Safety and infectivity of female cercariae in Schistosoma-naïve, healthy participants: a controlled human Schistosoma mansoni infection studyResearch in context
Jan Pieter R. Koopman,
Emma L. Houlder,
Jacqueline J. Janse,
Miriam Casacuberta-Partal,
Olivia A.C. Lamers,
Jeroen C. Sijtsma,
Claudia de Dood,
Stan T. Hilt,
Arifa Ozir-Fazalalikhan,
Vincent P. Kuiper,
Geert V.T. Roozen,
Laura M. de Bes-Roeleveld,
Yvonne C.M. Kruize,
Linda J. Wammes,
Hermelijn H. Smits,
Lisette van Lieshout,
Govert J. van Dam,
Inge M. van Amerongen-Westra,
Pauline Meij,
Paul L.A.M. Corstjens,
Simon P. Jochems,
Angela van Diepen,
Maria Yazdanbakhsh,
Cornelis H. Hokke,
Meta Roestenberg
Affiliations
Jan Pieter R. Koopman
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Emma L. Houlder
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Jacqueline J. Janse
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Miriam Casacuberta-Partal
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Olivia A.C. Lamers
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Jeroen C. Sijtsma
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Claudia de Dood
Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Stan T. Hilt
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
Arifa Ozir-Fazalalikhan
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Vincent P. Kuiper
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Geert V.T. Roozen
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Laura M. de Bes-Roeleveld
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Yvonne C.M. Kruize
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Linda J. Wammes
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Hermelijn H. Smits
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Lisette van Lieshout
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Govert J. van Dam
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Inge M. van Amerongen-Westra
Center for Cell and Gene Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Pauline Meij
Center for Cell and Gene Therapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Paul L.A.M. Corstjens
Department of Cell and Chemical Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Simon P. Jochems
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Angela van Diepen
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Maria Yazdanbakhsh
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Cornelis H. Hokke
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands
Meta Roestenberg
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands; Corresponding author. Leiden University Centre for Infectious Diseases, Leiden University Medical Centre, Building 1, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Summary: 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).
