Experimental Infection of Human Volunteers with Haemophilus ducreyi: 15 Years of Clinical Data and Experience

Abstract

Haemophilus ducreyi causes chancroid, which facilitates transmission of HIV-1. To better understand the biology of H. ducreyi, we developed a human inoculation model. Here, we describe the clinical outcomes of 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and dose. The outcome (pustule formation or resolution) of infected sites within a subject was not independent; the most important determinants of pustule formation were gender and host. When infected a second time, subjects (n = 41) segregated towards their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms, requiring termination from the study after a mean of 8.6 days. Hypertrophic scars developed in 16.2% of volunteers who were biopsied, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.