Clinical tolerance but no protective efficacy in a placebo-controlled trial of repeated controlled schistosome infection.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jan Pieter R Koopman, Emma L Houlder, Jacqueline J Janse, Olivia Ac Lamers, Geert Vt Roozen, Jeroen C Sijtsma, Miriam Casacuberta-Partal, Stan T Hilt, M Y Eileen C van der Stoep, Inge M van Amerongen-Westra, Eric At Brienen, Linda J Wammes, Lisette van Lieshout, Govert J van Dam, Paul Lam Corstjens, Angela van Diepen, Maria Yazdanbakhsh, Cornelis H Hokke, Meta Roestenberg
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引用次数: 0

Abstract

BACKGROUNDPartial protective immunity to schistosomiasis develops over time, following repeated praziquantel (PZQ) treatment. Moreover, animals develop protective immunity after repeated immunization with irradiated cercariae. Here, we evaluated the development of natural immunity through consecutive exposure-treatment cycles with Schistosoma mansoni in healthy, Schistosoma-naive participants using single-sex, controlled human S. mansoni infection.METHODSTwenty-four participants were randomized in a double-blinded (1:1) manner to either the reinfection group, which received 3 exposures (weeks 0, 9, and 18) to 20 male cercariae, or to the infection control group, which received 2 mock exposures with water (weeks 0 and 9) prior to cercariae exposure (week 18). Participants were treated with PZQ (or placebo) at weeks 8, 17, and 30. Attack rates (ARs) after the final exposure (weeks 19-30) using serum circulating anodic antigen (CAA) positivity were compared between groups. Adverse events (AEs) were collected for safety.RESULTSTwenty-three participants completed the follow-up. No protective efficacy was observed, given an 82% (9 of 11) AR after the final exposure in the reinfection group and 92% (11 of 12) in the infection control group (protective efficacy 11%; 95% CI -24% to 35%; P = 0.5). Related AEs were higher after the first infection (45%) compared with the second (27%) and third (28%) infections. Severe acute schistosomiasis was observed after the first infections only (2 of 12 in the reinfection group and 2 of 12 in the infection control group).CONCLUSIONRepeated Schistosoma exposure and treatment cycles resulted in apparent clinical tolerance, with fewer symptoms reported following subsequent infections, but did not result in protection against reinfection.TRIAL REGISTRATIONClinicalTrials.gov NCT05085470.FUNDINGEuropean Research Council (ERC) Starting Grant (no. 101075876).

在反复对照血吸虫感染的安慰剂对照试验中,临床耐受性但无保护作用。
背景:在吡喹酮反复治疗后,对血吸虫病的部分保护性免疫随着时间的推移而发展。此外,动物在多次接种辐照尾蚴后会产生保护性免疫。在这里,我们通过健康的Schistosoma-naïve参与者使用单性别控制的人感染曼氏血吸虫(Sm),通过连续暴露-治疗周期来评估自然免疫的发展。方法:24名参与者随机双盲(1:1)分为再感染组(第0、9、18周)和感染对照组(第18周)。再感染组接受3次接触(第0、9周)至20次男性尾蚴,感染对照组在接触尾蚴之前接受2次模拟水接触(第18周)。参与者在第8周、第17周和第30周接受吡喹酮(或安慰剂)治疗。比较各组血清循环阳极抗原(CAA)阳性最终暴露(19-30周)后的发作率。收集不良事件以确保安全性。结果:23名受试者完成随访。再感染组最终暴露后的发病率为82%(9/11),感染对照组为92%(11/12)(保护疗效11%;95% CI -24% ~ 35%;p = 0.5)。与第二次感染(27%)和第三次感染(28%)相比,第一次感染后的相关不良事件(45%)更高。首次感染后仅出现严重急性血吸虫病(2/12为再感染组,2/12为感染对照组)。结论:反复的血吸虫暴露和治疗周期导致明显的临床耐受性,随后感染的症状较少,但没有产生对再次感染的保护。试验注册:Clinicaltrials: gov NCT05085470。资助:ERC启动资助(编号:101075876)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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