Molecular surveillance of drug-resistance associated mutations of Plasmodium falciparum in south-west Tanzania

Mirjam Schönfeld,Thomas Löscher,Mirjam Schunk,Andrew Kitua,Isabel Barreto Miranda,Leonard Maboko,Michael Hoelscher,Ibrahim Maduhu,Nicole Berens-Riha

doi:10.1186/1475-2875-6-2

Abstract

BackgroundIn Tanzania, drug-resistant malaria parasites are an increasing public health concern. Because of widespread chloroquine (CQ) resistance Tanzania changed its first line treatment recommendations for uncomplicated malaria from CQ to sulfadoxine-pyrimethamine (SP) in 2001. Loss of SP sensitivity is progressing rapidly. SP resistance is associated with mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes.MethodsIn samples from 86 patients with uncomplicated Plasmodium falciparum malaria from Mbeya and Matema, Mbeya region, south-western Tanzania, the occurrence of mutations was investigated in the pfcrt and pfmdr1 genes which are associated with CQ resistance and in pfdhfr and pfdhps, conferring SP resistance, as well in cytb which is linked to resistance to atovaquone.ResultsPfcrt T76 occurs in 50% and pfmdr1 Y86 in 51.7%. Pfdhfr triple mutations coexisting with pfdhps double mutations were detected in 64.3% of the P. falciparum isolates. This quintuple mutation is seen as a possible predictive molecular marker for SP treatment failure. Mutations of the cytb gene were not detected.ConclusionThese findings of a high prevalence of mutations conferring SP resistance correspond to data of in vivo SP efficacy studies in other regions of Tanzania and underline the recommendation of changing first-line treatment to artemisinin-based combination therapy.

Highlights

In Tanzania, drug-resistant malaria parasites are an increasing public health concern
A useful alternative is artemisinin-based combination therapy (ACT), e.g., artemether-lumefantrine which is introduced as the new first line drug in Tanzania in mid 2006
The predictive value of these markers for SP treatment failure has not been established in the study regions, these results are in line with the high level of treatment failure (42.3%) in a multi-site survey in Tanzania [26]

Summary

Introduction

In Tanzania, drug-resistant malaria parasites are an increasing public health concern. Because of widespread chloroquine (CQ) resistance Tanzania changed its first line treatment recommendations for uncomplicated malaria from CQ to sulfadoxine-pyrimethamine (SP) in 2001. Over 10 Million malaria cases occurred in Tanzania in 2003, about 30% more compared to the previous year [2] Most of these cases were caused by Plasmodium falciparum. Increasing rates of CQ resistance led Tanzania to change its first line treatment of uncomplicated malaria to sulfadoxine-pyrimethamine (SP) in 2001 [3]. This antifolate combination seemed to be an effective and reasonable alternative, but resistance to SP was rapidly gaining ground, facilitated by the slow elimination from the body.

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