青蒿素耐药恶性疟原虫kelch13R561H突变株的出现和

本期文章：《自然—医学》：Online/在线发表

法国巴斯德研究所Didier Menard和卢旺达生物医学中心Aline Uwimana小组合作在研究中取得进展。他们研究揭示了对青蒿素耐药的kelch13 R561H恶性疟原虫突变株在卢旺达的出现和体外克隆扩增。相关论文发表在2020年8月3日出版的《自然-医学》杂志上。

研究人员对恶性疟原虫K13（Pfkelch13）螺旋桨结构域进行了基因分型，该突变可导致青蒿素耐药。K13突变株是从卢旺达最近进行的双氢青蒿素-哌喹和蒿甲醚-荧光黄素功效试验中收集的预处理样品中得到的。尽管两个治疗组的治愈率均超过 95％，但在马萨卡的257例患者中有19例（7.4％）出现了Pfkelch13 R561H突变。系统发育分析揭示了当地R561H谱系的扩增。

基因编辑证实该突变可以在体外促进青蒿素耐药。这项研究为卢旺达地区Pfkelch13介导青蒿素耐药株从头出现提供了证据，这有可能是破坏非洲抗疟药物持续功效的原因。

据介绍，青蒿素耐药性（青蒿素联合治疗后，恶性疟原虫清除延迟）在东南亚广泛存在，但迄今为止在非洲尚未出现耐药菌株。

附：英文原文

Title: Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

Author: Aline Uwimana, Eric Legrand, Barbara H. Stokes, Jean-Louis Mangala Ndikumana, Marian Warsame, Noella Umulisa, Daniel Ngamije, Tharcisse Munyaneza, Jean-Baptiste Mazarati, Kaendi Munguti, Pascal Campagne, Alexis Criscuolo, Frdric Ariey, Monique Murindahabi, Pascal Ringwald, David A. Fidock, Aimable Mbituyumuremyi, Didier Menard

Issue&Volume: 2020-08-03

Abstract: Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1,2,3,4. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance5,6, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda7. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.

DOI: 10.1038/s41591-020-1005-2

Source: https://www.nature.com/articles/s41591-020-1005-2

期刊信息

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：30.641
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex