Feline leprosy: two different clinical syndromes.

Feline leprosy refers to a condition in which cats develop granulomas of the subcutis and skin in association with intracellular acid-fast bacilli that do not grow on routine laboratory media. In this study, the definition was extended to include cases not cultured, but in which the polymerase chain reaction (PCR) identified amplicons characteristic of mycobacteria. Tissue specimens from 13 such cases from eastern Australia were obtained between 1988 and 2000. This cohort of cats could be divided into two groups on the basis of the patients' age, histology of lesions, clinical course and the sequence of 16S rRNA PCR amplicons. One group consisted of four young cats (less than 4 years) which initially developed localised nodular disease affecting the limbs. Lesions progressed rapidly and sometimes ulcerated. Sparse to moderate numbers of acid-fast bacilli were identified using cytology and/or histology, typically in areas of caseous necrosis and surrounded by pyogranulomatous inflammation. Organisms did not stain with haematoxylin and ranged from 2 to 6 microm (usually 2 to 4 microm). Mycobacterium lepraemurium was diagnosed in two cases based on the sequence of a 446 bp fragment encompassing the V2 and V3 hypervariable regions of the 16S rRNA gene a different sequence was obtained from one additional case, while no PCR product could be obtained from the remaining case. The clinical course was considered aggressive, with a tendency towards local spread, recurrence following surgery and development of widespread lesions over several weeks. The cats resided in suburban or rural environments. A second group consisted of nine old cats (greater than 9 years) with generalised skin involvement, multibacillary histology and a slowly progressive clinical course. Seven cats initially had localised disease which subsequently became widespread, while two cats allegedly had generalised disease from the outset. Disease progression was protracted (compared to the first group of cats), typically taking months to years, and skin nodules did not ulcerate. Microscopically, lesions consisted of sheets of epithelioid cells containing large to enormous numbers of acid-fast bacilli 2 to 8 microm (mostly 4 to 6 microm) which stained also with haematoxylin. A single unique sequence spanning a 557 bp fragment of the 16S rRNA gene was identified in six of seven cases in which it was attempted. Formalin-fixed paraffin-embedded material was utilised by one laboratory, while fresh tissue was used in another. The same unique sequence was identified despite the use of different primers and PCR methodologies in the two laboratories. A very slow, pure growth of a mycobacteria species was observed on Lowenstein-Jensen medium (supplemented with iron) and semi-solid agar in one of three cases in which culture was attempted at a reference laboratory. Affected cats were domicile in rural or semi-rural environments. These infections could generally be cured using two or three of rifampicin (10-15 mg/kg once a day), clofazimine (25 to 50 mg once a day or 50 mg every other day) and clarithromycin (62.5 mg per cat every 12 h). These findings suggest that feline leprosy comprises two different clinical syndromes, one tending to occur in young cats and caused typically by M lepraemurium and another in old cats caused by a single novel mycobacterial species.

Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs.

OBJECTIVE: To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. DESIGN: Multi-institutional retrospective/prospective case series using client-owned dogs. PROCEDURE: Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. RESULTS: Combination therapy using rifampicin (5 to 15 mg/kg p.o., every 24 h) and clarithromycin (8 to 24 mg/kg p.o. daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. CONCLUSION: Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg p.o., every 24 h) and clarithromycin (15 to 25 mg/kg p.o. total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition.

Prevalence of antibodies to hepatitis C virus among patients with leprosy in several African countries and the Yemen.

The prevalence of anti-HCV was determined in 1,309 leprosy patients and a control group of 1,469 subjects from 6 sub-Saharan African countries and the Yemen. Sera found positive by an initial second generation ELISA were subjected to 3 additional confirmatory tests. The anti-HCV prevalence in leprosy patients (7.1%) was significantly higher than in the control group (2.6%). HCV seroprevalence increased with age in both the control and leprosy groups. No statistically significant difference could be found between anti-HCV prevalence and the several clinical forms of leprosy among patients. The results of this study indicate a high degree of exposure or chronic carriage of hepatitis C among leprosy patients.

Leprosy in French Polynesia. The possible impact of multidrug therapy on epidemiological trends.

In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.