Presence of Plasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya.

IF 3.6 Q1 TROPICAL MEDICINE Tropical Medicine and Health Pub Date : 2024-10-18 DOI:10.1186/s41182-024-00640-1
Mark Makau, Bernard N Kanoi, Calvin Mgawe, Michael Maina, Mimie Bitshi, Edwin K Too, Taeko K Naruse, Hussein M Abkallo, Harrison Waweru, Ferdinand Adung'o, Osamu Kaneko, Jesse Gitaka
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Abstract

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.

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肯尼亚西部布西亚县存在耐青蒿素 K13 突变 C469Y 的恶性疟原虫菌株。
疟疾仍然是一个主要的健康和经济问题,尤其是在撒哈拉以南非洲地区。青蒿素抗药性(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。这是因为在撒哈拉以南非洲的大多数疟疾流行地区,青蒿素类复方疗法(ACTs)仍然是第一线治疗方法。恶性疟原虫凯氏 13 蛋白(K13)螺旋桨结构域中的某些单核苷酸多态性与体内和体外寄生虫清除延迟有关。这些突变是追踪抗药性出现和扩散的重要分子标记。最近,有关恶性疟原虫抗逆转录病毒寄生虫在东非地区出现和扩散的报道越来越多。因此有必要继续进行监测,以便为缓解工作提供最佳信息。本研究调查了已知疟疾流行地区肯尼亚布西亚县寄生虫群体中 K13 螺旋桨结构域所有已报道突变的存在情况。这项研究招募了 226 名经显微镜确诊为无并发症疟疾的患者。他们在观察下接受了第一剂蒿甲醚-本芴醇治疗,并在确保参与者服用第二剂和第三剂后,于一天后再次进行显微镜检查。所有样本中的恶性疟原虫 DNA 都使用半嵌套 PCR 方法进行了 K13 基因的定向扩增,然后进行了 Sanger 测序。在三个样本中发现了最近验证的 ART-R K13 突变 C469Y。这三个样本是第 1 天寄生虫血症下降率较低的 63 个样本中的一个,这表明第 1 天寄生虫血症下降率是一个有用的参数,可用于进一步分析 ART-R 寄生虫。我们的研究结果突出表明,有必要在肯尼亚西部和该地区对 ART-R 进行持续监测,以确定 ART-R 的传播情况并为遏制提供信息。
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来源期刊
Tropical Medicine and Health
Tropical Medicine and Health TROPICAL MEDICINE-
CiteScore
7.00
自引率
2.20%
发文量
90
审稿时长
11 weeks
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