Makau Mark, Kanoi Bernard N, Mgawe Calvin, Maina Michael, Bitshi Mimie, Too Edwin K, Naruse Taeko K, Abkallo Hussein M, Waweru Harrison, Adung'o Ferdinand, Kaneko Osamu, Gitaka Jesse
Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, Kenya.
Centre for Research in Infectious Diseases, Directorate of Research and Innovation, Mount Kenya University, Thika, Kenya.
Trop Med Health. 2024 Oct 18;52(1):72. doi: 10.1186/s41182-024-00640-1.
Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether-lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.
疟疾仍然是一个关键的健康和经济问题,尤其是在撒哈拉以南非洲地区。青蒿素耐药性(ART-R)寄生虫菌株的出现对控制和消除这一祸害构成了严重威胁。这是因为以青蒿素为基础的联合疗法(ACTs)仍然是撒哈拉以南非洲大多数疟疾流行地区的一线治疗方法。恶性疟原虫 Kelch 13 蛋白(K13)螺旋桨结构域中的某些单核苷酸多态性与体内外寄生虫清除延迟有关。这些突变是追踪耐药性出现和传播的重要分子标记。最近,有越来越多的报道称,恶性疟原虫 ART-R 寄生虫在东非地区出现并传播。这就需要持续监测,以便为缓解措施提供最佳信息。本研究调查了肯尼亚布西亚县(一个已知的疟疾流行地区)寄生虫种群中 K13 螺旋桨结构域所有已报道突变的存在情况。本研究招募了 226 名经显微镜确诊为非复杂性疟疾的参与者。他们接受了蒿甲醚-本芴醇治疗,首剂在观察下服用,在确保参与者服用了第二剂和第三剂后,1 天后再次进行显微镜检查。使用半巢式 PCR 方法对所有样本的恶性疟原虫 DNA 进行 K13 基因的靶向扩增,随后进行桑格测序。在三个样本中鉴定出最近验证的 ART-R K13 突变 C469Y。这三个样本是第 1 天寄生虫血症降低率较低的 63 个样本中的一部分,这表明第 1 天寄生虫血症降低率是富集 ART-R 寄生虫以进行进一步分析的有用参数。我们的研究结果强调了对肯尼亚西部和该地区 ART-R 进行持续监测的必要性,以确定 ART-R 的传播情况并为遏制措施提供信息。