A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion after Repeated Controlled Human Hookworm Infection

Marie Astrid Hoogerwerf, Jan Pieter R. Koopman, Jacqueline J. Janse, Marijke C.C. Langenberg, Roos Van Schuijlenburg, Yvonne C.M. Kruize, Eric A.T. Brienen, Mikhael D. Manurung, Petra Verbeek-Menken, Martha T. Van Der Beek, Inge M. Westra, Pauline Meij, Leo G. Visser, Lisette Van Lieshout, Sake J. De Vlas, Maria Yazdanbakhsh, Luc E. Coffeng, Meta Roestenberg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
83 Downloads (Pure)

Abstract

Background: Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability, and egg output of repeated exposure to hookworm larvae. Methods: Twenty-four healthy volunteers were randomized, double-blindly, to 1, 2, or 3 doses of 50 Necator americanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20. Results: There was no association between larval dose and number or severity of adverse events. Geometric mean egg loads stabilized at 697, 1668, and 1914 eggs per gram feces for the 1 × 50L3, 2 × 50L3, and 3 × 50L3 group, respectively. Bayesian statistical modeling showed that egg count variability relative to the mean was reduced with a second infectious dose; however, the third dose did not increase egg load or decrease variability. We therefore suggest 2 × 50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes the power of hypothetical vaccine trials. Conclusions: Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events.

Original languageEnglish
Pages (from-to)905-913
Number of pages9
JournalJournal of Infectious Diseases
Volume223
Issue number5
Early online date10 Jul 2020
DOIs
Publication statusPublished - 1 Mar 2021

Bibliographical note

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

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