Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania

Malaria Journal

Research

Michael Alifrangis¹  Jan B Koenderink²  Reginald A Kavishe³  Arnold Ndaro³  Frank W Mosha³  Dominick F Mosha³  Marco van Zwetselaar³  Asia Mohammed³  Hugh Reyburn⁴  Cally Roper⁵  Jackline F Mosha⁶  Alphaxard Manjurano⁶  Akili Kalinga⁷ 

[1] Centre for Medical Parasitology, Department of International Health, Immunology & Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands;Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania;Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania;London School of Hygiene and Tropical Medicine, London, UK;London School of Hygiene and Tropical Medicine, London, UK;National Institute for Medical Research, Mwanza Centre, Mwanza, Tanzania;National Institute for Medical Research, Tukuyu Centre, Tukuyu, Tanzania;

关键词: Plasmodium falciparum;    Chloroquine;    Pfcrt;    Tanzania;    Drug resistance;    Malaria;    Mutations;    Parasites;    Polymorphisms;   

DOI  :  10.1186/1475-2875-12-415

 received in 2013-08-28, accepted in 2013-11-11,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPlasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ-susceptibility in Malawi, Kenya, Mozambique, and Tanzania based on the prevalence of wild types at codon 76 of the Pfcrt gene in indigenous P. falciparum populations. The current prevalence of this Pfcrt- 76 CQ resistance marker from six regions of Tanzania mainland is hereby reported.MethodsDNA extracted from filter-paper dried blood spots and rapid diagnostics kit strips collected from finger-prick blood were used to genotype the Pfcrt-76 resistance marker using PCR-RFLP. Data from previously published studies were used to generate CQ susceptibility recovery trends using logistic regression model.ResultsSeven hundred and forty one (741) samples were genotyped. The current frequency of the CQ-susceptible Pfcrt-K76 was above 92% and did not differ between regions in Tanzania (χ 2 = 2.37; p = 0.795). The K76 allelic prevalence was between 85.7 and 93% in regions (χ 2 = 7.88, p = 0.163). The CQ resistance recovery trends showed regional variability that may be caused by differences in malaria transmission intensity, but overall the trends converge as the susceptibility levels in all regions approach >90%.ConclusionsCQ withdrawal in Tanzania has resulted into >90% recovery of susceptibility in ten years of withdrawal. These findings are in support of the search for CQ-based combination drugs as a possible future alternative to SP for IPTp in places where full recovery of CQ-susceptibility will be evident.

【 授权许可】

Unknown   
© Mohammed et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.