Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon.
Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon.
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DOI：
10.1016/j.ijid.2023.03.050
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发表时间：
2023-07
影响因子：
8.4
通讯作者：
Mbacham, Wilfred F.
中科院分区：
文献类型：
--
作者：
Niba, Peter Thelma Ngwa;Nji, Akindeh Mbuh;Chedjou, Jean Paul Kengne;Hansson, Helle;Hocke, Emma Filtenborg;Ali, Innocent Mbulli;Achonduh-Atijegbe, Olivia;Evehe, Marie-Solange B.;Jorgensen, Marie Helene Munck;Fomboh, Calvino Tah;Cui, Liwang;Stresman, Gillian;Bigoga, Jude D.;Alifrangis, Michael;Mbacham, Wilfred F.
关键词：
在调整青蒿素类联合疗法之前和之后，对耐药性标志物数据进行了比较。Pfcrt K76 T和Pfmdr 1 N86 Y突变随时间显著下降。Pfdhfr N51 I/C59 R/S108 N和Pfdhps A437 G突变随时间增加。在Pfk 13螺旋桨结构域中未鉴定出经验证的突变。必须持续加强对耐药性标志物的监测。本研究旨在通过比较喀麦隆雅温得采用青蒿素为基础的联合疗法前后恶性疟原虫抗疟药物耐药性标志物的演变。使用巢式聚合酶链反应，随后在Illumina MiSeq平台上进行靶向扩增子深度测序，对2014年和2019-2020年收集的恶性疟原虫阳性样本中已知抗疟药物耐药标志物（Pfcrt、Pfmdr 1、Pfdhfr、Pfdhps和Pfk 13）进行了分子表征。得出的数据进行了比较，在前ACT通过期间，从2004年至2006年公布。在ACT后采用期间观察到Pfmdr 1 184 F、Pfdhfr 51 I/59 R/108 N和Pfdhps 437 G突变等位基因的高患病率。2004年至2020年，Pfcrt 76 T和Pfmdr 1 86 Y突变等位基因显著下降（P <0.0001）。相反，在同一研究期间，对抗叶酸剂的抗性标记物Pfdhfr 51 I/59 R/108 N和Pfdhps 437 G显著增加（P <0.0001）。我们在Pfk 13的螺旋桨结构域中发现了9个突变;尽管它们都存在于单个寄生虫分离株中，但没有一个已知会产生青蒿素耐药性。本研究记录了雅温得对4-氨基喹啉类和芳氨基醇类耐药标志物的敏感寄生虫几乎完全逆转。相反，与乙胺嘧啶耐药相关的Pfdhfr突变正趋于饱和。
Drug resistance markers data were compared before and after the adaption of artemisinin-based combination therapies. The Pfcrt K76T and Pfmdr1 N86Y mutations significantly declined over time. The Pfdhfr N51I/C59R/S108N and Pfdhps A437G mutations increased over time. No validated mutations were identified in the Pfk13 propeller domain. Continuous heightened surveillance of drug resistance markers is necessary. This study aimed to investigate the evolution of Plasmodium falciparum antimalarial drug resistance markers by comparing the pre- and post-adoption of artemisinin-based combination therapies (ACTs) in Yaounde, Cameroon. The molecular characterization of known antimalarial drug resistance markers (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and Pfk13) in P. falciparum-positive samples collected in 2014 and 2019-2020 was achieved using nested polymerase chain reaction, followed by targeted amplicon deep sequencing on the Illumina MiSeq platform. Data derived were compared with those published during the pre-ACT adoption period from 2004 to 2006. A high prevalence of Pfmdr1 184F, Pfdhfr 51I/59R/108N, and Pfdhps 437G mutant alleles was observed during the post-ACT adoption period. The Pfcrt 76T and Pfmdr1 86Y mutant alleles significantly declined between 2004 and 2020 (P <0.0001). Conversely, the resistance markers to antifolates, Pfdhfr 51I/59R/108N and Pfdhps 437G, significantly increased during the same study period (P <0.0001). We identified nine mutations in the propeller domains of Pfk13; although they were all present in single parasite isolates, none of them are known to confer artemisinin resistance. This study documented a near-complete reversion to sensitive parasites for markers conferring resistance to the 4-aminoquinolines and arylamino alcohols in Yaounde. In contrast, the Pfdhfr mutations associated with pyrimethamine resistance are moving toward saturation.
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影响因子：
3
作者：
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通讯作者：
Houze, Sandrine
影响因子：
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3
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3.7
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通讯作者：
Nsango SE