Maternal and child nutrition programme of investigation within the 100 Million Brazilian Cohort: study protocol.

INTRODUCTION: There is a limited understanding of the early nutrition and pregnancy determinants of short-term and long-term maternal and child health in ethnically diverse and socioeconomically vulnerable populations within low-income and middle-income countries. This investigation programme aims to: (1) describe maternal weight trajectories throughout the life course; (2) describe child weight, height and body mass index (BMI) trajectories; (3) create and validate models to predict childhood obesity at 5 years of age; (4) estimate the effects of prepregnancy BMI, gestational weight gain (GWG) and maternal weight trajectories on adverse maternal and neonatal outcomes and child growth trajectories; (5) estimate the effects of prepregnancy BMI, GWG, maternal weight and interpregnancy BMI changes on maternal and child outcomes in the subsequent pregnancy; and (6) estimate the effects of maternal food consumption and infant feeding practices on child nutritional status and growth trajectories. METHODS AND ANALYSIS: Linked data from four different Brazilian databases will be used: the 100 Million Brazilian Cohort, the Live Births Information System, the Mortality Information System and the Food and Nutrition Surveillance System. To analyse trajectories, latent-growth, superimposition by translation and rotation and broken stick models will be used. To create prediction models for childhood obesity, machine learning techniques will be applied. For the association between the selected exposure and outcomes variables, generalised linear models will be considered. Directed acyclic graphs will be constructed to identify potential confounders for each analysis investigating potential causal relationships. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committees of the authors' institutions. The linkage will be carried out in a secure environment. After the linkage, the data will be de-identified, and pre-authorised researchers will access the data set via a virtual private network connection. Results will be reported in open-access journals and disseminated to policymakers and the broader public.

The impact of implementing the 10-valent pneumococcal conjugate vaccine on hospitalizations for pneumonia among children.

Pneumonia is a major cause of morbidity and mortality in children, with pneumococcus as the main etiologic agent. In Brazil, the 10-valent pneumococcal conjugate vaccine (PCV-10) was introduced into the childhood immunization schedule in 2010. The aim of this study was to assess the impact caused by implementing PCV-10 on the hospitalizations of children with pneumonia, between 2005 and 2015, in the state of Pernambuco, Brazil. An ecological time series study and a forecasting analysis were conducted. A comparison was made between the hospitalizations of children aged between seven months and four years due to pneumonia in the Brazilian Unified Health System, in the 5 years before (2005-2009) and after (2011-2015) implementation of PCV-10. Descriptive analysis included absolute and relative values, means and rates of hospitalization. The chi-square test was used to compare the annual incidence of hospitalizations and the t-Student test to compare the five-year mean values. For the temporal modeling of hospitalizations, an autoregressive integrated moving average was used, adjusted with seasonal-SARIMA (Box-Jenkins methodology), with a prediction of the monthly number of hospitalizations for 2011-2015. The predicted and observed values for 2011-2015 were then compared. The number of hospitalizations after implementing PCV-10 was reduced by 24.5 %. The monthly average of hospitalizations dropped from 681 (2005-2009) to 514 (2011-2015). The hospitalization rate dropped from 56.1 per thousand live births in the five-year period prior to PCV-10 to 43.4 in the following five-year period (a 22.7% reduction). Comparing the values predicted by the SARIMA model for a scenario without PCV-10 in the second five-year period, with those reported after implementing PCV-10, the estimated number of prevented hospitalizations was 8,682 in the five years following the introduction of the vaccine. In conclusion, in the five years following implementation of PCV-10, hospitalizations of children with pneumonia in Pernambuco decrease by 22%.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

A social network approach for the study of leprosy transmission beyond the household.

BACKGROUND: Mycobacterium leprae was the first microorganism directly associated with a disease, however, there are still important gaps in our understanding of transmission. Although household contacts are prioritized, there is evidence of the importance of extrahousehold contacts. The goal of this article is to contribute to our understanding of the transmission of leprosy ex-household. METHODS: We compare co-location data of 397 leprosy cases and 211 controls drawn from the Centro de Dermatologia Sanitária D. Libânia in Fortaleza, Brazil. We collected lifetime geolocation data related to residence, school attendance and workplace and developed novel methods to establish a critical distance (Rc) for exposure and evaluated the potential for transmission for residence, school and workplace. RESULTS: Our methods provide different threshold values of distance for residence, school and workplace. Residence networks demonstrate an Rc of about 500 m. Cases cluster in workplaces as well. Schools do not cluster cases. CONCLUSIONS: Our novel network approach offers a promising opportunity to explore leprosy transmission. Our networks confirm the importance of coresidence, provide a boundary and suggest a role for transmission in workplaces. Schools, on the other hand, do not demonstrate a clustering of cases. Our findings may have programmatic relevance.

A new insight into the definition of microcephaly in Zika congenital syndrome era.

This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.

Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

Epidemiological characteristics and temporal trends of new leprosy cases in Brazil: 2006 to 2017.

Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Physical disabilities caused by leprosy in 100 million cohort in Brazil.

BACKGROUND: Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population. METHODS: A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001-2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervals. RESULTS: Among the original cohort members 21,565 new leprosy cases were identified between 2007 and 2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21 and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2.39 and 1.95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3.5 and 8.22). Protective factors for both grades were being female (ORs 0.81 and 0.61) and living in a high incidence municipality (ORs 0.85 and 0.67). CONCLUSIONS: The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.

Comparison of Oropharyngeal Dysphagia in Brazilian Children with Prenatal Exposure to Zika Virus, With and Without Microcephaly.

Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were: to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015-2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used: a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.

A new insight into the definition of microcephaly in Zika congenital syndrome era / Uma nova visão da definição de microcefalia na era da síndrome congênita do vírus Zika / Una nueva perspectiva en la definición de microcefalia durante la era del síndrome congénito Zika

Abstract: This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.

Resumo: O estudo buscou comparar as medidas antropométricas e proporções corporais de recém-nascidos do período pré-Zika com os nascidos durante a epidemia de microcefalia congênita pelo vírus Zika. Comparamos 958 recém-nascidos do período pré-Zika com 264 nascidos durante o período epidêmico. Foram classificados o perímetro cefálico, peso e comprimento dos neonatos de acordo com a escala de crescimento de Fenton & Kim. Consideramos desproporcionais aqueles neonatos que apresentaram microcefalia e peso ou comprimento adequado para sexo e idade gestacional, além daqueles cujo perímetros cefálicos eram menores que a razão ((comprimento / 2) + 9,5) -2,5cm. Estimamos as frequências de positividade para Zika e resultados de imagens de cerebrais entre bebês com microcefalia nascidos no período epidêmico, em relação aos parâmetros antropométricos e de proporcionalidade corporal. Baixo peso e microcefalia proporcional foram semelhantes entre recém-nascidos de ambos os períodos. Entretanto, as frequências de neonatos com microcefalia e com comprimento muito curto e microcefalia desproporcional foram muito maiores entre os nascidos no período epidêmico com anomalias cerebrais e positivos para Zika. Concluímos que a desproporção entre perímetro cefálico e comprimento ao nascer pode ser um indicador da gravidade da microcefalia causada pela síndrome congênita do Zika vírus.

Resumen: El objetivo del estudio fue comparar las medidas antropométricas y de proporcionalidad corporal en neonatos nacidos durante un período pre-Zika, con quienes nacieron durante la epidemia de microcefalia por el síndrome congénito Zika. Comparamos a 958 neonatos nacidos durante la epidemia pre-Zika, con 264 neonatos nacidos durante el período epidémico. A los recién nacidos se les clasificó su circunferencia de la cabeza, peso y longitud según la tabla de crecimiento Fenton & Kim. Consideramos desproporcionados a quienes presentaron microcefalia y peso o longitud adecuada para sexo y edad gestacional, y quienes tenían unas circunferencias de cabeza cuyo ratio era menor que ((longitud / 2) + 9.5) - 2.5cm. Estimamos las frecuencias de positividad para Zika, así como los resultados de imágenes cerebrales entre neonatos nacidos con microcefalia durante el período epidémico, en relación con parámetros antropométricos y de proporcionalidad corporal. Bajo peso y microcefalia proporcional fueron similares entre los recién nacidos de ambos períodos. No obstante, las frecuencias de recién nacidos con microcefalia con una longitud muy baja y microcefalia desproporcionada fueron mayores entre los neonatos del período epidémico, con anormalidades cerebrales y positivos para Zika. Concluimos que la desproporción entre la circunferencia de cabeza y longitud al nacer puede ser un indicador de la gravedad de la microcefalia, causada por el Zika congénito.

Epidemiological characteristics and temporal trends of new leprosy cases in Brazil: 2006 to 2017 / Características epidemiológicas e tendências temporais de casos novos de hanseníase no Brasil: 2006 a 2017 / Características epidemiológicas y tendencias temporales de nuevos casos de lepra en Brasil: de 2006 a 2017

Abstract: Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.

Resumo: O estudo teve com objetivos descrever as tendências na taxa de detecção de casos novos (TDCN) de hanseníase no Brasil em 2006-2017, global e por subgrupos, e analisar a evolução das características clínicas e terapêuticas dos pacientes, com ênfase nos casos diagnosticados com incapacidade física grau 2. Realizamos um estudo descritivo par analisar casos novos de hanseníase registrados no Sistema de Informação de Agravos de Notificação (SINAN), 2006-2017. Calculamos a TDCN de hanseníase por 100.000 habitantes (global e para indivíduos < 15 e ≥ 15 anos de idade) por sexo, idade, raça/etnicidade, área urbana/rural e macrorregião do Brasil e estimamos as tendências com o teste não paramétrico de Mann-Kendall. Analisamos as distribuições de casos de acordo com características clínicas relevantes ao longo do tempo. No Brasil, houve uma queda marcante na TDCN global, de 23,4/100.000 em 2006 para 10,3/100.000 em 2017; entre crianças < 15 anos, de 6,94 para 3,20/100.000. A queda foi consistente em todas a regiões brasileiras e em todas as categorias de raça/etnicidade. Até 2017, 70,2% dos casos eram multibacilares, 30,5% apresentavam incapacidades físicas grau 1 (G1D) ou grau 2 (G2D) ao diagnóstico e 42,8% não foram avaliados ao encerramento do tratamento ou alta; os casos com G2D ao diagnóstico foram detectados majoritariamente nas áreas urbanas (80%), e 5% dos casos faleceram durante o tratamento (devido à hanseníase ou por outras causas). Embora a frequência da TDCN da hanseníase tenha diminuído no Brasil entre 2006 e 2017 em todos os grupos avaliados, o número grande de casos com hanseníase multibacilar, incapacidades físicas ou sem avaliação adequada e entre crianças sugere a necessidade de reforçar o diagnóstico e tratamento oportunos para controlar a hanseníase no Brasil.

Resumen: Se realizó este trabajo con el fin de describir la tendencia general y en subgrupos de la tasa de detección de nuevos casos de lepra (NCDR por sus siglas en inglés) en Brasil, entre 2006-2017, así como para analizar la evolución de las características clínicas y de tratamiento de los pacientes, con énfasis en los casos diagnosticados con un grado 2 de discapacidad física. Realizamos un estudio descriptivo para analizar los nuevos casos de lepra registrados en el Sistema Brasileño de Información de Enfermedades de Notificación (SINAN), 2006-2017. Calculamos la NCDR de lepra por cada 100.000 habitantes (general e individuos con una edad < 15 y ≥ 15 años) por sexo, edad, raza/etnicidad, áreas urbanas/rurales y regiones brasileñas, y estimamos las tendencias usando el test no paramétrico de Mann-Kendall. Analizamos las distribuciones de casos según las características clínicas relevantes a lo largo del tiempo. En Brasil, hubo una drástica disminución en general de NCDR de los 23,4/100.000 en 2006, a los 10,3/100.000 en 2017; entre niños < 15 años, desde los 6,94 a los 3,20/100.000. El decremento fue consistente en todas las regiones brasileñas y categorías de raza/etnicidad. En 2017, un 70,2% de los casos fueron multibacilares, un 30,5% tenían grado 1 (G1D) o 2 (G2D) discapacidad física en el diagnóstico y un 42,8% no fueron evaluados al completar el tratamiento/ser dados de alta; casos con G2D en el diagnóstico fueron en su mayoría detectados en áreas urbanas (80%) y un 5% de los casos murieron durante el tratamiento (lepra u otras causas). A pesar de la frecuencia de lepra los NCDR decrecieron en Brasil de 2006 a 2017, a través de todos los grupos de población evaluados, el elevado número de casos con lepra multibacilar, discapacidad física o sin una adecuada evaluación, y entre niños sugiere la necesidad de reforzar a tiempo el diagnóstico y tratamiento para controlar la lepra en Brasil.

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

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

Genetic variants in 17q12-21 locus and childhood asthma in Brazil: Interaction with Varicella zoster virus seropositivity.

BACKGROUND: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. OBJECTIVE: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. METHODS: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). RESULTS: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. CONCLUSIONS: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.

[Assessment of vaccination coverage of children in a medium-sized Brazilian city using electronic immunization registry]. / Avaliação de coberturas vacinais de crianças em uma cidade de médio porte (Brasil) utilizando registro informatizado de imunização.

Administrative data show high vaccination coverage rates in Brazil, but there is no assessment of the validity and timeliness of dose administration, or whether the vaccination schedule is complete. This study assessed timely and updated coverage rates in children 12 to 24 months of age. This was a longitudinal population-based study in Araraquara, São Paulo State, a predominantly urban medium-sized municipality, using the Juarez System, an electronic immunization registry (EIR). Coverage rates were assessed in 49,741 children born from 1998 to 2013, a period in which five different vaccination schedules were used. Trends were estimated with the Prais-Winsten linear regression method. Updated coverage of the complete schedule varied from 79.5% to 91.3% at 12 months and from 75.8% to 86.9%, at 24 months. Timely coverage (all doses applied at the recommended ages, with no delays) ranged from 53.3% to 74% at 12 months and from 36.7% to 53.8% at 24 months. There was an upward trend in updated coverage at 24 months. The delays in relation to recommended age increased starting at six months and appeared to relate more to age than to the number of doses in the schedule. The proportion of invalid and late doses was lower than in other studies. Despite the increase in the number of doses in the vaccination schedule, the study showed high updated coverage rates and higher timely coverage than reported in the national and international literature; however, more effort is needed to increase timeliness. EIR proved relevant for assessing and monitoring vaccination coverage with more accurate analyses.

Dados administrativos mostram altas coberturas vacinais no Brasil, porém não há avaliação da validade e oportunidade de aplicação das doses, nem se o esquema vacinal está completo. Este estudo avaliou as coberturas oportunas e atualizadas de crianças de 12 a 24 meses de idade. Estudo longitudinal de base populacional em Araraquara, São Paulo, uma cidade de médio porte predominantemente urbana, utilizando dados do Sistema Juarez, um registro informatizado de imunização (RII). As coberturas foram avaliadas para 49.741 crianças nascidas entre 1998 e 2013, período com cinco calendários de vacinação diferentes. As tendências foram estimadas pelo método de regressão linear Prais-Winsten. A cobertura atualizada do esquema completo variou entre 79,5% e 91,3%, aos 12 meses, e entre 75,8% e 86,9%, aos 24 meses. A cobertura oportuna (todas as doses aplicadas na idade recomendada, sem atraso) variou entre 53,3% e 74%, aos 12 meses, e entre 36,7% e 53,8%, aos 24 meses. Houve tendência crescente para a cobertura atualizada aos 24 meses. Os atrasos em relação à idade recomendada se acentuam em doses a partir dos seis meses e parecem estar mais relacionados à idade do que ao número de doses do esquema. A proporção de doses inválidas e atrasadas foi menor do que em outros estudos. Apesar do aumento do número de doses no calendário vacinal, foram alcançadas altas coberturas atualizadas e coberturas oportunas maiores do que as encontradas na literatura nacional e internacional, porém são necessários mais esforços para o aumento da oportunidade. O RII mostrou-se relevante para avaliação e monitoramento de coberturas vacinais, com análises mais acuradas.

Los datos administrativos muestran altas coberturas de vacunación en Brasil, sin embargo, no existe una evaluación de la validez y oportunidad de aplicación de las dosis, ni si la cartilla de vacunación ha sido completada. Este estudio evalúo las coberturas necesarias y actualizadas en niños de 12 a 24 meses de edad. Se trata de un estudio longitudinal con base poblacional en Araraquara, São Paulo, una ciudad media, predominantemente urbana, utilizando datos del Sistema Juarez, un registro informatizado de inmunización (RII). Las coberturas se evaluaron en 49.741 niños, nacidos entre 1998 y 2013, durante un período con cinco calendarios de vacunación diferentes. Las tendencias se estimaron mediante el método de regresión lineal Prais-Winsten. La cobertura actualizada del esquema completo varió entre 79,5% y 91,3%, a los 12 meses, y entre 75,8% y 86,9%, a los 24 meses. La cobertura necesaria (todas las dosis aplicadas a la edad recomendada, sin atrasos) varió entre 53,3% y 74%, a los 12 meses, y entre 36,7% y 53,8% a los 24 meses. Hubo una tendencia creciente en la cobertura actualizada a los 24 meses. Los atrasos, en relación con la edad recomendada, se acentúan en dosis a partir de los seis meses y parecen estar más relacionados con la edad que con el número de dosis del esquema. La proporción de dosis inválidas y atrasadas fue menor que en otros estudios. A pesar del aumento del número de dosis en el calendario de vacunas, se alcanzaron altas coberturas actualizadas y coberturas oportunas mayores que las encontradas en la literatura nacional e internacional, sin embargo, se necesitan más esfuerzos para el aumento de la oportunidad. El RII se mostró relevante en la evaluación y supervisión de coberturas de vacunación con análisis más exactos.

Who are the patients with tuberculosis who are diagnosed in emergency facilities? An analysis of treatment outcomes in the state of São Paulo, Brazil.

OBJECTIVE: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. METHODS: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. RESULTS: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. CONCLUSIONS: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement.

Who are the patients with tuberculosis who are diagnosed in emergency facilities? An analysis of treatment outcomes in the state of São Paulo, Brazil / Quem são os pacientes com tuberculose diagnosticados no pronto-socorro? Uma análise dos desfechos do tratamento no Estado de São Paulo, Brasil

ABSTRACT Objective: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. Methods: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. Results: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. Conclusions: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement.

RESUMO Objetivo: O diagnóstico e tratamento precoce da tuberculose são determinantes de melhores desfechos e controle eficaz da doença. Embora a tuberculose deva ser diagnosticada e tratada idealmente na atenção primária à saúde, uma porcentagem dos pacientes recebe o diagnóstico no pronto-socorro. Nosso objetivo foi descrever as características dos pacientes de acordo com o local onde o diagnóstico de tuberculose foi feito e determinar se há relação entre o local do diagnóstico e os desfechos do tratamento. Um objetivo secundário foi determinar se há relação entre indicadores municipais e a probabilidade de diagnóstico de tuberculose no PS. Métodos: Analisamos dados provenientes do banco de dados do Programa de Controle da Tuberculose do Estado de São Paulo, referentes ao período de janeiro de 2010 a dezembro de 2013. Foram incluídos no estudo pacientes recém-diagnosticados com mais de 15 anos de idade e tuberculose pulmonar, extrapulmonar ou disseminada. Modelos de regressão logística múltipla ajustados para levar em conta possíveis fatores de confusão foram usados para avaliar a relação entre o local do diagnóstico e os desfechos do tratamento. Resultados: De um total de 50.295 pacientes, 12.696 (25%) foram diagnosticados no PS. Em comparação com os pacientes que foram diagnosticados no ambulatório, os pacientes diagnosticados no PS eram mais jovens e mais vulneráveis socialmente. A probabilidade de tratamento com desfechos ruins, incluindo perda de seguimento e óbito, foi maior nos pacientes diagnosticados no PS (OR ajustada: 1,54; IC95%: 1,42-1,66). Nos municípios, a probabilidade de diagnóstico de tuberculose no PS relacionou-se com baixa cobertura da atenção primária, desigualdade e vulnerabilidade social. Em alguns municípios, mais de 50% dos casos de tuberculose foram diagnosticados no PS. Conclusões: No Estado de São Paulo, um em cada quatro pacientes com tuberculose é diagnosticado no PS; o diagnóstico de tuberculose no PS está relacionado com tratamento com desfechos ruins. Nos municípios, o diagnóstico de tuberculose no PS está relacionado com indicadores estruturais e socioeconômicos e indica pontos que precisam melhorar.

Use of electronic immunization registry in the surveillance of adverse events following immunization.

OBJECTIVE: To describe adverse events following vaccination (AEFV) of children under two years old and analyze trend of this events from 2000 to 2013, in the city of Araraquara (SP), Brazil. METHODS: This is a descriptive study conducted with data of the passive surveillance system of AEFV that is available in the electronic immunization registry (EIR) of the computerized medical record of the municipal health service (Juarez System). The study variables were: age, gender, vaccine, dose, clinical manifestations and hospitalization. We estimated rates using AEFV as numerator and administered doses of vaccines as denominator. The surveillance sensitivity was estimated by applying the method proposed by the Centers for Disease Control and Prevention. We used Prais-Winsten regression with a significance level of 5.0%. RESULTS: The average annual rate of AEFV was 11.3/10,000 administered doses, however without a trend in the study period (p=0.491). Most cases occurred after the first dose (41.7%) and among children under one year of age (72.6%). Vaccines with pertussis component, yellow fever and measles-mumps-rubella were the most reactogenic. We highlighted the rates of hypotonic-hyporesponsive episodes and convulsion that were 4.1/10,000 and 1.5/10,000 doses of vaccines with pertussis component, respectively, most frequently in the first dose; 60,0% of cases presented symptoms in the first 24 hours after vaccination, however, 18.6% showed after 96 hours. The sensitivity of surveillance was 71.9% and 78.9% for hypotonic-hyporesponsive episodes and convulsion, respectively. CONCLUSIONS: The EIR-based AEFV surveillance system proved to be useful and highly sensitive to describe the safety profile of vaccines in a medium-sized city. It was also shown that the significant increase of the vaccines included in the basic vaccination schedule in childhood in the last decade did not alter the high safety standard of the National Immunization Program.