RESUMO
Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1-19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration.
Assuntos
Hanseníase/imunologia , Macaca fascicularis , Doenças dos Macacos/microbiologia , Mycobacterium leprae/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Biópsia/veterinária , Modelos Animais de Doenças , Feminino , Glicolipídeos/imunologia , Histocitoquímica/veterinária , Antígeno de Mitsuda , Hanseníase/microbiologia , Masculino , Doenças dos Macacos/imunologiaRESUMO
In a randomized, double-blind, double-dummy controlled study, 22 men with erythema nodosum leprosum (ENL) received six capsules containing either 100 mg (group A, n = 12) or 300 mg (group B, n = 10) of thalidomide daily for one week. A six-week, four capsules per day taper followed, in which group A received 50 mg/day of thalidomide in weeks 2 and 3, then dummy capsules in weeks 4 through 7, while group B had gradual decrements every two weeks. Both regimens caused comparable improvement in 19 patients at day 7 (group A [12 of 12] versus group B [7 of 10]; P = 0.08), but slower tapering in group B showed less re-emergence of ENL through week 7 (P = 0.02, versus group A). Most patients developed new lesions soon after stopping treatment. Slower tapering from a higher initial thalidomide dose may improve clinical ENL responses, but high recurrence rates after discontinuation indicates further assessment is needed to identify better tapering regimens.
Assuntos
Eritema Nodoso/tratamento farmacológico , Hansenostáticos/administração & dosagem , Hanseníase Virchowiana/tratamento farmacológico , Talidomida/administração & dosagem , Adolescente , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Interleucina-6/sangue , Hansenostáticos/efeitos adversos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neopterina/urina , Talidomida/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Monthly doses of rifampin, ofloxacin, and minocycline (ROM) are expected to be effective treatment for multi-bacillary leprosy. Patients with MB leprosy received ROM (n = 10) or World Health Organization multi-drug therapy (MDT) (n = 11). Treatment with ROM was given as 24 consecutive monthly observed doses of rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg). Treatment with MDT was given as 24 consecutive monthly observed doses of rifampin (600 mg) and clofazimine (300 mg), and unobserved daily dapsone (100 mg) and clofazimine (50 mg). Twenty patients completed the 24-month regimens with > 99% compliance. Treatments with ROM and MDT were safe, tolerable, and caused similar improvements in lesions, bacterial indices, and histology. All MDT recipients developed clofazimine-induced pigmentation. Six ROM and nine MDT recipients assessed at five or more years after completion of treatment had no evidence of relapse. Twenty-four months of treatment with ROM is a safe, well-tolerated, and convenient regimen that may provide an alternate therapy to MDT for MB leprosy. Larger trials with sufficient follow-up would better define the role of ROM.
Assuntos
Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Minociclina/administração & dosagem , Ofloxacino/administração & dosagem , Rifampina/administração & dosagem , Adolescente , Adulto , Clofazimina/administração & dosagem , Dapsona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the Leonard Wood Memorial Leprosy Research Center, Cebu, the Philippines. Treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. Reactions and side effects were minimal. Single doses of either agent did not result in significant killing of Mycobacterium leprae, but significant bactericidal activity was observed for all fluoroquinolone-treated patients by one week of daily therapy (n = 21), and either agent independently by 3 weeks of daily therapy. At the completion of therapy only two of 10 pefloxacin-treated patients and 0 of 11 ofloxacin-treated patients harboured any detectable viable M. leprae from active lesions, confirming previous work that these fluoroquinolones exhibit bactericidal activity in leprosy patients and more than that found previously for dapsone and clofazimine.