Arginase 1 is a marker of protection against illness in contacts of leprosy patients.

Leprosy household contacts are generally more prone to develop the disease compared to the general population. Previous studies have demonstrated that genes related to the alternative activation (M2) profile in macrophages are associated with the increased bacillary load in multibacillary leprosy patients (MB), and that contacts of MB patients have a higher risk of contracting the disease. In addition, positive serological responses to PGL-1 or LID-1 are associated with a higher risk of disease. We performed a 5-year follow-up of contacts of leprosy patients and evaluated the pattern of gene and protein expression in cells from contacts that developed leprosy during this period. Leprosy household contacts had decreased soluble CD163 and heme oxygenase 1 (HO-1) serum levels when compared with healthy donors and leprosy patients. In contrast, arginase 1 activities were higher in contacts when compared with both healthy donors and leprosy patients. Of the contacts, 33 developed leprosy during the follow-up. Gene expression analysis revealed reduced ARG1 expression in these contacts when compared with contacts that did not develop disease. Arginase activity was a good predictive marker of protection in contacts (sensitivity: 90.0%, specificity: 96.77%) and the association with serology for anti-PGL-1 and anti-LID-1 increased the sensitivity to 100%. Altogether, the data presented here demonstrate a positive role of arginase against leprosy and suggest that the evaluation of arginase activity should be incorporated into leprosy control programs in order to aid in the decision of which contacts should receive chemoprophylaxis.

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients.

Reduction in incidence has been associated with the introduction of novel approaches, like chemo/immune-prophylaxis. Incidence determined through follow-up cohort studies can evaluate the implementation of these innovative policies towards control and prevention. We have assessed the incidence in our contacts cohort over past 33 years, considering the effect of demographic and clinical variables. Survival analysis was used to estimate the risk of leprosy. A total of 9024 contacts were evaluated, of which 192 developed leprosy, resulting in an overall incidence of 1.4/1000 person-years. The multivariate analysis showed that the major risk factors were (i) contact from MB index cases and (ii) consanguinity (iii) intra household contact. Lower risk was detected for contacts with BCG scar who were revaccinated. There was a significant decrease in accumulated risk between the 2011-2019 period compared with 1987, probably linked to the improvement in laboratory tools to monitor contacts, thereby providing early diagnosis of contacts at intake and reduction of transmission. Our findings suggest that a combination of contact surveillance and tracing, adequate neurodermatological examination, and availability of molecular tools is highly effective in supporting early diagnosis, while a second dose of the BCG vaccination can exert extra protection.

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment.

A case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011-2018.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.

Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

BACKGROUND: The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN: The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION: The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.

Interruption of persistent exposure to leprosy combined or not with recent BCG vaccination enhances the response to Mycobacterium leprae specific antigens.

Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-ß, IL-6, IL-17, TNF, IFN-γ, MIP1-ß, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through "trained immunity", that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.

Percepção do estigma e repercussões sociais em indivíduos com hanseníase / Perception of stigma and social impacts on individuals with Hansen's disease / Percepción del estigma y efectos sociales en personas con enfermedad de Hansen

Os portadores de hanseníase vivenciam situações de preconceito que, com o estigma e a discriminação, culminam para o isolamento social e a restrição dos relacionamentos sociais. Este estudo teve o objetivo de avaliar a percepção do estigma nos indivíduos com hanseníase e suas repercussões sociais. Caracterizou-se por um estudo qualitativo mediante aplicação de entrevistas semiestruturadas em 20 usuários cadastrados para tratamento poliquimioterápico nas unidades de referência na Zona da Mata Mineira, no primeiro semestre de 2014. A análise foi realizada por meio da análise de conteúdo e foram definidas as seguintes categorias de análise: Desconhecimento sobre a doença; Diagnóstico e cura; Discriminação e medo; Encobrimento da doença; Apoio social; e Vínculo e participação social. O desconhecimento sobre a doença interfere no enfrentamento por parte dos indivíduos e, aliado ao receio da discriminação, foi suficiente para que eles ocultassem seu diagnóstico para os outros. Dessa forma, não foi possível perceber nenhuma alteração em seu vínculo social. Destacaram-se as diversas reações emocionais no momento do diagnóstico além da ênfase dada à cura pelos entrevistados. Neste trabalho, ficou evidente que o encobrimento da doença e o suporte social atuaram como fatores de proteção que impediram momentos de discriminação e restrição de participação social.

The individuals with Hansen's disease experience situations of prejudice that, together with stigma and discrimination, culminate in social isolation and restrictions in social relationships. This study aimed to evaluate the perception of stigma in individuals with Hansen's disease and its social repercussions. It was configured as a qualitative study, by means of semi-structured interviews with 20 users registered to chemotherapy treatment in reference units of Zona da Mata Mineira, in the first half of 2014. The analysis was performed through content analysis and the following categories were defined: Lack of knowledge about the disease; Diagnosis and cure; Discrimination and fear; Concealment of the disease; Social support; and Bond and social participation. Lack of knowledge about the disease interferes with the individual's ability to cope with it, and coupled with fear of discrimination, it was enough for them to conceal their diagnosis from others. Thus, it was not possible to notice any changes in their social bonds. The different emotional reactions at the moment of diagnosis stood out, in addition to the emphasis on healing given by respondents. In this study, it became clear that the concealment of the disease and the social support acted as protective factors that prevented moments of discrimination and restriction in social participation.

Las personas con enfermedad de Hansen viven situaciones de prejuicio que, junto con el estigma y la discriminación, culminó con el aislamiento social y la restricción de las relaciones sociales. Este estudio tuvo como objetivo evaluar la percepción de estigma en personas con enfermedad de Hansen y sus repercusiones sociales. Caracterizado por un estudio cualitativo mediante la aplicación de entrevistas semiestructuradas con 20 usuarios registrados a tratamiento de quimioterapia en las unidades de referencia en la Zona da Mata Mineira, en el primer semestre de 2014. Se realizó el análisis mediante el análisis de contenido y las siguientes categorías del análisis se definieron: La ignorancia sobre la enfermedad; El diagnóstico y la cura; La discriminación y el miedo; El ocultamiento de la enfermedad; El apoyo social; y Enlace y la participación social. La ignorancia sobre la enfermedad interfiere con afrontamiento de los individuos y, junto con el temor a la discriminación fuera suficiente para ellos para ocultar su diagnóstico a los demás. Por lo tanto, no fue posible notar cualquier cambio en su enlace social. Destacado las diferentes reacciones emocionales al momento del diagnóstico, además del énfasis en la curación por los encuestados. En este estudio, se hizo evidente que el ocultamiento de la enfermedad y el apoyo social actuó como factores de protección que impedían momentos de la discriminación y la restricción de la participación social.

Impact of a Reference Center on Leprosy Control under a Decentralized Public Health Care Policy in Brazil.

OBJECTIVE: We evaluated the profile of patients referred to the Fiocruz Outpatient Clinic, a reference center for the diagnosis and treatment of leprosy in Rio de Janeiro, RJ, and analyzed the origins and outcomes of these referrals. METHODS: This is an observational retrospective study based on information collected from the Leprosy Laboratory database at Fiocruz, Rio de Janeiro, RJ, Brazil. A total of 1,845 suspected leprosy cases examined at the reference center between 2010 and 2014 were included. The originating health service referrals and diagnostic outcomes were analyzed as well as the clinical and epidemiological data of patients diagnosed with leprosy. RESULT: Our data show that the profile of the patients treated at the Clinic has changed in recent years. There was an increase in both the proportion of patients with other skin diseases and those who had visited only one health service prior to our Clinic. Among the total 1,845 cases analyzed, the outcomes of 1,380 were linked to other diseases and, in 74% of these cases, a biopsy was not necessary to reach a diagnostic conclusion. A decrease in new leprosy case detection among our patients was also observed. Yet, among the leprosy patients, 40% had some degree of disability at diagnosis. CONCLUSION: The results of the present study demonstrated the importance of referral centers in support of basic health services within the decentralization strategy. But, the success of the program depends on the advent of new developmental tools to augment diagnostic accuracy for leprosy. However, it should be emphasized that for new diagnostic methods to be developed, a greater commitment on the part of the health care system regarding research is urgently needed.

Human migration, railways and the geographic distribution of leprosy in Rio Grande do Norte State--Brazil.

INTRODUCTION: Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons. OBJECTIVES: We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region. RESULTS: The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte. CONCLUSIONS: Leprosy may disseminate slowly, over many decades in certain circumstances, such as in small cities with few cases. This is a very unusual situation currently and a unique opportunity for epidemiologic studies of leprosy as an emerging disease.

Progression of leprosy disability after discharge: is multidrug therapy enough?

OBJECTIVE: To evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO). METHODS: Cohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics. RESULTS: The total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02-2.56), when disability was 2, the risk was 2.37 (95% CI 1.35-4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07-3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08-2.52]). CONCLUSION: Impairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities.

Kinship and Leprosy in the Contacts of Leprosy Patients: Cohort at the Souza Araújo Outpatient Clinic, Rio de Janeiro, RJ, 1987-2010.

A broad variety of factors have been associated with leprosy among contacts, including socioeconomic, epidemiological, and genetic characteristics. Data from 7,174 contacts of leprosy patients from a leprosy outpatient clinic in Rio de Janeiro, Brazil, 1987-2010, were analyzed to investigate the effects of kinship, individual, and contextual factors on leprosy. Multivariate analyses were performed using a robust estimation method. In the prevalence analysis, close kinship (sibling OR = 2.75, offspring OR = 2.00, and other relatives OR = 1.70), socioeconomic factors, and the duration of exposure to the bacillus were associated to leprosy. In the incidence analysis, significant risks were found for all categories of kinship (parents RR = 10.93, spouse, boyfriend/girlfriend, and bride/groom RR = 7.53, sibling RR = 7.03, offspring RR = 5.34, and other relatives RR = 3.71). Once the treatment of the index case was initiated, other factors lost their significance, and the index case bacteriological index and BCG (Bacillus Calmette-Guérin vaccine) protection had a greater impact. Our findings suggested that both genetic susceptibility and physical exposure play an important role in the epidemiology of leprosy, but it was not possible establishing the role of genetic factor. Analyses of other factors related to the genotype of individuals, such as genetic polymorphisms, are needed.

Characteristics of leprosy diagnosed through the surveillance of contacts: a comparison with index cases in Rio de Janeiro, 1987-2010

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.

Leprosy exposure, infection and disease: a 25-year surveillance study of leprosy patient contacts

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.

[Patients from a reference center for leprosy: Rio de Janeiro and Duque de Caxias, 1986-2008]. / Pacientes em centro de referência para Hanseníase: Rio de Janeiro e Duque de Caxias, 1986-2008.

UNLABELLED: 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.

Pacientes em centro de referência para Hanseníase: Rio de Janeiro e Duque de Caxias, 1986-2008 / Patients from a Reference Center for Leprosy: Rio de Janeiro and Duque de Caxias, 1986-2008

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.

A profile of patients treated at a national leprosy outpatient referral clinic in Rio de Janeiro, Brazil, 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.

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8-8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.

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.