Emergence of lumefantrine resistance in Laos

Artemisinin-based combination therapies (ACTs) have played a crucial role in decreasing the impact of malaria worldwide. Since 2005, artemether-lumefantrine (AL) has been the main first-line treatment for uncomplicated Plasmodium falciparum malaria in Laos. We aimed to study the efficacy of AL in the context of malaria elimination in Laos. One isolate was confirmed as a true recrudescence and exhibited a LM IC50 of 59.94 nM, which was 2.5 times higher than the median IC50 of 22.3 nM observed in other Laos isolates. The same isolate was also resistant to DHA in vitro by showing the highest RSA survival rate (35.84%) associated with pfkelch13 mutation (R539T), as well as a microscopy positive parasitemia on day 3.

青蒿素联合疗法（Artemisinin-based combination therapies, ACTs）在全球范围内对降低疟疾的疾病负担起到了至关重要的作用。自2005年起，蒿甲醚-苯芴醇（artemether-lumefantrine, AL）一直是老挝治疗无并发症恶性疟原虫疟疾的一线首选方案。本研究旨在探讨老挝疟疾消除背景下AL的临床疗效。研究中1株疟原虫分离株被证实为真性复燃，其晚裂殖体成熟试验半数抑制浓度（LM IC50）为59.94 nM，较老挝其他分离株测得的中位IC50（22.3 nM）高出2.5倍。该分离株同时在体外对双氢青蒿素（DHA）表现出耐药性：其环状体存活试验（RSA）存活率达35.84%，且携带pfkelch13基因R539T突变（pfkelch13 mutation (R539T)），同时在治疗第3天显微镜镜检仍可检出阳性虫血症。