Mortality from Congenital Zika Syndrome - Nationwide Cohort Study in Brazil.

BACKGROUND: Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. METHODS: In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan-Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. RESULTS: A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. CONCLUSIONS: The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.).

Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study.

BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil.

An increase in microcephaly, associated with an epidemic of Zika virus (ZIKV) in Brazil, prompted the World Health Organization to declare a Public Health Emergency of International Concern in February 2016. While knowledge on biological and epidemiological aspects of ZIKV has advanced, demographic impacts remain poorly understood. This study uses time-series analysis to assess the impact of ZIKV on births. Data on births, fetal deaths, and hospitalizations due to abortion complications for Brazilian states, from 2010 to 2016, were used. Forecasts for September 2015 to December 2016 showed that 119,095 fewer births than expected were observed, particularly after April 2016 (a reduction significant at 0.05), demonstrating a link between publicity associated with the ZIKV epidemic and the decline in births. No significant changes were observed in fetal death rates. Although no significant increases in hospitalizations were forecasted, after the ZIKV outbreak hospitalizations happened earlier in the gestational period in most states. We argue that postponement of pregnancy and an increase in abortions may have contributed to the decline in births. Also, it is likely that an increase in safe abortions happened, albeit selective by socioeconomic status. Thus, the ZIKV epidemic resulted in a generation of congenital Zika syndrome (CZS) babies that reflect and exacerbate regional and social inequalities. Since ZIKV transmission has declined, it is unlikely that reductions in births will continue. However, the possibility of a new epidemic is real. There is a need to address gaps in reproductive health and rights, and to understand CZS risk to better inform conception decisions.

Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect.

The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries. In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor. Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes. The scaling up of breastfeeding to a near universal level could prevent 823,000 annual deaths in children younger than 5 years and 20,000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor.

Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation.

BACKGROUND: In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. METHODS: We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. FINDINGS: Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1·54 vs -3·13, difference 1·58 [95% CI 1·45-1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14-0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27-0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. INTERPRETATION: Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

The phenotypic spectrum of congenital Zika syndrome.

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

Coverage and equity in reproductive and maternal health interventions in Brazil: impressive progress following the implementation of the Unified Health System.

BACKGROUND: The Brazilian SUS (Unified Health System) was created in 1988 within the new constitution, based on the premises of being universal, comprehensive, and equitable. The SUS offers free health care, independent of contribution or affiliation. Since then, great efforts and increasing investments have been made for the system to achieve its goals. We assessed how coverage and equity in selected reproductive and maternal interventions progressed in Brazil from 1986 to 2013. METHODS: We reanalysed data from four national health surveys carried out in Brazil in 1986, 1996, 2006 and 2013. We estimated coverage for six interventions [use of modern contraceptives; antenatal care (ANC) 1+ visits by any provider; ANC 4+ visits by any provider; first ANC visit during the first trimester of pregnancy; institutional delivery; and Caesarean sections] using standard international definitions, and stratified results by wealth quintile, urban or rural residence and country regions. We also calculated two inequality indicators: the slope index of inequality (SII) and the concentration index (CIX). RESULTS: All indicators showed steady increases in coverage over time. ANC 1+ and 4+ and institutional delivery reached coverage above 90 % in 2013. Prevalence of use of modern contraceptives was 83 % in 2013, indicating nearly universal satisfaction of need for contraception. On a less positive note, the proportion of C-sections has also grown continuously, reaching 55 % in 2013. There were marked reductions in wealth inequalities for all preventive interventions. Inequalities were significantly reduced for all indicators except for the C-section rate (p = 0.06), particularly in absolute terms (SII). CONCLUSIONS: Despite the difficulties faced in the implementation of SUS, coverage of essential interventions increased and equity has improved dramatically, due in most cases to marked increase in coverage among the poorest 40 %. An increase in unnecessary Caesarean sections was also observed during the period. Further evaluation on the quality of healthcare provided is needed.

Progress in reducing inequalities in reproductive, maternal, newborn,' and child health in Latin America and the Caribbean: an unfinished agenda.

OBJECTIVE: To expand the "Countdown to 2015" analyses of health inequalities beyond the 75 countries being monitored worldwide to include all countries in Latin America and the Caribbean (LAC) that have adequate data available. METHODS: Demographic and Health Surveys and Multiple Indicator Cluster Surveys were used to monitor progress in health intervention coverage and inequalities in 13 LAC countries, five of which are included in the Countdown (Bolivia, Brazil, Guatemala, Haiti, and Peru) and eight that are not (Belize, Colombia, Costa Rica, Dominican Republic, Guyana, Honduras, Nicaragua, and Suriname). The outcomes included neonatal and under-5 year mortality rates, child stunting prevalence, and the composite coverage index-a weighted average of eight indicators of coverage in reproductive, maternal, newborn, and child health. The slope index of inequality and concentration index were used to assess absolute and relative inequalities. RESULTS: The composite coverage index showed monotonic patterns over wealth quintiles, with lowest levels in the poorest quintile. Under-5 and neonatal mortality as well as stunting prevalence were highest among the poor. In most countries, intervention coverage increased, while under-5 mortality and stunting prevalence fell most rapidly among the poor, so that inequalities were reduced over time. However, Bolivia, Guatemala, Haiti, Nicaragua, and Peru still show marked inequalities. Brazil has practically eliminated inequalities in stunting. CONCLUSIONS: LAC countries presented substantial progress in terms of reducing inequalities in reproductive, maternal, newborn, and child health interventions, child mortality, and nutrition. However, the poorest 20% of the population in most countries is still lagging behind, and renewed actions are needed to improve equity.

Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Equity in maternal, newborn, and child health interventions in Countdown to 2015: a retrospective review of survey data from 54 countries.

BACKGROUND: Countdown to 2015 tracks progress towards achievement of Millennium Development Goals (MDGs) 4 and 5, with particular emphasis on within-country inequalities. We assessed how inequalities in maternal, newborn, and child health interventions vary by intervention and country. METHODS: We reanalysed data for 12 maternal, newborn, and child health interventions from national surveys done in 54 Countdown countries between Jan 1, 2000, and Dec 31, 2008. We calculated coverage indicators for interventions according to standard definitions, and stratified them by wealth quintiles on the basis of asset indices. We assessed inequalities with two summary indices for absolute inequality and two for relative inequality. FINDINGS: Skilled birth attendant coverage was the least equitable intervention, according to all four summary indices, followed by four or more antenatal care visits. The most equitable intervention was early initation of breastfeeding. Chad, Nigeria, Somalia, Ethiopia, Laos, and Niger were the most inequitable countries for the interventions examined, followed by Madagascar, Pakistan, and India. The most equitable countries were Uzbekistan and Kyrgyzstan. Community-based interventions were more equally distributed than those delivered in health facilities. For all interventions, variability in coverage between countries was larger for the poorest than for the richest individuals. INTERPRETATION: We noted substantial variations in coverage levels between interventions and countries. The most inequitable interventions should receive attention to ensure that all social groups are reached. Interventions delivered in health facilities need specific strategies to enable the countries' poorest individuals to be reached. The most inequitable countries need additional efforts to reduce the gap between the poorest individuals and those who are more affluent. FUNDING: Bill & Melinda Gates Foundation, Norad, The World Bank.

How changes in coverage affect equity in maternal and child health interventions in 35 Countdown to 2015 countries: an analysis of national surveys.

BACKGROUND: Achievement of global health goals will require assessment of progress not only nationally but also for population subgroups. We aimed to assess how the magnitude of socioeconomic inequalities in health changes in relation to different rates of national progress in coverage of interventions for the health of mothers and children. METHODS: We assessed coverage in low-income and middle-income countries for which two Demographic Health Surveys or Multiple Indicator Cluster Surveys were available. We calculated changes in overall coverage of skilled birth attendants, measles vaccination, and a composite coverage index, and examined coverage of a newly introduced intervention, use of insecticide-treated bednets by children. We stratified coverage data according to asset-based wealth quintiles, and calculated relative and absolute indices of inequality. We adjusted correlation analyses for time between surveys and baseline coverage levels. FINDINGS: We included 35 countries with surveys done an average of 9·1 years apart. Pro-rich inequalities were very prevalent. We noted increased coverage of skilled birth attendants, measles vaccination, and the composite index in most countries from the first to the second survey, while inequalities were reduced. Rapid changes in overall coverage were associated with improved equity. These findings were not due to a capping effect associated with limited scope for improvement in rich households. For use of insecticide-treated bednets, coverage was high for the richest households, but countries making rapid progress did almost as well in reaching the poorest groups. National increases in coverage were primarily driven by how rapidly coverage increased in the poorest quintiles. INTERPRETATION: Equity should be accounted for when planning the scaling up of interventions and assessing national progress. FUNDING: Bill & Melinda Gates Foundation; World Bank; Governments of Australia, Brazil, Canada, Norway, Sweden, and UK.

Epidemiology, management, complications and costs associated with type 2 diabetes in Brazil: a comprehensive literature review.

BACKGROUND: With an estimated 74% of all deaths attributable to non-communicable diseases (NCDs) in 2010, NCDs have become a major health priority in Brazil. The objective of the study was to conduct a comprehensive literature review on diabetes in Brazil; specifically: the epidemiology of type 2 diabetes, the availability of national and regional sources of data (particularly in terms of direct and indirect costs) and health policies for the management of diabetes and its complications. METHODS: A literature search was conducted using PubMed to identify articles containing information on diabetes in Brazil. Official documents from the Brazilian government and the World Health Organization, as well as other grey literature and official government websites were also reviewed. RESULTS: From 2006 to 2010, an approximate 20% increase in the prevalence of self-reported diabetes was observed. In 2010, it was estimated that 6.3% of Brazilians aged 18 years or over had diabetes. Diabetes was estimated to be responsible for 278,778 years of potential life lost for every 100,000 people. In 2013, it is estimated that about 7% of patients with diabetes has had one or more of the following complications: diabetic foot ulcers, amputation, kidney disease, and fundus changes. The estimated annual direct cost of diabetes was USD $3.952 billion in 2000; the estimated annual indirect cost was USD $18.6 billion. The two main sources of data on diabetes are the information systems of the Ministry of Health and surveys. In the last few years, the Brazilian Ministry of Health has invested considerably in improving surveillance systems for NCDs as well as implementing specific programmes to improve diagnosis and access to treatment. CONCLUSIONS: Brazil has the capacity to address and respond to NCDs due to the leadership of the Ministry of Health in NCD prevention activities, including an integrated programme currently in place for diabetes. Strengthening the surveillance of NCDs is a national priority along with recognising the urgent need to invest in improving the coverage and quality of mortality data. It is also essential to conduct regular surveys of risk factors on a national scale in order to design effective preventive strategies.

Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil.

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Estimating the early impact of vaccination against COVID-19 on deaths among elderly people in Brazil: Analyses of routinely-collected data on vaccine coverage and mortality.

Background: Vaccination against COVID-19 in Brazil started in January 2021, with health workers and the elderly as the priority groups. We assessed whether there was an impact of vaccinations on the mortality of elderly individuals in a context of wide transmission of the SARS-CoV-2 gamma (P.1) variant. Methods: By May 15, 2021, 238,414 COVID-19 deaths had been reported to the Brazilian Mortality Information System. Denominators for mortality rates were calculated by correcting population estimates for all-cause deaths reported in 2020. Proportionate mortality at ages 70-79 and 80+ years relative to deaths at all ages were calculated for deaths due to COVID-19 and to other causes, as were COVID-19 mortality rate ratios relative to individuals aged 0-69 years. Vaccine coverage data were obtained from the Ministry of Health. All results were tabulated by epidemiological weeks 1-19, 2021. Findings: The proportion of all COVID-19 deaths at ages 80+ years was over 25% in weeks 1-6 and declined rapidly to 12.4% in week 19, whereas proportionate COVID-19 mortality for individuals aged 70-79 years started to decline by week 15. Trends in proportionate mortality due to other causes remained stable. Mortality rates were over 13 times higher in the 80+ years age group compared to that of 0-69 year olds up to week 6, and declined to 5.0 times in week 19. Vaccination coverage (first dose) of 90% was reached by week 9 for individuals aged 80+ years and by week 13 for those aged 70-79 years. Coronavac accounted for 65.4% and AstraZeneca for 29.8% of all doses administered in weeks 1-4, compared to 36.5% and 53.3% in weeks 15-19, respectively. Interpretation: Rapid scaling up of vaccination coverage among elderly Brazilians was associated with important declines in relative mortality compared to younger individuals, in a setting where the gamma variant predominates. Had mortality rates among the elderly remained proportionate to what was observed up to week 6, an estimated additional 43,802 COVID-related deaths would have been expected up to week 19. Funding: CGV and AJDB are funded by the Todos pela Saúde (São Paulo, Brazil) initiative.

Classification algorithm for congenital Zika Syndrome: characterizations, diagnosis and validation.

Zika virus was responsible for the microcephaly epidemic in Brazil which began in October 2015 and brought great challenges to the scientific community and health professionals in terms of diagnosis and classification. Due to the difficulties in correctly identifying Zika cases, it is necessary to develop an automatic procedure to classify the probability of a CZS case from the clinical data. This work presents a machine learning algorithm capable of achieving this from structured and unstructured available data. The proposed algorithm reached 83% accuracy with textual information in medical records and image reports and 76% accuracy in classifying data without textual information. Therefore, the proposed algorithm has the potential to classify CZS cases in order to clarify the real effects of this epidemic, as well as to contribute to health surveillance in monitoring possible future epidemics.

Measles-containing vaccines in Brazil: Coverage, homogeneity of coverage and associations with contextual factors at municipal level.

We aimed to (i) describe both the coverage and the homogeneity of coverage of the first and second doses of measles-containing vaccines (MCV) in Brazil in 2017, and (ii) to investigate the potential influence of contextual factors at municipal level. All 5570 Brazilian municipalities were included. The North and Center-West regions presented the lowest coverages of the first and second doses of MCV, respectively. We found significant associations of both first and second doses of MCV with population size, coverage of Family Health Strategy (FHS) and other indicators of living conditions and inequalities. Monitoring the homogeneity of MCV coverage at national, regional and state levels is essential, as it allows identifying areas at higher risk of measles spread that should be targeted for vaccination. Targeting large cities i.e. 100,000 or more inhabitants, especially poor neighborhoods and areas with low FHS coverage, could lead to improvements in coverage homogeneity.

Case Fatality Rate Related to Microcephaly Congenital Zika Syndrome and Associated Factors: A Nationwide Retrospective Study in Brazil †.

BACKGROUND: The clinical manifestations of microcephaly/congenital Zika syndrome (microcephaly/CZS) have harmful consequences on the child's health, increasing vulnerability to childhood morbidity and mortality. This study analyzes the case fatality rate and child-maternal characteristics of cases and deaths related to microcephaly/CZS in Brazil, 2015-2017. METHODS: Population-based study developed by linkage of three information systems. We estimate frequencies of cases, deaths, case fatality rate related to microcephaly/CZS according to child and maternal characteristics and causes of death. Multivariate logistic regression models were applied. RESULTS: The microcephaly/CZS case fatality rate was 10% (95% CI 9.2-10.7). Death related to microcephaly/CZS was associated to moderate (OR = 2.15; 95% CI 1.63-2.83), and very low birth weight (OR = 3.77; 95% CI 2.20-6.46); late preterm births (OR = 1.65; 95% CI 1.21-2.23), Apgar < 7 at 1st (OR = 5.98; 95% CI 4.46-8.02) and 5th minutes (OR = 4.13; 95% CI 2.78-6.13), among others. CONCLUSIONS: A high microcephaly/CZS case fatality rate and important factors associated with deaths related to this syndrome were observed. These results can alert health teams to these problems and increase awareness about the factors that may be associated with worse outcomes.

Trends and spatial distribution of MMR vaccine coverage in Brazil during 2007-2017.

We analyzed the time trends and spatial distribution of MMR vaccine coverage in Brazil during 2007-2017. In early 2018, a measles outbreak started in the North region of Brazil, reaching 11 of the 27 federal units by January 24, 2019. In this period, 10,302 cases were confirmed. Although the reintroduction of measles in Brazil is likely due to migration from Venezuela, the spread of the virus was made possible by the low levels of MMR coverage, as a result of significant decreases during the study period. Areas with high concentration of municipalities with low coverage are more susceptible to the spread of the virus, especially in the North and Northeast regions. Increasing vaccination coverage is essential to block the ongoing outbreak in Brazil. Vaccination strategies might target priority areas, especially those with a marked decrease in coverage. Moreover, it is essential to extend actions to travelers, migrants and refugees.

Breastfeeding moderates FTO related adiposity: a birth cohort study with 30 years of follow-up.

This study assessed the association of breastfeeding with body composition at 30 years, among subjects who have been prospectively followed since birth in a southern Brazilian city. We also evaluated whether breastfeeding moderated the association between the rs9939609 variant in the FTO gene and adiposity. At 30 years, total and predominant breastfeeding were positively associated with lean mass index and inversely with visceral fat thickness. Among subjects breastfed for <1 month, all outcomes showed monotonically increasing values with additional copies of the A allele in the FTO genotype (rs9939609). Associations among subjects breastfed for one month or longer tended to be in the same direction but showed lower magnitude and were less consistent; for all outcomes. Interactions had p values ≤ 0.05 for body mass index, fat mass index and waist circumference. Even among young adults, breastfeeding moderates the association between the FTO variant rs9939609 and body composition.