The impact of sequestration on artemisinin-induced parasite clearance in Plasmodium falciparum malaria in Africa.
The impact of sequestration on artemisinin-induced parasite clearance in Plasmodium falciparum malaria in Africa.
复制标题
非洲恶性疟原虫疟疾中封存对青蒿素诱导的寄生虫清除的影响。
DOI：
10.1093/cid/ciac944
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Mita T.
中科院分区：
文献类型：
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作者：
Fukuda N;Balikagala B;Ueno T;Anywar DA;Kimura E;Palacpac NMQ;Odongo-Aginya EI;Ogwang M;Horii T;Miida T;Mita T.
抗青蒿素恶性疟原虫在东南亚和非洲蔓延。通过观察外周寄生虫血症的下降率（寄生虫清除半衰期），研究了对青蒿素的体内敏感性。然而，在估计寄生虫清除率时，不考虑粘附/隔离在内皮上且在外周血中检测不到的寄生虫。在这里，我们评估了在乌干达，青蒿素耐药性正在蔓延的隔离对体内青蒿素疗效的影响。2018年和2019年在乌干达北方进行的青蒿素疗效体内研究中包括了恶性疟疾。从青蒿素单药治疗后的外周血寄生虫血症中估计寄生虫清除半衰期。在治疗前血浆中测定恶性疟原虫富组氨酸蛋白2（PfHRP 2）。根据PfHRP 2浓度和外周血寄生虫血症估计隔离寄生虫数。炎症、血小板减少和血脂异常与隔离显著相关，与外周寄生虫血症无关。感染Pfkelch 13野生型寄生虫的患者（n = 104）的中位寄生虫清除半衰期为1.65小时，A675 V青蒿素耐药突变体患者（n = 18）为3.95小时。在野生型人群的多变量模型中，估计1 000 000/μL隔离寄生虫延迟寄生虫清除16.8%（95%置信区间，5.1%-28.5%），尽管在A675 V人群中尚不清楚。在没有青蒿素抗药性突变的恶性疟疾中，密集隔离会延迟治疗后的寄生虫清除，这可能会导致青蒿素疗效降低。
BackgroundArtemisinin-resistantPlasmodium falciparumis spreading in Southeast Asia and Africa. In vivo susceptibility to artemisinin is studied by looking at the rate of decline of peripheral parasitemia (parasite clearance half-life). However, parasites that are adhered/sequestered to the endothelium and undetectable in the peripheral blood are not considered in the estimation of parasite clearance. Here, we evaluated the influence of sequestration on in vivo artemisinin efficacy in Uganda, where artemisinin resistance is spreading.MethodsWe analyzed 133 patients withP. falciparummalaria included in an in vivo study on artemisinin efficacy in northern Uganda in 2018 and 2019. The parasite clearance half-life was estimated from peripheral parasitemia after artemisinin monotherapy.P. falciparumhistidine-rich protein 2 (PfHRP2) was measured in pretreatment plasma. The number of sequestered parasites was estimated from PfHRP2 concentration and peripheral parasitemia.ResultsThe estimated number of sequestered parasites per plasma volume ranged from 0 to 2 564 000/μL. Inflammation, thrombocytopenia, and dyslipidemia were significantly associated with sequestration independent of peripheral parasitemia. The median parasite clearance half-lives were 1.65 hours in patients infected with Pfkelch13 wild-type parasites (n = 104) and 3.95 hours in those with A675V artemisinin-resistant mutant (n = 18). In the multivariable model for the wild-type population, 1 000 000/μL of sequestered parasites were estimated to delay parasite clearance by 16.8% (95% confidence interval, 5.1%–28.5%), although it was not clear in the A675V population.ConclusionsIn patients withP. falciparummalaria without artemisinin-resistant mutations, intensive sequestration delays parasite clearance after treatment, which may contribute to reduced artemisinin efficacy.