BACKGROUND Partial protective immunity to schistosomiasis develops over time, following repeated praziquantel treatment. Moreover, animals develop protective immunity after repeated immunisation with irradiated cercariae. Here, we evaluated development of natural immunity through consecutive exposure-treatment cycles with Schistosoma mansoni (Sm) in healthy, Schistosoma-naïve participants using single-sex controlled human Sm infection. METHODS Twenty-four participants were randomised double-blind (1:1) to either the reinfection group, which received three exposures (week 0,9,18) to 20 male cercariae or the infection control group, which received two mock exposures with water (week 0,9) prior to cercariae exposure (week 18). Participants were treated with praziquantel (or placebo) at week 8, 17 and 30. Attack rates after the final exposure (week 19-30) using serum circulating anodic antigen (CAA) positivity were compared between groups. Adverse events were collected for safety. RESULTS Twenty-three participants completed follow-up. No protective efficacy was seen, given 82% (9/11) attack rate after the final exposure in the reinfection group and 92% (11/12) in the infection control group (protective efficacy 11%; 95% CI -24% to 35%; p =0.5). Related adverse events were higher after the first infection (45%), compared to the second (27%) and third infection (28%). Severe acute schistosomiasis was observed after the first infections only (2/12 in reinfection group and 2/12 in infection control group). CONCLUSION Repeated Schistosoma exposure and treatment cycles resulted in apparent clinical tolerance, with fewer symptoms reported with subsequent infections, but did not result in protection against reinfection. TRIAL REGISTRATION CLINICALTRIALS gov NCT05085470. FUNDING ERC Starting grant (no. 101075876).

中文翻译：

---

临床耐受性，但在重复受控血吸虫感染的安慰剂对照试验中没有保护作用。


背景 在反复吡喹酮治疗后，对血吸虫病的部分保护性免疫会随着时间的推移而发展。此外，动物在用辐照尾蚴反复免疫后产生保护性免疫。在这里，我们评估了使用单一性别对照人类 Sm 感染的健康、未接受过血吸虫的参与者通过曼氏血吸虫 （Sm） 的连续暴露治疗周期自然免疫的发展。方法 24 名参与者被随机分为双盲 （1：1） 再感染组，再感染组接受 3 次暴露（第 0、9、18 周）至 20 只雄性尾蚴，或感染对照组接受两次模拟水暴露（第 0、9 周）在尾蚴暴露前（第 18 周）。参与者在第 8 、 17 和 30 周接受吡喹酮（或安慰剂）治疗。使用血清循环阳极抗原 （CAA） 阳性比较最后一次暴露后 （第 19-30 周） 的组间发作率。为了安全起见，收集了不良事件。结果 23 名参与者完成了随访。鉴于再感染组最后一次暴露后 82% （9/11） 的发作率和 92% （11/12） 感染对照组的发作率 （保护效力 11%;95% CI -24% 至 35%;p =0.5），未见保护效果。与第二次感染 （45%） 和第三次感染 （28%） 相比，第一次感染后相关不良事件 （27%） 更高。仅在首次感染后观察到重症急性血吸虫病 （再感染组 2/12 和感染对照组 2/12）。结论 反复血吸虫暴露和治疗周期导致明显的临床耐受性，后续感染报告的症状较少，但并未导致对再感染的保护。试验注册 临床试验 政府 NCT05085470. 资助 ERC 起始赠款（编号 101075876）。