Genetic micro-epidemiology of malaria in Papua Indonesia: Extensive P. vivax diversity and a distinct subpopulation of asymptomatic P. falciparum infections.

Zuleima Pava,Rintis Noviyanti,Farah Coutrier,Jeanne R Poespoprodjo,Irene Handayuni,Leily Trianty,Enny Kenangalem,Sarah Auburn,Ric N Price,Retno A S Utami,Hidayat Trimarsanto,Jutta Marfurt,Faustina H Burdam,Yusrifar K Tirta,Photini Sinnis

doi:10.1371/journal.pone.0177445

Abstract

BackgroundGenetic analyses of Plasmodium have potential to inform on transmission dynamics, but few studies have evaluated this on a local spatial scale. We used microsatellite genotyping to characterise the micro-epidemiology of P. vivax and P. falciparum diversity to inform malaria control strategies in Timika, Papua Indonesia.MethodsGenotyping was undertaken on 713 sympatric P. falciparum and P. vivax isolates from a cross-sectional household survey and clinical studies conducted in Timika. Standard population genetic measures were applied, and the data was compared to published data from Kalimantan, Bangka, Sumba and West Timor.ResultsHigher diversity (HE = 0.847 vs 0.625; p = 0.017) and polyclonality (46.2% vs 16.5%, p<0.001) were observed in P. vivax versus P. falciparum. Distinct P. falciparum substructure was observed, with two subpopulations, K1 and K2. K1 was comprised solely of asymptomatic infections and displayed greater relatedness to isolates from Sumba than to K2, possibly reflecting imported infections.ConclusionsThe results demonstrate the greater refractoriness of P. vivax versus P. falciparum to control measures, and risk of distinct parasite subpopulations persisting in the community undetected by passive surveillance. These findings highlight the need for complimentary new surveillance strategies to identify transmission patterns that cannot be detected with traditional malariometric methods.

Highlights

Indonesia has one of the highest burdens of malaria in Southeast Asia
Genotyping was undertaken on 713 sympatric P. falciparum and P. vivax isolates from a cross-sectional household survey and clinical studies conducted in Timika
The results demonstrate the greater refractoriness of P. vivax versus P. falciparum to control measures, and risk of distinct parasite subpopulations persisting in the community undetected by passive surveillance

Summary

Introduction

Indonesia has one of the highest burdens of malaria in Southeast Asia. Despite recent progress in reducing case incidence, more than a quarter of a million clinical cases were reported in 2013 with 230 million people at risk of infection [1]. All five species of Plasmodium that commonly infect humans are present in Indonesia [2]. Differences in the respective transmission of these species confound prioritization of malaria control activities. P. falciparum has historically been the predominant species, in recent years the proportion of P. vivax cases has risen [3]. This trend is especially concerning due to the occurrence of high-grade multidrug-resistance in the historically neglected P. vivax species, in Papua Province [4, 5]. We used microsatellite genotyping to characterise the micro-epidemiology of P. vivax and P. falciparum diversity to inform malaria control strategies in Timika, Papua Indonesia

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