Complexity of Infection and Genetic Diversity in Cambodian Plasmodium vivax

Abstract

BackgroundPlasmodium vivax is the most widely distributed human malaria parasite with 2.9 billion people living in endemic areas. Despite intensive malaria control efforts, the proportion of cases attributed to P. vivax is increasing in many countries. Genetic analyses of the parasite population and its dynamics could provide an assessment of the efficacy of control efforts, but, unfortunately, these studies are limited in P. vivax by the lack of informative markers and high-throughput genotyping methods.Methodology/Principal FindingsWe developed a sequencing-based assay to simultaneously genotype more than 100 SNPs and applied this approach to ~500 P. vivax-infected individuals recruited across nine locations in Cambodia between 2004 and 2013. Our analyses showed that the vast majority of infections are polyclonal (92%) and that P. vivax displays high genetic diversity in Cambodia without apparent geographic stratification. Interestingly, our analyses also revealed that the proportion of monoclonal infections significantly increased between 2004 and 2013, possibly suggesting that malaria control strategies in Cambodia may be successfully affecting the parasite population.Conclusions/SignificanceOur findings demonstrate that this high-throughput genotyping assay is efficient in characterizing P. vivax diversity and can provide valuable insights to assess the efficacy of malaria elimination programs or to monitor the spread of specific parasites.

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

“…We also have previously characterized the within-host diversity of coendemic P. vivax and P. falciparum in this region by amplicon deep sequencing, with results supporting the difference in polyclonality (59,60). The high proportion of polyclonal P. vivax infections and the lack of parasite substructuring also were observed in a recent report from Cambodia that used deep sequencing of more than 100 SNPs across the P. vivax genome (18,61).…”

Frequent Spread of Plasmodium vivax Malaria Maintains High Genetic Diversity at the Myanmar-China Border, Without Distance and Landscape Barriers

“…Nevertheless, in some areas of low endemicity, such as Central Asia, P. vivax retains much of the preexisting diversity despite recent decrease in effective population sizes or reduced transmission levels [37]. In Cambodia, the eastern and western P. vivax populations lack clear differentiation [38]. The overall high genetic diversity illustrates the impact of human movements on mixing the parasite gene pools.…”

Malaria Epidemiology at the Clone Level

“…The ability to track parasite migration on a national or regional level, and in parallel to identify isolated parasite populations that could be targeted for elimination, heavily depends on local context, and often differs for P. falciparum and P. vivax in the same country. In Cambodia, a P. vivax SNP barcode as well as whole genome sequencing failed to find population structure – most likely due to ongoing transmission throughout the country [15, 17]. Yet Cambodian P. falciparum infections exhibit strong population structure, which is mediated by geography as well as levels of resistance to artemisinin [41].…”

“…identification of half-siblings, sharing 25% of their genome) are hampered by stochastic variation due to the small number of markers and possible independent evolution of the same allele multiple times. Genome-wide SNP assays, including several SNPs on each of the parasite’s 14 chromosomes [17], will be better suited for such studies.…”