A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
A Plasmodium vivax experimental human infection model for evaluating efficacy of interventions
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DOI：
10.1172/jci134923
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发表时间：
2020-06-01
影响因子：
15.9
通讯作者：
McCarthy, James S.
中科院分区：
文献类型：
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作者：
Collins, Katharine A.;Wang, Claire Y. T.;McCarthy, James S.
背景阻断间日疟原虫传播或消灭休眠的间日疟原虫肝脏期寄生虫的干预措施对消灭疟疾至关重要。这些干预措施的发展受到缺乏间日疟原虫体外培养的阻碍，可以通过在疟疾初治个体中建立安全和可重复的临床模型来加速。健康的、未患疟疾的成人入组了2项研究，以评估一种新的间日疟原虫分离株的安全性、传染性和传播性。受试者（研究1，n = 2;研究2，n = 24）接种间日疟原虫感染的红细胞以启动感染，并接受蒿甲醚-本芴醇（研究1）或氯喹（研究2）治疗。主要终点是新分离株的安全性和感染性。在研究2中，还使用蚊子喂养试验评估了蚊子的传播，并使用体外培养的肝细胞评估了子孢子活力。所有参与者均出现寄生虫血症和配子体血症，并通过抗疟治疗清除。不良事件大多为轻度或中度，无严重不良事件。69%的参与者（11/16）在配子体血症高峰期感染按蚊。经配子体富集血膜喂养后，苔藓虫感染率达97%，子孢子在培养中发育为肝期孢子。我们已经证明了间日疟原虫配子体从人类到蚊子的安全，可重复和有效的传播，并建立了一个实验模型，将加速针对间日疟原虫生命周期多个阶段的干预措施的发展。
BACKGROUND. Interventions that interrupt Plasmodium vivax transmission or eliminate dormant P. vivax liver-stage parasites will be essential for malaria elimination. Development of these interventions has been hindered by the lack of P. vivax in vitro culture and could be accelerated by a safe and reproducible clinical model in malaria-naive individuals.METHODS. Healthy, malaria-naive adults were enrolled in 2 studies to assess the safety, infectivity, and transmissibility of a new P. vivax isolate. Participants (Study 1, n = 2; Study 2, n = 24) were inoculated with P. vivax-infected red blood cells to initiate infection, and were treated with artemether-lumefantrine (Study 1) or chloroquine (Study 2). Primary endpoints were safety and infectivity of the new isolate. In Study 2, transmission to mosquitoes was also evaluated using mosquito feeding assays, and sporozoite viability was assessed using in vitro cultured hepatocytes.RESULTS. Parasitemia and gametocytemia developed in all participants and was cleared by antimalarial treatment. Adverse events were mostly mild or moderate and none were serious. Sixty-nine percent of participants (11/16) were infectious to Anopheles mosquitoes at peak gametocytemia. Mosquito infection rates reached 97% following membrane feeding with gametocyte-enriched blood, and sporozoites developed into liver-stage schizonts in culture.CONCLUSION. We have demonstrated the safe, reproducible, and efficient transmission of P. vivax gametocytes from humans to mosquitoes, and have established an experimental model that will accelerate the development of interventions targeting multiple stages of the P. vivax life cycle.