Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction

Malaria Journal

Research

Sasithon Pukrittayakamee¹  Ghulam Rahim Awab²  Mallika Imwong³  Warunee Hanpithakpong⁴  Charles J. Woodrow⁵  Nicholas P. J. Day⁵  Arjen M. Dondorp⁵  Nicholas J. White⁵  Joel Tarning⁵  Fazel Alim⁶ 

[1] Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Ministry of Public Health, Kabul, Afghanistan;Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK;Ministry of Public Health, Kabul, Afghanistan;

关键词: Malaria;    Falciparum;    Afghanistan;    Artesunate;    Sulphadoxine;    Pyrimethamine;    Dihydrofolate reductase;    Dihydropteroate synthase;    Piperaquine;    Kelch;   

DOI  :  10.1186/s12936-016-1167-z

 received in 2015-08-04, accepted in 2016-02-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCombination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended treatment for Plasmodium falciparum infection in Afghanistan in 2003.MethodsA series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine (AS + SP) against P. falciparum were undertaken in sentinel sites in Afghanistan from 2007 to 2014, accompanied by relevant molecular studies. The first study was a randomized trial of AS + SP versus dihydroartemisinin-piperaquine, while two subsequent studies were standard therapeutic efficacy studies of AS + SP.ResultsThree hundred and three patients were enrolled across four provinces in the north and east of the country. Curative efficacy was high in all the trials, with an adequate clinical and parasitological response (ACPR) of more than 95 % in all groups and trial stages. Genotyping for drug-resistance alleles at dhfr indicated fixation of the S108 N mutation and a prevalence of the C59R mutation of approximately 95 % across all sites. Other mutations in dhfr and dhps remained rare or absent entirely, although five isolates from the first trial carried the dhps triple mutant SGEGA haplotype. In the last study undertaken in 2012–2014 the K13 artemisinin resistance marker was examined; only two of 60 successfully sequenced samples carried a K13-propeller mutation.ConclusionsThese data confirm maintained efficacy 10 years after introduction of artesunate plus SP as combination treatment of P. falciparum in Afghanistan. The molecular data indicate that despite a substantial fall in incidence, resistance has not developed to artemisinins, or intensified to the ACT partner drug components.Trial Registrationhttp://www.clinicaltrials.gov/ct NCT00682578, NCT01115439 and NCT01707199

【 授权许可】

CC BY   
© Awab et al. 2016