Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon

Abstract

BackgroundPeru is one of the Latin American countries with the highest malaria burden, mainly due to Plasmodium vivax infections. However, little is known about P. vivax transmission dynamics in the Peruvian Amazon, where most malaria cases occur. The genetic diversity and population structure of P. vivax isolates collected in different communities around Iquitos city, the capital of the Peruvian Amazon, was determined.MethodsPlasmodium vivax population structure was determined by multilocus genotyping with 16 microsatellites on 159 P. vivax infected blood samples (mono-infections) collected in four sites around Iquitos city. The population characteristics were assessed only in samples with monoclonal infections (n = 94), and the genetic diversity was determined by calculating the expected heterozygosity and allelic richness. Both linkage disequilibrium and the genetic differentiation (θ) were estimated.ResultsThe proportion of polyclonal infections varied substantially by site (11% - 70%), with the expected heterozygosity ranging between 0.44 and 0.69; no haplotypes were shared between the different populations. Linkage disequilibrium was present in all populations (IAS 0.14 - 0.61) but was higher in those with fewer polyclonal infections, suggesting inbreeding and a clonal population structure. Strong population differentiation (θ = 0.45) was found and the Bayesian inference cluster analysis identified six clusters based on distinctive allele frequencies.ConclusionThe P. vivax populations circulating in the Peruvian Amazon basin are genetically diverse, strongly differentiated and they have a low effective recombination rate. These results are in line with the low and clustered pattern of malaria transmission observed in the region around Iquitos city.

High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

“…Furthermore, recent data indicate that the P. vivax population is highly structured in the Iquitos region of the Peruvian Amazon, 29 similar to the limited number of haptotypes reported for P. falciparum in the Peruvian Amazon. 34 Nonetheless, the large-scale genomic structure underlying the population structure has yet to be determined.…”

“…The degree of diversity in P. vivax in the Iquitos region of the Peruvian Amazon is sufficiently high to allow for the differentiation of strains present in human infections using a variety of methods including microsatellites 29 and the combination of TRs and MSP3α PCR-RFLP. Furthermore, recent data indicate that the P. vivax population is highly structured in the Iquitos region of the Peruvian Amazon, 29 similar to the limited number of haptotypes reported for P. falciparum in the Peruvian Amazon.…”

“…13,28 Plasmodium vivax has been noted to be heterogeneous, highly structured according to microsatellite analysis, and to have a low effective recombination rate. 29 Transmission intensity is typically low (entomological inoculation rate 1 infective bite per year, based on data from the late 1990s 30 ), few Anopheles spp. vector mosquitoes are infected with malaria parasites 30,31 and mixed infections with P. falciparum and P. vivax in the Amazon region are uncommon.…”

High Genetic Diversity of Plasmodium vivax on the North Coast of Papua New Guinea

“…30,31 Although consensus markers are yet to be determined for P. vivax, MS16 and msp1F3 were recently reported as being highly diverse after evaluation of a panel of potential P. vivax genotyping markers. 13 MS16 has previously been used to assess the genetic diversity of P. vivax populations from Peru, 32 Brazil, 33 Vietnam, 12 PNG, 13,14 Sri Lanka, Ethiopia, 25 Myanmar, 25 and Korea. 34 The diversity of MS16 among P. vivax isolates from a range of global endemic areas is reported to be medium to high (H e [range] = 0.5-0.9), 12,14,25,[32][33][34] with the exception of a single report of very low levels of diversity among isolates from Ethiopia (H e = 0.19).…”

Using Mitochondrial Genome Sequences to Track the Origin of Imported Plasmodium vivax Infections Diagnosed in the United States

“…The parasites from these regions show a significant genetic divergence from other populations separated by relatively short distances. [34][35][36] A very recent analysis of mitochondrial lineages of P. vivax sampled across the Americas confirmed the high level of genetic diversity and substructuring of local parasite populations, with at least four well-defined haplotype clusters. 37 These data are consistent with the introduction of P. vivax in the Americas from multiple sources and at different times since the first humans reached the continent in preColumbian times.…”