Dama Souleymane, Niangaly Hamidou, Ouattara Amed, Sagara Issaka, Sissoko Sekou, Traore Oumar Bila, Bamadio Amadou, Dara Niawanlou, Djimde Moussa, Alhousseini Mohamed Lamine, Goita Siaka, Maiga Hamma, Dara Antoine, Doumbo Ogobara K, Djimde Abdoulaye A
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.
Malar J. 2017 Feb 2;16(1):59. doi: 10.1186/s12936-017-1700-8.
Artemisinin-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.
Study 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.
Overall 61 samples were successfully analysed in ex vivo studies. Mean ICs 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%.
Malian post-AL P. falciparum isolates were less susceptible to artemether and lumefantrine than baseline isolates.
基于青蒿素的联合疗法是全球推荐用于治疗非复杂性恶性疟的一线疗法。然而，近期在马里开展的研究显示，采用蒿甲醚-本芴醇（AL）治疗后，疟原虫血症复发的频率有所增加。
研究样本采集自一项大型WANECAM研究。采用基于氚化次黄嘌呤的检测方法评估恶性疟原虫对蒿甲醚和本芴醇的体外敏感性。通过聚合酶链反应（PCR）和/或测序测定抗疟药物耐药性分子标记（pfcrt K76T、pfmdr1 N86Y和K13螺旋桨）的流行情况。
体外研究共成功分析了61个样本。蒿甲醚（1.6纳摩尔对3.2纳摩尔，p<0.001）和本芴醇（1.4纳摩尔对3.4纳摩尔，p = 0.004）的平均半数抑制浓度（IC）在基线期和复发寄生虫之间均显著增加。治疗后野生型Pfmdr1 N86等位基因被选择（71%对91%，158个中的112个对105个中的95个，p<0.001），但野生型pfcrt K76变体未被选择（23.5%对24.
