests that reducing transmission might have less impact on the spread of resistance than previously expected.

  2. The prospect of malaria elimination in the Arabian Peninsula: a population genetic approach.

    PubMed

    Al-Hamidhi, Salama; Mahdy, Mohammed A K; Idris, Mohamed Ahmed; Bin Dajem, Saad M; Al-Sheikh, Adel Ali H; Al-Qahtani, Ahmed; Al-Hashami, Zainab; Al-Farsi, Hissa; Al-Mekhlafi, Abdulsalam M; Saif-Ali, Riyadh; Beja-Pereira, Albano; Babiker, Hamza A

    2014-10-01

    In the Arabian Peninsula malaria control is progressing steadily, backed by adequate logistic and political support. As a result, transmission has been interrupted throughout the region, with exception of limited sites in Yemen and Saudi Arabia. Here we examined Plasmodium falciparum parasites in these sites to assess if the above success has limited diversity and gene flow. We examined 108 P. falciparum isolates in three sites in Yemen (Taiz, Dhamar and Hodeidah) and 91 isolates from Saudi Arabia (Jazan). Nine microsatellites were analyzed for allelic diversity, multi-locus haplotype and inter-population differentiation. Diversity at each locus (unbiased heterozygosity [H]) was relatively lower in Yemen; (Hodeidah, H=0.615, Taiz, H=0.66, Dhamar, H=0.481), compared to Saudi Arabia (Jazan, H=0.76). Microsatellites were distributed widely and private alleles, detected in a single population, were rare. Pairwise comparisons revealed that parasites population in Dhamar was relatively distanced (FST=0.19). However, Taiz (Yemen) (FST=0.065) and Hodeidah (FST=0.107) populations were closer to that in Jazan (Saudi Arabia). Nonetheless, parasites in the four sites can be considered as one population. Although malaria risk in Saudi Arabia has been cut considerably, the extent of diversity and parasite genetic structure are indicative of a large population size. Elimination strategy should target demographic factors that favor parasite dispersal and flow of imported malaria. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Controlling malaria transmission with genetically-engineered, Plasmodium-resistant mosquitoes: milestones in a model system.

    PubMed

    James, A A; Beerntsen, B T; Capurro, M de L; Coates, C J; Coleman, J; Jasinskiene, N; Krettli, A U

    1999-09-01

    We are developing transgenic mosquitoes resistant to malaria parasites to test the hypothesis that genetically-engineered mosquitoes can be used to block the transmission of the parasites. We are developing and testing many of the necessary methodologies with the avian malaria parasite, Plasmodium gallinaceum, and its laboratory vector, Aedes aegypti, in anticipation of engaging the technical challenges presented by the malaria parasite, P. falciparum, and its major African vector, Anopheles gambiae. Transformation technology will be used to insert into the mosquito a synthetic gene for resistance to P. gallinaceum. The resistance gene will consist of a promoter of a mosquito gene controlling the expression of an effector protein that interferes with parasite development and/or infectivity. Mosquito genes whose promoter sequences are capable of sex- and tissue-specific expression of exogenous coding sequences have been identified, and stable transformation of the mosquito has been developed. We now are developing the expressed effector portion of the synthetic gene that will interfere with the transmission of the parasites. Mouse monoclonal antibodies that recognize the circumsporozoite protein of P. gallinaceum block sporozoite invasion of mosquito salivary glands, as well as abrogate the infectivity of sporozoites to a vertebrate host, the chicken, Gallus gallus, and block sporozoite invasion and development in susceptible cell lines in vitro. Using the genes encoding these antibodies, we propose to clone and express single-chain antibody constructs (scFv) that will serve as the effector portion of the gene that interferes with transmission of P. gallinaceum sporozoites.

  4. An Integrated Genetic and Physical Map for the Malaria Vector Anopheles funestus

    PubMed Central

    Wondji, Charles S.; Hunt, Richard H.; Pignatelli, Patricia; Steen, Keith; Coetzee, Maureen; Besansky, Nora; Lobo, Neil; Collins, Frank H.; Hemingway, Janet; Ranson, Hilary

    2005-01-01

    We have constructed a genetic map of the major African malaria vector, Anopheles funestus, using genetic markers segregating in F2 progeny from crosses between two strains colonized from different field sites. Genotyping was performed on 174 progeny from three families using 33 microsatellite markers, a single RFLP, and 15 single nucleotide polymorphism (SNP) loci. Four linkage groups were resolved and these were anchored to chromosomes X and 2 and chromosomal arms 3R and 3L by comparison with a physical map of this species. Five markers were linked to the X chromosome, 16 markers to chromosome 2, and 10 and 11 markers to chromosomal arms 3R and 3L, respectively. This significantly increases the number of chromosomally defined genetic markers for this species and will facilitate the identification of genes controlling epidemiologically important traits such as resistance to insecticides or vector competence. PMID:16143619

  5. Understanding the population genetics of Plasmodium vivax is essential for malaria control and elimination

    PubMed Central

    2012-01-01

    Traditionally, infection with Plasmodium vivax was thought to be benign and self-limiting, however, recent evidence has demonstrated that infection with P. vivax can also result in severe illness and death. Research into P. vivax has been relatively neglected and much remains unknown regarding the biology, pathogenesis and epidemiology of this parasite. One of the fundamental factors governing transmission and immunity is parasite diversity. An understanding of parasite population genetic structure is necessary to understand the epidemiology, diversity, distribution and dynamics of natural P. vivax populations. In addition, studying the population structure of genes under immune selection also enables investigation of the dynamic interplay between transmission and immunity, which is crucial for vaccine development. A lack of knowledge regarding the transmission and spread of P. vivax has been particularly highlighted in areas where malaria control and elimination programmes have made progress in reducing the burden of Plasmodium falciparum, yet P. vivax remains as a substantial obstacle. With malaria elimination back on the global agenda, mapping of global and local P. vivax population structure is essential prior to establishing goals for elimination and the roll-out of interventions. A detailed knowledge of the spatial distribution, transmission and clinical burden of P. vivax is required to act as a benchmark against which control targets can be set and measured. This paper presents an overview of what is known and what is yet to be fully understood regarding P. vivax population genetics, as well as the importance and application of P. vivax population genetics studies. PMID:22233585

  6. A genomic and evolutionary approach reveals non-genetic drug resistance in malaria.

    PubMed

    Herman, Jonathan D; Rice, Daniel P; Ribacke, Ulf; Silterra, Jacob; Deik, Amy A; Moss, Eli L; Broadbent, Kate M; Neafsey, Daniel E; Desai, Michael M; Clish, Clary B; Mazitschek, Ralph; Wirth, Dyann F

    2014-01-01

    Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use.

  7. Chlorine Clues

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This plot shows that levels of the element chlorine rise dramatically in the deeper rocks lining the walls of the crater dubbed 'Endurance.' The data shown here were taken by the Mars Exploration Rover Opportunity's alpha particle X-ray spectrometer at Endurance and 'Eagle Crater,' the site where Opportunity first landed at Meridiani Planum.

    Opportunity has been inching down the walls of Endurance Crater, investigating distinct layers of rock as it goes for clues to Mars' buried past. The various Endurance layers have been informally labeled 'A' through 'F.' Targets within these layers are listed on the graph along with previous targets from Eagle Crater. All the rocks listed here were observed after they had been drilled by the rover's rock abrasion tool.

    The observations indicate that the elements making up the shallow rock layers of Endurance Crater resemble those of Eagle, while the deeper layers of Endurance possess increasingly higher concentrations of the element chlorine.

    Opportunity will continue to roll deeper into Endurance to see if this puzzling trend continues. Scientists hope the new data will help them figure out how the presence of chlorine fits into the history of water at Endurance Crater.

  8. Chlorine Clues

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This plot shows that levels of the element chlorine rise dramatically in the deeper rocks lining the walls of the crater dubbed 'Endurance.' The data shown here were taken by the Mars Exploration Rover Opportunity's alpha particle X-ray spectrometer at Endurance and 'Eagle Crater,' the site where Opportunity first landed at Meridiani Planum.

    Opportunity has been inching down the walls of Endurance Crater, investigating distinct layers of rock as it goes for clues to Mars' buried past. The various Endurance layers have been informally labeled 'A' through 'F.' Targets within these layers are listed on the graph along with previous targets from Eagle Crater. All the rocks listed here were observed after they had been drilled by the rover's rock abrasion tool.

    The observations indicate that the elements making up the shallow rock layers of Endurance Crater resemble those of Eagle, while the deeper layers of Endurance possess increasingly higher concentrations of the element chlorine.

    Opportunity will continue to roll deeper into Endurance to see if this puzzling trend continues. Scientists hope the new data will help them figure out how the presence of chlorine fits into the history of water at Endurance Crater.

  9. Individual genetic diversity and probability of infection by avian malaria parasites in blue tits (Cyanistes caeruleus).

    PubMed

    Ferrer, E S; García-Navas, V; Sanz, J J; Ortego, J

    2014-11-01

    Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations.

  10. Population genetics and drug resistance markers: an essential for malaria surveillance in Pakistan.

    PubMed

    Raza, Afsheen; Beg, Mohammad Asim

    2013-12-01

    Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control.

  11. Bottlenecks and multiple introductions: Population genetics of the vector of avian malaria in Hawaii

    USGS Publications Warehouse

    Fonseca, Dina M.; LaPointe, Dennis A.; Fleischer, Robert C.

    2000-01-01

    Avian malaria has had a profound impact on the demographics and behaviour of Hawaiian forest birds since its vector, Culex quinquefasciatusthe southern house mosquito, was first introduced to Hawaii around 1830. In order to understand the dynamics of the disease in Hawaii and gain insights into the evolution of vector-mediated parasite–host interactions in general we studied the population genetics of Cx. quinquefasciatus in the Hawaiian Islands. We used both microsatellite and mitochondrial loci. Not surprisingly we found that mosquitoes in Midway, a small island in the Western group, are quite distinct from the populations in the main Hawaiian Islands. However, we also found that in general mosquito populations are relatively isolated even among the main islands, in particular between Hawaii (the Big Island) and the remaining Hawaiian Islands. We found evidence of bottlenecks among populations within the Big Island and an excess of alleles in Maui, the site of the original introduction. The mitochondrial diversity was typically low but higher than expected. The current distribution of mitochondrial haplotypes combined with the microsatellite information lead us to conclude that there have been several introductions and to speculate on some processes that may be responsible for the current population genetics of vectors of avian malaria in Hawaii.

  12. Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

    PubMed Central

    2010-01-01

    Background Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)n repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated. Methods Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM) and 80 cases with Plasmodium vivax malaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand. Results The number of (GT)n repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GTn repeats. The genotype of (GT)n repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed. Conclusions Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With

  13. Towards genome-wide experimental genetics in the in vivo malaria model parasite Plasmodium berghei.

    PubMed

    Matz, Joachim M; Kooij, Taco W A

    2015-03-01

    Plasmodium berghei was identified as a parasite of thicket rats (Grammomys dolichurus) and Anopheles dureni mosquitoes in African highland forests. Successful adaptation to a range of rodent and mosquito species established P. berghei as a malaria model parasite. The introduction of stable transfection technology, permitted classical reverse genetics strategies and thus systematic functional profiling of the gene repertoire. In the past 10 years following the publication of the P. berghei genome sequence, many new tools for experimental genetics approaches have been developed and existing ones have been improved. The infection of mice is the principal limitation towards a genome-wide repository of mutant parasite lines. In the past few years, there have been some promising and most welcome developments that allow rapid selection and isolation of recombinant parasites while simultaneously minimising animal usage. Here, we provide an overview of all the currently available tools and methods.

  14. Blindness Clues

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Age-related macular degeneration is the leading cause of blindness in older adults, yet researchers are still in the dark about many of the factors that cause this incurable disease. But new insight from University of Florida (UF) and German researchers about a genetic link between rhesus monkeys with macular degeneration and humans could unlock…

  15. Blindness Clues

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Age-related macular degeneration is the leading cause of blindness in older adults, yet researchers are still in the dark about many of the factors that cause this incurable disease. But new insight from University of Florida (UF) and German researchers about a genetic link between rhesus monkeys with macular degeneration and humans could unlock…

  16. Geographic genetic differentiation of a malaria parasite, Plasmodium mexicanum, and its lizard host, Sceloporus occidentalis.

    PubMed

    Fricke, Jennifer M; Vardo-Zalik, Anne M; Schall, Jos J

    2010-04-01

    Gene flow, and resulting degree of genetic differentiation among populations, will shape geographic genetic patterns and possibly local adaptation of parasites and their hosts. Some studies of Plasmodium falciparum in humans show substantial differentiation of the parasite in locations separated by only a few kilometers, a paradoxical finding for a parasite in a large, mobile host. We examined genetic differentiation of the malaria parasite Plasmodium mexicanum, and its lizard host, Sceloporus occidentalis, at 8 sites in northern California, with the use of variable microsatellite markers for both species. These lizards are small and highly territorial, so we expected local genetic differentiation of both parasite and lizard. Populations of P. mexicanum were found to be differentiated by analysis of 5 markers (F(st) values >0.05-0.10) over distances as short as 230-400 m, and greatly differentiated (F(st) values >0.25) for sites separated by approximately 10 km. In contrast, the lizard host had no, or very low, levels of differentiation for 3 markers, even for sites >40 km distant. Thus, gene flow for the lizard was great, but despite the mobility of the vertebrate host, the parasite was locally genetically distinct. This discrepancy could result if infected lizards move little, but their noninfected relatives were more mobile. Previous studies on the virulence of P. mexicanum for fence lizards support this hypothesis. However, changing prevalence of the parasite, without changes in density of the lizard, could also result in this pattern.

  17. Population genetics of the malaria vector Anopheles aconitus in China and Southeast Asia.

    PubMed

    Chen, Bin; Harbach, Ralph E; Walton, Catherine; He, Zhengbo; Zhong, Daibin; Yan, Guiyun; Butlin, Roger K

    2012-12-01

    Anopheles aconitus is a well-known vector of malaria and is broadly distributed in the Oriental Region, yet there is no information on its population genetic characteristics. In this study, the genetic differentiation among populations was examined using 140 mtDNA COII sequences from 21 sites throughout Southern China, Myanmar, Vietnam, Thailand, Laos and Sri Lanka. The population in Sri Lanka has characteristic rDNA D3 and ITS2, mtDNA COII and ND5 haplotypes, and may be considered a distinct subspecies. Clear genetic structure was observed with highly significant genetic variation present among population groups in Southeast Asia. The greatest genetic diversity exists in Yunnan and Myanmar population groups. All population groups are significantly different from one another in pairwise Fst values, except Northern Thailand with Central Thailand. Mismatch distributions and extremely significant F(s) values suggest that the populations passed through a recent demographic expansion. These patterns are discussed in relation to the likely biogeographic history of the region and compared to other Anopheles species. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Population genetics of the malaria vector Anopheles aconitus in China and Southeast Asia

    PubMed Central

    Chen, Bin; Harbach, Ralph E.; Walton, Catherine; He, Zhengbo; Zhong, Daibin; Yan, Guiyun; Butlin, Roger K.

    2012-01-01

    Anopheles aconitus is a well-known vector of malaria and is broadly distributed in the Oriental Region, yet there is no information on its population genetic characteristics. In this study, the genetic differentiation among populations was examined using 140 mtDNA COII sequences from 21 sites throughout southern China, Myanmar, Vietnam, Thailand, Laos and Sri Lanka. The population in Sri Lanka has characteristic rDNA D3 and ITS2, mtDNA COII and ND5 haplotypes, and may be considered a distinct subspecies. Clear genetic structure was observed with highly significant genetic variation present among population groups in Southeast Asia. The greatest genetic diversity exists in Yunnan and Myanmar population groups. All population groups are significantly different from one another in pairwise Fst values, except northern Thailand with central Thailand. Mismatch distributions and extremely significant Fs values suggest that the populations passed through a recent demographic expansion. These patterns are discussed in relation to the likely biogeographic history of the region and compared to other Anopheles species. PMID:22982161

  19. Genetic polymorphisms associated with sulphadoxine-pyrimethamine drug resistance among Plasmodium falciparum field isolates in malaria endemic areas of Assam.

    PubMed

    Sharma, J; Dutta, P; Khan, S A; Soni, M; Dey, D; Mahanta, J

    2015-01-01

    The emergence of antimalarial drug resistance malaria parasite is widespread in North eastern region of India. During January 2012-December 2013, we conducted active surveillance for detection of antifolate resistance-associated genetic polymorphisms in Plasmodium falciparum malaria parasite from different malaria endemic areas of Assam. A total of 281 field samples were collected from suspected malaria patients of which 106 malaria P. falciparum positive cases were detected in microscopic slide examination. A nested PCR was done for amplification of a 648 bp portion of the dhfr gene and 710 bp portion of the dhps gene. Mutation analysis revealed existence of three different haplotypes of the P. falciparum dhfr gene of which ANRNI was highly prevalent (90%). Triple mutant haplotypes AIRNI (N51I+C59R+S108N) of the dhfr gene associated with pyrimethamine resistance were prevalent in Chirang district of Assam. Whereas, dhps mutation study revealed that triple mutant haplotype AGEAA (S436A+A437G+K540E) associated with Sulphadoxine resistance was found among 26% of P. falciparum field isolates. However, P. falciparum dhfr-dhps two locus mutation analysis showed that there were a total of nine dhfr-dhps genotypes. It was noticed that 93.62% (88/94) isolates had mutations in the sequences of both enzymes, which is an indication of prevalence of high grade of Sulphadoxine - pyrimethamine resistance in P. falciparum malaria parasites in Assam.

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

    PubMed

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

    2016-04-01

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

  1. Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders.

    PubMed

    Kato, T; Iwamoto, K; Kakiuchi, C; Kuratomi, G; Okazaki, Y

    2005-07-01

    Classical twin research focused on differentiating genetic factors from environmental factors by comparing the concordance rate between monozygotic (MZ) and dizygotic twins. On the other hand, recent twin research tries to identify genetic or epigenetic differences between MZ twins discordant for mental disorders. There are a number of reports of MZ twins discordant for genetic disorders caused by genetic or epigenetic differences of known pathogenic genes. In the case of mental disorder research, for which the causative gene has not been established yet, we are trying to identify the 'pathogenic gene' by comprehensive analysis of genetic or epigenetic difference between discordant MZ twins. To date, no compelling evidence suggesting such difference between MZ twins has been reported. However, if the genetic or epigenetic difference responsible for the discordant phenotype is found, it will have impact on the biology of mental disorder, in which few conclusive molecular genetic evidences have been obtained.

  2. Patterns and dynamics of genetic diversity in Plasmodium falciparum: what past human migrations tell us about malaria.

    PubMed

    Mita, Toshihiro; Jombart, Thibaut

    2015-06-01

    Plasmodium falciparum is the main agent of malaria, one of the major human infectious diseases affecting millions of people worldwide. The genetic diversity of P. falciparum populations is an essential factor in the parasite's ability to adapt to changes in its environment, enabling the development of drug resistance and the evasion from the host immune system through antigenic variation. Therefore, characterizing these patterns and understanding the main drivers of the pathogen's genetic diversity can provide useful inputs for informing control strategies. In this paper, we review the pioneering work led by Professor Kazuyuki Tanabe on the genetic diversity of P. falciparum populations. In a first part, we recall basic results from population genetics for quantifying within-population genetic diversity, and discuss the main mechanisms driving this diversity. Then, we show how these approaches have been used for reconstructing the historical spread of malaria worldwide, and how current patterns of genetic diversity suggest that the pathogen followed our ancestors in their journey out of Africa. Because these results are robust to different types of genetic markers, they provide a baseline for predicting the pathogen's diversity in unsampled populations, and some useful elements for predicting vaccine efficacy and informing malaria control strategies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Genetic characterization, distribution and prevalence of avian pox and avian malaria in the Berthelot's pipit (Anthus berthelotii) in Macaronesia.

    PubMed

    Illera, Juan Carlos; Emerson, Brent C; Richardson, David S

    2008-11-01

    Exotic pathogens have been implicated in the decline and extinction of various native-island-bird species. Despite the fact that there is increasing concern about the introduction of diseases in island ecosystems, little is known about parasites in the islands of Macaronesia. We focus on Berthelot's pipit (Anthus berthelotii), an endemic and widespread Macaronesian bird species, using a combination of field studies and molecular techniques to determine: (1) the range and prevalence of avian pox and malaria in Berthelot's pipits throughout the species' distribution, (2) the genetic characterization of both parasites in order to ascertain the level of host specificity. We sampled 447 pipits across the 12 islands inhabited by this species. Overall, 8% of all individuals showed evidence of pox lesions and 16% were infected with avian malaria, respectively. We observed marked differences in the prevalence of parasites among islands both within and between archipelagos. Avian pox prevalence varied between 0-54% within and between archipelagos and avian malaria prevalence varied between 0-64% within and between archipelagos. The diversity of pathogens detected was low: only two genetic lineages of avian malaria and one lineage of avian pox were found to infect the pipit throughout its range. Interestingly, both avian malaria parasites found were Plasmodium spp. that had not been previously reported in the Macaronesian avifauna (but that had been observed in the lesser kestrel Falco naumannii), while the avian pox was a host specific lineage that had previously been reported on two of the Canary Islands.

  4. Various carrier system(s)- mediated genetic vaccination strategies against malaria.

    PubMed

    Tyagi, Rajeev K; Sharma, Pradeep Kumar; Vyas, Suresh P; Mehta, Abhinav

    2008-05-01

    The introduction of vaccine technology has facilitated an unprecedented multiantigen approach to develop an effective vaccine against complex pathogens, such as Plasmodium spp., that cause severe malaria. The capacity of multisubunit DNA vaccines encoding different stage Plasmodium antigens to induce CD8(+) cytotoxic T lymphocytes and IFN-gamma responses in mice, monkeys and humans has been observed. Moreover, genetic vaccination may be multi-immune (i.e., capable of eliciting more than one type of immune response, including cell-mediated and humoral). In the case of malaria parasites, a cytotoxic T-lymphocyte response is categorically needed against the intracellular hepatocyte stage while a humoral response, with antibodies targeted against antigens from all stages of the life cycle, is also needed. Therefore, the key to success for any DNA-based therapy is to design a vector able to serve as a safe and efficient delivery system. This has encouraged the development of nonviral DNA-mediated gene-transfer techniques, such as liposomes, virosomes, microspheres and nanoparticles. Efficient and relatively safe DNA transfection using lipoplexes makes them an appealing alternative to be explored for gene delivery. In addition, liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines, possibly by facilitating uptake of the plasmid by antigen-presenting cells. Another recent technology using cationic lipids has been deployed and has generated substantial interest in this approach to gene transfer. This review comprises various aspects that could be decisive in the formulation of efficient and stable carrier system(s) for the development of malaria vaccines.

  5. The influence of host genetics on erythrocytes and malaria infection: is there therapeutic potential?

    PubMed

    Lelliott, Patrick M; McMorran, Brendan J; Foote, Simon J; Burgio, Gaetan

    2015-07-29

    As parasites, Plasmodium species depend upon their host for survival. During the blood stage of their life-cycle parasites invade and reside within erythrocytes, commandeering host proteins and resources towards their own ends, and dramatically transforming the host cell. Parasites aptly avoid immune detection by minimizing the exposure of parasite proteins and removing themselves from circulation through cytoadherence. Erythrocytic disorders brought on by host genetic mutations can interfere with one or more of these processes, thereby providing a measure of protection against malaria to the host. This review summarizes recent findings regarding the mechanistic aspects of this protection, as mediated through the parasites interaction with abnormal erythrocytes. These novel findings include the reliance of the parasite on the host enzyme ferrochelatase, and the discovery of basigin and CD55 as obligate erythrocyte receptors for parasite invasion. The elucidation of these naturally occurring malaria resistance mechanisms is increasing the understanding of the host-parasite interaction, and as discussed below, is providing new insights into the development of therapies to prevent this disease.

  6. Genetic control of malaria parasite transmission: threshold levels for infection in an avian model system.

    PubMed

    Jasinskiene, Nijole; Coleman, Judy; Ashikyan, Aurora; Salampessy, Michael; Marinotti, Osvaldo; James, Anthony A

    2007-06-01

    Genetic strategies for controlling malaria transmission based on engineering pathogen resistance in Anopheles mosquitoes are being tested in a number of animal models. A key component is the effector molecule and the efficiency with which it reduces parasite transmission. Single-chain antibodies (scFvs) that bind the circumsporozoite protein of the avian parasite, Plasmodium gallinaceum, can reduce mean intensities of sporozoite infection of salivary glands by two to four orders of magnitude in transgenic Aedes aegypti. Significantly, mosquitoes with as few as 20 sporozoites in their salivary glands are infectious for a vertebrate host, Gallus gallus. Although scFvs hold promise as effector molecules, they will have to reduce mean intensities of infection to zero to prevent parasite transmission and disease. We conclude that similar endpoints must be reached with human pathogens if we are to expect an effect on disease transmission.

  7. Imputation-based population genetics analysis of Plasmodium falciparum malaria parasites.

    PubMed

    Samad, Hanif; Coll, Francesc; Preston, Mark D; Ocholla, Harold; Fairhurst, Rick M; Clark, Taane G

    2015-04-01

    Whole-genome sequencing technologies are being increasingly applied to Plasmodium falciparum clinical isolates to identify genetic determinants of malaria pathogenesis. However, genome-wide discovery methods, such as haplotype scans for signatures of natural selection, are hindered by missing genotypes in sequence data. Poor correlation between single nucleotide polymorphisms (SNPs) in the P. falciparum genome complicates efforts to apply established missing-genotype imputation methods that leverage off patterns of linkage disequilibrium (LD). The accuracy of state-of-the-art, LD-based imputation methods (IMPUTE, Beagle) was assessed by measuring allelic r2 for 459 P. falciparum samples from malaria patients in 4 countries: Thailand, Cambodia, Gambia, and Malawi. In restricting our analysis to 86 k high-quality SNPs across the populations, we found that the complete-case analysis was restricted to 21k SNPs (24.5%), despite no single SNP having more than 10% missing genotypes. The accuracy of Beagle in filling in missing genotypes was consistently high across all populations (allelic r2, 0.87-0.96), but the performance of IMPUTE was mixed (allelic r2, 0.34-0.99) depending on reference haplotypes and population. Positive selection analysis using Beagle-imputed haplotypes identified loci involved in resistance to chloroquine (crt) in Thailand, Cambodia, and Gambia, sulfadoxine-pyrimethamine (dhfr, dhps) in Cambodia, and artemisinin (kelch13) in Cambodia. Tajima's D-based analysis identified genes under balancing selection that encode well-characterized vaccine candidates: apical merozoite antigen 1 (ama1) and merozoite surface protein 1 (msp1). In contrast, the complete-case analysis failed to identify any well-validated drug resistance or candidate vaccine loci, except kelch13. In a setting of low LD and modest levels of missing genotypes, using Beagle to impute P. falciparum genotypes is a viable strategy for conducting accurate large-scale population genetics and

  8. NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria

    PubMed Central

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B.; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M. Paula; Coutinho, António; Narum, David L.

    2014-01-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E–04 < P < 7.57E–04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E–05 < P < 7.90E–04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E–4 < P < 4.33E–02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes. PMID:24379293

  9. NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.

    PubMed

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M Paula; Coutinho, António; Narum, David L; Penha-Gonçalves, Carlos

    2014-03-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.

  10. Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria

    PubMed Central

    2008-01-01

    Background The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. PMID:19014596

  11. Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria

    USGS Publications Warehouse

    Eggert, L.S.; Terwilliger, L.A.; Woodworth, B.L.; Hart, P.J.; Palmer, D.; Fleischer, R.C.

    2008-01-01

    Background. The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results. Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion. Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. ?? 2008 Eggert et al; licensee BioMed Central Ltd.

  12. Genetic predisposition of variants in TLR2 and its co-receptors to severe malaria in Odisha, India.

    PubMed

    Panigrahi, Subhendu; Kar, Avishek; Tripathy, Sagnika; Mohapatra, Manoj K; Dhangadamajhi, Gunanidhi

    2016-02-01

    Although the role of TLRs signalling in malaria pathogenesis is well established, contribution of individual TLR to clinical outcome of malaria still remains inconclusive. Given the importance of TLR2 and its co-receptors in recognising distinct structural forms of key malaria toxins and mediating innate immune response, it is essential to delineate their genetic contribution. Variants in TLR1 (I602S) and TLR6 (P249S) were genotyped by PCR-RFLP methods, and TLR2 (I/D) was genotyped by PCR in 200 samples each from uncomplicated malaria (UM) and severe malaria (SM). Further, SM was categorised into its sub-clinical groups (CM and NCSM or SOD and MODS) and analysed. The results showed the PP genotype of TLR6 (P249S) to be significantly more common in UM (P < 0.0001), whereas the 'SS' genotype was the risk factor for SM including its sub-clinical categories. The TLR1 (602S) and TLR2 (D) variants were significantly high in patients with CM; however, negative LD was observed between TLR2 and TLR6 in NCSM and MODS. Haplotype analysis showed significantly high frequency of I-I-S haplotype in all forms of subclinical SM and was associated with low parasite load in SM (P = 0.013). The haplotypes I-D-S and S-I-P were significantly high in SOD and CM, respectively. The TLR6 '249S' variant appeared to be the dominant determinant for genetic predisposition to SM and that its association with either TLR2 'D' or TLR1 '602S' modulates for CM development. The present study opens up several new avenues for their exploration and validation in future studies in different global settings for malaria.

  13. Clues to tRNA Evolution from the Distribution of Class II tRNAs and Serine Codons in the Genetic Code.

    PubMed

    Bernhardt, Harold S

    2016-02-24

    We have previously proposed that tRNA(Gly) was the first tRNA and glycine was the first amino acid incorporated into the genetic code. The next two amino acids incorporated would have been the other two small hydrophilic amino acids serine and aspartic acid, which occurred through the duplication of the tRNA(Gly) sequence, followed by mutation of its anticodon by single C to U transition mutations, possibly through spontaneous deamination. Interestingly, however, tRNA(Ser) has a different structure than most other tRNAs, possessing a long variable arm; because of this tRNA(Ser) is classified as a class II tRNA. Also, serine codons are found not only in the bottom right-hand corner of the genetic code table next to those for glycine and aspartic acid, but also in the top row of the table, next to those for two of the most hydrophobic amino acids, leucine and phenylalanine. In the following, I propose that the class II tRNA structure of tRNA(Ser) and the arrangement of serine codons in the genetic code provide clues to the early evolution of tRNA and the genetic code. In addition, I address Di Giulio's recent criticism of our proposal that tRNA(Gly) was the first tRNA, and discuss how early peptides produced from a restricted amino acid alphabet of glycine, serine and aspartic acid might have possessed proteolytic activity, which is possibly important for the early recycling of amino acid monomers.

  14. Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions.

    PubMed

    Kurose, K; Hoshaw-Woodard, S; Adeyinka, A; Lemeshow, S; Watson, P H; Eng, C

    2001-09-01

    Although numerous studies have reported that high frequencies of loss of heterozygosity (LOH) at various chromosomal arms have been identified in breast cancer, differential LOH in the neoplastic epithelial and surrounding stromal compartments has not been well examined. Using laser capture microdissection, which enables separation of neoplastic epithelium from surrounding stroma, we microdissected each compartment of 41 sporadic invasive adenocarcinomas of the breast. Frequent LOH was identified in both neoplastic epithelial and/or stromal compartments, ranging from 25 to 69% in the neoplastic epithelial cells, and from 17 to 61% in the surrounding stromal cells, respectively. The great majority of markers showed a higher frequency of LOH in the neoplastic epithelial compartment than in the stroma, suggesting that LOH in neoplastic epithelial cells might precede LOH in surrounding stromal cells. Furthermore, we sought to examine pair-wise associations of particular genetic alterations in either epithelial or stromal compartments. Seventeen pairs of markers showed statistically significant associations. We also propose a genetic model of multi-step carcinogenesis for the breast involving the epithelial and stromal compartments and note that genetic alterations occur in the epithelial compartments as the earlier steps followed by LOH in the stromal compartments. Our study strongly suggests that interactions between breast epithelial and stromal compartments might play a critical role in breast carcinogenesis and several genetic alterations in both epithelial and stromal compartments are required for breast tumour growth and progression.

  15. Genetic structure of Plasmodium vivax isolates from two malaria endemic areas in Afghanistan.

    PubMed

    Zakeri, Sedigheh; Safi, Najibullah; Afsharpad, Mandana; Butt, Waqar; Ghasemi, Faezeh; Mehrizi, Akram Abouie; Atta, Hoda; Zamani, Ghasem; Djadid, Navid Dinparast

    2010-01-01

    In this study, the nature and extent of genetic diversity of Plasmodium vivax populations circulating in Afghanistan have been investigated by analyzing three genetic markers: csp, msp-1, and msp-3 alpha. Blood samples (n=202) were collected from patients presenting with vivax malaria from south-western (Herat) and south-eastern (Nangarhar) parts of Afghanistan, and analysed using nested-PCR/RFLP and sequencing methods. Genotyping pvmsp-1 revealed type 1, type 2 and recombinant type 3 allelic variants, with type 1 predominant in parasites in both study areas. The sequence analysis of 57 P. vivax isolates identified a total of 26 distinct alleles. Genotyping pvcsp gene showed that VK210 type (86.6%) is predominant in Afghanistan. Moreover, three major types of the pvmsp-3 alpha locus: type A, type B and type C were distinguished among Afghani isolates. The predominant fragments among Nangarhar and Herat parasites were type A (70.8% and 67.9%, respectively). PCR/RFLP products with Hha I and Alu I were detected 52 and 38 distinct variants among Nangarhar and Herat isolates, respectively. These results strongly indicate that the P. vivax populations in Afghanistan are highly diverse.

  16. Environmental Mapping of Paracoccidioides spp. in Brazil Reveals New Clues into Genetic Diversity, Biogeography and Wild Host Association

    PubMed Central

    Arantes, Thales Domingos; Theodoro, Raquel Cordeiro; Teixeira, Marcus de Melo; Bosco, Sandra de Moraes Gimenes; Bagagli, Eduardo

    2016-01-01

    Background Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiological agents of Paracoccidioidomycosis (PCM), and are easily isolated from human patients. However, due to human migration and a long latency period, clinical isolates do not reflect the spatial distribution of these pathogens. Molecular detection of P. brasiliensis and P. lutzii from soil, as well as their isolation from wild animals such as armadillos, are important for monitoring their environmental and geographical distribution. This study aimed to detect and, for the first time, evaluate the genetic diversity of P. brasiliensis and P. lutzii for Paracoccidioidomycosis in endemic and non-endemic areas of the environment, by using Nested PCR and in situ hybridization techniques. Methods/Principal Findings Aerosol (n = 16) and soil (n = 34) samples from armadillo burrows, as well as armadillos (n = 7) were collected in endemic and non-endemic areas of PCM in the Southeastern, Midwestern and Northern regions of Brazil. Both P. brasiliensis and P. lutzii were detected in soil (67.5%) and aerosols (81%) by PCR of Internal Transcribed Spacer (ITS) region (60%), and also by in situ hybridization (83%). Fungal isolation from armadillo tissues was not possible. Sequences from both species of P. brasiliensis and P. lutzii were detected in all regions. In addition, we identified genetic Paracoccidioides variants in soil and aerosol samples which have never been reported before in clinical or armadillo samples, suggesting greater genetic variability in the environment than in vertebrate hosts. Conclusions/Significance Data may reflect the actual occurrence of Paracoccidioides species in their saprobic habitat, despite their absence/non-detection in seven armadillos evaluated in regions with high prevalence of PCM infection by P. lutzii. These results may indicate a possible ecological difference between P. brasiliensis and P. lutzii concerning their wild hosts. PMID:27045486

  17. Environmental Mapping of Paracoccidioides spp. in Brazil Reveals New Clues into Genetic Diversity, Biogeography and Wild Host Association.

    PubMed

    Arantes, Thales Domingos; Theodoro, Raquel Cordeiro; Teixeira, Marcus de Melo; Bosco, Sandra de Moraes Gimenes; Bagagli, Eduardo

    2016-04-01

    Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiological agents of Paracoccidioidomycosis (PCM), and are easily isolated from human patients. However, due to human migration and a long latency period, clinical isolates do not reflect the spatial distribution of these pathogens. Molecular detection of P. brasiliensis and P. lutzii from soil, as well as their isolation from wild animals such as armadillos, are important for monitoring their environmental and geographical distribution. This study aimed to detect and, for the first time, evaluate the genetic diversity of P. brasiliensis and P. lutzii for Paracoccidioidomycosis in endemic and non-endemic areas of the environment, by using Nested PCR and in situ hybridization techniques. Aerosol (n = 16) and soil (n = 34) samples from armadillo burrows, as well as armadillos (n = 7) were collected in endemic and non-endemic areas of PCM in the Southeastern, Midwestern and Northern regions of Brazil. Both P. brasiliensis and P. lutzii were detected in soil (67.5%) and aerosols (81%) by PCR of Internal Transcribed Spacer (ITS) region (60%), and also by in situ hybridization (83%). Fungal isolation from armadillo tissues was not possible. Sequences from both species of P. brasiliensis and P. lutzii were detected in all regions. In addition, we identified genetic Paracoccidioides variants in soil and aerosol samples which have never been reported before in clinical or armadillo samples, suggesting greater genetic variability in the environment than in vertebrate hosts. Data may reflect the actual occurrence of Paracoccidioides species in their saprobic habitat, despite their absence/non-detection in seven armadillos evaluated in regions with high prevalence of PCM infection by P. lutzii. These results may indicate a possible ecological difference between P. brasiliensis and P. lutzii concerning their wild hosts.

  18. Vaccines against malaria.

    PubMed

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease.

  19. Clues about the genetic basis of adaptation emerge from comparing the proteomes of two Ostreococcus ecotypes (Chlorophyta, Prasinophyceae).

    PubMed

    Jancek, Séverine; Gourbière, Sébastien; Moreau, Hervé; Piganeau, Gwenaël

    2008-11-01

    We compared the proteomes of two picoplanktonic Ostreococcus unicellular green algal ecotypes to analyze the genetic basis of their adaptation with their ecological niches. We first investigated the function of the species-specific genes using Gene Ontology databases and similarity searches. Although most species-specific genes had no known function, we identified several species-specific functions involved in various cellular processes, which could be critical for environmental adaptations. Additionally, we investigated the rate of evolution of orthologous genes and its distribution across chromosomes. We show that faster evolving genes encode significantly more membrane or excreted proteins, consistent with the notion that selection acts on cell surface modifications that is driven by selection for resistance to viruses and grazers, keystone actors of phytoplankton evolution. The relationship between GC content and chromosome length also suggests that both strains have experienced recombination since their divergence and that lack of recombination on the two outlier chromosomes could explain part of their peculiar genomic features, including higher rates of evolution.

  20. Female and Male Perspectives on the Neolithic Transition in Europe: Clues from Ancient and Modern Genetic Data

    PubMed Central

    Rasteiro, Rita; Chikhi, Lounès

    2013-01-01

    The arrival of agriculture into Europe during the Neolithic transition brought a significant shift in human lifestyle and subsistence. However, the conditions under which the spread of the new culture and technologies occurred are still debated. Similarly, the roles played by women and men during the Neolithic transition are not well understood, probably due to the fact that mitochondrial DNA (mtDNA) and Y chromosome (NRY) data are usually studied independently rather than within the same statistical framework. Here, we applied an integrative approach, using different model-based inferential techniques, to analyse published datasets from contemporary and ancient European populations. By integrating mtDNA and NRY data into the same admixture approach, we show that both males and females underwent the same admixture history and both support the demic diffusion model of Ammerman and Cavalli-Sforza. Similarly, the patterns of genetic diversity found in extant and ancient populations demonstrate that both modern and ancient mtDNA support the demic diffusion model. They also show that population structure and differential growth between farmers and hunter-gatherers are necessary to explain both types of data. However, we also found some differences between male and female markers, suggesting that the female effective population size was larger than that of the males, probably due to different demographic histories. We argue that these differences are most probably related to the various shifts in cultural practices and lifestyles that followed the Neolithic Transition, such as sedentism, the shift from polygyny to monogamy or the increase of patrilocality. PMID:23613761

  1. High prevalence and genetic diversity of Plasmodium malariae and no evidence of Plasmodium knowlesi in Bangladesh.

    PubMed

    Fuehrer, Hans-Peter; Swoboda, Paul; Harl, Josef; Starzengruber, Peter; Habler, Verena Elisabeth; Bloeschl, Ingrid; Haque, Rashidul; Matt, Julia; Khan, Wasif Ali; Noedl, Harald

    2014-04-01

    Although the prevalence of malaria remains high in parts of Bangladesh, there continues to be a substantial shortage of information regarding the less common malaria parasites such as Plasmodium malariae or Plasmodium knowlesi. Recent studies indicate that P. malariae may be extremely rare, and so far, there are no data on the presence (or absence) of P. knowlesi in southeastern Bangladesh. Genus- and species-specific nested polymerase chain reaction (PCR) analysis of the small subunit ribosomal RNA gene was performed to assess the presence and prevalence of P. malariae and P. knowlesi in 2,246 samples originating from asymptomatic and febrile participants of a cross-sectional and a febrile illnesses study in the Chittagong Hill Tracts in southeastern Bangladesh. P. malariae was detected in 60 samples (2.7%) corresponding to 8% of the 746 samples giving positive PCR results for Plasmodium sp., mainly because of the high prevalence (9.5%) among asymptomatic study participants testing positive for malaria. Symptomatic cases were more common (4.3% of all symptomatic malaria cases) during the dry season. Parasitemias were low (1,120-2,560/μl in symptomatic and 120-520/μl in asymptomatic carriers). Symptomatic patients presented mild to moderate symptoms like fever, chills, headache, dizziness, fatigue and myalgia.Although both the intermediate as well as the definite host are known to be endemic in southeastern Bangladesh, no evidence for the presence of P. knowlesi was found. We conclude that the role of P. malariae is highly underestimated in rural Bangladesh with major implications for malaria control and elimination strategies.

  2. Cryptic Genetic Diversity within the Anopheles nili group of Malaria Vectors in the Equatorial Forest Area of Cameroon (Central Africa)

    PubMed Central

    Ndo, Cyrille; Simard, Frédéric; Kengne, Pierre; Awono-Ambene, Parfait; Morlais, Isabelle; Sharakhov, Igor; Fontenille, Didier; Antonio-Nkondjio, Christophe

    2013-01-01

    Background The Anopheles nili group of mosquitoes includes important vectors of human malaria in equatorial forest and humid savannah regions of sub-Saharan Africa. However, it remains largely understudied, and data on its populations’ bionomics and genetic structure are crucially lacking. Here, we used a combination of nuclear (i.e. microsatellite and ribosomal DNA) and mitochondrial DNA markers to explore and compare the level of genetic polymorphism and divergence among populations and species of the group in the savannah and forested areas of Cameroon, Central Africa. Principal Findings All the markers provided support for the current classification within the An. nili group. However, they revealed high genetic heterogeneity within An. nili s.s. in deep equatorial forest environment. Nuclear markers showed the species to be composed of five highly divergent genetic lineages that differed by 1.8 to 12.9% of their Internal Transcribed Spacer 2 (ITS2) sequences, implying approximate divergence time of 0.82 to 5.86 million years. However, mitochondrial data only detected three major subdivisions, suggesting different evolutionary histories of the markers. Conclusions/Significance This study enlightened additional cryptic genetic diversity within An. nili s.s. in the deep equatorial forest environment of South Cameroon, reflecting a complex demographic history for this major vector of malaria in this environment. These preliminary results should be complemented by further studies which will shed light on the distribution, epidemiological importance and evolutionary history of this species group in the African rainforest, providing opportunities for in-depth comparative studies of local adaptation and speciation in major African malaria vectors. PMID:23516565

  3. Cryptic genetic diversity within the Anopheles nili group of malaria vectors in the equatorial forest area of Cameroon (Central Africa).

    PubMed

    Ndo, Cyrille; Simard, Frédéric; Kengne, Pierre; Awono-Ambene, Parfait; Morlais, Isabelle; Sharakhov, Igor; Fontenille, Didier; Antonio-Nkondjio, Christophe

    2013-01-01

    The Anopheles nili group of mosquitoes includes important vectors of human malaria in equatorial forest and humid savannah regions of sub-Saharan Africa. However, it remains largely understudied, and data on its populations' bionomics and genetic structure are crucially lacking. Here, we used a combination of nuclear (i.e. microsatellite and ribosomal DNA) and mitochondrial DNA markers to explore and compare the level of genetic polymorphism and divergence among populations and species of the group in the savannah and forested areas of Cameroon, Central Africa. All the markers provided support for the current classification within the An. nili group. However, they revealed high genetic heterogeneity within An. nili s.s. in deep equatorial forest environment. Nuclear markers showed the species to be composed of five highly divergent genetic lineages that differed by 1.8 to 12.9% of their Internal Transcribed Spacer 2 (ITS2) sequences, implying approximate divergence time of 0.82 to 5.86 million years. However, mitochondrial data only detected three major subdivisions, suggesting different evolutionary histories of the markers. This study enlightened additional cryptic genetic diversity within An. nili s.s. in the deep equatorial forest environment of South Cameroon, reflecting a complex demographic history for this major vector of malaria in this environment. These preliminary results should be complemented by further studies which will shed light on the distribution, epidemiological importance and evolutionary history of this species group in the African rainforest, providing opportunities for in-depth comparative studies of local adaptation and speciation in major African malaria vectors.

  4. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

    PubMed Central

    Hart, Robert J.; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S.; Ben Mamoun, Choukri; Aly, Ahmed S. I.

    2016-01-01

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes. PMID:27644319

  5. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.

    PubMed

    Hart, Robert J; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S; Ben Mamoun, Choukri; Aly, Ahmed S I

    2016-09-20

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.

  6. Microgeographic genetic variation of the malaria vector Anopheles darlingi root (Diptera: Culicidae) from Cordoba and Antioquia, Colombia.

    PubMed

    Gutiérrez, Lina A; Gómez, Giovan F; González, John J; Castro, Martha I; Luckhart, Shirley; Conn, Jan E; Correa, Margarita M

    2010-07-01

    Anopheles darlingi is an important vector of Plasmodium spp. in several malaria-endemic regions of Colombia. This study was conducted to test genetic variation of An. darlingi at a microgeographic scale (approximately 100 km) from localities in Córdoba and Antioquia states, in western Colombia, to better understand the potential contribution of population genetics to local malaria control programs. Microsatellite loci: nuclear white and cytochrome oxidase subunit I (COI) gene sequences were analyzed. The northern white gene lineage was exclusively distributed in Córdoba and Antioquia and shared COI haplotypes were highly represented in mosquitoes from both states. COI analyses showed these An. darlingi are genetically closer to Central American populations than southern South American populations. Overall microsatellites and COI analysis showed low to moderate genetic differentiation among populations in northwestern Colombia. Given the existence of high gene flow between An. darlingi populations of Córdoba and Antioquia, integrated vector control strategies could be developed in this region of Colombia.

  7. Microgeographic Genetic Variation of the Malaria Vector Anopheles darlingi Root (Diptera: Culicidae) from Córdoba and Antioquia, Colombia

    PubMed Central

    Gutiérrez, Lina A.; Gómez, Giovan F.; González, John J.; Castro, Martha I.; Luckhart, Shirley; Conn, Jan E.; Correa, Margarita M.

    2010-01-01

    Anopheles darlingi is an important vector of Plasmodium spp. in several malaria-endemic regions of Colombia. This study was conducted to test genetic variation of An. darlingi at a microgeographic scale (approximately 100 km) from localities in Córdoba and Antioquia states, in western Colombia, to better understand the potential contribution of population genetics to local malaria control programs. Microsatellite loci: nuclear white and cytochrome oxidase subunit I (COI) gene sequences were analyzed. The northern white gene lineage was exclusively distributed in Córdoba and Antioquia and shared COI haplotypes were highly represented in mosquitoes from both states. COI analyses showed these An. darlingi are genetically closer to Central American populations than southern South American populations. Overall microsatellites and COI analysis showed low to moderate genetic differentiation among populations in northwestern Colombia. Given the existence of high gene flow between An. darlingi populations of Córdoba and Antioquia, integrated vector control strategies could be developed in this region of Colombia. PMID:20595475

  8. Genetic characterization of uniparental lineages in populations from Southwest Iberia with past malaria endemicity.

    PubMed

    Pereira, Vânia; Gomes, Verónica; Amorim, António; Gusmão, Leonor; João Prata, Maria

    2010-01-01

    Malaria endemicity in Southwest Iberia afforded conditions for an increase of sickle cell disease (SCD), which in the region follows a clinal pattern toward the south, where foci of high prevalence were found. SCD distribution is associated with specific geographical areas, and therefore, its introduction into Iberia may be related to the migration of different populations. We have analyzed the variation of uniparental markers in Portuguese populations with high frequency of SCD--Coruche, Pias, and Alcacer do Sal--to evaluate if their present-day pattern of neutral diversity could provide evidence about people inhabiting the area over different time periods. Two hundred and eighty-five individuals were sampled in Coruche, Pias, and Alcacer do Sal. All were analyzed for the control region of mitochondrial DNA (mtDNA); males were additionally examined for Y-chromosome markers. Results were then compared with data from other Portuguese and non-Portuguese populations. In Coruche, the genetic profile was similar to the profile usually found in Portugal. In Alcacer do Sal, the frequency of sub-Saharan mtDNA L lineages was the highest ever reported (22%) in Europe. In Pias, mtDNA diversity revealed higher frequencies of Mediterranean haplogroups I, J, and T than usually found in surrounding populations. The presence of Sub-Saharan maternal lineages in Alcacer do Sal is likely associated with the influx of African slaves between the 15th and 19th centuries, whereas in Pias, the Mediterranean influence might be traced to ancient contacts with Greeks, Phoenicians, and Carthaginians, who established important trading networks in southern Iberia.

  9. Genetic analysis in mice identifies cysteamine as a novel partner for artemisinin in the treatment of malaria.

    PubMed

    Min-Oo, Gundula; Gros, Philippe

    2011-08-01

    Malaria continues to be a serious threat to global health. The malaria problem is compounded by the absence of an efficacious vaccine and widespread drug resistance in the Plasmodium malarial parasite. The host factors and parasite virulence determinants that regulate early response to infection and subsequent onset of protective immunity are poorly understood. The molecular characterization of this early host:pathogen interface may identify novel targets for prophylactic or therapeutic intervention. Genetic analyses in mouse model of malaria show that inactivation of the enzyme pantetheinase (Char9 locus) causes susceptibility to blood-stage infection. The pantetheinase product cysteamine is an inexpensive and non-toxic aminothiol that is approved for lifelong clinical management of nephropathic cystinosis. In mouse models of infection, cysteamine not only displays anti-malarial activity of its own, but also dramatically potentiates the anti-malarial activity of artemisinin, at doses currently used for the clinical management of cystinosis. Therefore, the inclusion of cysteamine in current artemisinin combination therapies may significantly increase efficacy and may also prove effective against emerging artemisinin-resistant human Plasmodium parasite.

  10. Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

    PubMed Central

    Mendonça, Vitor R. R.; Luz, Nívea F.; Santos, Nadja J. G.; Borges, Valéria M.; Gonçalves, Marilda S.; Andrade, Bruno B.

    2012-01-01

    Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria. PMID:22290142

  11. Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria.

    PubMed

    Mendonça, Vitor R R; Luz, Nívea F; Santos, Nadja J G; Borges, Valéria M; Gonçalves, Marilda S; Andrade, Bruno B; Barral-Netto, Manoel

    2012-04-01

    Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.

  12. PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS.

    PubMed

    Domingues, Wilson; Kanunfre, Kelly Aparecida; Rodrigues, Jonatas Cristian; Teixeira, Leandro Emidio; Yamamoto, Lidia; Okay, Thelma Suely

    2016-01-01

    Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation.

  13. PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS

    PubMed Central

    DOMINGUES, Wilson; KANUNFRE, Kelly Aparecida; RODRIGUES, Jonatas Cristian; TEIXEIRA, Leandro Emidio; YAMAMOTO, Lidia; OKAY, Thelma Suely

    2016-01-01

    Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation. PMID:27074324

  14. Clues to the Past

    ERIC Educational Resources Information Center

    Weaver, Julie K.

    2010-01-01

    Students love a mystery. So what do America's most majestic bird, a bag of habitat clues, and a soft-shelled egg have in common? This easy-to-do inquiry activity engages students as they connect clues to problem-solve how the bald eagle reached the brink of extinction in the 1960s in the lower 48 states. It was designed to give students an…

  15. Clues to the Past

    ERIC Educational Resources Information Center

    Weaver, Julie K.

    2010-01-01

    Students love a mystery. So what do America's most majestic bird, a bag of habitat clues, and a soft-shelled egg have in common? This easy-to-do inquiry activity engages students as they connect clues to problem-solve how the bald eagle reached the brink of extinction in the 1960s in the lower 48 states. It was designed to give students an…

  16. Glucose-6-phosphate dehydrogenase deficiency prevalence and genetic variants in malaria endemic areas of Colombia.

    PubMed

    Valencia, Sócrates Herrera; Ocampo, Iván Darío; Arce-Plata, María Isabel; Recht, Judith; Arévalo-Herrera, Myriam

    2016-05-26

    Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme involved in prevention of cellular oxidative damage, particularly protecting erythrocytes from haemolysis. An estimated 400 million people present variable degrees of inherited G6PD deficiency (G6PDd) which puts them at risk for developing haemolysis triggered by several risk factors including multiple drugs and certain foods. Primaquine (PQ) is a widely used anti-malarial drug that can trigger haemolysis in individuals with G6PDd. Intensification of malaria control programmes worldwide and particularly malaria elimination planning in some regions recommend a more extensive use of PQ and related drugs in populations with different G6PDd prevalence. This a preliminary study to assess the prevalence of G6PDd in representative malaria endemic areas of Colombia by measuring G6PD phonotype and genotypes. Volunteers (n = 426) from four malaria endemic areas in Colombia (Buenaventura, Tumaco, Tierralta and Quibdo) were enrolled. Blood samples were drawn to evaluate G6PD enzymatic activity by using a quantitative G6PD test and a subset of samples was analysed by PCR-RFLP to determine the frequency of the three most common G6PD genotypic variants: A-, A+ and Mediterranean. A total of 28 individuals (6.56 %) displayed either severe or intermediate G6PDd. The highest prevalence (3.51 %) was in Buenaventura, whereas G6PDd prevalence was lower (<1 %) in Tierralta and Quibdo. G6PD A alleles were the most frequent (15.23 %) particularly in Buenaventura and Tumaco. Overall, a high frequency of G6PD A- genotype, followed by A+ genotype was found in the analysed population. G6PDd based on enzymatic activity as well as G6PD A allelic variants were found in malaria-endemic populations on the Pacific coast of Colombia, where most of malaria cases are caused by Plasmodium vivax infections. These infections are treated for 14 days with PQ, however there are no official reports of PQ-induced haemolytic crises. Further

  17. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

    PubMed Central

    2010-01-01

    Background Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum. Results A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina® Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme. Conclusions This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations. PMID:20846421

  18. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites.

    PubMed

    Hunt, Paul; Martinelli, Axel; Modrzynska, Katarzyna; Borges, Sofia; Creasey, Alison; Rodrigues, Louise; Beraldi, Dario; Loewe, Laurence; Fawcett, Richard; Kumar, Sujai; Thomson, Marian; Trivedi, Urmi; Otto, Thomas D; Pain, Arnab; Blaxter, Mark; Cravo, Pedro

    2010-09-16

    Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum. A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (Illumina Solexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme. This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations.

  19. Towards genetic manipulation of wild mosquito populations to combat malaria: advances and challenges.

    PubMed

    Riehle, Michael A; Srinivasan, Prakash; Moreira, Cristina K; Jacobs-Lorena, Marcelo

    2003-11-01

    Malaria kills millions of people every year, yet there has been little progress in controlling this disease. For transmission to occur, the malaria parasite has to complete a complex developmental cycle in the mosquito. The mosquito is therefore a potential weak link in malaria transmission, and generating mosquito populations that are refractory to the parasite is a potential means of controlling the disease. There has been considerable progress over the last decade towards developing the tools for creating a refractory mosquito. Accomplishments include germline transformation of several important mosquito vectors, the completed genomes of the mosquito Anopheles gambiae and the malaria parasite Plasmodium falciparum, and the identification of promoters and effector genes that confer resistance in the mosquito. These tools have provided researchers with the ability to engineer a refractory mosquito vector, but there are fundamental gaps in our knowledge of how to transfer this technology safely and effectively into field populations. This review considers strategies for interfering with Plasmodium development in the mosquito, together with issues related to the transfer of laboratory-acquired knowledge to the field, such as minimization of transgene fitness load to the mosquito, driving genes through populations, avoiding the selection of resistant strains, and how to produce and release populations of males only.

  20. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine

    PubMed Central

    Griggs, A.; Lievens, M.; Abdulla, S.; Adjei, S.; Agbenyega, T.; Agnandji, S.T.; Aide, P.; Anderson, S.; Ansong, D.; Aponte, J.J.; Asante, K.P.; Bejon, P.; Birkett, A.J.; Bruls, M.; Connolly, K.M.; D’Alessandro, U.; Dobaño, C.; Gesase, S.; Greenwood, B.; Grimsby, J.; Tinto, H.; Hamel, M.J.; Hoffman, I.; Kamthunzi, P.; Kariuki, S.; Kremsner, P.G.; Leach, A.; Lell, B.; Lennon, N.J.; Lusingu, J.; Marsh, K.; Martinson, F.; Molel, J.T.; Moss, E.L.; Njuguna, P.; Ockenhouse, C.F.; Ogutu, B. Ragama; Otieno, W.; Otieno, L.; Otieno, K.; Owusu-Agyei, S.; Park, D.J.; Pellé, K.; Robbins, D.; Russ, C.; Ryan, E.M.; Sacarlal, J.; Sogoloff, B.; Sorgho, H.; Tanner, M.; Theander, T.; Valea, I.; Volkman, S.K.; Yu, Q.; Lapierre, D.; Birren, B.W.; Gilbert, P.B.; Wirth, D.F.

    2016-01-01

    BACKGROUND The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS We used polymerase chain reaction–based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P = 0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P = 0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health

  1. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

    PubMed

    Neafsey, D E; Juraska, M; Bedford, T; Benkeser, D; Valim, C; Griggs, A; Lievens, M; Abdulla, S; Adjei, S; Agbenyega, T; Agnandji, S T; Aide, P; Anderson, S; Ansong, D; Aponte, J J; Asante, K P; Bejon, P; Birkett, A J; Bruls, M; Connolly, K M; D'Alessandro, U; Dobaño, C; Gesase, S; Greenwood, B; Grimsby, J; Tinto, H; Hamel, M J; Hoffman, I; Kamthunzi, P; Kariuki, S; Kremsner, P G; Leach, A; Lell, B; Lennon, N J; Lusingu, J; Marsh, K; Martinson, F; Molel, J T; Moss, E L; Njuguna, P; Ockenhouse, C F; Ogutu, B Ragama; Otieno, W; Otieno, L; Otieno, K; Owusu-Agyei, S; Park, D J; Pellé, K; Robbins, D; Russ, C; Ryan, E M; Sacarlal, J; Sogoloff, B; Sorgho, H; Tanner, M; Theander, T; Valea, I; Volkman, S K; Yu, Q; Lapierre, D; Birren, B W; Gilbert, P B; Wirth, D F

    2015-11-19

    The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

  2. Population Genetics, Evolutionary Genomics, and Genome-Wide Studies of Malaria: A View Across the International Centers of Excellence for Malaria Research.

    PubMed

    Carlton, Jane M; Volkman, Sarah K; Uplekar, Swapna; Hupalo, Daniel N; Pereira Alves, João Marcelo; Cui, Liwang; Donnelly, Martin; Roos, David S; Harb, Omar S; Acosta, Monica; Read, Andrew; Ribolla, Paulo E M; Singh, Om P; Valecha, Neena; Wassmer, Samuel C; Ferreira, Marcelo; Escalante, Ananias A

    2015-09-01

    The study of the three protagonists in malaria-the Plasmodium parasite, the Anopheles mosquito, and the human host-is key to developing methods to control and eventually eliminate the disease. Genomic technologies, including the recent development of next-generation sequencing, enable interrogation of this triangle to an unprecedented level of scrutiny, and promise exciting progress toward real-time epidemiology studies and the study of evolutionary adaptation. We discuss the use of genomics by the International Centers of Excellence for Malaria Research, a network of field sites and laboratories in malaria-endemic countries that undertake cutting-edge research, training, and technology transfer in malarious countries of the world.

  3. Improving the population genetics toolbox for the study of the African malaria vector Anopheles nili: microsatellite mapping to chromosomes

    PubMed Central

    2011-01-01

    Background Anopheles nili is a major vector of malaria in the humid savannas and forested areas of sub-Saharan Africa. Understanding the population genetic structure and evolutionary dynamics of this species is important for the development of an adequate and targeted malaria control strategy in Africa. Chromosomal inversions and microsatellite markers are commonly used for studying the population structure of malaria mosquitoes. Physical mapping of these markers onto the chromosomes further improves the toolbox, and allows inference on the demographic and evolutionary history of the target species. Results Availability of polytene chromosomes allowed us to develop a map of microsatellite markers and to study polymorphism of chromosomal inversions. Nine microsatellite markers were mapped to unique locations on all five chromosomal arms of An. nili using fluorescent in situ hybridization (FISH). Probes were obtained from 300-483 bp-long inserts of plasmid clones and from 506-559 bp-long fragments amplified with primers designed using the An. nili genome assembly generated on an Illumina platform. Two additional loci were assigned to specific chromosome arms of An. nili based on in silico sequence similarity and chromosome synteny with Anopheles gambiae. Three microsatellites were mapped inside or in the vicinity of the polymorphic chromosomal inversions 2Rb and 2Rc. A statistically significant departure from Hardy-Weinberg equilibrium, due to a deficit in heterozygotes at the 2Rb inversion, and highly significant linkage disequilibrium between the two inversions, were detected in natural An. nili populations collected from Burkina Faso. Conclusions Our study demonstrated that next-generation sequencing can be used to improve FISH for microsatellite mapping in species with no reference genome sequence. Physical mapping of microsatellite markers in An. nili showed that their cytological locations spanned the entire five-arm complement, allowing genome-wide inferences

  4. Seeking consent to genetic and genomic research in a rural Ghanaian setting: A qualitative study of the MalariaGEN experience

    PubMed Central

    2012-01-01

    Background Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrolment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study. Methods The study used a rapid assessment incorporating multiple qualitative methods including in depth interviews, focus group discussions and observations of consent processes. Differences between verbal information provided during community engagement processes, and consent processes during the enrolment of cases and controls were identified, as well as the factors influencing the tailoring of such information. Results MalariaGEN participants and field staff seeking consent were generally satisfied with their understanding of the project and were familiar with aspects of the study relating to malaria. Some genetic aspects of the study were also well understood. Participants and staff seeking consent were less aware of the methodologies employed during genomic research and their implications, such as the breadth of data generated and the potential for future secondary research. Moreover, trust in and previous experience with the Navrongo Health Research Centre which was conducting the research influenced beliefs about the benefits of participating in the MalariaGEN study and subsequent decision-making about research participation. Conclusions It is important to recognise that some aspects of complex genomic research may be of less interest to and less well understood by research participants and that such gaps in understanding may not be entirely addressed by best practice in the design and conduct of consent processes. In such circumstances consideration needs to be given to additional

  5. Seeking consent to genetic and genomic research in a rural Ghanaian setting: a qualitative study of the MalariaGEN experience.

    PubMed

    Tindana, Paulina; Bull, Susan; Amenga-Etego, Lucas; de Vries, Jantina; Aborigo, Raymond; Koram, Kwadwo; Kwiatkowski, Dominic; Parker, Michael

    2012-07-02

    Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrollment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study. The study used a rapid assessment incorporating multiple qualitative methods including in depth interviews, focus group discussions and observations of consent processes. Differences between verbal information provided during community engagement processes, and consent processes during the enrollment of cases and controls were identified, as well as the factors influencing the tailoring of such information. MalariaGEN participants and field staff seeking consent were generally satisfied with their understanding of the project and were familiar with aspects of the study relating to malaria. Some genetic aspects of the study were also well understood. Participants and staff seeking consent were less aware of the methodologies employed during genomic research and their implications, such as the breadth of data generated and the potential for future secondary research.Moreover, trust in and previous experience with the Navrongo Health Research Centre which was conducting the research influenced beliefs about the benefits of participating in the MalariaGEN study and subsequent decision-making about research participation. It is important to recognise that some aspects of complex genomic research may be of less interest to and less well understood by research participants and that such gaps in understanding may not be entirely addressed by best practice in the design and conduct of consent processes. In such circumstances consideration needs to be given to additional protections for participants that may need

  6. Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test.

    PubMed

    Atroosh, Wahib M; Al-Mekhlafi, Hesham M; Al-Jasari, Adel; Sady, Hany; Al-Delaimy, Ahmed K; Nasr, Nabil A; Dawaki, Salwa; Abdulsalam, Awatif M; Ithoi, Init; Lau, Yee Ling; Fong, Mun Yik; Surin, Johari

    2015-07-22

    The genetic variation in the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P. falciparum isolates from Yemen. This study was conducted in Hodeidah and Al-Mahwit governorates, Yemen. A total of 622 individuals with fever were examined for malaria by CareStart malaria HRP2-RDT and Giemsa-stained thin and thick blood films. The Pfhrp2 gene was amplified and sequenced from 180 isolates, and subjected to amino acid repeat types analysis. A total of 188 (30.2%) participants were found positive for P. falciparum by the RDT. Overall, 12 different amino acid repeat types were identified in Yemeni isolates. Six repeat types were detected in all the isolates (100%) namely types 1, 2, 6, 7, 10 and 12 while types 9 and 11 were not detected in any of the isolates. Moreover, the sensitivity and specificity of the used PfHRP2-based RDTs were high (90.5% and 96.1%, respectively). The present study provides data on the genetic variation within the pfhrp2 gene, and its potential impact on the PfHRP2-based RDTs commonly used in Yemen. CareStart Malaria HRP2-based RDT showed high sensitivity and specificity in endemic areas of Yemen.

  7. Vaccines Against Malaria

    PubMed Central

    Ouattara, Amed; Laurens, Matthew B.

    2015-01-01

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

  8. Genetic population structure of the malaria vector Anopheles baimaii in north-east India using mitochondrial DNA

    PubMed Central

    2012-01-01

    Background Anopheles baimaii is a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic population genetic parameters of An. baimaii in north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene. Methods Anopheles baimaii were collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences of An. baimaii from six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history. Results A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion in An. baimaii with the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations of An. baimaii from north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations. Conclusions The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its

  9. Genetic population structure of the malaria vector Anopheles baimaii in north-east India using mitochondrial DNA.

    PubMed

    Sarma, Devojit K; Prakash, Anil; O'Loughlin, Samantha M; Bhattacharyya, Dibya R; Mohapatra, Pradumnya K; Bhattacharjee, Kanta; Das, Kanika; Singh, Sweta; Sarma, Nilanju P; Ahmed, Gias U; Walton, Catherine; Mahanta, Jagadish

    2012-03-20

    Anopheles baimaii is a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic population genetic parameters of An. baimaii in north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene. Anopheles baimaii were collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences of An. baimaii from six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history. A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion in An. baimaii with the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations of An. baimaii from north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations. The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its epidemiological significance further

  10. Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian population.

    PubMed

    Fernandes, Rayzel C; Hasan, Marriyah; Gupta, Himanshu; Geetha, K; Rai, Padmalatha S; Hande, Manjunath H; D'Souza, Sydney C; Adhikari, Prabha; Brand, Angela; Satyamoorthy, Kapaettu

    2015-06-01

    Antioxidant enzymes can contribute to disease susceptibility or determine response to therapy in individuals with malaria. Genetic variations due to polymorphisms in host genes encoding antioxidant enzymes such as glutathione S-transferases-theta, mu, pi (GSTT, GSTM, GSTP), superoxide dismutases (SOD) and catalase (CAT), may therefore, influence inter-individual response to malaria pathology and propensity of infection caused by Plasmodium vivax (Pv) and Plasmodium falciparum (Pf). Therefore, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, we investigated the association of deletions of GSTT1 and GSTM1, single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695), SOD1 (rs2234694), SOD2 (rs4880, rs1141718), SOD3 (rs2536512) and CAT (rs1001179) in individuals infected with Pf (n = 100) and Pv (n = 100) against healthy controls (n = 150). Our data suggest a significant role for GSTM1 deletions in complicated Pv (p = 0.0007) malaria with ODDs ratio 3.8 [with 95 % confidence interval (CI) 1.9-7.4]. The results also indicated that polymorphisms present in GSTP1, SOD1 and CAT genes may be associated with malaria susceptibility (p < 0.05), whereas SOD3 polymorphism may play a role in malarial resistance (p < 0.05). In addition, we observed significant SNP-SNP interactions with synergistic genetic effects in SOD2, SOD3 and CAT genes for Pv and in SOD2 and SOD3 genes for Pf. In conclusion, our results provide convincing evidence for a relationship between polymorphisms in host antioxidant enzymes and susceptibility to malaria infection.

  11. The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis

    PubMed Central

    Main, Bradley J; Lee, Yoosook; Ferguson, Heather M.; Kreppel, Katharina S.; Kihonda, Anicet; Govella, Nicodem J.; Collier, Travis C.; Cornel, Anthony J.; Eskin, Eleazar; Kang, Eun Yong; Nieman, Catelyn C.; Weakley, Allison M.; Lanzaro, Gregory C.

    2016-01-01

    Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bite humans (anthropophily) instead of other dead end hosts. Recent increases in the usage of Long Lasting Insecticide Treated Nets (LLINs) in Africa have been associated with reductions in highly anthropophilic and endophilic vectors such as Anopheles gambiae s.s., leaving species with a broader host range, such as Anopheles arabiensis, as the most prominent remaining source of transmission in many settings. An. arabiensis appears to be more of a generalist in terms of its host choice and resting behavior, which may be due to phenotypic plasticity and/or segregating allelic variation. To investigate the genetic basis of host choice and resting behavior in An. arabiensis we sequenced the genomes of 23 human-fed and 25 cattle-fed mosquitoes collected both in-doors and out-doors in the Kilombero Valley, Tanzania. We identified a total of 4,820,851 SNPs, which were used to conduct the first genome-wide estimates of “SNP heritability” for host choice and resting behavior in this species. A genetic component was detected for host choice (human vs cow fed; permuted P = 0.002), but there was no evidence of a genetic component for resting behavior (indoors versus outside; permuted P = 0.465). A principal component analysis (PCA) segregated individuals based on genomic variation into three groups which were characterized by differences at the 2Rb and/or 3Ra paracentromeric chromosome inversions. There was a non-random distribution of cattle-fed mosquitoes between the PCA clusters, suggesting that alleles linked to the 2Rb and/or 3Ra inversions may influence host choice. Using a novel inversion genotyping assay, we detected a significant enrichment of the standard arrangement (non-inverted) of 3Ra among cattle-fed mosquitoes (N = 129) versus all non-cattle-fed individuals (N = 234; χ2, p = 0.007). Thus, tracking the frequency of the 3Ra in An. arabiensis populations may be of use to infer

  12. The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis.

    PubMed

    Main, Bradley J; Lee, Yoosook; Ferguson, Heather M; Kreppel, Katharina S; Kihonda, Anicet; Govella, Nicodem J; Collier, Travis C; Cornel, Anthony J; Eskin, Eleazar; Kang, Eun Yong; Nieman, Catelyn C; Weakley, Allison M; Lanzaro, Gregory C

    2016-09-01

    Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bite humans (anthropophily) instead of other dead end hosts. Recent increases in the usage of Long Lasting Insecticide Treated Nets (LLINs) in Africa have been associated with reductions in highly anthropophilic and endophilic vectors such as Anopheles gambiae s.s., leaving species with a broader host range, such as Anopheles arabiensis, as the most prominent remaining source of transmission in many settings. An. arabiensis appears to be more of a generalist in terms of its host choice and resting behavior, which may be due to phenotypic plasticity and/or segregating allelic variation. To investigate the genetic basis of host choice and resting behavior in An. arabiensis we sequenced the genomes of 23 human-fed and 25 cattle-fed mosquitoes collected both in-doors and out-doors in the Kilombero Valley, Tanzania. We identified a total of 4,820,851 SNPs, which were used to conduct the first genome-wide estimates of "SNP heritability" for host choice and resting behavior in this species. A genetic component was detected for host choice (human vs cow fed; permuted P = 0.002), but there was no evidence of a genetic component for resting behavior (indoors versus outside; permuted P = 0.465). A principal component analysis (PCA) segregated individuals based on genomic variation into three groups which were characterized by differences at the 2Rb and/or 3Ra paracentromeric chromosome inversions. There was a non-random distribution of cattle-fed mosquitoes between the PCA clusters, suggesting that alleles linked to the 2Rb and/or 3Ra inversions may influence host choice. Using a novel inversion genotyping assay, we detected a significant enrichment of the standard arrangement (non-inverted) of 3Ra among cattle-fed mosquitoes (N = 129) versus all non-cattle-fed individuals (N = 234; χ2, p = 0.007). Thus, tracking the frequency of the 3Ra in An. arabiensis populations may be of use to infer

  13. Biochemical and genetic analysis of the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum.

    PubMed

    Reynolds, Jennifer M; Takebe, Sachiko; Choi, Jae-Yeon; El Bissati, Kamal; Witola, William H; Bobenchik, April M; Hoch, Jeffrey C; Voelker, Dennis R; Mamoun, Choukri Ben

    2008-03-21

    The PfPMT enzyme of Plasmodium falciparum, the agent of severe human malaria, is a member of a large family of known and predicted phosphoethanolamine methyltransferases (PMTs) recently identified in plants, worms, and protozoa. Functional studies in P. falciparum revealed that PfPMT plays a critical role in the synthesis of phosphatidylcholine via a plant-like pathway involving serine decarboxylation and phosphoethanolamine methylation. Despite their important biological functions, PMT structures have not yet been solved, and nothing is known about which amino acids in these enzymes are critical for catalysis and binding to S-adenosyl-methionine and phosphoethanolamine substrates. Here we have performed a mutational analysis of PfPMT focused on 24 residues within and outside the predicted catalytic motif. The ability of PfPMT to complement the choline auxotrophy of a yeast mutant defective in phospholipid methylation enabled us to characterize the activity of the PfPMT mutants. Mutations in residues Asp-61, Gly-83 and Asp-128 dramatically altered PfPMT activity and its complementation of the yeast mutant. Our analyses identify the importance of these residues in PfPMT activity and set the stage for advanced structural understanding of this class of enzymes.

  14. Resting behaviour, ecology and genetics of malaria vectors in large scale agricultural areas of Western Kenya.

    PubMed

    Githeko, A K; Service, M W; Mbogo, C M; Atieli, F K

    1996-12-01

    In Kenya indoor and outdoor resting densities of Anopheles arabiensis and Anopheles funestus at the Ahero rice irrigation scheme, and Anopheles gambiae s.s., An. arabiensis and An. funestus at the Miwani sugar belt were assessed for 13 months by pyrethrum spray collections in houses and granaries. The vector's house leaving behaviour was evaluated with exit traps and it was noted that early exophily (i.e., deliberate) was not detected in any of the vectors. Assortative indoor/outdoor resting behaviour was studied by a capture-mark-release-recapture method and showed that in An. arabiensis both indoor and outdoor resting traits were present in the same individuals. Samples of half-gravid female An. gambiae s.l. were chromosomally identified either as Anopheles gambiae s.s. or An. arabiensis and in a subsample chromosomal inversions were read. Anopheles gambiae s.s. and An. arabiensis had the 2Rb inversion but in addition the 2La inversion was found in An. gambiae s.s. and this is an indication of low chromosomal variation. At Ahero An. arabiensis was most abundant when the rice crop was immature and An. funestus when the crop was mature. This succession of vectors facilitated the transmission of malaria throughout the year. At Miwani, An. gambiae s.l. population peaked during the long rains but the proportion of An. arabiensis was highest during the dry season. The indoor resting density of males of the three vector species was less than half of the females.

  15. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

    PubMed Central

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M.; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K.; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L.; Crompton, Peter D.

    2015-01-01

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. PMID:26361633

  16. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens.

    PubMed

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L; Crompton, Peter D

    2015-09-01

    Background.  People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods.  In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results.  We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions.  These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

  17. Population Genetics, Evolutionary Genomics, and Genome-Wide Studies of Malaria: A View across the International Centers of Excellence for Malaria Research

    PubMed Central

    Carlton, Jane M.; Volkman, Sarah K.; Uplekar, Swapna; Hupalo, Daniel N.; Alves, João Marcelo Pereira; Cui, Liwang; Donnelly, Martin; Roos, David S.; Harb, Omar S.; Acosta, Monica; Read, Andrew; Ribolla, Paulo E. M.; Singh, Om P.; Valecha, Neena; Wassmer, Samuel C.; Ferreira, Marcelo; Escalante, Ananias A.

    2015-01-01

    The study of the three protagonists in malaria—the Plasmodium parasite, the Anopheles mosquito, and the human host—is key to developing methods to control and eventually eliminate the disease. Genomic technologies, including the recent development of next-generation sequencing, enable interrogation of this triangle to an unprecedented level of scrutiny, and promise exciting progress toward real-time epidemiology studies and the study of evolutionary adaptation. We discuss the use of genomics by the International Centers of Excellence for Malaria Research, a network of field sites and laboratories in malaria-endemic countries that undertake cutting-edge research, training, and technology transfer in malarious countries of the world. PMID:26259940

  18. Short-Lived Effector CD8 T Cells Induced by Genetically Attenuated Malaria Parasite Vaccination Express CD11c

    PubMed Central

    Cooney, Laura A.; Gupta, Megha; Thomas, Sunil; Mikolajczak, Sebastian; Choi, Kimberly Y.; Gibson, Claire; Jang, Ihn K.; Danziger, Sam; Aitchison, John; Gardner, Malcolm J.; Kappe, Stefan H. I.

    2013-01-01

    Vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent Plasmodium yoelii model. Protection is dependent on CD8+ T cells, involves perforin and gamma interferon (IFN-γ), and is correlated with the expansion of effector memory CD8+ T cells in the liver. Here, we have further characterized vaccine-induced changes in the CD8+ T cell phenotype and demonstrated significant upregulation of CD11c on CD3+ CD8b+ T cells in the liver, spleen, and peripheral blood. CD11c+ CD8+ T cells are predominantly CD11ahi CD44hi CD62L−, indicative of antigen-experienced effector cells. Following in vitro restimulation with malaria-infected hepatocytes, CD11c+ CD8+ T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a. CD11c− CD8+ T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8+ T cells. Coculture of CD11c+, but not CD11c−, CD8+ T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development. Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8+ T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c+ CD8+ T cell response, but CD11c expression was lost as the CD8+ T cells entered the memory phase. Further analyses showed that CD11c+ CD8+ T cells are primarily KLRG1+ CD127− terminal effectors, whereas all KLRG1− CD127+ memory precursor effector cells are CD11c− CD8+ T cells. Together, these results suggest that CD11c marks a subset of highly inflammatory, short-lived, antigen-specific effector cells, which may play an important role in eliminating infected hepatocytes. PMID:23980113

  19. Short-lived effector CD8 T cells induced by genetically attenuated malaria parasite vaccination express CD11c.

    PubMed

    Cooney, Laura A; Gupta, Megha; Thomas, Sunil; Mikolajczak, Sebastian; Choi, Kimberly Y; Gibson, Claire; Jang, Ihn K; Danziger, Sam; Aitchison, John; Gardner, Malcolm J; Kappe, Stefan H I; Wang, Ruobing

    2013-11-01

    Vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent Plasmodium yoelii model. Protection is dependent on CD8(+) T cells, involves perforin and gamma interferon (IFN-γ), and is correlated with the expansion of effector memory CD8(+) T cells in the liver. Here, we have further characterized vaccine-induced changes in the CD8(+) T cell phenotype and demonstrated significant upregulation of CD11c on CD3(+) CD8b(+) T cells in the liver, spleen, and peripheral blood. CD11c(+) CD8(+) T cells are predominantly CD11a(hi) CD44(hi) CD62L(-), indicative of antigen-experienced effector cells. Following in vitro restimulation with malaria-infected hepatocytes, CD11c(+) CD8(+) T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a. CD11c(-) CD8(+) T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8(+) T cells. Coculture of CD11c(+), but not CD11c(-), CD8(+) T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development. Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8(+) T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c(+) CD8(+) T cell response, but CD11c expression was lost as the CD8(+) T cells entered the memory phase. Further analyses showed that CD11c(+) CD8(+) T cells are primarily KLRG1(+) CD127(-) terminal effectors, whereas all KLRG1(-) CD127(+) memory precursor effector cells are CD11c(-) CD8(+) T cells. Together, these results suggest that CD11c marks a subset of highly inflammatory, short-lived, antigen-specific effector cells, which may play an important role in eliminating infected

  20. Epidemiologic clues to bioterrorism.

    PubMed Central

    Treadwell, Tracee A.; Koo, Denise; Kuker, Kathleen; Khan, Ali S.

    2003-01-01

    Public health investigators have successfully carried out epidemiologic investigations of outbreaks of disease for many years. By far the majority of these outbreaks have occurred naturally. With the recent illnesses resulting from deliberate dissemination of B. anthracis on an unsuspecting population, public health investigation of diseases must now include consideration of bioterrorism as a potential cause of outbreaks of disease. The features of naturally occurring outbreaks have a certain amount of predictability in terms of consistency with previous occurrences, or at least biological plausibility. However, with a deliberately introduced outbreak or infection among a population, this predictability is minimized. In this paper, the authors propose some epidemiologic clues that highlight features of outbreaks that may be suggestive of bioterrorism. They also describe briefly the general process of involvement of agencies at various levels of government, public health and non-public health, depending on the extent of an outbreak or level of suspicion. PMID:12690063

  1. Comparative Genomics of multiple Candidatus Liberibacter asiaticus isolates reveals genetic diversity in Florida and provides clues to the evolution of the bacteria in citrus

    USDA-ARS?s Scientific Manuscript database

    Understanding genetic diversity of within and among the populations of an organism provides information about the potential diversity in pathogenicity and susceptibility to host defenses as well as sustainable effectiveness of control treatments. A near whole genome sequencing strategy was used to c...

  2. Distribution of FcγR gene polymorphisms among two sympatric populations in Mali: differing allele frequencies, associations with malariometric indices and implications for genetic susceptibility to malaria.

    PubMed

    Cherif, Mariama; Amoako-Sakyi, Daniel; Dolo, Amagana; Pearson, Jan-Olov; Gyan, Ben; Obiri-Yeboah, Dorcas; Nebie, Issa; Sirima, Sodiomon B; Doumbo, Ogobara; Troye-Blomberg, Marita; Bakary, Maiga

    2016-01-19

    Genetic polymorphisms in the complex gene cluster encoding human Fc-gamma receptors (FcγRs) may influence malaria susceptibility and pathogenesis. Studying genetic susceptibility to malaria is ideal among sympatric populations because the distribution of polymorphic genes among such populations can help in the identification malaria candidate genes. This study determined the distribution of three FcyRs single nucleotide polymorphisms (SNPs) (FcγRIIB-rs1050519, FcγRIIC-rs3933769 and FcγRIIIA-rs396991) among sympatric Fulani and Dogon children with uncomplicated malaria. The association of these SNPs with clinical, malariometric and immunological indices was also tested. This study involved 242 Fulani and Dogon volunteers from Mali age under 15 years. All SNPs were genotyped with predesigned TaqMan(®) SNP Genotyping Assays. Genotypic and allelic distribution of SNPs was compared across ethnic groups using the Fisher exact test. Variations in clinical, malariometric and immunologic indices between groups were tested with Kruskal-Wallis H, Mann-Whitney U test and Fisher exact test where appropriate. The study confirmed known malariometric and immunologic differences between sympatric Fulani and non-Fulani tribes. Parasite density was lower in the Fulani than the Dogon (p < 0.0001). The mutant allele of FcγRIIC (rs3933769) was found more frequently in the Fulani than the Dogon (p < 0.0001) while that of FcγRIIIA (rs396991) occurred less frequently in the Fulani than Dogon (p = 0.0043). The difference in the mutant allele frequency of FcγRIIB (rs1050519) between the two ethnic groups was however not statistically significant (p = 0.064). The mutant allele of rs396991 was associated with high malaria-specific IgG1 and IgG3 in the entire study population and Dogon tribe, p = 0.023 and 0.015, respectively. Parasite burden was lower in carriers of the FcγRIIC (rs3933769) mutant allele than non-carriers in the entire study population (p < 0

  3. Malaria Molecular Epidemiology: Lessons from the International Centers of Excellence for Malaria Research Network

    PubMed Central

    Escalante, Ananias A.; Ferreira, Marcelo U.; Vinetz, Joseph M.; Volkman, Sarah K.; Cui, Liwang; Gamboa, Dionicia; Krogstad, Donald J.; Barry, Alyssa E.; Carlton, Jane M.; van Eijk, Anna Maria; Pradhan, Khageswar; Mueller, Ivo; Greenhouse, Bryan; Andreina Pacheco, M.; Vallejo, Andres F.; Herrera, Socrates; Felger, Ingrid

    2015-01-01

    Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax. Second, we describe and compare different parasite genotyping methods commonly used in malaria epidemiology and population genetics. Finally, we discuss potential applications of molecular epidemiological tools and methods toward malaria control and elimination efforts. PMID:26259945

  4. Malaria Molecular Epidemiology: Lessons from the International Centers of Excellence for Malaria Research Network.

    PubMed

    Escalante, Ananias A; Ferreira, Marcelo U; Vinetz, Joseph M; Volkman, Sarah K; Cui, Liwang; Gamboa, Dionicia; Krogstad, Donald J; Barry, Alyssa E; Carlton, Jane M; van Eijk, Anna Maria; Pradhan, Khageswar; Mueller, Ivo; Greenhouse, Bryan; Pacheco, M Andreina; Vallejo, Andres F; Herrera, Socrates; Felger, Ingrid

    2015-09-01

    Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax. Second, we describe and compare different parasite genotyping methods commonly used in malaria epidemiology and population genetics. Finally, we discuss potential applications of molecular epidemiological tools and methods toward malaria control and elimination efforts. © The American Society of Tropical Medicine and Hygiene.

  5. Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria.

    PubMed

    Lou, J; Gasche, Y; Zheng, L; Critico, B; Monso-Hinard, C; Juillard, P; Morel, P; Buurman, W A; Grau, G E

    1998-12-01

    Upon infection with Plasmodium berghei ANKA (PbA), various inbred strains of mice exhibit different susceptibility to the development of cerebral malaria (CM). Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma) have been shown to be crucial mediators in the pathogenesis of this neurovascular complication. Brain microvascular endothelial cells (MVEC) represent an important target of both cytokines. In the present study, we show that brain MVEC purified from CM-susceptible (CM-S) CBA/J mice and CM-resistant (CM-R) BALB/c mice exhibit a different sensitivity to TNF. CBA/J brain MVEC displayed a higher capacity to produce IL-6 and to up-regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in response to TNF than BALB/c brain MVEC. In contrast, no difference was found in the induction of E-selectin after TNF challenge. CM-S brain MVEC were also significantly more sensitive to TNF-induced lysis. This differential reactivity to TNF was further substantiated by comparing TNF receptor expression on CM-S and CM-R brain MVEC. Although the constitutive expression of TNF receptors was comparable on cells from the two origins, TNF induced an up-regulation of both p55 and p75 TNF receptors in CM-S, but not in CM-R brain MVEC. A similar regulation was found at the level of TNF receptor mRNA, but not for receptor shedding. Although a protein kinase C inhibitor blocked the response to TNF in both the brain MVEC, an inhibitor of protein kinase A selectively abolished the response to TNF in CM-R, but not CM-S brain MVEC, suggesting a differential protein kinase involvement in TNF-induced activation of CM-S and CM-R brain MVEC. These results indicate that brain MVEC purified from CM-S and CM-R mice exhibit distinctive sensitivity to TNF This difference may be partly due to a differential regulation of TNF receptors and via distinct protein kinase pathways.

  6. Country-wide assessment of the genetic polymorphism in Plasmodium falciparum and Plasmodium vivax antigens detected with rapid diagnostic tests for malaria.

    PubMed

    Mariette, Natacha; Barnadas, Céline; Bouchier, Christiane; Tichit, Magali; Ménard, Didier

    2008-10-28

    Rapid diagnostic tests (RDTs) are becoming increasingly indispensable in malaria management, as a means of increasing the accuracy of diagnosis. The WHO has issued recommendations, but the selection of the most suitable RDT remains difficult for users in endemic countries. The genetic variability of the antigens detected with RDTs has been little studied, but may affect the sensitivity of RDTs. This factor has been studied by comparisons between countries at continental level, but little information is available concerning antigen variability within a given country. A country-wide assessment of polymorphism of the PfHRP2, PfHRP3, pLDH and aldolase antigens was carried out in 260 Plasmodium falciparum and 127 Plasmodium vivax isolates, by sequencing the genes encoding these antigens in parasites originating from the various epidemiological strata for malaria in Madagascar. Higher levels of polymorphism were observed for the pfhrp2 and pfhrp3 genes than for the P. falciparum and P. vivax aldolase and pldh genes. Pfhrp2 sequence analysis predicted that 9% of Malagasy isolates would not be detected at parasite densities < or = 250 parasites/mul (ranging from 6% in the north to 14% in the south), although RDTs based on PfHRP2 detection are now recommended in Madagascar. These findings highlight the importance of training of health workers and the end users of RDTs in the provision of information about the possibility of false-negative results for patients with clinical symptoms of malaria, particularly in the south of Madagascar.

  7. Ecological and genetic relationships of the Forest-M form among chromosomal and molecular forms of the malaria vector Anopheles gambiae sensu stricto

    PubMed Central

    Lee, Yoosook; Cornel, Anthony J; Meneses, Claudio R; Fofana, Abdrahamane; Andrianarivo, Aurélie G; McAbee, Rory D; Fondjo, Etienne; Traoré, Sekou F; Lanzaro, Gregory C

    2009-01-01

    Background Anopheles gambiae sensu stricto, one of the principal vectors of malaria, has been divided into two subspecific groups, known as the M and S molecular forms. Recent studies suggest that the M form found in Cameroon is genetically distinct from the M form found in Mali and elsewhere in West Africa, suggesting further subdivision within that form. Methods Chromosomal, microsatellite and geographic/ecological evidence are synthesized to identify sources of genetic polymorphism among chromosomal and molecular forms of the malaria vector Anopheles gambiae s.s. Results Cytogenetically the Forest M form is characterized as carrying the standard chromosome arrangement for six major chromosomal inversions, namely 2La, 2Rj, 2Rb, 2Rc, 2Rd, and 2Ru. Bayesian clustering analysis based on molecular form and chromosome inversion polymorphisms as well as microsatellites describe the Forest M form as a distinct population relative to the West African M form (Mopti-M form) and the S form. The Forest-M form was the most highly diverged of the An. gambiae s.s. groups based on microsatellite markers. The prevalence of the Forest M form was highly correlated with precipitation, suggesting that this form prefers much wetter environments than the Mopti-M form. Conclusion Chromosome inversions, microsatellite allele frequencies and habitat preference all indicate that the Forest M form of An. gambiae is genetically distinct from the other recognized forms within the taxon Anopheles gambiae sensu stricto. Since this study covers limited regions of Cameroon, the possibility of gene flow between the Forest-M form and Mopti-M form cannot be rejected. However, association studies of important phenotypes, such as insecticide resistance and refractoriness against malaria parasites, should take into consideration this complex population structure. PMID:19383163

  8. Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China

    PubMed Central

    2013-01-01

    Background Anopheles sinensis is a principal vector for Plasmodium vivax malaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China. Methods The present study investigated the genetic structure of An. sinensis populations using a 729 bp fragment of mtDNA ND5 among 10 populations collected from seven provinces in China. Results ND5 was polymorphic by single mutations within three groups of An. sinensis that were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation of An. sinensis varied from low to moderate across China and with a FST range of 0.00065 – 0.341. Genealogy analysis clustered the populations of An. sinensis into three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in the An. sinensis populations from China. Three clusters of An. sinensis populations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations of An. sinensis (R2 = 0.058; P = 0.301). Conclusions The results indicate that the ND5 gene of mtDNA is highly polymorphic in An. sinensis and has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion in An. sinensis populations. PMID:24192424

  9. Can clues to the molecular defects in chronic myelogenous leukemia come from genetic studies on the Abelson tyrosine kinase in fruit flies?

    PubMed

    Comer, A R; Liebl, E C; Hoffmann, F M

    1995-06-01

    Translocations affecting the structure of the c-abl proto-oncogene are involved in the development or progression of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). Leukemic cells from patients with CML show alterations in adhesive properties that may play a part in the pathology of these diseases. Mutations in the Drosophila Abl homolog are lethal and indicate that Abl may mediate processes involving differential cell adhesion. These observations suggest that Abl may regulate similar adhesive processes in human beings and Drosophila. Genetic analysis of Abl function in Drosophila has identified novel proteins that function in Abl-related processes. Analysis of the functions of these new molecules may provide insight into mechanisms by which oncogenic abl proteins participate in the etiology of CML and ALL.

  10. Mystery in genetics: PUB4 gives a clue to the complex mechanism of CLV signaling pathway in the shoot apical meristem.

    PubMed

    Kinoshita, Atsuko; Seo, Mitsunori; Kamiya, Yuji; Sawa, Shinichiro

    2015-01-01

    Postembryonic growth and development in higher plants are ultimately reliant on the activity of meristems, where the cells divide frequently to provide source cells for new organs and tissues while in part maintain their pluripotent nature as stem cells. The shoot apical meristem (SAM) is maintained throughout the life of plants and responsible for the development of all areal tissues. In Arabidopsis thaliana, the size of SAM is controlled by a peptide ligand, CLAVATA3 (CLV3). Previously, genetic studies have identified several genes that function downstream of CLV3, many of which, intriguingly, encode receptors. Recently we identified an E3 ubiquitin ligase, PLANT U-BOX 4 (PUB4), as a key regulatory component of root meristem maintenance that functions downstream of an exogenous synthetic CLV3 peptide. Here, we report an additional function of PUB4 in the SAM.

  11. Unraveling Parkinson's: Three Clues

    MedlinePlus

    ... to an environmental risk factor such as a pesticide or a toxin. This theory is based on the fact that a number of toxins are known to induce Parkinsonian symptoms in humans. Genetics: A relatively new theory explores the role ...

  12. Quantification of labile heme in live malaria parasites using a genetically encoded biosensor

    PubMed Central

    Abshire, James R.; Rowlands, Christopher J.; Ganesan, Suresh M.; So, Peter T. C.; Niles, Jacquin C.

    2017-01-01

    Heme is ubiquitous, yet relatively little is known about the maintenance of labile pools of this cofactor, which likely ensures its timely bioavailability for proper cellular function. Quantitative analysis of labile heme is of fundamental importance to understanding how nature preserves access to the diverse chemistry heme enables, while minimizing cellular damage caused by its redox activity. Here, we have developed and characterized a protein-based sensor that undergoes fluorescence quenching upon heme binding. By genetically encoding this sensor in the human malarial parasite, Plasmodium falciparum, we have quantified cytosolic labile heme levels in intact, blood-stage parasites. Our findings indicate that a labile heme pool (∼1.6 µM) is stably maintained throughout parasite development within red blood cells, even during a period coincident with extensive hemoglobin degradation by the parasite. We also find that the heme-binding antimalarial drug chloroquine specifically increases labile cytosolic heme, indicative of dysregulation of this homeostatic pool that may be a relevant component of the antimalarial activity of this compound class. We propose that use of this technology under various environmental perturbations in P. falciparum can yield quantitative insights into fundamental heme biology. PMID:28242687

  13. Cerebral malaria

    PubMed Central

    Rénia, Laurent; Wu Howland, Shanshan; Claser, Carla; Charlotte Gruner, Anne; Suwanarusk, Rossarin; Hui Teo, Teck; Russell, Bruce; Ng, Lisa

    2012-01-01

    Cerebral malaria is the most severe pathology caused by the malaria parasite, Plasmodium falciparum. The pathogenic mechanisms leading to cerebral malaria are still poorly defined as studies have been hampered by limited accessibility to human tissues. Nevertheless, histopathology of post-mortem human tissues and mouse models of cerebral malaria have indicated involvement of the blood-brain barrier in cerebral malaria. In contrast to viruses and bacteria, malaria parasites do not infiltrate and infect the brain parenchyma. Instead, rupture of the blood-brain barrier occurs and may lead to hemorrhages resulting in neurological alterations. Here, we review the most recent findings from human studies and mouse models on the interactions of malaria parasites and the blood-brain barrier, shedding light on the pathogenesis of cerebral malaria, which may provide directions for possible interventions. PMID:22460644

  14. Genetic sex separation of the malaria vector, Anopheles arabiensis, by exposing eggs to dieldrin.

    PubMed

    Yamada, Hanano; Benedict, Mark Q; Malcolm, Colin A; Oliva, Clelia F; Soliban, Sharon M; Gilles, Jeremie R L

    2012-06-19

    The sterile insect technique (SIT) has been used with success for suppressing or eliminating important insect pests of agricultural or veterinary importance. In order to develop SIT for mosquitoes, female elimination prior to release is essential as they are the disease-transmitting sex. A genetic sexing strain (GSS) of Anopheles arabiensis was created based on resistance to dieldrin, and methods of sex separation at the egg stage were developed. The use of this strain for SIT will require sexually sterile males: useful radiation doses for this purpose were determined for pupae and adults. For the creation of the sexing strain, dieldrin-resistant males were irradiated with 40 Gy using a 60Co source and were subsequently crossed to homozygous susceptible virgin females. Individual families were screened for semi-sterility and for male resistance to dieldrin. For sex separation, eggs of a resulting GSS, ANO IPCL1, were exposed to varying concentrations of dieldrin for different durations. Percent hatch, larval survival, and male and female emergence were recorded. Radiation induced sterility was determined following adult and pupa exposure to gamma rays at 0-105 Gy. Mortality induced by dieldrin treatment, and levels of sterility post radiation were investigated. ANO IPCL1 contains a complex chromosome aberration that pseudo-links the male-determining Y chromosome and dieldrin resistance, conferring high natural semi-sterility. Exposure of eggs to 2, 3, and 4 ppm dieldrin solutions resulted in complete female elimination without a significant decrease of male emergence compared to the controls. A dose of 75 Gy reduced the fertility to 3.8 and 6.9% when males were irradiated as pupae or adults respectively, but the proportions of progeny of these males reaching adulthood were 0.6 and 1.5% respectively The GSS ANO IPCL1 was shown to be a suitable strain for further testing for SIT though high semi-sterility is a disadvantage for mass rearing.

  15. Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum.

    PubMed Central

    Escalante, A A; Lal, A A; Ayala, F J

    1998-01-01

    We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25. PMID:9584096

  16. Evidence for genetic linkage between a polymorphism in the GNAS gene and malaria in South Indian population.

    PubMed

    Gupta, Himanshu; Sakharwade, Sanica C; Angural, Arshia; Kotambail, Ananthapadmanabha; Bhat, Gopal K; Hande, Manjunath H; D'Souza, Sydney C; Rao, Purnima; Kumari, Veena; Saadi, Abdul V; Satyamoorthy, Kapaettu

    2013-12-01

    The complex imprinted GNAS locus which encodes G-alpha subunit (Gαs) is involved in a number of G-protein coupled signaling pathways in eukaryotic cells. Erythrocyte invasion by Plasmodium falciparum parasites is significantly regulated by protein of GNAS gene. This study was designed to evaluate the association between single nucleotide polymorphisms (SNPs) present in GNAS locus and susceptibility to malaria. In this case control study, individuals affected by P. falciparum malaria (n=230), Plasmodium vivax malaria (n=230) and normal controls (n=230) were tested for the association of eighteen (18) known SNPs to evaluate their role in the onset of the disease. There was no significant difference in genotype frequencies of all the SNPs tested between P. falciparum and P. vivax affected individuals. However, when Bonferroni correction for multiple comparisons were performed as a control, our results demonstrated alleles and genotypes of rs7121: C>T (NC_000020.10:g.57478807C>T), a silent polymorphism situated in the exon 5, were significantly (p<0.05) associated with susceptibility to malaria in the South Indians participants. Our results demonstrate that population specific polymorphisms that exist in GNAS gene may alter the risk of occurrence of malaria.

  17. Genetic sex separation of the malaria vector, Anopheles arabiensis, by exposing eggs to dieldrin

    PubMed Central

    2012-01-01

    Background The sterile insect technique (SIT) has been used with success for suppressing or eliminating important insect pests of agricultural or veterinary importance. In order to develop SIT for mosquitoes, female elimination prior to release is essential as they are the disease-transmitting sex. A genetic sexing strain (GSS) of Anopheles arabiensis was created based on resistance to dieldrin, and methods of sex separation at the egg stage were developed. The use of this strain for SIT will require sexually sterile males: useful radiation doses for this purpose were determined for pupae and adults. Methods For the creation of the sexing strain, dieldrin-resistant males were irradiated with 40 Gy using a 60Co source and were subsequently crossed to homozygous susceptible virgin females. Individual families were screened for semi-sterility and for male resistance to dieldrin. For sex separation, eggs of a resulting GSS, ANO IPCL1, were exposed to varying concentrations of dieldrin for different durations. Percent hatch, larval survival, and male and female emergence were recorded. Radiation induced sterility was determined following adult and pupa exposure to gamma rays at 0–105 Gy. Mortality induced by dieldrin treatment, and levels of sterility post radiation were investigated. Results ANO IPCL1 contains a complex chromosome aberration that pseudo-links the male-determining Y chromosome and dieldrin resistance, conferring high natural semi-sterility. Exposure of eggs to 2, 3, and 4 ppm dieldrin solutions resulted in complete female elimination without a significant decrease of male emergence compared to the controls. A dose of 75 Gy reduced the fertility to 3.8 and 6.9% when males were irradiated as pupae or adults respectively, but the proportions of progeny of these males reaching adulthood were 0.6 and 1.5% respectively Conclusion The GSS ANO IPCL1 was shown to be a suitable strain for further testing for SIT though high semi-sterility is a

  18. Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study

    PubMed Central

    Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D.; Almagro-Garcia, Jacob; Neal, Aaron T.; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P.; Fairhurst, Rick M.

    2017-01-01

    Summary Background As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong Subregion (GMS), emerging resistance to partner drugs in artemisinin combination therapies (ACTs) seriously threatens global efforts to treat and eliminate this disease. Molecular markers for ACT failure are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in Southeast Asia and beyond. Methods We performed a genome-wide association study (GWAS) of 297 P. falciparum isolates from Cambodia to investigate the relationship of 11,630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of dihydroartemisinin-piperaquine failures. We then performed a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Findings Piperaquine IC50s increased significantly from 2011 to 2013 in 3 Cambodian provinces. Genome-wide analysis of SNPs identified a chromosome 13 region that associates with elevated piperaquine IC50s. A nonsynonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin II and plasmepsin III genes on chromosome 14 also associate with elevated piperaquine IC50s. After adjusting for covariates, both exo-E415G and plasmepsin II-III markers significantly associate with decreased treatment efficacy (0.38 and 0.41 survival rates, respectively). Interpretation The exo-E415G SNP and plasmepsin II-III amplification are markers of piperaquine resistance and dihydroartemisinin

  19. Colonization of malaria vectors under semi-field conditions as a strategy for maintaining genetic and phenotypic similarity with wild populations.

    PubMed

    Ng'habi, Kija R; Lee, Yoosook; Knols, Bart G J; Mwasheshi, Dickson; Lanzaro, Gregory C; Ferguson, Heather M

    2015-01-21

    Malaria still accounts for an estimated 207 million cases and 627,000 deaths worldwide each year. One proposed approach to complement existing malaria control methods is the release of genetically-modified (GM) and/or sterile male mosquitoes. As opposed to laboratory colonization, this requires realistic semi field systems to produce males that can compete for females in nature. This study investigated whether the establishment of a colony of the vector Anopheles arabiensis under more natural semi-field conditions can maintain higher levels of genetic diversity than achieved by laboratory colonization using traditional methods. Wild females of the African malaria vector An. arabiensis were collected from a village in southern Tanzania and used to establish new colonies under different conditions at the Ifakara Health Institute. Levels of genetic diversity and inbreeding were monitored in colonies of An. arabiensis that were simultaneously established in small cage colonies in the SFS and in a large semi-field (SFS) cage and compared with that observed in the original founder population. Phenotypic traits that determine their fitness (body size and energetic reserves) were measured at 10(th) generation and compared to founder wild population. In contrast to small cage colonies, the SFS population of An. arabiensis exhibited a higher degree of similarity to the founding field population through time in several ways: (i) the SFS colony maintained a significantly higher level of genetic variation than small cage colonies, (ii) the SFS colony had a lower degree of inbreeding than small cage colonies, and (iii) the mean and range of mosquito body size in the SFS colony was closer to that of the founding wild population than that of small cage colonies. Small cage colonies had significantly lower lipids and higher glycogen abundances than SFS and wild population. Colonization of An. arabiensis under semi-field conditions was associated with the retention of a higher

  20. [Airport malaria].

    PubMed

    Queyriaux, Benjamin; Pradines, Bruno; Hasseine, Lilia; Coste, Sébastien; Rodriguez, Patrick; Coffinet, Thierry; Haus-Cheymol, Rachel; Rogier, Christophe

    2009-01-01

    Airport malaria is a particular form of autochthonous malaria: it happens when the Plasmodium infected Anopheles genus mosquito travels from an endemic area to a malaria free airport. Since 1969, 30 cases of airport malaria have been reported in France, 2 during summer 2008. The severity of airport malaria is explained by the frequency of Plasmodium falciparum infecting non immune individuals and an often important diagnosis delay. It is a compulsory notification disease in France. The International Health Regulations (IHR) require states to check that airplanes coming from malaria or arboviral endemic area are systematically disinsected. Vector control measures have to be implemented within a distance of at least 400 meters around the perimeter of airports in malaria or arboviral endemic areas. In France, this measure applies to all airports of French overseas territories, except for the island of Saint-Pierre and Miquelon.

  1. Genetic diversity and population structure of the primary malaria vector Anopheles sinensis (Diptera: Culicidae) in China inferred by cox1 gene.

    PubMed

    Feng, Xinyu; Huang, Libin; Lin, Lin; Yang, Manni; Ma, Yajun

    2017-02-10

    Anopheles sinensis is a primary vector for Plasmodium vivax malaria in most regions of China. A comprehensive understanding of genetic variation and structure of the mosquito would be of benefit to the vector control and in a further attempt to contribute to malaria elimination in China. However, there is only inadequate population genetic data pertaining to An. sinensis currently. Genetic variations and structure among populations of An. sinensis was examined and analyzed based on the nucleotide sequences of a 662 nt variable region of the mitochondrial cox1 gene among 15 populations from 20 collection sites in China. A total of 453 individuals in 15 populations were analyzed. The cox1 gene sequences were aligned, and 247 haplotypes were detected, 41 of these shared between populations. The range of haplotype diversity was from 0.709 (Yunnan) to 0.998 (Anhui). The genealogic network showed that the haplotypes were divided into two clusters, cluster I was at a high level of homoplasy, while cluster II included almost all individuals from the Yunnan population. The Yunnan population displayed a significantly high level of genetic differentiation (0.452-0.622) and a restricted gene flow with other populations. The pairwise F ST values among other populations were lower. The AMOVA result showed that the percentage of variation within populations (83.83%) was higher than that among populations (16.17%). Mantel test suggested that geographical distance did not significantly contribute to the genetic differentiation (R (2) = 0.0125, P = 0.59). Neutral test and mismatch analysis results showed that the An. sinensis population has undergone demographic expansions. Anopheles sinensis populations showed high genetic polymorphism by cox1 gene. The weak genetic structure may be a consequence of low genetic differentiation and high gene flow among populations, except the Yunnan samples. The Yunnan population was isolated from the other populations, gene flow limited by

  2. Population genetic structure of the malaria vector Anopheles funestus, in a recently re-colonized area of the Senegal River basin and human-induced environmental changes.

    PubMed

    Samb, Badara; Dia, Ibrahima; Konate, Lassana; Ayala, Diego; Fontenille, Didier; Cohuet, Anna

    2012-09-05

    Anopheles funestus is one of the major malaria vectors in tropical Africa. Because of several cycles of drought events that occurred during the 1970s, this species had disappeared from many parts of sahelian Africa, including the Senegal River basin. However, this zone has been re-colonized during the last decade by An. funestus, following the implementation of two dams on the Senegal River. Previous studies in that area revealed heterogeneity at the biological and chromosomal level among these recent populations. Here, we studied the genetic structure of the newly established mosquito populations using eleven microsatellite markers in four villages of the Senegal River basin and compared it to another An. funestus population located in the sudanian domain. Our results presume Hardy Weinberg equilibrium in each An. funestus population, suggesting a situation of panmixia. Moreover, no signal from bottleneck or population expansion was detected across populations. The tests of genetic differentiation between sites revealed a slight but significant division into three distinct genetic entities. Genetic distance between populations from the Senegal River basin and sudanian domain was correlated to geographical distance. In contrast, sub-division into the Senegal River basin was not correlated to geographic distance, rather to local adaptation. The high genetic diversity among populations from Senegal River basin coupled with no evidence of bottleneck and with a gene flow with southern population suggests that the re-colonization was likely carried out by a massive and repeated stepping-stone dispersion starting from the neighboring areas where An. funestus endured.

  3. Malaria (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Malaria KidsHealth > For Parents > Malaria Print A A A ... Prevention Diagnosis and Treatment en español Malaria About Malaria Malaria is a common infection in hot, tropical ...

  4. Imported malaria.

    PubMed

    Schultz, M G

    1974-01-01

    There have been 4 waves of imported malaria in the USA. They occurred during the colonization of the country and during the Second World War, the UN Police Action in Korea, and the Viet-Nam conflict. The first 3 episodes are briefly described and the data on imported malaria from Viet-Nam are discussed in detail.Endemic malaria is resurgent in many tropical countries and international travel is also on the rise. This increases the likelihood of malaria being imported from an endemic area and introduced into a receptive area. The best defence for countries threatened by imported malaria is a vigorous surveillance programme. The principles of surveillance are discussed and an example of their application is provided by a description of the methods used to conduct surveillance of malaria in the USA.

  5. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study.

    PubMed

    Amato, Roberto; Lim, Pharath; Miotto, Olivo; Amaratunga, Chanaki; Dek, Dalin; Pearson, Richard D; Almagro-Garcia, Jacob; Neal, Aaron T; Sreng, Sokunthea; Suon, Seila; Drury, Eleanor; Jyothi, Dushyanth; Stalker, Jim; Kwiatkowski, Dominic P; Fairhurst, Rick M

    2017-02-01

    As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine. We then did a survival analysis of 133 patients to determine whether candidate molecular markers predicted parasite recrudescence following dihydroartemisinin-piperaquine treatment. Piperaquine IC50s increased significantly from 2011 to 2013 in three Cambodian provinces (2011 vs 2013 median IC50s: 20·0 nmol/L [IQR 13·7-29·0] vs 39·2 nmol/L [32·8-48·1] for Ratanakiri, 19·3 nmol/L [15·1-26·2] vs 66·2 nmol/L [49·9-83·0] for Preah Vihear, and 19·6 nmol/L [11·9-33·9] vs 81·1 nmol/L [61·3-113·1] for Pursat; all p≤10(-3); Kruskal-Wallis test). Genome-wide analysis of SNPs identified a chromosome 13 region that associates with raised piperaquine IC50s. A non-synonymous SNP (encoding a Glu415Gly substitution) in this region, within a gene encoding an exonuclease, associates with parasite recrudescence following dihydroartemisinin-piperaquine treatment. Genome-wide analysis of CNVs revealed that a single copy of the mdr1 gene on chromosome 5 and a novel amplification of the plasmepsin 2 and plasmepsin 3 genes on chromosome 14 also associate with raised piperaquine IC50s. After adjusting for covariates, both

  6. Vocabulary Development with Contextual Clues

    ERIC Educational Resources Information Center

    Goodrich, Hubbard C.

    1977-01-01

    Advanced students can grasp the meaning of many new words from clues in the context. Such words often occur as obvious synonyms, as summarizing words, in comparisons and associations, etc. Two types of exercises are presented which may help to develop the students' ability to recognize such words. (IFS/WGA)

  7. Malaria vaccine against sporozoites?

    PubMed

    Nussenzweig, V; Nussenzweig, R S

    1985-01-01

    Malaria kills over one million people a year. A promising candidate suitable for either a synthetic or a genetically engineered malaria vaccine has been synthesized. The molecule, a string of 4 amino acids repeated 3 times, is modeled on a surface component of sporozoites apparent when they are injected by a mosquito into a human. An immune response to the peptide might neutralize sporozoites before they are sequestered in host liver cells. The peptide reacted with antibodies in serum of randomly selected individuals living where malaria is endemic and with serum from a volunteer protected from infection by immunization with irradiated parasites. It induced antibodies in animals; the antibodies prevented the parasite from entering human cells growing in culture.

  8. Transgenic mosquitoes and malaria transmission.

    PubMed

    Christophides, George K

    2005-03-01

    As the malaria burden persists in most parts of the developing world, the concept of implementation of new strategies such as the use of genetically modified mosquitoes to control the disease continues to gain support. In Africa, which suffers most from malaria, mosquito vector populations are spread almost throughout the entire continent, and the parasite reservoir is big and continuously increasing. Moreover, malaria is transmitted by many species of anophelines with specific seasonal and geographical patterns. Therefore, a well designed, evolutionarily robust and publicly accepted plan aiming at population reduction or replacement is required. The task is twofold: to engineer mosquitoes with a genetic trait that confers resistance to malaria or causes population suppression; and, to drive the new trait through field populations. This review examines these two issues, and describes the groundwork that has been done towards understanding of the complex relation between the parasite and its vector.

  9. Eradicating malaria.

    PubMed

    Breman, Joel G

    2009-01-01

    The renewed interest in malaria research and control is based on the intolerable toll this disease takes on young children and pregnant women in Africa and other vulnerable populations; 150 to 300 children die each hour from malaria amounting to 1 to 2 million deaths yearly. Malaria-induced neurologic impairment, anemia, hypoglycemia, and low birth weight imperil normal development and survival. Resistance of Plasmodium falciparum to drugs and Anopheles mosquitoes to insecticides has stimulated discovery and development of artemisinin-based combination treatments (ACTs) and other drugs, long-lasting insecticide-treated bednets (with synthetic pyrethroids) and a search for non-toxic, long-lasting, affordable insecticides for indoor residual spraying (IRS). Malaria vaccine development and testing are progressing rapidly and a recombinant protein (RTS,S/AS02A) directed against the circumsporozoite protein is soon to be in Phase 3 trials. Support for malaria control, research, and advocacy through the Global Fund for HIV/AIDS, Tuberculosis and Malaria, the U.S. President's Malaria Initiative, the Bill & Melinda Gates Foundation, WHO and other organizations is resulting in decreasing morbidity and mortality in many malarious countries. Sustainability of effective programs through training and institution strengthening will be the key to malaria elimination coupled with improved surveillance and targeted research.

  10. Microsatellite analysis of malaria parasites.

    PubMed

    Orjuela-Sánchez, Pamela; Brandi, Michelle C; Ferreira, Marcelo U

    2013-01-01

    Microsatellites have been increasingly used to investigate the population structure of malaria parasites, to map genetic loci contributing to phenotypes such as drug resistance and virulence in laboratory crosses and genome-wide association studies and to distinguish between treatment failures and new infections in clinical trials. Here, we provide optimized protocols for genotyping highly polymorphic microsatellites sampled from across the genomes of the human malaria parasites Plasmodium falciparum and P. vivax that have been extensively used in research laboratories worldwide.

  11. Molecular basis of human cerebral malaria development.

    PubMed

    Wah, Saw Thu; Hananantachai, Hathairad; Kerdpin, Usanee; Plabplueng, Chotiros; Prachayasittikul, Virapong; Nuchnoi, Pornlada

    2016-01-01

    Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.

  12. Nails: diagnostic clue to genodermatoses.

    PubMed

    Inamadar, Arun C; Palit, Aparna

    2012-01-01

    Nails are cutaneous appendages mostly involved in mechanical functions. However, nails may reflect presence of various systemic disorders evidenced by alteration of their shape, size, color or texture. Genodermatoses are multisystem disorders with cutaneous involvement. Many of the genodermatoses present with nail changes and some of these may be the clinical pointers to the diagnosis. Diagnostic clues to various genodermatoses derived from nail findings have been discussed.

  13. [Research progress on malaria vector control].

    PubMed

    Zhu, Guo-Ding; Cao, Jun; Zhou, Hua-Yun; Gao, Qi

    2013-06-01

    Vector control plays a crucial role in the stages of malaria control and elimination. Currently, it mainly relies on the chemical control methods for adult mosquitoes in malaria endemic areas, however, it is undergoing the serious threat by insecticide resistance. In recent years, the transgenic technologies of malaria vectors have made a great progress in the laboratory. This paper reviews the challenges of the traditional methods and the rapid developed genetic modified technology in the application of vector control.

  14. Gene-therapy for malaria prevention.

    PubMed

    Rodrigues, Mauricio M; Soares, Irene S

    2014-11-01

    The limited number of tools for malaria prevention and the inability to eradicate the disease have required large investments in vaccine development, as vaccines have been the only foreseeable type of immunoprophylaxis against malaria. An alternative strategy named vectored immunoprophylaxis (VIP) now would allow genetically transduced host cells to assemble and secrete antibodies that neutralize the infectivity of the malaria parasite and prevent disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. WHO Expert Committee on Malaria. Seventeenth report.

    PubMed

    1979-01-01

    This publication consists of guidelines to assist health administrators and planners in planning, implementing, and evaluating malaria control programs that reflect the reorientation of the World Health Organization malaria control strategy endorsed by the World Health Assembly. The report stresses approaches to malaria control, describing the recent resurgence of malaria and present constraints on malaria control; prerequisites for implementation of the revised antimalaria strategy; objectives of a malaria control program; factors affecting planning of control programs including epidemiological factors related to the environment, man, the vector, and the parasite; socioeconomic factors; and the use of antimalaria measures in 4 different situations for reduction and prevention of mortality due to malaria, reduction and prevention of mortality and morbidity particularly in high risk groups, reduction of prevalence and endemicity of malaria, or countrywide malaria control aimed ultimately at eradication; program implementation, including definition of targets, interrelationship of the malaria services, general health services, and community, and program implementation in relation to each of the 4 tactical variants; and general principles, operational and epidemiological criteria, and socioeconomic indicators for program evaluation. Factors determining malaria epidemics, outbreaks of malaria during eradication or control campaigns, forecasting and detection of malaria epidemics, and control of epidemics are then discussed. Training in malaria control and advances in antimalaria measures including drugs, immunological methods, antimosquito measures, and biological and genetic approaches to vector control and their potential value are assessed. Program coordination between countries and at regional and global levels and data collection and dissemination for international surveillance are discussed. A series of recommendations is offered for various aspects of malaria

  16. Molecular method for the diagnosis of imported pediatric malaria.

    PubMed

    Delhaes Jeanne, L; Berry, A; Dutoit, E; Leclerc, F; Beaudou, J; Leteurtre, S; Camus, D; Benoit-Vical, F

    2010-02-01

    Malaria is a polymorphous disease; it can be life threatening especially for children. We report a case of imported malaria in a boy, illustrating the epidemiological and clinical aspects of severe pediatric malaria. In this case real-time PCR was used to quantify Plasmodium falciparum DNA levels, to monitor the evolution under treatment, and to determine genetic mutations involved in chloroquine resistance. The major epidemiological features of imported malaria, and the difficulty to diagnose childhood severe malaria are described. The contribution of molecular methods for the diagnosis of imported malaria is discussed.

  17. Malaria Treatment (United States)

    MedlinePlus

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version ...

  18. Malaria and Travelers

    MedlinePlus

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria and Travelers Recommend on Facebook Tweet Share Compartir ... may be at risk for infection. Determine if malaria transmission occurs at the destinations Obtain a detailed ...

  19. Malaria Pathogenesis

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Good, Michael F.; Milon, Genevieve

    1994-06-01

    Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity.

  20. Molecular evolution and population genetics of a Gram-negative binding protein gene in the malaria vector Anopheles gambiae (sensu lato).

    PubMed

    Salgueiro, Patrícia; Lopes, Ana Sofia; Mendes, Cristina; Charlwood, Jacques Derek; Arez, Ana Paula; Pinto, João; Silveira, Henrique

    2016-09-23

    Clarifying the role of the innate immune system of the malaria vector Anopheles gambiae is a potential way to block the development of the Plasmodium parasites. Pathogen recognition is the first step of innate immune response, where pattern recognition proteins like GNBPs play a central role. We analysed 70 sequences of the protein coding gene GNBPB2 from two species, Anopheles gambiae (s.s.) and An. coluzzii, collected in six African countries. We detected 135 segregating sites defining 63 distinct haplotypes and 30 proteins. Mean nucleotide diversity (π) was 0.014 for both species. We found no significant genetic differentiation between species, but a significant positive correlation between genetic differentiation and geographical distance among populations. Species status seems to contribute less for the molecular differentiation in GNBPB2 than geographical region in the African continent (West and East). Purifying selection was found to be the most common form of selection, as in many other immunity-related genes. Diversifying selection may be also operating in the GNBPB2 gene.

  1. The genetics of green thorax, a new larval colour mutant, non-linked with ruby - eye locus in the malaria mosquito, Anopheles stephensi.

    PubMed

    Sanil, D; Shetty, N J

    2009-06-01

    Anopheles stephensi, an important vector of malaria continues to be distributed widely in the Indian subcontinent. The natural vigour of the species combined with its new tolerance, indeed resistance to insecticides has made it obligatory that we look for control methods involving genetic manipulation. Hence, there is an immediate need for greater understanding of the genetics of this vector species. One of the requirements for such genetic studies is the establishment of naturally occurring mutants, establishment of the genetic basis for the same and use of such mutants in the genetic transformation studies and other genetic control programme(s). This paper describes the isolation and genetic studies of a larval colour mutant, green thorax (gt), and linkage studies involving another autosomal recessive mutant ruby- eye (ru) in An. stephensi. After the initial discovery, the mutant green thorax was crossed inter se and pure homozygous stock of the mutant was established. The stock of the mutant ruby- eye, which has been maintained as a pure stock in the laboratory. Crosses were made between the wild type and mutant, green thorax to determine the mode of inheritance of green thorax. For linkage studies, crosses were made between the mutant green thorax and another autosomal recessive mutant ruby-eye. The percentage cross-over was calculated for the genes linkage relationship for gt and gt ru. Results of crosses between mutant and wild type showed that the inheritance of green thorax (gt) in An. stephensi is monofactorial in nature. The gt allele is recessive to wild type and is autosomal. The linkage studies showed no linkage between ru and gt. The mutant gt represents an excellent marker for An. stephensi as it is expressed in late III instar stage of larvae and is prominent in IV instar and pupal stages with complete penetrance and high viability. The said mutant could be easily identified without the aid of a microscope. This mutant can be used extensively to

  2. Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

    PubMed Central

    Taravella, Angela M.; Bustamante, Carlos D.; Sikora, Martin

    2017-01-01

    The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34–49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011–0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48–65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause. PMID:28282382

  3. Malaria vaccine.

    PubMed

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor.

  4. The role of vitamin D in malaria.

    PubMed

    Lương, Khanh Vinh Quốc; Nguyễn, Lan Thi Hoàng

    2015-01-15

    An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus Calmette-Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed.

  5. Designing malaria vaccines to circumvent antigen variability.

    PubMed

    Ouattara, Amed; Barry, Alyssa E; Dutta, Sheetij; Remarque, Edmond J; Beeson, James G; Plowe, Christopher V

    2015-12-22

    Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.

  6. Ethical aspects of malaria control and research.

    PubMed

    Jamrozik, Euzebiusz; de la Fuente-Núñez, Vânia; Reis, Andreas; Ringwald, Pascal; Selgelid, Michael J

    2015-12-22

    Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria--and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy.

  7. Biochemical Systematics and Population Genetic Structure of Anopheles Pseudopunctipennis, Vector of Malaria in Central and South America

    DTIC Science & Technology

    1995-01-01

    possibly due to reduced genetic variabil- ity accompanied by a diminished capacity of the species to adapt to environmental changes ,25 might result...produce pop- ulations less polymorphic. Insect colonies are characterized by rapid genetic changes , such as loss of heterozygosity.32 Loss of population...Ciencias Quimicas y Farmacia, Edi- ficio T-12, 2 Nivel, Ciudad Universitaria, Zona 12, Guatemala City, Guatemala, 01012. Renato Martinez Granaou

  8. Ecological zones rather than molecular forms predict genetic differentiation in the malaria vector Anopheles gambiae s.s. in Ghana.

    PubMed

    Yawson, Alexander E; Weetman, David; Wilson, Michael D; Donnelly, Martin J

    2007-02-01

    The malaria mosquito Anopheles gambiae s.s. is rapidly becoming a model for studies on the evolution of reproductive isolation. Debate has centered on the taxonomic status of two forms (denoted M and S) within the nominal taxon identified by point mutations in the X-linked rDNA region. Evidence is accumulating that there are significant barriers to gene flow between these forms, but that the barriers are not complete throughout the entire range of their distribution. We sampled populations from across Ghana and southern Burkina Faso, West Africa, from areas where the molecular forms occurred in both sympatry and allopatry. Neither Bayesian clustering methods nor F(ST)-based analysis of microsatellite data found differentiation between the M and S molecular forms, but revealed strong differentiation among different ecological zones, irrespective of M/S status and with no detectable effect of geographical distance. Although no M/S hybrids were found in the samples, admixture analysis detected evidence of contemporary interform gene flow, arguably most pronounced in southern Ghana where forms occur sympatrically. Thus, in the sampled area of West Africa, lack of differentiation between M and S forms likely reflects substantial introgression, and ecological barriers appear to be of greater importance in restricting gene flow.

  9. The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

    PubMed Central

    Papathanos, Philippos A; Windbichler, Nikolai; Menichelli, Miriam; Burt, Austin; Crisanti, Andrea

    2009-01-01

    Background Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector Anopheles gambiae. Results We have identified the Anopheles gambiae vasa-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous vasa locus. Two reporter constructs indicate the existence of distinct vasa regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. vasa driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae. Conclusion We have characterized the vasa regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early vasa driven homing endonuclease expression. PMID:19573226

  10. Coadaptation and malaria control.

    PubMed

    Tosta, Carlos Eduardo

    2007-06-01

    Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM). If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1) the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2) human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the maintenance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3) coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments) between the partners; (4) plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity) and artificial (drugs, insecticides, vaccines) measures aiming at destroying them; (5) since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6) the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components, that means, panadaptive

  11. Malaria Surveillance - United States, 2013.

    PubMed

    Cullen, Karen A; Mace, Kimberly E; Arguin, Paul M

    2016-03-04

    corrected the species for 85 of the 137 (62%) samples evaluated for drug resistance marker testing. Of the 904 patients who reported purpose of travel, 635 (70%) were visiting friends or relatives (VFR). Among the 961 cases in U.S. civilians for whom information on chemoprophylaxis use and travel region was known, 42 (4%) patients reported that they had initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-six cases were reported in pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, approximately 270 (16%) were classified as severe illnesses in 2013. Of these, 10 persons with malaria died in 2013, the highest number since 2001. In 2013, a total of 137 blood samples submitted to CDC were tested for molecular markers associated with antimalarial drug resistance. Of the 100 P. falciparum-positive samples, 95 were tested for pyrimethamine resistance: 88 (93%) had genetic polymorphisms associated with pyrimethamine drug resistance, 74 (76%) with sulfadoxine resistance, 53 (53%) with chloroquine resistance, one (1%) with atovaquone resistance, none with mefloquine drug resistance, and none with artemisinin resistance. The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2013 is the third highest annual total since then. Despite progress in reducing the global burden of malaria, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. Completion of data elements on the malaria case report form increased slightly in 2013 compared with 2012, but still remains unacceptably low. This incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFRs continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFRs need to be developed

  12. Malaria Surveillance - United States, 2014.

    PubMed

    Mace, Kimberly E; Arguin, Paul M

    2017-05-26

    . 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

  13. The HFE genotype and a formulated diet controlling for iron status attenuate experimental cerebral malaria in mice.

    PubMed

    Leitner, Dominique F; Stoute, José A; Landmesser, Mary; Neely, Elizabeth; Connor, James R

    2015-10-01

    Plasmodium falciparum infects approximately 500million individuals each year. A small but significant number of infections lead to complications such as cerebral malaria. Cerebral malaria is associated with myelin damage and neurological deficits in survivors, and iron status is thought to impact the outcome of infection. We evaluated whether a mouse model of experimental cerebral malaria with Plasmodium berghei ANKA strain was altered by dietary iron deficiency or genetic iron overload (H67D HFE). We found that H67D mice had increased survival over H67H (wild type) mice. Moreover, a specifically designed formulation diet increased survival regardless of whether the diet was iron deficient or iron adequate. To determine potential mechanisms underlying demyelination in experimental cerebral malaria, we measured Semaphorin4A (Sema4A) protein levels in the brain because we found it is cytotoxic to oligodendrocytes. Sema4A was increased in wild type mice that developed experimental cerebral malaria while consuming standard rodent chow, consistent with a decrease in myelin basic protein, an indicator of myelin integrity. The brains of iron deficient and H67D mice had lower levels of Sema4A. Myelin basic protein was decreased in brains of mice fed the iron deficient diet as has been previously reported. We also examined erythropoietin, which is under consideration for treatment of cerebral malaria, and IL-6, which is known to increase during infection. We found that plasma erythropoietin was elevated and IL-6 was low in H67D mice and in the mice fed the formulation diets. These data reveal a paradigm-shifting concept that maintaining iron status may not increase the mortality associated with malaria and provide a dietary strategy for further examination. Moreover, the data provide clues for exploring the mechanism to limit the co-morbidity associated with experimental cerebral malaria that appears to include decreased Sema4A in brain as well as elevated erythropoietin

  14. Cerebral Malaria.

    PubMed

    Marsden, P D; Bruce-Chwatt, L J

    1975-01-01

    Cerebral malaria is an acute diffuse encephalopathy associated only with Plasmodium falciparum. It is probably a consequence of the rapid proliferation of the parasites in the body of man in relation to red cell invasion, and results in stagnation of blood flow in cerebralcapillaries with thromobotic occlusion of large numbers of cerebral capillaries. The subsequent cerebral pathology is cerebral infarction with haemorrhage and cerebral oedema. The wide prevalence of P. falciparum in highly endemic areas results in daily challenges to patients from several infected mosquitoes. It is thus important to understand the characteristics of P. falciparum, since this is one of the most important protozoan parasites of man and severe infection from it constitutes one of the few real clinical emergencies in tropical medicine. One of the more important aspects of the practice of medicine in the tropics is to establish a good understanding of the pattern of medical practice in that area. This applies to malaria as well as to other diseases. The neophyte might be somewhat surprised to learn, for example that an experienced colleague who lives in a holoendemic malarious area such as West Africa, sees no cerebral malaria. But the explanation is simple when the doctor concerned has a practice which involves treating adults only. Cerebral malaria is rare in adults, because in highly endemic areas, by the age of 1 year most of the infants in a group under study have already experienced their first falciparum infection. By the time they reach adult life, they have a solid immunity against severe falciparum infections. In fact, "clinical malaria" could occur in such a group under only two circumstances: 1) in pregnancy, a patent infection with P. falciparum might develop, probably due to an IgG drain across the placenta to the foetus;2) in an individual who has constantly taken antimalarials and who may have an immunity at such a low level that when antimalarial therapy is interrupted

  15. A Keen Eye for Clues

    NASA Astrophysics Data System (ADS)

    Logan, Jonothan

    2010-03-01

    Samuel Goudsmit, a pioneering atomic theorist who specialized in the exacting, quantitative art of interpreting line spectra and who, with George Uhlenbeck, discovered electron spin, also contributed key studies of nuclear moments, neutron scattering, and the statistics of experimental measurement. Beyond the traditional ambit of laboratory, desk, and blackboard, Goudsmit was drawn to a wider world of inquiry -- to museums and archaeological sites in Cairo as a respected amateur Egyptologist; to the MIT Radiation Lab early in WWII and to the briefing rooms of British pilots, analyzing the effectiveness of radar; and across wartime Europe by jeep, as head of an Allied mission in pursuit of clear information on Germany's secret fission program. After the war he took up chairmanship of a major physics department and editorship of the Physical Review, where he created the ambitious new journal, Physical Review Letters. The present author, Goudsmit's assistant at the journal forty years ago, looks for a common element that might explain this extraordinary diversity of interests and contributions, and finds one in Goudsmit's abiding delight in solving puzzles of every kind, coupled with a detective's keen eye for clues.

  16. Plasmodium simium, a Plasmodium vivax-Related Malaria Parasite: Genetic Variability of Duffy Binding Protein II and the Duffy Antigen/Receptor for Chemokines

    PubMed Central

    Camargos Costa, Daniela; Pereira de Assis, Gabriela Maíra; de Souza Silva, Flávia Alessandra; Araújo, Flávia Carolina; de Souza Junior, Júlio César; Braga Hirano, Zelinda Maria; Satiko Kano, Flora; Nóbrega de Sousa, Taís; Carvalho, Luzia Helena; Ferreira Alves de Brito, Cristiana

    2015-01-01

    Plasmodium simium is a parasite from New World monkeys that is most closely related to the human malaria parasite Plasmodium vivax; it also naturally infects humans. The blood-stage infection of P. vivax depends on Duffy binding protein II (PvDBPII) and its cognate receptor on erythrocytes, the Duffy antigen receptor for chemokines (hDARC), but there is no information on the P. simium erythrocytic invasion pathway. The genes encoding P. simium DBP (PsDBPII) and simian DARC (sDARC) were sequenced from Southern brown howler monkeys (Alouatta guariba clamitans) naturally infected with P. simium because P. simium may also depend on the DBPII/DARC interaction. The sequences of DBP binding domains from P. vivax and P. simium were highly similar. However, the genetic variability of PsDBPII was lower than that of PvDBPII. Phylogenetic analyses demonstrated that these genes were strictly related and clustered in the same clade of the evolutionary tree. DARC from A. clamitans was also sequenced and contained three new non-synonymous substitutions. None of these substitutions were located in the N-terminal domain of DARC, which interacts directly with DBPII. The interaction between sDARC and PvDBPII was evaluated using a cytoadherence assay of COS7 cells expressing PvDBPII on their surfaces. Inhibitory binding assays in vitro demonstrated that antibodies from monkey sera blocked the interaction between COS-7 cells expressing PvDBPII and hDARC-positive erythrocytes. Taken together, phylogenetic analyses reinforced the hypothesis that the host switch from humans to monkeys may have occurred very recently in evolution, which sheds light on the evolutionary history of new world plasmodia. Further invasion studies would confirm whether P. simium depends on DBP/DARC to trigger internalization into red blood cells. PMID:26107662

  17. Plasmodium simium, a Plasmodium vivax-related malaria parasite: genetic variability of Duffy binding protein II and the Duffy antigen/receptor for chemokines.

    PubMed

    Camargos Costa, Daniela; Pereira de Assis, Gabriela Maíra; de Souza Silva, Flávia Alessandra; Araújo, Flávia Carolina; de Souza Junior, Júlio César; Braga Hirano, Zelinda Maria; Satiko Kano, Flora; Nóbrega de Sousa, Taís; Carvalho, Luzia Helena; Ferreira Alves de Brito, Cristiana

    2015-01-01

    Plasmodium simium is a parasite from New World monkeys that is most closely related to the human malaria parasite Plasmodium vivax; it also naturally infects humans. The blood-stage infection of P. vivax depends on Duffy binding protein II (PvDBPII) and its cognate receptor on erythrocytes, the Duffy antigen receptor for chemokines (hDARC), but there is no information on the P. simium erythrocytic invasion pathway. The genes encoding P. simium DBP (PsDBPII) and simian DARC (sDARC) were sequenced from Southern brown howler monkeys (Alouatta guariba clamitans) naturally infected with P. simium because P. simium may also depend on the DBPII/DARC interaction. The sequences of DBP binding domains from P. vivax and P. simium were highly similar. However, the genetic variability of PsDBPII was lower than that of PvDBPII. Phylogenetic analyses demonstrated that these genes were strictly related and clustered in the same clade of the evolutionary tree. DARC from A. clamitans was also sequenced and contained three new non-synonymous substitutions. None of these substitutions were located in the N-terminal domain of DARC, which interacts directly with DBPII. The interaction between sDARC and PvDBPII was evaluated using a cytoadherence assay of COS7 cells expressing PvDBPII on their surfaces. Inhibitory binding assays in vitro demonstrated that antibodies from monkey sera blocked the interaction between COS-7 cells expressing PvDBPII and hDARC-positive erythrocytes. Taken together, phylogenetic analyses reinforced the hypothesis that the host switch from humans to monkeys may have occurred very recently in evolution, which sheds light on the evolutionary history of new world plasmodia. Further invasion studies would confirm whether P. simium depends on DBP/DARC to trigger internalization into red blood cells.

  18. Engineering mosquito resistance to malaria parasites: the avian malaria model.

    PubMed

    James, A A

    2002-10-01

    Genetic approaches to controlling the transmission of mosquito-borne diseases are being developed to augment the available chemical control practices and environmental manipulation methods. Much progress has been made in laboratory-based research that seeks to develop antipathogen or antivector effector genes and methods for genetically manipulating host vector strains. Research is summarized here in the development of a malaria-resistant phenotype using as a model system the avian parasite, Plasmodium gallinaceum, and the mosquito, Aedes aegypti. Robust transformation technology based on a number of transposable elements, the identification of promoter regions derived from endogenous mosquito genes, and the development of single-chain antibodies as effector genes have made it possible to produce malaria-resistant mosquitoes. Future challenges include discovery of methods for spreading antiparasite genes through mosquito populations, determining the threshold levels below which parasite intensities of infection must be held, and defining the circumstances in which a genetic control strategy would be employed in the field.

  19. The implementation of long-lasting insecticidal bed nets has differential effects on the genetic structure of the African malaria vectors in the Anopheles gambiae complex in Dielmo, Senegal.

    PubMed

    Sougoufara, Seynabou; Sokhna, Cheikh; Diagne, Nafissatou; Doucouré, Souleymane; Sembène, Pape MBacké; Harry, Myriam

    2017-08-15

    Mosquitoes belonging to the Anopheles gambiae complex are the main vectors of malaria in sub-Saharan Africa. Among these, An. gambiae, Anopheles coluzzii and Anopheles arabiensis are the most efficient vectors and are largely distributed in sympatric locations. However, these species present ecological and behavioural differences that impact their vectorial capacity and complicate vector-control efforts, mainly based on long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS). In this study, the genetic structure of these three species in a Senegalese village (Dielmo) was investigated using microsatellite data in samples collected in 2006 before implementation of LLINs, in 2008, when they were introduced, and in 2010, 2 years after the use of LLINs. In this study 611 individuals were included, namely 136 An. coluzzii, 101 An. gambiae, 6 An. coluzzii/An. gambiae hybrids and 368 An. arabiensis. According to the species, the effect of the implementation of LLINs in Dielmo is differentiated. Populations of the sister species An. coluzzii and An. gambiae regularly experienced bottleneck events, but without significant inbreeding. The Fst values suggested in 2006 a breakdown of assortative mating resulting in hybrids, but the introduction of LLINs was followed by a decrease in the number of hybrids. This suggests a decrease in mating success of hybrids, ecological maladaptation, or a lesser probability of mating between species due to a decrease in An. coluzzii population size. By contrast, the introduction of LLINs has favoured the sibling species An. arabiensis. In this study, some spatial and temporal structuration between An. arabiensis populations were detected, especially in 2008, and the higher genetic diversity observed could result from a diversifying selection. This work demonstrates the complexity of the malaria context and shows the need to study the genetic structure of Anopheles populations to evaluate the effectiveness of vector

  20. Scientists Discover More Clues to Stuttering

    MedlinePlus

    ... fullstory_162368.html Scientists Discover More Clues to Stuttering MRI shows involvement of brain areas controlling speech, ... speech, attention and emotion are all linked to stuttering. Stuttering is characterized by involuntarily repeating certain sounds, ...

  1. Ancient Magnetic Reversals: Clues to the Geodynamo.

    ERIC Educational Resources Information Center

    Hoffman, Kenneth A.

    1988-01-01

    Discusses the question posed by some that the earth's magnetic field may reverse. States that rocks magnetized by ancient fields may offer clues to the underlying reversal mechanism in the earth's core. (TW)

  2. Ancient Magnetic Reversals: Clues to the Geodynamo.

    ERIC Educational Resources Information Center

    Hoffman, Kenneth A.

    1988-01-01

    Discusses the question posed by some that the earth's magnetic field may reverse. States that rocks magnetized by ancient fields may offer clues to the underlying reversal mechanism in the earth's core. (TW)

  3. Cerebral malaria

    PubMed Central

    Newton, C.; Hien, T. T.; White, N.

    2000-01-01

    Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogenous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications—for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.

 PMID:10990500

  4. Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes.

    PubMed

    Gupta, Himanshu; Jain, Aditya; Saadi, Abdul Vahab; Vasudevan, Thanvanthri G; Hande, Manjunath H; D'Souza, Sydney C; Ghosh, Susanta K; Umakanth, Shashikiran; Satyamoorthy, Kapaettu

    2015-08-01

    In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case-control study of adults, individuals affected by Pf malaria (complicated n=168; uncomplicated n=282) and healthy controls (n=450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing. Single-locus analysis showed significant association of 2 SNPs; rs5751876 (OR=3.2(2.0-5.2); p=0.0006) of ADORA2A and rs2230345 (OR=0.3(0.2-0.5); p=0.0006) of GRK5 with malaria. The mean of the serum creatinine levels were significantly higher in patients with variant GG (p=0.006) of rs9624472 in ADORA2A gene compared to AA and AG genotypes in complicated Pf malaria cases, with the G allele also showing increased risk for malaria (OR=1.3(1.1-1.6); p=0.017). Analyses of predicted haplotypes of the two ADORA2A and the four GRK5 SNPs have identified the haplotypes that conferred risk as well as resistance to malaria with statistical significance. Molecular docking analysis of evolutionary rs2230345 SNP indicated a stable activity of GRK5 for the mutant allele compared to the wild type. Further, generalized multifactor dimensionality reduction to test the contribution of individual effects of the six polymorphisms and higher-order interactions to risk of symptoms/clinical complications of malaria suggested a best six-locus model showing statistical significance. The

  5. Vivax malaria

    PubMed Central

    Price, Ric N; Tjitra, Emiliana; Guerra, Carlos A; Yeung, Shunmay; White, Nicholas J; Anstey, Nicholas M

    2009-01-01

    Plasmodium vivax threatens almost 40% of the world’s population, resulting in 132 - 391 million clinical infections each year. Most of these cases originate from South East Asia and the Western Pacific, although a significant number also occur in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates and the parasite’s ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers and funding bodies. PMID:18165478

  6. Association of candidate gene polymorphisms and TGF-beta/IL-10 levels with malaria in three regions of Cameroon: a case–control study

    PubMed Central

    2014-01-01

    Background Plasmodium falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical host genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity and improve vaccine development initiatives. Methods The effect of single nucleotide polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) levels on malaria pathology was investigated in a case–control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Thirty-four malaria candidate polymorphisms, including the sickle cell trait (HbS), were assayed on the Sequenom iPLEX platform while plasma TGF-β and IL-10 levels were measured by sandwich ELISA. Results The study confirms the known protective effect of HbS against severe malaria and also reveals a protective effect of SNPs in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO rs8176746 AC individuals were associated with protection from hyperpyrexia and hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533 GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more susceptible to hyperpyrexia while both females and males with the rs1050828 and rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF-β levels were strongly correlated with heterozygosity for the ADCY9 rs2230739 and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower IL-10 levels. Conclusion Taken together, this study suggests that some rare polymorphisms in candidate genes may have important implications for the susceptibility of Cameroonians to

  7. Association of candidate gene polymorphisms and TGF-beta/IL-10 levels with malaria in three regions of Cameroon: a case-control study.

    PubMed

    Apinjoh, Tobias O; Anchang-Kimbi, Judith K; Njua-Yafi, Clarisse; Ngwai, André N; Mugri, Regina N; Clark, Taane G; Rockett, Kirk A; Kwiatkowski, Dominic P; Achidi, Eric A

    2014-06-16

    Plasmodium falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical host genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity and improve vaccine development initiatives. The effect of single nucleotide polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) levels on malaria pathology was investigated in a case-control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Thirty-four malaria candidate polymorphisms, including the sickle cell trait (HbS), were assayed on the Sequenom iPLEX platform while plasma TGF-β and IL-10 levels were measured by sandwich ELISA. The study confirms the known protective effect of HbS against severe malaria and also reveals a protective effect of SNPs in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO rs8176746 AC individuals were associated with protection from hyperpyrexia and hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533 GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more susceptible to hyperpyrexia while both females and males with the rs1050828 and rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF-β levels were strongly correlated with heterozygosity for the ADCY9 rs2230739 and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower IL-10 levels. Taken together, this study suggests that some rare polymorphisms in candidate genes may have important implications for the susceptibility of Cameroonians to severe malaria. Moreover using the

  8. Nifs and Sufs in malaria.

    PubMed

    Ellis, K E; Clough, B; Saldanha, J W; Wilson, R J

    2001-09-01

    This review assembles data from three bodies of literature (bacterial genetics, plastid biogenesis and parasitology) that seldom have much direct cross-talk. After overcoming terminological complications to sort out microbial nifS from sufS genes, we connect a bacterial operon, recently found to be involved in iron metabolism, the formation of [Fe-S] clusters and oxidative stress to a potentially important gene (sufB) carried on the degenerate plastid genome of malaria and related parasites.

  9. Radar Monitoring of Wetlands for Malaria Control

    NASA Technical Reports Server (NTRS)

    Pope, Kevin O.

    1997-01-01

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

  10. Prophylaxis of Malaria

    PubMed Central

    Schwartz, Eli

    2012-01-01

    Malaria prevention in travelers to endemic areas remains dependent principally on chemoprophylaxis. Although malaria chemoprophylaxis refers to all malaria species, a distinction should be drawn between falciparum malaria prophylaxis and the prophylaxis of the relapsing malaria species (vivax & ovale). While the emergence of drug resistant strains, as well as the costs and adverse reactions to medications, complicate falciparum prophylaxis use, there are virtually no drugs available for vivax prophylaxis, beside of primaquine. Based on traveler’s malaria data, a revised recommendation for using chemoprophylaxis in low risk areas should be considered. PMID:22811794

  11. Genetic variants that confer resistance to malaria are associated with red blood cell traits in African-Americans: an electronic medical record-based genome-wide association study.

    PubMed

    Ding, Keyue; de Andrade, Mariza; Manolio, Teri A; Crawford, Dana C; Rasmussen-Torvik, Laura J; Ritchie, Marylyn D; Denny, Joshua C; Masys, Daniel R; Jouni, Hayan; Pachecho, Jennifer A; Kho, Abel N; Roden, Dan M; Chisholm, Rex; Kullo, Iftikhar J

    2013-07-08

    To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria-HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)-were associated (P ≤ 1 × 10(-6)) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 5 × 10(-8)) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.

  12. [WHO's malaria program Roll Back Malaria].

    PubMed

    Myrvang, B; Godal, T

    2000-05-30

    Malaria is one of the main health problems in the world with 300-500 millions cases yearly and about one million deaths, mainly children in Sub-Saharan Africa. In the 1990s the malaria problem in Africa has increased, although we have methods to control the disease. In 1998 the new secretary general of WHO, Gro Harlem Brundtland, established the Roll Back Malaria programme, with the aim to markedly reduce malaria morbidity and mortality. Governments in malaria-affected countries have to take the lead in Roll Back Malaria. Their health systems must be improved and malaria control integrated into the general health system, and the methods available for prevention and treatment have to be intensified and improved. At the same time, Roll Back Malaria will encourage and promote malaria research which hopefully will result in new medicines, vaccines and other tools which will improve the chances of reducing malaria-related deaths and suffering. Roll Back Malaria is a cabinet project within the WHO, and the organisation has a key role as manager, co-ordinator and monitor of the project. However, it depends for resources on international support and commitment from other UN bodies, the World Bank, governments in the western world, pharmaceutical industry, philanthropists and other sources. At present an optimistic view prevails, and the preliminary aim, to halve the malaria mortality by the year 2010, seems realistic even with the control methods of today. However, if research efforts result in new and better tools to combat the disease, the task will definitely be easier.

  13. Clues in diagnosing congenital heart disease.

    PubMed Central

    Moss, A. J.

    1992-01-01

    A number of practical office and bedside clues to cardiac disease in infants and children have been passed on through the years. They relate to the history, to the inspection and palpation components of the physical examination, and to knowledge of the specific cardiac defects that are likely to be associated with certain clinical syndromes. With the possible exception of coarctation of the aorta, the clues are not diagnostically specific. In many instances, however, they serve to narrow a broad array of diagnostic possibilities to 2 or 3 and, with the aid of other clues and auscultation, they can often be distinguished from one another. When a primary care physician is confronted with a child who has an incidental murmur that is "probably" innocent but could be organic, useful clues favoring an organic murmur are a history of congenital heart disease in a first-degree relative; a history of maternal rubella syndrome, alcohol use, or teratogenic drug use during pregnancy; a history of inappropriate sweating; a history of syncope, chest pain, or squatting; maternal diabetes mellitus; premature birth; birth at a high altitude; cyanosis; abnormal pulsations; recurrent bronchiolitis or pneumonia; chronic unexplained hoarseness; asymmetric facies with crying; and a physical appearance suggestive of a clinical syndrome. PMID:1574882

  14. Malaria (For Parents)

    MedlinePlus

    ... period for malaria is the time between the mosquito bite and the release of parasites from the ... Health authorities try to prevent malaria by using mosquito-control programs aimed at killing mosquitoes that carry ...

  15. Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa.

    PubMed

    Bereczky, S; Dolo, A; Maiga, B; Hayano, M; Granath, F; Montgomery, S M; Daou, M; Arama, C; Troye-Blomberg, M; Doumbo, O K; Färnert, A

    2006-03-01

    The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2-9 years were 75% in the Fulani and 44% in the Dogon (P<0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P=0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65-8.15, P=0.003), but not found in the Fulani, 1.36 (95% CI 0.53-3.48, P=0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.

  16. Malaria surveillance--United States, 2012.

    PubMed

    Cullen, Karen A; Arguin, Paul M

    2014-12-05

    infecting species was unreported or undetermined in 17% of cases, a decrease of 6 percentage points from 2011. Polymerase chain reaction testing determined or corrected the species for 45 (43%) of the 104 samples submitted for drug resistance testing. Of the 909 patients who reported purpose of travel, 604 (66%) were visiting friends or relatives (VFR). Among the 983 cases in U.S. civilians for whom information on chemoprophylaxis use and travel region was known, 63 (6%) patients reported that they had followed and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were reported in pregnant women, among whom only one adhered to chemoprophylaxis. Among all reported cases, 231 (14%) were classified as severe infections in 2012. Of these, six persons with malaria died in 2012. Beginning in 2012, there were 104 blood samples submitted to CDC that were tested for molecular markers associated with antimalarial drug resistance. Of the 65 P. falciparum-positive samples, 53 (82%) had genetic polymorphisms associated with pyrimethamine drug resistance, 61 (94%) with sulfadoxine resistance, 29 (45%) with chloroquine resistance, 1 (2%) with mefloquine drug resistance, 2 (3%) with atovaquone resistance, and none with artemisinin resistance. Despite the 12% decline in the number of cases reported in 2012 compared with 2011, the overall trend in malaria cases has been increasing since 1973. Although progress has been made in reducing the global burden of malaria, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. Completion of data elements on the malaria case report form increased slightly in 2012 compared with 2011, but still remains unacceptably low. This incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFRs continue to be a difficult population to reach with effective malaria prevention

  17. Malaria in selected non-Amazonian countries of Latin America

    PubMed Central

    Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Ángel; Padilla, Julio Cesar; Escalante, Ananias A.; Beier, John C.; Herrera, Socrates

    2011-01-01

    Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent’s contribution to the global malaria burden is small, at least 1 to 1.2 million malaria cases are reported annually. Sixty per cent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2 %) followed by P. falciparum (25.7 %) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA

  18. Malaria in selected non-Amazonian countries of Latin America.

    PubMed

    Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Angel; Padilla, Julio Cesar; Escalante, Ananias A; Beier, John C; Herrera, Socrates

    2012-03-01

    Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent's contribution to the global malaria burden is small, at least 1-1.2 million malaria cases are reported annually. Sixty percent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2%) followed by P. falciparum (25.7%) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by

  19. Malaria. Can WHO roll back malaria?

    PubMed

    Balter, M

    2000-10-20

    In October 1998, World Health Organization Director-General Gro Harlem Brundtland announced Roll Back Malaria, a multiagency crusade that aims to cut malaria mortality in half over the next 10 years. Brundtland might just be the one to pull it off, say numerous public health experts, although some researchers question whether the goal is realistic.

  20. Heterogeneities of the malaria vectorial system in tropical Africa and their significance in malaria epidemiology and control

    PubMed Central

    Coluzzi, Mario

    1984-01-01

    The most important units of the malaria vectorial system in tropical Africa are included in the Linnaean taxon Anopheles gambiae, which has been split into six sibling species recognized by the application of genetic techniques. More recent studies have shown further complexities involving chromosomal inversion polymorphism in some vector populations as well as incipient speciation processes. The significance for field research in malaria of the splitting of a morphological taxon into genetically defined units and subunits is discussed. PMID:6335681

  1. Malaria in Children.

    PubMed

    Cohee, Lauren M; Laufer, Miriam K

    2017-08-01

    Malaria is a leading cause of morbidity and mortality in endemic areas, leading to an estimated 438,000 deaths in 2015. Malaria is also an important health threat to travelers to endemic countries and should be considered in evaluation of any traveler returning from a malaria-endemic area who develops fever. Considering the diagnosis of malaria in patients with potential exposure is critical. Prompt provision of effective treatment limits the complications of malaria and can be life-saving. Understanding Plasmodium species variation, epidemiology, and drug-resistance patterns in the geographic area where infection was acquired is important for determining treatment choices. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Incidence of Severe Malaria Syndromes and Status of Immune Responses among Khat Chewer Malaria Patients in Ethiopia.

    PubMed

    Ketema, Tsige; Bacha, Ketema; Alemayehu, Esayas; Ambelu, Argaw

    2015-01-01

    Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years) seeking medication in Halaba Kulito and Jimma Health Centers. In addition, incidences of severe malaria symptoms were assessed. The data were analyzed using SPSS (version 20) software. Prevalence of current khat chewer malaria patients was 57.38% (95%CI =53-61.56%). Malaria symptoms such as hyperpyrexia, prostration and hyperparasitemia were significantly lower (P<0.05) among khat chewer malaria patients. However, relative risk to jaundice and renal failure were significantly higher (P<0.05) in khat chewers than in non-khat chewer malaria patients. Longer duration of khat use was positively associated with incidence of anemia. IgM and IgG antibody titers were significantly higher (P<0.05) among khat chewer malaria patients than among malaria positive non-chewers. Although levels of IgG subclasses in malaria patients did not show significant differences (P>0.05), IgG3 antibody was significantly higher (P<0.001) among khat chewer malaria patients. Moreover, IgM, IgG, IgG1and IgG3 antibodies had significant negative association (P<0.001) with parasite burden and clinical manifestations of severe malaria symptoms, but not with severe anemia and hypoglycemia. Additionally, a significant increment (P<0.05) in CD4+ T-lymphocyte population was observed among khat users. Khat might be an important risk factor for incidence of some severe malaria complications. Nevertheless, it

  3. Designing malaria vaccines to circumvent antigen variability✩

    PubMed Central

    Ouattara, Amed; Barry, Alyssa E.; Dutta, Sheetij; Remarque, Edmond J.; Beeson, James G.; Plowe, Christopher V.

    2016-01-01

    Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines. PMID:26475447

  4. Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria

    PubMed Central

    Small, Dylan S; Taylor, Terrie E; Postels, Douglas G; Beare, Nicholas AV; Cheng, Jing; MacCormick, Ian JC; Seydel, Karl B

    2017-01-01

    Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial. Because hospitals in malaria-endemic areas often lack diagnostic facilities to identify non-malarial causes of coma, it has not been possible to evaluate the contribution of malaria infection to retinopathy-negative CM. To overcome this barrier, we studied a natural experiment involving genetically inherited traits, and find evidence that malaria parasitemia does contribute to the pathogenesis of retinopathy-negative CM. A lower bound for the fraction of retinopathy-negative CM that would be prevented if malaria parasitemia were to be eliminated is estimated to be 0.93 (95% confidence interval: 0.68, 1). DOI: http://dx.doi.org/10.7554/eLife.23699.001 PMID:28590246

  5. Childhood cancer: etiologic clues from epidemiology.

    PubMed

    Safyer, A W; Miller, R W

    1977-03-01

    Epidemiologic reseach has revealed a wide spectrum of etiologic information concerning childhood cancer. Often, important clues have come from observations made by alert practitioners. The school health professional can help further progress in cancer research by observing peculiarities of environmental exposures as well as the family's medical history when cancer affects a child. Any unusual findings should be referred to an appropriate research center for evaluation.

  6. Malaria in South Asia: Prevalence and control

    PubMed Central

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

    2013-01-01

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

  7. Malaria in South Asia: prevalence and control.

    PubMed

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

    2012-03-01

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

  8. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  9. Molecular entomology and prospects for malaria control.

    PubMed Central

    Collins, F. H.; Kamau, L.; Ranson, H. A.; Vulule, J. M.

    2000-01-01

    During the past decade, the techniques of molecular and cell biology have been embraced by many scientists doing research on anopheline vectors of malaria parasites. Some of the most important research advances in molecular entomology have concerned the development of sophisticated molecular tools for procedures such as genetic and physical mapping and germ line transformation. Major advances have also been made in the study of specific biological processes such as insect defence against pathogens and the manner in which malaria parasites and their anopheline hosts interact during sporogony. One of the most important highlights of this research trend has been the emergence during the past year of a formal international Anopheles gambiae genome project, which at present includes investigators in several laboratories in Europe and the USA. Although much of this molecular research is directed towards the development of malaria control strategies that are probably many years from implementation, there are some important areas of molecular entomology that may have a more near-term impact on malaria control. We highlight developments over the past decade in three such areas that we believe can make important contributions to the development of near-term malaria control strategies. These areas are anopheline species identification, the detection and monitoring of insecticide susceptibility/resistance in wild anopheline populations and the determination of the genetic structure of anopheline populations. PMID:11196488

  10. The High Blood Pressure-Malaria Protection Hypothesis.

    PubMed

    Gallego-Delgado, Julio; Walther, Thomas; Rodriguez, Ana

    2016-10-28

    A recently proposed hypothesis states that malaria may contribute to hypertension in endemic areas,(1) but the role of angiotensin II (Ang II), a major regulator of blood pressure, was not considered. Elevated levels of Ang II may confer protection against malaria morbidity and mortality, providing an alternative explanation for hypertension in malaria endemic areas. To discuss a possible alternative cause for hypertension in populations who have been under the selective pressure of malaria. We reviewed published scientific literature for studies that could establish a link between Ang II and malaria. Both genetic and functional studies suggested that high levels of Ang II may confer protection against cerebral malaria by strengthening the integrity of the endothelial brain barrier. We also describe strong experimental evidence supporting our hypothesis through genetic, functional, and interventional studies. A causal association between high levels of Ang II and protection from malaria pathogenesis can provide a likely explanation for the increased prevalence in hypertension observed in populations of African and South Asian origin. Furthermore, this potential causative connection might also direct unique approaches for the effective treatment of cerebral malaria. © 2016 American Heart Association, Inc.

  11. Sickle cell protection from malaria

    PubMed Central

    Eridani, Sandro

    2011-01-01

    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

  12. Molecular Genetics Evidence for the in Vivo Roles of the Two Major NADPH-dependent Disulfide Reductases in the Malaria Parasite*

    PubMed Central

    Buchholz, Kathrin; Putrianti, Elyzana D.; Rahlfs, Stefan; Schirmer, R. Heiner; Becker, Katja; Matuschewski, Kai

    2010-01-01

    Malaria-associated pathology is caused by the continuous expansion of Plasmodium parasites inside host erythrocytes. To maintain a reducing intracellular milieu in an oxygen-rich environment, malaria parasites have evolved a complex antioxidative network based on two central electron donors, glutathione and thioredoxin. Here, we dissected the in vivo roles of both redox pathways by gene targeting of the respective NADPH-dependent disulfide reductases. We show that Plasmodium berghei glutathione reductase and thioredoxin reductase are dispensable for proliferation of the pathogenic blood stages. Intriguingly, glutathione reductase is vital for extracellular parasite development inside the insect vector, whereas thioredoxin reductase is dispensable during the entire parasite life cycle. Our findings suggest that glutathione reductase is the central player of the parasite redox network, whereas thioredoxin reductase fulfils a specialized and dispensable role for P. berghei. These results also indicate redundant roles of the Plasmodium redox pathways during the pathogenic blood phase and query their suitability as promising drug targets for antimalarial intervention strategies. PMID:20852334

  13. Psychosomatics of malaria.

    PubMed

    Houghton, D L

    1980-03-01

    Cerebral malaria with psychosomatic manifestations is one aspect of malaria which may be mistaken for mental illness. However, the psychosomatic aspects of the disease also relate to the biological, psychological and social influences which may determine changes in disease incidence and distribution. The history of the Global Malaria Eradication Campaign and the resurgence of malaria in many countries of the world have influenced attitudes and the professional milieu in which present day malaria control programmes seek to operate. The individual in a malarious area may obstruct malaria control operations by refusing to allow indoor spraying or to take prophylactic medication. Cultural beliefs often described the history of malaria in a community and the way in which the community had come to terms with this disease. Socio-economic development and population movement may disturb this equilibrium and result in a rise in malaria incidence. Behavioural habits may increase malaria risk and the degree to which the community is prepared to become involved in malaria control may influence its experience with the disease.

  14. PATRONAGE AND COST OF MALARIA TREATMENT IN PRIVATE HOSPITALS IN IBADAN NORTH L.G.A SOUTH WESTERN, NIGERIA

    PubMed Central

    Salawu, A.T.; Fawole, O.I.; Dairo, M.D.

    2016-01-01

    Background: Malaria accounts for about 60% of all clinic attendance in Nigeria. About 300,000 children die of malaria annually while an estimated 4,500 pregnant women are lost annually on account of malaria in Nigeria alone. High cost of treatment is a barrier to the uptake of health services in low resource settings, therefore an exploration of the cost of malaria management will reveal possible components that may benefit from intervention and thus reveal important clues for improving access to malaria treatment. Objective of this study therefore is to describe patronage and cost of malaria treatment in private hospitals in Ibadan. Method: This was a descriptive cross sectional study, carried out in private hospitals in Ibadan, South Western Nigeria. A self-administered questionnaire with open and close-ended questions was used to collect data on patronage and cost of treatment in adults, children and pregnant women attending private health facilities in Ibadan, Nigeria. Data were presented using tables of frequencies and proportions while analysis was by descriptive statistics. Results: A total of 40 doctors and hospitals participated in the study. Average patronage for malaria, both complicated and uncomplicated per month was 153 patients per hospital. Malaria cases accounts for 331 (46.2%) of total clinic cases seen in private hospitals in a month. About 121 (78%) of malaria cases seen were uncomplicated while 32 (21%) of cases were complicated malaria. Average amount charged patient for treating uncomplicated malaria in private hospitals was N3,941. Average amount spent on antimalarial drugs was about N2,443 (62%) while N1,064 (27.7%) was spent on laboratory investigation and N406.00 (10.3%) for medical consultation. Conclusion: Drugs cost constitute the bulk of expenses on malaria treatment. Policy makers may improve access to malaria treatment by subsidizing the cost of anti-malaria drugs for pregnant women and children, who might not be able to afford

  15. Congenital malaria in China.

    PubMed

    Tao, Zhi-Yong; Fang, Qiang; Liu, Xue; Culleton, Richard; Tao, Li; Xia, Hui; Gao, Qi

    2014-03-01

    Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum-endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax-endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine

  16. Congenital Malaria in China

    PubMed Central

    Liu, Xue; Culleton, Richard; Tao, Li; Xia, Hui; Gao, Qi

    2014-01-01

    Abstract Background Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. Methods/Principal Findings Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured

  17. Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.

    PubMed

    Munde, Elly O; Okeyo, Winnie A; Raballah, Evans; Anyona, Samuel B; Were, Tom; Ong'echa, John M; Perkins, Douglas J; Ouma, Collins

    2017-04-20

    Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcγRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcγR polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in FcγRIIA -131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 modulate immune responses through altered binding preferences to IgGs and immune complexes. Differential binding, in turn, changes ability of immune cells to respond to infection through production of inflammatory mediators during P. falciparum infection. We determined the association between haplotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 variants and severe malarial anemia (SMA; hemoglobin < 6.0 g/dL, any density parasitemia) in children (n = 274; aged 6-36 months) presenting for their first hospital visit with P. falciparum malaria in a holoendemic transmission region of western Kenya. FcγRIIA-131Arg/His and FcγRIIIA-176F/V genotypes were determined using TaqMan® SNP genotyping, while FcγRIIIBNA1/NA2 genotypes were determined using restriction fragment length polymorphism. Hematological and parasitological indices were measured in all study participants. Carriage of FcγRIIA-131Arg/FcγRIIIA-176F/FcγRIIIBNA2 haplotype was associated with susceptibility to SMA (OR = 1.70; 95% CI; 1.02-2.93; P = 0.036), while the FcγRIIA-131His/ FcγRIIIA-176F/ FcγRIIIB NA1 haplotype was marginally associated with enhanced susceptibility to SMA (OR: 1.80, 95% CI; 0.98-3.30, P = 0.057) and higher levels of parasitemia (P = 0.009). Individual genotypes of FcγRIIA-131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 were not associated with susceptibility to SMA. The study revealed that haplotypes of FcγRs are important in conditioning susceptibility to SMA in immune

  18. Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015.

    PubMed

    Lo, Eugenia; Nguyen, Kristie; Nguyen, Jennifer; Hemming-Schroeder, Elizabeth; Xu, Jiaobao; Etemesi, Harrisone; Githeko, Andrew; Yan, Guiyun

    2017-04-01

    In Africa, control programs that target primarily Plasmodium falciparum are inadequate for eliminating malaria. To learn more about prevalence and genetic variability of P. malariae in Africa, we examined blood samples from 663 asymptomatic and 245 symptomatic persons from western Kenya during June-August of 2014 and 2015. P. malariae accounted for 5.3% (35/663) of asymptomatic infections and 3.3% (8/245) of clinical cases. Among asymptomatic persons, 71% (32/45) of P. malariae infections detected by PCR were undetected by microscopy. The low sensitivity of microscopy probably results from the significantly lower parasitemia of P. malariae. Analyses of P. malariae circumsporozoite protein gene sequences revealed high genetic diversity among P. malariae in Africa, but no clear differentiation among geographic populations was observed. Our findings suggest that P. malariae should be included in the malaria elimination strategy in Africa and highlight the need for sensitive and field-applicable methods to identify P. malariae in malaria-endemic areas.

  19. Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015

    PubMed Central

    Nguyen, Kristie; Nguyen, Jennifer; Hemming-Schroeder, Elizabeth; Xu, Jiaobao; Etemesi, Harrisone; Githeko, Andrew

    2017-01-01

    In Africa, control programs that target primarily Plasmodium falciparum are inadequate for eliminating malaria. To learn more about prevalence and genetic variability of P. malariae in Africa, we examined blood samples from 663 asymptomatic and 245 symptomatic persons from western Kenya during June–August of 2014 and 2015. P. malariae accounted for 5.3% (35/663) of asymptomatic infections and 3.3% (8/245) of clinical cases. Among asymptomatic persons, 71% (32/45) of P. malariae infections detected by PCR were undetected by microscopy. The low sensitivity of microscopy probably results from the significantly lower parasitemia of P. malariae. Analyses of P. malariae circumsporozoite protein gene sequences revealed high genetic diversity among P. malariae in Africa, but no clear differentiation among geographic populations was observed. Our findings suggest that P. malariae should be included in the malaria elimination strategy in Africa and highlight the need for sensitive and field-applicable methods to identify P. malariae in malaria-endemic areas. PMID:28322694

  20. Investigation of host candidate malaria-associated risk/protective SNPs in a Brazilian Amazonian population.

    PubMed

    da Silva Santos, Simone; Clark, Taane G; Campino, Susana; Suarez-Mutis, Martha Cecília; Rockett, Kirk A; Kwiatkowski, Dominic P; Fernandes, Octavio

    2012-01-01

    The Brazilian Amazon is a hypo-endemic malaria region with nearly 300,000 cases each year. A variety of genetic polymorphisms, particularly in erythrocyte receptors and immune response related genes, have been described to be associated with susceptibility and resistance to malaria. In order to identify polymorphisms that might be associated with malaria clinical outcomes in a Brazilian Amazonian population, sixty-four human single nucleotide polymorphisms in 37 genes were analyzed using a Sequenom massARRAY iPLEX platform. A total of 648 individuals from two malaria endemic areas were studied, including 535 malaria cases (113 individuals with clinical mild malaria, 122 individuals with asymptomatic infection and 300 individuals with history of previous mild malaria) and 113 health controls with no history of malaria. The data revealed significant associations (p<0.003) between one SNP in the IL10 gene (rs1800896) and one SNP in the TLR4 gene (rs4986790) with reduced risk for clinical malaria, one SNP in the IRF1 gene (rs2706384) with increased risk for clinical malaria, one SNP in the LTA gene (rs909253) with protection from clinical malaria and one SNP in the TNF gene (RS1800750) associated with susceptibility to clinical malaria. Also, a new association was found between a SNP in the CTL4 gene (rs2242665), located at the major histocompatibility complex III region, and reduced risk for clinical malaria. This study represents the first association study from an Amazonian population involving a large number of host genetic polymorphisms with susceptibility or resistance to Plasmodium infection and malaria outcomes. Further studies should include a larger number of individuals, refined parameters and a fine-scale map obtained through DNA sequencing to increase the knowledge of the Amazonian population genetic diversity.

  1. Naked megakaryocyte nuclei: a clue to malignancy.

    PubMed

    Lefkowitz, M; Lefkowitz, E

    1977-10-01

    Bone marrow smears from 63 patients with various malignancies and a series of 51 controls were examined for the presence and percentage of naked megakaryocyte nuclei (NMN). Patients with malignancy had more than 15% NMN, which, when compared with the incidence in controls, was statistically significant. The etiology of this artifact is unknown. It is a clue to the presence of malignancy, and might be useful in following treated cases of malignancy for evidence of relapse. NMN should not be confused with metastatic malignant cells.

  2. Declining Efficacy of Artemisinin Combination Therapy Against P. Falciparum Malaria on the Thai–Myanmar Border (2003–2013): The Role of Parasite Genetic Factors

    PubMed Central

    Phyo, Aung Pyae; Ashley, Elizabeth A.; Anderson, Tim J. C.; Bozdech, Zbynek; Carrara, Verena I.; Sriprawat, Kanlaya; Nair, Shalini; White, Marina McDew; Dziekan, Jerzy; Ling, Clare; Proux, Stephane; Konghahong, Kamonchanok; Jeeyapant, Atthanee; Woodrow, Charles J.; Imwong, Mallika; McGready, Rose; Lwin, Khin Maung; Day, Nicholas P. J.; White, Nicholas J.; Nosten, Francois

    2016-01-01

    Background. Deployment of mefloquine–artesunate (MAS3) on the Thailand–Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of Plasmodium falciparum K13 mutations (a marker of artemisinin resistance) in reducing treatment efficacy remains controversial. Methods. Between 2003 and 2013, we studied the efficacy of MAS3 in 1005 patients with uncomplicated P. falciparum malaria in relation to molecular markers of resistance. Results. Polymerase chain reaction (PCR)–adjusted cure rates declined from 100% in 2003 to 81.1% in 2013 as the proportions of isolates with multiple Pfmdr1 copies doubled from 32.4% to 64.7% and those with K13 mutations increased from 6.7% to 83.4%. K13 mutations conferring moderate artemisinin resistance (notably E252Q) predominated initially but were later overtaken by propeller mutations associated with slower parasite clearance (notably C580Y). Those infected with both multiple Pfmdr1 copy number and a K13 propeller mutation were 14 times more likely to fail treatment. The PCR-adjusted cure rate was 57.8% (95% confidence interval [CI], 45.4, 68.3) compared with 97.8% (95% CI, 93.3, 99.3) in patients with K13 wild type and Pfmdr1 single copy. K13 propeller mutation alone was a strong risk factor for recrudescence (P = .009). The combined population attributable fraction of recrudescence associated with K13 mutation and Pfmdr1 amplification was 82%. Conclusions. The increasing prevalence of K13 mutations was the decisive factor for the recent and rapid decline in efficacy of artemisinin-based combination (MAS3) on the Thailand–Myanmar border. PMID:27313266

  3. Malaria prophylaxis and guidelines.

    PubMed

    Calleri, Guido

    2014-10-01

    Malaria prophylaxis recommendations issued by different health authorities in Europe are inhomogeneous, and so is the opinion of experts, but a general trend towards reducing its use is evident, and prescribers apparently adhere more easily to more restrictive recommendations. A new Italian guideline has been produced, looking both at scientific evidence (data on malaria risk and drugs' side effects) and at the opinion of experts (surveys and previously issued recommendations). Collecting data on imported malaria, stating a clear methodology and introduce a discussion at international level should be the next goals in order to homogenise recommendations for malaria prophylaxis in Europe.

  4. Malaria ecotypes and stratification.

    PubMed

    Schapira, Allan; Boutsika, Konstantina

    2012-01-01

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

  5. A variant in the gene FUT9 is associated with susceptibility to placental malaria infection.

    PubMed

    Sikora, Martin; Ferrer-Admetlla, Anna; Laayouni, Hafid; Menendez, Clara; Mayor, Alfredo; Bardaji, Azucena; Sigauque, Betuel; Mandomando, Inacio; Alonso, Pedro L; Bertranpetit, Jaume; Casals, Ferran

    2009-08-15

    Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200 000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A single nucleotide polymorphism (SNP) located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (odds ratio = 2.31, permutation P-value=0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.

  6. MicroRNAs as genetic sculptors: fishing for clues

    PubMed Central

    Takacs, Carter M.; Giraldez, Antonio J.

    2010-01-01

    microRNAs (miRNA) encode small RNA molecules of ~22nts in length that regulate the deadenylation, translation, and decay of their target mRNAs. The identification of miRNAs in plants and animals has uncovered a new layer of gene regulation with important implications for development, cellular homeostasis and disease. Because each miRNA is predicted to regulate several hundred genes, a major challenge in the field remains to elucidate the precise roles for each miRNA and to understand the physiological relevance of individual miRNA-target interactions in vivo. Despite the wide variety of biological contexts where miRNAs function, a common theme emerges, whereby miRNAs shape gene expression within both spatial and temporal dimensions by removing messages from previous cellular states as well as modulating the levels of actively transcribed genes. This review will focus on the role that the teleost Danio rerio (zebrafish) has played in shaping our understanding of miRNA function in vertebrates. PMID:20152922

  7. Malaria transmission modelling: a network perspective.

    PubMed

    Liu, Jiming; Yang, Bo; Cheung, William K; Yang, Guojing

    2012-11-01

    Malaria transmission can be affected by multiple or even hidden factors, making it difficult to timely and accurately predict the impact of elimination and eradication programs that have been undertaken and the potential resurgence and spread that may continue to emerge. One approach at the moment is to develop and deploy surveillance systems in an attempt to identify them as timely as possible and thus to enable policy makers to modify and implement strategies for further preventing the transmission. Most of the surveillance data will be of temporal and spatial nature. From an interdisciplinary point of view, it would be interesting to ask the following important as well as challenging question: Based on the available surveillance data in temporal and spatial forms, how can we build a more effective surveillance mechanism for monitoring and early detecting the relative prevalence and transmission patterns of malaria? What we can note from the existing clustering-based surveillance software systems is that they do not infer the underlying transmission networks of malaria. However, such networks can be quite informative and insightful as they characterize how malaria transmits from one place to another. They can also in turn allow public health policy makers and researchers to uncover the hidden and interacting factors such as environment, genetics and ecology and to discover/predict malaria transmission patterns/trends. The network perspective further extends the present approaches to modelling malaria transmission based on a set of chosen factors. In this article, we survey the related work on transmission network inference, discuss how such an approach can be utilized in developing an effective computational means for inferring malaria transmission networks based on partial surveillance data, and what methodological steps and issues may be involved in its formulation and validation.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-02-02

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

  10. A review of malaria transmission dynamics in forest ecosystems

    PubMed Central

    2014-01-01

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

  11. Application of Genomics to Field Investigations of Malaria by the International Centers for Excellence in Malaria Research

    PubMed Central

    Volkman, Sarah K.; Ndiaye, Daouda; Diakite, Mahamadou; Koita, Ousmane; Nwakanma, Davis; Daniels, Rachel; Park, Danny; Neafsey, Dan; Muskavitch, Marc; Krogstad, Don; Sabeti, Pardis; Hartl, Dan; Wirth, Dyann

    2011-01-01

    Success of the global research agenda toward eradication of malaria will depend on development of new tools, including drugs, vaccines, insecticides and diagnostics. Genomic information, now available for the malaria parasites, their mosquito vectors, and human host, can be leveraged to both develop these tools and monitor their effectiveness. Although knowledge of genomic sequences for the malaria parasites, Plasmodium falciparum and P. vivax, have helped advance our understanding of malaria biology, simply knowing this sequence information has not yielded a plethora of new interventions to reduce the burden of malaria. Here we review and provide specific examples of how genomic information has increased our knowledge of parasite biology, focusing on P. falciparum malaria. We then discuss how population genetics can be applied toward the epidemiological and transmission-related goals outlined by the International Centers of Excellence in Malaria Research groups recently established by the National Institutes of Health. Finally, we propose genomics is a research area that can promote coordination and collaboration between various ICEMR groups, and that working together as a community can significantly advance the value of this information toward reduction of the global malaria burden. PMID:22182668

  12. Application of genomics to field investigations of malaria by the international centers of excellence for malaria research.

    PubMed

    Volkman, Sarah K; Ndiaye, Daouda; Diakite, Mahamadou; Koita, Ousmane A; Nwakanma, Davis; Daniels, Rachel F; Park, Daniel J; Neafsey, Daniel E; Muskavitch, Marc A T; Krogstad, Donald J; Sabeti, Pardis C; Hartl, Daniel L; Wirth, Dyann F

    2012-03-01

    Success of the global research agenda toward eradication of malaria will depend on development of new tools, including drugs, vaccines, insecticides and diagnostics. Genomic information, now available for the malaria parasites, their mosquito vectors, and human host, can be leveraged to both develop these tools and monitor their effectiveness. Although knowledge of genomic sequences for the malaria parasites, Plasmodium falciparum and Plasmodium vivax, have helped advance our understanding of malaria biology, simply knowing this sequence information has not yielded a plethora of new interventions to reduce the burden of malaria. Here we review and provide specific examples of how genomic information has increased our knowledge of parasite biology, focusing on P. falciparum malaria. We then discuss how population genetics can be applied toward the epidemiological and transmission-related goals outlined by the International Centers of Excellence for Malaria Research groups recently established by the National Institutes of Health. Finally, we propose genomics is a research area that can promote coordination and collaboration between various ICEMR groups, and that working together as a community can significantly advance the value of this information toward reduction of the global malaria burden. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Malaria Epidemiology and Control Within the International Centers of Excellence for Malaria Research.

    PubMed

    Moss, William J; Dorsey, Grant; Mueller, Ivo; Laufer, Miriam K; Krogstad, Donald J; Vinetz, Joseph M; Guzman, Mitchel; Rosas-Aguirre, Angel M; Herrera, Socrates; Arevalo-Herrera, Myriam; Chery, Laura; Kumar, Ashwani; Mohapatra, Pradyumna K; Ramanathapuram, Lalitha; Srivastava, H C; Cui, Liwang; Zhou, Guofa; Parker, Daniel M; Nankabirwa, Joaniter; Kazura, James W

    2015-09-01

    Understanding the epidemiological features and metrics of malaria in endemic populations is a key component to monitoring and quantifying the impact of current and past control efforts to inform future ones. The International Centers of Excellence for Malaria Research (ICEMR) has the opportunity to evaluate the impact of malaria control interventions across endemic regions that differ in the dominant Plasmodium species, mosquito vector species, resistance to antimalarial drugs and human genetic variants thought to confer protection from infection and clinical manifestations of plasmodia infection. ICEMR programs are conducting field studies at multiple sites with the aim of generating standardized surveillance data to improve the understanding of malaria transmission and to monitor and evaluate the impact of interventions to inform malaria control and elimination programs. In addition, these epidemiological studies provide a vast source of biological samples linked to clinical and environmental "meta-data" to support translational studies of interactions between the parasite, human host, and mosquito vector. Importantly, epidemiological studies at the ICEMR field sites are integrated with entomological studies, including the measurement of the entomological inoculation rate, human biting index, and insecticide resistance, as well as studies of parasite genetic diversity and antimalarial drug resistance.

  14. Malaria: Obstacles and Opportunities.

    DTIC Science & Technology

    1991-01-01

    Development Command, Fort Detrick, Frederick, Maryland CARLOS C. CAMPBELL, Malaria Branch, Centers for Disease Control, At- lanta, Georgia TORE GODAL ...Washington. D.C. UDOM CHITPRAROP, Malaria Center. Chiangmai. Thailand JANE COOLEY, International Health Programs. Centers for Disease Con- trol. Atlanta

  15. Targeted mutagenesis in the malaria mosquito using TALE nucleases.

    PubMed

    Smidler, Andrea L; Terenzi, Olivier; Soichot, Julien; Levashina, Elena A; Marois, Eric

    2013-01-01

    Anopheles gambiae, the main mosquito vector of human malaria, is a challenging organism to manipulate genetically. As a consequence, reverse genetics studies in this disease vector have been largely limited to RNA interference experiments. Here, we report the targeted disruption of the immunity gene TEP1 using transgenic expression of Transcription-Activator Like Effector Nucleases (TALENs), and the isolation of several TEP1 mutant A. gambiae lines. These mutations inhibited protein production and rendered TEP1 mutants hypersusceptible to Plasmodium berghei. The TALEN technology opens up new avenues for genetic analysis in this disease vector and may offer novel biotechnology-based approaches for malaria control.

  16. Genetic Characterisation of Plasmodium falciparum Isolates with Deletion of the pfhrp2 and/or pfhrp3 Genes in Colombia: The Amazon Region, a Challenge for Malaria Diagnosis and Control

    PubMed Central

    Dorado, Erika Jimena; Okoth, Sheila Akinyi; Montenegro, Lidia Madeline; Diaz, Gustavo; Barnwell, John W.; Udhayakumar, Venkatachalam; Murillo Solano, Claribel

    2016-01-01

    Most Plasmodium falciparum-detecting rapid diagnostic tests (RDTs) target histidine-rich protein 2 (PfHRP2). However, P. falciparum isolates with deletion of the pfhrp2 gene and its homolog gene, pfhrp3, have been detected. We carried out an extensive investigation on 365 P. falciparum dried blood samples collected from seven P. falciparum endemic sites in Colombia between 2003 and 2012 to genetically characterise and geographically map pfhrp2- and/or pfhrp3-negative P. falciparum parasites in the country. We found a high proportion of pfhrp2-negative parasites only in Amazonas (15/39; 38.5%), and these parasites were also pfhrp3-negative. These parasites were collected between 2008 and 2009 in Amazonas, while pfhrp3-negative parasites (157/365, 43%) were found in all the sites and from each of the sample collection years evaluated (2003 to 2012). We also found that all pfhrp2- and/or pfhrp3-negative parasites were also negative for one or both flanking genes. Six sub-population clusters were established with 93.3% (14/15) of the pfhrp2-negative parasites grouped in the same cluster and sharing the same haplotype. This haplotype corresponded with the genetic lineage BV1, a multidrug resistant strain that caused two outbreaks reported in Peru between 2010 and 2013. We found this BV1 lineage in the Colombian Amazon as early as 2006. Two new clonal lineages were identified in these parasites from Colombia: the genetic lineages EV1 and F. PfHRP2 sequence analysis revealed high genetic diversity at the amino acid level, with 17 unique sequences identified among 53 PfHRP2 sequences analysed. The use of PfHRP2-based RDTs is not recommended in Amazonas because of the high proportion of parasites with pfhrp2 deletion (38.5%), and implementation of new strategies for malaria diagnosis and control in Amazonas must be prioritised. Moreover, studies to monitor and genetically characterise pfhrp2-negative P. falciparum parasites in the Americas are warranted, given the extensive

  17. Genetic Characterisation of Plasmodium falciparum Isolates with Deletion of the pfhrp2 and/or pfhrp3 Genes in Colombia: The Amazon Region, a Challenge for Malaria Diagnosis and Control.

    PubMed

    Dorado, Erika Jimena; Okoth, Sheila Akinyi; Montenegro, Lidia Madeline; Diaz, Gustavo; Barnwell, John W; Udhayakumar, Venkatachalam; Murillo Solano, Claribel

    2016-01-01

    Most Plasmodium falciparum-detecting rapid diagnostic tests (RDTs) target histidine-rich protein 2 (PfHRP2). However, P. falciparum isolates with deletion of the pfhrp2 gene and its homolog gene, pfhrp3, have been detected. We carried out an extensive investigation on 365 P. falciparum dried blood samples collected from seven P. falciparum endemic sites in Colombia between 2003 and 2012 to genetically characterise and geographically map pfhrp2- and/or pfhrp3-negative P. falciparum parasites in the country. We found a high proportion of pfhrp2-negative parasites only in Amazonas (15/39; 38.5%), and these parasites were also pfhrp3-negative. These parasites were collected between 2008 and 2009 in Amazonas, while pfhrp3-negative parasites (157/365, 43%) were found in all the sites and from each of the sample collection years evaluated (2003 to 2012). We also found that all pfhrp2- and/or pfhrp3-negative parasites were also negative for one or both flanking genes. Six sub-population clusters were established with 93.3% (14/15) of the pfhrp2-negative parasites grouped in the same cluster and sharing the same haplotype. This haplotype corresponded with the genetic lineage BV1, a multidrug resistant strain that caused two outbreaks reported in Peru between 2010 and 2013. We found this BV1 lineage in the Colombian Amazon as early as 2006. Two new clonal lineages were identified in these parasites from Colombia: the genetic lineages EV1 and F. PfHRP2 sequence analysis revealed high genetic diversity at the amino acid level, with 17 unique sequences identified among 53 PfHRP2 sequences analysed. The use of PfHRP2-based RDTs is not recommended in Amazonas because of the high proportion of parasites with pfhrp2 deletion (38.5%), and implementation of new strategies for malaria diagnosis and control in Amazonas must be prioritised. Moreover, studies to monitor and genetically characterise pfhrp2-negative P. falciparum parasites in the Americas are warranted, given the extensive

  18. Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate.

    PubMed

    Singh, Balwan; Cabrera-Mora, Monica; Jiang, Jianlin; Galinski, Mary; Moreno, Alberto

    2010-03-19

    We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four Plasmodium yoelii merozoite surface protein 1 (PyMSP1) CD4(+) promiscuous T cell epitopes fused in tandem to the homologous carboxyl terminal PyMSP1(19) fragment. This Recombinant Modular Chimera (PyRMC-MSP1(19)) was tested for immunogenicity and protective efficacy in comparative experiments with a recombinant protein expressing only the PyMSP1(19) fragment. Both proteins induced comparable antibody responses. However PyRMC-MSP1(19) elicited higher anti-parasite antibody titers and more robust protection against both hyper-parasitemia and malarial anemia. Most importantly, passive transfer of anti-PyRMC-MSP1(19), but not anti-PyMSP1(19) antibodies protected against heterologous challenge. These studies show that protective efficacy can be significantly improved by inclusion of an array of autologous promiscuous T cell epitopes in vaccine constructs. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Clues to prolific productivity among prominent scientists.

    PubMed

    Kantha, S S

    1992-10-01

    In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer, Margaret Mead, Giulio Natta, Hans Selye, Herbert C Brown, Tetsuji Kametani and Carl Djerassi. Among these, Karrer, Natta and Brown were Nobelists in chemistry. Four criteria which can be identified as clues to their prolific productivity are, 1) enthusiasm for compulsive work and eccentric life style, 2) physical and/or environmental handicap, 3) pioneering efforts in a new research field, and 4) selection of research area, predominantly organic chemistry.

  20. [Malaria in Algerian Sahara].

    PubMed

    Hammadi, D; Boubidi, S C; Chaib, S E; Saber, A; Khechache, Y; Gasmi, M; Harrat, Z

    2009-08-01

    Thanks to the malaria eradication campaign launched in Algeria in 1968, the number of malaria cases fell down significantly from 95,424 cases in 1960 to 30 cases in 1978. At that time the northern part of the country was declared free of Plasmodium falciparum. Only few cases belonging to P. vivax persisted in residual foci in the middle part of the country. In the beginning of the eighties, the south of the country was marked by an increase of imported malaria cases. The resurgence of the disease in the oases coincided with the opening of the Trans-Saharan road and the booming trade with the neighbouring southern countries. Several authors insisted on the risk of introduction of malaria or its exotic potential vectors in Algeria via this new road. Now, the totality of malaria autochthonous cases in Algeria are located in the south of the country where 300 cases were declared during the period (1980-2007). The recent outbreak recorded in 2007 at the borders with Mall and the introduction of Anopheles gambiae into the Algerian territory show the vulnerability of this area to malaria which is probably emphasized by the local environmental changes. The authors assess the evolution of malaria in the Sahara region and draw up the distribution of the anopheles in this area.

  1. Modern malaria chemoprophylaxis.

    PubMed

    Shanks, G Dennis; Edstein, Michael D

    2005-01-01

    Currently available medications for malaria chemoprophylaxis are efficacious but the problems of patient compliance, the advance of parasite drug resistance, and real or perceived serious adverse effects mean that new chemical compounds are needed.Primaquine, which has been widely used to treat relapsing malaria since the 1950s, has been shown to prevent malaria when taken daily. Tafenoquine is a new 8-aminoquinoline with a much longer half-life than primaquine. Field trials to date indicate that tafenoquine is efficacious and can be taken weekly or perhaps even less frequently. Both primaquine and tafenoquine require exact knowledge of a person's glucose 6-phosphate dehydrogenase status in order to prevent drug-induced haemolysis. Other potential malaria chemoprophylactic drugs such as third-generation antifol compounds and Mannich bases have reached advanced preclinical testing. Mefloquine has been seen to cause serious neuropsychiatric adverse effects on rare occasions. Recent public controversy regarding reputedly common serious adverse effects has made many Western travellers unwilling to take mefloquine. Special risk groups exposed to malaria, such as long-term travellers, children, pregnant women, aircrew and those requiring unimpeded psychomotor reactions, migrants returning to visit malarious countries of origin and febrile persons who have returned from malaria endemic areas, all require a nuanced approach to the use of drugs to prevent malaria. The carrying of therapeutic courses of antimalarial drugs to be taken only if febrile illness develops is indicated in very few travellers despite its appeal to some who fear adverse effects more than they fear potentially lethal malaria infection. Travellers with a significant exposure to malaria require a comprehensive plan for prevention that includes anti-mosquito measures but which is still primarily be based on the regular use of efficacious antimalarial medications.

  2. Malaria and Vascular Endothelium

    PubMed Central

    de Alencar, Aristóteles Comte; de Lacerda, Marcus Vinícius Guimarães; Okoshi, Katashi; Okoshi, Marina Politi

    2014-01-01

    Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease. PMID:25014058

  3. Malaria: prevention in travellers

    PubMed Central

    Croft, Ashley

    2000-01-01

    Definition Malaria is caused by a protozoan infection of red blood cells with one of four species of the genus plasmodium: P falciparum, P vivax, P ovale, or P malariae.1 Clinically, malaria may present in different ways, but it is usually characterised by fever (which may be swinging), tachycardia, rigors, and sweating. Anaemia, hepatosplenomegaly, cerebral involvement, renal failure, and shock may occur. Incidence/prevalence Each year there are 300-500 million clinical cases of malaria. About 40% of the world's population is at risk of acquiring the disease.23 Each year 25-30 million people from non-tropical countries visit areas in which malaria is endemic,4 of whom between 10 000 and 30 000 contract malaria.5 Aetiology/risk factors Malaria is mainly a rural disease, requiring standing water nearby. It is transmitted by bites6 from infected female anopheline mosquitoes,7 mainly at dusk and during the night.18 In cities, mosquito bites are usually from female culicene mosquitoes, which are not vectors of malaria.9 Malaria is resurgent in most tropical countries and the risk to travellers is increasing.10 Prognosis Ninety per cent of travellers who contract malaria do not become ill until after they return home.5 “Imported malaria” is easily treated if diagnosed promptly, and it follows a serious course in only about 12% of people.1112 The most severe form of the disease is cerebral malaria, with a case fatality rate in adult travellers of 2-6%,3 mainly because of delays in diagnosis.5 Aims To reduce the risk of infection; to prevent illness and death. Outcomes Rates of malarial illness and death, and adverse effects of treatment. Proxy measures include number of mosquito bites and number of mosquitoes in indoor areas. We found limited evidence linking number of mosquito bites and risk of malaria.13 Methods Clinical Evidence search and appraisal in November 1999. We reviewed all identified systematic reviews and randomised controlled trials (RCTs

  4. Online biomedical resources for malaria-related red cell disorders.

    PubMed

    Piel, Frédéric B; Howes, Rosalind E; Nyangiri, Oscar A; Moyes, Catherine L; Williams, Thomas N; Weatherall, David J; Hay, Simon I

    2013-07-01

    Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.

  5. Online Biomedical Resources for Malaria-Related Red Cell Disorders

    PubMed Central

    Piel, Frédéric B; Howes, Rosalind E; Nyangiri, Oscar A; Moyes, Catherine L; Williams, Thomas N; Weatherall, David J; Hay, Simon I

    2013-01-01

    Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed. PMID:23568771

  6. Malaria epidemiological research in the Republic of Congo.

    PubMed

    Koukouikila-Koussounda, Felix; Ntoumi, Francine

    2016-12-23

    Reliable and comprehensive information on the burden of malaria is critical for guiding national and international efforts in malaria control. The purpose of this review is to provide an overview of published data and available information on malaria resulting from field studies/investigations conducted in the Republic of Congo (RoC) from 1992 to 2015, as baseline for assisting public health authorities and researchers to define future research priorities as well as interventions. This review considers data from peer-reviewed articles and information from the National Malaria Control Programme reports, based on field investigations or samples collected from 1992 to 2015. Peer-reviewed papers were searched throughout online bibliographic databases PubMed, HINARI and Google Scholar using the following terms: "malaria", "Congo", "Brazzaville", "prevalence", "antimalarial", "efficacy", "falciparum", "genetic", "diversity". Original articles and reviews were included and selection of relevant papers was made. Twenty-eight published articles were included in this review and two additional records from the National Malaria Control Programme were also considered. The majority of studies were conducted in Brazzaville and Pointe-Noire. The present systematic review reveals that number of studies have been conducted in the RoC with regard to malaria. However, their results cannot formally be generalized at the country level. This suggests a need for implementing regular multisite investigations and surveys that may be representative of the country, calling for the support and lead of the Ministry of Health.

  7. Adjuvants for malaria vaccines.

    PubMed

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  8. Evaluating the usefulness of paratransgenesis for malaria control.

    PubMed

    Kotnis, Bhushan; Kuri, Joy

    2016-07-01

    Malaria is a serious global health problem which is especially devastating to the developing world. Most malaria control programs use insecticides for controlling mosquito populations. Large scale usage of these insecticides exerts massive selection pressure on mosquitoes resulting in insecticide resistant mosquito breeds. Thus, developing alternative strategies are crucial for sustainable malaria control. Here, we explore the usefulness of an alternative strategy, paratransgenesis: the introduction of genetically engineered plasmodium killing bacteria inside the mosquito gut. The genetically modified bacterial culture is housed in cotton balls dipped in a sugar solution (sugar bait) and they enter a mosquito's midgut when it drinks from a sugar bait. We study scenarios where vectors and hosts mix homogeneously as well as heterogeneously and calculate the amount of baits required to prevent a malaria outbreak. Given the baits are attractive, we show that the basic reproductive number drops rapidly with the increase in bait density. Furthermore, we propose a targeted bait distribution strategy for minimizing the reproductive number for the heterogeneous case. Our results can prove to be useful for designing future experiments and field trials of alternative malaria control mechanisms and they also have implications on the development of malaria control programs.

  9. Common Gene Variants Account for Most Genetic Risk for Autism

    MedlinePlus

    ... in a unique Swedish sample in the journal Nature Genetics, July 20, 2014. “Thanks to the boost ... National Institute of Mental Health (NIMH). “Knowing the nature of the genetic risk will reveal clues to ...

  10. Malaria Diagnosis: A Brief Review

    PubMed Central

    Duangdee, Chatnapa; Wilairatana, Polrat; Krudsood, Srivicha

    2009-01-01

    Malaria is a major cause of death in tropical and sub-tropical countries, killing each year over 1 million people globally; 90% of fatalities occur in African children. Although effective ways to manage malaria now exist, the number of malaria cases is still increasing, due to several factors. In this emergency situation, prompt and effective diagnostic methods are essential for the management and control of malaria. Traditional methods for diagnosing malaria remain problematic; therefore, new technologies have been developed and introduced to overcome the limitations. This review details the currently available diagnostic methods for malaria. PMID:19488414

  11. MALARIA RESEARCH PROGRAM.

    DTIC Science & Technology

    Analytical clinical summaries are presented on the following: Summary and analysis of therapeutic effect of new drugs in human volunteers with...Falciparum Malaria; Summary and analysis of therapeutic effect of new drugs in human volunteers with Vivax Malaria; Potentiation by drug combination...Problems of resistance for both old and new drugs ; Analysis of P. berghei infections; Studies on mechanisms of drug action; Cumulative summary of all new drug trials.

  12. Malaria in pregnancy.

    PubMed

    Alvarez, Jesus R; Al-Khan, Abdulla; Apuzzio, Joseph J

    2005-12-01

    Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be alert of the disease and its effects on pregnancy.

  13. Ophthalmic clues to the endocrine disorders.

    PubMed

    Liu, Z; Chen, Y; Lin, Z; Shi, X

    2017-01-01

    Eye is a vital sense organ and reflects the physical and mental wellbeing of a person. Detailed examination of the eye is an essential part in the clinical evaluation of patients with any systemic disorder. The interaction between ophthalmologists and endocrinologists is often limited to Graves' ophthalmopathy and diabetic retinopathy. However, there are many ophthalmic manifestations, which are characteristically seen in endocrine disorders. In this review, we shall discuss the ocular manifestations of the endocrine syndromes excluding the Graves' ophthalmopathy and diabetic retinopathy. We performed a PubMed search of articles published in English showing the ophthalmic features in the endocrine disorders. Relevant cited articles were also retrieved. Most of the publications included in the review were case reports and review articles. Many endocrine disorders have characteristic manifestations pertaining to the various structures of the eye. The involvement is seen from the external structures of the eye to the inner most layers of the retina. Many ocular-endocrine syndromes also exist with characteristic clues to the clinical diagnosis. The endocrinologists need to be aware of these ocular signs that help in the early diagnosis of the underlying disorder. A syndromic approach is essential in the diagnosis of endocrinopathy in patients presenting with ophthalmic features.

  14. Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria.

    PubMed

    Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E; Hartl, Daniel L; Barillas-Mury, Carolina

    2016-11-23

    Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits.

  15. Antimalarial Drug Resistance: A Threat to Malaria Elimination.

    PubMed

    Menard, Didier; Dondorp, Arjen

    2017-07-05

    Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance. Single point mutations in the gene coding for the Kelch propeller domain of the K13 protein strongly correlate with artemisinin resistance. Novel regimens and strategies using existing antimalarial drugs will be needed until novel compounds can be deployed. Elimination of artemisinin resistance will imply elimination of all falciparum malaria from the same areas. In vivax malaria, chloroquine resistance is an increasing problem. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

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

    PubMed

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

    2017-09-18

    Controlled Human Malaria Infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or direct injection of sporozoites or parasitised erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of anti-malarial 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 malaria-endemic areas. Controlled infections have also been used to immunise 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 P. falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well characterised and genetically distinct cultured malaria cell banks for blood-stage infection, and P. 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.

  17. UK malaria treatment guidelines.

    PubMed

    Lalloo, David G; Shingadia, Delane; Pasvol, Geoffrey; Chiodini, Peter L; Whitty, Christopher J; Beeching, Nicholas J; Hill, David R; Warrell, David A; Bannister, Barbara A

    2007-02-01

    Malaria is the tropical disease most commonly imported into the UK, with 1500-2000 cases reported each year, and 10-20 deaths. Approximately three-quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other two species of Plasmodium: Plasmodium ovale or Plasmodium malariae. Mixed infections with more than 1 species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until 3 blood specimens have been examined by an experienced microscopist. There are no typical clinical features of malaria, even fever is not invariably present. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites; P. falciparum malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens or enzymes, although RDTs for other Plasmodium species are not as reliable. The treatment of choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which only a limited proportion of P. vivax strains have gained resistance. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine. This must be avoided or given with caution under expert supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone) or co-artemether (Riamet

  18. Protective role of brain water channel AQP4 in murine cerebral malaria.

    PubMed

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

    2013-01-15

    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.

  19. 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

  20. Genetics

    USDA-ARS?s Scientific Manuscript database

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  1. Genetics

    USDA-ARS?s Scientific Manuscript database

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  2. Can Dirty Diapers Offer Clues to the Infant Brain?

    MedlinePlus

    ... hold clues to their brain development, a new study suggests. Researchers analyzed fecal samples from dozens of 1-year-olds and assessed their thinking (cognitive) skills a year later. The results revealed a link ...

  3. Hair shafts in trichoscopy: clues for diagnosis of hair and scalp diseases.

    PubMed

    Rudnicka, Lidia; Rakowska, Adriana; Kerzeja, Marta; Olszewska, Małgorzata

    2013-10-01

    Trichoscopy (hair and scalp dermoscopy) analyzes the structure and size of growing hair shafts, providing diagnostic clues for inherited and acquired causes of hair loss. Types of hair shaft abnormalities observed include exclamation mark hairs (alopecia areata, trichotillomania, chemotherapy-induced alopecia), Pohl-Pinkus constrictions (alopecia areata, chemotherapy-induced alopecia, blood loss, malnutrition), comma hairs (tinea capitis), corkscrew hairs (tinea capitis), coiled hairs (trichotillomania), flame hairs (trichotillomania), and tulip hairs (in trichotillomania, alopecia areata). Trichoscopy allows differential diagnosis of most genetic hair shaft disorders. This article proposes a classification of hair shaft abnormalities observed by trichoscopy. Copyright © 2013. Published by Elsevier Inc.

  4. Basosquamous carcinoma: Dermoscopic clues to diagnosis.

    PubMed

    Akay, Bengu Nisa; Saral, Secil; Heper, Aylin O; Erdem, Cengizhan; Rosendahl, Cliff

    2017-02-01

    Basosquamous carcinoma (BSC) is a rare skin cancer which has areas of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and a transition zone between them. However, dermoscopic features of BSC are not well described in the published work, except one study. The aim of the present study was to better identify and clarify the dermoscopic findings of BSC in the largest group of patients in the published work and to describe its dermoscopic features according to histopathologically BCC-dominant, SCC-dominant and intermediate categories. Dermoscopic features of 36 histopathologically proven BSC and their dermatopathological correlates were retrospectively analyzed. Dermoscopic features were evaluated by pattern analysis. Keratin mass (91.7%) was the most common dermoscopic feature. Surface scaling (77.8%), ulceration (69.4%), white structureless areas (69.4%), white clods (66.7%) and blood spots on keratin mass (66.7%) were the other frequent findings. Polymorphous vascular pattern consisting of various combinations of branched, serpentine, straight, coiled or looped vessels were detected in 61% of the lesions. BSC has BCC-dominant vascular features together with otherwise SCC-dominant morphology, the common pattern seen in BSC lesions being BCC-dominant polymorphous or monomorphous vasculature, together with dermoscopic findings of keratinization. White circles, known to be a valuable clue to SCC and keratoacanthoma, were present at the same magnitude in BSC in our study. The observed histological correlation of eosinophilic keratin overlying the epithelium which lined follicular infundibulae in these tumors, provides a plausible new perspective on dermoscopic white circles. © 2016 Japanese Dermatological Association.

  5. [Malaria in the Americas].

    PubMed

    Carme, B; Venturin, C

    1999-01-01

    In 1996, malaria involving Plasmodium vivax, Plasmodium falciparum, and, to a lesser extent, Plasmodium malariae was endemic in 21 countries in the Americas. The Amazon river basin and bordering areas including the Guyanas were the most affected zones. Until the mid 1970s, endemic malaria appeared to be under control. However in the ensuing 15 year period, the situation deteriorated drastically. Although trends varied depending on location, aggregate indexes indicated a twofold increase with recrudescence in previously settled areas and emergence in newly populated zones. Since 1990, the situation has worsened further in some areas where increased incidences have been associated with a high levels of drug-resistant Plasmodium falciparum. However this species remains in minority except in the Guyanas where the highest annual incidences (100 to 500 cases per 1000) and the most drug-resistant Plasmodium have been reported. The causes underlying this deterioration are numerous and complex. In regions naturally prone to transmission of the disease, outbreaks have been intensified by unrestrained settlement. The resulting deforestation has created new breeding areas for Anopheles darlingi, the main vector of malaria in the Americas. Migration of poor populations to newly opened farming and mining areas has created highly exposed areas for malaria infection. Implementation of adequate medical care and prevention measures has been hindered by a lack of money and sociopolitical unrest. Climatic phenomenon related the El Nino have also been favorable to the return of malaria to the region. Except with regard to financial resources and political unrest, the same risk factors for malaria are present in French Guiana.

  6. The treatment of malaria.

    PubMed

    White, N J

    1996-09-12

    Increasing drug resistance in Plasmodium falciparum and a resurgence of malaria in tropical areas have effected a change in treatment of malaria in the last two decades. Symptoms of malaria are fever, chills, headache, and malaise. The prognosis worsens as the parasite counts, counts of mature parasites, and counts of neutrophils containing pigment increase. Treatment depends on severity, age of patient, degree of background immunity, likely pattern of susceptibility to antimalarial drugs, and the cost and availability of drugs. Chloroquine should be used for P. vivax, P. malariae, and P. ovale. P. vivax has shown high resistance to chloroquine in Oceania, however. Primaquine may be needed to treat P. vivax and P. ovale to rid the body of hypnozoites that survive in the liver. Chloroquine can treat P. falciparum infections acquired in North Africa, Central America north of the Panama Canal, Haiti, or the Middle East but not in most of Africa and some parts of Asia and South America. In areas of low grade resistance to chloroquine, amodiaquine can be used to effectively treat falciparum malaria. A combination of sulfadoxine-pyrimethamine is responsive to falciparum infections with high grade resistance to chloroquine. Mefloquine, halofantrine, or quinine with tetracycline can be used to treat multidrug-resistant P. falciparum. Derivatives of artemisinin obtained from qinghao or sweet wormwood developed as pharmaceuticals in China are the most rapidly acting of all antimalarial drugs. Children tend to tolerate antimalarial drugs well. Children who weigh less than 15 kg should not be given mefloquine. Health workers should not prescribe primaquine to pregnant women or newborns due to the risk of hemolysis. Chloroquine, sulfadoxine-pyrimethamine, quinine, and quinidine can be safely given in therapeutic doses throughout pregnancy. Clinical manifestations of severe malaria are hypoglycemia, convulsions, severe anemia, acute renal failure, jaundice, pulmonary edema

  7. A population genetic model for the initial spread of partially resistant malaria parasites under anti-malarial combination therapy and weak intrahost competition.

    PubMed

    Kim, Yuseob; Escalante, Ananias A; Schneider, Kristan A

    2014-01-01

    To develop public-health policies that extend the lifespan of affordable anti-malarial drugs as effective treatment options, it is necessary to understand the evolutionary processes leading to the origin and spread of mutations conferring drug resistance in malarial parasites. We built a population-genetic model for the emergence of resistance under combination drug therapy. Reproductive cycles of parasites are specified by their absolute fitness determined by clinical parameters, thus coupling the evolutionary-genetic with population-dynamic processes. Initial mutations confer only partial drug-resistance. Therefore, mutant parasites rarely survive combination therapy and within-host competition is very weak among parasites. The model focuses on the early phase of such unsuccessful recurrent mutations. This ends in the rare event of mutants enriching in an infected individual from which the successful spread of resistance over the entire population is initiated. By computer simulations, the waiting time until the establishment of resistant parasites is analysed. Resistance spreads quickly following the first appearance of a host infected predominantly by mutant parasites. This occurs either through a rare transmission of a resistant parasite to an uninfected host or through a rare failure of drugs in removing "transient" mutant alleles. The emergence of resistance is delayed with lower mutation rate, earlier treatment, higher metabolic cost of resistance, longer duration of high drug dose, and higher drug efficacy causing a stronger reduction in the sensitive and resistant parasites' fitnesses. Overall, contrary to other studies' proposition, the current model based on absolute fitness suggests that aggressive drug treatment delays the emergence of drug resistance.

  8. Controlled human malaria infection.

    PubMed

    Spring, Michele; Polhemus, Mark; Ockenhouse, Christian

    2014-06-15

    Since 1986, investigators at Walter Reed Army Institute of Research (WRAIR) have been using controlled human malaria challenge (CHMI) in malaria-naive adults in order to define the protective efficacy of a malaria vaccine and thus guide programmatic decisions on vaccine candidates. Adapting this model to the dengue field could provide similar evidential support for a vaccine or therapeutic product. After completing a vaccine regimen, volunteers are bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled environment. Volunteers are then monitored daily for peripheral parasitemia in a hotel setting with 24-hour access to a nurse and physician. If a single verified parasite is detected, effective antimalarials are promptly administered. The vast majority of the over 1000 volunteers having participated in CHMI clinical studies have done so at US military research centers. Numerous pre-erythrocytic and erythrocytic vaccine candidates have been evaluated safely and without any related serious adverse events using this model, including the soon-to-be licensed RTS,S malaria vaccine. The lessons learned from over 25 years of experience in consistent, careful preparation and execution of the CHMI model at WRAIR can provide a foundation from which the dengue field can begin to develop a rigorous and safe "CHDI" model. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Singular Clues to Causality and Their Use in Human Causal Judgment

    ERIC Educational Resources Information Center

    White, Peter A.

    2014-01-01

    It is argued that causal understanding originates in experiences of acting on objects. Such experiences have consistent features that can be used as clues to causal identification and judgment. These are singular clues, meaning that they can be detected in single instances. A catalog of 14 singular clues is proposed. The clues function as…

  10. Progress toward a malaria vaccine: efficient induction of protective anti-malaria immunity.

    PubMed

    Tsuji, M; Rodrigues, E G; Nussenzweig, S

    2001-04-01

    Malaria can be a very severe disease, particularly in young children, pregnant women (mostly in primipara), and malaria naïve adults, and currently ranks among the most prevalent infections in tropical and subtropical areas throughout the world. The widespread occurrence and the increased incidence of malaria in many countries, caused by drug-resistant parasites (Plasmodium falciparum and P. vivax) and insecticide-resistant vectors (Anopheles mosquitoes), indicate the need to develop new methods of controlling this disease. Experimental vaccination with irradiated sporozoites can protect animals and humans against the disease, demonstrating the feasibility of developing an effective malaria vaccine. However, developing a universally effective, long lasting vaccine against this parasitic disease has been a difficult task, due to several problems. One difficulty stems from the complexity of the parasite's life cycle. During their life cycle, malaria parasites change their residence within the host, thus avoiding being re-exposed to the same immunological environment. These parasites also possess some distinct antigens, present at different life stages of the parasite, the so-called stage-specific antigens. While some of the stage-specific antigens can induce protective immune responses in the host, these responses are usually genetically restricted, this being another reason for delaying the development of a universally effective vaccine. The stage-specific antigens must be used as immunogens and introduced into the host by using a delivery system that should efficiently induce protective responses against the respective stages. Here we review several research approaches aimed at inducing protective anti-malaria immunity, overcoming the difficulties described above.

  11. Dynamic modelling of future land-use change: a comparison between CLUE-S and Dinamica EGO models

    NASA Astrophysics Data System (ADS)

    Yi, Wei; Gao, Zhiqiang; Chen, Maosi

    2012-10-01

    Land-use and land-cover change has been a research focus in global environmental change. Recent research found that land-use change could influence the structure of biogeochemical spheres as well as material and energy recycle directly or indirectly. Land-use dynamic models are considered as an effective technique to study the processes of land-use modification. The objective of this paper is to compare two widely use land-use dynamic models, CLUE-S and Dinamica EGO, from the perspective of land-use change amount, spatial characteristics, and their utility. A case study was conducted to examine the ascendants of each model and Kappa coefficient was used to compare the simulation accuracy. The modelling experiments reflected that the predictions of land-use change based on CLUE-S and Dinamica EGO matched broadly with actual situation. CLUE-S was better in overall accuracy whereas the Markov process in Dinamica EGO could precisely predict the amount of land-use change. Moreover, the spatial pattern of simulation map based on Dinamica EGO was more consistent with empirical result. Both results indicate their possible further applicability for forecasting future land-use change and corresponding studies.

  12. Prior Clues of Internal Activity on Pluto

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-08-01

    New Horizons scientists Kelsi Singer and Alan Stern predicted that Pluto may have subsurface activity, in this study published even before New Horizon's recent observations of Pluto's strangely uncratered surface areas. Where Does the Nitrogen Come From? Pluto's surface and atmosphere contain a significant amount of nitrogen, but the gas leaks out of Pluto's atmosphere at an tremendous rate -- estimated at about 1.5 × 1012-13 grams per year (roughly 200-2000 tons/hr!). But if the nitrogen has been escaping at this rate since the solar system was formed, the entire atmospheric reservoir of would have been lost long before now. So what is resupplying Pluto's nitrogen? Singer and Stern explore several possible sources: Delivery by comet impact: The authors calculate that over the 4-billion-year span since Pluto's formation, it has been impacted by a total of 600 million comets of varying sizes, all likely containing nitrogen. But their estimates show that the amount of nitrogen this would supply falls several orders of magnitude shy of explaining the escape rate. Excavation by cratering: Could comet impacts simply expose nitrogen buried in reservoirs just beneath Pluto's surface? That method, too, falls short of resupplying atmospheric nitrogen escape by at least an order of magnitude, even using the most generous estimates. Internal activity: Unless the believed atmospheric loss rate of Pluto is overestimated, the authors conclude that Pluto must experience some sort of internal activity such as cryovolcanism that brings nitrogen from below its surface up and into the atmosphere. The Study in Context of Current Events. Singer and Stern wrote and submitted this paper before the New Horizons spacecraft's recent flyby of Pluto. Data from this mission has recently provided surprise after surprise -- from images of smooth, crater-free regions on Pluto's surface to evidence of sheets of carbon monoxide, methane, and nitrogen ices flowing like glaciers. These clues support

  13. Picking up Clues from the Discard Pile

    NASA Technical Reports Server (NTRS)

    2008-01-01

    As NASA's Phoenix Mars Lander excavates trenches, it also builds piles with most of the material scooped from the holes. The piles, like this one called 'Caterpillar,' provide researchers some information about the soil.

    On Aug. 24, 2008, during the late afternoon of the 88th Martian day after landing, Phoenix's Surface Stereo Imager took separate exposures through red, green and blue filters that have been combined into this approximately true-color image.

    This conical pile of soil is about 10 centimeters (4 inches) tall. The sources of material that the robotic arm has dropped onto the Caterpillar pile have included the 'Dodo' and ''Upper Cupboard' trenches and, more recently, the deeper 'Stone Soup' trench.

    Observations of the pile provide information, such as the slope of the cone and the textures of the soil, that helps scientists understand properties of material excavated from the trenches.

    For the Stone Soup trench in particular, which is about 18 centimeters (7 inches) deep, the bottom of the trench is in shadow and more difficult to observe than other trenches that Phoenix has dug. The Phoenix team obtained spectral clues about the composition of material from the bottom of Stone Soup by photographing Caterpillar through 15 different filters of the Surface Stereo Imager when the pile was covered in freshly excavated material from the trench.

    The spectral observation did not produce any sign of water-ice, just typical soil for the site. However, the bigger clumps do show a platy texture that could be consistent with elevated concentration of salts in the soil from deep in Stone Soup. The team chose that location as the source for a soil sample to be analyzed in the lander's wet chemistry laboratory, which can identify soluble salts in the soil.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif

  14. Picking up Clues from the Discard Pile

    NASA Technical Reports Server (NTRS)

    2008-01-01

    As NASA's Phoenix Mars Lander excavates trenches, it also builds piles with most of the material scooped from the holes. The piles, like this one called 'Caterpillar,' provide researchers some information about the soil.

    On Aug. 24, 2008, during the late afternoon of the 88th Martian day after landing, Phoenix's Surface Stereo Imager took separate exposures through red, green and blue filters that have been combined into this approximately true-color image.

    This conical pile of soil is about 10 centimeters (4 inches) tall. The sources of material that the robotic arm has dropped onto the Caterpillar pile have included the 'Dodo' and ''Upper Cupboard' trenches and, more recently, the deeper 'Stone Soup' trench.

    Observations of the pile provide information, such as the slope of the cone and the textures of the soil, that helps scientists understand properties of material excavated from the trenches.

    For the Stone Soup trench in particular, which is about 18 centimeters (7 inches) deep, the bottom of the trench is in shadow and more difficult to observe than other trenches that Phoenix has dug. The Phoenix team obtained spectral clues about the composition of material from the bottom of Stone Soup by photographing Caterpillar through 15 different filters of the Surface Stereo Imager when the pile was covered in freshly excavated material from the trench.

    The spectral observation did not produce any sign of water-ice, just typical soil for the site. However, the bigger clumps do show a platy texture that could be consistent with elevated concentration of salts in the soil from deep in Stone Soup. The team chose that location as the source for a soil sample to be analyzed in the lander's wet chemistry laboratory, which can identify soluble salts in the soil.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif

  15. Mosquito ecology and control of malaria.

    PubMed

    Godfray, H Charles J

    2013-01-01

    Mosquitoes transmit some of the most important infectious diseases of man including malaria that today kills around 0.6-1.2 million people a year, the majority children in low-income countries. There is increasing realisation that no single intervention is likely to halt malaria and a multipronged approach is needed including vector control. Very effective vector control measures are currently available, most involving insecticides, although there is evidence of growing problems with the spread of resistance. A variety of novel genetic approaches to vector control are under active development. Research on targeting the mosquito has been greatly facilitated by huge investment in molecular resources, including the provision of numerous full-genome sequences. Vector control is applied population biology, and I argue here that further progress will require as much attention to mosquito ecology as has been paid to mosquito molecular biology. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

  16. Gene expression divergence between malaria vector sibling species Anopheles gambiae and An. coluzzii from rural and urban Yaoundé Cameroon

    PubMed Central

    Cassone, Bryan J.; Kamdem, Colince; Cheng, Changde; Tan, John C.; Hahn, Matthew W.; Costantini, Carlo; Besansky, Nora J.

    2014-01-01

    Divergent selection based on aquatic larval ecology is a likely factor in the recent isolation of two broadly sympatric and morphologically identical African mosquito species, the malaria vectors Anopheles gambiae and An. coluzzii. Population-based genome scans have revealed numerous candidate regions of recent positive selection, but have provided few clues as to the genetic mechanisms underlying behavioral and physiological divergence between the two species, phenotypes which themselves remain obscure. To uncover possible genetic mechanisms, we compared global transcriptional profiles of natural and experimental populations using gene-based microarrays. Larvae were sampled as second and fourth instars from natural populations in and around the city of Yaoundé, capital of Cameroon, where the two species segregate along a gradient of urbanization. Functional enrichment analysis of differentially expressed genes revealed that An. coluzzii—the species that breeds in more stable, biotically complex and potentially polluted urban water bodies—over-expresses genes implicated in detoxification and immunity relative to An. gambiae, which breeds in more ephemeral and relatively depauperate pools and puddles in suburbs and rural areas. Moreover, our data suggest that such over-expression by An. coluzzii is not a transient result of induction by xenobiotics in the larval habitat, but an inherent and presumably adaptive response to repeatedly encountered environmental stressors. Finally, we find no significant overlap between the differentially expressed loci and previously identified genomic regions of recent positive selection, suggesting that transcriptome divergence is regulated by trans-acting factors rather than cis-acting elements. PMID:24673723

  17. Malaria: Biology and Disease.

    PubMed

    Cowman, Alan F; Healer, Julie; Marapana, Danushka; Marsh, Kevin

    2016-10-20

    Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite. This has catalyzed a major effort resulting in development and regulatory approval of the first vaccine against malaria (RTS,S/AS01) as well as identification of novel drug targets and antimalarial compounds, some of which are in human clinical trials.

  18. Intraerythrocytic Killing of Malaria Parasites

    DTIC Science & Technology

    1989-05-12

    immunity (23, 24) and its relevance to human malaria (25). 4. The effect of the B- thalassemia mutation on ralaria-infectcd mice arid the role of the spleen...detected. Thus, Pc96 shares a cross-reactive epitope with these three primate malaria antigens. 4. Effect of B- thalassemia on malaria-infected mice and...B- thalassemia against malaria, rodent malaria parasites were studied in C57BL/6J mice with B- thalassemia , in mice in which the thalassemia had been

  19. Malaria evolution in South Asia: knowledge for control and elimination.

    PubMed

    Narayanasamy, Krishnamoorthy; Chery, Laura; Basu, Analabha; Duraisingh, Manoj T; Escalante, Ananias; Fowble, Joseph; Guler, Jennifer L; Herricks, Thurston; Kumar, Ashwani; Majumder, Partha; Maki, Jennifer; Mascarenhas, Anjali; Rodrigues, Janneth; Roy, Bikram; Sen, Somdutta; Shastri, Jayanthi; Smith, Joseph; Valecha, Neena; White, John; Rathod, Pradipsinh K

    2012-03-01

    The study of malaria parasites on the Indian subcontinent should help us understand unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. The Malaria Evolution in South Asia (MESA) research program is one of ten International Centers of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. In this second of two reviews, we describe why population structures of Plasmodia in India will be characterized and how we will determine their consequences on disease presentation, outcome and patterns. Specific projects will determine if genetic diversity, possibly driven by parasites with higher genetic plasticity, plays a role in changing epidemiology, pathogenesis, vector competence of parasite populations and whether innate human genetic traits protect Indians from malaria today. Deep local clinical knowledge of malaria in India will be supplemented by basic scientists who bring new research tools. Such tools will include whole genome sequencing and analysis methods; in vitro assays to measure genome plasticity, RBC cytoadhesion, invasion, and deformability; mosquito infectivity assays to evaluate changing parasite-vector compatibilities; and host genetics to understand protective traits in Indian populations. The MESA-ICEMR study sites span diagonally across India and include a mixture of very urban and rural hospitals, each with very different disease patterns and patient populations. Research partnerships include government-associated research institutes, private medical schools, city and state government hospitals, and hospitals with industry ties. Between 2012 and 2017, in addition to developing clinical research and basic science infrastructure at new clinical sites, our training workshops will engage new scientists and clinicians throughout South Asia in the malaria research field.

  20. Malaria Evolution in South Asia: Knowledge for Control and Elimination

    PubMed Central

    Narayanasamy, Krishnamoorthy; Chery, Laura; Basu, Analabha; Duraisingh, Manoj T.; Escalante, Ananias; Fowble, Joseph; Guler, Jennifer L.; Herricks, Thurston; Kumar, Ashwani; Majumder, Partha; Maki, Jennifer; Mascarenhas, Anjali; Rodrigues, Janneth; Roy, Bikram; Sen, Somdutta; Shastri, Jayanthi; Smith, Joseph; Valecha, Neena; White, John; Rathod, Pradipsinh K.

    2013-01-01

    The study of malaria parasites on the Indian subcontinent should help us understand unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and from Plasmodium vivax infections. The Malaria Evolution in South Asia (MESA) research program is one of ten International Centers of Excellence for Malaria Research (ICEMR) sponsored by the US National Institute of Health. In this second of two reviews, we describe why population structures of Plasmodia in India will be characterized and how we will determine their consequences on disease presentation, outcome and patterns. Specific projects will determine if genetic diversity, possibly driven by parasites with higher genetic plasticity, plays a role in changing epidemiology, pathogenesis, vector competence of parasite populations, and whether innate human genetic traits protect Indians from malaria today. Deep local clinical knowledge of malaria in India will be supplemented by basic scientists who bring new research tools. Such tools will include whole genome sequencing and analysis methods; in vitro assays to measure genome plasticity, RBC cytoadhesion, invasion, and deformability; mosquito infectivity assays to evaluate changing parasite-vector compatibilities; and host genetics to understand protective traits in Indian populations. The MESA-ICEMR study sites span diagonally across India, including a mixture of very urban and rural hospitals, each with very different disease patterns and patient populations. Research partnerships include government-associated research institutes, private medical schools, city and state government hospitals, and hospitals with industry ties. Between 2012-2017, in addition to developing clinical research and basic science infrastructure at new clinical sites, our training workshops will engage new scientists and clinicians throughout South Asia in the malaria research field. PMID:22266213

  1. Modelling malaria population structure and its implications for control.

    PubMed

    Buckee, Caroline O; Gupta, Sunetra

    2010-01-01

    Mathematical models of malaria transmission have been used to inform the design of malaria control programs since the mid 20th century, and many of these models have provided useful insights into the complexity of the disease. Among developing countries, however and particularly in sub-Saharan Africa, malaria remains a major cause of morbidity and mortality. One of the main difficulties in controlling the most virulent human malaria parasite, Plasmodium falciparum, is its genetic diversity, which confounds attempts to design an effective vaccine. The population structure of P. falciparum remains poorly understood but plays a key role in determining epidemiological patterns of disease and the development of immunity. We discuss the seminal model of malaria transmission developed by Ross and MacDonald, and the modifications that have been made since to include more realism. We show that age profiles of disease and serological data support a theoretical model in which the parasite population is diverse and structured into several antigenic types and highlight the implications of this structure for controlling malaria. Lastly, we discuss the current sequence data on parasite antigen genes that are important for the aquisition of immunity, and the results of a new analysis of P. falciparum population structure at the genomic level.

  2. Imported malaria in Kuwait.

    PubMed

    Hira, P R; Behbehani, K; Al-Kandari, S

    1985-01-01

    The number of imported malaria cases in Kuwait rose from 87 in 1980 to 504 in 1983, an increase of 579%. The continued resurgence of malaria in endemic zones, improved diagnostic techniques and a heightened awareness of imported malaria have contributed to the increase in the number of microscopically proved cases. Thick blood films fixed in acetone and stained in Giemsa proved a rapid method of diagnosis; species identification on the basis of a thin film on the same slide was performed with ease. Malaria was acquired in 38 countries. Most patients were young male adults. Most of the cases were due to Plasmodium vivax originating from India, although an increasing number of P. falciparum cases are also now being diagnosed from there. P. falciparum infections were evenly distributed throughout the year and most cases presented within 14 days of their arrival in the country. The highest number of P. vivax cases were diagnosed between May and October, when heat stress might have been a factor in precipitating a clinical attack of an infection previously acquired in the endemic zone. Attention is drawn to the importance of delayed attacks of P. vivax and, in semi-immunes, of P. falciparum. The time interval involved in establishing a history of "recent" travel in clinically suspected cases of malaria needs to be more clearly defined in each geographical area. Cases of induced malaria due to transfusion, accidental and congenital infections were identified. The fatality rate due to P. falciparum infections was low. In terms of the risk of renewed transmission, Kuwait may be considered a vulnerable area.

  3. Research toward Malaria Vaccines

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  4. Metabolomics and malaria biology

    PubMed Central

    Lakshmanan, Viswanathan; Rhee, Kyu Y.; Daily, Johanna P.

    2010-01-01

    Metabolomics has ushered in a novel and multi-disciplinary realm in biological research. It has provided researchers with a platform to combine powerful biochemical, statistical, computational, and bioinformatics techniques to delve into the mysteries of biology and disease. The application of metabolomics to study malaria parasites represents a major advance in our approach towards gaining a more comprehensive perspective on parasite biology and disease etiology. This review attempts to highlight some of the important aspects of the field of metabolomics, and its ongoing and potential future applications to malaria research. PMID:20970461

  5. Severity of imported malaria: protective effect of taking malaria chemoprophylaxis

    PubMed Central

    2013-01-01

    Background Although chemoprophylaxis remains an important strategy for preventing malaria in travellers, its effectiveness may be compromised by lack of adherence. Inappropriate use of chemoprophylaxis is likely to increase the risk of acquiring malaria, but may probably also worsen the severity of imported cases. The aim of this study was to assess the impact of use of malaria chemoprophylaxis on clinical features and outcome of imported malaria. Methods Demographic, clinical and laboratory data of patients included in the Rotterdam Malaria Cohort between 1998 and 2011 were systematically collected and analysed. Patients were classified as self-reported compliant or non-compliant users or as non-users of chemoprophylaxis. Severe malaria was defined using the 2010 WHO criteria. Results Details on chemoprophylaxis were available for 559 of the 604 patients, of which 64.6% were non-users, 17.9% were inadequate users and 17.5% reported to be adequate users. The group of non-users was predominated by patients with African ethnicity, partial immunity and people visiting friends and relatives. The majority contracted Plasmodium falciparum malaria. In contrast, compliant users acquired non-falciparum malaria more frequently, had significant lower P. falciparum loads on admission, shorter duration of hospitalization and significant lower odds for severe malaria as compared with non-users. Patients with P. falciparum malaria were more likely to have taken their chemoprophylaxis less compliantly than those infected with non-P. falciparum species. Multivariate analysis showed that self-reported adequate prophylaxis and being a partially immune traveller visiting friends and relatives was associated with significantly lower odds ratio of severe malaria. In contrast, age, acquisition of malaria in West-Africa and being a non-immune tourist increased their risk significantly. Conclusions Compliant use of malaria chemoprophylaxis was associated with significantly lower odds

  6. Research priorities for the development and implementation of serological tools for malaria surveillance

    PubMed Central

    Elliott, Salenna R.; Fowkes, Freya J.I.; Richards, Jack S.; Reiling, Linda; Drew, Damien R.

    2014-01-01

    Surveillance is a key component of control and elimination programs. Malaria surveillance has been typically reliant on case reporting by health services, entomological estimates and parasitemia (Plasmodium species) point prevalence. However, these techniques become less sensitive and relatively costly as transmission declines. There is great potential for the development and application of serological biomarkers of malaria exposure as sero-surveillance tools to strengthen malaria control and elimination. Antibodies to malaria antigens are sensitive biomarkers of population-level malaria exposure and can be used to identify hotspots of malaria transmission, estimate transmission levels, monitor changes over time or the impact of interventions on transmission, confirm malaria elimination, and monitor re-emergence of malaria. Sero-surveillance tools could be used in reference laboratories or developed as simple point-of-care tests for community-based surveillance, and different applications and target populations dictate the technical performance required from assays that are determined by properties of antigens and antibody responses. To advance the development of sero-surveillance tools for malaria elimination, major gaps in our knowledge need to be addressed through further research. These include greater knowledge of potential antigens, the sensitivity and specificity of antibody responses, and the longevity of these responses and defining antigens and antibodies that differentiate between exposure to Plasmodium falciparum and P. vivax. Additionally, a better understanding of the influence of host factors, such as age, genetics, and comorbidities on antibody responses in different populations is needed. PMID:25580254

  7. Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans

    PubMed Central

    Randall, Louise M.; Kenangalem, Enny; Lampah, Daniel A; Tjitra, Emiliana; Mwaikambo, Esther D; Handojo, Tjandra; Piera, Kim A; Zhao, Zhen Zhen; de Labastida Rivera, Fabian; Zhou, Yonghong; McSweeney, Karli M.; Le, Lien; Amante, Fiona H.; Haque, Ashraful; Stanley, Amanda C.; Woodberry, Tonia; Salwati, Ervi; Granger, Donald L; Hobbs, Maurine R; Price, Ric N.; Weinberg, J Brice; Montgomery, Grant W.; Anstey, Nicholas M.; Engwerda, Christian R.

    2010-01-01

    Background Age and host genetics are important determinants of malaria severity. Lymphotoxin-alpha (LTα) has been linked to the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTα production contribute to other acute vascular diseases and may contribute to malaria pathogenesis. Methods We tested the association between rs7291467, a single nucleotide polymorphism (SNP) in the LTα-related gene encoding galectin-2 (LGALS2), disease severity and function in a case-control study of ethnic Highland Papuan adults and children with SM (n=380) and asymptomatic malaria-exposed controls (n=356), originating from a non-malaria-endemic region but residing in a lowland malaria-endemic area of Papua, Indonesia. Results The LGALS2 SNP showed significant association with susceptibility to SM (including CM), in children (OR 2.02 [95% CI:1.14-3.57]) but not adults. In SM, the C-allele at rs7291467 was associated with enhanced galectin-2 transcript levels. In a separate group of Tanzanian children originating from a malaria-endemic region, we found preservation of the major ancestral LGALS2 allele and no association with susceptibility to CM. Conclusions Results suggest differences in the inflammatory contribution to the development of SM between children and adults in the same population, and potential differences between individuals originating from malaria-endemic and non-endemic areas. PMID:20500087

  8. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells

    PubMed Central

    Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-01-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control. PMID:27598328

  9. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.

    PubMed

    Yamamoto, Daisuke S; Sumitani, Megumi; Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-09-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control.

  10. Development of the Contact Lens User Experience: CLUE Scales.

    PubMed

    Wirth, R J; Edwards, Michael C; Henderson, Michael; Henderson, Terri; Olivares, Giovanna; Houts, Carrie R

    2016-08-01

    The field of optometry has become increasingly interested in patient-reported outcomes, reflecting a common trend occurring across the spectrum of healthcare. This article reviews the development of the Contact Lens User Experience: CLUE system designed to assess patient evaluations of contact lenses. CLUE was built using modern psychometric methods such as factor analysis and item response theory. The qualitative process through which relevant domains were identified is outlined as well as the process of creating initial item banks. Psychometric analyses were conducted on the initial item banks and refinements were made to the domains and items. Following this data-driven refinement phase, a second round of data was collected to further refine the items and obtain final item response theory item parameters estimates. Extensive qualitative work identified three key areas patients consider important when describing their experience with contact lenses. Based on item content and psychometric dimensionality assessments, the developing CLUE instruments were ultimately focused around four domains: comfort, vision, handling, and packaging. Item response theory parameters were estimated for the CLUE item banks (377 items), and the resulting scales were found to provide precise and reliable assignment of scores detailing users' subjective experiences with contact lenses. The CLUE family of instruments, as it currently exists, exhibits excellent psychometric properties.

  11. Ultrasonographic clues for diagnosis of spina bifida occulta in children

    PubMed Central

    Cinar, Hasibe Gokce; Uner, Cigdem; Ucan, Berna; Eksioglu, Ayse Secil; Pala, Melek; Yildiz, Yasemin Tasci; Cakmakci, Selma; Yikmaz, Hulya Seker

    2016-01-01

    Background The aim of the current study was to find out if spinal ultrasonography might have a predictive potential for detection of spina bifida occulta (SBO) in pediatric nocturnal enuresis patients. Methods A total of 108 children (58 females, 50 males) with a mean age of 8 (range, 6–15) years diagnosed for nocturnal enuresis in our tertiary care center were included in this cross-sectional analysis. Half of the cases (n=54, 50%) were found to have SBO, while the other half did not have SBO. After obtaining radiographs and computed tomography examinations of L5-S1 vertebra, patients were examined by spinal ultrasound regarding radiologic clues which may aid in the detection of SBO. Results The clues of “single and double echogeneous cap signs and the V-shaped tip of spine” were found useful for diagnosing SBO at levels of L5 and S1 in pediatric patients suspected for SBO. Receiver operating curve (ROC) curve analysis of CT and ultrasonographic clues for diagnosis of SBO on S1 level revealed that these clues yielded a comparable diagnostic accuracy to CT. Areas under curve for CT and studied ultrasonographic clues were are 0.667±0.053 and 0.907±0.032 (P<0.001) respectively. Conclusions Ultrasonography seems to be a useful and practical diagnostic tool for diagnosing spina bifida. However, to implement our ultrasonographic criteria in routine radiological practice, further studies in larger series are warranted. PMID:27942474

  12. Ultrasonographic clues for diagnosis of spina bifida occulta in children.

    PubMed

    Cakmakci, Emin; Cinar, Hasibe Gokce; Uner, Cigdem; Ucan, Berna; Eksioglu, Ayse Secil; Pala, Melek; Yildiz, Yasemin Tasci; Cakmakci, Selma; Yikmaz, Hulya Seker

    2016-10-01

    The aim of the current study was to find out if spinal ultrasonography might have a predictive potential for detection of spina bifida occulta (SBO) in pediatric nocturnal enuresis patients. A total of 108 children (58 females, 50 males) with a mean age of 8 (range, 6-15) years diagnosed for nocturnal enuresis in our tertiary care center were included in this cross-sectional analysis. Half of the cases (n=54, 50%) were found to have SBO, while the other half did not have SBO. After obtaining radiographs and computed tomography examinations of L5-S1 vertebra, patients were examined by spinal ultrasound regarding radiologic clues which may aid in the detection of SBO. The clues of "single and double echogeneous cap signs and the V-shaped tip of spine" were found useful for diagnosing SBO at levels of L5 and S1 in pediatric patients suspected for SBO. Receiver operating curve (ROC) curve analysis of CT and ultrasonographic clues for diagnosis of SBO on S1 level revealed that these clues yielded a comparable diagnostic accuracy to CT. Areas under curve for CT and studied ultrasonographic clues were are 0.667±0.053 and 0.907±0.032 (P<0.001) respectively. Ultrasonography seems to be a useful and practical diagnostic tool for diagnosing spina bifida. However, to implement our ultrasonographic criteria in routine radiological practice, further studies in larger series are warranted.

  13. Development of the Contact Lens User Experience: CLUE Scales

    PubMed Central

    Wirth, R. J.; Edwards, Michael C.; Henderson, Michael; Henderson, Terri; Olivares, Giovanna; Houts, Carrie R.

    2016-01-01

    ABSTRACT Purpose The field of optometry has become increasingly interested in patient-reported outcomes, reflecting a common trend occurring across the spectrum of healthcare. This article reviews the development of the Contact Lens User Experience: CLUE system designed to assess patient evaluations of contact lenses. CLUE was built using modern psychometric methods such as factor analysis and item response theory. Methods The qualitative process through which relevant domains were identified is outlined as well as the process of creating initial item banks. Psychometric analyses were conducted on the initial item banks and refinements were made to the domains and items. Following this data-driven refinement phase, a second round of data was collected to further refine the items and obtain final item response theory item parameters estimates. Results Extensive qualitative work identified three key areas patients consider important when describing their experience with contact lenses. Based on item content and psychometric dimensionality assessments, the developing CLUE instruments were ultimately focused around four domains: comfort, vision, handling, and packaging. Item response theory parameters were estimated for the CLUE item banks (377 items), and the resulting scales were found to provide precise and reliable assignment of scores detailing users’ subjective experiences with contact lenses. Conclusions The CLUE family of instruments, as it currently exists, exhibits excellent psychometric properties. PMID:27383257

  14. Spatio-temporal analysis of malaria within a transmission season in Bandiagara, Mali.

    PubMed

    Coulibaly, Drissa; Rebaudet, Stanislas; Travassos, Mark; Tolo, Youssouf; Laurens, Matthew; Kone, Abdoulaye K; Traore, Karim; Guindo, Ando; Diarra, Issa; Niangaly, Amadou; Daou, Modibo; Dembele, Ahmadou; Sissoko, Mody; Kouriba, Bourema; Dessay, Nadine; Gaudart, Jean; Piarroux, Renaud; Thera, Mahamadou A; Plowe, Christopher V; Doumbo, Ogobara K

    2013-03-01

    Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old". Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station.Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan(®) software according to a Bernoulli model. From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two "hot spots" of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara

  15. The Cloud Detection and UV Monitoring Experiment (CLUE)

    NASA Technical Reports Server (NTRS)

    Barbier, L.; Loh, E.; Sokolsky, P.; Streitmatter, R.

    2004-01-01

    We propose a large-area, low-power instrument to perform CLoud detection and Ultraviolet monitoring, CLUE. CLUE will combine the W detection capabilities of the NIGHTGLOW payload, with an array of infrared sensors to perform cloud slicing measurements. Missions such as EUSO and OWL which seek to measure UHE cosmic-rays at 1W20 eV use the atmosphere as a fluorescence detector. CLUE will provide several important correlated measurements for these missions, including: monitoring the atmospheric W emissions &om 330 - 400 nm, determining the ambient cloud cover during those W measurements (with active LIDAR), measuring the optical depth of the clouds (with an array of narrow band-pass IR sensors), and correlating LIDAR and IR cloud cover measurements. This talk will describe the instrument as we envision it.

  16. The Cloud Detection and UV Monitoring Experiment (CLUE)

    NASA Technical Reports Server (NTRS)

    Barbier, L.; Loh, E.; Sokolsky, P.; Streitmatter, R.

    2004-01-01

    We propose a large-area, low-power instrument to perform CLoud detection and Ultraviolet monitoring, CLUE. CLUE will combine the W detection capabilities of the NIGHTGLOW payload, with an array of infrared sensors to perform cloud slicing measurements. Missions such as EUSO and OWL which seek to measure UHE cosmic-rays at 1W20 eV use the atmosphere as a fluorescence detector. CLUE will provide several important correlated measurements for these missions, including: monitoring the atmospheric W emissions &om 330 - 400 nm, determining the ambient cloud cover during those W measurements (with active LIDAR), measuring the optical depth of the clouds (with an array of narrow band-pass IR sensors), and correlating LIDAR and IR cloud cover measurements. This talk will describe the instrument as we envision it.

  17. Nanomedicine against malaria.

    PubMed

    Urbán, Patricia; Fernàndez-Busquets, Xavier

    2014-01-01

    Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium sp. The clinical, social and economic burden of malaria has led for the last 100 years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial drugs exclusively to Plasmodium-infected cells. Different types of encapsulating structure, targeting molecule, and antimalarial compound will be discussed for the assembly of Trojan horse nanocapsules capable of targeting with complete specificity diseased cells and of delivering inside them their antimalarial cargo with the objective of eliminating the parasite with a single dose. Nanotechnology can also be applied to the discovery of new antimalarials through single-molecule manipulation approaches for the identification of novel drugs targeting essential molecular components of the parasite. Finally, methods for the diagnosis of malaria can benefit from nanotools applied to the design of microfluidic-based devices for the accurate identification of the parasite's strain, its precise infective load, and the relative content of the different stages of its life cycle, whose knowledge is essential for the administration of adequate therapies. The benefits and drawbacks of these nanosystems will be considered in different possible scenarios, including cost-related issues that might be hampering the development of nanotechnology-based medicines against malaria with the dubious argument that they are too expensive to be used in developing areas.

  18. Phylogenetic inference of Indian malaria vectors from multilocus DNA sequences.

    PubMed

    Dixit, Jyotsana; Srivastava, Hemlata; Sharma, Meenu; Das, Manoj K; Singh, O P; Raghavendra, K; Nanda, Nutan; Dash, Aditya P; Saksena, D N; Das, Aparup

    2010-08-01

    Inferences on the taxonomic positions, phylogenetic interrelationships and divergence time among closely related species of medical importance is essential to understand evolutionary patterns among species, and based on which, disease control measures could be devised. To this respect, malaria is one of the important mosquito borne diseases of tropical and sub-tropical parts of the globe. Taxonomic status of malaria vectors has been so far documented based on morphological, cytological and few molecular genetic features. However, utilization of multilocus DNA sequences in phylogenetic inferences are still in dearth. India contains one of the richest resources of mosquito species diversity but little molecular taxonomic information is available in Indian malaria vectors. We herewith utilized the whole genome sequence information of An. gambiae to amplify and sequence three orthologous nuclear genetic regions in six Indian malaria vector species (An. culicifacies, An. minimus, An. sundaicus, An. fluviatilis, An. annularis and An. stephensi). Further, we utilized the previously published DNA sequence information on the COII and ITS2 genes in all the six species, making the total number of loci to five. Multilocus molecular phylogenetic study of Indian anophelines and An. gambiae was conducted at each individual genetic region using Neighbour Joining (NJ), Maximum Likelihood (ML), Maximum Parsimony (MP) and Bayesian approaches. Although tree topologies with COII, and ITS2 genes were similar, for no other three genetic regions similar tree topologies were observed. In general, the reconstructed phylogenetic status of Indian malaria vectors follows the pattern based on morphological and cytological classifications that was reconfirmed with COII and ITS2 genetic regions. Further, divergence times based on COII gene sequences were estimated among the seven Anopheles species which corroborate the earlier hypothesis on the radiation of different species of the Anopheles

  19. Use of integrated malaria management reduces malaria in Kenya.

    PubMed

    Okech, Bernard A; Mwobobia, Isaac K; Kamau, Anthony; Muiruri, Samuel; Mutiso, Noah; Nyambura, Joyce; Mwatele, Cassian; Amano, Teruaki; Mwandawiro, Charles S

    2008-01-01

    During an entomological survey in preparation for malaria control interventions in Mwea division, the number of malaria cases at the Kimbimbi sub-district hospital was in a steady decline. The underlying factors for this reduction were unknown and needed to be identified before any malaria intervention tools were deployed in the area. We therefore set out to investigate the potential factors that could have contributed to the decline of malaria cases in the hospital by analyzing the malaria control knowledge, attitudes and practices (KAP) that the residents in Mwea applied in an integrated fashion, also known as integrated malaria management (IMM). Integrated Malaria Management was assessed among community members of Mwea division, central Kenya using KAP survey. The KAP study evaluated community members' malaria disease management practices at the home and hospitals, personal protection measures used at the household level and malaria transmission prevention methods relating to vector control. Concurrently, we also passively examined the prevalence of malaria parasite infection via outpatient admission records at the major referral hospital in the area. In addition we studied the mosquito vector population dynamics, the malaria sporozoite infection status and entomological inoculation rates (EIR) over an 8 month period in 6 villages to determine the risk of malaria transmission in the entire division. A total of 389 households in Mwea division were interviewed in the KAP study while 90 houses were surveyed in the entomological study. Ninety eight percent of the households knew about malaria disease while approximately 70% of households knew its symptoms and methods to manage it. Ninety seven percent of the interviewed households went to a health center for malaria diagnosis and treatment. Similarly a higher proportion (81%) used anti-malarial medicines bought from local pharmacies. Almost 90% of households reported owning and using an insecticide treated bed net

  20. Diagnosis and Treatment of Plasmodium vivax Malaria

    PubMed Central

    Baird, J. Kevin; Valecha, Neena; Duparc, Stephan; White, Nicholas J.; Price, Ric N.

    2016-01-01

    The diagnosis and treatment of Plasmodium vivax malaria differs from that of Plasmodium falciparum malaria in fundamentally important ways. This article reviews the guiding principles, practices, and evidence underpinning the diagnosis and treatment of P. vivax malaria. PMID:27708191

  1. Tutorials for Africa - Malaria: MedlinePlus

    MedlinePlus

    Tutorials for Africa: Malaria In Uganda, the burden of malaria outranks that of all other diseases. This tutorial includes information about how malaria spreads, the importance of treatment and techniques for ...

  2. World Malaria Report: time to acknowledge Plasmodium knowlesi malaria.

    PubMed

    Barber, Bridget E; Rajahram, Giri S; Grigg, Matthew J; William, Timothy; Anstey, Nicholas M

    2017-03-31

    The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report. Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation. The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.

  3. Global phylogeographic limits of Hawaii's avian malaria

    USGS Publications Warehouse

    Beadell, J.S.; Ishtiaq, F.; Covas, R.; Melo, M.; Warren, B.H.; Atkinson, C.T.; Bensch, S.; Graves, G.R.; Jhala, Y.V.; Peirce, M.A.; Rahmani, A.R.; Fonseca, D.M.; Fleischer, R.C.

    2006-01-01

    The introduction of avian malaria (Plasmodium relictum) to Hawaii has provided a model system for studying the influence of exotic disease on naive host populations. Little is known, however, about the origin or the genetic variation of Hawaii's malaria and traditional classification methods have confounded attempts to place the parasite within a global ecological and evolutionary context. Using fragments of the parasite mitochondrial gene cytochrome b and the nuclear gene dihydrofolate reductase-thymidylate synthase obtained from a global survey of greater than 13 000 avian samples, we show that Hawaii's avian malaria, which can cause high mortality and is a major limiting factor for many species of native passerines, represents just one of the numerous lineages composing the morphological parasite species. The single parasite lineage detected in Hawaii exhibits a broad host distribution worldwide and is dominant on several other remote oceanic islands, including Bermuda and Moorea, French Polynesia. The rarity of this lineage in the continental New World and the restriction of closely related lineages to the Old World suggest limitations to the transmission of reproductively isolated parasite groups within the morphological species. ?? 2006 The Royal Society.

  4. Population structure of an island malaria vector.

    PubMed

    Foley, D H; Torres, E P

    2006-12-01

    The impact of islands on the population structure of Anopheles flavirostris (Ludlow) (Diptera: Culicidae), the primary malaria vector in the Philippines, was assessed. A phylogenetic analysis of 16 cytochrome oxidase subunit 1 (CO1) haplotypes revealed three clades: one basal clade containing genetically disparate haplotypes from Mindanao, and two derived clades, one of which was largely confined to the largest island, Luzon, and one that was widespread except for Luzon. For the Luzon clade, nested clade analysis revealed an isolation-by-distance effect, and a mismatch distribution analysis diagnosed a recent demographic expansion (sum of squared deviation, SDD = 0.0093, P= 0.075), which mirrors demographic attributes found in mainland primary malaria vectors and could inflate estimates of gene flow from F(ST). For the widespread clade, evidence of range expansion and past fragmentation and/or long distance colonization from the Visayas or Mindanao to Palawan is suggested. A south-to-north range expansion of An. flavirostris is suggested; estimates of coalescence for the Luzon clade was 214 000 years ago (ya) (95% confidence interval 35 600-298 000 ya), i.e. late Pleistocene. Present day rather than Pleistocene island association and some, but not all, sea barriers appeared to be important for An. flavirostris population structure. Our results suggest that endemic island malaria vector species need to be considered before any generalizations are made about the population structure of primary and secondary vectors.

  5. Immune Escape Strategies of Malaria Parasites

    PubMed Central

    Gomes, Pollyanna S.; Bhardwaj, Jyoti; Rivera-Correa, Juan; Freire-De-Lima, Celio G.; Morrot, Alexandre

    2016-01-01

    Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins, and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission. PMID:27799922

  6. Immune Escape Strategies of Malaria Parasites.

    PubMed

    Gomes, Pollyanna S; Bhardwaj, Jyoti; Rivera-Correa, Juan; Freire-De-Lima, Celio G; Morrot, Alexandre

    2016-01-01

    Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins, and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  7. VLA Study Offers Clue to Galaxy Formation

    NASA Astrophysics Data System (ADS)

    2004-11-01

    Astronomers using the National Science Foundation's Very Large Array (VLA) radio telescope to study the most distant known quasar have found a tantalizing clue that may answer a longstanding cosmic chicken-and-egg question: which came first, supermassive black holes or giant galaxies? VLA Image of Quasar VLA Image of Quasar J1148+5251 CREDIT: Walter et al., NRAO/AUI/NSF (Click on Image for Larger Version) For years, astronomers have noted a direct relationship between the mass of a galaxy's central, supermassive black hole and the total mass of the "bulge" of stars at its core. The more massive the black hole, the more massive the bulge. Scientists have speculated extensively about whether the black hole or the stellar bulge formed first. Recently, some theories have suggested that the two may form simultaneously. However, the new VLA observations of a quasar and its host galaxy seen as they were when the Universe was less than a billion years old indicate that the young galaxy has a supermassive black hole but no massive bulge of stars. "We found a large amount of gas in this young galaxy, and, when we add the mass of this gas to that of the black hole, they add up to nearly the total mass of the entire system. The dynamics of the galaxy imply that there isn't much mass left to make up the size of stellar bulge predicted by current models," said Chris Carilli, of the National Radio Astronomy Observatory (NRAO), in Socorro, NM. The scientists studied a quasar dubbed J1148+5251, that, at more than 12.8 billion light-years, is the most distant quasar yet found. Discovered in 2003 by the Sloan Digital Sky Survey, J1148+5251 is a young galaxy with a bright quasar core seen as it was when the Universe was only 870 million years old. The Universe now is 13.7 billion years old. Aiming the VLA at J1148+4241 for about 60 hours, the researchers were able to determine the amount of molecular gas in the system. In addition, they were able to measure the motions of that gas

  8. Astronomers Gain Clues About Fundamental Physics

    NASA Astrophysics Data System (ADS)

    2005-12-01

    An international team of astronomers has looked at something very big -- a distant galaxy -- to study the behavior of things very small -- atoms and molecules -- to gain vital clues about the fundamental nature of our entire Universe. The team used the National Science Foundation's Robert C. Byrd Green Bank Telescope (GBT) to test whether the laws of nature have changed over vast spans of cosmic time. The Green Bank Telescope The Robert C. Byrd Green Bank Telescope CREDIT: NRAO/AUI/NSF (Click on image for GBT gallery) "The fundamental constants of physics are expected to remain fixed across space and time; that's why they're called constants! Now, however, new theoretical models for the basic structure of matter indicate that they may change. We're testing these predictions." said Nissim Kanekar, an astronomer at the National Radio Astronomy Observatory (NRAO), in Socorro, New Mexico. So far, the scientists' measurements show no change in the constants. "We've put the most stringent limits yet on some changes in these constants, but that's not the end of the story," said Christopher Carilli, another NRAO astronomer. "This is the exciting frontier where astronomy meets particle physics," Carilli explained. The research can help answer fundamental questions about whether the basic components of matter are tiny particles or tiny vibrating strings, how many dimensions the Universe has, and the nature of "dark energy." The astronomers were looking for changes in two quantities: the ratio of the masses of the electron and the proton, and a number physicists call the fine structure constant, a combination of the electron charge, the speed of light and the Planck constant. These values, considered fundamental physical constants, once were "taken as time independent, with values given once and forever" said German particle physicist Christof Wetterich. However, Wetterich explained, "the viewpoint of modern particle theory has changed in recent years," with ideas such as

  9. Heritability of P. falciparum and P. vivax malaria in a Karen population in Thailand.

    PubMed

    Phimpraphi, Waraphon; Paul, Richard; Witoonpanich, Bhee; Turbpaiboon, Chairat; Peerapittayamongkol, Chayanon; Louicharoen, Chalisa; Casademont, Isabelle; Tungpradabkul, Sumalee; Krudsood, Srivicha; Kaewkunwal, Jaranit; Sura, Thanyachai; Looareesuwan, Sornchai; Singhasivanon, Pratap; Sakuntabhai, Anavaj

    2008-01-01

    The majority of studies concerning malaria host genetics have focused on individual genes that confer protection against rather than susceptibility to malaria. Establishing the relative impact of genetic versus non-genetic factors on malaria infection and disease is essential to focus effort on key determinant factors. This relative contribution has rarely been evaluated for Plasmodium falciparum and almost never for Plasmodium vivax. We conducted a longitudinal cohort study in a Karen population of 3,484 individuals in a region of mesoendemic malaria, Thailand from 1998 to 2005. The number of P. falciparum and P. vivax clinical cases and the parasite density per person were determined. Statistical analyses were performed to account for the influence of environmental factors and the genetic heritability of the phenotypes was calculated using the pedigree-based variance components model. The genetic contribution to the number of clinical episodes resulting from P. falciparum and P. vivax were 10% and 19% respectively. There was also moderate genetic contribution to the maximum and overall parasite trophozoite density phenotypes for both P. falciparum (16%&16%) and P. vivax (15%&13%). These values, for P. falciparum, were similar to those previously observed in a region of much higher transmission intensity in Senegal, West Africa. Although environmental factors play an important role in acquiring an infection, genetics plays a determinant role in the outcome of an infection with either malaria parasite species prior to the development of immunity.

  10. Rapid diagnostic tests for malaria.

    PubMed

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

    2015-12-01

    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.

  11. Plasmodium vivax Malaria in Cambodia

    PubMed Central

    Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier

    2016-01-01

    The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. PMID:27708187

  12. Malaria, a difficult diagnosis in a febrile patient with sub-microscopic parasitaemia and polyclonal lymphocyte activation outside the endemic region, in Brazil

    PubMed Central

    2013-01-01

    A case of autochthonous Plasmodium vivax malaria with sub-microscopic parasitaemia and polyclonal B-cell activation (PBA) (as reflected by positive IgM and IgG serology for toxoplasmosis, cytomegalovirus, and antinuclear and rheumatoid factors) was diagnosed by polymerase chain reaction (PCR) after consecutive negative rapid diagnostic test results and blood films. The patient, a 44-year-old man from Rio de Janeiro state, Brazil, had visited the Atlantic Forest, a tourist, non-malaria-endemic area where no autochthonous cases of ’bromeliad malaria‘ has ever been described. The characteristic pattern of fever, associated with PBA, was the clue to malaria diagnosis, despite consecutive negative thick blood smears. The study highlights a need for changes in clinical and laboratory diagnostic approaches, namely the incorporation of PCR as part of the current routine malaria diagnostic methods in non-endemic areas. PMID:24200365

  13. Artemisinin-resistant Plasmodium falciparum malaria

    PubMed Central

    Fairhurst, Rick M.; Dondorp, Arjen M.

    2016-01-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins – the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs) – the first-line treatments for malaria – are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in-vitro, genomics, and transcriptomics studies in SEA have defined in-vivo and in-vitro phenotypes of artemisinin resistance; identified its causal genetic determinant; explored its molecular mechanism; and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's ‘K13’ gene; is associated with an upregulated “unfolded protein response” pathway that may antagonize the pro-oxidant activity of artemisinins; and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent; test whether new combinations of currently-available drugs cure ACT failures; and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to Sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest. PMID:27337450

  14. Artemisinin-Resistant Plasmodium falciparum Malaria.

    PubMed

    Fairhurst, Rick M; Dondorp, Arjen M

    2016-06-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

  15. Malaria surveillance counts.

    PubMed

    Breman, Joel G; Holloway, Cherice N

    2007-12-01

    Clinical and epidemiologic surveillance of malaria cases and deaths is required to follow the progress of the reinvigorated malaria control programs nationally and internationally. Current recording, transmittal, analysis, feedback, and use of malaria surveillance information is delayed and imprecise: substantially < 10% of the malaria cases and deaths are being reported. Improvements are occurring, but more emphasis should be placed on prompt, accurate diagnosis, patient management, and recording of clinical manifestations at hospitals. Neurologic signs, severe anemia, metabolic changes, hyperparasitemia, and concurrent sepsis are medical emergencies and require proper clinical and laboratory detection; equipment, reagents, supervision, and certification of laboratorians and clinicians are necessary. Birth weight should also be a major measure of progress in malarial control and overall prenatal care. Although malaria is the most frequent diagnosis at outpatient clinics and hospitals in Africa, co-existing conditions also mandate improved diagnosis, treatment, and registration. Monthly transmittal of information from health units and collation, analysis and feedback through electronic reporting systems using modern information technologies are necessary for resource planning and staff motivation. Denominators to compute rates of illness and death require accurate censuses of communities from which patients come to health units: specialized disease and demographic household surveys designed and performed by nationals are needed to complement hospital-based numerator data. Plasmodium falciparum and P. vivax should be distinguished in the laboratory; the former causes the greatest mortality but the latter is increasingly recognized as a major peril. Because vector control is now a major component of all malaria control programs, there is an urgent need to monitor anopheline sensitivity to insecticides and entomologic inoculation rates. Where interrupting transmission

  16. Malaria in Pregnancy

    PubMed Central

    Takem, Ebako Ndip; D’Alessandro, Umberto

    2013-01-01

    Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired since 2000 on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP) include low maternal age, low parity, and low gestational age. The main effects of MIP include maternal anaemia, low birth weight (LBW), preterm delivery and increased infant and maternal mortality. P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA), that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non-recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery), anaemia, and high cytokines levels have been implicated. Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections in African women, respectively. Compared to microscopy, RDTs have a lower sensitivity though when the quality of microscopy is low RDTs may be more reliable. Insecticide treated nets (ITN) and intermittent preventive treatment in pregnancy (IPTp) are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28–47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria during the first trimester, quinine plus clindamycin for 7 days is the first line treatment and artesunate plus clindamycin for 7 days is indicated if

  17. [Malaria and memory in the Veneto region of Italy].

    PubMed

    Pegoraro, Manuela; Crotti, Daniele

    2009-09-01

    Malaria and emigration are two terms deeply embedded in Veneto history, related to images far back in the past, unknown to younger generations. Losing one's own collective historical memory is a source of personal and cultural impoverishment and inevitably compromises one's awareness of the present, possibly leading to superficial judgements and hastily formed opinions. Such a situation is all the more serious in a geographical area, north-eastern Italy, where immigration is so abundant. In this paper the authors seek to retrieve, at least in part, this memory, especially in terms of history (to what extent malaria afflicted residents in Veneto and migrants from the region) and biology (how much imprinting from malaria has remained in the native population's genetic make-up).

  18. An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand.

    PubMed

    Imwong, Mallika; Jindakhad, Thantip; Kunasol, Chanon; Sutawong, Kreepol; Vejakama, Phisitt; Dondorp, Arjen M

    2015-11-30

    Artemisinin resistant falciparum malaria is an increasing problem in Southeast Asia, but has not been associated with increased transmission of the disease, yet. During a recent outbreak in 2014 in Ubon Ratchatani, Eastern Thailand, parasites from 101 patients with falciparum malaria were genotyped for antimalarial drug resistance markers. Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing. Resistance markers for antifolates and chloroquine were also highly prevalent. Most strains (91%) carried single copy number PfMDR1, suggesting sustained sensitivity to mefloquine, the partner drug in the local first-line artemisinin combination therapy (ACT). The high prevalence of artemisinin resistance in this recent malaria outbreak suggests but does not prove a causative role in increased transmission. Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

  19. Malaria Host Candidate Genes Validated by Association With Current, Recent, and Historical Measures of Transmission Intensity.

    PubMed

    Sepúlveda, Nuno; Manjurano, Alphaxard; Campino, Susana G; Lemnge, Martha; Lusingu, John; Olomi, Raimos; Rockett, Kirk A; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Clark, Taane G; Riley, Eleanor M; Drakeley, Chris J

    2017-07-01

    Human malaria susceptibility is determined by multiple genetic factors. It is unclear, however, which genetic variants remain important over time. Genetic associations of 175 high-quality polymorphisms within several malaria candidate genes were examined in a sample of 8096 individuals from northeast Tanzania using altitude, seroconversion rates, and parasite rates as proxies of historical, recent, and current malaria transmission intensity. A principal component analysis was used to derive 2 alternative measures of overall malaria propensity of a location across different time scales. Common red blood cell polymorphisms (ie, hemoglobin S, glucose-6-phosphate dehydrogenase, and α-thalassemia) were the only ones to be associated with all 3 measures of transmission intensity and the first principal component. Moderate associations were found between some immune response genes (ie, IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium- to long-term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals.

  20. Genital ulcer as a new clinical clue to PFAPA syndrome.

    PubMed

    Scattoni, R; Verrotti, A; Rinaldi, V E; Paglino, A; Carelli, A; D'Alonzo, R

    2015-04-01

    Vaginal ulcers can be associated with a number of different diseases. We describe two girls who presented genital ulcers as a persistent symptom of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. The possibility of considering this clinical manifestation as a clue for the diagnosis of PFAPA is discussed.

  1. Clue Insensitivity in Remote Associates Test Problem Solving

    ERIC Educational Resources Information Center

    Smith, Steven M.; Sifonis, Cynthia M.; Angello, Genna

    2012-01-01

    Does spreading activation from incidentally encountered hints cause incubation effects? We used Remote Associates Test (RAT) problems to examine effects of incidental clues on impasse resolution. When solution words were seen incidentally 3-sec before initially unsolved problems were retested, more problems were resolved (Experiment 1). When…

  2. Sex Behavior as a Clue to Mental Disease

    ERIC Educational Resources Information Center

    Chrzanowski, Gerard

    1971-01-01

    While certain forms of sex behavior may serve as a clue to the existence of mental illness, care must be taken not to view such behavior outside the overall context of a person's particular life situation, since sex behavior is a reflection of the totality of human existence. (Author)

  3. Clue Insensitivity in Remote Associates Test Problem Solving

    ERIC Educational Resources Information Center

    Smith, Steven M.; Sifonis, Cynthia M.; Angello, Genna

    2012-01-01

    Does spreading activation from incidentally encountered hints cause incubation effects? We used Remote Associates Test (RAT) problems to examine effects of incidental clues on impasse resolution. When solution words were seen incidentally 3-sec before initially unsolved problems were retested, more problems were resolved (Experiment 1). When…

  4. Tinea imbricata as a clue to occult immunodeficiency.

    PubMed

    Maroñas Jiménez, Lidia; Monsálvez, Verónica; Gutiérrez García-Rodrigo, Carlota; Postigo Llorente, Concepción

    2014-01-01

    Tinea imbricata (TI) is a geographically restricted dermatophytosis with distinctive clinical and immunologic features. We present a case of TI occurring in a native Brazilian child with previously undiagnosed human immunodeficiency virus infection. Physicians should bear in mind that diagnosis of TI may be a clinical clue to potentially serious underlying immunodeficiency.

  5. Clue to the unification of gravitation and particle physics

    SciTech Connect

    Wesson, P.S.

    1981-04-15

    Astrophysical data reveal the existence of a (broken) symmetry of the gravitational interaction implying the existence of a new dimensional constant papprox. =8 x 10/sup -16/ g/sup -1/ cm/sup 2/ sec/sup -1/. The existence of this constant provides a clue to the unification of gravitation and particle physics.

  6. Possible selection of host folate pathway gene polymorphisms in patients with malaria from a malaria endemic region in North East India

    PubMed Central

    Mirgal, Darshana; Ghosh, Kanjaksha; Mahanta, Jagadish; Dutta, Prafulla; Shetty, Shrimati

    2016-01-01

    Background Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway. Methods A total of 401 subjects including 131 symptomatic malaria, 97 asymptomatic malaria and 173 normal healthy controls were analysed for nine polymorphisms (single-nucleotide polymorphisms [SNPs] in eight genes and insertion/deletion in one gene): MTHFR C677T, methionine synthase reductase (MTRR) A66G, glutamate carboxypeptidase II (GCPII) C1561T, cystathionine beta-synthase (CBS) 844ins68, reduced folate carrier-1 (RFC-1) G80A, serine hydroxymethyltransferase (SHMT) C1420T, methionine synthase (MTR) A2756G, MTHFR G1793A (D 919G), glycine N-methyltransferase (GNMT) 1289 by PCR-RFLP technique. Differences in frequencies of genotype distribution of each polymorphic marker between these groups were evaluated. Results MTRR A2756G, SHMT C1420T, GCPII C1561T, MTRR A2756G and GNMT C1289T and RFC1 G80A polymorphisms showed significantly different prevalence between different groups analyzed. No significant differences were seen in the distribution of other polymorphisms. Conclusions The study gives a clue for the possible selection of specific polymorphisms in the genes involved in the folate metabolism pathway by malaria parasite. PMID:27198213

  7. [Prophylaxis of malaria].

    PubMed

    Gentilini, M; Caumes, E; Danis, M

    1992-01-01

    The prevention of malaria is based on chemoprophylaxis and protection against the vector. Nocturnal mosquito bites can be avoided by individual and collective measures, while chemoprophylaxis involves the use of various agents according to the place and duration of stay. Three endemic zones can be defined on the basis of chemoresistance. Chloroquine, proguanil and mefloquine are the three drugs used in this setting, the latter being contraindicated for pregnant women and children. Travellers making long stays in areas of low-level chemoresistance and short stays in areas of high-level resistance and for whom mefloquine is contraindicated are advised to take antimalarial drugs at the first signs of potentially malarial fever when medical care is unavailable. Quinine, halofantrine and mefloquine are used for the curative treatment of malaria in areas of chloroquine resistance.

  8. Malaria control in Tanzania

    SciTech Connect

    Yhdego, M.; Majura, P. )

    1988-01-01

    A review of the malaria control programs and the problem encountered in the United Republic of Tanzania since 1945 to the year 1986 is discussed. Buguruni, one of the squatter areas in the city of Dar es Salaam, is chosen as a case study in order to evaluate the economic advantage of engineering methods for the control of malaria infection. Although the initial capital cost of engineering methods may be high, the cost effectiveness requires a much lower financial burden of only about Tshs. 3 million compared with the conventional methods of larviciding and insecticiding which requires more than Tshs. 10 million. Finally, recommendations for the adoption of engineering methods are made concerning the upgrading of existing roads and footpaths in general with particular emphasis on drainage of large pools of water which serve as breeding sites for mosquitoes.

  9. Epidemiological and clinical correlates of malaria-helminth co-infections in southern Ethiopia

    PubMed Central

    2013-01-01

    Background In many areas of the world, including Ethiopia, malaria and helminths are co-endemic, therefore, co-infections are common. However, little is known how concurrent infections affect the epidemiology and/or pathogenesis of each other. Therefore, this study was conducted to assess the effects of intestinal helminth infections on the epidemiology and clinical patterns of malaria in southern Ethiopia where both infections are prevalent. Methods A cross-sectional study was conducted in 2006 at Wondo Genet Health Center and Bussa Clinic, southern Ethiopia. Consecutive blood film positive malaria patients (N=230) and malaria negative asymptomatic individuals (N=233) were recruited. Malaria parasite detection and quantification was diagnosed using Giemsa-stained thick and thin blood films, respectively. Helminths were detected using direct microscopy and formol-ether concentration techniques. Coarse quantification of helminths ova was made using Kato Katz method. Results The over all magnitude of intestinal parasitic infection was high irrespective of malaria infection (67% among malaria positive patients versus 53.1% among malaria non-infected asymptomatic individuals). Trichuris trichiura infection was associated with increased malaria prevalence while increased worm burden of helminths as expressed by egg intensity was associated with increased malaria parasitaemia which could be a potential factor for development of severe malarial infection with the course of the disease. Majority (77%) of the subjects had multiple helminths infection. T. trichiura, Ascaris lumbricoides, Schistosoma mansoni, and hookworm infestation accounted for 64.5, 57.7 %, 28.4%, and 12.2% of the infections, respectively. Conclusions Populations in malaria-endemic areas of southern Ethiopia are multi-parasitized with up to four helminths. Mass deworming may be a simple practical approach in endemic areas in reducing the risk of severe malarial attack particularly for those at high risk

  10. Oxidative Stress in Malaria

    PubMed Central

    Percário, Sandro; Moreira, Danilo R.; Gomes, Bruno A. Q.; Ferreira, Michelli E. S.; Gonçalves, Ana Carolina M.; Laurindo, Paula S. O. C.; Vilhena, Thyago C.; Dolabela, Maria F.; Green, Michael D.

    2012-01-01

    Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. PMID:23208374

  11. Molecular Vaccines for Malaria

    DTIC Science & Technology

    2010-01-01

    pathogen-associated molecular patterns for cancer immunotherapy. Cancer Gene Ther 200S; 16:310-9. 105. Dempsey PW, Allison ME, Akkaraju S, Goodnow CC ...malaria immunity elicited by recombinant adenovirus. Parasite lmmunol 2000; 22:157-60. 149. Sridhar S, Reyes- Sandoval A, Draper SJ, Moore AC...AT, Koup RA, Roederer M, Bailer RT, 166. Fitzgerald JC, Gao GP, Reyes- Sandoval A, Pavlakis hyperanenuated strain of Listeria monocytogenes. J Enama

  12. Unexpected fold in the circumsporozoite protein target of malaria vaccines

    PubMed Central

    Doud, Michael B.; Koksal, Adem C.; Mi, Li-Zhi; Song, Gaojie; Lu, Chafen; Springer, Timothy A.

    2012-01-01

    Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an “αTSR” domain. The αTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but αTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized αTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket. PMID:22547819

  13. Unexpected fold in the circumsporozoite protein target of malaria vaccines

    SciTech Connect

    Doud, Michael B.; Koksal, Adem C.; Mi, Li-Zhi; Song, Gaojie; Lu, Chafen; Springer, Timothy A.

    2012-10-09

    Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an '{alpha}TSR' domain. The {alpha}TSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but {alpha}TSR does not. Interestingly, polymorphic T-cell epitopes map to specialized {alpha}TSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.

  14. [Malaria in hominids].

    PubMed

    Snounou, Georges; Escalante, Ananias; Kasenene, John; Rénia, Laurent; Grüner, Anne-Charlotte; Krief, Sabrina

    2011-11-01

    Malaria parasites (Plasmodium spp) that infect great apes are very poorly documented Malaria was first described in gorillas, chimpanzees and orangutans in the early 20th century, but most studies were confined to a handful of chimpanzees in the 1930-1950s and a few orangutans in the 1970s. The three Plasmodium species described in African great apes were very similar to those infecting humans. The most extensively studied was P reichenowi, because of its close phylogenetic relation to P. falciparum, the predominant parasite in Africa and the most dangerous for humans. In the last three years, independent molecular studies of various chimpanzee and gorilla populations have revealed an unexpected diversity in the Plasmodium species they harbor, which are also phylogenetically close to P falciparum. In addition, cases of non human primate infection by human malaria parasites have been observed. These observations shed fresh light on the origin and evolutionary history of P. falciparum and provide a unique opportunity to probe the biological specificities of this major human parasite.

  15. Malaria parasite clearance.

    PubMed

    White, Nicholas J

    2017-02-23

    Following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. Damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. Splenic clearance functions increase markedly in acute malaria. Either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of drug-damaged parasites is an important mechanism of clearance. The once-infected erythrocytes returned to the circulation have shortened survival. This contributes to post-artesunate haemolysis that may follow recovery in non-immune hyperparasitaemic patients. As the parasites mature Plasmodium vivax-infected erythrocytes become more deformable, whereas Plasmodium falciparum-infected erythrocytes become less deformable, but they escape splenic filtration by sequestering in venules and capillaries. Sequestered parasites are killed in situ by anti-malarial drugs and then disintegrate to be cleared by phagocytic leukocytes. After treatment with artemisinin derivatives some asexual parasites become temporarily dormant within their infected erythrocytes, and these may regrow after anti-malarial drug concentrations decline. Artemisinin resistance in P. falciparum reflects reduced ring stage susceptibility and manifests as slow parasite clearance. This is best assessed from the slope of the log-linear phase of parasitaemia reduction and is commonly measured as a parasite clearance half-life. Pharmacokinetic-pharmacodynamic modelling of anti-malarial drug effects on parasite clearance has proved useful in predicting therapeutic responses and in dose-optimization.

  16. The genome of Anopheles darlingi, the main neotropical malaria vector.

    PubMed

    Marinotti, Osvaldo; Cerqueira, Gustavo C; de Almeida, Luiz Gonzaga Paula; Ferro, Maria Inês Tiraboschi; Loreto, Elgion Lucio da Silva; Zaha, Arnaldo; Teixeira, Santuza M R; Wespiser, Adam R; Almeida E Silva, Alexandre; Schlindwein, Aline Daiane; Pacheco, Ana Carolina Landim; Silva, Artur Luiz da Costa da; Graveley, Brenton R; Walenz, Brian P; Lima, Bruna de Araujo; Ribeiro, Carlos Alexandre Gomes; Nunes-Silva, Carlos Gustavo; de Carvalho, Carlos Roberto; Soares, Célia Maria de Almeida; de Menezes, Claudia Beatriz Afonso; Matiolli, Cleverson; Caffrey, Daniel; Araújo, Demetrius Antonio M; de Oliveira, Diana Magalhães; Golenbock, Douglas; Grisard, Edmundo Carlos; Fantinatti-Garboggini, Fabiana; de Carvalho, Fabíola Marques; Barcellos, Fernando Gomes; Prosdocimi, Francisco; May, Gemma; Azevedo Junior, Gilson Martins de; Guimarães, Giselle Moura; Goldman, Gustavo Henrique; Padilha, Itácio Q M; Batista, Jacqueline da Silva; Ferro, Jesus Aparecido; Ribeiro, José M C; Fietto, Juliana Lopes Rangel; Dabbas, Karina Maia; Cerdeira, Louise; Agnez-Lima, Lucymara Fassarella; Brocchi, Marcelo; de Carvalho, Marcos Oliveira; Teixeira, Marcus de Melo; Diniz Maia, Maria de Mascena; Goldman, Maria Helena S; Cruz Schneider, Maria Paula; Felipe, Maria Sueli Soares; Hungria, Mariangela; Nicolás, Marisa Fabiana; Pereira, Maristela; Montes, Martín Alejandro; Cantão, Maurício E; Vincentz, Michel; Rafael, Miriam Silva; Silverman, Neal; Stoco, Patrícia Hermes; Souza, Rangel Celso; Vicentini, Renato; Gazzinelli, Ricardo Tostes; Neves, Rogério de Oliveira; Silva, Rosane; Astolfi-Filho, Spartaco; Maciel, Talles Eduardo Ferreira; Urményi, Turán P; Tadei, Wanderli Pedro; Camargo, Erney Plessmann; de Vasconcelos, Ana Tereza Ribeiro

    2013-08-01

    Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector-human and vector-parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles-darlingi.

  17. The Genome of Anopheles darlingi, the main neotropical malaria vector

    PubMed Central

    Marinotti, Osvaldo; Cerqueira, Gustavo C.; de Almeida, Luiz Gonzaga Paula; Ferro, Maria Inês Tiraboschi; Loreto, Elgion Lucio da Silva; Zaha, Arnaldo; Teixeira, Santuza M. R.; Wespiser, Adam R.; Almeida e Silva, Alexandre; Schlindwein, Aline Daiane; Pacheco, Ana Carolina Landim; da Silva, Artur Luiz da Costa; Graveley, Brenton R.; Walenz, Brian P.; Lima, Bruna de Araujo; Ribeiro, Carlos Alexandre Gomes; Nunes-Silva, Carlos Gustavo; de Carvalho, Carlos Roberto; Soares, Célia Maria de Almeida; de Menezes, Claudia Beatriz Afonso; Matiolli, Cleverson; Caffrey, Daniel; Araújo, Demetrius Antonio M.; de Oliveira, Diana Magalhães; Golenbock, Douglas; Grisard, Edmundo Carlos; Fantinatti-Garboggini, Fabiana; de Carvalho, Fabíola Marques; Barcellos, Fernando Gomes; Prosdocimi, Francisco; May, Gemma; de Azevedo Junior, Gilson Martins; Guimarães, Giselle Moura; Goldman, Gustavo Henrique; Padilha, Itácio Q. M.; Batista, Jacqueline da Silva; Ferro, Jesus Aparecido; Ribeiro, José M. C.; Fietto, Juliana Lopes Rangel; Dabbas, Karina Maia; Cerdeira, Louise; Agnez-Lima, Lucymara Fassarella; Brocchi, Marcelo; de Carvalho, Marcos Oliveira; Teixeira, Marcus de Melo; Diniz Maia, Maria de Mascena; Goldman, Maria Helena S.; Cruz Schneider, Maria Paula; Felipe, Maria Sueli Soares; Hungria, Mariangela; Nicolás, Marisa Fabiana; Pereira, Maristela; Montes, Martín Alejandro; Cantão, Maurício E.; Vincentz, Michel; Rafael, Miriam Silva; Silverman, Neal; Stoco, Patrícia Hermes; Souza, Rangel Celso; Vicentini, Renato; Gazzinelli, Ricardo Tostes; Neves, Rogério de Oliveira; Silva, Rosane; Astolfi-Filho, Spartaco; Maciel, Talles Eduardo Ferreira; Ürményi, Turán P.; Tadei, Wanderli Pedro; Camargo, Erney Plessmann; de Vasconcelos, Ana Tereza Ribeiro

    2013-01-01

    Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector–human and vector–parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles-darlingi. PMID:23761445

  18. 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

  19. World Antimalarial Resistance Network (WARN) III: Molecular markers for drug resistant malaria

    PubMed Central

    Plowe, Christopher V; Roper, Cally; Barnwell, John W; Happi, Christian T; Joshi, Hema H; Mbacham, Wilfred; Meshnick, Steven R; Mugittu, Kefas; Naidoo, Inbarani; Price, Ric N; Shafer, Robert W; Sibley, Carol H; Sutherland, Colin J; Zimmerman, Peter A; Rosenthal, Philip J

    2007-01-01

    Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason for the failure of molecular resistance markers to live up to their potential is that data on the their prevalence is scattered in disparate databases with no linkage to the clinical, in vitro and pharmacokinetic data that are needed to relate the genetic data to relevant phenotypes. The ongoing replacement of older monotherapies for malaria by new, more effective combination therapies presents an opportunity to create an open access database that brings together standardized data on molecular markers of drug resistant malaria from around the world. This paper presents a rationale for creating a global database of molecular markers for drug resistant malaria and for linking it to similar databases containing results from clinical trials of drug efficacy, in vitro studies of drug susceptibility, and pharmacokinetic studies of antimalarial drugs, in a World Antimalarial Resistance Network (WARN). This database will be a global resource, guiding the selection of first line drugs for treating uncomplicated malaria, for preventing malaria in travelers and for intermittent preventive treatment of malaria in pregnant women, infants and other vulnerable groups. Perhaps most important, a global database for molecular markers of drug resistant malaria will accelerate the identification and validation of markers for resistance to artemisinin-based combination therapies and, thereby, potentially prolong the useful therapeutic lives of these important new drugs. PMID:17822535

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria. PMID:26376293

  2. Profiling the host response to malaria vaccination and malaria challenge

    PubMed Central

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

    2015-01-01

    A vaccine for malaria is urgently required. The RTS,S vaccine represents major progress, but is only partially effective. Development of the next generation of highly effective vaccines requires elucidation of the protective immune response. Immunity to malaria is known to be complex, and pattern-based approaches such as global gene expression profiling are ideal for understanding response to vaccination and protection against disease. The availability of experimental sporozoite challenge in humans to test candidate malaria vaccines offers a precious opportunity unavailable for other current targets of vaccine research such as HIV, tuberculosis and Ebola. However, a limited number of transcriptional profiling studies in the context of malaria vaccine research have been published to date. This review outlines the background, existing studies, limits and opportunities for gene expression studies to accelerate malaria vaccine research. PMID:26256528

  3. Immunity to malaria in an era of declining malaria transmission.

    PubMed

    Fowkes, Freya J I; Boeuf, Philippe; Beeson, James G

    2016-02-01

    With increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the development of naturally acquired immunity to malaria, which develops after repeated exposure to Plasmodium spp. However, it is currently unclear how declining transmission and malaria exposure will affect the development and maintenance of naturally acquired immunity. Here we review the key processes which underpin this knowledge; the amount of Plasmodium spp. exposure required to generate effective immune responses, the longevity of antibody responses and the ability to mount an effective response upon re-exposure through memory responses. Lastly we identify research priorities which will increase our understanding of how changing transmission will impact on malarial immunity.

  4. Profiling the host response to malaria vaccination and malaria challenge.

    PubMed

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

    2015-09-29

    A vaccine for malaria is urgently required. The RTS,S vaccine represents major progress, but is only partially effective. Development of the next generation of highly effective vaccines requires elucidation of the protective immune response. Immunity to malaria is known to be complex, and pattern-based approaches such as global gene expression profiling are ideal for understanding response to vaccination and protection against disease. The availability of experimental sporozoite challenge in humans to test candidate malaria vaccines offers a precious opportunity unavailable for other current targets of vaccine research such as HIV, tuberculosis and Ebola. However, a limited number of transcriptional profiling studies in the context of malaria vaccine research have been published to date. This review outlines the background, existing studies, limits and opportunities for gene expression studies to accelerate malaria vaccine research.

  5. Malaria Diagnostics in Clinical Trials

    PubMed Central

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

    2013-01-01

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

  6. Malaria early warning in Kenya.

    PubMed

    Hay, S I; Rogers, D J; Shanks, G D; Myers, M F; Snow, R W

    2001-02-01

    Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics.

  7. Malaria early warning in Kenya

    PubMed Central

    Hay, Simon I.; Rogers, David J.; Shanks, G. Dennis; Myers, Monica F.; Snow, Robert W.

    2011-01-01

    Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics. PMID:11228016

  8. Malaria diagnostics in clinical trials.

    PubMed

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

    2013-11-01

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

  9. Newer approaches to malaria control.

    PubMed

    Damodaran, Se; Pradhan, Prita; Pradhan, Suresh Chandra

    2011-07-01

    Malaria is the third leading cause of death due to infectious diseases affecting around 243 million people, causing 863,000 deaths each year, and is a major public health problem. Most of the malarial deaths occur in children below 5 years and is a major contributor of under-five mortality. As a result of environmental and climatic changes, there is a change in vector population and distribution, leading to resurgence of malaria at numerous foci. Resistance to antimalarials is a major challenge to malaria control and there are new drug developments, new approaches to treatment strategies, combination therapy to overcome resistance and progress in vaccine development. Now, artemisinin-based combination therapy is the first-line therapy as the malarial parasite has developed resistance to other antimalarials. Reports of artemisinin resistance are appearing and identification of new drug targets gains utmost importance. As there is a shift from malaria control to malaria eradication, more research is focused on malaria vaccine development. A malaria vaccine, RTS,S, is in phase III of development and may become the first successful one. Due to resistance to insecticides and lack of environmental sanitation, the conventional methods of vector control are turning out to be futile. To overcome this, novel strategies like sterile insect technique and transgenic mosquitoes are pursued for effective vector control. As a result of the global organizations stepping up their efforts with continued research, eradication of malaria can turn out to be a reality.

  10. Molecular Characterization of a Cluster of Imported Malaria Cases in Puerto Rico.

    PubMed

    Chenet, Stella M; Silva-Flannery, Luciana; Lucchi, Naomi W; Dragan, Ljolje; Dirlikov, Emilio; Mace, Kimberly; Rivera-García, Brenda; Arguin, Paul M; Udhayakumar, Venkatachalam

    2017-09-01

    The Caribbean island of Hispaniola is targeted for malaria elimination. Currently, this is the only island with ongoing transmission of malaria in the Caribbean. In 2015, six patients from Puerto Rico and one from Massachusetts, who traveled to Punta Cana, Dominican Republic, were confirmed to be infected with Plasmodium falciparum. Additional molecular analysis was performed at the Centers for Disease Control and Prevention to characterize the drug-resistant alleles and Plasmodium population genetic markers. All specimens carried wildtype genotypes for chloroquine, sulfadoxine-pyrimethamine, and artemisinin resistance genetic markers. A mutation in codon 184 (Y/F) of Pfmdr-1 gene was observed in all samples and they shared an identical genetic lineage as determined by microsatellite analysis. This genetic profile was similar to one previously reported from Hispaniola suggesting that a clonal P. falciparum residual parasite population present in Punta Cana is the source population for these imported malaria cases.

  11. Orthographic Analogies and Early Reading: Evidence from a Multiple Clue Word Paradigm

    ERIC Educational Resources Information Center

    Savage, Robert S.; Deault, Louise; Daki, Julia; Aouad, Julie

    2011-01-01

    Two experiments using a variation of the clue word analogy task (Goswami, 1986) explored whether children can make orthographic analogies when given multiple clue words, beyond the known effects of purely phonological activation. In Experiment 1, 42 children (mean age 6 years and 8 months) were first taught 3 "clue" words (e.g.,…

  12. Tacrolimus prevents murine cerebral malaria.

    PubMed

    Bao, Lam Quoc; Nhi, Dang My; Huy, Nguyen Tien; Hamano, Shinjiro; Hirayama, Kenji

    2017-02-01

    Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. Tacrolimus is also reported to inhibit Plasmodium falciparum growth in vitro. Here, we report that tacrolimus prevented the death from cerebral malaria of Plasmodium berghei ANKA-infected C57BL/6J mice, but not their death from malaria due to the high parasitaemia and severe anaemia. The mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malaria earlier than tacrolimus-treated littermates. Tacrolimus attenuated the infiltration of mononuclear cells including pathogenic CD8(+) T cells into the brain. It appears to prevent murine cerebral malaria through the inhibition of cerebral infiltration of CD8(+) T cells. © 2016 John Wiley & Sons Ltd.

  13. 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

  14. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission

    PubMed Central

    Bobenchik, April M.; Witola, William H.; Augagneur, Yoann; Nic Lochlainn, Laura; Garg, Aprajita; Pachikara, Niseema; Choi, Jae-Yeon; Zhao, Yang O.; Usmani-Brown, Sahar; Lee, Albert; Adjalley, Sophie H.; Samanta, Swapna; Fidock, David A.; Voelker, Dennis R.; Fikrig, Erol; Ben Mamoun, Choukri

    2013-01-01

    Efficient transmission of Plasmodium species between humans and Anopheles mosquitoes is a major contributor to the global burden of malaria. Gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and Plasmodium genetic diversity. Nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication are also capable of inhibiting gametocyte development and blocking malaria transmission. Here we provide genetic and pharmacological evidence indicating that the pathway for synthesis of phosphatidylcholine in Plasmodium falciparum membranes from host serine is essential for parasite gametocytogenesis and malaria transmission. Parasites lacking the phosphoethanolamine N-methyltransferase enzyme, which catalyzes the limiting step in this pathway, are severely altered in gametocyte development, are incapable of producing mature-stage gametocytes, and are not transmitted to mosquitoes. Chemical screening identified 11 inhibitors of phosphoethanolamine N-methyltransferase that block parasite intraerythrocytic asexual replication and gametocyte differentiation in the low micromolar range. Kinetic studies in vitro as well as functional complementation assays and lipid metabolic analyses in vivo on the most promising inhibitor NSC-158011 further demonstrated the specificity of inhibition. These studies set the stage for further optimization of NSC-158011 for development of a class of dual activity antimalarials to block both intraerythrocytic asexual replication and gametocytogenesis. PMID:24145416

  15. Chimpanzee malaria parasites related to Plasmodium ovale in Africa.

    PubMed

    Duval, Linda; Nerrienet, Eric; Rousset, Dominique; Sadeuh Mba, Serge Alain; Houze, Sandrine; Fourment, Mathieu; Le Bras, Jacques; Robert, Vincent; Ariey, Frederic

    2009-01-01

    Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.

  16. Chimpanzee Malaria Parasites Related to Plasmodium ovale in Africa

    PubMed Central

    Duval, Linda; Nerrienet, Eric; Rousset, Dominique; Sadeuh Mba, Serge Alain; Houze, Sandrine; Fourment, Mathieu; Le Bras, Jacques; Robert, Vincent; Ariey, Frederic

    2009-01-01

    Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes. PMID:19436742

  17. Malaria vector control: from past to future.

    PubMed

    Raghavendra, Kamaraju; Barik, Tapan K; Reddy, B P Niranjan; Sharma, Poonam; Dash, Aditya P

    2011-04-01

    Malaria is one of the most common vector-borne diseases widespread in the tropical and subtropical regions. Despite considerable success of malaria control programs in the past, malaria still continues as a major public health problem in several countries. Vector control is an essential part for reducing malaria transmission and became less effective in recent years, due to many technical and administrative reasons, including poor or no adoption of alternative tools. Of the different strategies available for vector control, the most successful are indoor residual spraying and insecticide-treated nets (ITNs), including long-lasting ITNs and materials. Earlier DDT spray has shown spectacular success in decimating disease vectors but resulted in development of insecticide resistance, and to control the resistant mosquitoes, organophosphates, carbamates, and synthetic pyrethroids were introduced in indoor residual spraying with needed success but subsequently resulted in the development of widespread multiple insecticide resistance in vectors. Vector control in many countries still use insecticides in the absence of viable alternatives. Few developments for vector control, using ovitraps, space spray, biological control agents, etc., were encouraging when used in limited scale. Likewise, recent introduction of safer vector control agents, such as insect growth regulators, biocontrol agents, and natural plant products have yet to gain the needed scale of utility for vector control. Bacterial pesticides are promising and are effective in many countries. Environmental management has shown sufficient promise for vector control and disease management but still needs advocacy for inter-sectoral coordination and sometimes are very work-intensive. The more recent genetic manipulation and sterile insect techniques are under development and consideration for use in routine vector control and for these, standardized procedures and methods are available but need thorough

  18. Age at onset of Alzheimer's disease: clue to the relative importance of etiologic factors

    SciTech Connect

    Horner, R.D.

    1987-09-01

    Clues to the relative importance of possible etiologic factors for dementia of the Alzheimer type may be gained by examining the fit of case series to Sartwell's model of the distribution of incubation periods. If age at disease onset is used as the incubation period of this disease, a genetic or environmental factor acting during the prenatal period is suggested if the distribution of these ages fits the lognormal curve; otherwise, environmental factors acting after birth are implicated. Case series were identified from the literature. Four case series were found which contained sufficiently detailed data to permit this secondary analysis; only one case series was population-based. The distribution of age at disease onset for each series was graphically and statistically assessed for fit to the logarithmic normal distribution. Each case series fit the lognormal curve well. This suggests that research into the etiology of dementia of the Alzheimer type should focus on the prenatal experiences of patients with this disease.

  19. An outbreak of locally acquired Plasmodium vivax malaria among migrant workers in Oman.

    PubMed

    Simon, Bruno; Sow, Fatimata; Al Mukhaini, Said K; Al-Abri, Seif; Ali, Osama A M; Bonnot, Guillaume; Bienvenu, Anne-Lise; Petersen, Eskild; Picot, Stéphane

    2017-01-01

    Plasmodium vivax is the most widely distributed human malaria parasite. Outside sub-Saharan Africa, the proportion of P. vivax malaria is rising. A major cause for concern is the re-emergence of Plasmodium vivax in malaria-free areas. Oman, situated in the south-eastern corner of the Arabian Peninsula, has long been an area of vivax malaria transmission but no locally acquired cases were reported in 2004. However, local transmission has been registered in small outbreaks since 2007. In this study, a local outbreak of 54 cases over 50 days in 2014 was analyzed retrospectively and stained blood slides have been obtained for parasite identification and genotyping. The aim of this study was to identify the geographical origin of these cases, in an attempt to differentiate between imported cases and local transmission. Using circumsporozoite protein (csp), merozoite surface protein 1 (msp1), and merozoite surface protein 3 (msp3) markers for genotyping of parasite DNA obtained by scrapping off the surface of smears, genetic diversity and phylogenetic analysis were performed. The study found that the samples had very low genetic diversity, a temperate genotype, and a high genetic distance, with most of the reference strains coming from endemic countries. We conclude that a small outbreak of imported malaria is not associated with re-emergence of malaria transmission in Oman, as no new cases have been seen since the outbreak ended. © B. Simon et al., published by EDP Sciences, 2017.

  20. An outbreak of locally acquired Plasmodium vivax malaria among migrant workers in Oman

    PubMed Central

    Simon, Bruno; Sow, Fatimata; Al Mukhaini, Said K.; Al-Abri, Seif; Ali, Osama A.M.; Bonnot, Guillaume; Bienvenu, Anne-Lise; Petersen, Eskild; Picot, Stéphane

    2017-01-01

    Plasmodium vivax is the most widely distributed human malaria parasite. Outside sub-Saharan Africa, the proportion of P. vivax malaria is rising. A major cause for concern is the re-emergence of Plasmodium vivax in malaria-free areas. Oman, situated in the south-eastern corner of the Arabian Peninsula, has long been an area of vivax malaria transmission but no locally acquired cases were reported in 2004. However, local transmission has been registered in small outbreaks since 2007. In this study, a local outbreak of 54 cases over 50 days in 2014 was analyzed retrospectively and stained blood slides have been obtained for parasite identification and genotyping. The aim of this study was to identify the geographical origin of these cases, in an attempt to differentiate between imported cases and local transmission. Using circumsporozoite protein (csp), merozoite surface protein 1 (msp1), and merozoite surface protein 3 (msp3) markers for genotyping of parasite DNA obtained by scrapping off the surface of smears, genetic diversity and phylogenetic analysis were performed. The study found that the samples had very low genetic diversity, a temperate genotype, and a high genetic distance, with most of the reference strains coming from endemic countries. We conclude that a small outbreak of imported malaria is not associated with re-emergence of malaria transmission in Oman, as no new cases have been seen since the outbreak ended. PMID:28695821

  1. Plasmodium malariae in Haitian Refugees, Jamaica

    PubMed Central

    Bryce, Jeanette Horner; Ducasse, Marion Bullock; Howitt, Christina; Barrett, Donnett M.; Morales, Jacob Lorenzo; Ord, Rosalynn; Burke, Martina; Chiodini, Peter L.; Sutherland, Colin J.

    2007-01-01

    Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P. vivax, and P. malariae. PCR confirmed the P. malariae and P. falciparum but not P. vivax infections. DNA sequencing and rRNA gene sequences showed transmission of P. malariae. This report confirms that P. malariae is still being transmitted in Haiti. PMID:17553241

  2. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali.

    PubMed

    Maiga, Bakary; Dolo, Amagana; Campino, Susana; Sepulveda, Nuno; Corran, Patrick; Rockett, Kirk A; Troye-Blomberg, Marita; Doumbo, Ogobara K; Clark, Taane G

    2014-07-11

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (<1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in

  3. Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali

    PubMed Central

    2014-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. Methods A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. Results It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was

  4. Characterizing the malaria rural-to-urban transmission interface: The importance of reactive case detection.

    PubMed

    Molina Gómez, Karen; Caicedo, M Alejandra; Gaitán, Alexandra; Herrera-Varela, Manuela; Arce, María Isabel; Vallejo, Andrés F; Padilla, Julio; Chaparro, Pablo; Pacheco, M Andreína; Escalante, Ananias A; Arevalo-Herrera, Myriam; Herrera, Sócrates

    2017-07-01

    Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods. A descriptive study that combines active (ACD), passive (PCD), and reactive (RCD) case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604) and 9% by quantitative polymerase chain reaction (qPCR) (52/604) were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence). Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93), most of them being asymptomatic (46/71). Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2%) and An. Darlingi (42,5%). One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA. This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that lead to

  5. Bioorganometallic Chemistry and Malaria

    NASA Astrophysics Data System (ADS)

    Biot, Christophe; Dive, Daniel

    This chapter summarizes recent developments in the design, synthesis, and structure-activity relationship studies of organometallic antimalarials. It begins with a general introduction to malaria and the biology of the parasite Plasmodium falciparum, with a focus on the heme detoxification system. Then, a number of metal complexes from the literature are reported for their antiplasmodial activity. The second half of the chapter deals with the serendipitous discovery of ferroquine, its mechanism(s) of action, and the failure to induce a resistance. Last, but not least, we suggest that the bioorganometallic approach offers the potential for the design of novel therapeutic agents.

  6. [Malaria--chemoprophylaxis 2001].

    PubMed

    Hatz, F R; Beck, B; Blum, J; Funk, M; Furrer, H; Genton, B; Holzer, B; Loutan, L; Markwalder, K; Raeber, P A; Schlagenhauf, P; Siegl, G; Steffen, R; Stürchler, D; Wyss, R

    2001-06-01

    An estimated 20,000 to 30,000 cases of imported malaria are annually diagnosed in industrialised countries. Some 700 of them concern Swiss travellers and foreign guests. Exposure prophylaxis and chemoprophylaxis for high risk destinations lower the risk of malarial disease. The latter is defined as regular intake of antimalarial drugs in subtherapeutic dosage in order to suppress the development of clinical disease. Drugs are usually taken from one week before travel until four weeks after return from an endemic area. Mefloquine, doxycycline, chloroquine plus proguanil, and presumably soon also atovaquone plus proguanil are available in Switzerland for chemoprophylaxis.

  7. [Fake malaria drugs].

    PubMed

    Bygbjerg, Ib Christian

    2009-03-02

    The literature on fake medicaments is sparse, even if approximately 15% of all medicaments are fake, a figure that for antimalarials in particular reaches 50% in parts of Africa and Asia. Sub-standard and fake medicines deplete the public's confidence in health systems, health professionals and in the pharmaceutical industry - and increase the risk that resistance develops. For a traveller coming from a rich Western country, choosing to buy e.g. preventive antimalarials over the internet or in poor malaria-endemic areas, the consequences may be fatal. International trade-, control- and police-collaboration is needed to manage the problem, as is the fight against poverty and poor governance.

  8. Influence of climate and river level on the incidence of malaria in Cacao, French Guiana.

    PubMed

    Basurko, Célia; Hanf, Matthieu; Han-Sze, René; Rogier, Stéphanie; Héritier, Philippe; Grenier, Claire; Joubert, Michel; Nacher, Mathieu; Carme, Bernard

    2011-02-04

    The epidemiological profiles of vector-borne diseases, such as malaria, are strongly associated with environmental conditions. An understanding of the effect of the climate on the occurrence of malaria may provide indirect insight into the anopheles mosquito vectors endemic to a particular region. The association between meteorological and hydrographical factors and the occurrence of malaria was studied in a village in French Guiana during an epidemic caused essentially by Plasmodium vivax. A cohort of confirmed cases of P. vivax malaria occurring between 2002 and 2007 was studied to search for an association between the number of new infection episodes occurring each month, mean, maximum and minimum monthly temperatures, cumulative rainfall for the month and the mean monthly height of the river bordering the village, with the aid of time series. Cross-correlation analysis revealed that these meteorological factors had large effects on the number of episodes, over a study period of 12 months. Climatic factors supporting the continuance of the epidemic were identified in the short-term (low minimum temperatures during the month), medium-term (low maximum temperatures two months before) and long-term (low maximum temperatures nine months before and high lowest level of the river 12 months before). Cross-correlation analysis showed that the effects of these factors were greatest at the beginning of the short rainy season. The association between the river level and the number of malaria attacks provides clues to better understand the environment of malaria transmission and the ecological characteristics of the vectors in the region.

  9. Placental hypoxia during placental malaria

    PubMed Central

    Boeuf, Philippe; Tan, Aimee; Romagosa, Cleofe; Radford, Jane; Mwapasa, Victor; Molyneux, Malcolm E.; Meshnick, Steven R.; Hunt, Nicholas H.; Rogerson, Stephen J.

    2009-01-01

    Background Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR. Methods We studied the hypoxia markers hypoxia inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), placental growth factor, VEGF receptor 1 and its soluble form and VEGF receptor 2. We used real time PCR (in 59 women) to examine gene transcription, immunohistochemistry (in 30 women) to describe protein expression and laser capture microdissection (in 23 women) to examine syncytiotrophoblast-specific changes in gene expression. We compared gene and protein expression in relation to malaria infection, monocytes infiltrates and birth weight. Results we could not associate any hallmark of placental malaria with a transcription, expression or tissue distribution profile characteristic of a response to hypoxia but found higher HIF-1α (P=.0005) and lower VEGF levels (P=.0026) in the syncytiotrophoblast of malaria cases versus asymptomatic controls. Conclusion our data are inconsistent with a role for placental hypoxia in the pathogenesis of malaria-associated FGR. The laser capture microdissection study was small, but suggests that malaria affects syncytiotrophoblast gene transcription, and proposes novel potential mechanisms for placental malaria-associated FGR. PMID:18279052

  10. The Malaria Vaccine Epidemiology and Evaluation Project of Papua New Guinea: rationale and baseline studies.

    PubMed

    Alpers, M P; al-Yaman, F; Beck, H P; Bhatia, K K; Hii, J; Lewis, D J; Paru, R; Smith, T A

    1992-12-01

    The range of possible malaria vaccines, against different species of Plasmodium and various stages in the life cycle of the parasite in both human host and mosquito vector, is reviewed. The importance, in a malaria-endemic area, of protection by a malaria vaccine against disease rather than infection is emphasized, and the ways by which disease prevention may be achieved are discussed. Mechanisms of production and presentation of vaccines are considered, including the importance of appropriate and more effective adjuvants. The variety of immune responses to malaria is set out and linked to both human and plasmodial genetic factors. Host genetics may also modify susceptibility to malaria through mechanisms which are not immunological. There is a need for entomological studies of the Anopheles vectors, especially but not only in preparation for transmission-blocking vaccines. This overall complexity justifies a multidimensional approach to epidemiology and field-site preparation. An iterative procedure is proposed for initial field evaluation, through adult male volunteers to community studies in immune adults and then to semi-immune school children, before evaluation in the principal target population of nonimmune young children. The outcome variables for epidemiological evaluation are specified. After this brief review of malaria vaccines, the baseline studies being undertaken by the Malaria Vaccine Epidemiology and Evaluation Project of the Papua New Guinea Institute of Medical Research in the Wosera area of East Sepik Province are discussed in some detail, and their rationale linked to the range and complexity of the malaria vaccines that have been reviewed. These studies are described under the headings of their principal components of epidemiology, parasitology, immunology, genetics and entomology.

  11. Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks.

    PubMed

    Gonçalves, Bronner P; Gupta, Sunetra; Penman, Bridget S

    2016-01-12

    Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC. A higher fitness of sickle cell heterozygotes relative to HbC heterozygotes could certainly have allowed the sickle cell allele to spread more rapidly. However, observations that carrying either HbC or HbS enhances an individual's capacity to transmit malaria parasites to mosquitoes could also shed light on this conundrum. A population genetic model was used to investigate the evolutionary consequences of the strength of malaria selection being correlated with either HbS frequency or HbC frequency. If the selection pressure from malaria is positively correlated with the frequency of either HbS or HbC, it is easier for HbS to succeed in the competitive interaction between the two alleles. A feedback process whereby the presence of variant haemoglobins increases the level of malaria selection in a population could have contributed to the global success of HbS relative to HbC, despite the former's higher blood disorder cost.

  12. Determinants of relapse periodicity in Plasmodium vivax malaria

    PubMed Central

    2011-01-01

    Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important

  13. Malaria in Poland in 2011.

    PubMed

    Stepień, Małgorzata

    2013-01-01

    To assess the epidemiological situation of malaria in Poland in 2011 as compared with previous years. evaluation of incidence of malaria registered in Poland in 2011, based on the results of the analysis of individual reports sent to the NIPH-NIH by the Sanitary-Epidemiological Stations and on aggregate data published in the annual bulletin "Infectious diseases and poisonings in Poland." Case classification in the epidemiological surveillance based on case definition for malaria approved by EC in the EU countries in 2008. Only symptomatic laboratory-confirmed cases were recorded. In 2011 14 cases of malaria were registered in Poland. All were imported from malaria-endemic countries: 64% of the cases were brought from Africa, and 21% from Asia. In comparison with the previous year number of reported cases was smaller by 21 cases. No deaths were reported. In one person who did not leave Poland in the last year there was probably a recurrence of malaria, though Plasmodium species has not been established. Among the cases with species-specific diagnosis 7 (63%) were caused by P. falciparum, 2 (18%) by P. vivax and P. malariae in one. Also in one case the mixed invasion was found. In 50% of cases the infection occurred during work-related trips, 43% in tourist trips and in one case, the student fell ill, who was in Cameroon a year earlier. Chemoprophylaxis was applied to five people but only in one person appropriately. In 2011, in connection with an outbreak of malaria in Greece, restrictions on blood donation for returnees from certain regions of Greece were implemented. Despite marked fluctuations in the total annual number of reported cases, incidence in Poland remains low. The main problem for the Polish imported malaria remains seriousness of illness in many patients, most often as a result of delayed diagnosis.

  14. Malaria in Poland in 2012.

    PubMed

    Stępień, Małgorzata

    2014-01-01

    To describe the epidemiological situation of imported malaria in Poland in 2012 as compared with previous years. Evaluation of malaria epidemiological situation in Poland in 2012, based on the results of the analysis of individual reports sent to the NIPH-NIH by the Sanitary-Epidemiological Stations and aggregate data published in the annual bulletins "Infectious Diseases and Poisonings in Poland". Cases were registered according to the case definition approved in the EU countries. In 2012, a total of 21 malaria cases were registered in Poland, including one fatal case. All cases were imported from malaria-endemic countries: 52% from Africa and remaining cases from Asia. Overall, compared to 2011, 7 more cases were reported. Given a median for the years 2006-2010, the number remained at the same level. In one patient the recurrence of malaria falciparum was observed following the failure of treatment undertaken in Cameroon. Plasmodium species was determined in 18 cases (86%); including 10 (61%) caused by P. falciparum, 6 (33%) by P. vivax and one by P. malariae. One patient was diagnosed with mixed invasion. Infections were occurred most frequently during work-related trips (43%) or tourist trips (38%), in other cases the purpose of the journey was to visit the country of origin (14%) or its purpose remained unknown. Only four people took any chemoprophylaxis; in one case, a drug matched inappropriately to the destination was applied, the remaining three persons applied drugs contrary to the recommended drug regimen. The number of cases of imported malaria in Poland remained at a low level, similar to that observed in previous years. A large number of delayed diagnoses (more than half of the reported cases) and another case of fatal outcome in the course of malaria indicate still low awareness of malaria threat among both travelers and primary care physicians.

  15. Land use scenarios simulation based on the CLUE-S model of the Lijiang River Basin in Guilin, China

    NASA Astrophysics Data System (ADS)

    Jin, Qingwen; Liu, Guang; Li, Lei; He, Chengxin; Huang, Yuqing; Yao, Yuefeng

    2016-11-01

    The relationship between government policy and land use change is very important, which can provide important information for understanding of land use change and for helping in development of sustainable policy. Returning Farmland to Forest Program is simulated by the CLUE-S model. Land use maps in 1993, 2006, 2010 and 2015 in Lijiang River Basin are interpreted based on remote sensing change from 1993 to 2025 under two scenarios (i.e., Natural Growth Scenarios, Government Intervention Scenarios). In the “Natural Growth Scenarios”, the area of construction land and cultivated land are increased, the others are decreased. In the “Government Intervention Scenarios”, the area of construction land, woodland, cultivated land, and water are increased, the others is in declined. The compared results of two scenarios provide a scientific support for the government policy in the Lijiang River Basin.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Acquired Immunity to Malaria

    PubMed Central

    Doolan, Denise L.; Dobaño, Carlota; Baird, J. Kevin

    2009-01-01

    Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity. PMID:19136431

  19. Ungulate malaria parasites

    PubMed Central

    Templeton, Thomas J.; Asada, Masahito; Jiratanh, Montakan; Ishikawa, Sohta A.; Tiawsirisup, Sonthaya; Sivakumar, Thillaiampalam; Namangala, Boniface; Takeda, Mika; Mohkaew, Kingdao; Ngamjituea, Supawan; Inoue, Noboru; Sugimoto, Chihiro; Inagaki, Yuji; Suzuki, Yasuhiko; Yokoyama, Naoaki; Kaewthamasorn, Morakot; Kaneko, Osamu

    2016-01-01

    Haemosporida parasites of even-toed ungulates are diverse and globally distributed, but since their discovery in 1913 their characterization has relied exclusively on microscopy-based descriptions. In order to bring molecular approaches to bear on the identity and evolutionary relationships of ungulate malaria parasites, we conducted Plasmodium cytb-specific nested PCR surveys using blood from water buffalo in Vietnam and Thailand, and goats in Zambia. We found that Plasmodium is readily detectable from water buffalo in these countries, indicating that buffalo Plasmodium is distributed in a wider region than India, which is the only area in which buffalo Plasmodium has been reported. Two types (I and II) of Plasmodium sequences were identified from water buffalo and a third type (III) was isolated from goat. Morphology of the parasite was confirmed in Giemsa-reagent stained blood smears for the Type I sample. Complete mitochondrial DNA sequences were isolated and used to infer a phylogeny in which ungulate malaria parasites form a monophyletic clade within the Haemosporida, and branch prior to the clade containing bird, lizard and other mammalian Plasmodium. Thus it is likely that host switching of Plasmodium from birds to mammals occurred multiple times, with a switch to ungulates independently from other mammalian Plasmodium. PMID:26996979

  20. Evaluation of parasite subpopulations and genetic diversity of the msp1, msp2 and glurp genes during and following artesunate monotherapy treatment of Plasmodium falciparum malaria in Western Cambodia.

    PubMed

    Gosi, Panita; Lanteri, Charlotte A; Tyner, Stuart D; Se, Youry; Lon, Chanthap; Spring, Michele; Char, Mengchuor; Sea, Darapiseth; Sriwichai, Sabaithip; Surasri, Sittidech; Wongarunkochakorn, Saowaluk; Pidtana, Kingkan; Walsh, Douglas S; Fukuda, Mark M; Manning, Jessica; Saunders, David L; Bethell, Delia

    2013-11-09

    Despite widespread coverage of the emergence of artemisinin resistance, relatively little is known about the parasite populations responsible. The use of PCR genotyping around the highly polymorphic Plasmodium falciparum msp1, msp2 and glurp genes has become well established both to describe variability in alleles within a population of parasites, as well as classify treatment outcome in cases of recurrent disease. The primary objective was to assess the emergence of minority parasite clones during seven days of artesunate (AS) treatment in a location with established artemisinin resistance. An additional objective was to investigate whether the classification of clinical outcomes remained valid when additional genotyping was performed. Blood for parasite genotyping was collected from 143 adult patients presenting with uncomplicated falciparum malaria during a clinical trial of AS monotherapy in Western Cambodia. Nested allelic type-specific amplification of the genes encoding the merozoite surface proteins 1 and 2 (msp1 and msp2) and the glutamate-rich protein (glurp) was performed at baseline, daily during seven days of treatment, and again at failure. Allelic variants were analysed with respect to the size of polymorphisms using Quantity One software to enable identification of polyclonal infections. Considerable variation of msp2 alleles but well-conserved msp1 and glurp were identified. At baseline, 31% of infections were polyclonal for one or more genes. Patients with recurrent malaria were significantly more likely to have polyclonal infections than patients without recurrence (seven of nine versus 36 of 127, p = 0.004). Emergence of minority alleles during treatment was detected in only one of twenty-three cases defined as being artemisinin resistant. Moreover, daily genotyping did not alter the final outcome classification in any recurrent cases. The parasites responsible for artemisinin-resistant malaria in a clinical trial in Western Cambodia comprise

  1. Evaluation of parasite subpopulations and genetic diversity of the msp1, msp2 and glurp genes during and following artesunate monotherapy treatment of Plasmodium falciparum malaria in Western Cambodia

    PubMed Central

    2013-01-01

    Background Despite widespread coverage of the emergence of artemisinin resistance, relatively little is known about the parasite populations responsible. The use of PCR genotyping around the highly polymorphic Plasmodium falciparum msp1, msp2 and glurp genes has become well established both to describe variability in alleles within a population of parasites, as well as classify treatment outcome in cases of recurrent disease. The primary objective was to assess the emergence of minority parasite clones during seven days of artesunate (AS) treatment in a location with established artemisinin resistance. An additional objective was to investigate whether the classification of clinical outcomes remained valid when additional genotyping was performed. Methods Blood for parasite genotyping was collected from 143 adult patients presenting with uncomplicated falciparum malaria during a clinical trial of AS monotherapy in Western Cambodia. Nested allelic type-specific amplification of the genes encoding the merozoite surface proteins 1 and 2 (msp1 and msp2) and the glutamate-rich protein (glurp) was performed at baseline, daily during seven days of treatment, and again at failure. Allelic variants were analysed with respect to the size of polymorphisms using Quantity One software to enable identification of polyclonal infections. Results Considerable variation of msp2 alleles but well-conserved msp1 and glurp were identified. At baseline, 31% of infections were polyclonal for one or more genes. Patients with recurrent malaria were significantly more likely to have polyclonal infections than patients without recurrence (seven of nine versus 36 of 127, p = 0.004). Emergence of minority alleles during treatment was detected in only one of twenty-three cases defined as being artemisinin resistant. Moreover, daily genotyping did not alter the final outcome classification in any recurrent cases. Conclusions The parasites responsible for artemisinin-resistant malaria in a

  2. Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya.

    PubMed

    Kariuki, Simon K; Njunge, James; Muia, Ann; Muluvi, Geofrey; Gatei, Wangeci; Ter Kuile, Feiko; Terlouw, Dianne J; Hawley, William A; Phillips-Howard, Penelope A; Nahlen, Bernard L; Lindblade, Kim A; Hamel, Mary J; Slutsker, Laurence; Shi, Ya Ping

    2013-08-27

    Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). A total of 12 MSP-1(19kDa) haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32-37%), with an overall haplotype diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide

  3. The Molecular Epidemiology of Malaria in Western Kenya

    DTIC Science & Technology

    2002-09-01

    HbC Hemoglobin C HbS Hemoglobin S ( sickle cell trait) HLA Human Leukocyte Antigen IL Interleukin IRB Institutional Review Board LPS...identified) genetic factors are the inherited disorders of hemoglobin ( sickle cell and thalassemia). Individuals that are homozygous for the HbS variant of...hemoglobin suffer the consequences of sickle - cell disease, but heterozygosity at this locus is strongly protective against severe malaria. The

  4. Microsporidians as evolution-proof agents of malaria control?

    PubMed

    Koella, Jacob C; Lorenz, Lena; Bargielowski, Irka

    2009-01-01

    Despite our efforts at malaria control, malaria remains one of our most serious and deadly diseases. The failure of control stems in part from the parasite's intense transmission in many areas and from the emergence and spread of resistance of the malaria parasites and their mosquito vectors against most of the chemicals used to attack them. New methods for control are desperately needed. However, new methods will be useful only if they are effective (i.e., decrease transmission substantially) and evolutionarily sustainable (i.e., evolution-proof, in that they prevent evolution from eroding efficacy). We suggest microsporidian parasites that infect mosquitoes could be potentially effective and sustainable agents for malaria control. They may be effective because they target several epidemiologically important traits: survival of larvae (and thus number of adult mosquitoes), adult longevity, biting rate and the development of malaria within the mosquitoes. Even if each trait is affected only moderately, the intensity of transmission can be reduced considerably. They may be evolution-proof, for the evolutionarily most important trait is juvenile survival, whereas the two epidemiologically most important factors are traits of the adult mosquito: biting rate and longevity. Under the intense microsporidian pressure of a control programme, it is likely (if not inevitable) that the larvae evolve to survive microsporidian infection. However, if this larval tolerance to microsporidians is genetically correlated with the adult traits, tolerant mosquitoes may not live as long and bite less frequently than microsporidian-sensitive ones. While such a trade-off has not been measured, combining several studies suggests indirectly a negative genetic correlation between larval tolerance and adult longevity. Therefore, evolution might not undermine control; rather it might increase its effectiveness. While the evolution of resistance may be inevitable, the failure of control need

  5. Testing in Mice the Hypothesis That Melanin Is Protective in Malaria Infections

    PubMed Central

    Waisberg, Michael; Vickers, Brandi K.; Yager, Stephanie B.; Lin, Christina K.; Pierce, Susan K.

    2012-01-01

    Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria. PMID:22242171

  6. Pyruvate Kinase and Fcγ Receptor Gene Copy Numbers Associated With Malaria Phenotypes.

    PubMed

    Faik, Imad; van Tong, Hoang; Lell, Bertrand; Meyer, Christian G; Kremsner, Peter G; Velavan, Thirumalaisamy P

    2017-07-15

    Genetic factors are associated with susceptibility to many infectious diseases and may be determinants of clinical progression. Gene copy number variation (CNV) has been shown to be associated with phenotypes of numerous diseases, including malaria. We quantified gene copy numbers of the pyruvate kinase, liver, and red blood cell (PKLR) gene as well as of the Fcγ receptor 2A and Fcγ receptor 2C (FCGR2A, FCGR2C) and Fcγ receptor 3 (FCGR3) genes using real-time quantitative polymerase chain reaction (RT-qPCR) assays in Gabonese children with severe (n = 184) or and mild (n = 189) malaria and in healthy Gabonese and white individuals (n = 76 each). The means of PKLR, FCGR2A, FCGR2C, and FCGR3 copy numbers were significantly higher among children with severe malaria compared to those with mild malaria (P < .002), indicating that a surplus of copies of those genes is significantly associated with malaria severity. Copy numbers of the FCGR2A and FCGR2C genes were significantly lower (P = .005) in Gabonese individuals compared with white individuals. In conclusion, CNV of the PKLR, FCGR2A, FCGR2C, and FCGR3 genes is associated with malaria severity, and our results provide evidence for a role of CNV in host responses to malaria. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Heme dampens T-cell sequestration by modulating glial cell responses during rodent cerebral malaria.

    PubMed

    Dalko, Esther; Genete, Delphine; Auger, Florent; Dovergne, Claire; Lambert, Claire; Herbert, Fabien; Cazenave, Pierre-André; Roland, Jacques; Pied, Sylviane

    2016-11-01

    Cerebral malaria is the deadliest complication of Plasmodium falciparum infection. Its pathophysiology is associated with a strong pro-inflammatory reaction and the activation of glial cells. Among modulators released during the infection, heme seems to play a controversial role in the pathophysiology of malaria. Herein, we first investigated the phenotype of glial cells during cerebral malaria in C57BL/6 mice infected with P. berghei ANKA. Given the fact that high levels of heme were associated with cerebral malaria, we then investigated its impact on microglial, astrocyte, and T cell responses to further clarify its contribution in the neuropathophysiology. Surprisingly, we found that administration of heme twice a day from day three of infection induced the expression of the Heme oxygenase-1 (Hmox1) gene and prevented brain damages. More specifically, heme inhibited the M1 phenotype of microglia, hampered the activation of astrocytes, and decreased the cerebral expression of Ifng, Tnfa and Ip10. Heme might that way alter the migration of pathogenic CD4 and CD8 T lymphocytes within the brain observed during cerebral malaria. Taking into account that cerebral malaria results from a complex interplay between host- and parasite-derived factors, it is possible that genetic polymorphisms of Hmox1, which could be associated with the control of systemic levels of heme during P. falciparum infection, might explain its dual role and its contribution to the resistance to cerebral malaria. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Plant-Mediated Effects on Mosquito Capacity to Transmit Human Malaria.

    PubMed

    Hien, Domonbabele F D S; Dabiré, Kounbobr R; Roche, Benjamin; Diabaté, Abdoulaye; Yerbanga, Rakiswende S; Cohuet, Anna; Yameogo, Bienvenue K; Gouagna, Louis-Clément; Hopkins, Richard J; Ouedraogo, Georges A; Simard, Frédéric; Ouedraogo, Jean-Bosco; Ignell, Rickard; Lefevre, Thierry

    2016-08-01

    The ecological context in which mosquitoes and malaria parasites interact has received little attention, compared to the genetic and molecular aspects of malaria transmission. Plant nectar and fruits are important for the nutritional ecology of malaria vectors, but how the natural diversity of plant-derived sugar sources affects mosquito competence for malaria parasites is unclear. To test this, we infected Anopheles coluzzi, an important African malaria vector, with sympatric field isolates of Plasmodium falciparum, using direct membrane feeding assays. Through a series of experiments, we then examined the effects of sugar meals from Thevetia neriifolia and Barleria lupilina cuttings that included flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and mosquito traits that are key for determining the intensity of malaria transmission. We found that the source of plant sugar meal differentially affected infection prevalence and intensity, the development duration of the parasites, as well as the survival and fecundity of the vector. These effects are likely the result of complex interactions between toxic secondary metabolites and the nutritional quality of the plant sugar source, as well as of host resource availability and parasite growth. Using an epidemiological model, we show that plant sugar source can be a significant driver of malaria transmission dynamics, with some plant species exhibiting either transmission-reducing or -enhancing activities.

  9. Plant-Mediated Effects on Mosquito Capacity to Transmit Human Malaria

    PubMed Central

    Hien, Domonbabele F. d. S.; Roche, Benjamin; Diabaté, Abdoulaye; Yerbanga, Rakiswende S.; Cohuet, Anna; Yameogo, Bienvenue K.; Gouagna, Louis-Clément; Hopkins, Richard J.; Ouedraogo, Georges A.; Simard, Frédéric; Ignell, Rickard; Lefevre, Thierry

    2016-01-01

    The ecological context in which mosquitoes and malaria parasites interact has received little attention, compared to the genetic and molecular aspects of malaria transmission. Plant nectar and fruits are important for the nutritional ecology of malaria vectors, but how the natural diversity of plant-derived sugar sources affects mosquito competence for malaria parasites is unclear. To test this, we infected Anopheles coluzzi, an important African malaria vector, with sympatric field isolates of Plasmodium falciparum, using direct membrane feeding assays. Through a series of experiments, we then examined the effects of sugar meals from Thevetia neriifolia and Barleria lupilina cuttings that included flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and mosquito traits that are key for determining the intensity of malaria transmission. We found that the source of plant sugar meal differentially affected infection prevalence and intensity, the development duration of the parasites, as well as the survival and fecundity of the vector. These effects are likely the result of complex interactions between toxic secondary metabolites and the nutritional quality of the plant sugar source, as well as of host resource availability and parasite growth. Using an epidemiological model, we show that plant sugar source can be a significant driver of malaria transmission dynamics, with some plant species exhibiting either transmission-reducing or -enhancing activities. PMID:27490374

  10. Asymptomatic Multiclonal Plasmodium falciparum Infections Carried Through the Dry Season Predict Protection Against Subsequent Clinical Malaria

    PubMed Central

    Sondén, Klara; Doumbo, Safiatou; Hammar, Ulf; Vafa Homann, Manijeh; Ongoiba, Aissata; Traoré, Boubacar; Bottai, Matteo; Crompton, Peter D.; Färnert, Anna

    2015-01-01

    Background Immunity to the antigenically diverse parasite Plasmodium falciparum is acquired gradually after repeated exposure. Studies in areas of high malaria transmission have shown that asymptomatic individuals infected with multiclonal infections are at reduced risk of febrile malaria during follow-up. Methods We assessed the relationship between the genetic diversity of clones in P. falciparum infections that persist through the dry season and the subsequent risk of febrile malaria in 225 individuals aged 2–25 years in Mali, where the 6-month malaria and dry seasons are sharply demarcated. Polymerase chain reaction–based genotyping of the highly polymorphic merozoite surface protein 2 gene was performed on blood samples collected at 5 cross-sectional surveys. Results In an age-adjusted analysis, individuals with multiclonal P. falciparum infections before the rainy season were at reduced risk of febrile malaria, compared with individuals who were uninfected (hazard ratio [HR], 0.28; 95% confidence interval [CI], .11–.69). In contrast, there was no significant association between risk of malaria and having 1 clone at baseline (HR, 0.71; 95% CI, .36–1.40). Conclusions The results suggest that persistent multiclonal infections carried through the dry season contribute to protection against subsequent febrile malaria, possibly by maintaining protective immune responses that depend on ongoing parasite infection. PMID:25712968

  11. Testing in mice the hypothesis that melanin is protective in malaria infections.

    PubMed

    Waisberg, Michael; Vickers, Brandi K; Yager, Stephanie B; Lin, Christina K; Pierce, Susan K

    2012-01-01

    Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria.

  12. Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection

    PubMed Central

    Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose

    2016-01-01

    The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite’s enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host–pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally

  13. Malaria Prophylaxis: A Comprehensive Review

    PubMed Central

    Castelli, Francesco; Odolini, Silvia; Autino, Beatrice; Foca, Emanuele; Russo, Rosario

    2010-01-01

    The flow of international travellers to and from malaria-endemic areas, especially Africa, has increased in recent years. Apart from the very high morbidity and mortality burden imposed on malaria-endemic areas, imported malaria is the main cause of fever possibly causing severe disease and death in travellers coming from tropical and subtropical areas, particularly Sub-Saharan Africa. The importance of behavioural preventive measures (bed nets, repellents, etc.), adequate chemoprophylaxis and, in selected circumstances, stand-by emergency treatment may not be overemphasized. However, no prophylactic regimen may offer complete protection. Expert advice is needed to tailor prophylactic advice according to traveller (age, baseline clinical conditions, etc.) and travel (destination, season, etc.) characteristics in order to reduce malaria risk.

  14. Malaria: new vaccines for old?

    PubMed

    Waters, Andrew

    2006-02-24

    Detailed analyses of the 5500 genes revealed by the complete Plasmodium genome sequence are yielding new candidate parasite antigens and strategies that may contribute to a successful vaccine against malaria in the coming decade.

  15. Malaria ecology and climate change

    NASA Astrophysics Data System (ADS)

    McCord, G. C.

    2016-05-01

    Understanding the costs that climate change will exact on society is crucial to devising an appropriate policy response. One of the channels through while climate change will affect human society is through vector-borne diseases whose epidemiology is conditioned by ambient ecology. This paper introduces the literature on malaria, its cost on society, and the consequences of climate change to the physics community in hopes of inspiring synergistic research in the area of climate change and health. It then demonstrates the use of one ecological indicator of malaria suitability to provide an order-of-magnitude assessment of how climate change might affect the malaria burden. The average of Global Circulation Model end-of-century predictions implies a 47% average increase in the basic reproduction number of the disease in today's malarious areas, significantly complicating malaria elimination efforts.

  16. 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

  17. 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

  18. 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

  19. An Integrated Atmospheric and Hydrological Based Malaria Epidemic Alert System

    NASA Astrophysics Data System (ADS)

    Asefi Najafabady, S.; Li, J.; Nair, U. S.; Welch, R. M.; Srivastava, A.; Nagpal, B. N.; Saxena, R.; Benedict, M. E.

    2005-05-01

    resolution QuickBird data has been used to identify small mosquito breeding sites with an accuracy of 90 %, as verified by ground observations. These layers of information, along with a 30m resolution Digital Elevation Model and field measurements of malaria incidence, larvae and mosquito counts, were examined in a GIS system to identify the environmental parameters effective in mosquito distribution. The Genetic Algorithm for Rule Set Production (GARP) has been applied to the region using the parameters defined above to predict regions susceptible to malaria transmission.

  20. A new malaria agent in African hominids.

    PubMed

    Ollomo, Benjamin; Durand, Patrick; Prugnolle, Franck; Douzery, Emmanuel; Arnathau, Céline; Nkoghe, Dieudonné; Leroy, Eric; Renaud, François

    2009-05-01

    Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually, mainly among African infants. The origin and evolution of this pathogen within the human lineage is still unresolved. A single species, P. reichenowi, which infects chimpanzees, is known to be a close sister lineage of P. falciparum. Here we report the discovery of a new Plasmodium species infecting Hominids. This new species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa). Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes P. falciparum and P. reichenowi (approximately 21+/-9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature). This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification. Investigation of the nuclear genome of this new species will further the understanding of the genetic adaptations of P. falciparum to humans. The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria.

  1. Management of relapsing Plasmodium vivax malaria

    PubMed Central

    Chu, Cindy S; White, Nicholas J

    2016-01-01

    ABSTRACT Introduction: Relapses are important contributors to illness and morbidity in Plasmodium vivax and P. ovale infections. Relapse prevention (radical cure) with primaquine is required for optimal management, control and ultimately elimination of Plasmodium vivax malaria. A review was conducted with publications in English, French, Portuguese and Spanish using the search terms ‘P. vivax’ and ‘relapse’. Areas covered: Hypnozoites causing relapses may be activated weeks or months after initial infection. Incidence and temporal patterns of relapse varies geographically. Relapses derive from parasites either genetically similar or different from the primary infection indicating that some derive from previous infections. Malaria illness itself may activate relapse. Primaquine is the only widely available treatment for radical cure. However, it is often not given because of uncertainty over the risks of primaquine induced haemolysis when G6PD deficiency testing is unavailable. Recommended dosing of primaquine for radical cure in East Asia and Oceania is 0.5 mg base/kg/day and elsewhere is 0.25 mg base/kg/day. Alternative treatments are under investigation. Expert commentary: Geographic heterogeneity in relapse patterns and chloroquine susceptibility of P. vivax, and G6PD deficiency epidemiology mean that radical treatment should be given much more than it is today. G6PD testing should be made widely available so primaquine can be given more safely. PMID:27530139

  2. Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region.

    PubMed

    Koch, O; Rockett, K; Jallow, M; Pinder, M; Sisay-Joof, F; Kwiatkowski, D

    2005-06-01

    Interferon-gamma, encoded by IFNG, is a key immunological mediator that is believed to play both a protective and a pathological role in malaria. Here, we investigate the relationship between IFNG variation and susceptibility to malaria. We began by analysing West African and European haplotype structure and patterns of linkage disequilibrium across a 100 kb genomic region encompassing IFNG and its immediate neighbours IL22 and IL26. A large case-control study of severe malaria in a West Africa population identified several weak associations with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and defined two IL22 haplotypes that are, respectively, associated with resistance and susceptibility. These data provide a starting point for functional and genetic analysis of the IFNG genomic region in malaria and other infectious and inflammatory conditions affecting African populations.

  3. Blood Coagulation, Inflammation and Malaria

    PubMed Central

    Francischetti, Ivo M. B.; Seydel, Karl B.; Monteiro, Robson Q.

    2010-01-01

    I. ABSTRACT Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year. Plasmodium falciparum infection is often associated with a procoagulant tonus characterized by thrombocytopenia and activation of the coagulation cascade and fibrinolytic system; however, bleeding and hemorrhage are uncommon events, suggesting that a compensated state of blood coagulation activation occurs in malaria. This article i) reviews the literature related to blood coagulation and malaria in a historic perspective, ii) describes basic mechanisms of coagulation, anticoagulation, and fibrinolysis, iii) explains the laboratory changes in acute and compensated disseminated intravascular coagulation (DIC), iv) discusses the implications of tissue factor (TF) expression in the endothelium of P. falciparum-infected patients, and v) emphasizes the pro-coagulant role of parasitized erythrocytes (pRBC) and activated platelets in the pathogenesis of malaria. This article also presents the ‘Tissue Factor Model’ (TFM) for malaria pathogenesis, which places TF as the interface between sequestration, endothelial cell activation, blood coagulation disorder and inflammation often associated with the disease. The relevance of the coagulation-inflammation cycle for the multiorgan dysfunction and coma is discussed in the context of malaria pathogenesis. PMID:18260002

  4. Composition of the gut microbiota modulates the severity of malaria.

    PubMed

    Villarino, Nicolas F; LeCleir, Gary R; Denny, Joshua E; Dearth, Stephen P; Harding, Christopher L; Sloan, Sarah S; Gribble, Jennifer L; Campagna, Shawn R; Wilhelm, Steven W; Schmidt, Nathan W

    2016-02-23

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

  5. Composition of the gut microbiota modulates the severity of malaria

    PubMed Central

    Villarino, Nicolas F.; LeCleir, Gary R.; Denny, Joshua E.; Dearth, Stephen P.; Harding, Christopher L.; Sloan, Sarah S.; Gribble, Jennifer L.; Campagna, Shawn R.; Wilhelm, Steven W.; Schmidt, Nathan W.

    2016-01-01

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from “resistant” or “susceptible” mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID:26858424

  6. Fighting malaria with engineered symbiotic bacteria from vector mosquitoes.

    PubMed

    Wang, Sibao; Ghosh, Anil K; Bongio, Nicholas; Stebbings, Kevin A; Lampe, David J; Jacobs-Lorena, Marcelo

    2012-07-31

    The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)(4), four copies of Plasmodium enolase-plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.

  7. Fighting malaria with engineered symbiotic bacteria from vector mosquitoes

    PubMed Central

    Wang, Sibao; Ghosh, Anil K.; Bongio, Nicholas; Stebbings, Kevin A.; Lampe, David J.; Jacobs-Lorena, Marcelo

    2012-01-01

    The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)4, four copies of Plasmodium enolase–plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria. PMID:22802646

  8. Pulmonary pathology in pediatric cerebral malaria.

    PubMed

    Milner, Danny; Factor, Rachel; Whitten, Rich; Carr, Richard A; Kamiza, Steve; Pinkus, Geraldine; Molyneux, Malcolm; Taylor, Terrie

    2013-12-01

    Respiratory signs are common in African children where malaria is highly endemic, and thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre, Malawi, many of whom death was attributed to Plasmodium falciparum malaria. Our aim was to describe the pathologic manifestations of fatal malaria; to understand the role of parasites, pigment, and macrophages; and to catalog comorbidities. From available patients, which included 55 patients with cerebral malaria and 45 controls, we obtained 4 cores of lung tissue for immunohistochemistry and morphological evaluation. We found that, in patients with cerebral malaria, large numbers of malaria parasites were present in pulmonary alveolar capillaries, together with extensive deposits of malaria pigment (hemozoin). The number of pulmonary macrophages in this vascular bed did not differ between patients with cerebral malaria, noncerebral malaria, and nonmalarial diagnoses. Comorbidities found in some cerebral malaria patients included pneumonia, pulmonary edema, hemorrhage, and systemic activation of coagulation. We conclude that the respiratory distress seen in patients with cerebral malaria does not appear to be anatomic in origin but that increasing malaria pigment is strongly associated with cerebral malaria at autopsy. © 2013.

  9. Pulmonary pathology in pediatric cerebral malaria

    PubMed Central

    Milner, Danny; Factor, Rachel; Whitten, Rich; Carr, Richard A.; Kamiza, Steve; Pinkus, Geraldine; Molyneux, Malcolm; Taylor, Terrie

    2013-01-01

    Respiratory signs are common in African children where malaria is highly endemic and, thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre, Malawi, in many of whom death was attributed to P falciparum malaria. Our aim was to describe the pathological manifestations of fatal malaria, to understand the role of parasites, pigment, and macrophages, and to catalogue co-morbidities. From available patients which included 55 patients with cerebral malaria and 45 controls, we obtained 4 cores of lung tissue for immunohistochemistry and morphological evaluation. We found that in patients with cerebral malaria, large numbers of malaria parasites were present in pulmonary alveolar capillaries, together with extensive deposits of malaria pigment (hemozoin). The number of pulmonary macrophages in this vascular bed did not differ between patients with cerebral malaria, non-cerebral malaria and non-malarial diagnoses. Co-morbidities found in some cerebral malaria patients included pneumonia, pulmonary edema, hemorrhage, and systemic activation of coagulation. We conclude that the respiratory distress seen in patients with cerebral malaria does not appear to be anatomic in origin but that increasing malaria pigment is strongly associated with cerebral malaria at autopsy. PMID:24074535

  10. Association of CD40L gene polymorphism with severe Plasmodium falciparum malaria in Indian population.

    PubMed

    Purohit, Prasanta; Mohanty, Pradeep Kumar; Patel, Siris; Das, Padmalaya; Das, Kishalaya; Panigrahi, Jogeswar

    2017-01-01

    Many host genetic factors are associated with the disease severity and fatal outcome of falciparum malaria. CD40L gene has been found to be one of the most important factors associated with malaria in African countries. This study was aimed to investigate the possible association of CD40L gene polymorphism in severe falciparum malaria in Indian adults. One hundred fifteen adult cases with severe falciparum malaria were included in the study. Two single- nucleotide polymorphisms (SNPs) of CD40L gene, CD40L-726(C/T) and CD40L+220(C/T) were investigated, and the possible association with different clinical sub-phenotypes of severe falciparum malaria were analyzed. Statistically no significant difference was observed in the incidence of CD40L-726C between the patients and control group. The incidence of CD40L+220C allele was found to be significantly higher (OR, 2.25; p = 0.03) in male patients compared to controls but no significant difference was observed in females. Haplotype data showed the susceptibility of -726T/+220C haplotype to severe malaria whereas -726C/+220T was associated with protection against severe malaria. CD40L+220C allele was associated with severe malarial anaemia in males (χ2 = 6.60; p = 0.01). CD40L gene polymorphism was found to be associated with severe falciparum malaria in Indian population especially in severe malarial anaemia. CD40L may be considered as a factor of immunity in understanding the pathophysiology of falciparum malaria.

  11. [Current malaria situation in Turkmenistan].

    PubMed

    Amangel'diev, K A

    2001-01-01

    Malaria is one of the main health problems facing most developing countries having a hot climate. It is a problem in Turkmenistan. The country is situated in Central Asia, north of the Kopetdag mountains, between the Caspian Sea to the west and the Amu-Darya river to the east. Turkmenistan stretches for a distance of 1,100 km from west to east and 650 km from north to south. It borders Kazakhstan in the north, Uzbekistan in the east and north-east, Iran in the south, and Afghanistan in the south-east. Seven malaria vector species are found in Turkmenistan, the main ones being Anopheles superpictus, An. pulcherrimus, and An. martinius. The potentially endemic area consists of the floodplains of the Tejen and Murgab rivers, with a long chain of reservoirs built along them. In 1980 most cases of imported malaria were recorded in military personnel who had returned from service in Afghanistan. In the past years, only tertian (Plasmodium vivax) malaria has been recorded and there have been no death from malaria over that period. In the Serkhetabad (Gushgi) district there are currently 5 active foci of malaria infection, with a population of 22,000 people. In 1999, forty nine cases of P. vivax malaria were recorded in Turkmenistan. Of them, 36 cases, including 4 children under 14 years were diagnosed for the first time while 13 were relapses. There were 88 fewer cases than those in the previous year (by a factor of 2.8). There were 17 more cases of imported malaria than those in 1998 (by a factor of 1.7), most of which occurred in the foci of malaria infection (Serkhetabad, Tagtabazar, and Kerki districts), in the city of Ashkhabat and in Lebap, Dashkhovuz and Akhal Regions. The emergence of indigenous malaria in the border areas was due to the importation of the disease at intervals by infected mosquitoes flying in from neighbouring countries (e.g. Afghanistan), the lack of drugs to treat the first cases and the lack of alternative insecticides. Most patients suffer

  12. 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

  13. Adaptive Potential of Hybridization among Malaria Vectors: Introgression at the Immune Locus TEP1 between Anopheles coluzzii and A. gambiae in ‘Far-West’ Africa

    PubMed Central

    Mancini, Emiliano; Spinaci, Maria Ida; Gordicho, Vasco; Caputo, Beniamino; Pombi, Marco; Vicente, José Luis; Dinis, João; Rodrigues, Amabélia; Petrarca, Vincenzo; Weetman, David; Pinto, João; della Torre, Alessandra

    2015-01-01

    “Far-West” Africa is known to be a secondary contact zone between the two major malaria vectors Anopheles coluzzii and A. gambiae. We investigated gene-flow and potentially adaptive introgression between these species along a west-to-east transect in Guinea Bissau, the putative core of this hybrid zone. To evaluate the extent and direction of gene flow, we genotyped site 702 in Intron-1 of the para Voltage-Gated Sodium Channel gene, a species-diagnostic nucleotide position throughout most of A. coluzzii and A. gambiae sympatric range. We also analyzed polymorphism in the thioester-binding domain (TED) of the innate immunity-linked thioester-containing protein 1 (TEP1) to investigate whether elevated hybridization might facilitate the exchange of variants linked to adaptive immunity and Plasmodium refractoriness. Our results confirm asymmetric introgression of genetic material from A. coluzzii to A. gambiae and disruption of linkage between the centromeric "genomic islands" of inter-specific divergence. We report that A. gambiae from the Guinean hybrid zone possesses an introgressed TEP1 resistant allelic class, found exclusively in A. coluzzii elsewhere and apparently swept to fixation in West Africa (i.e. Mali and Burkina Faso). However, no detectable fixation of this allele was found in Guinea Bissau, which may suggest that ecological pressures driving segregation between the two species in larval habitats in this region may be different from those experienced in northern and more arid parts of the species’ range. Finally, our results also suggest a genetic subdivision between coastal and inland A. gambiae Guinean populations and provide clues on the importance of ecological factors in intra-specific differentiation processes. PMID:26047479

  14. Malaria in southeast Bangladesh: a descriptive study.

    PubMed

    Maude, Richard J; Dondorp, A M; Faiz, M A; Yunus, Emran Bin; Samad, R; Hossain, Amir; Rahman, M Ridwanur

    2008-12-01

    Malaria in Asia is thought to be grossly under-reported and this is evident from previously published statistics from Bangladesh. Malaria screening data from four Upazillas was analysed alongside census data to assess the trends in malaria incidence over time and distribution of malaria by age and gender. Malaria incidence in this area has decreased by around two thirds since 2003, although control measures were not significantly increased until 2005. Malaria occurred in people of all ages with the highest incidence being in young adults. This is consistent with higher occupational exposure in this group. The probability of being screened for malaria decreased with age suggesting significant numbers of adults with malaria may be being missed.

  15. Mapping residual transmission for malaria elimination.

    PubMed

    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

    2015-12-29

    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.

  16. Malaria, photomicrograph of cellular parasites (image)

    MedlinePlus

    Malaria is a disease caused by parasites. This picture shows dark orange-stained malaria parasites inside red blood cells (a) and outside the cells (b). Note the large cells that look like targets; ...

  17. Malaria, microscopic view of cellular parasites (image)

    MedlinePlus

    Malaria is a disease caused by parasites that are carried by mosquitoes. Once in the bloodstream, the parasite inhabits the red blood cell (RBC). This picture shows purple-stained malaria parasites inside red blood cells.

  18. Decoding the Role of Glycans in Malaria

    PubMed Central

    Gomes, Pollyanna S.; Feijó, Daniel F.; Morrot, Alexandre; Freire-de-Lima, Celio G.

    2017-01-01

    Complications arising from malaria are a concern for public health authorities worldwide, since the annual caseload in humans usually exceeds millions. Of more than 160 species of Plasmodium, only 4 infect humans, with the most severe cases ascribed to Plasmodium falciparum and the most prevalent to Plasmodium vivax. Over the past 70 years, since World War II, when the first antimalarial drugs were widely used, many efforts have been made to combat this disease, including vectorial control, new drug discoveries and genetic and molecular approaches. Molecular approaches, such as glycobiology, may lead to new therapeutic targets (both in the host and the parasites), since all interactions are mediated by carbohydrates or glycan moieties decorating both cellular surfaces from parasite and host cells. In this review, we address the carbohydrate-mediated glycobiology that directly affects Plasmodium survival or host resistance. PMID:28649240

  19. Genome-wide association study indicates two novel resistance loci for severe malaria.

    PubMed

    Timmann, Christian; Thye, Thorsten; Vens, Maren; Evans, Jennifer; May, Jürgen; Ehmen, Christa; Sievertsen, Jürgen; Muntau, Birgit; Ruge, Gerd; Loag, Wibke; Ansong, Daniel; Antwi, Sampson; Asafo-Adjei, Emanuel; Nguah, Samuel Blay; Kwakye, Kingsley Osei; Akoto, Alex Osei Yaw; Sylverken, Justice; Brendel, Michael; Schuldt, Kathrin; Loley, Christina; Franke, Andre; Meyer, Christian G; Agbenyega, Tsiri; Ziegler, Andreas; Horstmann, Rolf D

    2012-09-20

    Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

  20. 'Hints' in the horn: diagnostic clues in the stratum corneum.

    PubMed

    Cardoso, José Carlos; Veraitch, Ophelia; Gianotti, Raffaele; Ferrara, Gerardo; Tomasini, Carlo F; Singh, Manuraj; Zalaudek, Iris; Stefanato, Catherine M

    2017-03-01

    The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.