Date Published: April 15, 2015
Publisher: Public Library of Science
Author(s): Charlie Jennison, Alicia Arnott, Natacha Tessier, Livingstone Tavul, Cristian Koepfli, Ingrid Felger, Peter M. Siba, John C. Reeder, Melanie Bahlo, Ivo Mueller, Alyssa E. Barry, Marcelo U. Ferreira. http://doi.org/10.1371/journal.pntd.0003634
Abstract: IntroductionThe human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs.Methodology/Principle findingsP. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83–0.85) was higher than that of P. falciparum (He = 0.64–0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21–28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043–69142) was larger than that of P. falciparum (18871; 8109–42986).Conclusions/SignificanceDespite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods.
Partial Text: Plasmodium vivax and Plasmodium falciparum are responsible for the majority of the human malaria burden worldwide. Malaria control and elimination initiatives have had enormous success, preventing an estimated 1.1 million deaths and approximately 274 million cases between 2001 and 2011 . P. falciparum has traditionally attracted the greatest interest, as it is responsible for the majority of malaria deaths, while P. vivax has been relatively neglected. However, the classification of P. vivax malaria as “benign” has been revised in recent years as reports of severe vivax malaria have become commonplace in scientific literature [2,3]. Indeed, this species is estimated to be responsible for up to 300 million episodes of clinical malaria each year, predominantly in malaria-endemic regions outside sub-Saharan Africa . Alongside the acknowledgment that P. vivax is of major global health significance, control programmes have revealed that this species is more resistant to control measures than P. falciparum . Several unique features of P. vivax biology are thought to facilitate evasion of control efforts, including: relapse [6,7], the early appearance of transmission stages (gametocytes) [6,8] and a more rapid acquisition of clinical immunity [8,9]. P. vivax transmission is therefore likely to be more stable over time and during control efforts, when compared to P. falciparum .
Higher diversity among global P. vivax isolates than among P. falciparum isolates has been proposed to be consistent with more stable transmission over a long period of time and/or deeper evolutionary roots . In some co-endemic areas, such as South America, the higher microsatellite diversity of P. vivax can be explained by its more stable transmission than P. falciparum [19,67]. A higher mutation rate of P. vivax microsatellites has also been proposed as one possible mechanism for the higher diversity of this species in South East Asia . Within PNG, we have shown that despite comparably high transmission, as measured by EIR [31–33] and slightly lower infection prevalence than P. falciparum [36,37], P. vivax has greater genetic diversity and larger effective population sizes. Furthermore, we show for the first time that populations of P. vivax are highly admixed compared to sympatric populations of P. falciparum, which appear to be fragmented according to the analyses of genetic differentiation and population structure. In addition to the previous explanations for the higher diversity of P. vivax, we propose that the contrasting patterns of population structure at least partially reflect differences in the biology of these species. In particular, the ability of P. vivax to develop dormant hypnozoites and cause consecutive relapses is likely to provide more opportunities for the exchange and dissemination of alleles.