Abstract

BackgroundThe emergence of drug resistance is a major problem in malaria control. Combination of molecular genotyping and characterization of mutations or single nucleotide polymorphisms (SNPs) correlated with drug resistance can provide information for subsequent surveillance of existing and developing drug resistance patterns. The introduction of artemether/lumefantrine (AL) as first-line treatment, never used before in Ethiopia, allowed the collection of baseline data of molecular polymorphisms before a selection due to AL could occur.Method97 patients with uncomplicated falciparum malaria were recruited from April to June 2006 and treated with either AL, quinine (Q) or atovaquone/proguanil (AP) in Jimma University Hospital, Ethiopia. Mutations or SNPs associated with resistance to these drugs were analysed by RFLP (pfdhfr, pfmdr1) and sequencing of the target genes (pfcytb, pfserca ).ResultsSNPs previously reported to be associated with resistance to the study drugs were identified in recrudescent and treatment sensitive isolates. A total of seven recrudescences were obtained. The pfmdr1 N86Y mutation was found in 84.5% of isolates. The triple mutation 51I,59R,108N of the pfdhfr gene occured in high frequency (83.3%) but no pfcytb mutation was detected. Sequencing showed a variety of previously described and new mutations in the pfserca gene.ConclusionThe prevalence of mutations was in accordance with the expected patterns considering recent drug regimens. The broad introduction of AL and the cessation of former drug regimens might probably change the current distribution of polymorphisms, possibly leading to decreased sensitivity to AL in future. Continuous surveillance of molecular patterns in this region is, therefore, recommended.

Highlights

  • The emergence of drug resistance is a major problem in malaria control

  • Malaria is endemic in large parts of Ethiopia including the town of Jimma and its surroundings with most cases occurring from September to December and April to June during and after the rainy seasons [1]

  • Until day 28, three patients in the Q group and two in the AP group presented with polymerase chain reaction (PCR)-confirmed recrudescent falciparum malaria

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Summary

Introduction

The emergence of drug resistance is a major problem in malaria control. Combination of molecular genotyping and characterization of mutations or single nucleotide polymorphisms (SNPs) correlated with drug resistance can provide information for subsequent surveillance of existing and developing drug resistance patterns. The introduction of artemether/lumefantrine (AL) as first-line treatment, never used before in Ethiopia, allowed the collection of baseline data of molecular polymorphisms before a selection due to AL could occur. Malaria is endemic in large parts of Ethiopia including the town of Jimma and its surroundings with most cases occurring from September to December and April to June during and after the rainy seasons [1]. High levels of drug resistance of Plasmodium falciparum strains against anti-malarials, first chloroquine and later sulphadoxine/pyrimethamine (SP), resulted in new drug artemisinin [5,6,7,8]. Increased sensitivity to (Dihydro-) Artemisinin in the presence of wild type codon 86 in pfmdr and in vivo selection of pfmdr 86N during AL treatment has been reported [9,10,11,12]. Recent reports about high in vivo tolerance of artemisinin-based combination therapy (ACT) and artesunate monotherapy in Cambodia and Thailand are all the more alarming [18,19,20]

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