Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.
Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.
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DOI：
10.1093/immadv/ltad010
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发表时间：
2023
影响因子：
--
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中科院分区：
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血吸虫病的控制依赖于单一药物吡喹酮，其治愈率参差不齐，再感染率高，且存在耐药风险。疫苗可以改变血吸虫病的控制。临床前数据表明疫苗研发是可能的，但常规疫苗功效试验需要高发生率、长期随访和大样本量。受控人类感染研究 (CHI) 可以提供早期疗效数据，从而可以选择最佳候选药物进行进一步试验。荷兰已经建立了血吸虫 CHI，但流行国家的目标人群对感染和疫苗的反应有所不同。我们的目标是为乌干达曼氏血吸虫开发 CHI，以在流行环境中测试候选疫苗。这是一项在两个人群中进行的开放标签剂量递增试验：既往有极少或强烈的血吸虫暴露。在每个人群中，参与者将被纳入连续剂量递增组。最初，三名志愿者将接触 10 条尾蚴。如果所有人都出现感染，那么另外七个人将受到相同剂量的暴露。如果没有，后续组中的三名志愿者将按照相同的算法暴露于更高剂量（20或30尾蚴），直到所有接受特定剂量的10名志愿者都被感染，此时该人群的研究将停止。感染后每周都会对志愿者进行随访，直至 CAA 呈阳性或 12 周。一旦呈阳性，他们将接受吡喹酮治疗并随访一年。试验注册号为ISRCTN14033813，并已获得所有批准。试验将受到监控、检查和/或审计。
Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.
暴露史对曼氏血吸虫免疫学和耐药性发展的影响。
影响因子：
3.8
作者：
Black CL;Mwinzi PN;Muok EM;Abudho B;Fitzsimmons CM;Dunne DW;Karanja DM;Secor WE;Colley DG
通讯作者：
Colley DG