Safety and infectivity of female cercariae in Schistosoma-naïve, healthy participants: a controlled human Schistosoma mansoni infection study.

Autor:	Koopman JPR; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Houlder EL; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Janse JJ; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Casacuberta-Partal M; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Lamers OAC; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Sijtsma JC; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., de Dood C; Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Hilt ST; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands; Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Ozir-Fazalalikhan A; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Kuiper VP; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Roozen GVT; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., de Bes-Roeleveld LM; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Kruize YCM; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Wammes LJ; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Smits HH; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., van Lieshout L; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., van Dam GJ; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., van Amerongen-Westra IM; Center for Cell and Gene Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Meij P; Center for Cell and Gene Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Corstjens PLAM; Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Jochems SP; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., van Diepen A; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Yazdanbakhsh M; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Hokke CH; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Roestenberg M; Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands. Electronic address: M.Roestenberg@lumc.nl.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2023 Nov; Vol. 97, pp. 104832. Date of Electronic Publication: 2023 Oct 12.
DOI:	10.1016/j.ebiom.2023.104832
Abstrakt:	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. Findings: 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. Interpretation: 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. Funding: European Union's Horizon 2020 (grant no. 81564). Competing Interests: Declaration of interests Authors declare that they have no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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