Dataset Information

Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.

ABSTRACT: BACKGROUND: Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. METHODS: Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. RESULTS AND CONCLUSION: A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n?=?77) for pvama-1; 23 (n?=?84) for pvcsp; and 23 (n?=?35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n?=?30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n?=?11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.

SUBMITTER: Lopez AC

PROVIDER: S-EPMC3519596 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.

Lopez Ana Cecilia AC Ortiz Andres A Coello Jorge J Sosa-Ochoa Wilfredo W Torres Rosa E Mejia RE Banegas Engels I EI Jovel Irina I Fontecha Gustavo A GA

Malaria journal 20121126

<h4>Background</h4>Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates f ...[more]

PMID: 23181845

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Project description:BACKGROUND: In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. METHODS: Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. RESULTS: Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. CONCLUSION: The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P. falciparum and P. vivax is therefore essential also in Honduras.

Project description:Background:Plasmodium lactate dehydrogenase (pLDH) is a major target in diagnosing the erythrocytic stage of malaria parasites because it is highly expressed during blood-stage parasites and is distinguished from human LDH. Rapid diagnostic tests (RDTs) for malaria use pLDH as a target antigen; however, genetic variations in pLDH within the natural population threaten the efficacy of pLDH-based RDTs.Methods:Genetic polymorphisms of Plasmodium vivax LDH (PvLDH) and Plasmodium falciparum LDH (PfLDH) in Myanmar isolates were analysed by nucleotide sequencing analysis. Genetic polymorphisms and the natural selection of PvLDH and PfLDH were analysed using DNASTAR, MEGA6, and DnaSP ver. 5.10.00 programs. The genetic diversity and natural selection of global PvLDH and PfLDH were also analysed. The haplotype network of global PvLDH and PfLDH was constructed using NETWORK ver. 5.0.0.3. Three-dimensional structures of PvLDH and PfLDH were built with YASARA Structure ver. 18.4.24 and the impact of mutations on structural change and stability was evaluated with SDM ver. 2, CUPSAT and MAESTROweb.Results:Forty-nine PvLDH and 52 PfLDH sequences were obtained from Myanmar P. vivax and P. falciparum isolates. Non-synonymous nucleotide substitutions resulting in amino acid changes were identified in both Myanmar PvLDH and PfLDH. Amino acid changes were also identified in the global PvLDH and PfLDH populations, but they did not produce structural alterations in either protein. Low genetic diversity was observed in global PvLDH and PfLDH, which may be maintained by a strong purifying selection.Conclusion:This study extends knowledge for genetic diversity and natural selection of global PvLDH and PfLDH. Although amino acid changes were observed in global PvLDH and PfLDH, they did not alter the conformational structures of the proteins. These suggest that PvLDH and PfLDH are genetically well-conserved in global populations, which indicates that they are suitable antigens for diagnostic purpose and attractive targets for drug development.

Project description:Malaria continues to be an important health problem in Honduras despite major progress achieved reducing its incidence in the last two decades. In a context of case reduction, continuing surveillance of parasite diversity and drug resistance is an important component to assist effective malaria control strategies and support risk assessments. In this study, we employed next generation sequencing on collected Plasmodium vivax and P. falciparum samples from the Hospital Escuela (University Hospital) in Honduras between 2005 and 2017. Hospital Escuela is the main public health hospital in Honduras and receives suspected malaria cases from endemic regions within the country. The resulting sequencing data was used to assess complexity of infections, parasite population structure, parasite diversity and drug resistance profiling. All P. vivax samples and all autochtonous P. falciparum samples were monoclonal and presented a low intra population diversity (π = 0.25 and 0.07, respectively). Genotyping of drug resistance markers showed that three P. falciparum samples presented the chloroquine resistant haplotype SVMNT on pfcrtr (positions 72-76). Epidemiological data suggested that two of these samples were imported cases from Africa whereas the third one was a local case. Three suspected imported cases (two of which were also pfcrt mutants) presented the pfmdr1 86Y mutation that further enhances the CQ resistant genotype. No evidence was found for kelch13 artemisinin resistance associated mutations nor parasite genetic background mutations. Discriminant analysis of principal components and phylogenetic analysis showed two P. vivax and two P. falciparum parasite sub-populations with limited recombination between them. It also confirmed the closer relationship of the three imported cases with African strains. Our findings showed that local Honduras P. falciparum strains do not hold CQ resistance polymorphisms which aligns with clinical data reported by the country and supports the continuity of CQ based treatment in Honduras. In addition, our findings highlight the need of using genomic approaches to provide key information about parasite biology including drug resistance, population structure and HRP2/HRP3 deletions which are becoming relevant as the country move towards elimination.

Project description:In Central China the declining incidence of Plasmodium vivax has been interrupted by epidemic expansions and imported cases. The impact of these changes on the local parasite population, and concurrent risks of future resurgence, was assessed.Plasmodium vivax isolates collected from Anhui and Jiangsu provinces, Central China between 2007 and 2010 were genotyped using capillary electrophoresis at seven polymorphic short tandem repeat markers. Spatial and temporal analyses of within-host and population diversity, population structure, and relatedness were conducted on these isolates.Polyclonal infections were infrequent in the 94 isolates from Anhui (4%) and 25 from Jiangsu (12%), with a trend for increasing frequency from 2008 to 2010 (2 to 19%) when combined. Population diversity was high in both provinces and across the years tested (H(E)?=?0.8 - 0.85). Differentiation between Anhui and Jiangsu was modest (F'(ST)?=?0.1). Several clusters of isolates with identical multi-locus haplotypes were observed across both Anhui and Jiangsu. Linkage disequilibrium was strong in both populations and in each year tested (I(A)(S)?=?0.2 - 0.4), but declined two- to four-fold when identical haplotypes were accounted for, indicative of occasional epidemic transmission dynamics. None of five imported isolates shared identical haplotypes to any of the central Chinese isolates.The population genetic structure of P. vivax in Central China highlights unstable transmission, with limited barriers to gene flow between the central provinces. Despite low endemicity, population diversity remained high, but the reservoirs sustaining this diversity remain unclear. The challenge of imported cases and risks of resurgence emphasize the need for continued surveillance to detect early warning signals. Although parasite genotyping has potential to inform the management of outbreaks, further studies are required to identify suitable marker panels for resolving local from imported P. vivax isolates.

Project description:BACKGROUND: We present the first population genetic analysis of homologous loci from two sympatric human malaria parasite populations sharing the same human hosts, using full-length sequences of ama1 genes from Plasmodium vivax and P. falciparum collected in the Venezuelan Amazon. METHODOLOGY/PRINCIPAL FINDINGS: Significant differences between the two species were found in genetic diversity at the ama1 locus, with 18 distinct haplotypes identified among the 73 Pvama1 sequences obtained, compared to 6 unique haplotypes from 30 Pfama1 sequences, giving overall diversity estimates of h = 0.9091, and h = 0.538 respectively. Levels of recombination were also found to differ between the species, with P. falciparum exhibiting very little recombination across the 1.77 kb sequence. In contrast, analysis of patterns of nucleotide substitutions provided evidence that polymorphisms in the ama1 gene of both species are maintained by balancing selection, particularly in domain I. The two distinct population structures observed are unlikely to result from different selective forces acting upon the two species, which share both human and mosquito hosts in this setting. Rather, the highly structured P. falciparum population appears to be the result of a population bottleneck, while the much less structured P. vivax population is likely to be derived from an ancient pool of diversity, as reflected in a larger estimate of effective population size for this species. Greatly reduced mosquito transmission in 1997, due to low rainfall prior to the second survey, was associated with far fewer P. falciparum infections, but an increase in P. vivax infections, probably due to hypnozoite activation. CONCLUSIONS/SIGNIFICANCE: The relevance of these findings to putative competitive interactions between these two important human pathogen species is discussed. These results highlight the need for future control interventions to employ strategies targeting each of the parasite species present in endemic areas.

Dataset Information

Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.

Publications

Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras.

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