RESUMO
For 20 years, Plasmodium vivax has been the only prevalent malaria species in Mexico, and cases have declined significantly and continuously. Spatiotemporal genetic studies can be helpful for understanding parasite dynamics and developing strategies to weaken malaria transmission, thus facilitating the elimination of the parasite. The aim of the current contribution was to analyze P. vivax-infected blood samples from patients in southern Mexico during the control (1993-2007) and pre-elimination phases (2008-2011). Nucleotide and haplotype changes in the pvmsp142 fragment were evaluated over time. The majority of multiple genotype infections occurred in the 1990s, when the 198 single nucleotide sequences exhibited 57 segregating sites, 64 mutations, and 17 haplotypes. Nucleotide and genetic diversity parameters showed subtle fluctuations from across time, in contrast to the reduced haplotype diversity and the increase in the R2 index and Tajima's D value from 2008 to 2011. The haplotype network consisted of four haplogroups, the geographical distribution of which varied slightly over time. Haplogroup-specific B-cell epitopes were predicted. Since only high-frequency and divergent haplotypes persisted, there was a contraction of the parasite population. Given that 84% of haplotypes were exclusive to Mesoamerica, P. vivax flow is likely circumscribed to this region, representing important information for parasite surveillance.
RESUMO
Malaria is still a grave public health problem in tropical areas of the world. The greater genetic diversity of Plasmodium vivax at geographic sites with less control over infection evidences the importance of genetic studies of these parasites. The present genetic study compares P. vivax in Nicaragua, which is still in the control phase, with this species in several other countries. In Nicaragua, P. vivax causes over 80% of malaria cases, most occurring in two remote northern regions. Plasmodium asexual blood-stage antigens, implicated in reticulocyte invasion, are possible molecular markers for analyzing parasite population genetics and for developing vaccines. The aim of this work was to investigate the genetic structure of P. vivax based on the 42kDa merozoite surface protein-1 (PvMSP-142), which may represent a sensitive marker for evaluating malaria transmission control. From blood samples of patients with P. vivax, we amplified PvMSP-142, obtained the nucleotide sequences, and compared them to homologous sequences of parasites from other geographic sites, retrieved from the GenBank. The 92 nucleotide sequences of P. vivax resulted in the resolution of eight haplotypes, six exclusive to Nicaragua. The great nucleotide diversity (π=0.020), the minimal recombination events (Rm=11), and the dN-dS values were similar to other control phase countries. FST values between parasites were low (0.069) for Nicaragua versus Brazil but higher for Nicaragua versus other regions (0.134-0.482). The haplotype network revealed five lineages: two were very frequent in Nicaragua and closely related to American parasites; three have been detected in multiple geographic sites around the world. These results suggest that P. vivax in Nicaragua is a differentiated and genetically diverse population (mainly due to mutation, positive balancing selection and recombination) and that PvMSP-142 may be a sensitive marker for evaluating sustained reduction in malaria transmission and for developing vaccines.
Assuntos
Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Proteína 1 de Superfície de Merozoito/genética , Plasmodium vivax/classificação , Plasmodium vivax/genética , Domínios Proteicos/genética , Evolução Molecular , Variação Genética , Genética Populacional , Haplótipos , Humanos , Malária Vivax/diagnóstico , Proteína 1 de Superfície de Merozoito/química , Nicarágua/epidemiologia , Filogenia , Filogeografia , Reação em Cadeia da Polimerase , Recombinação Genética , Seleção Genética , Análise de Sequência de DNARESUMO
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. Methods: 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...
Assuntos
Humanos , Malária/diagnóstico , Malária/epidemiologia , Malária/transmissão , Plasmodium malariae/crescimento & desenvolvimento , Plasmodium malariae/genéticaRESUMO
To infer recent patterns of malaria transmission, we measured naturally acquired IgG antibodies to the conserved 19-kDa C-terminal region of the merozoite surface protein (MSP)-1 of both Plasmodium vivax (PvMSP-1(19)) and Plasmodium falciparum (PfMSP-1(19)) in remote malaria-exposed populations of the Amazon Basin. Community-based cross-sectional surveys were carried out between 2002 and 2003 in subjects of all age groups living along the margins of the Unini and Jaú rivers, Northwestern Brazil. We found high prevalence rates of IgG antibodies to PvMSP-1(19) (64.0 - 69.6 percent) and PfMSP-1(19) (51.6 - 52.0 percent), with significant differences in the proportion of subjects with antibodies to PvMSP-1(19) according to age, place of residence and habitual involvement in high-risk activities, defining some groups of highly exposed people who might be preferential targets of malaria control measures. In contrast, no risk factor other than age was significantly associated with seropositivity to PfMSP-1(19). Only 14.1 percent and 19.3 percent of the subjects tested for antibodies to PvMSP-1(19) and PfMSP-1(19) in consecutive surveys (142 - 203 days apart) seroconverted or had a three fold or higher increase in the levels of antibodies to these antigens. We discuss the extent to which serological data correlated with the classical malariometric indices and morbidity indicators measured in the studied population at the time of the seroprevalence surveys and highlight some limitations of serological data for epidemiological inference.