Contact surveillance is an important strategy to ensure effective early diagnosis and control of leprosy; passive detection may not be as efficient because it is directly tied to the ready availability of heath care services and health education campaigns. The aim of this study was to reinforce that contact surveillance is the most effective strategy for the control of leprosy. The analysed data were obtained from a cohort of contacts and cases diagnosed through a national referral service for leprosy. We analysed data from patients diagnosed between 1987-2010 at the Souza Araújo Ambulatory in Rio de Janeiro. Epidemiological characteristics of leprosy cases diagnosed through contact surveillance and characteristics of passively detected index cases were compared using a conditional logistic regression model. Cases diagnosed by contact surveillance were found earlier in the progression of the disease, resulting in less severe clinical presentations, lower levels of initial and final disability grades, lower initial and final bacterial indices and a lower prevalence of disease reaction. In this respect, contact surveillance proved to be an effective tertiary prevention strategy, indicating that active surveillance is especially important in areas of high endemicity, such as Brazil.

Contact surveillance is a valuable strategy for controlling leprosy. A dynamic cohort study of leprosy contacts was initiated in 1987 at Oswaldo Cruz Foundation. The objective of this work was to review the data on the major risk factors leading up to the infectious stage of the disease, estimate incidence rates of leprosy in the cohort and characterise the risk factors for the disease among the contacts under surveillance. The incidence rate of leprosy among contacts of leprosy patients was estimated at 0.01694 cases per person-year in the first five years of follow-up. The following factors were associated with acquiring the disease: (i) not receiving the BCG vaccine, (ii) a negative Mitsuda reaction and (iii) contact with a patient with a multibacillary clinical form of leprosy. The contacts of index patients who had high bacilloscopic index scores > 1 were at especially high risk of infection. The following factors were associated with infection, which was defined as a seropositive reaction for anti-phenolic glicolipid-1 IgM: (i) young age (< 20 years), (ii) a low measured Mitsuda reaction (< 5 mm) and (iii) contact with an index patient who had a high bacilloscopic index. BCG vaccination and re-vaccination were shown to be protective among household contacts. The main conclusions of this study indicate an urgent need for additional leprosy control strategies in areas with a high incidence of the disease.

O objetivo deste trabalho foi comparar dados epidemiológicos de pacientes de hanseníase residentes em dois municípios com perfil socioeconômico e nível de endemicidade diferentes e que foram acompanhados em um mesmo centro de referência. Foi realizado um estudo descritivo dos dados de pacientes tratados no ambulatório Souza Araújo, 1986 a 2008, residentes nos municípios do Rio de Janeiro (n = 1353) e Duque de Caxias (n = 336). Entre os pacientes desta cidade, em comparação com os da outra, observou-se maior proporção de casos: com idade inferior a 15 anos, multibalicares, com maior índice baciloscópico (IB) inicial, e detectados através da vigilância de contatos. Os pacientes de Duque de Caxias apresentaram menor renda média e nível de escolaridade. Não foram observadas diferenças estatisticamente significativas quanto ao sexo, grau de incapacidade inicial, reação no diagnóstico, IB final, abandono e regularidade do tratamento. As diferenças encontradas entre os pacientes acompanhados em um mesmo centro de referência poderiam estar, em parte, relacionadas a diferenças contextuais existentes entre os municípios. Por outro lado, observou-se que a oferta de tratamento e acompanhamento podem minimizar o efeito que os fatores contextuais apresentam sobre os desfechos de saúde.

The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). Results: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.

O objetivo deste trabalho foi comparar dados epidemiológicos de pacientes de hanseníase residentes em dois municípios com perfil socioeconômico e nível de endemicidade diferentes e que foram acompanhados em um mesmo centro de referência. Foi realizado um estudo descritivo dos dados de pacientes tratados no ambulatório Souza Araújo, 1986 a 2008, residentes nos municípios do Rio de Janeiro (n = 1353) e Duque de Caxias (n = 336). Entre os pacientes desta cidade, em comparação com os da outra, observou-se maior proporção de casos: com idade inferior a 15 anos, multibalicares, com maior índice baciloscópico (IB) inicial, e detectados através da vigilância de contatos. Os pacientes de Duque de Caxias apresentaram menor renda média e nível de escolaridade. Não foram observadas diferenças estatisticamente significativas quanto ao sexo, grau de incapacidade inicial, reação no diagnóstico, IB final, abandono e regularidade do tratamento. As diferenças encontradas entre os pacientes acompanhados em um mesmo centro de referência poderiam estar, em parte, relacionadas a diferenças contextuais existentes entre os municípios. Por outro lado, observou-se que a oferta de tratamento e acompanhamento podem minimizar o efeito que os fatores contextuais apresentam sobre os desfechos de saúde.

The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). Results: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.

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.

O reconhecimento clínico precoce dos episódios reacionais traz grandes benefícios para os pacientes com hanseníase, devido à possibilidade de intervenção terapêutica imediata e adequada, evitando o desenvolvimento de incapacidades que tanto estigmatizam e complicam a doença. Existem três formas de episódios reacionais: os tipos 1 e 2, e a neurite. Esta última pode aparecer isoladamente ou acompanhar as formas anteriores. Em alguns casos só são observadas as manifestações cutâneas e/ou neurológicas das reações, enquanto em outros, alterações sistêmicas podem acrescentar-se ao quadro. O tratamento utilizando a associação de medicamentos antiinflamatórios e imunossupressores parece ser o mais adequado para evitar as recorrências e os efeitos colaterais.

The early clinical recognition of reactional states brings great benefits to leprosy patients due to the possibility of appropriate and immediate therapeutic intervention, thus avoiding the development of disabilities that so much stigmatize and complicate the disease. There are three types of reactional episodes: types 1, 2 and neuritis. The latter may occur alone or together with the former forms. In some cases only neurological and/or skin manifestations are observed in the reactions; in others, patients present systemic alterations. The treatment with an association of immunosuppressors and anti-inflammatory drugs seems to be the most effective to avoid recurrences and side effects

La estrategia actual para el control de la lepra en Brasil se basa en dos actividades principales: la detección precoz de casos y el tratamiento de casos con farmacoterapia combinada. Además de dichas medidas, se realizan esfuerzos complementarios para identificar los contactos domésticos para el diagnóstico precoz y la vacunación con el bacilo de Calmette-Guérin (BCG). Sin embargo, la eficacia de estas acciones a la hora de reducir la incidencia de la lepra es aún discutible. Esto genera dudas acerca de la factibilidad de eliminar la lepra en Brasil e indica que deberían adoptarse otras medidas de prevención. A pesar del hecho de que la vacunación de los contactos se practica desde hace varios años, falta información sobre el impacto de esta medida sobre la incidencia de la lepra en la comunidad. Además, con frecuencia no se tiene en cuenta el impacto de la vacunación neonatal con la vacuna BCG. Sostenemos que hay lugar para la investigación de métodos alternativos en el control y recomendamos que el programa brasileño de control haga un seguimiento esmerado de las tasas de cobertura para la vacunación neonatal en aquellas zonas donde la lepra es endémica, con el fin de lograr que la cobertura siga siendo elevada. Además, recomendamos la realización de estudios, orientados hacia el desarrollo de políticas, sobre la eficacia, factibilidad e impacto de estrategias alternativas más previsoras. Algunos posibles temas para estos estudios serían: 1) el impacto de la vacunación de contactos sobre la incidencia de la enfermedad en la población en general, 2) la factibilidad y el impacto de la quimioprofilaxis, y 3) el impacto de la identificación de grupos de alto riesgo (o mediante la adopción de una definición amplia de los contactos expuestos a la lepra, o mediante la creación de nuevas herramientas diagnósticas), y del diseño de programas para la detección precoz y la administración de farmacoterapia combinada específicamente para estos grupos.

DNA samples from blood and nasal swabs of 125 healthy household contacts was submitted to amplification by polymerase chain reaction (PCR) using a Mycobacterium leprae-specific sequence as a target for the detection of subclinical infection with M. leprae.All samples were submitted to hybridization analysis in order to exclude any false positive or negative results. Two positive samples were confirmed from blood out of 119 (1.7%) and two positive samples from nasal secretion out of 120 (1.7%). The analysis of the families with positive individuals showed that 2.5% (n = 3) of the contacts were relatives of multibacilary patients while 0.8% of the cases (n = 1) had a paucibacilary as an index case. All positive contacts were followed up and after one year none of them presented clinical signs of the disease. In spite of the PCR sensitivity to detect the presence of the M. leprae in a subclinical stage, this molecular approach did not seem to be a valuable tool to screen household contacts, since we determined a spurious association of the PCR positivity and further development of leprosy.

Este trabalho foi desenvolvido para estudar os fatores que influem no adoecimento dos contatos intradomiciliares de hanseníase. Foi estabelecida uma coorte de contatos intradomiciliares de hanseníase no setor de Hanseníase da Fiocruz, no Rio de Janeiro. Entre 1987 e 1991, em que foram acompanhados 670 contatos saudáveis, a taxa de incidência por pessoa-ano de follow-up foi de 0,01694. Porém, houve variação com o tempo de acompanhamento de cada indivíduo, sendo de 0,06385 ao final do primeiro ano, de 0,03299 ao final do segundo, 0,02370 ao final do terceiro, 0,018622 ao final do quarto e 0,01694 ao final do período. Foi especificado um modelo de regressão logística para os indivíduos acompanhados nos primeiros cinco anos, envolvendo 758 contatos, incluindo nessa situação os casos co-prevalentes. O risco de incidência de hanseníase está relacionado com a negatividade do teste de Mitsuda, com OR de 3,093 (IC95% = 1,735-5,514), com a vacinação pelo BCG, OR de 0,3802 (IC95% = 0,2151-0,66719), e com a forma multibacilar do caso-índice, OR de 2,547 (IC95% = 1,249-5,192). Os resultados indicam que a incidência da hanseníase em contatos está associada à forma multibacilar da doença e aos fatores imunes dos contatos.

This study aimed to identify factors influencing the development of leprosy (Hansen's disease) in household contacts. A dynamic cohort was analyzed from 1987 to 1991 at the Hansen's Disease Department of the Oswaldo Cruz Foundation in Rio de Janeiro. The incidence rate was 0.01694 person-years of follow-up. Nevertheless, for subjects at the end of the first year of follow-up the incidence rate was 0.06385 (end of second year, 0.03299; end of third year, 0.02370; end of fourth year, 0.018622; and end of observation period, 0.01694). A stepwise multivariate logistic regression model was proposed to study the risk of developing leprosy, including co-prevalent cases, totaling 758 contacts. In the final model, the risk was associated with a negative Mitsuda skin test (OR = 3.093; CI 95% = 1.735-5.514), prior BCG vaccination (OR = 0.3802; CI 95% = 0.2151-0.66719), and multibacillary primary clinical form (OR = 2.547; CI 95% = 1.249-5.192). The results showed that both multibacillary leprosy and specific immune status are significant indicators for developing the disease in a cohort of household contacts.

Este trabalho foi desenvolvido para estudar os fatores que influem no adoecimento dos contatos intradomiciliares de hanseníase. Foi estabelecida uma coorte de contatos intradomiciliares de hanseníase no setor de Hanseníase da Fiocruz, no Rio de Janeiro. Entre 1987 e 1991, em que foram acompanhados 670 contatos saudáveis, a taxa de incidência por pessoa-ano de follow-up foi de 0,01694. Porém, houve variação com o tempo de acompanhamento de cada indivíduo, sendo de 0,06385 ao final do primeiro ano, de 0,03299 ao final do segundo, 0,02370 ao final do terceiro, 0,018622 ao final do quarto e 0,01694 ao final do período. Foi especificado um modelo de regressão logística para os indivíduos acompanhados nos primeiros cinco anos, envolvendo 758 contatos, incluindo nessa situação os casos co-prevalentes. O risco de incidência de hanseníase está relacionado com a negatividade do teste de Mitsuda, com OR de 3,093 (IC95% = 1,735-5,514), com a vacinação pelo BCG, OR de 0,3802 (IC95% = 0,2151-0,66719), e com a forma multibacilar do caso-índice, OR de 2,547 (IC95% = 1,249-5,192). Os resultados indicam que a incidência da hanseníase em contatos está associada à forma multibacilar da doença e aos fatores imunes dos contatos.

This study aimed to identify factors influencing the development of leprosy (Hansen's disease) in household contacts. A dynamic cohort was analyzed from 1987 to 1991 at the Hansen's Disease Department of the Oswaldo Cruz Foundation in Rio de Janeiro. The incidence rate was 0.01694 person-years of follow-up. Nevertheless, for subjects at the end of the first year of follow-up the incidence rate was 0.06385 (end of second year, 0.03299; end of third year, 0.02370; end of fourth year, 0.018622; and end of observation period, 0.01694). A stepwise multivariate logistic regression model was proposed to study the risk of developing leprosy, including co-prevalent cases, totaling 758 contacts. In the final model, the risk was associated with a negative Mitsuda skin test (OR = 3.093; CI 95% = 1.735-5.514), prior BCG vaccination (OR = 0.3802; CI 95% = 0.2151-0.66719), and multibacillary primary clinical form (OR = 2.547; CI 95% = 1.249-5.192). The results showed that both multibacillary leprosy and specific immune status are significant indicators for developing the disease in a cohort of household contacts.

Dados recentes sugerem que o curso clínico dos estados reacionais na lepra está estritamente relacionado à liberação local ou sistêmica de citocinas. Neste estudo, pacientes com ENL (erythema nodosum leprosum) foram grupados segundo a intensidade de seus sintomas clínicos. Os aspectos clínicos e imunológicos do ENL e os efeitos desses parâmetros na carga bacilar foram estabelecidos em conjunção com a resposta imune in vitro desses pacientes, a antígenos microbacterianos. Em 10 de 17 pacientes testados, o índice bacteriano (IB) foi reduzido cm pelo menos 1 log desde o diagnóstico da lepra até o aparecimento do primeiro episódio reacional, comparado a uma redução esperada de 0.3 log no grupo não reacional no mesmo período de MDT (multidrogaterapia). Entretanto, nenhuma diferença na taxa de redução do IB foi notada no final da MDT entre os pacientes ENL e os lepromatosos não reacionais. Assim também, embora os níveis de TNF-alfa (fator de necrose tumoral) estivessem aumentados no soro de 70,6% dos pacientes com ENL testados, nenhuma relação foi notada entre os níveis circulantes de TNF-alfa e a diminuição do IB detectada no aparecimento do primeiro episódio reacional. A avaliação da viabilidade bacteriana do M. leprae isolado de lesões reacionais não mostrou crescimento na pata de camundongo. Somente 20% dos pacientes demonstraram resposta imune específica ao M. leprae durante o ENL. Além disso altos níveis de IL-2R (receptor de interleucina 2) solúvel estiveram presentes em 78% dos pacientes. Anticorpos circulantes anti-nervo (anti-ceramídio e anti-galactocerebrosídio) e anti-micobacterianos foram também detectados no soro dos pacientes, e não estiveram relacionados ao curso clínico da doença. Nossos dados sugerem que a morte bacteriana está aumentada durante as reações. A emergência de resposta imune específica ao M. leprae e o papel efetivo do TNF-alfa na mediação de fragmentação bacteriana necessita ainda ser esclarecida

Recent data suggest that the clinical course of reactional states in leprosy is closely related to the cytokine profile released locally or systemically by the patients. In the present study, patients with erythema nodosum leprosum (ENL) were grouped according to the intensity of their clinical symptoms. Clinical and immunological aspects of ENL and the impact of these parameters on bacterial load were assessed in conjunction with patients' in vitro immune response to mycobacterial antigens. In 10 out of the 17 patients tested, BI (bacterial index) was reduced by at least 1 log from leprosy diagnosis to the onset of their first reactional episode (ENL), as compared to an expected 0.3 log reduction in the unreactional group for the same MDT (multidrug therapy) period. However, no difference in the rate of BI reduction was noted at the end of MDT among ENL and unreactional lepromatous patients. Accordingly, although TNF-alpha (tumor necrosis factor) levels were enhanced in the sera of 70.6% of the ENL patients tested, no relationship was noted between circulating TNF-alpha levels and the decrease in BI detected at the onset of the reactional episode. Evaluation of bacterial viability of M. leprae isolated from the reactional lesions showed no growth in the mouse footpads. Only 20% of the patients demonstrated specific immune response to M. leprae during ENL. Moreover, high levels of soluble IL-2R (interleukin-2 receptor) were present in 78% of the patients. Circulating anti-neural (anti-ceramide and anti-galactocerebroside antibodies) and anti-mycobacterial antibodies were detected in ENL patients' sera as well, which were not related to the clinical course of disease. Our data suggest that bacterial killing is enhanced during reactions. Emergence of specific immune response to M. leprae and the effective role of TNF-alpha in mediating fragmentation of bacteria still need to be clarified.