[Feline leprosy in a 5-month-old male cat in Germany]. / Feline Lepra bei einem 5 Monate alten Kater in Deutschland.

A 5-month-old, male, 4 kg European shorthair cat presented with ulcera ted cutaneous nodules in many areas over its entire body. The serological results for feline immunodeficiency virus and the feline leukaemia virus were negative. Following detection of acid-proof bacilli in histological examination of three skin biopsies, the diagnosis of mycobacteriosis of the skin was made. Polymerase chain reaction revealed the presence of Mycobacteriumlepraemurium. After surgical excision of all cutaneous nodules and a 14.5-week antibiotic therapy with Rifampicin and Clarithromycin, the cat was classified as being cured. During the observation period of 1 year after the end of the therapy, no relapse occurred.

Feline leprosy due to Mycobacterium lepraemurium.

OBJECTIVES: This paper, the second in a series of three on 'feline leprosy', provides a detailed description of disease referable to Mycobacterium lepraemurium, the most common cause of feline leprosy worldwide. METHODS: Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with M lepraemurium infection. RESULTS: A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Sixty-five cats were definitively diagnosed with M lepraemurium infection. Typically, cats were 1-3 years of age when first infected, with a male gender predilection. Affected cats were generally systemically well. All had outdoor access. Lesions tended to consist of one or more cutaneous/subcutaneous nodules, typically located on the head and/or forelimbs, possibly reflecting the most likely locations for a rodent bite as the site of inoculation for organisms. Nodules had the propensity to ulcerate at some stage in the clinical course. The cytological and histological picture varied from tuberculoid, with relatively low bacterial numbers, to lepromatous with moderate to high bacterial numbers. Treatment was varied, although most cats underwent surgical resection of lesions with adjunctive medical therapy, most often using a combination of oral clarithromycin and rifampicin. Prognosis for recovery was generally good, and in two cases there was spontaneous remission without the requirement for medical intervention. Untreated cats continued to enjoy an acceptable quality of life despite persistence of the disease, which extended locally but had no apparent tendency to disseminate to internal organs. CONCLUSIONS AND RELEVANCE: M lepraemurium causes high bacterial index (lepromatous) or low bacterial index (tuberculoid) feline leprosy. The infection typically causes nodules of the skin and/or subcutis (which tend towards ulceration) on the head and/or forelimbs. The disease usually has an indolent clinical course and infected cats have a generally favourable response to therapeutic interventions, with rare cases undergoing spontaneous resolution. Genomic analysis may yield clues as to the environmental niche and culture requirements of this elusive organism. Prospective treatment trials and/or additional drug susceptibility testing in specialised systems would further inform treatment recommendations.

Scabies Among Elderly Korean Patients with Histories of Leprosy.

A scabies epidemic, traced by the hospital-based surveillance system, was reported in a Korean leprosarium. A total of 200 symptomatic cases were found during 2012-2014 among 570 elderly former leprosy patients. Most of cases were classic type scabies (87%) and aged 75 years and older (72%). Surveillance system for early diagnosis and prompt intervention was applied and the scabies epidemic was controlled effectively in this long-term care facility.

Integrated pathways for neutrophil recruitment and inflammation in leprosy.

Neutrophil recruitment is pivotal to the host defense against microbial infection, but it also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by means of bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy and is characterized by neutrophil infiltration in lesions, the most overrepresented biological functional group was cell movement, including E-selectin, which was coordinately regulated with interleukin 1beta (IL-1beta). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1beta, which together with interferon gamma induced E-selectin expression on and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2 and Fc receptor activation, neutrophil migration, and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.

[Sensory-motor neuropathy: a slow and misleading case of leprosy]. / Neuropathie périphérique sensitivomotrice : une forme lente et trompeuse de maladie de Hansen.

The diagnostic process of sensory-motor neuropathies is difficult. Atypical variants and rare etiologies also contribute to delay the diagnosis. We report the case of a 70-year-old woman with slowly progressive asymmetric axonal sensory-motor neuropathy. Leprosy was identified after an eight-year delay. Nerve biopsy was required to establish the diagnosis: electron microscopy revealed debris of Hansen's bacillus in the nerve. Treatment was fully curative after several months. Leprosy is a rare cause of neuropathy in Europeans. Systematic inquiry about travel to endemic areas would be helpful in establishing the diagnosis. In such cases, nerve biopsy is crucial.

A case of feline leprosy caused by Mycobacterium lepraemurium originating from the island of Kythira (Greece): diagnosis and treatment.

A 2-year-old, 4 kg, healthy, domestic shorthair female cat presented with ulcerated subcutaneous nodules on the commissures of its mouth. The cat was negative for feline leukaemia virus and feline immunodeficiency virus. Skin mycobacteriosis was diagnosed after detection of numerous acid-fast bacilli in Ziehl Neelsen-stained smears from the ulcers. Feline leprosy was suspected following preliminary polymerase chain reaction results: positive for Mycobacterium genus but negative for Mycobacterium tuberculosis and Mycobacterium avium complexes. Mycobacterium lepraemurium was later identified following DNA sequence analysis of the 5' end of the 16S rRNA gene and the 16S-23S internal transcribed spacer region. Microscopic lesions consisted of pyogranulomas containing mainly large foamy macrophages with 10-100 intra-cellular acid-fast bacilli per field. The cat was cured after surgery and a 14-week course of clofazimine (30 mg daily) and clarithromycin (50 mg twice daily).

PCR studies of feline leprosy cases.

16S rRNA gene sequence analysis provided evidence for two different mycobacterial species, Mycobacterium lepraemurium and a potentially novel species, as causative agents of 'feline leprosy'. Comparison of 16S rRNA gene sequence data obtained for M. lepraemurium and the potentially novel species indicated 12 nucleotide differences over a 446 bp region encompassing the V2 and V3 hypervariable regions. From available 16S rRNA gene sequence data, M. lepraemurium shared greatest nucleotide identity with M. avium subsp paratuberculosis and M. avium. The novel species had a long helix 18 in the V3 region and shared greatest nucleotide identity with M. leprae, M. haemophilum and M. malmoense. The novel species had an additional 'A' nucleotide at position 105 of the aligned 16S rRNA gene sequence, the only other mycobacterial database sequence having this same extra nucleotide being M. leprae. This nucleotide variation was exploited to develop specific PCR assays for the two species. These were found to be effective and specific when tested against a panel of mycobacteria including species found in feline leprosy lesions and closely related mycobacteria and also when applied directly to formalin-fixed, paraffin-embedded tissues from feline leprosy cases.

Determination of the etiology of presumptive feline leprosy by 16S rRNA gene analysis.

PCR-amplified 16S rRNA gene sequences were obtained directly from tissue specimens from eight cats with presumptive feline leprosy. Acid-fast bacilli were observed in sections from all eight specimens, but culture for mycobacteria was successful for one specimen only. Analysis of the V2 variable region of each 16S rRNA PCR product identified a sequence with 100% nucleotide identity to the sequences of Mycobacterium lepraemurium, Mycobacterium avium, and Mycobacterium paratuberculosis in four of the specimens from cats with feline leprosy. Separate M. paratuberculosis- and M. avium-specific PCR amplifications of the four specimens were negative, thus substantiating the identification of M. lepraemurium in these specimens from cats with feline leprosy. Further sequence analysis of the V3 variable region of one of the four specimens provided conclusive evidence of the presence of M. lepraemurium. This is the first report of the definitive identification of M. lepraemurium in cats with feline leprosy by molecular biology-based analyses. M. avium, which is rarely reported in cats, and Mycobacterium chitae, a reported nonpathogenic, rapidly growing mycobacterial species found in the environment, were identified in the specimen from which acid-fast bacilli were cultured. Two of the specimens from cats were infected with a potentially novel species of mycobacteria which had a 16S rRNA gene sequence sharing the closest nucleotide sequence identity with that of Mycobacterium malmoense. Molecular biology-based analyses provided for the accurate and rapid diagnosis of mycobacterial infections in cats and circumvented the problems of culture and misdiagnosis of feline leprosy associated with traditional methods.

Coexistence of an unusual form of scabies and lepromatous leprosy. A case report.

A case of unusual crusted (Norwegian) scabies involving the entire skin of a 26 year old Brazilian patient with lepromatous leprosy is reported. The more prominent histopathological findings were acanthosis, hyperkeratosis and crusting with many mites of Sarcoptes scabiei. In the dermis, numerous foamy histiocytes filled with abundant acid-fast bacilli were seen.

[The identification of the antigenic determinants of Mycobacterium leprae passed through laboratory animals by using monoclonal antibodies]. / Identifikatsiia antigennykh determinant Mycobacterium leprae, passiruemykh na laboratornykh zhivotnykh, s pomoshch'iu monoklonal'nykh antitel.

The antigenic preparations of M. leprae isolated from the biopsy leproma material of leprosy patients, M. leprae obtained by passage through laboratory animals (armadillos, rats) and M. lepraemurium have been identified by indirect solid-phase enzyme immunoassay. Experiments made with the use of the set of monoclonal antibodies (McAb) to different M. leprae antigenic determinants, supplied by the WHO Bank of Monoclonal Antibodies (IMMLEP), have demonstrated the presence of common antigenic determinants in 65-kD protein of M. leprae obtained by passage through armadillos and rats and M. lepraemurium, as well as in 12-kD protein of M. leprae isolated from armadillos and rats and M. leprae isolated from the biotic material of human lepromas. The passage of M. leprae through experimental animals leads to the appearance of a new antigenic determinant in their structure, which is recognized by McAb 111E4.

Complemento, daño renal y lepra murina / Complement, renal damage and murine leprosy

A pesar de que la lepra de los ratones es una enfermedad sistémica, el tejido renal de los animales infectados rara vez es invadido por el Mycobacterium lepraemurium. Nuestros resultados indicaron que los animales afectados con el Mycobacterium lepraemurium desarrollaron un defecto en sus niveles de complemento hemolítico que es proporcional al grado de infección. El defecto afecta principalmente la vía clásica de activación del complemento y menor marcadamente la vía alterna. La inactivación de la actividad de complemento, mientras transcurre la infección, disminuye la posibilidad del daño medido por completo y prolonga la vida del huésped murino; ésta es, sin duda, una eficiente estrategia del microorganismo para prolongar también su supervivencia

The Ity/Lsh/Bcg gene significantly affects mouse resistance to Mycobacterium lepraemurium.

Mouse resistance to infection with Mycobacterium lepraemurium was measured by counting the total number of intact acid-fast bacilli in the spleen 8 weeks after i.v. injection of a standard inoculation. The effect of Ityr on resistance to M. lepraemurium was confirmed and the results extended to two Ityr strains of mice, A and C57L, not previously tested. Resistance to M. lepraemurium was also examined in the F1, backcross and F2 generations of BALB/c X CBA crosses, and in the congenic strain B10.LLshr that is Ityr. In all experiments the results were consistent with the view that resistance to M. lepraemurium is significantly affected by a gene close to or identical to the Ity/Lsh/Bcg gene on mouse chromosome 1. Sex had a marked effect on resistance to M. lepraemurium, so that the males of some genetically resistant strains were almost as susceptible as some genetically susceptible females.

Influence of route of inoculation on anti-Mycobacterium lepraemurium antibody isotypes in murine leprosy.

Mice of the C57BL/6 strain were injected either subcutaneously (s.c.) in the foot pad or intravenously (i.v.) with 10(5) or 10(8) Mycobacterium lepraemurium (MLM). Anti-MLM sonicate total immunoglobulin (Ig), IgM, and IgG antibody production was followed during the course of the infection. The kinetics of appearance and the magnitude of anti-MLM antibodies were found to be related to the size and route of inoculation. The i.v. route induced earlier and higher amounts of anti-MLM antibodies than did the s.c. route. In i.v.-infected mice, a relatively predominant IgM response to MLM was observed, while a relatively higher IgG response was seen in s.c.-infected mice. IgM antibody level was found to increase sharply with the bacterial load as assessed in the spleens of mice with i.v.-disseminated infection; whereas a slow progression of both IgM and IgG levels was noted with time in s.c.-infected mice.