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非洲的青蒿素耐药性疟疾证据
Evidence of Artemisinin-Resistant Malaria in Africa


Betty Balikagala ... 传染病 • 2021.09.23
相关阅读
• “青蒿素耐药”的应势解决方案

摘要


背景

在组成大湄公河次区域的6个东南亚国家,恶性疟原虫对青蒿素衍生物产生了耐药性,而青蒿素是疟疾一线治疗的主要成分。在包括非洲在内的世界其他地区,恶性疟原虫对青蒿素单药治疗的临床耐药性也将产生问题。

 

方法

在乌干达北部进行的此项纵向研究中,我们对恶性疟原虫感染者进行了青蒿琥酯(水溶性青蒿素衍生物)静脉给药治疗,并估算寄生虫清除半衰期。我们应用环状体阶段生存测定法(ring-stage survival assay)评估了恶性疟原虫的体外敏感性,并对耐药相关基因进行了基因分型。

 

结果

2017—2019年,在接受青蒿琥酯静脉给药的240例患者中,共计14例有体内青蒿素耐药证据(寄生虫清除半衰期,>5小时)。这14例患者中有13例感染了kelch13基因发生A675V或C469Y等位基因突变的恶性疟原虫。这些突变与寄生虫清除半衰期延长相关(几何均值,A675V 3.95小时,C469Y 3.30小时 vs. 野生型等位基因1.78小时;分别为P<0.001和P=0.05)。环状体阶段生存测定表明,携带A675V等位基因的恶性疟原虫的存活率高于携带野生型等位基因的恶性疟原虫。携带kelch13突变的寄生虫流行率显著增加,从2015年的3.9%增加至2019年的19.8%,主要原因是A675V和C469Y等位基因频率增加(分别为P<0.001和P=0.004)。乌干达A675V突变侧翼的单核苷酸多态性与东南亚有显著不同。

 

结论

青蒿素临床耐药性恶性疟原虫在非洲独立出现并在当地传播。两种kelch13突变可能是检测这些耐药寄生虫的标志(由日本学术振兴会[Japan Society for the Promotion of Science]等资助)。





作者信息

Betty Balikagala, M.D., Ph.D., Naoyuki Fukuda, M.D., D.T.M.H., Ph.D., Mie Ikeda, Ph.D., Osbert T. Katuro, B.Sc., Shin-Ichiro Tachibana, Ph.D., Masato Yamauchi, M.P.H., Ph.D., Walter Opio, M.D., Sakurako Emoto, M.D., Denis A. Anywar, M.Sc., Eisaku Kimura, M.D., Ph.D., Nirianne M.Q. Palacpac, Ph.D., Emmanuel I. Odongo-Aginya, Ph.D., Martin Ogwang, M.D., M.M.E.D., Toshihiro Horii, Ph.D., and Toshihiro Mita, M.D., Ph.D.
From the Department of Tropical Medicine and Parasitology, School of Medicine (B.B., N.F., M.I., S.-I.T., M.Y., S.E., T.M.), and the Atopy Research Center, Graduate School of Medicine (B.B.), Juntendo University, Tokyo, the School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki (E.K.), and the Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Osaka (N.M.Q.P., T.H.) — all in Japan; and Mildmay Uganda, Nazibwa Hill, Kampala (O.T.K.), and St. Mary’s Hospital Lacor (W.O., M.O.) and the Faculty of Medicine, Gulu University (D.A.A., E.I.O.-A.), Gulu — all in Uganda. Address reprint requests to Dr. Mita at the Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan, or at tmita@juntendo.ac.jp.

 

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