RESUMO
It has been speculated that, as seen in tuberculosis, human immunodeficiency virus (HIV) and Mycobacterium leprae (M. leprae) co-infection may exacerbate the pathogenesis of leprosy lesions and/or lead to increased susceptibility to leprosy. However, to date, HIV infection has not appeared to increase susceptibility to leprosy. In contrast, initiation of antiretroviral treatment (ART) has been reported to be associated with anecdotal activation of M. leprae infection and exacerbation of existing leprosy lesions. To determine whether ART is associated with worsening of the manifestations of leprosy, a cohort of leprosy patients recruited between 1996 and 2006 at the Oswaldo Cruz Foundation (FIOCRUZ) Leprosy Outpatient Clinic in Rio de Janeiro, Brazil, was studied longitudinally. ART treatment of HIV/leprosy co-infection was associated with the tuberculoid type, paucibacillary disease, and lower bacillary loads. CD4 lymphocyte counts were higher among HIV/leprosy patients at the time of leprosy diagnosis, while viral loads were lower compared with the time of HIV diagnosis. The conclusion was that ART and immune reconstitution were critical factors driving the development and/or clinical appearance of leprosy lesions.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/etiologia , Hanseníase/imunologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Comorbidade , Suscetibilidade a Doenças , Feminino , Infecções por HIV/epidemiologia , Humanos , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Hanseníase/epidemiologia , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Antígenos CD , Antígenos HLA-DR , Citometria de Fluxo , Células Dendríticas , Células de Langerhans , Dermatopatias/dietoterapia , Dermatopatias/imunologia , Dermatopatias/patologia , Fator de Necrose Tumoral alfa , Fármacos Dermatológicos/imunologia , Fármacos Dermatológicos/uso terapêutico , Imuno-Histoquímica , Imunossupressores/uso terapêutico , /sangue , /sangue , Linfócitos T , Resultado do Tratamento , Sarcoidose/imunologia , Sarcoidose/patologia , Sarcoidose/tratamento farmacológico , Talidomida/imunologia , Talidomida/uso terapêuticoAssuntos
Antígenos CD1/análise , /análise , /análise , Biópsia , Cicatrização/imunologia , Hanseníase/imunologia , Hanseníase/metabolismo , Hanseníase/patologia , Hipersensibilidade Tardia/imunologia , Imuno-Histoquímica , Mycobacterium leprae/imunologia , Neuritos/imunologia , Neuritos/metabolismo , Neuritos/patologia , Teste TuberculínicoRESUMO
Previous studies have shown that when multibacillary leprosy patients were treated with recombinant human interferon gamma (rhuIFN-gamma) for 6-10 months there was an accelerated reduction in the number of acid-fast bacilli in the skin at the site of injection as well as an accelerated bacillary reduction at distal sites. However, this favorable out-come of IFN-gamma treatment was associated with the development of erythema nodosum leprosum (ENL). The present study was undertaken to investigate whether rhuIFN-gamma-induced bacillary clearance could be disassociated from the induction of ENL. rhuIFN-gamma was administered together with thalidomide and conventional multidrug chemotherapy to newly diagnosed leprosy patients. During treatment with this combination of drugs, the mean reduction in bacterial load was the same as the reduction observed with chemotherapy alone. Moreover, the inclusion of thalidomide in the treatment regimen was associated with a low frequency of ENL episodes. A second group of leprosy patients, who had already completed 2 years of chemotherapy, were treated with rhuIFN-gamma only. In those patients who were skin bacilli negative, ENL did not occur during rhuIFN-gamma treatment. In contrast, in bacilli-positive patients the frequency of ENL during rhuIFN-gamma treatment was higher, as was the occurrence of local erythema and induration. However, rhuIFN-gamma treatment without concomitant chemotherapy did not result in a reduction in the bacterial load in the skin of bacilli-positive patients. These findings, taken together, indicate that rhuIFN-gamma does not, by itself, accelerate bacterial clearance, but requires concomitant chemotherapy to achieve the accelerated reduction in bacillary load. Thalidomide reduces the frequency of IFN-gamma-induced ENL, but also eliminates the IFN-gamma-induced bacillary clearance.
Assuntos
Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/tratamento farmacológico , Interferon gama/uso terapêuticoAssuntos
Citocinas/administração & dosagem , Citocinas/uso terapêutico , Hanseníase/prevenção & controle , Infecção por Mycobacterium avium-intracellulare/prevenção & controle , Infecções por Mycobacterium/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Tuberculose/prevenção & controleAssuntos
HIV-1 , Citocinas/fisiologia , Eritema Nodoso/etiologia , Eritema Nodoso/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Hanseníase Virchowiana/etiologia , Hanseníase Virchowiana/terapia , Imunidade Celular , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Injeções Intradérmicas , Interferon gama/administração & dosagem , Interferon gama/efeitos adversos , Talidomida/administração & dosagem , Tuberculose/complicações , Tuberculose/etiologia , Tuberculose/tratamento farmacológicoAssuntos
Cicatrização , Cricetinae , Células CHO , Células de Langerhans , Células de Langerhans/fisiologia , Células de Langerhans/patologia , Escherichia coli/genética , Fator Estimulador de Colônias de Granulócitos , Fatores de Tempo , Hanseníase Dimorfa/fisiopatologia , Hanseníase Dimorfa/patologia , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/fisiopatologia , Hanseníase Virchowiana/patologia , Hanseníase Virchowiana/tratamento farmacológico , Injeções Intradérmicas , Injeções Subcutâneas , Leucócitos , Leucócitos/fisiologia , Macrófagos , Microscopia Eletrônica , Pele , Pele/fisiopatologia , Pele/patologia , Pele/ultraestrutura , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Queratinócitos , Queratinócitos/fisiologia , Queratinócitos/patologiaAssuntos
Eritema Nodoso/induzido quimicamente , Eritema Nodoso/patologia , Eritema Nodoso/tratamento farmacológico , Fator de Necrose Tumoral alfa/biossíntese , Fatores de Tempo , Hanseníase Dimorfa/patologia , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/induzido quimicamente , Hanseníase Virchowiana/patologia , Hanseníase Virchowiana/terapia , Interferon gama , Interferon gama/uso terapêutico , Monócitos , Monócitos/fisiologia , Pele/patologia , Talidomida/uso terapêuticoAssuntos
Adolescente , Anticorpos Antibacterianos/análise , Antígenos de Bactérias/análise , Contagem de Leucócitos , Fatores de Tempo , Hanseníase Virchowiana/terapia , Imunidade Celular , /administração & dosagem , Microscopia Eletrônica , Mycobacterium leprae/imunologia , Proteínas Recombinantes/uso terapêutico , Relação Dose-Resposta a DrogaRESUMO
The local response to single intradermal injection of 10 ug recombinat gamma-interferon (rIFNgamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 ug rIFNgamma at received another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm pinch biopsies were obtained and axamined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell eccumulation peaked at 72 hours but then persisted for 5-7 days. Only smal numbers (one-third or less of toal T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFNgamma led to a more intense accumulation of cells. Ten ug of rIFNgamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidemir exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFNgamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably aloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells