Klebsiella granulomatis (Donovanosis, Granuloma Inguinale)


Donovanosis is a chronic, progressive ulcerative disease of the skin and subcutaneous tissues that is caused by the encapsulated, gram-negative bacterium Klebsiella (formerly Calymmatobacterium ) granulomatis. The infection is also commonly referred to as granuloma inguinale, but because this term can easily be confused with lymphogranuloma venereum (caused by the invasive L-serovars of Chlamydia trachomatis ), many experts now recommend donovanosis as the preferred term. McLeod is credited with providing the first description of donovanosis based on his work in India in 1881; this was followed by the discovery of the causative organism by Donovan in 1905. Donovanosis is uncommon in developed, nontropical settings, and cases are sporadically reported from Papua New Guinea, South Africa, India, Brazil, and Australia.

Biology of Causative Organism

K. granulomatis is an encapsulated intracellular pleomorphic gram-negative bacillus (dimensions approximately 1–2 µm long by 0.5–0.7 µm wide) that resides in cytoplasmic vacuoles of large mononuclear cells. The bacteria are described as having bipolar densities when stained (Donovan bodies), which give the appearance of closed safety pins on microscopic examination. The bacteria multiply intracellularly and are subsequently released on rupture of mature intracytoplasmic vacuoles leading to infection of surrounding cells. Ultrastructurally the organisms are described as having a clearly defined capsule and the absence of flagella, along with small surface projections resembling pili or fimbriae and electron-dense granules (35–45 µm in diameter) in the cell periphery. These granules had previously been thought to represent evidence of bacteriophage infection; however, this hypothesis remains controversial.

In the 1940s investigators reported successful culture of the organism in chick embryo yolk sacs and subsequently in egg yolk–based media and defined liquid media. However, no pure isolates were stored for further study, hampering further characterization of the organism. In the 1990s renewed efforts to isolate the bacterium from clinical specimens were successful using human monocyte cultures and Hep-2 cell monolayers. In 1999 detailed molecular analyses of Calymmatobacterium granulomatis phylogeny ultimately resulted in its proposed reclassification as a Klebsiella species.

Geographic Distribution and Epidemiology

Donovanosis is a relatively rare disease in developed countries. In the United States, it is estimated that less than 100 cases occur annually, although epidemiologic tracking is difficult because it is not a nationally reportable condition. Donovanosis is recognized as a cause of genital ulcer disease in parts of India, Papua New Guinea, the Caribbean, and South America (particularly Brazil) and has been identified in Zambia, Zimbabwe, South Africa, Southeast Asia, and among Aboriginals and Torres Strait Islanders in Australia. The fact that these are all tropical locations raises the possibility of ecologic tropism, that is, preferential organismal survival and infectivity in tropical environments, although this has not been proved. The reported incidence has decreased significantly in recent years in Australia, Papua New Guinea, India, South Africa, India, and Jamaica, owing to either greater recognition of donovanosis as a public health problem and the implementation of appropriate measures for prevention and control or general improvements in living standards and health service provision in endemic areas. Still, cases of donovanosis continue to be encountered in parts of the world remote from these endemic regions (e.g., metropolitan France ) as a result of immigration to developed countries or alternatively through increased global travel to predominantly tropical areas. In most cases the disease is considered to be sexually acquired: infection rates of 52% have been reported among steady sex partners of individuals with donovanosis. However, the possibility of nonsexual transmission remains a controversial hypothesis. In the 1960s Goldberg postulated that the causative organism may be a gastrointestinal tract commensal and that the vagina may be infected through autoinoculation. Nonsexual transmission is further suggested by lesions in very young children and the occurrence of infection in extragenital sites (e.g., mastoiditis and meningitis). However, the age distribution in endemic areas, the common co-occurrence of other sexually transmitted infections, and the high frequency of genital tract lesions support the assertion that donovanosis is predominantly transmitted through sexual contact.

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