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

Abstract

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).