Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania

Malaria Journal

Research

Michael Alifrangis¹  Reginald A Kavishe²  Robert D Kaaya²  Jaffu Chilongola²  Petro Paulo²  Marco van Zwetselaar²  Cally Roper³  Akili Kalinga⁴ 

[1] Department of International Health, Centre for Medical Parasitology, Immunology & Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania;London School of Hygiene and Tropical Medicine, London, UK;National Institute for Medical Research, Tukuyu Centre, Mbeya, Tanzania;

关键词: Plasmodium falciparum;    pfmdr1;    Anti-malarial drug resistance;    Artemether-lumefantrine;    Tanzania;    Polymorphisms;    Malaria;    Molecular markers;   

DOI  :  10.1186/1475-2875-13-264

 received in 2014-04-23, accepted in 2014-07-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundResistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malaria parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania.MethodsA total of 687 Plasmodium falciparum positive dried blood spots on filter paper and rapid diagnostic test strips collected by finger pricks from patients attending health facilities in six regions of Tanzania mainland between June 2010 and August 2011 were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect Pfmdr1 SNPs N86Y, Y184F and D1246Y.ResultsThere were variations in the distribution of Pfmdr1 polymorphisms among regions. Tanga region had exceptionally high prevalence of mutant alleles, while Mbeya had the highest prevalence of wild type alleles. The haplotype YFY was exclusively most prevalent in Tanga (29.6%) whereas the NYD haplotype was the most prevalent in all other regions. Excluding Tanga and Mbeya, four, most common Pfmdr1 haplotypes did not vary between the remaining four regions (χ2 = 2.3, p = 0.512). The NFD haplotype was the second most prevalent haplotype in all regions, ranging from 17% - 26%.ConclusionThis is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution of common Pfmdr1 haplotypes reflecting strict implementation of ALu policy in Tanzania with overall prevalence of NFD haplotype ranging from 17 to 26% among other haplotypes. With continuation of ALu as first-line drug this haplotype is expected to keep rising, thus there is need for continued pharmacovigilance studies to monitor any delayed parasite clearance by the drug.

【 授权许可】

CC BY   
© Kavishe et al.; licensee BioMed Central Ltd. 2014