Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether–lumefantrine treatment in Mali

Malaria Journal

Research

Mohamed Lamine Alhousseini¹  Amed Ouattara¹  Sekou Sissoko¹  Amadou Bamadio¹  Issaka Sagara¹  Abdoulaye A. Djimde¹  Moussa Djimde¹  Hamidou Niangaly¹  Niawanlou Dara¹  Oumar Bila Traore¹  Ogobara K. Doumbo¹  Hamma Maiga¹  Souleymane Dama¹  Siaka Goita¹  Antoine Dara¹ 

[1] Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali;

关键词: Artemether;    Lumefantrine;    Plasmodium;    Ex vivo;    In vivo;    K13 propeller;   

DOI  :  10.1186/s12936-017-1700-8

 received in 2016-09-08, accepted in 2017-01-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundArtemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. However, recent studies conducted in Mali showed an increased frequency of recurrent parasitaemia following artemether–lumefantrine (AL) treatment.MethodsStudy samples were collected during a large WANECAM study. Ex-vivo Plasmodium falciparum sensitivity to artemether and lumefantrine was assessed using the tritiated hypoxanthine-based assay. The prevalence of molecular markers of anti-malarial drug resistance (pfcrt K76T, pfmdr1 N86Y and K13-propeller) were measured by PCR and/or sequencing.ResultsOverall 61 samples were successfully analysed in ex vivo studies. Mean IC50s increased significantly between baseline and recurrent parasites for both artemether (1.6 nM vs 3.2 nM, p < 0.001) and lumefantrine (1.4 nM vs 3.4 nM, p = 0.004). Wild type Pfmdr1 N86 allele was selected after treatment (71 vs 91%, 112 of 158 vs 95 of 105, p < 0.001) but not the wild type pfcrt K76 variant (23.5 vs 24.8%, 40 of 170 vs 26 of 105, p = 0.9). Three non-synonymous K13-propeller SNPs (A522C, A578S, and G638R) were found with allele frequencies <2%.ConclusionMalian post-AL P. falciparum isolates were less susceptible to artemether and lumefantrine than baseline isolates.

【 授权许可】

CC BY   
© The Author(s) 2017