Artemisinin pressure in field isolates can select highly resistant Plasmodium falciparum parasites with unconventional phenotype and no K13 mutation.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Antimicrobial Agents and Chemotherapy Pub Date : 2025-03-05 Epub Date: 2025-02-04 DOI:10.1128/aac.01541-24
Lucie Paloque, Luana Mathieu, Marion Laurent, Romain Coppée, Stéphanie Blandin, Pascal Campagne, Jean-Michel Augereau, Lise Musset, Françoise Benoit-Vical
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Abstract

Artemisinin resistance, which poses a serious threat to malaria control efforts, is monitored in the field by delayed parasite clearance in patients, elevated parasite survival rate in the ring-stage survival assay, and mutations in the Plasmodium falciparum kelch13 gene. However, sporadic cases of artemisinin-resistant malaria do not meet all of these criteria, highlighting that our understanding of artemisinin resistance is still incomplete. Here, we selected for artemisinin resistance in vitro in nine P. falciparum field isolates from Africa, Asia, and South America. Artemisinin pressure selected highly resistant parasites in all lineages, but only one acquired a validated pfkelch13 mutation. Phenotypic tests evidenced an unconventional response of selected parasites that can be artemisinin-resistant only at an advanced ring age, making them undetectable by the standard "0-3 h" test used to monitor resistance. These results highlight the need for broader approaches to artemisinin resistance monitoring.

青蒿素耐药性对疟疾控制工作构成严重威胁,通过患者体内寄生虫清除延迟、环期生存试验中寄生虫存活率升高以及恶性疟原虫kelch13基因突变等方式在现场监测。然而,散发的青蒿素耐药疟疾病例并不符合所有这些标准,这突出表明我们对青蒿素耐药的了解仍然不完整。在这里,我们选择了来自非洲、亚洲和南美洲的9株恶性疟原虫野外分离株的体外青蒿素耐药性。青蒿素压力在所有谱系中选择了高度耐药的寄生虫,但只有一种获得了有效的pfkelch13突变。表型试验证明了某些寄生虫的一种非常规反应,这些寄生虫只有在高龄时才具有青蒿素耐药性,这使得用于监测耐药性的标准“0-3小时”试验无法检测到它们。这些结果突出表明需要更广泛的方法来监测青蒿素耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
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