Human Plasmodium vivax diversity, population structure and evolutionary origin

Abstract

More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from PLOS NEGLECTED TROPICAL DISEASES PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.Among the five Plasmodium species infecting humans, P. vivax is the most prevalent parasite outside Africa. To date, there has been less research on this species than for Plasmodium falciparum, a more lethal species, principally because of the lack of an in vitro culture system and also because P. vivax is considered relatively benign. Nevertheless, P. vivax is responsible for severe and incapacitating clinical symptoms with significant effects on human health. The emergence of new drug resistance and the discovery of severe and even fatal cases due to P. vivax question the benign status of P. vivax malaria. In recent years, there has been increased interest in characterizing the distribution of genetic variation in P. vivax. However, these studies either generated genetic information from a regional geographic scale or combine genetic datasets generated in different molecular platforms, which is known to generate biased results. In this study, we used a single genotyping platform to genotype 14 microsatellite markers in 834 samples of P. vivax obtained from 28 locations in 20 countries from around the world, including several populations from East and West Africa. We discuss the worldwide population genetic structure and the evolutionary origins of P. vivax, as well as its introduction into the Americas.

Population genomic evidence of a Southeast Asian origin ofPlasmodium vivax

“…Certain studies placed the origin of the human P. vivax in Southeast Asia (“out of Asia” hypothesis) based on its phylogenetic position in a clade of parasites infecting Asian monkeys ( 17–19 ). This scenario was also supported by genotyping data at 11 microsatellite markers collected across four continents, showing the highest microsatellite diversity in Southeast Asia ( 20, 21 ). However, the Asian-origin has been challenged by an “out of Africa” scenario, with the recent discovery of a closely related Plasmodium species circulating in wild-living African great apes (chimpanzees and gorillas) ( 22 ).…”

Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa

“…A recent survey of 14 microsatellite loci has also indicated the distinctiveness of P . vivax samples from Mauritania compared to most other sampled populations in Africa, Asia or the Americas [ 10 ], further supporting the evidence for an established focus of endemicity.…”

“…There is evidence suggesting that P . vivax in humans emerged in Africa as a spill-over zoonosis from a reservoir in great apes [ 5 , 6 ], but this parasite species is now rare in most of the continent apart from the Horn of East Africa [ 7 , 8 ] and some analyses suggest historical emergence from southeast Asia [ 9 , 10 ], so the origin and epidemiology in northwest Africa remains obscure. It is vital to know whether P .…”

Multi-locus genotyping reveals established endemicity of a geographically distinctPlasmodium vivaxpopulation in Mauritania, West Africa

“…The P. vivax population in Mauritania is clearly genetically divergent from other geographical populations of the parasite, including Ethiopia which is the source of most other samples from the African continent that have been analysed so far. A recent survey of 14 microsatellite loci has also indicated the distinctiveness of P. vivax samples from Mauritania compared to most other sampled populations in Africa, Asia or the Americas [10], further supporting the evidence for an established focus of endemicity.…”

“…Routine laboratory-based diagnostic testing is insufficient for highly accurate assessment, but molecular analysis of parasites indicates that most malaria in the Sahel zone in the south of the country is caused by P. falciparum [2], whereas P. vivax predominates in the central and northern regions of the country within the arid Saharan zone [2-4]. There is evidence suggesting that P. vivax in humans emerged in Africa as a spill-over zoonosis from a reservoir in great apes [5, 6], but this parasite species is now rare in most of the continent apart from the Horn of East Africa [7, 8] and some analyses suggest historical emergence from southeast Asia [9, 10], so the origin and epidemiology in northwest Africa remains obscure.…”