Experimental Human Infection with Haemophilus ducreyi

Abstract

Four subjects were experimentally infected with Haemophilus ducreyi. Lesions developed only at sites where live bacteria were inoculated on abraded skin. No subject developed fever, lymphadenopathy, or disseminated infection during a 3-day observation period. Two subjects who were rechallenged 2 months after initial infection also developed lesions. The amount of H. ducreyi recovered from 10 of 12 biopsies that were semiquantitatively cultured varied widely. Similar histologic features were present in initial and second infections. The epidermis contained pustules; the dermis contained an infiltrate of T cells and macrophages and reactive endothelial cells. Keratinocytes and T cells expressed HLA-DR, consistent with a delayed-type hypersensitivity response. The subjects did not mount humoral responses to bacterial proteins and to lipooligosaccharides after primary and secondary challenges. Thus, human experimental infection with H. ducreyi is well tolerated and safe. Recruitment of T cells and macrophages into chancroid lesions may partially explain the association between chancroid and human immunodeficiency virus transmission.

Haemophilus ducreyi-Induced Interleukin-10 Promotes a Mixed M1 and M2 Activation Program in Human Macrophages

“…To study the immunopathogenesis of H. ducreyi infection, we developed a human challenge model in which the skin of the upper arm of healthy adult volunteers is inoculated with H. ducreyi strain 35000HP or its derivatives (21,46,47). Papules form within 24 h of inoculation and either spontaneously resolve or evolve into pustules within 2 to 5 days, mimicking the early stages of natural infection.…”

Evaluation of an Isogenic Major Outer Membrane Protein-Deficient Mutant in the Human Model of Haemophilus ducreyi Infection

“…In an effort to understand the early events of H. ducreyi pathogenesis, our laboratory developed a human challenge model of H. ducreyi infection (32). Human volunteers are inoculated on the skin of the upper arm via puncture wounds made by an allergy-testing device.…”

Characterization of lipooligosaccharides from Haemophilus ducreyi containing polylactosamine repeats

“…Similar structures, if expressed by H. ducreyi under in vivo conditions, would likely play important roles in allowing the organism to survive and/or replicate. The analysis of H. ducreyi recovered from the human challenge model may be able to confirm or disprove the presence of polyLacNAc, although such an analysis will be difficult because of the very low number of organisms that are present in these lesions [39]. However, should this polyLacNAc structural phenotype be stable enough to allow for growth in primary culture after human challenge, sufficient material should be obtainable.…”