%0 Journal Article
%T Safety and infectivity of female cercariae in Schistosoma-naïve, healthy participants: a controlled human Schistosoma mansoni infection study.
%A Koopman JPR
%A Houlder EL
%A Janse JJ
%A Casacuberta-Partal M
%A Lamers OAC
%A Sijtsma JC
%A de Dood C
%A Hilt ST
%A Ozir-Fazalalikhan A
%A Kuiper VP
%A Roozen GVT
%A de Bes-Roeleveld LM
%A Kruize YCM
%A Wammes LJ
%A Smits HH
%A van Lieshout L
%A van Dam GJ
%A van Amerongen-Westra IM
%A Meij P
%A Corstjens PLAM
%A Jochems SP
%A van Diepen A
%A Yazdanbakhsh M
%A Hokke CH
%A Roestenberg M
%J EBioMedicine
%V 97
%N 0
%D 2023 Nov 12
%M 37837930
%F 11.205
%R 10.1016/j.ebiom.2023.104832
%X BACKGROUND: A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S model using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences in antigenic profile and human immune responses to schistosomes of different sex, we pioneered a single-sex female-only CHI-S model for future use in vaccine development.
METHODS: We exposed 13 healthy, Schistosoma-naïve adult participants to 10 (n = 3) or 20 (n = 10) female cercariae and followed for 20 weeks, receiving treatment with praziquantel (PZQ) 60 mg/kg at week 8 and 12 after exposure.
RESULTS: The majority (11/13) participants reported rash and/or itch at the site of exposure, 5/13 had transient symptoms of acute schistosomiasis. Exposure to 20 cercariae led to detectable infection, defined as serum circulating anodic antigen levels >1.0 pg/mL, in 6/10 participants. Despite two rounds of PZQ treatment, 4/13 participants showed signs of persistent infection. Additional one- or three-day PZQ treatment (1 × 60 mg/kg and 3 × 60 mg/kg) or artemether did not result in cure, but over time three participants self-cured. Antibody, cellular, and cytokine responses peaked at week 4 post infection, with a mixed Th1, Th2, and regulatory profile. Cellular responses were (most) discriminative for symptoms.
CONCLUSIONS: Female-only infections exhibit similar clinical and immunological profiles as male-only infections but are more resistant to PZQ treatment. This limits future use of this model and may have important implications for disease control programs.
BACKGROUND: European Union's Horizon 2020 (grant no. 81564).