The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi.

Elena Artimovich,Ananias A Escalante,Paul Pensulo,Don Mathanga,Terrie E Taylor,Osward Nyirenda,Shannon Takala-Harrison,Miriam K Laufer,Sarah Brown,Sudhaunshu Joshi,Atupele Kapito-Tembo

doi:10.1186/s12936-015-0860-7

Abstract

BackgroundPersistence of sulfadoxine–pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. Higher malaria transmission is associated with greater genetic diversity and more frequent genetic recombination, which could lead to a more rapid re-emergence of SP-sensitive parasites, as well as more rapid degradation of selective sweeps. In this study, the impact of local variation in malaria transmission on the prevalence of SP-resistant haplotypes and selective sweep characteristics was investigated at an urban site with low parasite prevalence and two rural sites with moderate and high parasite prevalence.MethodsSamples from three sites with different parasite prevalence were genotyped for resistance markers within pfdhfr-ts and pfdhps and at microsatellites flanking these genes. Expected heterozygosity (He) was estimated to evaluate genetic diversity.ResultsNo difference in the prevalence of highly resistant DHFR 51I/59R/108N and DHPS 437G/540E was found between sites. Small differences in He flanking pfdhfr-ts and pfdhps were seen between rural-moderate and the other sites, as well as some shared haplotypes between the rural-high and urban-low sites.ConclusionsThe results do not show an effect of local variation in malaria transmission, as inferred from parasite prevalence, on SP-resistant haplotype prevalence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0860-7) contains supplementary material, which is available to authorized users.

Highlights

Persistence of sulfadoxine–pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low
Parasite prevalence from a community-based, cross-sectional survey was used as a surrogate measure of transmission intensity; 8.4, 14.3 and 29.6 % of individuals surveyed in the urban-low, ruralmoderate and rural-high settings, respectively, were quantita‐ tive polymerase chain reaction (qPCR)-positive for P. falciparum parasites
The analysis focused on sweep characteristics flanking dihydrofolate reductase (DHFR) 51I/59R/108N and dihydropteroate synthase (DHPS) 437G/540E due to limited prevalence of other haplotypes in all three settings

Summary

Introduction

Persistence of sulfadoxine–pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. The return of chloroquine sensitivity was shown, via the analysis of selective sweeps, to be the result of the re-emergence of genetically diverse sensitive parasites that had survived selective pressure [2]. This relatively rapid and nationwide re-emergence of genetically diverse drug-sensitive parasites in Malawi was unexpected, as drug resistance had persisted in South America and Southeast Asia many years after reduction in drug pressure [1, 3, 4]. Selective sweep analysis suggested little to no fitness cost of SP resistance in the urban setting of Ndirande where local transmission intensity is presumed relatively low

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Results

Conclusion