Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas.

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.

National Health Survey reveals high percentage of signs and symptoms of leprosy in Brazil. / Pesquisa Nacional de Saúde revela alto percentual de sinais e sintomas de hanseníase no Brasil.

Leprosy is a debilitating, infectious, systemic or localized dermato-neurological disease caused by Mycobacterium lepra. In Brazil, the magnitude and high disabling power keep the disease as a public health problem. Skin spotting and numbness are pathognomonic signs and symptoms in leprosy. The Instituto Brasileiro de Geografia e Estatística (IBGE) 2019 National Health Survey (PNS-2019) considered the following question as a proxy to estimate its magnitude in the country. "Do you have a spot with numbness or part of the skin with numbness?". In Brazil, 1,921,289 adults reported having a patch or part of the skin with numbness, with no regional differences. As for the age group, the older, the higher the prevalence, for example, between 18 to 29 years old (235,445) and 30 to 39 years old (236,485), 0.7% had the condition, between 40 to 59 years old (827,887), 1.5% and among the elderly, 1.8% (621,472). Being able to estimate, in population-based surveys, with statistical representativeness, a reported morbidity such as leprosy is essential to support the formulation of public policies, notably those related to primary health care actions. In this way, the IBGE fulfills its constitutional role of portraying the reality of the Brazilian population and today it is the main external evaluator of the Unified Health System (SUS) and of public policies developed by the federal level.

A hanseníase é uma doença dermato-neurológica, infecciosa, sistêmica ou localizada, debilitante, causada por Mycobacterium leprae. No Brasil, a magnitude e o alto poder incapacitante mantêm a doença como um problema de saúde pública. Mancha na pele e dormência são sinais e sintomas patognomônicos na hanseníase. A Pesquisa Nacional de Saúde de 2019 (PNS-2019), do Instituto Brasileiro de Geografia e Estatística (IBGE), considerou a seguinte pergunta como proxy para estimar sua magnitude no país. "O(a) sr(a). tem mancha com dormência ou parte da pele com dormência?". No Brasil, 1.921.289 adultos referiram ter mancha ou parte da pele com dormência, sem diferenças regionais. Com relação ao grupo etário, quanto mais velho, maior a prevalência. Por exemplo, entre os de 18 a 29 anos (235.445) e de 30 a 39 anos (236.485), 0,7% possuía a condição, entre 40 e 59 anos (827.887), 1,5%, e entre os idosos, 1,8% (621.472). Poder estimar, em pesquisas de base populacional, com representatividade estatística, uma morbidade referida tal como a hanseníase é fundamental para apoiar a formulação de políticas públicas, notadamente as relativas às ações da atenção primária à saúde. Dessa forma, o IBGE cumpre seu papel constitucional de retratar a realidade da população brasileira e hoje é o principal avaliador externo do Sistema Único de Saúde (SUS) e das políticas públicas instituídas no âmbito federal.

Pesquisa Nacional de Saúde revela alto percentual de sinais e sintomas de hanseníase no Brasil / National Health Survey reveals high percentage of signs and symptoms of leprosy in Brazil

Resumo A hanseníase é uma doença dermato-neurológica, infecciosa, sistêmica ou localizada, debilitante, causada por Mycobacterium leprae. No Brasil, a magnitude e o alto poder incapacitante mantêm a doença como um problema de saúde pública. Mancha na pele e dormência são sinais e sintomas patognomônicos na hanseníase. A Pesquisa Nacional de Saúde de 2019 (PNS-2019), do Instituto Brasileiro de Geografia e Estatística (IBGE), considerou a seguinte pergunta como proxy para estimar sua magnitude no país. "O(a) sr(a). tem mancha com dormência ou parte da pele com dormência?". No Brasil, 1.921.289 adultos referiram ter mancha ou parte da pele com dormência, sem diferenças regionais. Com relação ao grupo etário, quanto mais velho, maior a prevalência. Por exemplo, entre os de 18 a 29 anos (235.445) e de 30 a 39 anos (236.485), 0,7% possuía a condição, entre 40 e 59 anos (827.887), 1,5%, e entre os idosos, 1,8% (621.472). Poder estimar, em pesquisas de base populacional, com representatividade estatística, uma morbidade referida tal como a hanseníase é fundamental para apoiar a formulação de políticas públicas, notadamente as relativas às ações da atenção primária à saúde. Dessa forma, o IBGE cumpre seu papel constitucional de retratar a realidade da população brasileira e hoje é o principal avaliador externo do Sistema Único de Saúde (SUS) e das políticas públicas instituídas no âmbito federal.

Abstract Leprosy is a debilitating, infectious, systemic or localized dermato-neurological disease caused by Mycobacterium lepra. In Brazil, the magnitude and high disabling power keep the disease as a public health problem. Skin spotting and numbness are pathognomonic signs and symptoms in leprosy. The Instituto Brasileiro de Geografia e Estatística (IBGE) 2019 National Health Survey (PNS-2019) considered the following question as a proxy to estimate its magnitude in the country. "Do you have a spot with numbness or part of the skin with numbness?". In Brazil, 1,921,289 adults reported having a patch or part of the skin with numbness, with no regional differences. As for the age group, the older, the higher the prevalence, for example, between 18 to 29 years old (235,445) and 30 to 39 years old (236,485), 0.7% had the condition, between 40 to 59 years old (827,887), 1.5% and among the elderly, 1.8% (621,472). Being able to estimate, in population-based surveys, with statistical representativeness, a reported morbidity such as leprosy is essential to support the formulation of public policies, notably those related to primary health care actions. In this way, the IBGE fulfills its constitutional role of portraying the reality of the Brazilian population and today it is the main external evaluator of the Unified Health System (SUS) and of public policies developed by the federal level.

Detection of anti-M. leprae antibodies in children in leprosy-endemic areas: A systematic review.

BACKGROUND: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. METHODS AND FINDINGS: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. CONCLUSIONS: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.

Misdiagnosis of leprosy in Brazil in the period 2003 - 2017: spatial pattern and associated factors.

BACKGROUND: Leprosy causes a range of symptoms, and most diagnoses are established based on the clinical picture. Therefore, false negative and positive diagnoses are relatively common. We analyzed the spatial pattern of leprosy misdiagnosis and associated factors in Brazil. METHOD: Exploratory analyses of Kernel density of the new case detection rate (NCDR) and proportion of misdiagnosis in Brazil, 2003-2017. Factors associated with misdiagnosis were identified by logistic regression at the 5% significance level. RESULT: A total of 574,181 new leprosy cases were recorded in Brazil within the study period, of which 7,477 (1.3%) were misdiagnoses. No spatial correlation was observed between the proportion of misdiagnoses and the NCDR. The likelihood of misdiagnosis was elevated for females [OR: 1.58 (1.51-1.66)], children [OR: 1.49 (1.36-1.64)]; paucibacillary [OR: 1.08 (1.02-1.13)], indeterminate clinical forms [OR: 2.37 (2.15-2.62)], for cases diagnosed in the frame of mass screenings [OR: 3.36 (3.09- 3.73)] and contact examination [OR: 2.30 (2.13-2.49)] and for cases with affected nerves but no skin lesions [OR: 2.47 (2.19-2.77)] when compared with those presenting both skin lesion and affected nerves. CONCLUSION: Misdiagnosis of leprosy is not correlated with the endemicity level in Brazil but rather with personal, diagnosis-related and disease characteristics.

[Epidemiological characteristics of leprosy in elderly Brazilians and comparison with other age groups (2016-2018)]. / Características epidemiológicas da hanseníase nos idosos e comparação com outros grupos etários, Brasil (2016-2018).

The article aimed to describe epidemiological indicators and characteristics of new cases of leprosy in elderly Brazilians in 2016-2018, compared to other age groups. A descriptive cross-sectional cohort study was conducted with data from the Information System on Diseases of Notification (SINAN). New leprosy cases were categorized by age groups: 60 or more, 40-59, 15-39, and 15 years of age. Pearson's chi-square test was used to verify differences between groups. A total of 81,205 new leprosy cases were reported in Brazil. Of these, 24.1% were elderly, 37.7% from 40-59 years, 31.9% from 15-39 years, and 6.3% in individuals under 15 years of age. The elderly showed higher proportions (p < 0.001) of cases in males (60.1%), with multibacillary classification (81.3%), and with physical disability grade 2 (PDG2) (11.4%) when compared to the other groups. However, the proportion of new cases detected in the elderly based on contact testing (4.9%) was the lowest among all the age brackets (p < 0.001). The mean detection rate and rate of new cases with PDG2 at diagnosis were higher among the elderly (25.1/100,000 and 28.6/million inhabitants, respectively) compared to other age groups in Brazil as a whole and in the regions and states. Important differences were seen in the epidemiological and clinical profile of leprosy in the elderly compared to other age brackets, especially higher proportions of multibacillary cases, new cases with PDG2, and low detection by contact testing. The findings highlighted the need for leprosy control in this age group, aimed at contributing to interruption of transmission of the disease.

O objetivo foi descrever indicadores epidemiológicos e características dos casos novos de hanseníase em idosos no Brasil, no triênio 2016-2018, comparando a outros grupos etários. Estudo descritivo de corte transversal com dados do Sistema de Informação de Agravos de Notificação (SINAN). Os casos novos de hanseníase foram categorizados por grupos etários: 60 ou mais, 40-59, 15-39 e menores de 15 anos. Utilizou-se o teste qui-quadrado de Pearson para testar diferenças entre grupos. Foram notificados 81.205 casos novos de hanseníase no Brasil. Desses, 24,1% foram em idosos, 37,7% de 40-59 anos, 31,9% de 15-39 e 6,3% em menores de 15 anos. Nos idosos, foram observadas proporções maiores (p < 0,001) de casos no sexo masculino (60,1%), com classificação operacional multibacilar (81,3%) e com grau 2 de incapacidade física (GIF2) (11,4%) em relação aos outros grupos. Contudo, a proporção de casos novos detectados em idosos, por exame de contatos (4,9%), foi a menor entre todas as faixas etárias (p < 0,001). As taxas médias de detecção e de casos novos com GIF2 no diagnóstico foram maiores entre idosos (25,1/100 mil e 28,6/1 milhão de habitantes, respectivamente) em comparação aos demais grupos etários, para o país, regiões e Unidades da Federação. Foram observadas importantes diferenças nos perfis epidemiológico e clínico da hanseníase nos idosos, em relação às demais faixas etárias, destacando-se maiores proporções de casos multibacilares, de casos novos com GIF2 e baixa detecção por exame de contatos. Evidencia-se a necessidade do controle da hanseníase nessa população, visando a contribuir para a interrupção da transmissão da doença.

El objetivo fue describir indicadores epidemiológicos y características de los nuevos casos de hanseniasis en ancianos en Brasil, durante el trienio 2016-2018, comparándolos con otros grupos etarios. Se realizó un estudio descriptivo de corte transversal con datos del Sistema de Información sobre Enfermedades de Notificación obligatoria (Sinan). Los nuevos casos de hanseniasis fueron categorizados por grupos etarios: 60 o más, 40-59, 15-39 y menores de 15 años. Se utilizó el test chi-cuadrado de Pearson para probar diferencias entre grupos. Se notificaron 81.205 casos nuevos de hanseniasis en Brasil. De estos, un 24,1% fueron en ancianos, 37,7% de 40-59 anos, 31,9% de 15-39 años y 6,3% en menores de 15 años. En los ancianos, se observaron proporciones mayores (p < 0,001) de casos del sexo masculino (60,1%), con clasificación operacional multibacilar (81,3%) y con grado 2 de incapacidad física (GIF2) (11,4%), respecto a otros grupos. No obstante, la proporción de casos nuevos detectados en ancianos, por examen de contactos (4,9%), fue la menor entre todas las franjas de edad (p < 0,001). Las tasas medias de detección y de casos nuevos con GIF2 en el diagnóstico fueron mayores entre ancianos (25,1/100.000 y 28,6/1 millón de habitantes, respectivamente), en comparación con los demás grupos etarios, respecto al país, regiones y Unidades de la Federación. Se observaron importantes diferencias en el perfil epidemiológico y clínico de la hanseniasis en ancianos, en relación con las demás franjas de edad, destacándose mayores proporciones de casos multibacilares, de casos nuevos con GIF2 y baja detección por examen de contactos. Se evidencia la necesidad del control de la hanseniasis en esa población, con el fin de contribuir a la interrupción de la transmisión de la enfermedad.

Operational failures of leprosy control in household social networks with overlapping cases in endemic areas in Brazil. / Falhas operacionais no controle da hanseníase em redes de convívio domiciliar com sobreposição de casos em áreas endêmicas no Brasil.

OBJECTIVE: To analyze institutional/programmatic vulnerability of health services in the development of health care actions for people affected by leprosy and contact surveillance. METHODS: This was a cross-sectional study conducted in 2017 based on primary data from a sample of leprosy cases notified between 2001-2014 with overlapping cases in household social networks (HSN) in municipalities in the states of Bahia, Piauí and Rondônia, Brazil. RESULTS: A total of 233 leprosy cases were analyzed, 154 (66.1%) belonged to HSN with 3 or more leprosy cases. In 53.2% of cases, 2 or more generations were affected, this being an outcome associated with absence of dermato-neurological examination (prevalence ratio 1.32; confidence interval [95%CI 1.10;1.59]; p-value=0.004). CONCLUSION: Operational failures in the surveillance of leprosy contacts in areas of high endemicity reinforce the character of institutional/programmatic vulnerability in HSN contexts with more than one case of leprosy in the three states analyzed.

Temporal trend of leprosy among the elderly in Brazil, 2001 - 2018.

OBJECTIVE: To describe the temporal trends of leprosy indicators among the elderly in Brazil in 2001 - 2018. METHODS: This was an ecological time-series study of new leprosy cases in the elderly reported to the Notifiable Diseases Information System. Prais-Winsten generalized linear regression was used to estimate temporal variations. RESULTS: There were 687 317 new leprosy cases in Brazil from 2001 - 2018, of which 129 214 (18.8%) were among elderly people. Overall detection rates in the elderly and of new cases with grade-2 disability showed a falling trend, with an annual percent change of -4.6% (95%CI = -5.1 to -4.0) and -3.9% (95%CI = -4.6 to -3.2). New case and new multibacillary case proportions showed an increasing trend, with an annual percent change of 2.9% (95%CI = 2.6 to 3.3) and 1.4% (95%CI = 1.0 to 1.7), respectively. Detection rates for new leprosy cases in elderly people in Brazil are decreasing, but the proportion of new cases and multibacillary cases are trending upwards. CONCLUSIONS: New cases are shifting to older age groups, and demographic transition and immunosenescence are an influence. Inadequate reduction of grade-2 disability indicates a high risk of physical disability persists. Improved contact tracing and more effective action are needed in this age group.

Temporal trend of leprosy among the elderly in Brazil, 2001 – 2018

[ABSTRACT]. Objective. To describe the temporal trends of leprosy indicators among the elderly in Brazil in 2001 – 2018. Methods. This was an ecological time‑series study of new leprosy cases in the elderly reported to the Notifiable Diseases Information System. Prais-Winsten generalized linear regression was used to estimate temporal variations. Results. There were 687 317 new leprosy cases in Brazil from 2001 – 2018, of which 129 214 (18.8%) were among elderly people. Overall detection rates in the elderly and of new cases with grade-2 disability showed a falling trend, with an annual percent change of -4.6% (95%CI = -5.1 to -4.0) and -3.9% (95%CI = -4.6 to -3.2). New case and new multibacillary case proportions showed an increasing trend, with an annual percent change of 2.9% (95%CI = 2.6 to 3.3) and 1.4% (95%CI = 1.0 to 1.7), respectively. Detection rates for new leprosy cases in elderly people in Brazil are decreasing, but the proportion of new cases and multibacillary cases are trending upwards. Conclusions. New cases are shifting to older age groups, and demographic transition and immunosenescence are an influence. Inadequate reduction of grade-2 disability indicates a high risk of physical disability persists. Improved contact tracing and more effective action are needed in this age group.

[RESUMEN]. Objetivo. Describir las tendencias temporales de los indicadores de lepra en la población anciana en Brasil entre 2001 y 2018. Métodos. Estudio ecológico de series temporales de casos nuevos de lepra en ancianos reportados al Sistema de Información de Enfermedades Notificables. Se utilizó regresión lineal generalizada de Prais-​Winsten para estimar las variaciones temporales. Resultados. Entre 2001 y 2018 en Brasil hubo 687 317 casos nuevos de lepra, de los cuales 129 214 (18.8%) fueron en personas de edad avanzada. Las tasas de detección en los ancianos y los casos nuevos con discapacidad de grado 2 mostraron una tendencia descendente, con un cambio porcentual anual de –4,6% (IC 95%, –5,1 a –4,0) y –3,9% (IC 95%, – 4,6 a –3,2), respectivamente. Las proporciones de casos nuevos y de casos nuevos multibacilares mostraron una tendencia creciente, con un cambio porcentual anual de 2,9% (IC 95%, 2,6 a 3,3) y 1,4% (IC 95%, 1,0 a 1,7), respectivamente. Las tasas de detección de casos nuevos de lepra en los ancianos en Brasil están disminuyendo, pero la proporción de casos nuevos y de casos multibacilares tiende a aumentar. Conclusiones. Los casos nuevos se están desplazando hacia los grupos de mayor edad, posiblemente debido a factores relacionados con la transición demográfica y la inmunosenescencia. La insuficiente reducción de la discapacidad de grado 2 indica que el riesgo de discapacidad física continúa siendo elevado. En este grupo etario se requiere mejorar el seguimiento de los contactos y las medidas de acción.

[RESUMO]. Objetivo. Descrever as tendências temporais dos indicadores da hanseníase na população idosa do Brasil de 2001 a 2018. Métodos. O presente estudo ecológico de séries temporais analisou os novos casos de hanseníase em idosos (60 anos ou mais) notificados ao Sistema de Informação de Agravos de Notificação (SINAN). Foi usada regressão linear generalizada de Prais-Winsten para estimar as variações temporais. Resultados. De 2001 a 2018, houve 687 317 novos casos de hanseníase no Brasil, dos quais 129 214 (18,8%) foram em idosos. As taxas de detecção em idosos e os casos novos com grau 2 de incapacidade apresentaram tendência decrescente, com variação percentual anual de –4,6% (IC95%: –5,1 a –4,0) e –3,9% (IC95%: –4,6 a –3,2), respectivamente. Por sua vez, a tendência foi crescente para novos casos e novos casos multibacilares, com variação percentual anual de 2,9% (IC95%: 2,6 a 3,3) e 1,4% (IC95%: 1,0 a 1,7), respectivamente. As taxas de detecção de novos casos de hanseníase em idosos no Brasil estão diminuindo, mas a proporção de novos casos e de casos multibacilares tende a aumentar. Conclusões. Os novos casos estão se deslocando para os grupos etários mais velhos, possivelmente devido a fatores relacionados com a transição demográfica e a imunossenescência. A redução insuficiente na incapacidade de grau 2 indica que o risco de incapacidade física permanece elevado. Nessa faixa etária, é necessário um melhor monitoramento dos contatos e uma ação mais efetiva.

Características epidemiológicas da hanseníase nos idosos e comparação com outros grupos etários, Brasil (2016-2018) / Epidemiological characteristics of leprosy in elderly Brazilians and comparison with other age groups (2016-2018) / Características epidemiológicas de la hanseniasis en ancianos y comparación con otros grupos etarios, Brasil (2016-2018)

O objetivo foi descrever indicadores epidemiológicos e características dos casos novos de hanseníase em idosos no Brasil, no triênio 2016-2018, comparando a outros grupos etários. Estudo descritivo de corte transversal com dados do Sistema de Informação de Agravos de Notificação (SINAN). Os casos novos de hanseníase foram categorizados por grupos etários: 60 ou mais, 40-59, 15-39 e menores de 15 anos. Utilizou-se o teste qui-quadrado de Pearson para testar diferenças entre grupos. Foram notificados 81.205 casos novos de hanseníase no Brasil. Desses, 24,1% foram em idosos, 37,7% de 40-59 anos, 31,9% de 15-39 e 6,3% em menores de 15 anos. Nos idosos, foram observadas proporções maiores (p < 0,001) de casos no sexo masculino (60,1%), com classificação operacional multibacilar (81,3%) e com grau 2 de incapacidade física (GIF2) (11,4%) em relação aos outros grupos. Contudo, a proporção de casos novos detectados em idosos, por exame de contatos (4,9%), foi a menor entre todas as faixas etárias (p < 0,001). As taxas médias de detecção e de casos novos com GIF2 no diagnóstico foram maiores entre idosos (25,1/100 mil e 28,6/1 milhão de habitantes, respectivamente) em comparação aos demais grupos etários, para o país, regiões e Unidades da Federação. Foram observadas importantes diferenças nos perfis epidemiológico e clínico da hanseníase nos idosos, em relação às demais faixas etárias, destacando-se maiores proporções de casos multibacilares, de casos novos com GIF2 e baixa detecção por exame de contatos. Evidencia-se a necessidade do controle da hanseníase nessa população, visando a contribuir para a interrupção da transmissão da doença.

The article aimed to describe epidemiological indicators and characteristics of new cases of leprosy in elderly Brazilians in 2016-2018, compared to other age groups. A descriptive cross-sectional cohort study was conducted with data from the Information System on Diseases of Notification (SINAN). New leprosy cases were categorized by age groups: 60 or more, 40-59, 15-39, and 15 years of age. Pearson's chi-square test was used to verify differences between groups. A total of 81,205 new leprosy cases were reported in Brazil. Of these, 24.1% were elderly, 37.7% from 40-59 years, 31.9% from 15-39 years, and 6.3% in individuals under 15 years of age. The elderly showed higher proportions (p < 0.001) of cases in males (60.1%), with multibacillary classification (81.3%), and with physical disability grade 2 (PDG2) (11.4%) when compared to the other groups. However, the proportion of new cases detected in the elderly based on contact testing (4.9%) was the lowest among all the age brackets (p < 0.001). The mean detection rate and rate of new cases with PDG2 at diagnosis were higher among the elderly (25.1/100,000 and 28.6/million inhabitants, respectively) compared to other age groups in Brazil as a whole and in the regions and states. Important differences were seen in the epidemiological and clinical profile of leprosy in the elderly compared to other age brackets, especially higher proportions of multibacillary cases, new cases with PDG2, and low detection by contact testing. The findings highlighted the need for leprosy control in this age group, aimed at contributing to interruption of transmission of the disease.

El objetivo fue describir indicadores epidemiológicos y características de los nuevos casos de hanseniasis en ancianos en Brasil, durante el trienio 2016-2018, comparándolos con otros grupos etarios. Se realizó un estudio descriptivo de corte transversal con datos del Sistema de Información sobre Enfermedades de Notificación obligatoria (Sinan). Los nuevos casos de hanseniasis fueron categorizados por grupos etarios: 60 o más, 40-59, 15-39 y menores de 15 años. Se utilizó el test chi-cuadrado de Pearson para probar diferencias entre grupos. Se notificaron 81.205 casos nuevos de hanseniasis en Brasil. De estos, un 24,1% fueron en ancianos, 37,7% de 40-59 anos, 31,9% de 15-39 años y 6,3% en menores de 15 años. En los ancianos, se observaron proporciones mayores (p < 0,001) de casos del sexo masculino (60,1%), con clasificación operacional multibacilar (81,3%) y con grado 2 de incapacidad física (GIF2) (11,4%), respecto a otros grupos. No obstante, la proporción de casos nuevos detectados en ancianos, por examen de contactos (4,9%), fue la menor entre todas las franjas de edad (p < 0,001). Las tasas medias de detección y de casos nuevos con GIF2 en el diagnóstico fueron mayores entre ancianos (25,1/100.000 y 28,6/1 millón de habitantes, respectivamente), en comparación con los demás grupos etarios, respecto al país, regiones y Unidades de la Federación. Se observaron importantes diferencias en el perfil epidemiológico y clínico de la hanseniasis en ancianos, en relación con las demás franjas de edad, destacándose mayores proporciones de casos multibacilares, de casos nuevos con GIF2 y baja detección por examen de contactos. Se evidencia la necesidad del control de la hanseniasis en esa población, con el fin de contribuir a la interrupción de la transmisión de la enfermedad.

Falhas operacionais no controle da hanseníase em redes de convívio domiciliar com sobreposição de casos em áreas endêmicas no Brasil / Fallas operacionales en el control de la lepra en redes de convivencia domiciliar con sobreposición de casos en zonas endémicas de Brasil / Operational failures of leprosy control in household social networks with overlapping cases in endemic areas in Brazil

Objetivo: Analisar a vulnerabilidade institucional/programática de serviços de saúde no desenvolvimento das ações de atenção a pessoas acometidas pela hanseníase e de vigilância de contatos. Métodos: Estudo transversal, conduzido em 2017, sobre dados primários de amostra de casos de hanseníase notificados no período 2001-2014, com sobreposição de casos em redes de convívio domiciliar (RCD), em municípios dos estados da Bahia, Piauí e Rondônia, Brasil. Resultados: Dos 233 casos de hanseníase analisados, 154 (66,1%) pertenciam a RCD com 3 ou mais casos de hanseníase. Em 53,2% dos casos, houve acometimento de duas ou mais gerações, um desfecho significativamente associado a não realização do exame dermato-neurológico (razão de prevalências [RP] 1,32; intervalo de confiança [IC95%1,10;1,59]; p-valor=0,004). Conclusão: Falhas operacionais na vigilância de contatos de hanseníase em áreas de alta endemicidade reforçam o caráter de vulnerabilidade institucional/programática em contextos de RCD com mais de um caso de hanseníase, nos três estados analisados.

Objetivo: Analizar la vulnerabilidad institucional/programática de los servicios de salud para el desarrollo de acciones de atención a personas afectadas por lepra y de vigilancia de sus contactos. Métodos: Estudio transversal realizado en 2017 basado en datos primarios de una muestra de casos de lepra notificados entre 2001-2014 con casos superpuestos en redes de convivencia domiciliar (RCD) en Municipios de los Estados de Bahía, Piauí y Rondônia, Brasil. Resultados: Del total de 233 casos de lepra analizados, 154 (66,1%) pertenecían a RCD con 3 o más casos de lepra. En el 53.2% de los casos hubo 2 o más generaciones afectadas, resultado significativamente asociado con la no realización del dermato-neurológico (razón de prevalencias [RP] 1,32; intervalo de confianza [IC95%1,10;1,59]; valor-p=0.004). Conclusión: Las fallas operativas en la vigilancia de los contactos de lepra en áreas de alta endemicidad refuerzan el carácter de vulnerabilidad institucional/programática en los contextos de redes de convivencia domiciliar (RCD) con más de un caso de lepra en los tres estados analizados.

Objective: To analyze institutional/programmatic vulnerability of health services in the development of health care actions for people affected by leprosy and contact surveillance. Methods: This was a cross-sectional study conducted in 2017 based on primary data from a sample of leprosy cases notified between 2001-2014 with overlapping cases in household social networks (HSN) in municipalities in the states of Bahia, Piauí and Rondônia, Brazil. Results: A total of 233 leprosy cases were analyzed, 154 (66.1%) belonged to HSN with 3 or more leprosy cases. In 53.2% of cases, 2 or more generations were affected, this being an outcome associated with absence of dermato-neurological examination (prevalence ratio 1.32; confidence interval [95%CI 1.10;1.59]; p-value=0.004). Conclusion: Operational failures in the surveillance of leprosy contacts in areas of high endemicity reinforce the character of institutional/programmatic vulnerability in HSN contexts with more than one case of leprosy in the three states analyzed.

Multibacillary leprosy by population groups in Brazil: Lessons from an observational study.

BACKGROUND: Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control. METHODS: A national databank of cases reported in Brazil (2001-2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads. RESULTS: A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65-69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33-2.38; OR = 1.99, CI95% = 1.96-2.02, respectively). Bacillary load was higher in male and in patients aged 20-39 and 40-59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country. CONCLUSION: Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.

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.

Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen’s disease) in Brazil

Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from the state of Pará (PA). All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37-7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034) leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN) and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.

Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen's disease) in Brazil.

Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. To determine whether polymorphisms at the ERBB2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from the state of Pará (PA). All three tag-SNPs were associated with leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37-7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034) leprosy both contributed to the association, which is consistent with the previous linkage to chromosome 17q11-q21 in the population from PA and supports the functional role of ErbB2 in disease pathogenesis. To attempt to replicate these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200, rs1058808) were genotyped in a population-based sample of 570 leprosy cases and 370 controls from the state of Rio Grande do Norte (RN) and the results were analysed using logistic regression analysis. However, none of the associations were replicated in the RN sample, whether analysed for leprosy per se, LL leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions. The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in Brazil therefore remains unclear.

Intolerance to leprosy multi-drug therapy: more common in women?

OBJECTIVES: The objective was to characterise and identify potential risk factors for intolerance to multi-drug leprosy therapy (MDT) which prompted a medication change in a leprosy referral centre in northeastern Brazil. DESIGN: A retrospective chart review of leprosy patients treated at a state referral centre for leprosy in Natal, Rio Grande do Norte, Brazil was completed. Chart review focus was on adverse effects necessitating modification of MDT regimen. RESULTS: Six hundred and twelve records were reviewed with detection of 91 (14.8%) adverse effects with associated change in MDT regimen. The most common recorded causes of medication intolerance were anemia (8.7%), headache (4.2%), cyanosis (1.8%), and gastrointestinal symptoms (1-6%). Both female gender (OR = 2.63) and age less than 42 years old (OR = 2.7) remained risk factors for MDT intolerance in a multivariate model including gender, age, and WHO regimen type. With intolerance due to anemia as the outcome, female gender (OR = 2.36) and age less than 42 years (OR = 1.86) were associated. CONCLUSIONS: In this study, female gender and younger age were associated with greater risk of medication intolerance and medication intolerance related to anemia. These findings have important operational implications for drug intolerance monitoring during therapy for leprosy.

Nodular secondary syphilis simulating lepromatous leprosy.

There are diverse skin manifestations of both leprosy and syphilis. These diseases can appear similar to many other dermatologic conditions as well as to systemic diseases with dermatologic signs. Nodular syphilis is an uncommon type of secondary syphilis. We present here a person from a leprosy-endemic area with diffuse nodular skin lesions of secondary syphilis who was initially suspected of having lepromatous leprosy.

Geographic information systems and applied spatial statistics are efficient tools to study Hansen's disease (leprosy) and to determine areas of greater risk of disease.

Applied Spatial Statistics used in conjunction with geographic information systems (GIS) provide an efficient tool for the surveillance of diseases. Here, using these tools we analyzed the spatial distribution of Hansen's disease in an endemic area in Brazil. A sample of 808 selected from a universe of 1,293 cases was geocoded in Mossoró, Rio Grande do Norte, Brazil. Hansen's disease cases were not distributed randomly within the neighborhoods, with higher detection rates found in more populated districts. Cluster analysis identified two areas of high risk, one with a relative risk of 5.9 (P = 0.001) and the other 6.5 (P = 0.001). A significant relationship between the geographic distribution of disease and the social economic variables indicative of poverty was observed. Our study shows that the combination of GIS and spatial analysis can identify clustering of transmissible disease, such as Hansen's disease, pointing to areas where intervention efforts can be targeted to control disease.

The use of Geographical Information System (GIS) to improve active leprosy case finding campaigns in the municipality of Mossoró, Rio Grande do Norte State, Brazil.

There is a high incidence of leprosy in the municipality of Mossor6, Rio Grande do Norte state, where the detection coefficient has risen from 2.78/10,000 population in 1998 to 5.14 in 2004. While cases have been registered throughout the urban area, the disease is concentrated in select neighbourhoods. This study was undertaken using Geographical Information System (GIS) with the objective of defining low-cost, effective strategies to control leprosy. The land registry map of the city, Ikonos satellite images and the SINAN (National Morbidity Notification Information System) database were used as the cartographical basis for the study. The sample for the leprosy mapping was drawn from the 358 new cases of the disease diagnosed in the municipality between 1998 and 2002. The houses of 281 patients were located (78.5% of the total) and their addresses geo-referenced using a GPS handheld device. Subsequently, geographical analysis was carried out using ArcView 9.0 software showing predominant concentration of cases in the neighbourhoods of Barrocas, Santo Antônio, Bom Jardim and Paredões. This mapping served as the basis for four active case finding campaigns conducted in the most highly concentrated areas between March and September of 2005. Campaigns guided by spatial analysis led to the diagnosis of 104 new cases of the disease (50% of the total number of new cases detected in the municipality in 2005). The use of GIS in leprosy diagnosis has shown to be extremely effective, providing a clear visual understanding of the distribution of the disease in the municipality, which results in targeted interventions and important cost reductions in leprosy control activities.