Building bridges: a multidisciplinary approach to controlled human hookworm infection

Hoogerwerf, M. (2024)

Doctoral Thesis

This thesis described the further development of the controlled human hookworm model and several applications of this model. First, the hookworm egg excretion is modelled over time using Bayesian statistics, resulting in the description of a plateau phase in egg output. Repeated infections a re then investigated as a means to improve the accuracy and statistical power of this output as an outcome measure. The hereby established model is then applied in an immunization study, which shows that it is possible to develop a protective response against short-term larval infection. The skin phase and IgG1 seem to play a role in the development of this protection. Furthermore, gut microbiome changes during controlled hookworm infection are described. Also, volunteers’ motivations and decision making process are investigated, resulting in the characterization of controlled human infection participants as ‘deliberate decision-makers’ and not ‘money-oriented risk-takers’. Following up on the findings in the study described, the importance of a multidisciplinary approach for the improvement of controlled human infection trials is argued in the discussion, with several recommendations made for further collaborative efforts in order to maximise social and scientific output of these studies.

• Hookworm
• Controlled human infection models
• Research ethics
• Vaccine development
• Bayesian statistics
• Microbiome

• All authors: Hoogerwerf, M.
• Supervisor: Roestenberg, M.; Vries, M.C. de
• Committee: Kuijper, E.J.; Loukas, A.; Bogaert, D.; Lieshout, E.A. van: Graaf, R. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2024-06-05
• ISBN (print): 9789464837865