CHAPTER 70: DONOVANOSIS

Donovanosis is a chronic, progressive bacterial infection that usually involves the genital region. The condition is generally regarded as a sexually transmitted infection of low infectivity. This infection has been known by many other names, the most common being granuloma inguinale.

The causative organism has been reclassified as Klebsiella granulomatis comb nov on the basis of phylogenetic analysis, although there is ongoing debate about this decision. Some authorities consider the original nomenclature (Calymmatobacterium granulomatis) to be more appropriate in light of analysis of 16S rRNA gene sequences.

Donovanosis was first described in Calcutta in 1882, and the causative organism was recognized by Charles Donovan in Madras in 1905. He identified the characteristic Donovan bodies, measuring 1.5 × 0.7 μm, in macrophages and the stratum malpighii. The organism was not reproducibly cultured until the mid-1990s, when its isolation in peripheral-blood monocytes and human epithelial cell lines was reported.

Donovanosis has an unusual geographic distribution that includes Papua New Guinea, parts of southern Africa, India, the Caribbean, French Guyana, Brazil, and aboriginal communities in Australia. In Australia, donovanosis has been almost entirely eliminated through a sustained program backed by strong political commitment and resources at the primary health care level. Although few cases are now reported in the United States, donovanosis was once prevalent in this country, with 5000–10,000 cases recorded in 1947. The largest epidemic recorded was in Dutch South Guinea, where 10,000 cases were identified in a population of 15,000 (the Marind-anim people) between 1922 and 1952.

Donovanosis is associated with poor hygiene and is more common in lower socioeconomic groups than in those who are better off and in men than in women. Infection in sexual partners of index cases occurs to a limited extent. Donovanosis is a risk factor for HIV infection (Chap. 97).

Globally, the incidence of donovanosis has decreased significantly in recent times. This decline probably reflects a greater focus on effective management of genital ulcers because of their role in facilitating HIV transmission.

A lesion starts as a papule or subcutaneous nodule that later ulcerates after trauma. The incubation period is uncertain, but experimental infections in humans indicate a duration of ~50 days. Four types of lesions have been described: (1) the classic ulcerogranulomatous lesion (Fig. 70-1), a beefy red ulcer that bleeds readily when touched; (2) a hypertrophic or verrucous ulcer with a raised irregular edge; (3) a necrotic, offensive-smelling ulcer causing tissue destruction; and (4) a sclerotic or cicatricial lesion with fibrous and scar tissue.

The genitals are affected in 90% of patients and the inguinal region in 10%. The most common sites of infection are the prepuce, coronal sulcus, frenum, and glans in men and the labia minora and fourchette in women. Cervical lesions may mimic cervical carcinoma. In men, lesions are associated with lack of circumcision. Lymphadenitis is uncommon. Extragenital lesions occur in 6% of cases and may involve the lip, gums, cheek, palate, pharynx, larynx, and chest. Hematogenous spread with involvement of liver and bone has been reported. During pregnancy, lesions tend to develop more quickly and respond more slowly to treatment. Polyarthritis and osteomyelitis are rare complications. In newborn infants, donovanosis may present with ear infection. Cases in children have been attributed to sitting on the laps of infected adults. As the incidence of donovanosis has decreased, the number of unusual case reports has appeared to be increasing.

Complications include neoplastic changes, pseudo-elephantiasis, and stenosis of the urethra, vagina, or anus.

A clinical diagnosis of donovanosis made by an experienced practitioner on the basis of the lesion’s appearance usually has a high positive predictive value. The diagnosis is confirmed by microscopic identification of Donovan bodies (Fig. 70-2) in tissue smears. Preparation of a good-quality smear is important. If donovanosis is suspected on clinical grounds, the smear for Donovan bodies should be taken before swab samples are collected to be tested for other causes of genital ulceration so that enough material can be collected from the ulcer. A swab should be rolled firmly over an ulcer previously cleaned with a dry swab to remove debris. Smears can be examined in a clinical setting by direct microscopy with a rapid Giemsa or Wright’s stain. Alternatively, a piece of granulation tissue crushed and spread between two slides can be used. Donovan bodies can be seen in large, mononuclear (Pund) cells as gram-negative intracytoplasmic cysts filled with deeply staining bodies that may have a safety-pin appearance. These cysts eventually rupture and release the infective organisms. Histologic changes include chronic inflammation with infiltration of plasma cells and neutrophils. Epithelial changes include ulceration, microabscesses, and elongation of rete ridges.

A diagnostic polymerase chain reaction (PCR) test was based on the observation that two unique base changes in the phoE gene eliminate Hae111 restriction sites, enabling differentiation of K. granulomatis comb nov from related Klebsiella species. PCR analysis with a colorimetric detection system can now be used in routine diagnostic laboratories. A genital ulcer multiplex PCR that includes K. granulomatis has been developed. Serologic tests are only poorly specific and are not currently used.

The differential diagnosis of donovanosis includes primary syphilitic chancres, secondary syphilis (condylomata lata), chancroid, lymphogranuloma venereum, genital herpes, neoplasm, and amebiasis. Mixed infections are common. Histologic appearances should be distinguished from those of rhinoscleroma, leishmaniasis, and histoplasmosis.

TREATMENT

Donovanosis is probably the cause of genital ulceration that is most readily recognizable clinically. Donovanosis is now limited to a few specific locations, and its global eradication is a distinct possibility.