Experimental infection of human volunteers with Haemophilus ducreyi: fifteen years of clinical data and experience.
Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology of H. ducreyi, we developed a human inoculation model. In the present article, we describe clinical outcomes for 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and estimated delivered dose. The outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the most important determinants of pustule formation were sex and host effects. When 41 subjects were infected a second time, their outcomes segregated toward their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms that required withdrawal from the study after a mean of 8.6 days. There were 191 volunteers who had tissue biopsy performed, 173 of whom were available for follow-up analysis; 28 (16.2%) of these developed hypertrophic scars, 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.
Janowicz
Diane M
DM
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA. dmjanowi@iupui.edu
Ofner
Susan
S
Katz
Barry P
BP
Spinola
Stanley M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D002602:Chancroid / Q000235:genetics / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D005260:Female; D006191:Haemophilus ducreyi / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012872:Skin Diseases, Vesiculobullous / Q000473:pathology; D055815:Young Adult