Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: protocol for safety and dose-finding trial.

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2023-07-20 eCollection Date: 2023-01-01 DOI:10.1093/immadv/ltad010
Andrew Abaasa, Moses Egesa, Emmanuella Driciru, Jan Pieter R Koopman, Ronald Kiyemba, Richard E Sanya, Jacent Nassuuna, Agnes Ssali, Geofrey Kimbugwe, Anne Wajja, Govert J van Dam, Paul L A M Corstjens, Stephen Cose, Janet Seeley, Dorcas Kamuya, Emily L Webb, Maria Yazdanbakhsh, Pontiano Kaleebu, Afzal A Siddiqui, Narcis Kabatereine, Edridah Tukahebwa, Meta Roestenberg, Alison M Elliott
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Abstract

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.

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为乌干达建立单性别对照人类曼氏血吸虫感染模型:安全性和剂量摸底试验方案。
血吸虫病的控制依赖于一种单一的药物--吡喹酮,其治愈率参差不齐,再感染率高,且有产生耐药性的风险。疫苗可以改变血吸虫病的控制。临床前数据显示,疫苗开发是可能的,但传统的疫苗疗效试验需要高发病率、长期跟踪和大样本量。控制性人体感染研究(CHI)可提供早期疗效数据,从而为进一步试验选择最佳候选者。荷兰已经建立了血吸虫对照人类感染研究(CHI),但流行国家的目标人群对感染和疫苗的反应各不相同。我们的目标是在乌干达开展曼氏血吸虫CHI,以便在地方病流行的环境中测试候选疫苗。这是一项开放标签、剂量递增试验,针对两种人群:极少或大量接触过血吸虫的人群。在每种人群中,参与者将按顺序加入剂量递增组。最初,三名志愿者将接触 10 个carcariae。如果全部出现感染,则再让七名志愿者接触相同剂量的恙虫。如果没有感染,后续组中的三名志愿者将按照同样的算法接触更高的剂量(20 或 30 个carcariae),直到接受特定剂量的 10 名志愿者全部感染为止,届时将停止该组的研究。感染后将每周对志愿者进行随访,直至 CAA 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。试验登记号为 ISRCTN14033813,并已获得所有批准。该试验将接受监督、检查和/或审计。
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