Chancroid

Definition

Chancroid is a sexually transmitted disease that is characterized by painful genital ulcers and inguinal lymphadenitis caused by Haemophilus ducreyi . H. ducreyi also is a major cause of nonsexually transmitted cutaneous ulcers in children who live in regions of the South Pacific and Africa where yaws ( Chapter 295 ), which is a nonsyphilitic treponematosis that causes a disfiguring and debilitating childhood infectious disease, is endemic.

H. ducreyi is a gram-negative coccobacillus that is not a true Haemophilus species. Within the Pasteurellaceae, H. ducreyi is grouped in a distinct lineage with Mannheimia haemolytica and Aggregatibacter (formerly Actinobacillus ) pleuropneumoniae . H. ducreyi is likely to have diverged from these animal respiratory pathogens to occupy its niche in the human epithelium.

Epidemiology

Chancroid, which is endemic in resource-poor regions of Africa and Asia, facilitates the transmission of human immunodeficiency virus (HIV-1). In the 1990s, the World Health Organization estimated the annual global prevalence of chancroid to be 4 to 6 million cases. Because of the widespread use of syndromic management, which consists of treatment for syphilis and chancroid without diagnostic testing, the prevalence of chancroid has dramatically declined in endemic areas. Chancroid can be maintained only in networks with high rates of multiple sex partners. Infected female sex workers play an important role in its epidemiology, and targeted treatment of sex workers can eradicate the disease in endemic areas. Despite these successes, chancroid persists in many countries, thereby implying a reservoir of untreated sex workers. Although urban outbreaks of chancroid associated with sex work occurred in the United States in the 1980s and 1990s, only 3 to 11 cases were reported annually from 2015 to 2019, most likely imported after contact with infected persons in endemic areas.

The male-to-female ratio of chancroid is 3:1, in part because of infection of multiple partners by sex workers. However, human inoculation experiments indicate that men are twice as susceptible as women to develop pustules, thereby suggesting that gender plays a role in the predominance of disease in men.

In yaws-endemic countries, H. ducreyi causes a chronic limb ulceration syndrome that occurs primarily in children. ^, Close contact of family members with ulcer cases is implicated in transmission. In yaws-endemic villages in Papua New Guinea, the prevalence of this syndrome has been 2 cases per 100 persons, and H. ducreyi is more common than T. pallidum subsp. pertenue in this setting. The overall prevalence of H. ducreyi infection in children aged 5 to 15 years can be as high as 7%. Similar data are reported from Ghana, the Solomon Islands, and Vanuatu, which together with Papua New Guinea are reported to have the highest prevalence of yaws. Travelers to endemic areas can acquire limb ulcers following minor trauma; the first case of cutaneous ulcers caused by H. ducreyi in the Netherlands was reported in 2018 in a person who imported it from Indonesia.

Pathobiology

In human inoculation experiments, puncture wounds are required to initiate infection, and the estimated infectious dose is as low as one bacterium. Papules develop within 24 hours and either spontaneously resolve or evolve into pustules in 2 to 5 days. Neutrophils and macrophages surround the organism and form an abscess that erodes the epidermis. Below the abscess is a collar of macrophages and regulatory T cells and a dermal infiltrate of macrophages, CD4 and CD8 T cells, natural killer cells, and dendritic cells. This histopathology, which resembles a suppurative granuloma, is associated with neutrophils and macrophages that fail to ingest the organism.

Whole-genome sequencing suggests cutaneous ulcer strains diverged from multiple lineages of genital ulcer strains during the past 180,000 years. RNA sequencing and metabolomics show that H. ducreyi changes its gene expression to adapt to the anaerobic, glucose-poor environment of the abscess and to scavenge alternative carbon sources, such as ascorbic acid. Differential host susceptibility is associated with distinct dendritic cell responses, which may shape the responses of T cells and natural killer cells, and thereby influence the ability of phagocytes to ingest the organism.