Spatial heterogeneity in projected leprosy trends in India

Background: Leprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually. Methods: We analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary. Results: Our analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate. Conclusions: Trend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control

A Zebrafish Model of Mycobacterium leprae Granulomatous Infection.

Understanding the pathogenesis of leprosy granulomas has been hindered by a paucity of tractable experimental animal models. Mycobacterium leprae, which causes leprosy, grows optimally at approximately 30°C, so we sought to model granulomatous disease in the ectothermic zebrafish. We found that noncaseating granulomas develop rapidly and eventually eradicate infection. rag1 mutant zebrafish, which lack lymphocytes, also form noncaseating granulomas with similar kinetics, but these control infection more slowly. Our findings establish the zebrafish as a facile, genetically tractable model for leprosy and reveal the interplay between innate and adaptive immune determinants mediating leprosy granuloma formation and function

La lepra en Brasil : monitoreo de las discapacidades

Introdução: A doença de Hansen é uma patologia infectocontagiosa, curável, causada pelo Mycobacteria Leprae, com predileção pelo sistema nervoso periférico. Objetivos: Determinar as formas clínicas e a classificação operacional dos portadores de doença de Hansen; Identificar o grau de incapacidade dos pacientes diagnosticados com doença de Hansen; Métodos: Estudo transversal, com abordagem quantitativa de natureza descritiva, realizado com 104 pacientes diagnosticados com doença de Hansen. A maioria era do sexo masculino 63 (60,6%) com uma média de idades de 37 anos, 49% eram de cor parda e 34,6% detinham o ensino fundamental completo.Os dados foram retirados de: Sistema de Informação de Notificação de Agravos Notificáveis – SINAN em 2014; - Ficha de Avaliação Neurológica Simplificada para avaliação do Grau de Incapacidades, (Brasil, 2010, p.35), extraída do Manual de Prevenção de Incapacidades (Brasil, 2008, p. 112-113). Resultados: A classificação operacional dos portadores de doença de Hansen revelou que 47,1% eram paucibacilares e 52,9% multibacilares e que 31,7% foram diagnosticados com a forma Dimorfa e 25,9% Tuberculóide. O Grau de Incapacidade Física (GIF) no diagnóstico foi o seguinte: Grau 0 - 73 (70,20%); Grau I - 17 (16,35%) e 9 (8,65%) possuíam deformidades instalados de Grau II. Os odds ratios indicam de forma significativa que o risco das mulheres com doença de Hansen não apresentarem incapacidades físicas no momento do diagnóstico, é cerca de 4 vezes superior ao dos homens (OR= 3,868; IC 95%= 1,316-11,368). Conclusões: A ocorrência de incapacidades originadas pela doença de Hansen sobretudo nos homens é ainda um problema de saúde pública no Brasil, pelo que a busca ativa de casos na comunidade, o exame dos contatos domiciliares, o acompanhamento dos pacientes pelas unidades de saúde, as campanhas educativas e investigações com alunos nas escolas são exemplos de políticas que devem ser implementadas para que se consiga erradicar a endemia e reduzir as suas sequelas.ABSTRACT Introdution: Hansen’s disease is an infecto-contagious, chronic and curable disease, caused by the Mycobacterium Leprae with a preference for the peripheral nervous system. Objectives: To determine the clinical forms and the operational classification of patients suffering from Hansen's disease; to identify the disability grade of patients diagnosed with Hansen’s disease. Methods: Cross-sectional study with a quantitative approach of a descriptive nature performed on 104 patients diagnosed with Hansen’s disease. Most were male, 63 (60.6%), with an average age of 37 years, 49% had pardo complexion and 34.6% had an elementary education level. Data was collected from the: Notifiable Diseases Information System – SINAN in 2014; Simplified Neurologic Assessment Form for assessing the Grade of Disability (Brasil, 2010, p.35), taken from the Guide for Prevention of Disabilities (Brasil, 2008, p. 112- 113). Results: The operational classification of patients suffering from Hansen’s disease revealed that 47.1% were paucibacillary while 52.9% were multibacillary and that 31.7% were diagnosed with the Borderline form and 25.9% with the Tuberculoid form. The Physical Disability Grade (PDG) at the time of diagnosis was the following: Grade 0 – 73 (70.20%); Grade 1 - 17 (16.35%); and 9 patients (8.65%) had developed Grade 2 disabilities. The odds ratios significantly indicate that for women with Hansen’s disease the risk of not having physical disabilities at the time of diagnosis is about 4 times higher than it is for men (OR= 3.868; CI 95%= 1.316-11.368). Conclusions: The occurrence of disabilities resulting from Hansen’s disease mostly in men is still a public health problem in Brazil. Therefore, active search for cases within the community, examining household contacts, monitoring of patients by the healthcare units, educational campaigns and research with students in schools are examples of policies which should be implemented in order to eradicate this endemic disease and reduce sequelae thereof.RESUMEN Introducción: La enfermedad de Hansen es una patología infectocontagiosa, crónica y curable, causada por el Mycobacteria Leprae, con predilección por el sistema nervioso periférico. Objetivos: Determinar las formas clínicas y la clasificación operativa de los portadores de lepra; Identificar el grado de incapacidad de los pacientes diagnosticados con enfermedad de Hansen. Métodos: Estudio transversal, con abordaje cuantitativo de naturaleza descriptiva, realizado con 104 pacientes diagnosticados con enfermedad de Hansen. La mayoría era del sexo masculino 63 (60,6%) con una media de edades de 37 años, el 49% eran de color pardo y el 34,6% tenía la enseñanza fundamental completa. Los datos fueron retirados de: Sistema de Información de Notificación de Agravios Notificables – SINAN en 2014; - Ficha de Evaluación Neurológica Simplificada para la evaluación del Grado de Incapacidades, (Brasil, 2010, p.35), extraída del Manual de Prevención de Incapacidades (Brasil, 2008, p. 112-113). Resultados: La clasificación operativa de los portadores de enfermedad de Hansen, reveló que el 47,1% eran paucibacilares y el 52,9% multi-cilares y que el 31,7% fue diagnosticado con la forma Dimorfa y el 25,9% Tuberculosis. El Grado de Incapacidad Física (GIF) en el diagnóstico fue el siguiente: Grado 0 - 73 (70,20%); Grado I - 17 (16,35%) y 9 (8,65%) poseía deformidades instaladas de Grado II. Los odds ratios indican de forma significativa que el riesgo de que las mujeres con enfermedad de Hansen no presenten incapacidades físicas en el momento del diagnóstico, es aproximadamente 4 veces superior al de los hombres (OR = 3,868; IC 95% = 1,316-11,368). Conclusiones: La ocurrencia de incapacidades originadas por enfermedad de Hansen sobre todo en los hombres es todavía un problema de salud pública en Brasil, por lo que la búsqueda activa de casos en la comunidad, el examen de los contactos domiciliarios, el acompañamiento de los pacientes por las unidades de salud, las campañas educativas E investigaciones con alumnos en las escuelas son ejemplos de políticas que deben ser implementadas para que se pueda erradicar la endemia y reducir sus secuelas.info:eu-repo/semantics/publishedVersio

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy

Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Design Single centre, double blind, cluster randomised, placebo controlled trial. SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million. Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient’s treatment, with follow-up for four years. Main outcome measure Development of clinical leprosy. Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. ConclusionA single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Trial registration Current Controlled Trials ISRCTN61223447

Neurological Manifestations in Leprosy: A Study in Tribal! Community of Hill Tracts

Background: Leprosy is a chronic granulomatous infectious disease having major burden on humans over thousands of years. If untreated, it results in permanent damage to various systems and organs. So we designed this study to evaluate the neurological complications in early stage in adult leprosy patients. Objective: The aim of this study was to find out the pattern of neurological manifestations among adult leprosy patients. Materials and Methods: This cross-sectional hospital-based study on 85 adult tribal leprosy patients was conducted in a district level health care facility from January to December 2014 using simple, direct, standardized questionnaire including history and neurological examinations. Results: The commonest age group affected was 18–30 years (62.4%). Male group was predominant (68.2%). Majority cases (66%) had multibacillary leprosy. At first visit 72.7% cases with neurological findings could not be diagnosed correctly by primary health care personnel. More than six months were required for correct diagnosis in 61.2% cases. Numbness was the commonest (74.5%) neurological symptom. In upper limb, motor findings were predominant with wasting in 50.9% cases. In lower limb, sensory findings were predominant with stock pattern sensory impairment being the commonest (56.4%). Ulnar nerve was the commonest peripheral nerve to enlarge with tenderness. Facial nerve was the commonest cranial nerve involved. All cases with multiple cranial nerves involvement were of multibacillary type. Due to physical disability 92.7% cases lost their jobs

Determinants and Associated Disability of Leprosy Patients Attending GMLF, Sevagram

Background: Leprosy, as an oldest disease known to a man and already eliminated from India in 2005, still poses a public health problem with steady new case detection rate. Method: The present study was carried out in Gandhi memorial leprosy foundation, Wardha, with the aim to find out proportion of multibacillary leprosy cases and various grading of disability and factors associated with it in this part of country. All the successive new OPD patients were included in study and examined for type of leprosy and grade of disability if present. Analysis done by Descriptive statistics. Result: 66 % had multibacillary type of leprosy and 44 % the disability. Higher age group, females, illiterate and less educated, unskilled and low income group were mostly affected. Conclusion: high proportion of multibacillary cases and disabilities reflects the need for active thrust to identify new cases

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

Back-calculating the incidence of infection of leprosy in a Bayesian framework

Background: The number of new leprosy cases reported annually is falling worldwide, but remains relatively high in some populations. Because of the long and variable periods between infection, onset of disease, and diagnosis, the recently detected cases are a reflection of infection many years earlier. Estimation of the numbers of sub-clinical and clinical infections would be useful for management of elimination programmes. Back-calculation is a methodology that could provide estimates of prevalence of undiagnosed infections, future diagnoses and the effectiveness of control. Methods: A basic back-calculation model to investigate the infection dynamics of leprosy has been developed using Markov Chain Monte Carlo in a Bayesian context. The incidence of infection and the detection delay both vary with calendar time. Public data from Thailand are used to demonstrate the results that are obtained as the incidence of diagnosed cases falls. Results: The results show that the underlying burden of infection and short-term future predictions of cases can be estimated with a simple model. The downward trend in new leprosy cases in Thailand is expected to continue. In 2015 the predicted total number of undiagnosed sub-clinical and clinical infections is 1,168 (846–1,546) of which 466 (381–563) are expected to be clinical infections. Conclusions: Bayesian back-calculation has great potential to provide estimates of numbers of individuals in health/infection states that are as yet unobserved. Predictions of future cases provides a quantitative measure of understanding for programme managers and evaluators. We will continue to develop the approach, and suggest that it might be useful for other NTD in which incidence of diagnosis is not an immediate measure of infection