Dynamics of pfcrt alleles CVMNK and CVIET in chloroquine-treated Sudanese patients infected with Plasmodium falciparum

Malaria Journal

Research

Salah Eldin Elzaki¹  Ebtihal Mukhtar¹  Badria El-Sayed¹  David C Warhurst²  Colin J Sutherland²  Nahla B Gadalla³ 

[1] Department of Epidemiology, Tropical Medicine Research Institute, Khartoum, Sudan;Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK;Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK;Department of Epidemiology, Tropical Medicine Research Institute, Khartoum, Sudan;

关键词: Chloroquine;    Artesunate;    Resistant Parasite;    Early Treatment Failure;    Parasitological Response;   

DOI  :  10.1186/1475-2875-9-74

 received in 2009-09-14, accepted in 2010-03-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundParasite resistance to the anti-malarial drug chloroquine is common in eastern Sudan. Dynamic within-host changes in the relative abundance of both sensitive and resistant Plasmodium falciparum parasites were examined in a cohort of chloroquine-treated patients presenting with uncomplicated falciparum malaria, using a novel allele-specific quantitative approach.MethodsTreatment outcomes were determined for 93 patients of all ages in a per protocol cohort using a modified 14-day WHO protocol. Parasite DNA samples at days 0, 1, 2, 3, 7 and 14 following treatment were analysed using real-time quantitative PCR methods that distinguished resistant and sensitive genotypes at amino acids 72 - 76 of the pfcrt locus.ResultsChloroquine treatment was not efficacious, and of 93 assessable patients, only 10 individuals (10.7%; 95% C.I. 4.34 - 17.2%) enjoyed an adequate clinical and parasitological response. Resistant parasites with the haplotype CVIET at codons 72-76 of the pfcrt locus were dominant in the starting population. Chloroquine sensitive parasites with the haplotype CVMNK were detected in 19 individuals prior to treatment (20.43%; 95% C.I. 5.14 - 18.5%). In these patients, CQ treatment rapidly selected CVIET parasites, and this haplotype overwhelmingly dominated the parasite population in each individual by day 2 after treatment.ConclusionsSuch rapid intra-host selection of particular genotypes after the introduction of drug will cause frequent misidentification of parasite genotypes present in the starting population. This will have a potentially serious confounding effect on clinical trials which employ PCR-corrected estimates of treatment failure, as resistant parasites below the detection threshold in the pre-treatment sample can be erroneously classified as "new" infections during follow-up, over-estimating drug efficacy.

【 授权许可】

Unknown   
© Gadalla et al; licensee BioMed Central Ltd. 2010. 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.