RESUMO
Leprosy remains an important health problem wordwide. The disease in caused by a chronic granulomatous infection of the skin and peripheral nerves with Mycobacterium leprae. The clinical range from tuberculoid to lepromatous leprosy is a result of variation in the cellular immune response to the mycobacterium. The resulting impairment of nerve fuinction causes be disabilities associated with leprosy. This review summarises recent advances in understanding of the biology of leprosy, clinical features of the disease, the current diagnostic criteria, and the new approaches to treatment of the infection and the immune-mediated complications. Supervesed multi-drug therapy (MDT) for fixed durations is highly effective for all forms of the disease. The widespread implemantation of MDT has been associated with a fall in the prevalence of the leprosy but as yet no reduction in the case-detection rate globally. Thus, leprosy control activities must be maintained for decades to interrupt transmission of infection
Assuntos
Humanos , Hanseníase/complicações , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/terapia , Hanseníase/transmissão , Mycobacterium leprae/citologia , Mycobacterium leprae/imunologia , Mycobacterium leprae/patogenicidade , Mycobacterium leprae/química , Quimioterapia Combinada , Educação em Saúde/tendências , Interações Hospedeiro-Parasita/imunologia , Neuritos/etiologia , Neuritos/imunologia , Neuritos/microbiologiaRESUMO
We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.
Assuntos
Feminino , Masculino , Adolescente , Adulto , Criança , Humanos , Antígenos de Bactérias , Especificidade da Espécie , Hanseníase , Interferon gama , Linfócitos T , Malaui , Mycobacterium , Mycobacterium bovis , Mycobacterium leprae , Mycobacterium tuberculosis , Proteínas Recombinantes de Fusão , Teste Tuberculínico , Tuberculose , Vacina BCG , VacinaçãoRESUMO
A DNA vaccine composed of the gene for the common mycobacterial secreted protein antigen 85B was demonstrated to protect the mouse foot pad against infection with Mycobacterium leprae. The protective effect was demonstrated by a 61%-88% reduction in the bacterial number, a protective effect less than that of BCG. The same DNA vaccine has been shown to protect mice against M. tuberculosis infection, and the importance of testing other candidate tuberculosis vaccines for their potential to protect against leprosy is discussed.
Assuntos
Humanos , DNA , Mycobacterium leprae/imunologia , Mycobacterium tuberculosis/imunologiaRESUMO
A new rapid immuno-chromatographic test card for the detection of antibodies to the Mycobacterium leprae 35-kD protein is described. The new assay is compared in the same group of subjects with a direct enzyme ELISA method for 35-kD antibodies and with assays for anti-phenolic glycolipid-I (PGL-I) antibodies using a standard ELISA as well as the recently described [quot ]dipstick[quot ] method. Good concordance was found between the rapid methods and the corresponding ELISA methods. The detection of untreated paucibacillary leprosy by the 35-kD test card was 59% compared with 27% for the PGL-I dipstick; however, the specificity for the 35-kD test card was 90% compared with 100% for the PGL-I dipstick in an endemic population. The potential application of these new, rapid serologic methods for the diagnosis of leprosy under field conditions is discussed.
Assuntos
Humanos , /imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Mycobacterium leprae/fisiologia , Mycobacterium leprae/genéticaAssuntos
Ativação Linfocitária , Clonagem Molecular , Cobaias , Dados de Sequência Molecular , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Genes Bacterianos , Hanseníase/imunologia , Hipersensibilidade Tardia , Homologia de Sequência de Aminoácidos , Leucócitos Mononucleares/imunologia , Mycobacterium avium/genética , Mycobacterium avium/imunologia , Mycobacterium leprae/genética , Proteínas Recombinantes , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Sequência de Aminoácidos , Sequência de Bases , Tuberculose Pulmonar/imunologiaRESUMO
Although multidrug therapy (MDT) was introduced into Nepal in 1983, the MDT coverage only recently exceeded 67%. In view of the large number of patients who were still receiving dapsone monotherapy, it is relevant to investigate the current levels of dapsone and rifampin resistance. The study was undertaken at a leprosy referral hospital near Kathmandu. Over a 5 1/2-year period, 157 leprosy patients with a bacterial index (BI) > or = 2.0 were investigated for drug resistance according to the method of Rees. Among previously untreated cases, 6% of 88 isolates showed low-dose dapsone resistance; among previously treated patients with a presumed relapse, 47% of 34 isolates demonstrated dapsone resistance. In the remaining 35 cases there was no growth in control mice. Rifampin resistance was not confirmed in any case.