Chancroid, often referred to as “soft” chancre, represents an acute ulcerative disease associated with painful inguinal lymphadenitis. Lymph nodes may suppurate and break down, causing a rounded swelling known as ‘bubo.’ Akin to some other sexually transmitted diseases, chancroid has been recognized as an important risk factor for the transmission of human immunodeficiency virus (HIV).
Chancroid is caused by a bacterial pathogen Haemophilus ducreyi that has also been implicated in chronic skin ulcers commonly observed in the South Pacific region. The condition is characterized by pain and tenderness of the ulcer (that also presents with indeterminate and ragged edges), in contrast to the painless chancre seen in syphilis.
Classical cultivation and molecular methods are used in the diagnostic algorithm, although the diagnosis is often made only on clinical grounds – especially considering the disease is widespread in less-developed countries of the world. Chancroid can be successfully treated with macrolides, fluoroquinolones, and some representatives of the third-generation cephalosporins.
Microbiology of the Causative Agent
Chancroid was distinguished from syphilis and deemed a separate disease entity in the mid 1800 by Ricord and Basserau from France. A Neapolitan microbiologist Augusto Ducrey identified the causative agent in 1889, which was confirmed by Unna and Krefting in tissue sections three years later.
Haemophilus ducreyi is a small, non-motile, Gram-negative, rod-shaped bacterium with rounded corners. The organism tends to form chains that are often described as “schools of fish” or “railroad track”. This morphologic trait can sometimes be observed in Gram-stained smears that are prepared directly from clinical specimens, albeit it is not a reliable or consistent finding.
The causative agent (which is a strict human pathogen) requires special growth media enriched with hemin and serum in order to achieve successful cultivation. Moreover, cultures should be incubated at 33 °C in a highly humid atmosphere that is supplemented with 5% carbon dioxide. The colonies on agar plates are grayish, and slide intact across the plate if pushed.
A majority of Haemophilus ducreyi strains from various geographical areas have been found to be genetically related, albeit some local diversity is noted in strains from Thailand. When electrophoretic analysis of Haemophilus ducreyi lipooligosaccharide (LOS) was pursued, the obtained migration patterns were analogous with other mucosal pathogenic bacteria – such as other Haemophilus and Neisseria species.
Disease Pathogenesis
There are still some question marks regarding the pathogenesis of chancroid. Haemophilus ducreyi enters the tissues by using skin microabrasions that arise during sexual intercourse (as the microorganism usually does not show the propensity for intact skin). Lesions are found in the areas of genital tract that are most easily traumatized, such as the prepuce and coronal sulcus of the penis, as well as the vaginal walls or cervix.
Upon infection, the microorganism instigates a local tissue reaction that results in an intraepithelial lesion full of lymphocytes, granulocytes and macrophages. Swelling and proliferation of the blood vessels, as well as extravasation of erythrocytes (red blood cells) also occurs. Aforementioned intraepithelial lesion is a stage that precedes erythematous papule and pustule development.
Lymphadenitis seen in chancroid is principally a pyogenic inflammatory reaction, which is potentiated by virulence determinants of Haemophilus ducreyi (such as hemolysin and superoxide dismutase enzymes). The organism is shed intermittently before ulceration occurs, suggesting infectious potential even in the incubation period.
Although the immune cells are recruited by the innate response, immunity that develops is incomplete, as second infections are often seen after the initial one. In addition, Haemophilus ducreyi can be located within a granulocytic infiltrate where it can continue to replicate by evading phagocytosis. This, in turn, prevents spontaneous clearance of the infection.
Further Reading