Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection

Abstract

We aimed to determine if the clinical and histological features of chancroid are altered by HIV infection. Male patients presenting to the Nairobi special treatment clinic with a clinical diagnosis of chancroid were eligible for the study. A detailed history, physical examination, swabs for Haemophilus ducreyi culture and blood for HIV serology, syphilis serology and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees C. Patients were treated with erythromycin and followed for 3 weeks. Chi-square and Student's t-test were used to determine if the clinical and laboratory features of chancroid differed between HIV-seropositive and seronegative individuals. Cox regression survival analysis was used to determine if HIV infection altered cure rates of chancroid at 21 days. Immunohistochemical staining was performed using lymphocytic and macrophage markers and tissue sections were analysed by 2 pathologists in a blinded manner. Between February and November 1994, 109 HIV-seropositive and 211 HIV-seronegative individuals were enrolled in the study. HIV patients had ulcers of longer duration than HIV-seronegative patients (P=0.03). Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%, P=0.002). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. This consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and negative patients. HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. This clinical difference cannot be attributed to an altered histopathological response to HIV infection. Additional studies are needed to elucidate the mechanisms responsible for this finding.

Haemophilus ducreyi Inhibits Phagocytosis by U-937 Cells, a Human Macrophage-Like Cell Line

“…In vivo, H. ducreyi is found in association with macrophages in naturally acquired chancroid lesions and in the human experimental infection model (2,25,26,31,42,43). To under- stand the mechanisms by which H. ducreyi persists and survives in the presence of these phagocytes, we explored the in vitro interactions of H. ducreyi with the human macrophage-like cell line, U-937.…”

“…Chancroid lesions involve cells of the epidermis and dermis and contain an immune cell infiltrate consisting of polymorphonuclear leukocytes (PMNs), T cells, and macrophages (2,25,26,42,43). Despite this immune cell infiltrate, viable H. ducreyi can be isolated from these ulcers weeks or months after initial infection (31).…”

Trafficking Pathways and Characterization of CD4 and CD8 Cells Recruited to the Skin of Humans Experimentally Infected withHaemophilus ducreyi

“…Papules develop at inoculated sites, which evolve into pustules, simulating natural chancroid. The histopathology of experimental infection closely parallels that of naturally occurring disease (22,25,26). The lesion consists of a polymorphonuclear leukocyte infiltrate that forms an epidermal abscess and a deep dermal perivascular infiltrate of T cells and macrophages that resembles a poorly formed granuloma that extends interstitially to just below the epidermis (26,36).…”

The Cytolethal Distending Toxin of Haemophilus ducreyi Inhibits Endothelial Cell Proliferation

“…Below this zone, ECs are the dominating cell type and small, dilated blood vessels are oriented in a vertical arrangement (12,15,30). This observation and the fact that angiogenesis is important in wound healing suggest that ECs may be important targets in chancroid pathogenesis.…”