Risk assessment for the implementation of controlled human Schistosoma mansoni infection trials in Uganda

Abstract

Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a “road-map” to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion.

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

“…However, to minimise the risk of co-infections, we shall carefully select and educate possible volunteers, and early abrogation of infection will be used to minimise this risk. On the other hand, importation of the non-native Biomphalaria glabrata snail species used in Leiden will require sound containment processes in the laboratory, since escape into the environment could have important consequences for snail and schistosome ecology [ 43 ].…”

Recent Advances and Methodological Considerations on Vaccine Candidates for Human Schistosomiasis

“…The Sm CHIM model developed in the Netherlands (181) might be an important vaccine assessment tool providing guidance without being a gatekeeper of clinical efficacy trials. Because responses to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, it has been proposed to establish a Sm-CHIM in Uganda where also Sh is endemic (182). A first dose-escalating clinical safety trial in 17 volunteers using male Sm cercariae, which do not produce eggs and therefore do not cause lasting pathology, as a challenge was recently conducted in Leiden, the Netherlands (NCT02755324).…”