Dataset Information

Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America.

ABSTRACT: BACKGROUND: Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations. METHODS: The genetic diversity of eight P. vivax populations (n=543) was investigated by using two microsatellites (MS), m1501 and m3502, chosen because of their seven and eight base-pair (bp) repeat lengths, respectively. These were compared with published data of the same loci from six other P. vivax populations. RESULTS: In total, 1,440 P. vivax samples from 14 countries on three continents were compared. There was highest heterozygosity within Asian populations, where expected heterozygosity (He) was 0.92-0.98, and alleles with a high repeat number were more common. Pairwise FST revealed significant differentiation between most P. vivax populations, with the highest divergence found between Asian and South American populations, yet the majority of the diversity (~89%) was found to exist within rather than between populations. CONCLUSIONS: The MS markers used were informative in both global and local P. vivax population comparisons and their seven and eight bp repeat length facilitated population comparison using data from independent studies. A complex spatial pattern of MS polymorphisms among global P. vivax populations was observed which has potential utility in future epidemiological studies of the P. vivax parasite.

SUBMITTER: Schousboe ML

PROVIDER: S-EPMC4200131 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America.

Schousboe Mette L ML Ranjitkar Samir S Rajakaruna Rupika S RS Amerasinghe Priyanie H PH Konradsen Flemming F Morales Francisco F Ord Rosalynn R Pearce Richard R Leslie Toby T Rowland Mark M Gadalla Nahla N Bygbjerg Ib C IC Alifrangis Michael M Roper Cally C

Malaria journal 20141002

<h4>Background</h4>Even though Plasmodium vivax has the widest worldwide distribution of the human malaria species and imposes a serious impact on global public health, the investigation of genetic diversity in this species has been limited in comparison to Plasmodium falciparum. Markers of genetic diversity are vital to the evaluation of drug and vaccine efficacy, tracking of P. vivax outbreaks, and assessing geographical differentiation between parasite populations.<h4>Methods</h4>The genetic ...[more]

PMID: 25277367

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Project description:BackgroundMechanical transmission of the major livestock pathogen Trypanosoma vivax by other biting flies than tsetse allows its spread from Africa to the New World. Genetic studies are restricted to a small number of isolates and based on molecular markers that evolve too slowly to resolve the relationships between American and West African populations and, thus, unable us to uncover the recent history of T. vivax in the New World.MethodsT. vivax genetic diversity, population structure and the source of outbreaks was investigated through the microsatellite multiloci (7 loci) genotype (MLGs) analysis in South America (47isolates from Brazil, Venezuela and French Guiana) and West Africa (12 isolates from The Gambia, Burkina Faso, Ghana, Benin and Nigeria). Relationships among MLGs were explored using phylogenetic, principal component and STRUCTURE analyses.ResultsAlthough closely phylogenetically related, for the first time, genetic differences were detected between T. vivax isolates from South America (11 genotypes/47 isolates) and West Africa (12 genotypes/12 isolates) with no MLGs in common. Diversity was far greater across West Africa than in South America, where genotypes from Brazil (MLG1-6), Venezuela (MLG7-10) and French Guiana (MLG11) shared similar but not identical allele composition. No MLG was exclusive to asymptomatic (endemic areas) or sick (outbreaks in non-endemic areas) animals, but only MLGs1, 2 and 3 were responsible for severe haematological and neurological disorders.ConclusionsOur results revealed closely related genotypes of T. vivax in Brazil and Venezuela, regardless of endemicity and clinical conditions of the infected livestock. The MLGs analysis from T. vivax across SA and WA support clonal propagation, and is consistent with the hypothesis that the SA populations examined here derived from common ancestors recently introduced from West Africa. The molecular markers defined here are valuable to assess the genetic diversity, to track the source and dispersion of outbreaks, and to explore the epidemiological and pathological significance of T. vivax genotypes.

Project description:Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well as the other neglected non-Pf parasites, which are currently invisible to most public health authorities in Africa, but which can cause severe clinical illness and require specific control interventions.

Project description:Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). Deepening our knowledge of parasite biology and its molecular components is key to develop new tools for malaria control and elimination. This study aims to investigate and characterize a P. vivax protein (PvVir14) for its role in parasite biology and its interactions with the immune system. We collected sera or plasma from P.vivax-infected subjects in Brazil (n = 121) and Cambodia (n = 55), and from P. falciparum-infected subjects in Mali (n = 28), to assess antibody recognition of PvVir14. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. IgG1 and IgG3 most frequently contributed to anti-PvVir14 responses. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21- CD27-) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. When analyzed at a single-cell level, the B cell receptor gene hIGHV3-23 was only seen in subjects with active P.vivax infection where it comprised 20% of V gene usage. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. Specific B cell subsets, anti-PvVir14 circulating antibodies, and NKT cell levels declined after treatment of P. vivax. This study provides the immunological characterization of PvVir14, a unique P. vivax protein, and possible association with acute host's immune responses, providing new information of specific host-parasite interaction. Trial registration: TrialClinicalTrials.gov Identifier: NCT00663546 & ClinicalTrials.gov NCT02334462.

Project description:BackgroundBrazil is a unique and understudied setting for malaria, with complex foci of transmission associated with human and environmental conditions. An understanding of the population genomic diversity of P. vivax parasites across Brazil can support malaria control strategies.MethodsThrough whole genome sequencing of P. vivax isolates across 7 Brazilian states, we use population genomic approaches to compare genetic diversity within country (n = 123), continent (6 countries, n = 315) and globally (26 countries, n = 885).FindingsWe confirm that South American isolates are distinct, have more ancestral populations than the other global regions, with differentiating mutations in genes under selective pressure linked to antimalarial drugs (pvmdr1, pvdhfr-ts) and mosquito vectors (pvcrmp3, pvP45/48, pvP47). We demonstrate Brazil as a distinct parasite population, with signals of selection including ABC transporter (PvABCI3) and PHIST exported proteins.InterpretationBrazil has a complex population structure, with evidence of P. simium infections and Amazonian parasites separating into multiple clusters. Overall, our work provides the first Brazil-wide analysis of P. vivax population structure and identifies important mutations, which can inform future research and control measures.FundingAI is funded by an MRC LiD PhD studentship. TGC is funded by the Medical Research Council (Grant no. MR/M01360X/1, MR/N010469/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1). SC is funded by Medical Research Council UK grants (MR/M01360X/1, MR/R025576/1, MR/R020973/1 and MR/X005895/1) and Bloomsbury SET (ref. CCF17-7779). FN is funded by The Shloklo Malaria Research Unit - part of the Mahidol Oxford Research Unit, supported by the Wellcome Trust (Grant no. 220211). ARSB is funded by São Paulo Research Foundation - FAPESP (Grant no. 2002/09546-1). RLDM is funded by Brazilian National Council for Scientific and Technological Development - CNPq (Grant no. 302353/2003-8 and 471605/2011-5); CRFM is funded by FAPESP (Grant no. 2020/06747-4) and CNPq (Grant no. 302917/2019-5 and 408636/2018-1); JGD is funded by FAPESP fellowships (2016/13465-0 and 2019/12068-5) and CNPq (Grant no. 409216/2018-6).

Dataset Information

Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America.

Publications

Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America.

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