PDF(Pubmed)
Abstract：
Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasite K13 gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGA version 11 software. The data were analysed using STATA version 15, and the Mann‒Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method and pfkelch13 mutations. The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients. P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. The K13 mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearance p = 0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730). There was a high prevalence of day 3 P. falciparum among malaria patients treated using artemether-lumefantrine. We conclude the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.
摘要：
青蒿素耐药性威胁着全球疟疾控制和消除工作。最近的研究报告说，在撒哈拉以南非洲出现了对青蒿素药物耐受的恶性疟原虫寄生虫，包括乌干达。本研究评估了在蒿甲醚-卢美特林（AL）治疗下从无并发症的疟疾患者中分离出的恶性疟原虫寄生虫的第3天寄生虫清除及其与恶性疟原虫K13螺旋桨基因（pfkelch13）突变的相关性。这项研究纳入了100名恶性疟原虫阳性患者，他们在2022年9月9日和2022年11月6日之间服用了AL。在治疗开始前(第0天)和第3天,在EDTA管中收集血样。通过来自血液涂片的显微镜检查和来自提取的DNA的定量聚合酶链反应(qPCR)评估寄生虫血症。使用Sanger测序对第0天寄生虫K13基因进行测序。使用MEGA版本11软件分析序列数据。使用STATA第15版分析数据，并使用Mann-WhitneyU检验，使用比较CT值法和pfkelch13突变比较第3天的PCR寄生虫清除率。来自AL治疗患者的第3天寄生虫血症的患病率通过显微镜检查为24％（24/100），通过qPCR为63％（63/100）。在18.8%(15/80)的第0天DNA样本中检测到恶性疟原虫K13-螺旋桨基因多态性。发现的K13突变是C469Y，12.5%（10/80）；A675V，2.5%（2/80）；A569S，1.25%,（1/80）A578S,1.25%,(1/80)和;F491S,1.25%,（1/80）一个新的等位基因在任何地方都没有报道。C469Y突变,与野生型相比，与延迟寄生虫清除相关p=0.0278，对数尺度上的霍奇斯-莱曼估计3.2108，（95CI1.7076，4.4730）。在使用蒿甲醚-lumefantrine治疗的疟疾患者中，第3天的恶性疟原虫的患病率很高。我们得出结论，在Adjumani区，恶性疟原虫存在与青蒿素抗性相关的K13突变，乌干达，有必要在该国定期监测蒿甲醚-本美特林的有效性和功效。
