Abstract

BackgroundDrug resistance is one of the main reasons of anti-malarial treatment failures and impedes malaria containment strategies. As single nucleotide polymorphisms (SNPs) have been found to correlate with anti-malarial drug resistance, the surveillance strategy includes continuous monitoring of known molecular markers and detection of new mutation patterns. With the introduction of artemisinin-based combination therapy, selection of specific patterns has been observed worldwide.MethodsFrom March to June 2013, whole blood was collected on filter paper from microscopically malaria positive patients in Jimma zone (District), southwestern Ethiopia. Plasmodium falciparum, Plasmodium vivax and mixed infections were included. SNPs were investigated by conventional or real-time PCR, restriction fragment length pattern analysis or sequencing. Results were compared to molecular patterns from Ethiopian isolates in 2004, 2006 and 2008/9.ResultsPlasmodium falciparum, P. vivax, and mixed infections were molecularly confirmed in 177, 80, and 14 samples, respectively. In P. falciparum, mutations in the pfcrt, pfmdr 1and pfATP 6 (SERCA) gene were investigated. Whereas the mutation in the pfcrt gene at codon 76 K was still found in 95.6 % of all samples, the pfmdr 1 86 T mutation fell to 1.2 % (2/163) in 2013 compared to 9 % in 2008/9 and 86 % in 2006 (P <0.001). The pfmdr 1 184 F mutation dominated with 100.0 % (172/172) in 2013. Sequencing of the recently reported PF3D7_1343700 kelch propeller domain showed no mutation at codon 476. First sequencing data of the pvmdr 1 gene from Jimma region revealed a prevalence of the mutations 976 F and 1076 L in 72.7 % (16/23) and 100.0 % (19/19) of the isolates, respectively.ConclusionSince the introduction of artemether-lumefantrine (AL) in Jimma, Ethiopia, in 2006, the prevalence of certain SNPs associated with AL use has increased. Markers for chloroquine resistance in P. vivax were highly frequent. Continuous molecular and clinical surveillance are of paramount importance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0723-2) contains supplementary material, which is available to authorized users.

Highlights

  • Drug resistance is one of the main reasons of anti-malarial treatment failures and impedes malaria containment strategies

  • Plasmodium falciparum and P. vivax single infections as well as mixed infections were included in the study

  • Plasmodium falciparum and P. vivax could be detected by microscopy in 197 (61.2 %) and 98 (30.4 %) samples, respectively

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Summary

Introduction

Drug resistance is one of the main reasons of anti-malarial treatment failures and impedes malaria containment strategies. As single nucleotide polymorphisms (SNPs) have been found to correlate with anti-malarial drug resistance, the surveillance strategy includes continuous monitoring of known molecular markers and detection of new mutation patterns. The rise of drug-resistant parasites threatens to hamper malaria containment strategies. After the introduction of artemisinin-based combination therapy (ACT) in Jimma zone in 2006 [1], a certain shift in the distribution of wild types and mutations of defined single nucleotide polymorphisms (SNPs), associated with anti-malarial drug resistance, was expected. A variety of polymorphisms located in the pfATP 6 gene have been reported [20,21,22,23] Their actual importance concerning artimisinin resistance remains unclear. Its actual function within the parasite organism is unknown and can only be assumed, as homologous proteins in other organism can be found participating in a wide variety of pathways [24,25,26]

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