Increased risk of atrial fibrillation in patients with psoriasis: A meta-analysis of observational studies.

BACKGROUND: Several epidemiological studies have shown that psoriasis increases the risk of developing atrial fibrillation but evidence of this is still scarce. AIMS: Our objective was to systematically review, synthesise and critique the epidemiological studies that provided information about the relationship between psoriasis and atrial fibrillation risk. METHODS: We searched through PubMed, EMBASE and the bibliographies for articles published between 1 January 2000, and 1 November 2017, that reported on the association between psoriasis and atrial fibrillation. All abstracts, full-text articles and sources were reviewed with duplicate data excluded. Summary relative risks (RRs) with 95% CI were pooled using a random effects model. RESULTS: We identified 252 articles, of these eight unique abstracts underwent full-text review. We finally selected six out of these eight studies comprising 11,187 atrial fibrillation patients. The overall pooled relative risk (RR) of atrial fibrillation was 1.39 (95% CI: 1.257-1.523, P < 0.0001) with significant heterogeneity (I2 = 80.316, Q = 45.723, τ2 = 0.017, P < 0.0001) for the random effects model. In subgroup analysis, the greater risk was found in studies from North America, RR 1.482 (95% CI: 1.119-1.964, P < 0.05), whereas a moderate risk was observed in studies from Europe RR 1.43 (95% CI: 1.269-1.628, P < 0.0001). LIMITATIONS: We were only able to include six studies with 11,178 atrial fibrillation patients, because only a few such studies have been published. CONCLUSION: Our results showed that psoriasis is significantly associated with an increased risk of developing atrial fibrillation. Therefore, physicians should monitor patient's physical condition on a timely basis.

Spatial-temporal analysis of leprosy in a priority Brazilian northeast municipality for disease control.

OBJECTIVES: to analyze the spatial-temporal distribution of leprosy in a priority municipality for leprosy control. METHODS: ecological study, conducted in a city in the Northeast of Brazil, whose analysis units were census sectors. The study used compulsory notification data for cases registered between 2008 and 2017. TerraView software and the Batch Geocode tool was used for geocoding. The detection of spatial-temporal agglomerations of high relative risks was done by scanning statistics. RESULTS: the spatial-temporal distribution of cases was heterogeneous, creating four agglomerations of high relative risks in the urban area of the municipality between the years 2008 and 2012; and annual prevalence rates classified from high to hyperendemic. CONCLUSIONS: areas of higher risk and concentration of the disease in space-time were linked to the characteristics of high population density and social vulnerability of these spaces, raising the prioritization of health professionals' actions, systems, and services for control, and monitoring the disease.

Association of PTPN22-C1858T Polymorphism With Susceptibility to Mycobacterium tuberculosis and Mycobacterium leprae Infection: A Meta-Analysis.

It was previously published that single-nucleotide polymorphism rs2476601 (PTPN22 [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased sensibility to Mycobacterium tuberculosis and M. leprae infection. However, the results were inconclusive despite a high degree of similarity between both parameters. Herein, we carried out this meta-analysis to systematically summarize and articulate the correlation between PTPN22-C1858T polymorphism and mycobacterial infection. The susceptibility of PTPN22-C1858T carriers with autoimmune conditions receiving immunosuppressive therapy to M. tuberculosis and M. leprae infection was determined. A systematic retrieval of studies on relevance of PTPN22-C1858T polymorphism to susceptibility of M. tuberculosis or M. leprae infection was performed in Chinese National Knowledge Infrastructure, PubMed and Embase databases. We regarded Odds ratios (ORs) and 95% confidence intervals (CIs) as the determined effect size. Finally, four and two case-control studies on tuberculosis and leprosy, respectively, were included. In all genetic models, without indicated association between PTPN22-C1858T polymorphism and tuberculosis's susceptibility. [C versus T: OR = 0.22 (95% CI: 0.09-0.50, PH = 0.887); CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889); TT+CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, PH = 0.889)]. A significantly increased risk of leprosy was perceived in patients with the PTPN22-C1858T polymorphism [C versus T: OR = 2.82 (95% CI: 1.02-7.81, PH = 0.108)]. While the PTPN22-C1858T polymorphism is irrelevant to higher susceptibility to the infection of M. tuberculosis in Caucasians and Asians, it is relevant to increased susceptibility to the infection of M. leprae. However, the results of M. leprae are supposed to interpreted with prudence owing to the limited quantity of studies and heterogeneity. Further well-designed studies with sufficient populations are required to verify our conclusions.

Geospatial epidemiology of leprosy in northwest Bangladesh: a 20-year retrospective observational study.

BACKGROUND: Leprosy is known to be unevenly distributed between and within countries. High risk areas or 'hotspots' are potential targets for preventive interventions, but the underlying epidemiologic mechanisms that enable hotspots to emerge, are not yet fully understood. In this study, we identified and characterized leprosy hotspots in Bangladesh, a country with one of the highest leprosy endemicity levels globally. METHODS: We used data from four high-endemic districts in northwest Bangladesh including 20 623 registered cases between January 2000 and April 2019 (among ~ 7 million population). Incidences per union (smallest administrative unit) were calculated using geospatial population density estimates. A geospatial Poisson model was used to detect incidence hotspots over three (overlapping) 10-year timeframes: 2000-2009, 2005-2014 and 2010-2019. Ordinal regression models were used to assess whether patient characteristics were significantly different for cases outside hotspots, as compared to cases within weak (i.e., relative risk (RR) of one to two), medium (i.e., RR of two to three), and strong (i.e., RR higher than three) hotspots. RESULTS: New case detection rates dropped from 44/100 000 in 2000 to 10/100 000 in 2019. Statistically significant hotspots were identified during all timeframes and were often located at areas with high population densities. The RR for leprosy was up to 12 times higher for inhabitants of hotspots than for people living outside hotspots. Within strong hotspots (1930 cases among less than 1% of the population), significantly more child cases (i.e., below 15 years of age) were detected, indicating recent transmission. Cases in hotspots were not significantly more likely to be detected actively. CONCLUSIONS: Leprosy showed a heterogeneous distribution with clear hotspots in northwest Bangladesh throughout a 20-year period of decreasing incidence. Findings confirm that leprosy hotspots represent areas of higher transmission activity and are not solely the result of active case finding strategies.

[Leprosy-related mortality in the State of Piauí, Brazil: time trends and spatial patterns, 2000-2015]. / Mortalidade relacionada à hanseníase no Estado do Piauí, Brasil: tendências temporais e padrões espaciais, 2000-2015.

The study aimed to analyze spatial patterns and time trends in leprosy-related mortality in the State of Piauí, Brazil, from 2000 to 2015. This was a mixed ecological study with a spatial and temporal state-based approach, using data from the Brazilian Mortality Information System. The analysis includes epidemiological characteristics, mortality trends by Joinpoint regression, and spatial analysis, using the state's 224 municipalities (counties) as the geographic unit. Of the 245,413 deaths identified, leprosy was identified in 234 death certificates, 135 (41.7%) as the underlying cause of death and 189 (58.3%) as an associated cause of death. The highest leprosy-related mortality rates were associated with male gender (relative risk - RR = 2.38; 95%CI: 1.87; 3.03), elderly age (RR = 10.52; 95%CI: 7.16; 15.46), brown skin color (RR = 2.22; 95%CI: 1.47; 3.35), and residents of the state's interior (RR = 5.72; 95%CI: 4.54; 7.21). The crude leprosy-related mortality rate showed a significant increase among the elderly (70 years), brown race/color, cities with fewer than 20,000 inhabitants, and the Central region of the state, but not significant for the State of Piauí as a whole. The spatial distribution by age-adjusted mortality was heterogeneous in the municipalities, concentrating high mortality rates in the northern region of the state, close to the coastline. There was a pattern of increasing smoothed mortality rates over the course of the study's four-year periods in the Mid-northern Central and Semiarid regions. Leprosy mortality was spatially heterogeneous and growing over the years. The findings highlight the importance of enhancing integrated surveillance and healthcare activities.

O estudo teve por objetivo analisar padrões espaciais e tendências temporais da mortalidade relacionada à hanseníase no Estado do Piauí, Brasil, de 2000 a 2015. Trata-se de estudo ecológico misto, com abordagem espacial e temporal, de base estadual, a partir de dados do Sistema de Informaçãos sobre Mortalidade. A análise inclui características epidemiológicas, tendências de mortalidade por regressão Joinpoint e análise espacial, usando os 224 municípios como unidade geográfica. Dos 245.413 óbitos identificados, a hanseníase foi identificada em 324 declarações, 135 (41,7%) como causa básica de óbito e 189 (58,3%) como associada. Os maiores coeficientes de mortalidade relacionados à hanseníase foram observados entre homens (risco relativo - RR = 2,38; IC95%: 1,87; 3,03), idosos (RR = 10,52; IC95%: 7,16; 15,46), cor parda (RR = 2,22; IC95%: 1,47; 3,35) e residentes do interior do estado (RR = 5,72; IC95%: 4,54; 7,21). O coeficiente bruto de mortalidade relacionado à hanseníase apresentou incremento significativo entre idosos (70 anos), raça/cor parda, em cidades com menos de 20 mil habitantes e região Meio-norte, mas não significativo para o Estado do Piauí. A distribuição espacial pelos coeficientes de mortalidade ajustada por idade foi heterogênea nos municípios, concentrando altos coeficientes de mortalidade no norte do estado, próximo ao litoral. Verificou-se padrão de aumento dos coeficientes de mortalidade suavizados no decorrer dos quadriênios do estudo, concentrando altos coeficientes nas regiões Meio-norte e Semiárido. A mortalidade por hanseníase é espacialmente heterogênea e crescente ao longo dos anos. Ressalta-se a importância de potencializar ações integradas de vigilância e atenção à saúde.

El objetivo del estudio fue analizar patrones espaciales y tendencias temporales de mortalidad, relacionada con la hanseniasis en el Estado de Piauí, Brasil, de 2000 a 2015. Se trata de un estudio ecológico mixto, con un abordaje espacial y temporal, de base estatal, a partir de datos del Sistema de Información sobre Mortalidad. El análisis incluye características epidemiológicas, tendencias de mortalidad por regresión Joinpoint y análisis espacial, usando 224 municipios como unidad geográfica. De los 245.413 óbitos identificados, la hanseniasis fue identificada en 324 declaraciones, 135 (41,7%) como causa básica de óbito y 189 (58,3%) como asociada. Los mayores coeficientes de mortalidad relacionada con la hanseniasis se observaron entre hombres (riesgo relativo - RR = 2,38; IC95%: 1,87; 3,03), ancianos (RR = 10,52; IC95%: 7,16; 15,46), color pardo (RR = 2,22; IC95%: 1,47; 3,35) y residentes en el interior del estado (RR = 5,72; IC95%: 4,54; 7,21). El coeficiente bruto de mortalidad relacionado con la hanseniasis presentó un incremento significativo entre ancianos (70 años), raza/color pardo, en ciudades con menos de 20.000 habitantes y región Medio-norte, pero no es significativo para el Estado de Piauí. La distribución espacial por los coeficientes de mortalidad ajustada por edad fue heterogénea en los municipios, concentrando altos coeficientes de mortalidad en el norte del estado, cercano al litoral. Se verificó un patrón de aumento de los coeficientes de mortalidad suavizados en el transcurso de los cuatrienios del estudio, concentrando altos coeficientes en las regiones Medio-norte y Semiárida. La mortalidad por hanseniasis es heterogénea espacialmente y creciente a lo largo de los años. Se resalta la importancia de potenciar acciones integradas de vigilancia y atención a la salud.

Mortalidade relacionada à hanseníase no Estado do Piauí, Brasil: tendências temporais e padrões espaciais, 2000-2015 / Leprosy-related mortality in the State of Piauí, Brazil: time trends and spatial patterns, 2000-2015 / Mortalidad relacionada con la hanseniasis en el Estado de Piauí, Brasil: tendencias temporales y patrones espaciales, 2000-2015

O estudo teve por objetivo analisar padrões espaciais e tendências temporais da mortalidade relacionada à hanseníase no Estado do Piauí, Brasil, de 2000 a 2015. Trata-se de estudo ecológico misto, com abordagem espacial e temporal, de base estadual, a partir de dados do Sistema de Informaçãos sobre Mortalidade. A análise inclui características epidemiológicas, tendências de mortalidade por regressão Joinpoint e análise espacial, usando os 224 municípios como unidade geográfica. Dos 245.413 óbitos identificados, a hanseníase foi identificada em 324 declarações, 135 (41,7%) como causa básica de óbito e 189 (58,3%) como associada. Os maiores coeficientes de mortalidade relacionados à hanseníase foram observados entre homens (risco relativo - RR = 2,38; IC95%: 1,87; 3,03), idosos (RR = 10,52; IC95%: 7,16; 15,46), cor parda (RR = 2,22; IC95%: 1,47; 3,35) e residentes do interior do estado (RR = 5,72; IC95%: 4,54; 7,21). O coeficiente bruto de mortalidade relacionado à hanseníase apresentou incremento significativo entre idosos (70 anos), raça/cor parda, em cidades com menos de 20 mil habitantes e região Meio-norte, mas não significativo para o Estado do Piauí. A distribuição espacial pelos coeficientes de mortalidade ajustada por idade foi heterogênea nos municípios, concentrando altos coeficientes de mortalidade no norte do estado, próximo ao litoral. Verificou-se padrão de aumento dos coeficientes de mortalidade suavizados no decorrer dos quadriênios do estudo, concentrando altos coeficientes nas regiões Meio-norte e Semiárido. A mortalidade por hanseníase é espacialmente heterogênea e crescente ao longo dos anos. Ressalta-se a importância de potencializar ações integradas de vigilância e atenção à saúde.

The study aimed to analyze spatial patterns and time trends in leprosy-related mortality in the State of Piauí, Brazil, from 2000 to 2015. This was a mixed ecological study with a spatial and temporal state-based approach, using data from the Brazilian Mortality Information System. The analysis includes epidemiological characteristics, mortality trends by Joinpoint regression, and spatial analysis, using the state's 224 municipalities (counties) as the geographic unit. Of the 245,413 deaths identified, leprosy was identified in 234 death certificates, 135 (41.7%) as the underlying cause of death and 189 (58.3%) as an associated cause of death. The highest leprosy-related mortality rates were associated with male gender (relative risk - RR = 2.38; 95%CI: 1.87; 3.03), elderly age (RR = 10.52; 95%CI: 7.16; 15.46), brown skin color (RR = 2.22; 95%CI: 1.47; 3.35), and residents of the state's interior (RR = 5.72; 95%CI: 4.54; 7.21). The crude leprosy-related mortality rate showed a significant increase among the elderly (70 years), brown race/color, cities with fewer than 20,000 inhabitants, and the Central region of the state, but not significant for the State of Piauí as a whole. The spatial distribution by age-adjusted mortality was heterogeneous in the municipalities, concentrating high mortality rates in the northern region of the state, close to the coastline. There was a pattern of increasing smoothed mortality rates over the course of the study's four-year periods in the Mid-northern Central and Semiarid regions. Leprosy mortality was spatially heterogeneous and growing over the years. The findings highlight the importance of enhancing integrated surveillance and healthcare activities.

El objetivo del estudio fue analizar patrones espaciales y tendencias temporales de mortalidad, relacionada con la hanseniasis en el Estado de Piauí, Brasil, de 2000 a 2015. Se trata de un estudio ecológico mixto, con un abordaje espacial y temporal, de base estatal, a partir de datos del Sistema de Información sobre Mortalidad. El análisis incluye características epidemiológicas, tendencias de mortalidad por regresión Joinpoint y análisis espacial, usando 224 municipios como unidad geográfica. De los 245.413 óbitos identificados, la hanseniasis fue identificada en 324 declaraciones, 135 (41,7%) como causa básica de óbito y 189 (58,3%) como asociada. Los mayores coeficientes de mortalidad relacionada con la hanseniasis se observaron entre hombres (riesgo relativo - RR = 2,38; IC95%: 1,87; 3,03), ancianos (RR = 10,52; IC95%: 7,16; 15,46), color pardo (RR = 2,22; IC95%: 1,47; 3,35) y residentes en el interior del estado (RR = 5,72; IC95%: 4,54; 7,21). El coeficiente bruto de mortalidad relacionado con la hanseniasis presentó un incremento significativo entre ancianos (70 años), raza/color pardo, en ciudades con menos de 20.000 habitantes y región Medio-norte, pero no es significativo para el Estado de Piauí. La distribución espacial por los coeficientes de mortalidad ajustada por edad fue heterogénea en los municipios, concentrando altos coeficientes de mortalidad en el norte del estado, cercano al litoral. Se verificó un patrón de aumento de los coeficientes de mortalidad suavizados en el transcurso de los cuatrienios del estudio, concentrando altos coeficientes en las regiones Medio-norte y Semiárida. La mortalidad por hanseniasis es heterogénea espacialmente y creciente a lo largo de los años. Se resalta la importancia de potenciar acciones integradas de vigilancia y atención a la salud.

Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study.

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Dermatitis Herpetiformis and Celiac Disease Increase the Risk of Bullous Pemphigoid.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are autoimmune bullous skin diseases. DH has been described to evolve into BP and the two diseases can have overlapping clinical appearances and diagnostic findings, but the association between DH and BP has not previously been studied in a large population. To evaluate DH and celiac disease as risk factors for BP, we conducted a retrospective case-control study of patients with BP and matched controls with basal cell carcinoma diagnosed in Finland between 1997 and 2013. A total of 3,397 patients with BP and 12,941 controls were included in the study. Forty-one (1.2%) BP patients and 7 (0.1%) controls had preceding DH. Diagnosed DH increased the risk of BP 22-fold (odds ratio = 22.30; 95% confidence interval = 9.99-49.70) and celiac disease 2-fold (odds ratio = 2.54; 95% confidence interval = 1.64-3.92) compared to controls. Eighteen (43.9%) of the patients who had DH and subsequent BP had bought dapsone during the 2 years prior to their BP diagnosis. Mean time between diagnosed DH and BP was 3 years. We conclude that diagnosis of DH is associated with a striking increase in the risk for BP.

Limitação de atividade e consciência de risco em clientes acometidos pela hanseníase / Activities limitation and risk awareness in leprosy patients

Objetivo: Caracterizar a limitação de atividade e a consciência de risco entre pacientes com hanseníase e analisar a correla-ção entre os escores da escala SALSA para limitação com a Classificação Operacional, Forma Clínica, Reação Hansênica e Consciência de Risco. Material e Métodos: Estudo descritivo, seccional, quantitativo realizado com indivíduos com hanse-níase utilizando a Screening of Activity Limitation and Safety Awarenes (Escala SALSA) para diagnóstico situacional. Para análise dos dados adotou-se o software estatístico SPSS 20.0. Resultados: O perfil sociodemográfico da amostra aponta ele-vados índices de detecção da doença na população masculina (70,5%), com escolaridade de nível fundamental (58,8%), baixa renda, em faixa etária economicamente produtiva. A faixa etária oscilou entre 15 e 69 anos. Identificou-se leve limitação (escores 25 a 39) e baixa consciência de risco (escores 0 a 5), havendo forte significância estatística entre as mesmas (p=0,001). Ve-rificou-se correlação positiva da limitação de atividade com a reação hansênica (r=0,068) e a consciência de risco (r=0,801). Observou-se ainda que a consciência de risco foi baixa em to-dos os aspectos, contudo estiveram correlacionadas as formas mais graves da doença e aos clientes que já apresentavam alguma limitação. Conclusão: A existência de limitação para AVD's, embora em categoria leve, bem como nenhuma e baixa consciência de risco sinalizam para a necessidade de fortale-cimento de ações de prevenção das incapacidades, dentre as quais, a educação em saúde consolida-se como ferramenta relevante, mediadora de reversibilidade destas consequências. (AU)

Objective: To characterize activity limitation and risk awareness among leprosy patients and analyze the correlation between the SALSA scale scores for limitation with the Operational Classi-fication, Clinical Form, Hansen Reaction and Risk Awareness. Material and Methods: Descriptive, sectional, quantitative study carried out with individuals with leprosy using the Screening of Activity Limitation and Safety Awareness (SALSA Scale) for situational diagnosis. Data analysis was performed using the statistical software SPSS 20.0. Results: The sociodemographic profile of the sample shows high rates of detection of the disease in the male population (70.5%), with a low level of schooling (58.8%), in an economically productive age range. The age ranged from 15 to 69 years. A slight limitation was identified (scores 25 to 39) and low risk awareness (scores 0 to 5), with a strong statistical significance between them (p = 0.001). There was a positive correlation of the activity limitation with the leprosy reaction (r = 0.068) and risk awareness (r = 0.801). It was also observed that the risk awareness was low in all aspects, but the most severe forms of the disease were correlated with the clients that already had some limitation. Conclusion: The existence of limitations for ADLs, although in a mild category, as well as none and low risk awareness, point to the need to strengthen actions to prevent disabilities, among them, health education is consolidated as a relevant tool, mediator of reversibility of these consequences. (AU)

Epidemiological and geographical characterization of leprosy in a Brazilian hyperendemic municipality.

This study aimed to identify the distribution pattern of leprosy in a hyperendemic municipality in Brazil and determine its relationship with the clinico-epidemiological situation over 11 years. The geographic information system, MapInfo, spatial scan statistics and the Moran I index were used to analyze new cases. The digital cartographic base was used to map clusters of new paucibacillary and multibacillary cases and cases in minors under 15 years old. Socioeconomic indicators are shown using the choropleth mapping technique. A reduction in the detection coefficient, increases in high-risk spatial clusters, marked changes in the distribution of high-risk and low-risk clusters, and high-risk clusters of minors under 15 years old were observed from 2006 to 2010, showing recent illness, the presence of active foci, and overlapping of high-risk clusters of multibacillary infection in minors under 15 years old. Leprosy remains a public health problem in Rondonópolis, Mato Grosso State; the high-risk areas require an intensification of control measures and active search strategies to detect new cases.

Evidence of zoonotic leprosy in Pará, Brazilian Amazon, and risks associated with human contact or consumption of armadillos.

Mycobacterium leprae (M. leprae) is a human pathogen and the causative agent for leprosy, a chronic disease characterized by lesions of the skin and peripheral nerve damage. Zoonotic transmission of M. leprae to humans by nine-banded armadillos (Dasypus novemcinctus) has been shown to occur in the southern United States, mainly in Texas, Louisiana, and Florida. Nine-banded armadillos are also common in South America, and residents living in some areas in Brazil hunt and kill armadillos as a dietary source of protein. This study examines the extent of M. leprae infection in wild armadillos and whether these New World mammals may be a natural reservoir for leprosy transmission in Brazil, similar to the situation in the southern states of the U.S. The presence of the M. leprae-specific repetitive sequence RLEP was detected by PCR amplification in purified DNA extracted from armadillo spleen and liver tissue samples. A positive RLEP signal was confirmed in 62% of the armadillos (10/16), indicating high rates of infection with M. leprae. Immunohistochemistry of sections of infected armadillo spleens revealed mycobacterial DNA and cell wall constituents in situ detected by SYBR Gold and auramine/rhodamine staining techniques, respectively. The M. leprae-specific antigen, phenolic glycolipid I (PGL-I) was detected in spleen sections using a rabbit polyclonal antibody specific for PGL-I. Anti-PGL-I titers were assessed by ELISA in sera from 146 inhabitants of Belterra, a hyperendemic city located in western Pará state in Brazil. A positive anti-PGL-I titer is a known biomarker for M. leprae infection in both humans and armadillos. Individuals who consumed armadillo meat most frequently (more than once per month) showed a significantly higher anti-PGL-I titer than those who did not eat or ate less frequently than once per month. Armadillos infected with M. leprae represent a potential environmental reservoir. Consequently, people who hunt, kill, or process or eat armadillo meat are at a higher risk for infection with M. leprae from these animals.

Social determinants, their relationship with leprosy risk and temporal trends in a tri-border region in Latin America.

BACKGROUND: Brazil is the only country in Latin America that has adopted a national health system. This causes differences in access to health among Latin American countries and induces noticeable migration to Brazilian regions to seek healthcare. This phenomenon has led to difficulties in the control and elimination of diseases related to poverty, such as leprosy. The aim of this study was to evaluate social determinants and their relationship with the risk of leprosy, as well as to examine the temporal trend of its occurrence in a Brazilian municipality located on the tri-border area between Brazil, Paraguay and Argentina. METHODS: This ecological study investigated newly-diagnosed cases of leprosy between 2003 and 2015. Exploratory analysis of the data was performed through descriptive statistics. For spatial analysis, geocoding of the data was performed using spatial scan statistic techniques to obtain the Relative Risk (RR) for each census tract, with their respective 95% confidence intervals calculated. The Bivariate Moran I test, Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR) models were applied to analyze the spatial relationships of social determinants and leprosy risk. The temporal trend of the annual coefficient of new cases was obtained through the Prais-Winsten regression. A standard error of 5% was considered statistically significant (p < 0.05). RESULTS: Of the 840 new cases identified in the study, there was a predominance of females (n = 427, 50.8%), of white race/color (n = 685, 81.6%), age range 15 to 59 years (n = 624, 74.3%), and incomplete elementary education (n = 504, 60.0%). The results obtained from multivariate analysis revealed that the proportion of households with monthly nominal household income per capita greater than 1 minimum wage (ß = 0.025, p = 0.036) and people of brown race (ß = -0.101, p = 0.024) were statistically-significantly associated with risk of illness due to leprosy. These results also confirmed that social determinants and risk of leprosy were significantly spatially non-stationary. Regarding the temporal trend, a decrease of 4% (95% CI [-0.053, -0.033], p = 0.000) per year was observed in the rate of detection of new cases of leprosy. CONCLUSION: The social determinants income and race/color were associated with the risk of leprosy. The study's highlighting of these social determinants can contribute to the development of public policies directed toward the elimination of leprosy in the border region.

Epidemiological and geographical characterization of leprosy in a Brazilian hyperendemic municipality / Caracterização epidemiológica e geográfica da hanseníase em um município brasileiro hiperendêmico / Caracterización epidemiológica y geográfica de lepra en un municipio brasileño hiperendémico

Abstract: This study aimed to identify the distribution pattern of leprosy in a hyperendemic municipality in Brazil and determine its relationship with the clinico-epidemiological situation over 11 years. The geographic information system, MapInfo, spatial scan statistics and the Moran I index were used to analyze new cases. The digital cartographic base was used to map clusters of new paucibacillary and multibacillary cases and cases in minors under 15 years old. Socioeconomic indicators are shown using the choropleth mapping technique. A reduction in the detection coefficient, increases in high-risk spatial clusters, marked changes in the distribution of high-risk and low-risk clusters, and high-risk clusters of minors under 15 years old were observed from 2006 to 2010, showing recent illness, the presence of active foci, and overlapping of high-risk clusters of multibacillary infection in minors under 15 years old. Leprosy remains a public health problem in Rondonópolis, Mato Grosso State; the high-risk areas require an intensification of control measures and active search strategies to detect new cases.

Resumo: O estudo teve como objetivos identificar o padrão de distribuição da hanseníase em um município brasileiro hiperendêmico e determinar a relação com o quadro clínico-epidemiológico ao longo de 11 anos. Os casos novos foram analisados com o sistema de informação geográfica, MapInfo, estatística scan espacial e índice Moran I. A base cartográfica digital foi usada para mapear os clusters de casos paucibacilares e multibacilares novos e casos em menores de 15 anos. Os indicadores socioeconômicos são mostrados através da técnica de mapeamento coroplético. Entre 2006 e 2010, foram observados uma redução no coeficiente de detecção, aumento no clusters espaciais de alto risco, mudanças marcantes na distribuição de clusters de alto e baixo risco e clusters de alto risco em menores de 15 anos, sugerindo doença recente, a presença de focos ativos e a sobreposição de clusters de alto risco para infecção multibacilar em menores de 15 anos. A hanseníase persiste enquanto problema de saúde pública em Rondonópolis, Mato Grosso; as áreas de alto risco exigem a intensificação de medidas de controle, além de estratégias de busca ativa para detectar casos novos.

Resumen: Este estudio tuvo como objetivo identificar la distribución de los patrones de lepra en una municipalidad hiperendémica en Brasil y determinar su relación con la situación clínico-epidemiológica durante 11 años. El sistema de información geográfica, MapInfo, estadísticas de escaneo espacial y el índice de Moran se usaron para analizar nuevos casos. La base cartográfica digital se usó para mapear clústeres de nuevos casos multibacilares y paucibacilares, así como casos en menores por debajo de 15 años de edad. Los indicadores socioeconómicos se presentan usando la técnica de mapeo de coropletas. La reducción en la detección del coeficiente, se incrementa en los clústeres de alto riesgo espaciales, asimismo, se observaron de 2006 a 2010 cambios considerables en la distribución de los clústeres de alto riesgo y bajo riesgo, así como en clústeres de alto riesgo con menores con menos de 15 años de edad, mostrando los casos de enfermedad reciente la presencia de focos activos, así como solapando clústeres de alto riesgo de infección multibacilar en menores por debajo de los 15 años de edad. La lepra continúa siendo un problema de salud pública en Rondonópolis, Mato Grosso; las áreas de alto riesgo necesitan una intensificación de las medidas de control y una búsqueda activa de estrategias, con el fin de detectar nuevos casos.

Áreas de Risco para ocorrência de hanseníase no município de Ribeirão Preto/SP / Areas of Risk for the occurrence of leprosy in Ribeirão Preto/SP

Em 2015 ocorreram no mundo 210.758 casos novos de hanseníase, representando uma taxa de detecção de 3,2 casos para cada 100.000 habitantes. O Brasil foi o segundo país em número de casos, com um coeficiente de detecção de 14,6 casos por 100.000 habitantes. Uma das principais características epidemiológicas da hanseníase é sua heterogeneidade e desigualdade de distribuição em um local geograficamente definido, o que torna relevante identificar áreas mais suscetíveis que explicam a ocorrência da doença nesses locais. Objetivo: Identificar áreas de maior e de menor risco para a ocorrência de hanseníase em Ribeirão Preto/SP. Materiais e Métodos: Trata-se de um estudo ecológico, realizado no município de Ribeirão Preto/SP, em que foram considerados os casos de hanseníase notificados no SINAN no período de janeiro de 2006 a dezembro de 2013. Para detecção de risco para aglomerados espaciais e espaço-temporais dos casos de hanseníase procedeu-se inicialmente a geocodificação dos casos por meio do software TerraView versão 4.2.2, utilizando como unidade de análise ecológica o setor censitário urbano. A técnica de estatística de varredura foi processada controlando- se a ocorrência de casos pelo tamanho da população dos setores censitários, por sua distribuição etária e do sexo, com vistas a detecção de aglomerados no espaço e no espaço-tempo de alto e baixo risco relativo (RR) com seus respectivos intervalos de confiança em 95%. Fixou-se erro tipo I em 5% (p<0,05) como estatisticamente significativos. A técnica de varredura foi processada no software SaTScan 9.4 e os mapas temáticos contendo o RR dos aglomerados foram feitos por meio do software ArcGIS 10.1. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da Escola de Enfermagem de Ribeirão Preto/USP (nº 44637215.0.0000.5393). Resultados: Foram notificados 434 casos de hanseníase no período de investigação, dos quais 392 casos foram geocodificados (95%). A análise de varredura dos casos de hanseníase possibilitou a detecção de dois aglomerados espaciais estatisticamente significativos (p<0,05), no qual um aglomerado de alto risco (RR=3,41; IC95%: 2,721-4,267; p=0,000), e um de baixo risco (RR=0,41; IC95%: 0,326-0,528; p=0,000). Na análise espaço-temporal, foram identificados três aglomerados estatisticamente significativos (p<0,05), sendo dois de alto risco (RR=24,35; IC95%: 11,133-52,984; p=0,006), (RR=15,24, IC95%: 10,114-22,919; p=0,000) ocorridos no período de 2012 a 2012 e 2012 a 2013, respectivamente; e um aglomerado de baixo risco (RR=0,35; IC95%: 0,252-0,485) no período de 2008 a 2011. Conclusões: O estudo possibilitou a identificação das áreas de maior e menor risco para o acometimento pela hanseníase. Os locais com maior RR situam-se nos distritos de saúde Norte, Oeste e Central, caracterizados por apresentar os piores indicadores socioeconômicos do município, com carências em habitação, renda, escolaridade e acesso a serviços de saúde, o que evidencia a desigualdade social no local sob estudo

In 2015, 210,758 new cases of leprosy occurred in the world, representing a detection rate of 3.2 cases per 100,000 inhabitants. Brazil was the second country in terms of number of cases, with a detection coefficient of 14.6 cases per 100,000 inhabitants. The main epidemiological characteristics of leprosy is its heterogeneity and inequality distribution in an area geographically located, which becomes the disease an important issue to identify areas with Risk. Objective: To identify areas with high and low risk for occurrence of leprosy in Ribeirão Preto / SP. Materials and Methods: This is an ecological study, carried out in Ribeirão Preto / SP, in which the cases were gathered through SINAN from January 2006 to December 2013. For the detection of areas with Spatial Risk and Spatial Temporal Risk, initially the cases of leprosy cases were geocoded cases using TerraView software version 4.2.2; Census tract was considered as ecological analysis unit or urban. The scan statistic was performed considering occurrence of cases by size of the population in census tract according age and sex. It was measured the Relative Risk and its confident interval by 95%. Type I error was set at 5% (p <0.05) as statistically significant. The scanning technique was used by SaTScan 9.4 software and the thematic maps was constructed by ArcGIS 10.1. The study was approved by the Research Ethics Committee of Ribeirão Preto School of Nursing - USP (nº 44637215.0.0000.5393). Results: A total of 434 leprosy cases were reported, of which 392 cases were geocoded (95%). Through Scan Statistic two areas were observed as statistically significant (p <0.05), being one area with high risk (RR = 3.41; CI95%: 2.721-4.267; p=0.000), and another one with low risk (RR = 0.41; CI95%: 0.326-0.528; p=0.000). In the space-time analysis, three statistically significant clusters (p <0.05) were identified, two of them were with high risk (RR = 24.35; CI95%: 11.133-52.984; p=0.006), (RR = 15.24; CI95%: 10.114-22.919; p=0.000) and one with low risk (RR = 0, 35; CI95%: 0.252-0.485; p=0.000). Conclusions: The study provided the identification of the areas with high and low risk for transmission of leprosy. The areas with high Risk are located in the districts of North, West and Central health, which also present the social vulnerability in terms of dwelling, income, schooling and access to the health services

C13orf31 (FAMIN) is a central regulator of immunometabolic function.

Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Saúde nas metrópoles – doenças infecciosas / Health in metropolises - Infectious Diseases

A urbanização é um processo irreversível em escala mundial e estima-se que o número de pessoas que vivem em cidades deverá atingir 67% da população do planeta até 2050. Os países de baixa ou média renda, por sua vez, possuem 30% a 40% da população urbana vivendo atualmente em favelas, em situação de risco para diversos agravos de saúde. No Brasil, embora 84,3% da população residissem em áreas urbanas já em 2010, não se verificam no momento ações consistentes voltadas ao enfrentamento das questões de saúde urbana. Neste artigo discute-se a situação epidemiológica de agravos infecciosos de interesse para a saúde pública (dengue, infecção por HIV/aids, leptospirose, hanseníase e tuberculose) a partir do ano 2000 nas 17 metrópoles do país, de modo a esclarecer o papel atual das doenças infecciosas no contexto da saúde urbana brasileira...

Urbanization is an irreversible global process and the number of people living in cities is estimated to reach 67% of the world population by 2050. In low- and middle-income countries, 30% to 40% of the population currently lives in slum areas, under risk of several diseases. Even though 84.3% of the Brazilian population already lived in urban areas in 2010, no consistent initiatives have been implemented to address urban health issues. We discuss here the epidemiological features of communicable diseases that are relevant to public health (dengue, HIV/aids, leptospirosis, leprosy and tuberculosis) in Brazil’s 17 metropolitan areas since 2000 to help clarify the current role of infections in the context of Brazilian urban health...

Association of Taq I, Fok I and Apa I polymorphisms in Vitamin D Receptor (VDR) gene with leprosy.

BACKGROUND: Vitamin D Receptor (VDR) is a transacting transcription factor which mediates immunomodulatory function and plays a key role in innate and adaptive immune responses through its ligand and polymorphisms in VDR gene may affect its regulatory function. OBJECTIVE: To investigate the association of three VDR gene polymorphisms (TaqI rs731236, FokI rs2228570 and ApaI rs7975232) with leprosy. METHODS: The study group includes 404 participants of which 222 were leprosy patients (paucibacillary=87, multibacillary=135) and 182 healthy controls. Genotyping was done using PCR-RFLP technique. Statistical analysis was performed using SNP Stats and PLINK software. RESULTS: The VDR FokI (rs2228570) ff genotype, ApaI (rs7975232) AA, Aa genotype and haplotype T-f-a, T-F-A were positively associated with leprosy when compared to healthy controls. CONCLUSION: The two variants at Fok and Apa positions in VDR gene are significantly associated with leprosy. Genotypes at FokI (ff), ApaI (aa) and haplotype (T-F-a, T-f-a) may contribute to the risk of developing leprosy by altering VDR phenotype/levels subsequently modulation of immune response.

Tuberculosis risk-associated single nucleotide polymorphisms do not show association with leprosy in Chinese population.

OBJECTIVE: Leprosy and tuberculosis (TB) are chronic granulomatous infectious diseases. As well as pathogen and environmental factors, host genetic factors make a substantial contribution to susceptibility to both diseases. More importantly, leprosy and TB also have pathogenic mechanisms and clinical features in common. In this study, the genetic association between leprosy and TB was investigated in a Chinese Han population. METHODS: A genetic association study that included 46 TB susceptibility single nucleotide polymorphisms (SNPs) was performed, involving 1150 leprosy cases and 1150 controls from the Chinese Han population. The Sequenom MassARRAY system was used. RESULTS: No significant association was found between the 46 SNPs and leprosy. Therefore, according to the present study, there is no shared susceptibility locus between leprosy and TB in the Chinese Han population. CONCLUSIONS: Although leprosy and TB have a number of similar characteristics, no shared susceptibility loci were found in the Chinese Han population. Thus, this study demonstrated that the genetic basis of the pathogenesis of the two diseases may vary greatly.

Leprosy decline in Amazonas State, Brazil.

OBJECTIVE: To analyse the leprosy case detection rates in Amazonas State, Brazil, by age group from 1980 to 2009. METHOD: The historical data series of leprosy cases by age group from 1980 to 2009 were fitted as a function of time using Poisson regression models. Relative annual reduction in the detection rate (RAR) by age group was estimated as one minus the exponential of the estimated regression coefficient for time. To compare the regression coefficients, we used their 95% confidence interval. RESULTS: The relative annual reduction varied from 9% in the age group of 0-4 years to 1% in the age group of 60-69 years. There was a declining trend of the RAR in the younger age groups that disappeared after 29 years of age. The detection rate in people >29 years old declined very little over time, with no statistically significant difference between age groups. CONCLUSION: Our findings show a reduction in the infection risk in the last 30 years and a birth cohort effect: cohorts born in more recent years faced smaller risks of leprosy infection than older cohorts.