A profile of patients treated at a national leprosy outpatient referral clinic in Rio de Janeiro, Brazil, 1986-2007 / Perfil de los enfermos tratados en un servicio nacional de remisión de pacientes ambulatorios con lepra en Río de Janeiro, Brasil, 1986-2007

OBJECTIVE: To analyze a profile of patients treated at a national leprosy outpatient referral clinic in metropolitan Rio de Janeiro, Brazil, over a period of more than two decades, and the subgroup of nationally registered leprosy cases from the same residential area, as well as all registered cases statewide. METHODS: An observational, descriptive analysis was carried out for patients treated from 1986 to 2007 at the Souza Araújo Outpatient Clinic (Ambulatório Souza Araújo, ASA), a national referral center for the diagnosis and treatment of leprosy at the Oswaldo Cruz Foundation (Fiocruz) that serves clients from the city of Rio de Janeiro and other municipalities in the metropolitan area of Rio de Janeiro State. Demographic and clinical data for the subgroup of leprosy cases registered with Brazil's National Disease Notification System (Sistema Nacional de Informação de Agravos de Notificação, SINAN) between 2001 and 2007 and residing in the same municipalities as the ASA patients, and for all registered cases statewide, were also analyzed. RESULTS: Among the ASA patients, there was a decrease in average family income (from 3.9 to 2.7 times the minimum salary between the periods 1998-2002 and 2003-2007); the proportion of multibacillary (MB) patients (from 52.7% to 46.9%); and the proportion of patients younger than 15 years old (from 12.8% to 8.7%). Among the MB patients, the average initial and final bacilloscopic indices were significantly higher in 2003-2007. Compared with the SINAN cases, more ASA cases involved disability and were younger than 15 years old. CONCLUSIONS: Patients living with leprosy in the metropolitan area of the state of Rio de Janeiro belong to the most deprived social strata and have not benefited from the overall improvement in socioeconomic conditions in Brazil.

OBJETIVO: Analizar el perfil de los enfermos tratados en un servicio nacional de remisión de pacientes ambulatorios con lepra ubicado en la zona metropolitana de Río de Janeiro, Brasil, durante más de dos decenios, y el subgrupo de casos de lepra registrados a nivel nacional de la misma zona de residencia, así como todos los casos registrados a nivel estatal. MÉTODOS: Se llevó a cabo un análisis observacional y descriptivo de los pacientes tratados desde 1986 a 2007 en el servicio ambulatorio Souza Araújo (ASA), un centro de remisión nacional para el diagnóstico y el tratamiento de la lepra en la Fundación Oswaldo Cruz, que atiende a pacientes de la ciudad de Río de Janeiro y de otros municipios de la zona metropolitana del Estado de Río de Janeiro. También se analizaron los datos demográficos y clínicos del subgrupo de casos de lepra registrados con el Sistema Nacional de Notificación de Enfermedades del Brasil (SINAN) entre el 2001 y el 2007 residentes en los mismos municipios que los pacientes atendidos en el ASA, y de todos los casos registrados a nivel estatal. RESULTADOS: En los pacientes atendidos en el ASA hubo una disminución en los ingresos familiares promedio (de 3,9 a 2,7 veces el sueldo mínimo entre los períodos 1998-2002 y 2003-2007), en la proporción de pacientes multibacilares (de 52,7% a 46,9%), y en la proporción de pacientes menores de 15 años de edad (de 12,8% a 8,7%). En los pacientes multibacilares, los índices baciloscópicos promedio inicial y final fueron significativamente mayores en el período 2003-2007. En comparación con los casos del SINAN, en el ASA hubo más casos con discapacidad y en menores de 15 años de edad. CONCLUSIONES: Los pacientes con lepra de la zona metropolitana del Estado de Río de Janeiro pertenecen al estrato social más bajo y no se han beneficiado con el mejoramiento general de la situación socioeconómica en el Brasil.

Pure neural leprosy: steroids prevent neuropathy progression

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88 percent male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3 percent) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42 percent of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.

A poliquimioterapia (PQT), com rifampicina, dapsona, e clofazimina, trata a infecção na hanseníase, mas é insuficiente para interromper ou prevenir o comprometimento neurológico que causa as incapacidades e desabilidades, nesta enfermidade. Este estudo de série de casos avalia o benefício do uso combinado de prednisona e PQT na prevenção do dano neurológico em pacientes com a forma neural pura da hanseníase (FNP). Além do PQT, 24 pacientes (88 por cento homens, com idade variando entre 20-79, mediana=41) receberam uma dose diária de 60 mg prednisona que foi reduzida gradualmente na dose de 10 mg durante cada um dos 5 meses subseqüentes. FNP foi diagnosticada clinicamente e confirmada através do estudo histopatológico ou PCR. Baixa prevalência de reação (8,3 por cento) foi observada apenas após o final do tratamento. A maioria dos parâmetros clínicos mostrou melhora significativa e redução do bloqueio de condução foi observada em 42 por cento dos pacientes. A administração de doses altas de prednisona melhora a evolução clínica e eletrofisiológica de pacientes com a FNP de hanseníase, contribuindo na prevenção de novos comprometimentos neurológicos.

Whole blood assay to access T cell-immune responses to Mycobacterium tuberculosis antigens in healthy Brazilian individuals

The production of interferon gamma (IFNgamma) guarantees effective T cell-mediated immunity against Mycobacterium tuberculosis infection. In the present study, we simply compare the in vitro immune responses to Mycobacterium antigens in terms of IFNg production in a total of 10 healthy Brazilian volunteers. Whole blood and mononuclear cells were cultivated in parallel with PPD, Ag85B, and M. bovis hsp65, and five-days supernatants were harvested for cytokine detection by ELISA. The inter-assay result was that the overall profile of agreement in response to antigens was highly correlated (r² = 0.9266; p = 0.0102). Potential analysis is in current progress to dictate the usefulness of this method to access the immune responses also in tuberculosis patients and its contacts.

Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05) on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease

Edema na hanseníase: aspectos clínicos e terapêuticos / Edema in leprosy: clinical and therapeutical aspects

Durante o curso da hanseníase, o edema comumente descrito como um sintoma de estados reacionais, pode ocorrer. Tanto o diagnóstico como a terapêutica adequada säo, freqüentemente, difíceis de conseguir e assim podem acarretar permanente dano aos membros inferiores. Em um ano de acompanhamento, pacientes hansenianos - 10 multibacilares e 1 paucibacilar -, que foram submetidos a um protocolo clínico para o diagnóstico e classificaçäo histopatológica, apresentaram clinicamente edema, localizado ou sistêmico. Entre estes pacientes, cinco apresentaram simultaneamente outros sintomas de reaçäo, 4 foram classificados como reaçäo Tipo I e um como reaçäo tipo II. Por outro lado, três pacientes näo apresentaram reaçäo no momento do diagnóstico, mas desenvolveram alguns aspectos de reaçäo posteriormente (2 tiveram neurite e um teve reaçäo tipo I). Os edemas observados precedendo ou associados a quadros reacionais apresentaram ótima resposta clínica às drogas de açäo anti-inflamatória (corticóide, talidomida e pentoxifilina) utilizadas para o tratamento dos estados reacionais, na ausência de qualquer outro tratamento normalmente usado para edema. Embora necessitem ser confirmados por estudos controlados, estes dados sugerem fortemente que mecanismos imunológicos estejam envolvidos na fisiopatologia dos edemas na hanseníase

Reactional states in multibacilary hansen disease patients during multidrug therapy

It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI 3

Reactional states in multibacillary Hansen disease patients during multidrug therapy

Reacoes sao ocorrencias comuns no curso da hanseniase e sao responsaveis pelo agravamento das lesoes neurais. Uma coorte de 162 pacientes recem-diagnosticados, baciloscopicamente positivos, em acompanhamento no Ambulatorio de Hanseniase da Fundacao Oswaldo Cruz (FIOCRUZ) foi selecionada para estudo. Observou-se que 46 por cento dos pacientes multibacilares submetidos a 24 doses fixas de poliquimioterapia (PQT) apresentaram reacoes durante o tratamento; todos multibacilares eram suscetiveis e cuidados e atencao constantes eram necessarios. Quatorze por cento foram classificados como BB, 52 por cento como BL e 33 por cento foram classificados como LL. Nenhuma das variaveis em estudo, tais como: sexo, idade, forma clinica, tempo de doenca, extensao das lesoes dermatologicas, indice baciloscopico (IB), ou grau de incapacidade associaram-se a reacao entre os pacientes estudados...

Estudo de auto-anticorpos para ilhotas pancreáticas (ICA e ICA-CF) e evoluçäo para o diabetes insulino-dependente (DM ID) / Progression to IDDM and islet cell antibodies (ICA; ICA-CF)

Foram acompanhados, por três anos, oito familiares em 1§ grau de pacientes com Diabetes insulino-dependentes (DMID) regularmente atendidos no ambulatório de Diabetes da Disciplina de Diabetes e Metodologia do HUPE-UERJ, todos ICA e/ou ICA-CF positivos. Dois oito casos, três casos, todos com idade inferior a 15 anos, evoluíram para o DMID respectivamente 12, 21 e 8 meses após a primeira detecçäo dos auto-anticorpos. Quatro casos persistiram ICA e/ou ICA-CF positivos e em um caso houve negativaçäo da reaçäo no período de observaçäo. A evoluçäo para o DMID foi correlacionada à titulaçäo dos ICA e/ou ICA-CF (ò1/16). Pelo tamanho da amostra concluímos que, em três anos de observaçäo, 37,5 por cento dos familiares em 1§ grau com títulos de ICA elevados e positividade aos ICA-CF evoluíram para o DMID, enfatizando a importância de ambos como marcadores de previsäo para o DMID.

Immunological status of ENL (erythema nodosum leprosum) patients: its relationship to bacterial load and levels of circulating IL-2R

Dados recentes sugerem que o curso clinico dos estados reacionais na lepra esta estritamente relacionado a liberacao local ou sistemica de citocinas. Neste estudo, pacientes com ENL (erythema nodosum leprosum) foram agrupadas segundo a intensidade de seus sintomas clinicos. Os aspectos clinicos e imunologicos do ENL e os efeitos desses parametros na carga bacilar foram estabelecidos em conjuncao com a resposta imune in vitro desses pacientes, a antigenos microbacterianos. Em 10 de 17 pacientes testados, o indice bacteriano (IB) foi reduzido em pelo menos 1 log desde o diagnostico da lepra ate o aparecimento do primeiro episodio reacional, comparado a uma reducao esperada de 0.3 log no grupo reacional no mesmo periodo de MDT (multidrogaterapia)...

Interaction of the leprosy bacillus and human host: relevant components and mechanism of disease

The study of the relationship between Mycobacterium leprae and its human host, by investigating the bacterial components and the host immune response, will certainly provide the basis for a better treatment and control of leprosy. In addition, leprosy represents an attractive model from where important aspects regarding pathogen survival strategies, and the basic mechanisms involved in the regulation of the immune system can be learned. This review describes the definition of a major protein of the leprosy bacillus with a potential role in its virulence. The involvement of key cytokines and leukocyte subsets in protection and pathophysiology of this disease is also presented.

Cellular response to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients

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