Abstract
Plasmodium vivax has become the predominant malaria parasite and a major challenge for malaria elimination in the Greater Mekong Subregion (GMS). Yet, our knowledge about the evolution of P. vivax populations in the GMS is fragmental. We performed whole genome sequencing on 23 P. vivax samples from the China-Myanmar border (CMB) and used 21 high-coverage samples to compare to over 200 samples from the rest of the GMS. Using genome-wide single nucleotide polymorphisms (SNPs), we analyzed population differentiation, genetic structure, migration and potential selection using an array of methods. The CMB parasites displayed a higher proportion of monoclonal infections, and 52% shared over 90% of their genomes in identity-by-descent segments with at least one other sample from the CMB, suggesting preferential expansion of certain parasite strains in this region, likely resulting from the P. vivax outbreaks occurring during this study period. Principal component, admixture, fixation index and phylogenetic analyses all identified that parasites from the CMB were genetically distinct from parasites from eastern parts of the GMS (Cambodia, Laos, Vietnam, and Thailand), whereas the eastern GMS parasite populations were largely undifferentiated. Such a genetic differentiation pattern of the P. vivax populations from the GMS parasite was largely explainable through geographic distance. Using the genome-wide SNPs, we narrowed down to a set of 36 SNPs for differentiating parasites from different areas of the GMS. Genome-wide scans to determine selection in the genome with two statistical methods identified genes potentially under drug selection, including genes associated with antifolate resistance and genes linked to chloroquine resistance in Plasmodium falciparum.
Highlights
The Greater Mekong Subregion (GMS) in Southeast Asia is in the pursuit of malaria elimination, aiming to achieve this goal by 2030 [1]
Plasmodium vivax is an understudied malaria parasite compared to P. falciparum despite that it is the most common Plasmodium species outside of Africa
In the Greater Mekong Subregion (GMS), the increased proportion of P. vivax proves its resilience to conventional malaria control measures
Summary
The Greater Mekong Subregion (GMS) in Southeast Asia is in the pursuit of malaria elimination, aiming to achieve this goal by 2030 [1]. The GMS consists of six countries, Laos, Vietnam, Myanmar, Thailand, Cambodia, and Yunnan and Guangxi provinces of China, and is especially concerning due to the repeated emergence of drug resistance in Plasmodium falciparum to frontline treatments [1–5]. Myanmar has especially high country-wide malaria endemicity, and malaria re-introduction into the neighboring countries, such as China and Thailand, is a major concern [9–11]. On the CMB, P. vivax was the cause of multiple malaria outbreaks in the past decade, including one in 2013 and one in 2016 [7]. It is unclear exactly what caused these outbreaks, but some potential causes include increased drug resistance or the expansion of introduced or relapsed parasite lineages [7]. It is crucial that we monitor the epidemiology of P. vivax along the CMB in order to understand the composition of the local population and its relationship with nearby populations, allowing us to implement targeted control efforts
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