Incidence of and Factors Associated With Leprosy Among Household Contacts of Patients With Leprosy in Brazil.

Importance: Despite progress toward reducing global incidence, leprosy control remains a challenge in low- and middle-income countries. Objective: To estimate new case detection rates of leprosy among household contacts of patients with previously diagnosed leprosy and to investigate its associated risk factors. Design, Setting, and Participants: This population-based cohort study included families registered in the 100 Million Brazilian Cohort linked with nationwide registries of leprosy; data were collected from January 1, 2007, through December 31, 2014. Household contacts of patients with a previous diagnosis of leprosy from each household unit were followed up from the time of detection of the primary case to the time of detection of a subsequent case or until December 31, 2014. Data analysis was performed from May to December 2018. Exposures: Clinical characteristics of the primary case and sociodemographic factors of the household contact. Main Outcomes and Measures: Incidence of leprosy, estimated as the new case detection rate of leprosy per 100 000 household contacts at risk (person-years at risk). The association between occurrence of a subsequent leprosy case and the exposure risk factors was assessed using multilevel mixed-effects logistic regressions allowing for state- and household-specific random effects. Results: Among 42 725 household contacts (22 449 [52.5%] female; mean [SD] age, 22.4 [18.5] years) of 17 876 patients detected with leprosy, the new case detection rate of leprosy was 636.3 (95% CI, 594.4-681.1) per 100 000 person-years at risk overall and 521.9 (95% CI, 466.3-584.1) per 100 000 person-years at risk among children younger than 15 years. Household contacts of patients with multibacillary leprosy had higher odds of developing leprosy (adjusted odds ratio [OR], 1.48; 95% CI, 1.17-1.88), and the odds increased among contacts aged 50 years or older (adjusted OR, 3.11; 95% CI, 2.03-4.76). Leprosy detection was negatively associated with illiterate or preschool educational level (adjusted OR, 0.59; 95% CI, 0.38-0.92). For children, the odds were increased among boys (adjusted OR, 1.70; 95% CI, 1.20-2.42). Conclusions and Relevance: The findings in this Brazilian population-based cohort study suggest that the household contacts of patients with leprosy may have increased risk of leprosy, especially in households with existing multibacillary cases and older contacts. Public health interventions, such as contact screening, that specifically target this population appear to be needed.

Factors associated with leprosy in a municipality of the Pre-Amazon region, state of Maranhão, Brazil

Abstract INTRODUCTION: The Integrated Program of Leprosy Control was initiated in the municipality of Buriticupu, Maranhão, Brazil, an area considered hyperendemic for leprosy in 2003. It aims at assessing the clinical and epidemiological characteristics of the disease to reduce the detection rate of new cases until 2015. Here, we present the evolution of the indicators of leprosy within the period from 2003 to 2015. METHODS: We conducted a descriptive analytical study based on the active search for and voluntary referral of cases of leprosy. The detection rate of new cases was analyzed over time. We included individuals diagnosed with leprosy between January 2003 and December 2015. The association between categorical variables was assessed using the chi-square test of independence, considering a level of significance of 5%. When the association was significant, the detection rate (with a confidence interval of 95%) was calculated. RESULTS: Overall, 879 new leprosy cases were detected; the majority of the affected individuals were men (65.9%). Multibacillary leprosy was the most common type of the disease, according to the operational classification (55.5%); it showed the strongest association with an age ≥60 years. We also detected an association between the male sex and both, lepromatous and multibacillary leprosy. The detection rate reduced from 211.09/100,000 population in 2003 to 50.26/100,000 population in 2015. CONCLUSIONS: We found an improvement in leprosy control, with a reduction in the detection rate and the absolute number of cases. Strengthening of disease control measures should be prioritized to eliminate leprosy as a public health concern in this municipality.

Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy.

Leprosy is a chronic disease caused by M. leprae infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant M. leprae antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts (M. leprae cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of M. tuberculosis Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against M. leprae infection that prevents the development of leprosy. These data further our understanding of M. leprae infection/leprosy and are instructive for vaccine development.

Tendências da hanseníase após implementação de um projeto de intervenção em uma capital da Região Norte do Brasil, 2002-2016 / Leprosy trends following implementation of an intervention project in a state capital in the North of Brazil, 2002-2016 / Tendencias de la hanseniasis tras la implementación de un proyecto de intervención en una capital de la región norte de Brasil, 2002-2016

Resumo: O projeto Palmas Livre da Hanseníase foi implementado para o incremento dos indicadores e o enfrentamento da doença, visto que a capital do Tocantins é a mais hiperendêmica do país. Este estudo mede o impacto da intervenção do projeto por meio da análise da tendência de indicadores prioritários em Palmas, 2002-2016. Baseia-se em análise de dados advindos do Sistema de Informação de Agravos de Notificação (SINAN) e de relatórios de capacitações aplicadas com metodologia de problematização. Os indicadores dos casos novos de hanseníase residentes em Palmas foram investigados, e suas tendências foram identificadas por análise de regressão joinpoint para avaliação dos resultados. No ano de implementação do projeto de intervenção (2016), o coeficiente de detecção de casos novos na população geral foi de 236,3/100 mil habitantes, e esse indicador apresentava decréscimo significativo de -7,5% no período de 2002 a 2014. Nos anos entre 2014 e 2016, houve aumento significativo de 104,6% para a detecção geral. O coeficiente de detecção em menores de 15 anos também apresentava queda de -4,6%, mas nos anos de 2014, 2015 e 2016, houve aumento de 111,1%, juntamente com os coeficientes de detecção de casos com grau 0, 1 e 2, com 59,3%, 225,2% e 121,7%, respectivamente. A proporção de casos detectados por avaliação de contatos teve acréscimo significativo de 201,1% no período de 2014 a 2016. Os dados comprovaram a efetividade e potencialidade da estratégia de intervenção do projeto para as ações de diagnóstico e controle da hanseníase em Palmas. Trouxe evidências de que a agilidade diagnóstica dos serviços de atenção primária resulta em indicadores que refletem a incidência real de casos.

Abstract: The project Palmas Free of Leprosy was implemented to improve indicators and deal with the disease, since the capital of Tocantins State is the most hyperendemic state capital in Brazil. This study measures the impact of the project's intervention through trend analysis of the priority indicators in Palmas, from 2002 to 2016. The study was based on an analysis of data from the Brazilian Information System for Notifiable Diseases (SINAN) and reports of applied training courses with problem-solving methodology. The indicators for new leprosy cases in Palmas residents were investigated, and the trends were identified by joinpoint regression analysis to assess the results. In the year the intervention project was implemented (2016), the detection rate for new cases in the overall population was 236.3/100,000 inhabitants, and this indicator showed a significant decrease of -7.5% from 2002 to 2014. From 2014 to 2016, there was a significant increase of 104.6% in overall detection. The detection rate in individuals under 15 years of age also showed a reduction of -4.6%, but in the years 2014, 2015, and 2016 there was an increase of 111.1%, together with detection rates for grades 0, 1, and 2, with 59.3%, 225.2%, and 121.7%, respectively. The proportion of cases detected by contact assessment showed a significant increase of 201.1% from 2014 to 2016. The data proved the effectiveness and potentiality of the project's intervention strategy for the diagnosis and control of leprosy in Palmas. The study provided evidence that timely diagnosis by primary care services results in indicators that reflect the real incidence of cases.

Resumen: El proyecto Palmas Libre de Hanseniasis se implementó para el incremento de indicadores y combate a la enfermedad, dado que la capital de Tocantins es la más hiperendémica de Brasil. Este estudio mide el impacto de la intervención del proyecto, mediante el análisis de la tendencia de indicadores prioritarios en Palmas, 2002-2016. Se basa en un análisis de datos procedentes del Sistema de Información sobre Enfermedades de Notificación Obligatoria (SINAN por sus siglas en portugués) y de informes de capacitaciones, aplicadas con metodología de problematización. Se investigaron los indicadores de casos nuevos de hanseniasis, en residentes de Palmas, y se identificaron sus tendencias mediante análisis de regresión joinpoint para la evaluación de los resultados. En el año de implementación del proyecto de intervención (2016), el coeficiente de detección de casos nuevos en la población general fue de 236,3/100 mil habitantes, y ese indicador presentaba una disminución significativa de un -7,5%, durante el período de 2002 a 2014. Entre los años de 2014 a 2016, hubo un aumento significativo de un 104,6% en la detección general. El coeficiente de detección en menores de 15 años también presentaba una bajada de -4,6%, pero durante los años de 2014, 2015 y 2016, hubo un aumento de 111,1%, junto a los coeficientes de detección de casos con grado 0, 1 y 2, con un 59,3%, 225,2% y 121,7%, respectivamente. La proporción de casos detectados por la evaluación de contactos tuvo un aumento significativo de un 201,1%, durante el período de 2014 a 2016. Los datos comprobaron la efectividad y potencialidad de la estrategia de intervención del proyecto para las acciones de diagnóstico y control de la hanseniasis en Palmas. Hubo evidencias de que la agilidad diagnóstica de los servicios de atención primaria se traduce en indicadores que reflejan la incidencia real de casos.

[Leprosy in children in the region of Thiès, Senegal: study determining whether or not it is a signal of recrudescence]. / La lèpre de l'enfant à Thiès/Sénégal: signal d'une recrudescence?

Leprosy is an infectious and transmissible disease. According to the WHO, the number of new cases of leprosy in children in Senegal has risen moderately since 2013. This study aimed to analyze the epidemiological, clinical, therapeutic and evolutionary features of leprosy in children in the geographical areas of two social rehabilitation villages in the region of Thiès. We conducted a retrospective study over a period of 3 years (2013-2015). All new cases of Hansen's disease aged 0 -15 years were included. Over the three year period, 39 children were included in the study, with a boy predominance (n=23, 59%). Among these children, 27 (66.7%) came from a social rehabilitation village for leprosy patients. One family member was affected by leprosy in 27 cases (69.2%). More than half of the children (23 cases, 58.9%) had multibacillary leprosy (lepromatous-lepromatous). All children underwent a 12-month treatment, at the end of which thirty-six (92.3%) children were healed. Leprosy is still present in Senegal despite the efforts made by the national programme to combat leprosy. In the light of these results, it is important to emphasize the role of active screening strategy targeted to children, which seems to have shown its effectiveness in the region. Early detection, contact tracing and early treatment are important factors in the reduction of the contagiousity of leprosy.

Active search for leprosy cases in Midwestern Brazil: a serological evaluation of asymptomatic household contacts before and after prophylaxis with bacillus Calmette-Guérin / Busca ativa por casos de hanseníase no Centro-Oeste do Brasil: avaliação sorológica dos contatos domiciliares assintomáticos antes e após a profilaxia com Bacillus Calmette-Guérin

Leprosy is a disease caused by Mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. This study aimed to determine the applicability of anti-PGL-1 IgM antibody detection, using the ML FLOW technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (AHHC) of multibacillary leprosy index cases from Midwest Brazil. Serological changes induced by the prophylaxis of these household contacts with Bacillus Calmette-Guérin (BCG) were also verified. A total of 91 AHHC were assessed, among which, 18.68% (n = 17) presented both positive bacilloscopy and positive anti-PGL-1 IgM serology. Positivity concordance between these two laboratorial exams (Kappa Index = 1; p < 0.001) was indicated, however, one case did not demonstrate concordance between the semiquantitative assessment of anti-PGL-1 IgM and the bacilloscopy index (Kappa Index = 0.96; p < 0.001). Among the 17 AHHC with positive bacilloscopy, eight were reassessed after prophylaxis with BCG and two of them presented negative anti-PGL-1 IgM serology, being these patients who had presented a bacilloscopy index of < 2[+] in the initial assessment. This study shows that anti-PGL-1 IgM detection may be used as a tool to determine the bacillary load in AHHC and to detect immune changes related to prophylaxis by nonspecific vaccination.

A hanseníase é doença causada pelo Mycobacterium leprae, apresentando elevado potencial incapacitante, o que torna indispensável seu diagnóstico precoce. O estudo visa determinar a aplicabilidade da detecção de anticorpos anti-PGL1-IgM por meio da técnica do ML FLOW como ferramenta adjuvante ao diagnóstico de hanseníase em contatos domiciliares assintomáticos (AHHC) de pacientes multibacilares procedentes da região Centro-Oeste do Brasil, bem como, documentar o comportamento sorológico após a profilaxia com a vacina Bacillus Calmette-Guérin (BCG). Foram avaliados 91 AHHC atendidos no Hospital Universitário de Brasília - Brasil, dos quais 18,68% (n = 17) apresentaram positividade para baciloscopia e anti-PGL1-IgM, totalizando uma concordância completa entre os dois grupos (Índice Kappa = 1; p < 0,001). Em apenas um dos casos não observou-se concordância entre a avaliação semi-quantitativa do anti-PGL1-IgM e índice baciloscópico (Índice Kappa = 0,96; p < 0,001). Oito dos 17 AHHC com baciloscopia positiva foram reavaliados após profilaxia com BCG e apenas dois apresentaram negativação dos títulos anti-PGL1-IgM, sendo tais casos correspondentes aos que haviam apresentado índice baciloscópico menor do que 2[+] na avaliação inicial. O estudo corrobora o potencial do anti-PGL1-IgM como ferramenta de predição da carga bacilar em AHHC da região Centro-Oeste do Brasil, e surpreende alterações imunes relacionadas à profilaxia obtida pela vacinação não específica com BCG.