Maternal and congenital syphilis attributable to ethnoracial inequalities: a national record-linkage longitudinal study of 15 million births in Brazil.

BACKGROUND: This study estimated ethnoracial inequalities in maternal and congenital syphilis in Brazil, understanding race as a relational category product of a sociopolitical construct that functions as an essential tool of racism and its manifestations. METHODS: We linked routinely collected data from Jan 1, 2012 to Dec 31, 2017 to conduct a population-based study in Brazil. We estimated the attributable fraction of race (skin colour) for the entire population and specific subgroups compared with White women using adjusted logistic regression. We also obtained the attributable fraction of the intersection between two social markers (race and education) and compared it with White women with more than 12 years of education as the baseline. FINDINGS: Of 15 810 488 birth records, 144 564 women had maternal syphilis and 79 580 had congenital syphilis. If all women had the same baseline risk as White women, 35% (95% CI 34·89-36·10) of all maternal syphilis and 41% (40·49-42·09) of all congenital syphilis would have been prevented. Compared with other ethnoracial categories, these percentages were higher among Parda/Brown women (46% [45·74-47·20] of maternal syphilis and 52% [51·09-52·93] of congenital syphilis would have been prevented) and Black women (61% [60·25-61·75] of maternal syphilis and 67% [65·87-67·60] of congenital syphilis would have been prevented). If all ethnoracial groups had the same risk as White women with more than 12 years of education, 87% of all maternal syphilis and 89% of all congenital syphilis would have been prevented. INTERPRETATION: Only through effective control of maternal syphilis among populations at higher risk (eg, Black and Parda/Brown women with lower educational levels) can WHO's global health initiative to eliminate mother-to-child transmission of syphilis be made feasible. Recognising that racism and other intersecting forms of oppression affect the lives of minoritised groups and advocating for actions through the lens of intersectionality is imperative for attaining and guaranteeing health equity. Achieving health equality needs to be addressed to achieve syphilis control. Given the scale and complexity of the problem (which is unlikely to be unique to Brazil), structural issues and social markers of oppression, such as race and education, must be considered to prevent maternal and congenital syphilis and improve maternal and child outcomes globally. FUNDING: Wellcome Trust, CNPq-Brazil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Mortality among over 6 million internal and international migrants in Brazil: a study using the 100 Million Brazilian Cohort.

Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98-0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03-1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09-1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80-0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40-0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17-4.05). Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. Funding: The Wellcome Trust.

Ethnoracial inequalities and child mortality in Brazil: a nationwide longitudinal study of 19 million newborn babies.

BACKGROUND: Racism is a social determinant of health inequities. In Brazil, racial injustices lead to poor outcomes in maternal and child health for Black and Indigenous populations, including greater risks of pregnancy-related complications; decreased access to antenatal, delivery, and postnatal care; and higher childhood mortality rates. In this study, we aimed to estimate inequalities in childhood mortality rates by maternal race and skin colour in a cohort of more than 19 million newborns in Brazil. METHODS: We did a nationwide population-based, retrospective cohort study using linked data on all births and deaths in Brazil between Jan 1, 2012, and Dec 31, 2018. The data consisted of livebirths followed up to age 5 years, death, or Dec 31, 2018. Data for livebirths were extracted from the National Information System for livebirths, SINASC, and for deaths from the Mortality Information System, SIM. The final sample consisted of complete data for all cases regarding maternal race and skin colour, and no inconsistencies were present between date of birth and death after linkage. We fitted Cox proportional hazard regression models to calculate the crude and adjusted hazard ratios (HRs) and 95% CIs for the association between maternal race and skin colour and all-cause and cause-specific younger than age 5 mortality rates, by age subgroups. We calculated the trend of HRs (and 95% CI) by time of observation (calendar year) to indicate trends in inequalities. FINDINGS: From the 20 526 714 livebirths registered in SINASC between Jan 1, 2012, and Dec 31, 2018, 238 436 were linked to death records identified from SIM. After linkage, 1 010 871 records were excluded due to missing data on maternal race or skin colour or inconsistent date of death. 19 515 843 livebirths were classified by mother's race, of which 224 213 died. Compared with children of White mothers, mortality risk for children younger than age 5 years was higher among children of Indigenous (HR 1·98 [95% CI 1·92-2·06]), Black (HR 1·39 [1·36-1·41]), and Brown or Mixed race (HR 1·19 [1·18-1·20]) mothers. The highest hazard ratios were observed during the post-neonatal period (Indigenous, HR 2·78 [95% CI 2·64-2·95], Black, HR 1·54 [1·48-1·59]), and Brown or Mixed race, HR 1·25 [1·23-1·27]) and between the ages of 1 year and 4 years (Indigenous, HR 3·82 [95% CI 3·52-4·15]), Black, HR 1·51 [1·42-1·60], and Brown or Mixed race, HR 1·30 [1·26-1·35]). Children of Indigenous (HR 16·39 [95% CI 12·88-20·85]), Black (HR 2·34 [1·78-3·06]), and Brown or Mixed race mothers (HR 2·05 [1·71-2·45]) had a higher risk of death from malnutrition than did children of White mothers. Similar patterns were observed for death from diarrhoea (Indigenous, HR 14·28 [95% CI 12·25-16·65]; Black, HR 1·72 [1·44-2·05]; and Brown or Mixed race mothers, HR 1·78 [1·61-1·98]) and influenza and pneumonia (Indigenous, HR 6·49 [95% CI 5·78-7·27]; Black, HR 1·78 [1·62-1·96]; and Brown or Mixed race mothers, HR 1·60 [1·51-1·69]). INTERPRETATION: Substantial ethnoracial inequalities were observed in child mortality in Brazil, especially among the Indigenous and Black populations. These findings demonstrate the importance of regular racial inequality assessments and monitoring. We suggest implementing policies to promote ethnoracial equity to reduce the impact of racism on child health. FUNDING: MCTI/CNPq/MS/SCTIE/Decit/Bill & Melinda Gates Foundation's Grandes Desafios Brasil, Desenvolvimento Saudável para Todas as Crianças, and Wellcome Trust core support grant awarded to CIDACS-Center for Data and Knowledge Integration for Health.

Conditional cash transfer program and child mortality: A cross-sectional analysis nested within the 100 Million Brazilian Cohort.

BACKGROUND: Brazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1-4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management. METHODS AND FINDINGS: This is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil's Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses. CONCLUSIONS: In this study, we observed a significant association between BFP participation and child mortality in children aged 1-4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP.

Small-area level socio-economic deprivation and tuberculosis rates in England: An ecological analysis of tuberculosis notifications between 2008 and 2012.

BACKGROUND: Tuberculosis (TB) rates in England are among the highest in high-income countries. Poverty and historic and current immigration from high TB incidence parts of the world are two major drivers of tuberculosis in England. However, little has been done in recent years to examine socio-economic trends in TB rates in England, and to disentangle the role of deprivation from that of place of birth in the current TB epidemiology. OBJECTIVES: To assess the association between England's 2008-2012 TB notification rates and small area-level deprivation, together and separately in the UK-born and foreign-born populations. METHODS: Ecological analysis of the association between quintiles of England's 2010 Index of Multiple Deprivation (IMD) and TB rates at the Lower-layer Super Output Area (LSOA; average population ~1500) level, using negative binomial and zero-inflated negative binomial regression models, adjusting for age, sex, urban/rural area classification, and area-level percentage of non-White residents. RESULTS: There was a log-linear gradient between area-deprivation levels and TB rates, with overall TB rates in the most deprived quintile areas three times higher than the least deprived quintile after adjustment for age and sex (IRR = 3.35; 95%CI: 3.16 to 3.55). The association and gradient were stronger in the UK-born than the foreign-born population, with UK-born TB rates in the most deprived quintiles about two-and-a-half times higher than the least deprived quintile (IRR = 2.39; 95%CI: 2.19 to 2.61) after controlling for age, sex, urban/rural classification and percentage of non-White residents; whereas the comparable figure for foreign-born persons was 80% higher (IRR = 1.78; 95%CI: 1.66 to 1.91). CONCLUSIONS: Socio-economic deprivation continues to play a substantial role in sustaining the TB epidemic in England, especially in the UK-born population. This supports the case for further investigations of the underlying social- determinants of TB.

Correction: Geographic and socioeconomic factors associated with leprosy treatment default: An analysis from the 100 Million Brazilian Cohort.

[This corrects the article DOI: 10.1371/journal.pntd.0007714.].

Conditional Cash Transfer Program and Leprosy Incidence: Analysis of 12.9 Million Families From the 100 Million Brazilian Cohort.

Leprosy is a neglected tropical disease predominately affecting poor and marginalized populations. To test the hypothesis that poverty-alleviating policies might be associated with reduced leprosy incidence, we evaluated the association between the Brazilian Bolsa Familia (BFP) conditional cash transfer program and new leprosy case detection using linked records from 12,949,730 families in the 100 Million Brazilian Cohort (2007-2014). After propensity score matching BFP beneficiary to nonbeneficiary families, we used Mantel-Haenszel tests and Poisson regressions to estimate incidence rate ratios for new leprosy case detection and secondary endpoints related to operational classification and leprosy-associated disabilities at diagnosis. Overall, cumulative leprosy incidence was 17.4/100,000 person-years at risk (95% CI: 17.1, 17.7) and markedly higher in "priority" (high-burden) versus "nonpriority" (low-burden) municipalities (22.8/100,000 person-years at risk, 95% confidence interval (CI): 22.2, 23.3, compared with 14.3/100,000 person-years at risk, 95% CI: 14.0, 14.7). After matching, BFP participation was not associated with leprosy incidence overall (incidence rate ratio (IRR)Poisson = 0.97, 95% CI: 0.90, 1.04) but was associated with lower leprosy incidence when restricted to families living in high-burden municipalities (IRRPoisson = 0.86, 95% CI: 0.77, 0.96). In high-burden municipalities, the association was particularly pronounced for paucibacillary cases (IRRPoisson = 0.82, 95% CI: 0.68, 0.98) and cases with leprosy-associated disabilities (IRRPoisson = 0.79, 95% CI: 0.65, 0.97). These findings provide policy-relevant evidence that social policies might contribute to ongoing leprosy control efforts in high-burden communities.

Social, Environmental and Behavioral Determinants of Asthma Symptoms in Brazilian Middle School Students-A National School Health Survey (Pense 2012).

Biological and psychosocial factors are recognized contributors to the worldwide burden of asthma. However, the relationship between psychosocial factors and asthma symptoms among students in low- and middle-income countries remains underexplored. We aimed to identify socioeconomic, environmental, psychosocial, family-related and lifestyle factors associated with the self-reporting of asthma symptoms in Brazilian adolescents. This is a cross-sectional study using data from the 2012 PeNSE survey (n = 109,104). We analyzed the following variables: socioeconomic conditions, demographic characteristics, lifestyle, family context and dynamics, psychosocial indicators, smoking, and exposure to violence. Our outcome variable was the self-report of asthma symptoms in the past 12 months. The prevalence of wheezing was 22.7% (21.5⁻23.9). After adjusting for sex, age and the variables from higher hierarchical levels, exposure to violence (feeling unsafe at school, being frequently bullied, being exposed to fights with firearms) and physical aggression by an adult in the family were the environmental factors that showed the strongest associations with self-reporting of asthma symptoms. For psychosocial indicators of mental health and social integration, feelings of loneliness and sleeping problems were the strongest factors, and among individual behavioral factors, the largest associations were found for tobacco consumption. Our findings were consistent with previous studies, showing an association between self-reported asthma symptoms and socio-economic status, family context and dynamics, psychosocial indicators of mental health, exposure to violence and social integration, as well as a sedentary lifestyle and tobacco use.

Socioeconomic risk markers of leprosy in high-burden countries: A systematic review and meta-analysis.

Over 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For achieving leprosy elimination, one of the main challenges will be targeting higher risk groups within endemic communities. Nevertheless, the socioeconomic risk markers of leprosy remain poorly understood. To address this gap we systematically reviewed MEDLINE/PubMed, Embase, LILACS and Web of Science for original articles investigating the social determinants of leprosy in countries with > 1000 cases/year in at least five years between 2006 and 2016. Cohort, case-control, cross-sectional, and ecological studies were eligible for inclusion; qualitative studies, case reports, and reviews were excluded. Out of 1,534 non-duplicate records, 96 full-text articles were reviewed, and 39 met inclusion criteria. 17 were included in random-effects meta-analyses for sex, occupation, food shortage, household contact, crowding, and lack of clean (i.e., treated) water. The majority of studies were conducted in Brazil, India, or Bangladesh while none were undertaken in low-income countries. Descriptive synthesis indicated that increased age, poor sanitary and socioeconomic conditions, lower level of education, and food-insecurity are risk markers for leprosy. Additionally, in pooled estimates, leprosy was associated with being male (RR = 1.33, 95% CI = 1.06-1.67), performing manual labor (RR = 2.15, 95% CI = 0.97-4.74), suffering from food shortage in the past (RR = 1.39, 95% CI = 1.05-1.85), being a household contact of a leprosy patient (RR = 3.40, 95% CI = 2.24-5.18), and living in a crowded household (≥5 per household) (RR = 1.38, 95% CI = 1.14-1.67). Lack of clean water did not appear to be a risk marker of leprosy (RR = 0.94, 95% CI = 0.65-1.35). Additionally, ecological studies provided evidence that lower inequality, better human development, increased healthcare coverage, and cash transfer programs are linked with lower leprosy risks. These findings point to a consistent relationship between leprosy and unfavorable economic circumstances and, thereby, underscore the pressing need of leprosy control policies to target socially vulnerable groups in high-burden countries.

Biogeographical ancestry is associated with socioenvironmental conditions and infections in a Latin American urban population.

Racial inequalities are observed for different diseases and are mainly caused by differences in socioeconomic status between ethnoracial groups. Genetic factors have also been implicated, and recently, several studies have investigated the association between biogeographical ancestry (BGA) and complex diseases. However, the role of BGA as a proxy for non-genetic health determinants has been little investigated. Similarly, studies comparing the association of BGA and self-reported skin colour with these determinants are scarce. Here, we report the association of BGA and self-reported skin colour with socioenvironmental conditions and infections. We studied 1246 children living in a Brazilian urban poor area. The BGA was estimated using 370,539 genome-wide autosomal markers. Standardised questionnaires were administered to the children's guardians to evaluate socioenvironmental conditions. Infection (or pathogen exposure) was defined by the presence of positive serologic test results for IgG to seven pathogens (Toxocara spp, Toxoplasma gondii, Helicobacter pylori, and hepatitis A, herpes simplex, herpes zoster and Epstein-Barr viruses) and the presence of intestinal helminth eggs in stool samples (Ascaris lumbricoides and Trichiuris trichiura). African ancestry was negatively associated with maternal education and household income and positively associated with infections and variables, indicating poorer housing and living conditions. The self-reported skin colour was associated with infections only. In stratified analyses, the proportion of African ancestry was associated with most of the outcomes investigated, particularly among admixed individuals. In conclusion, BGA was associated with socioenvironmental conditions and infections even in a low-income and highly admixed population, capturing differences that self-reported skin colour miss. Importantly, our findings suggest caution in interpreting significant associations between BGA and diseases as indicative of the genetic factors involved.

Infectious causes of microcephaly: epidemiology, pathogenesis, diagnosis, and management.

Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities.

Conditional cash transfer programme: Impact on homicide rates and hospitalisations from violence in Brazil.

BACKGROUND: Homicide kills more people than war globally and is associated with income inequality. In Brazil, one of the most unequal countries of the world, the homicide rate is four times higher than the world average. Establishing if the Brazilian conditional cash transfer programme [Bolsa Familia Programme (BFP)], the largest in the world, is associated with a reduction in the rate of homicide is relevant for violence prevention programs. We aimed to assess the effect of BFP coverage on homicide and hospitalization rates from violence. METHODS: BFP coverage and rates of homicide (overall and disaggregated by sex and age) and hospitalizations from violence from all 5,507 Brazilian municipalities between 2004 and 2012 were explored using multivariable negative binomial regression models with fixed effect for panel data. Robustness of results was explored using sensitivity analyses such as difference-in-difference models. FINDINGS: Homicide rates and hospitalization from violence decreased as BFP coverage in the target population increased. For each percent increase in the uptake of the BFP, the homicide rate decreased by 0.3% (Rate Ratio:0.997; 95%CI:0.996-0.997) and hospitalizations from violence by 0.4% (RR: 0.996;95%CI:0.995-0.996). Rates of homicide and hospitalizations from violence were also negatively associated with the duration of BFP coverage. When, coverage of the target population was at least 70% for one-year, hospitalizations from violence decreased by 8%; two-years 14%, three-years 20%, and four years 25%. INTERPRETATION: Our results support the hypothesis that conditional cash transfer programs might have as an additional benefit the prevention of homicides and hospitalizations from violence. Social protection interventions could contribute to decrease levels of violence in low-and-middle-income-countries through reducing poverty and/or socioeconomic inequalities.

The duration of protection of school-aged BCG vaccination in England: a population-based case-control study.

Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. Methods: We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive intervals more than 10 years following vaccination. Results: We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, and more evident after 20 years. VE 10-15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. Conclusions: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.

Symptomatic dengue infection during pregnancy and the risk of stillbirth in Brazil, 2006-12: a matched case-control study.

BACKGROUND: Maternal infections during pregnancy can increase the risk of fetal death. Dengue infection is common, but little is known about its role in fetal mortality. We aimed to investigate the association between symptomatic dengue infection during pregnancy and fetal death. METHODS: We did a nested case-control study using obstetrician-collected data from the Brazilian livebirth information system (SINASC), the mortality information system (SIM), and the national reportable disease information system (SINAN). We identified all pregnancies ending in stillbirth and a random sample of livebirths between Jan 1, 2006, and Dec 31, 2012. We did linkage to determine which mothers were diagnosed with dengue infection during pregnancy. By use of stillbirths as cases and a sample of matched livebirths as a control, we calculated matched odds ratios (mORs) using conditional logistic regression adjusted for maternal age and education. FINDINGS: 275 (0·2%) of 162 188 women who had stillbirths and 1507 (0·1%) of 1 586 105 women who had livebirths were diagnosed with dengue infection during pregnancy. Symptomatic dengue infection during pregnancy almost doubled the odds of fetal death (mOR 1·9, 95% CI 1·6-2·2). The increase in risk was similar when analyses were restricted to laboratory-confirmed cases of dengue infection (1·8, 1·4-2·4). Severe dengue infection increased the risk of fetal death by about five times (4·9, 2·3-10·2). INTERPRETATION: Symptomatic dengue infection during pregnancy is associated with an increased risk of fetal death. We recommend further epidemiological and biological studies of the association between dengue and poor birth outcomes to measure the burden of subclinical infections and elucidate pathological mechanisms. FUNDING: Brazilian National Council for Scientific and Technological Development, Horizon 2020.

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

BACKGROUND: Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. OBJECTIVES: To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. METHODS: Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. RESULTS: In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5-10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10-15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. LIMITATIONS: The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. CONCLUSIONS: Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. FUNDING: The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

End TB strategy: the need to reduce risk inequalities.

BACKGROUND: Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. DISCUSSION: Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle.

Dengue during pregnancy and adverse fetal outcomes: a systematic review and meta-analysis.

BACKGROUND: Little is known about the possible adverse effects of dengue infection during pregnancy on fetal outcomes. In this systematic review and meta-analysis we aimed to estimate the increase in risk of four adverse fetal outcomes in women who had dengue infection during pregnancy. METHODS: For this systematic review and meta-analysis, we searched Medline, Embase, Global Health Library, and Scopus for articles published before Aug 1, 2015. We included original studies that reported any fetal outcomes for pregnant women who had dengue infection during the gestational period. Case-control, cohort, and cross-sectional studies and unselected case series were eligible for inclusion. We excluded case reports, ecological studies, reviews, in-vitro studies, and studies without data for pregnancy outcomes. We independently screened titles and abstracts to select papers for inclusion and scored the quality of those included in meta-analyses. For each study, we recorded study design, year of publication, study location, period of study, and authors and we extracted data for population characteristics such as the number of pregnancies, dengue diagnostic information, and the frequency of outcomes. We investigated four adverse fetal outcomes: stillbirth, miscarriage, preterm birth, and low birthweight. We estimated the increase in risk of these adverse fetal outcomes by use of Mantel-Haenszel methods. We assessed heterogeneity of odds ratios (OR) with the I(2) statistic. FINDINGS: We identified 278 non-duplicate records, of which 107 full-text articles were screened for eligibility. 16 studies were eligible for inclusion in the systematic review and eight were eligible for the meta-analyses, which included 6071 pregnant women, 292 of whom were exposed to dengue during pregnancy. For miscarriage, the OR was 3·51 (95% CI 1·15-10·77, I(2)=0·0%, p=0·765) for women with dengue infection during pregnancy compared with those without. We did not do a meta-analysis for stillbirth because this outcome was investigated in only one study with a comparison group; we calculated the crude relative risk to be 6·7 (95% CI 2·1-21·3) in women with symptomatic dengue compared with women without dengue. Preterm birth and low birthweight were the most common adverse pregnancy outcomes. The OR for the association with dengue was 1·71 (95% CI 1·06-2·76, I(2)=56·1%, p=0·058) for preterm birth and 1·41 (95% CI 0·90-2·21, I(2)=0·0%, p=0·543) for low birthweight. INTERPRETATION: Evidence suggests that symptomatic dengue during pregnancy might be associated with fetal adverse outcomes. If confirmed, it would be important to monitor pregnancies during which dengue is diagnosed and to consider pregnant women in dengue control policies. FUNDING: National Council for Scientific and Technological Development (CNPq).

The effect of internalization and other psychologic factors on the remission and severity of wheeze in children.

BACKGROUND: Asthma prevalence in Latin America is high and continues to increase. There is evidence that the psychologic characteristics of the child are associated with greater asthma morbidity. This study aimed to investigate the independent effect of internalizing/externalizing problems on two asthma/wheeze outcomes: (i) remission and (ii) progression to severity on Latin American children with mild asthma symptoms at baseline. METHODS: This was a prospective study in a cohort of 371 asthmatic children living in a poor urban area in Salvador, Brazil. The psychologic characteristics of the child were assessed using the Child Behavior Checklist (CBCL), and wheezing was defined using the ISAAC questionnaire at the start and end of follow-up. A multiple logistic regression model with random effects was used to examine the association between the psychologic components and both outcomes. RESULTS: Remission of symptoms of wheeze was observed among 229 (61.73%) children. Remission was 56% lower among children with internalizing problems (OR = 0.54, 95% CI 0.33-0.87, p = 0.01). In addition, we found that 19 (8.76%) of the children acquired severe symptoms during follow-up and there was strong evidence of the effect of internalizing problems in increasing the risk of progression to severe wheeze symptoms (OR = 4.03, 95% CI 1.39-11.70, p = 0.01). CONCLUSIONS: Children with internalizing problems but not externalizing had less remission of wheezing, and a higher risk of acquiring severe symptoms. These results highlight the importance of psychologic care for children with asthma, to improve the prognosis of this condition.

Family planning, antenatal and delivery care: cross-sectional survey evidence on levels of coverage and inequalities by public and private sector in 57 low- and middle-income countries.

OBJECTIVE: The objective of this study was to assess the role of the private sector in low- and middle-income countries (LMICs). We used Demographic and Health Surveys for 57 countries (2000-2013) to evaluate the private sector's share in providing three reproductive and maternal/newborn health services (family planning, antenatal and delivery care), in total and by socio-economic position. METHODS: We used data from 865 547 women aged 15-49, representing a total of 3 billion people. We defined 'met and unmet need for services' and 'use of appropriate service types' clearly and developed explicit classifications of source and sector of provision. RESULTS: Across the four regions (sub-Saharan Africa, Middle East/Europe, Asia and Latin America), unmet need ranged from 28% to 61% for family planning, 8% to 22% for ANC and 21% to 51% for delivery care. The private-sector share among users of family planning services was 37-39% across regions (overall mean: 37%; median across countries: 41%). The private-sector market share among users of ANC was 13-61% across regions (overall mean: 44%; median across countries: 15%). The private-sector share among appropriate deliveries was 9-56% across regions (overall mean: 40%; median across countries: 14%). For all three healthcare services, women in the richest wealth quintile used private services more than the poorest. Wealth gaps in met need for services were smallest for family planning and largest for delivery care. CONCLUSIONS: The private sector serves substantial numbers of women in LMICs, particularly the richest. To achieve universal health coverage, including adequate quality care, it is imperative to understand this sector, starting with improved data collection on healthcare provision.