Genomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics

消除前马来西亚间日疟原虫种群的基因组分析揭示了选择压力和不断变化的传播动态

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作者:Sarah Auburn, Ernest D Benavente, Olivo Miotto, Richard D Pearson, Roberto Amato, Matthew J Grigg, Bridget E Barber, Timothy William, Irene Handayuni, Jutta Marfurt, Hidayat Trimarsanto, Rintis Noviyanti, Kanlaya Sriprawat, Francois Nosten, Susana Campino, Taane G Clark, Nicholas M Anstey, Dominic P

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.

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