Donovanosis

 

Donovanosis

Gavin Hart

Donovanosis is a chronic, progressively destructive bacterial infection of the genital region that is generally regarded as sexually transmitted. The disease has been known by many other names, the most common of which are granuloma inguinale and granuloma venereum.

 

ETIOLOGY

Donovanosis is caused by Calymmatobacterium granulomatis, an intracellular, gram-negative, pleomorphic, encapsulated (when mature) bacterium measuring 1.5 by 0.7 µm. C. granulomatis shares many morphologic and serologic characteristics and >99% homology at the nucleotide level with Klebsiella species that are pathogenic to humans. Polymerase chain reaction (PCR) amplification of the phoE gene shows it to be closely related to that in Klebsiella pneumoniae, K. rhinoscleromatis, and K. ozaenae. Electron microscopy shows typical gram-negative morphology and a large capsule but no flagella. Filiform or vesicular protrusions occur on a corrugated cell wall.

EPIDEMIOLOGY

Donovanosis is endemic among Aborigines in central Australia as well as in Papua New Guinea, southeastern India, southern Africa, and the Caribbean and adjacent areas of South America. In the first half of the twentieth century, the disease was endemic in parts of the United States (with an estimated 5000 to 10,000 cases in 1947); small epidemics still occur in this country and in other developed countries. The decline in the United States to fewer than 20 reported cases annually in the past decade has probably resulted from lower transmission rates due to earlier presentation for increasingly effective antibiotic therapy. Over 70% of cases involve persons 20 to 40 years of age. The infection is predominantly sexually transmitted, but extragenital skin lesions can follow transmission from concurrent genital lesions via the fingers or through other nonsexual contact, and autoinoculation may produce new lesions from contact with adjacent skin (“kissing” lesions). Infants born to infected mothers have acquired infection at birth.

The classification of donovanosis as a sexually transmitted disease (STD) has been disputed because of cases in young children and occasionally in sexually inactive individuals, transmission by direct body contact and via inanimate intermediaries, and the low and variable prevalence of donovanosis among sexual partners (0.4 to 52%). The dominance of sexual transmission is suggested by the combined factors of lesions predominantly affecting the genitalia, the highest prevalence among persons in age and socioeconomic groups that are most often affected by STDs, and the predictable occurrence of disease in visitors to areas of endemicity following sexual exposure.

CLINICAL MANIFESTATIONS

The incubation period is usually 1 to 4 weeks but may extend to 1 year. Skin lesions have been detected in infants 6 weeks to 6 months after birth. The disease begins as one or more subcutaneous nodules that erode through the skin to produce clean, granulomatous, sharply defined, usually painless lesions. These lesions, which bleed readily on contact, slowly enlarge. The genitalia are involved in 90% of cases, the inguinal region in 10%, and the anal region in 5 to 10%. Genital swelling, particularly of the labia, is a common feature and occasionally progresses to pseudoelephantiasis. Phimosis and paraphimosis are common local complications, and progressive erosion of affected tissues may completely destroy the penis or other organs. Less common clinical variants include a hypertrophic form (cauliflower- or wartlike lesions), a necrotic form (destructive lesions with foul-smelling exudate, often resembling amebiasis), and a sclerotic or cicatricial form, which has a dry base with extensive scar tissue.

Extragenital lesions occur in at least 6% of cases. Oral donovanosis, the most common extragenital manifestation, presents as pain or bleeding in the mouth, lesions on the lips, or extensive swelling of the gums and palate. Donovanosis may affect most bones, and sometimes many bones are affected at the same time; the tibia is involved in over 50% of such cases. Bony lesions are associated with constitutional symptoms (weight loss, fever, night sweats, and malaise) and are usually found in women. More than 50% of women with donovanosis have primary lesions on the cervix. Prompt pelvic examinations and early diagnosis are likely to substantially decrease the morbidity and mortality (likely outcomes in misdiagnosed spinal lesions) associated with extragenital donovanosis in women.

DIAGNOSIS

Laboratory Diagnosis

The preferred diagnostic method involves demonstration of typical intracellular Donovan bodies within large mononuclear cells visualized in smears prepared from lesions or biopsy specimens. With typical beefy lesions, a small piece of tissue is removed with forceps and scalpel, and a crush impression of the deep surface is made on a glass slide. The smear is air-dried, heat-fixed, and stained with Giemsa, Leishman's, or Wright's stain. For dry, flat, or necrotic lesions, a punch-biopsy specimen should be obtained from the advancing edge. This specimen can be used to prepare a smear or embedded for histologic examination (with a silver stain). Histologic examination shows epithelial proliferation, often simulating neoplasia, with a heavy inflammatory infiltrate of plasma cells, some neutrophils, and few if any lymphocytes. The large mononuclear cells are 25 to 90 µm in diameter, with a vesicular or pyknotic nucleus. Up to 20 intracytoplasmic vacuoles contain pleomorphic Donovan bodies in either young unencapsulated forms (which often resemble closed safety pins) or mature encapsulated forms. C. granulomatis has never been grown on artificial solid media but has been cultured in chicken embryonic yolk sacs, on human monocytes, and on human epithelial (HEp-2) cells. A diagnostic PCR test has been developed and incorporated into a colorimetric detection system for C. granulomatis. A serologic test, based on indirect immunofluorescence, is more useful in confirming the diagnosis in cases with long-standing lesions than in early disease.

Differential Diagnosis

The differential diagnosis of donovanosis is summarized in Table 1. Syphilis and donovanosis frequently coexist because syphilis is usually highly prevalent in areas where donovanosis is endemic; thus positive syphilis serology does not exclude a diagnosis of donovanosis. Genital ulcers are a risk factor for HIV acquisition in developing countries, and patients with donovanosis should be tested for HIV infection.

TABLE 1 Differential Diagnosis of Donovanosis

Disease (Chapter) Distinguishing Features   Secondary syphilis: condylomata lata White or pale moist plaques in anogenital region (as opposed to bright red donovanosis lesions); lesions subside within 1 week of treatment with benzathine penicillin, 2.4 mU (whereas donovanosis lesions remain unchanged) Squamous cell carcinoma Histologic appearance Penile amebiasis Microscopic identification of Entamoeba histolytica Chancroid: pseudogranuloma inguinale Culture of Haemophilus ducreyi Tuberculosis Histologic features of bony lesions Actinomycosis Microscopic identification of sulfur granules Rhinoscleroma Histologic features Leishmaniasis Histologic features Histoplasmosis Histologic features

TREATMENT

Table 2 shows the most effective regimens for treating donovanosis. Doxycycline offers the advantage of convenient administration and has been widely used in developed countries, but azithromycin is increasingly being used as first-choice therapy. Extensive lesions have been cured with oral azithromycin at a dosage of 500 mg/d, but the more convenient dose of 1 g weekly is also effective. Although chloramphenicol is the drug of choice in some developing countries, it is unlikely to be acceptable in developed countries because of bone marrow toxicity. Penicillin is not effective for treating donovanosis. Patients should be examined weekly, and therapy should be continued until lesions have healed (3 to 5 weeks, except in severe cases). If antibiotic therapy is stopped earlier, lesions often continue to heal, but the relapse rate is higher. If the lesions are unchanged after 2 weeks of treatment, an alternative antibiotic regimen should be used.

TABLE 2 The Most Effective Antibiotic Regimens for Treatment of Donovanosis

Antibiotic Oral Dosage   Azithromycin 1 g weekly or 500 mg/d Erythromycin 500 mg qid Tetracycline 500 mg qid Doxycycline 100 mg bid Trimethoprim-sulfamethoxazole 1 double-strength tablet bid Chloramphenicol 500 mg tid   Patients should be examined weekly, and therapy should be continued until lesions have healed (3 to 5 weeks, except in severe cases). 160 mg/800 mg.

The treatment regimens listed in Table 2 are usually adequate in HIV-infected patients without immunosuppression, but an increasing failure rate has been reported in immunosuppressed patients, for whom daily administration of azithromycin is recommended if other regimens fail to elicit a response.