Prevention of ExperimentalHaemophilus ducreyiInfection: A Randomized, Controlled Clinical Trial

Abstract

Human subjects were infected with Haemophilus ducreyi. All subjects developed papules and were randomized to treatment with a single dose of azithromycin (1 g) or ciprofloxacin (500 mg). At weekly intervals, volunteers were reinoculated with H. ducreyi, and drug concentrations were measured in peripheral blood mononuclear cells (PBMC). When papules developed, the subjects were treated with antibiotics and dismissed from the study. Eight of the ciprofloxacin-treated subjects developed papules 1 week after the initial treatment, and the ninth subject developed disease 2 weeks after treatment. The 9 azithromycin-treated subjects developed papules 4-10 weeks (mean, 6.8) after the initial treatment (P < .001). Azithromycin was detected in PBMC for 3-6 weeks (mean, 4). Pre- and posttreatment lesions had histology typical of experimental chancroid or were culture positive. Azithromycin prevents experimental chancroid for nearly 2 months. These findings have implications for strategies to prevent chancroid.

Characterization ofHaemophilus ducreyi-Specific T-Cell Lines from Lesions of Experimentally Infected Human Subjects

“…In the human model, sites inoculated with heat-killed bacteria do not contain an inflammatory infiltrate (51). PBMCs isolated on the day of infection, at end point, and 21 days after inoculation exhibit low levels of blastogenesis to H. ducreyi that do not vary over time, even in subjects who have been rechallenged (5,48).…”

Standardization of the Experimental Model ofHaemophilus ducreyiInfection in Human Subjects

“…However, 2 volunteers developed hypertrophic scars at sites that were biopsied. To date, we have completed several trials of human experimental infection with H. ducreyi [6][7][8][9][10]. Of 65 subjects who were challenged, 53 underwent biopsy, and 7 (13.2% of those biopsied) formed hypertrophic scars.…”

“…Inoculation of ∼30 cfu causes a papule formation rate of 95% and a pustule formation rate of 69%. Thus, for chemoprophylaxis or vaccine trials, subjects are inoculated at 2 sites with 30-60 cfu to ensure that a susceptible subject will become infected [9]. Lesion outcome at multiple sites inoculated with the same isolate in an individual subject may be independent.…”

Chancroid transmission dynamics: a mathematical modeling approach

“…The study presented here is not exhaustive as it can be extended to include condom use, as well as co-infection with HIV given the high rates of HIV among those infected with chancroid infections (Steen 2001). Given that some antibiotics confer some degree of immunity against re-infection ( Thornton et al 1998), the model can be extended to incorporate some degree of immunity for those treated and recovered. Furthermore, the model can be extended to incorporate bisexuality in the transmission dynamics of chancroid.…”

“…Single doses of certain antibiotics, such as ciprofloxacin and azithromycin, are highly effective (Schmid 1999;Ballard et al 1996) although longer treatments may be more effective in uncircumcised males and patients with HIV infection (Malonza et al 1999;Tyndall et al 1993). Antibiotics may also provide some protection from reinfection: one study estimated that the prophylactic effect of a single dose of azithromycin against new H. ducreyi infection lasted as long as 2 months after treatment (Thornton et al 1998).…”