RESUMO
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.
Assuntos
Malária Vivax/parasitologia , Repetições de Microssatélites , Plasmodium vivax/genética , Ásia , Variação Genética , Humanos , América do Sul , SudãoRESUMO
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.
Assuntos
Antígenos de Protozoários/genética , Variação Genética , Genética Populacional , Proteínas de Membrana/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Recombinação Genética , Animais , Antígenos de Protozoários/metabolismo , Sequência de Bases , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Malária/genética , Proteínas de Membrana/metabolismo , Plasmodium falciparum/metabolismo , Plasmodium vivax/metabolismo , Proteínas de Protozoários/metabolismo , Seleção Genética , VenezuelaRESUMO
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.
Assuntos
Malária/genética , Plasmodium malariae/genética , Animais , Sequência de Bases , Haiti/epidemiologia , Haiti/etnologia , Humanos , Jamaica/epidemiologia , Malária/epidemiologia , Malária/transmissão , Dados de Sequência Molecular , Plasmodium malariae/patogenicidade , Prevalência , RefugiadosRESUMO
The genetic diversity of a defined Plasmodium vivax population from the Venezuelan Amazon was evaluated by direct sequencing of the gene encoding the P. vivax merozoite surface protein-3alpha, Pvmsp3alpha. Three allele sizes (1.9, 1.4 and 1.1kb) were amplified from 58 isolates with frequencies of 59.3%, 21.9% and 18.8%, respectively. 27 Pvmsp3alpha nucleotide sequences were determined, with nine distinct haplotypes observed. The genetic diversity (h) at this single locus was 0.774. The P. vivax population in this region exhibits significant diversity in contrast to the genetically restricted diversity of the sympatric P. falciparum population. Despite sharing vector and human hosts, different control strategies may be required for these two species in this region. Substitution patterns in the conserved C-terminus of Pvmsp3alpha showed a significant departure from neutrality, suggesting these polymorphisms are being maintained by frequency-dependent selection as the result of an effective immune response from the host. Our findings support the use of Pvmsp3alpha genotyping as a tool for monitoring interventions aimed at control of P. vivax.
Assuntos
Antígenos de Protozoários/genética , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Alelos , Animais , Sequência de Bases , Variação Genética , Humanos , Malária Vivax/parasitologia , Filogenia , Estrutura Terciária de Proteína/genética , Seleção Genética , VenezuelaRESUMO
BACKGROUND: The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires. METHODS: Distinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-alpha domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-alpha of known location in the 3D7 genome. RESULTS: Sympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci. CONCLUSION: The parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.