Abstract
The incidence of Plasmodium vivax infection has declined markedly in Malaysia over the past decade despite evidence of high-grade chloroquine resistance. Here we investigate the genetic changes in a P. vivax population approaching elimination in 51 isolates from Sabah, Malaysia and compare these with data from 104 isolates from Thailand and 104 isolates from Indonesia. Sabah displays extensive population structure, mirroring that previously seen with the emergence of artemisinin-resistant P. falciparum founder populations in Cambodia. Fifty-four percent of the Sabah isolates have identical genomes, consistent with a rapid clonal expansion. Across Sabah, there is a high prevalence of loci known to be associated with antimalarial drug resistance. Measures of differentiation between the three countries reveal several gene regions under putative selection in Sabah. Our findings highlight important factors pertinent to parasite resurgence and molecular cues that can be used to monitor low-endemic populations at the end stages of P. vivax elimination.
Highlights
The incidence of Plasmodium vivax infection has declined markedly in Malaysia over the past decade despite evidence of high-grade chloroquine resistance
Whilst several genomic studies have explored the molecular dynamics of P. vivax populations with stable transmission[9,10,11,12,13], aside from a small selection of microsatellite-based studies[14,15,16], little is known about the molecular epidemiology during the critical, end stages of malaria elimination
The parasite population structure in Sabah was examined for evidence of unstable transmission and bottlenecking, and comparative analyses were undertaken against Thailand and Indonesia to identify genomic regions under putative selection
Summary
The incidence of Plasmodium vivax infection has declined markedly in Malaysia over the past decade despite evidence of high-grade chloroquine resistance. Whilst several genomic studies have explored the molecular dynamics of P. vivax populations with stable transmission[9,10,11,12,13], aside from a small selection of microsatellite-based studies[14,15,16], little is known about the molecular epidemiology during the critical, end stages of malaria elimination. The parasite population structure in Sabah was examined for evidence of unstable transmission and bottlenecking, and comparative analyses were undertaken against Thailand and Indonesia to identify genomic regions under putative selection. A high prevalence of known resistance determinants is observed in Sabah, and several new signals of selection have been revealed, requiring further investigation with clinical phenotypes These findings highlight the substantial adaptive potential in a pre-elimination P. vivax population, and the need for a stronger framework for molecular surveillance to track the early emergence of adaptive new strains
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