Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration

Malaria Journal

Research

Krongkan Srimuang¹  Mallika Imwong²  Pharath Lim³  Rick M. Fairhurst³  Charles J. Woodrow⁴  Olivo Miotto⁵  Dominic P. Kwiatkowski⁶ 

[1] Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand;Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 20852, Rockville, MD, USA;Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand;Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK;Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand;Wellcome Trust Sanger Institute, Hinxton, UK;Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK;Wellcome Trust Sanger Institute, Hinxton, UK;Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK;

关键词: Malaria;    Plasmodium falciparum;    Anti-malarial resistance;    Chloroquine;    Amodiaquine;    Mefloquine;    Artemisinin;    Combination therapy;    pfcrt;    pfmdr1;   

DOI  :  10.1186/s12936-016-1598-6

 received in 2016-08-06, accepted in 2016-10-31,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDeclining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials.MethodsThe markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011–2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods.ResultsPfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand–Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30–40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam.ConclusionsThese findings generate cause for concern regarding the mid-term efficacy of artemether–lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA.

【 授权许可】

CC BY   
© The Author(s) 2016