A Primate Model for Chancroid

Abstract

Adult pigtailed macaques (Macaca nemestrina) were evaluated for their usefulness as a primate model for chancroid. To initiate infection, 10(7)-10(8) cfu of Haemophilus ducreyi were inoculated into the foreskins of 5 adult males and into the vaginal labia of 4 adult females. Lesions developed in the male macaques that were similar in appearance, histopathologic changes, and progression to those of human disease, including the development of ulcers 6-12 days after infection. In addition, H. ducreyi could be recovered from the lesions up to 20 days after inoculation, humoral antibodies were induced beginning 1 week after inoculation, and inguinal lymphadenopathy was noted in 4 of the 5 males. None of the 4 female macaques inoculated with the same preparation of live H. ducreyi developed comparable lesions. Thus, experimental chancroid in adult male macaques closely resembles human disease and should be useful for future studies of the pathogenesis of chancroid.

Immunopathogenesis ofHaemophilus ducreyiInfection (Chancroid)

“…Lesions persist up to 2 weeks before resolving. In the macaque model, 10 7 CFU of H. ducreyi are injected intradermally into the foreskin of male primates, who develop lesions within 1 to 2 days of infection (104). Exudative ulcers reminiscent of human chancroid develop in 1 to 2 weeks, and inguinal lymphadenopathy develops in most primates.…”

“…PMNs and lymphocytes are recruited to infected sites in the TDRM, macaque, and swine models (50,78,104). In contrast to the human model and to most recent studies of natural infection (1,54,55,63,72), numerous plasma cells are present in ulcers of the macaque model.…”

“…All three species of animals develop serum antibodies to H. ducreyi antigens within 1 to 2 weeks of infection (50,78,104). No serum antibody response develops after 2 weeks of human experimental infection, even in subjects who are challenged twice (6,72,89).…”

In vitro stimulation of peripheral blood mononuclear cells (PBMC) from HIV- and HIV+ chancroid patients by Haemophilus ducreyi antigens

“…As yet no data are available on lymphoproliferative responses in the temperature-dependent rabbit model [3], nor in the primate model [4] for chancroid. This study provides the basic information necessary to prove the validity of observations done in the suggested animal models for evaluation of the human system.…”

“…Various animal models for chancroid were developed [3.4]. Thus, chancroidal ulcers were induced in a temperature-dependent rabbit model [3] as well as in a primate model [4], but the relevance of these models for the pathogenesis and cellular immune responses in human chancroid remains to be established. Yet, little is known about the pathogenesis of H. ducreyi infection in humans.…”