Publications by authors named "Laura C Rodrigues"

202 Publications

Differences in Placental Histology Between Zika Virus-infected Teenagers and Older Women.

Int J Gynecol Pathol 2021 Aug 4. Epub 2021 Aug 4.

Departments of Morphology and Basic Pathology (G.R.S., C.A.L.P., R.C.S.P.) Pathology and Cytology Laboratory, Jundiaí Medical School (JMS) (G.R.S., C.A.L.P.); Pediatrics (Z.C., S.D.P.) Laboratory of Pediatrics Infectology, Jundiai Medical School (FMJ) (Z.C., S.D.P.) Department of Pediatrics, University Hospital of Jundiai Medical School (HU-FMJ) (Z.C., S.D.P.) Jundiai Department of Pathology, AC Camargo Cancer Center (C.A.L.P.) Center of Research about Human Genome and Stem Cells, Bioscience Institute of University of Sao Paulo (CEGH-CEL/IB-USP) (M.Z.) Department of Legal Medicine, University of São Paulo (USP) (E.M.) Foundation for Research Support of the State of Sao Paulo (FAPESP) (E.M.) Sao Paulo School of Advanced Applied Mathematics of Getulio Vargas Foundation (EMAp-FGV), Rio de Janeiro (E.M.) National Council for Scientific and Technological Development (CNPq), Brasilia (E.M.) Brazil Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York (S.S.W.) Department of Infectious Maladies and Pediatric Immunodeficiencies, VallD´Hebron Hospital, Barcelona, Spain (A.S.A.) Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM) (L.C.R., E.M.) Royal Society of Medicine, London, UK (E.M.).

In pregnant women, Zika virus (ZIKV) is associated with a congenital syndrome, most frequently involving damage to embryo brain formation and the development of microcephaly. The mechanism(s) by which ZIKV enters the maternal-fetal interface and is transmitted to the fetus remains incompletely determined. We sought to evaluate histologic changes in the placenta of ZIKV-infected pregnant women and to determine if this varied by maternal age. Placental samples were obtained from 66 women, 33 of whom were positive for ZIKV. Histologic evaluations were performed on 4 areas of the placenta: fetal surface, maternal surface, umbilical cord, and membranes. Samples were analyzed by the tissue microarray technique and tested for CD4, CD8, CD20, CD68, FOXP3, and cyclooxygenase-2 expression. Data were evaluated using Fisher exact test. ZIKV infection was more frequent in women less than 18 yr of age (9/11, 81.8%) than in women above 18 yr old (24/55, 43.6%) (P=0.0440). ZIKV detection was associated with neutrophilic chorioamnionitis (P=0.0332) and with septal (P=0.0244) and villous (P=0.0534) calcification. Hofbauer cell hyperplasia (P=0.0260) and cyclooxygenase-2 expression (P=0.0346) were more prevalent in ZIKV-positive women aged 18 yr and below than in the older ZIKV-positive women. ZIKV infection during pregnancy occurs more frequently in adolescents and induces higher rates of damage at the maternal-fetal interface than in older women.
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http://dx.doi.org/10.1097/PGP.0000000000000807DOI Listing
August 2021

Seroprevalence of Chikungunya virus and living conditions in Feira de Santana, Bahia-Brazil.

PLoS Negl Trop Dis 2021 04 20;15(4):e0009289. Epub 2021 Apr 20.

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition.

Methodology/principal Findings: We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033).

Conclusions/significance: The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population.
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http://dx.doi.org/10.1371/journal.pntd.0009289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087031PMC
April 2021

Factors associated with small- and large-for-gestational-age in socioeconomically vulnerable individuals in the 100 Million Brazilian Cohort.

Am J Clin Nutr 2021 07;114(1):109-116

Centre for Data and Knowledge Integration for Health (CIDACS), Oswaldo Cruz Foundation, Salvador, Brazil.

Background: Evidence points to diverse risk factors associated with small- (SGA) and large-for-gestational-age (LGA) births. A more comprehensive understanding of these factors is imperative, especially in vulnerable populations.

Objectives: To estimate the occurrence of and sociodemographic factors associated with SGA and LGA births in poor and extremely poor populations of Brazil.

Methods: The study population consisted of women of reproductive age (14-49 y), whose last child was born between 2012 and 2015. INTERGROWTH 21st consortium criteria were used to classify weight for gestational age according to sex. Multinomial logistic regression modeling was performed to investigate associations of interest.

Results: Of 5,521,517 live births analyzed, SGA and LGA corresponded to 7.8% and 17.1%, respectively. Multivariate analysis revealed greater odds of SGA in children born to women who self-reported as black (OR: 1.21; 95% CI: 1.19, 1.22), mixed-race (parda) (OR: 1.08; 95% CI: 1.07, 1.09), or indigenous (OR: 1.11; 95% CI: 1.06, 1.15), were unmarried (OR: 1.08; 95% CI: 1.07, 1.08), illiterate (OR: 1.47; 95% CI: 1.42, 1.52), did not receive prenatal care (OR: 1.57; 95% CI: 1.53, 1.60), or were aged 14-20 y (OR: 1.21; 95% CI: 1.20, 1.22) or 35-49 y (OR: 1.12; 95% CI: 1.10, 1.13). Considering LGA children, higher odds were found in infants born to women living in households with ≥3 inadequate housing conditions (OR: 1.11; 95% CI: 1.10, 1.12), in indigenous women (OR: 1.22; 95% CI: 1.19, 1.25), those who had 1-3 y of schooling (OR: 1.18; 95% CI: 1.17, 1.19), 1-3 prenatal visits (OR: 1.16; CI 95%: 1.14, 1.17), or were older (OR: 1.26; 95% CI: 1.25, 1.27).

Conclusions: In poorer Brazilian populations, socioeconomic, racial, and maternal characteristics are consistently associated with the occurrence of SGA births, but remain less clearly linked to the occurrence of LGA births.
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http://dx.doi.org/10.1093/ajcn/nqab033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246620PMC
July 2021

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

PLoS Negl Trop Dis 2021 03 8;15(3):e0009216. Epub 2021 Mar 8.

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.

Methods: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy.

Findings: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.
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http://dx.doi.org/10.1371/journal.pntd.0009216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971861PMC
March 2021

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

PLoS One 2020 19;15(10):e0240879. Epub 2020 Oct 19.

Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, and Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240879PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571683PMC
December 2020

Factors associated with low birth weight at term: a population-based linkage study of the 100 million Brazilian cohort.

BMC Pregnancy Childbirth 2020 Sep 14;20(1):536. Epub 2020 Sep 14.

Center for Data and Knowledge Integration for Health (CIDACS), Oswaldo Cruz Foundation, Salvador, Brazil.

Background: Factors associated with low birth weight at term (TLBW), a proxy for intrauterine growth restriction (IUGR), are not well-elucidated in socioeconomically vulnerable populations. This study aimed to identify the factors associated with TLBW in impoverished Brazilian women.

Methods: Records in the 100 Million Brazilian Cohort database were linked to those in the National System of Information on Live Births (SINASC) to obtain obstetric, maternal, birth and socioeconomic data between 2001 and 2015. Multivariate logistic regression was performed to investigate associations between variables of exposure and TLBW.

Results: Of 8,768,930 term live births analyzed, 3.7% presented TLBW. The highest odds of TLBW were associated with female newborns (OR: 1.49; 95% CI: 1.47-1.50), whose mothers were black (OR: 1.20; 95% CI: 1.18-1.22), had a low educational level (OR: 1.57; 95% CI: 1.53-1.62), were aged ≥35 years (OR: 1.44; 95% CI: 1.43-1.46), had a low number of prenatal care visits (OR: 2.48; 95% CI: 2.42-2.54) and were primiparous (OR: 1.62; 95% CI: 1.60-1.64). Lower odds of TLBW were found among infants whose mothers lived in the North, Northeast and Center-West regions of Brazil compared to those in the South.

Conclusion: Multiple aspects were associated with TLBW, highlighting the need to comprehensively examine the mechanisms underlying these factors, especially in more vulnerable Brazilian populations, in order to contribute to the elaboration of health policies and promote better conditions of life for poor and extremely poor mothers and children.
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http://dx.doi.org/10.1186/s12884-020-03226-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491100PMC
September 2020

Zika virus infection in pregnancy and adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study.

Sci Rep 2020 07 29;10(1):12673. Epub 2020 Jul 29.

Jundiaí Medical School, Jundiaí University, São Paulo, Brazil.

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.
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http://dx.doi.org/10.1038/s41598-020-69235-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391725PMC
July 2020

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

Am J Epidemiol 2020 12;189(12):1547-1558

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.
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http://dx.doi.org/10.1093/aje/kwaa127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705605PMC
December 2020

Drug misuse, tobacco smoking, alcohol and other social determinants of tuberculosis in UK-born adults in England: a community-based case-control study.

Sci Rep 2020 03 27;10(1):5639. Epub 2020 Mar 27.

Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.

Addressing social determinants of tuberculosis (TB) is essential to achieve elimination, including in low-incidence settings. We measured the association between socio-economic status and intermediate social determinants of health (SDHs, including drug misuse, tobacco smoking and alcohol), and TB, taking into account their clustering in individuals. We conducted a case-control study in 23-38 years old UK-born White adults with first tuberculosis episode, and randomly selected age and sex frequency-matched community controls. Data was collected on education, household overcrowding, tobacco smoking, alcohol and drugs use, and history of homelessness and prison. Analyses were done using logistic regression models, informed by a formal theoretical causal framework (Directed Acyclic Graph). 681 TB cases and 1183 controls were recruited. Tuberculosis odds were four times higher in subjects with education below GCSE O-levels, compared to higher education (OR = 3.94; 95%CI: 2.74, 5.67), after adjusting for other TB risk factors (age, sex, BCG-vaccination and stays ≥3 months in Africa/Asia). When simultaneously accounting for respective SDHs, higher tuberculosis risk was independently associated with tobacco smoking, drugs use (especially injectable drugs OR = 5.67; 95%CI: 2.68, 11.98), homelessness and area-level deprivation. Population Attributable Fraction estimates suggested that tobacco and class-A drug use were, respectively, responsible for 18% and 15% of TB cases in this group. Our findings suggest that socio-economic deprivation remains a driver of tuberculosis in England, including through drugs misuse, tobacco smoking, and homelessness. These findings further support the integration of health and social services in high-risk young adults to improve TB control efforts.
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http://dx.doi.org/10.1038/s41598-020-62667-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101386PMC
March 2020

Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study.

Lancet Infect Dis 2020 05 14;20(5):618-627. Epub 2020 Feb 14.

Centre for Data and Knowledge Integration for Health (CIDACS), Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil; Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.

Background: Indirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil.

Methods: In this quasi-experimental study, we linked baseline demographic and socioeconomic information for individuals who entered the 100 Million Brazilian Cohort between Jan 1, 2007, and Dec 31, 2014, with the PBF payroll database and the Information System for Notifiable Diseases, which includes nationwide leprosy registries. Individuals were eligible for inclusion if they had a household member older than 15 years and had not received PBF aid or been diagnosed with leprosy before entering the 100 Million Brazilian Cohort; they were excluded if they were partial receivers of PBF benefits, had missing data, or had a monthly per-capita income greater than BRL200 (US$50). Individuals who were PBF beneficiaries before leprosy diagnosis were matched to those who were not beneficiaries through propensity-score matching (1:1) with replacement on the basis of baseline covariates, including sex, age, race or ethnicity, education, work, income, place of residence, and household characteristics. We used logistic regression to assess the average treatment effect on the treated of receipt of PBF benefits on leprosy treatment adherence (six or more multidrug therapy doses for paucibacillary cases or 12 or more doses for multibacillary cases) and cure in individuals of all ages. We stratified our analysis according to operational disease classification (paucibacillary or multibacillary). We also did a subgroup analysis of paediatric leprosy restricted to children aged up to 15 years.

Findings: We included 11 456 new leprosy cases, of whom 8750 (76·3%) had received PBF before diagnosis and 2706 (23·6%) had not. Overall, 9508 (83·0%) patients adhered to treatment and 10 077 (88·0%) were cured. After propensity score matching, receiving PBF before diagnosis was associated with adherence to treatment (OR 1·22, 95% CI 1·01-1·48) and cure (1·26, 1·01-1·58). PBF receipt did not significantly improve treatment adherence (1·37, 0·98-1·91) or cure (1·12, 0·75-1·67) in patients with paucibacillary leprosy. For patients with multibacillary disease, PBF beneficiaries had better treatment adherence (1·37, 1·08-1·74) and cure (1·43, 1·09-1·90) than non-beneficiaries. In the propensity score-matched analysis in 2654 children younger than 15 years with leprosy, PBF exposure was not associated with leprosy treatment adherence (1·55, 0·89-2·68) or cure (1·57, 0·83-2·97).

Interpretation: Our results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease.

Funding: CONFAP/ESRC/MRC/BBSRC/CNPq/FAPDF-Doenças Negligenciadas, the UK Medical Research Council, the Wellcome Trust, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES).
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http://dx.doi.org/10.1016/S1473-3099(19)30624-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191267PMC
May 2020

Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazil.

Int J Environ Res Public Health 2020 01 21;17(3). Epub 2020 Jan 21.

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife PE, 50740-465, Brazil.

Since an outbreak in Brazil, which started in 2015, Zika has been recognized as an important cause of microcephaly. The highest burden of this outbreak was in northeast Brazil, including the state of Pernambuco. The prevalence of congenital microcephaly in Pernambuco state was estimated from the RESP (Registro de Eventos em Saúde Pública) surveillance system, from August 2015 to August 2016 inclusive. The denominators were estimated at the municipality level from official demographic data. Microcephaly was defined as a neonatal head circumference below the 3rd percentile of the Intergrowth standards. Smoothed maps of the prevalence of microcephaly were obtained from a Bayesian model which was conditional autoregressive (CAR) in space, and first order autoregressive in time. A total of 742 cases were identified. Additionally, high and early occurrences were identified in the Recife Metropolitan Region, on the coast, and in a north-south band about 300 km inland. Over a substantial part of the state, the overall prevalence, aggregating over the study period, was above 0.5%. The reasons for the high occurrence in the inland area remain unclear.
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http://dx.doi.org/10.3390/ijerph17030700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037094PMC
January 2020

Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010-15: a population-based, longitudinal study.

Lancet Infect Dis 2020 01 31;20(1):123-132. Epub 2019 Oct 31.

Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background: Long-term survival and cause-specific mortality of patients who start tuberculosis treatment is rarely described. We aimed to assess the long-term survival of these patients and evaluate the association between vulnerable conditions (social, health behaviours, and comorbidities) and cause-specific mortality in a country with a high burden of tuberculosis.

Methods: In this population-based, longitudinal study in São Paulo state, Brazil, we described the 5-year survival of patients who were newly diagnosed with tuberculosis in 2010. We included patients with newly-diagnosed tuberculosis, aged 15 years or older, and notified to the São Paulo State Tuberculosis Program in 2010. We excluded patients whose diagnosis had changed during follow-up (ie, they did not have tuberculosis) and patients who had multidrug-resistant (MDR) tuberculosis. We selected our population with tuberculosis from the dedicated electronic system TBweb. Our primary objective was to estimate the excess mortality over 5 years and within the group who survived the first year, compared with the general São Paulo state population. We also estimated the association between social vulnerability (imprisonment and homelessness), health behaviours (alcohol and drug use), and comorbidities (diabetes and mental disorders) with all-cause and cause-specific mortality. We used the competing risk analysis framework, estimating cause-specific hazard ratios (HRs) adjusted for potential confounding factors.

Findings: In 2010, there were 19 252 notifications of tuberculosis cases. We excluded 550 cases as patients were younger than 15 years, 556 cases that were not tuberculosis, 2597 retreatments, and 48 cases of MDR tuberculosis, resulting in a final cohort of 15 501 patients with tuberculosis. Over a period of 5 years from tuberculosis diagnosis, 2660 (17%) of 15 501 patients died. Compared with the source population, matched by age, sex, and calendar year, the standardised mortality ratio was 6·47 (95% CI 6·22-6·73) over 5 years and 3·93 (3·71-4·17) among those who survived the first year. 1197 (45%) of 2660 deaths were due to infection. Homelessness and alcohol and drug use were associated with death from infection (adjusted cause-specific HR 1·60, 95% CI 1·39-1·85), cardiovascular (1·43, 1·06-1·95), and external or ill-defined causes of death (1·80, 1·37-2·36). Diabetes was associated with deaths from cardiovascular causes (1·70, 1·23-2·35).

Interpretation: Patients newly diagnosed with tuberculosis were at a higher risk of death than were the source population, even after tuberculosis treatment. Post-tuberculosis sequelae and vulnerability are associated with excess mortality and must be addressed to mitigate the tuberculosis burden worldwide.

Funding: Wellcome Trust.
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http://dx.doi.org/10.1016/S1473-3099(19)30518-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928568PMC
January 2020

Zika virus infection in pregnancy: Establishing a case definition for clinical research on pregnant women with rash in an active transmission setting.

PLoS Negl Trop Dis 2019 10 7;13(10):e0007763. Epub 2019 Oct 7.

Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brasil.

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV's overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015-2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0-72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.
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http://dx.doi.org/10.1371/journal.pntd.0007763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797234PMC
October 2019

Impact evaluation of Zika epidemic on congenital anomalies registration in Brazil: An interrupted time series analysis.

PLoS Negl Trop Dis 2019 09 23;13(9):e0007721. Epub 2019 Sep 23.

Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil. We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies. We obtained monthly data from Brazilian Live Birth Information System and used two outcome definitions: 1) rate of congenital malformation of the brain and eye (likely to be affected by Zika and its complications) 2) rate of congenital malformation not related to the brain or eye unlikely to be causally affected by Zika. The period between maternal infection with Zika and diagnosis of congenital abnormality attributable to the infection is around six months. We therefore used September 2015 as the interruption point in the time series, six months following March 2015 when cases of Zika started to increase. For the purposes of this analysis, we considered the period from January 2010 to September 2015 to be "pre-Zika event," and the period from just after September 2015 to December 2017 to be "post-Zika event." We found that immediately after the interruption point, there was a great increase in the notification rate of congenital anomalies of 14.9/10,000 live births in the brain and eye group and of 5.2/10,000 live births in the group not related with brain or eye malformations. This increase in reporting was in all regions of the country (except in the South) and especially in the Northeast. In the period "post-Zika event", unlike the brain and eye group which showed a monthly decrease, the group without brain or eye malformations showed a slow but significant increase (relative to the pre-Zika trend) of 0.2/10,000 live births. These findings suggest an overall improvement in the registration of birth malformations, including malformations that were not attributed to Zika, during and after the Zika epidemic.
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http://dx.doi.org/10.1371/journal.pntd.0007721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776346PMC
September 2019

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

PLoS Negl Trop Dis 2019 09 6;13(9):e0007714. Epub 2019 Sep 6.

Tropical Medicine Centre, University of Brasília, Fiocruz School of Government, Fiocruz Brasília, Brazil.

Background: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil.

Methodology/principal Findings: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66).

Conclusions: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.
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http://dx.doi.org/10.1371/journal.pntd.0007714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750604PMC
September 2019

Dengue during pregnancy and live birth outcomes: a cohort of linked data from Brazil.

BMJ Open 2019 07 24;9(7):e023529. Epub 2019 Jul 24.

IDE, London School of Hygiene & Tropical Medicine Faculty of Epidemiology and Population Health, London, UK.

Objectives: Dengue is the most common viral mosquito-borne disease, and women of reproductive age who live in or travel to endemic areas are at risk. Little is known about the effects of dengue during pregnancy on birth outcomes. The objective of this study is to examine the effect of maternal dengue severity on live birth outcomes.

Design And Setting: We conducted a population-based cohort study using routinely collected Brazilian data from 2006 to 2012.

Participating: We linked birth registration records and dengue registration records to identify women with and without dengue during pregnancy. Using multinomial logistic regression and Firth method, we estimated risk and ORs for preterm birth (<37 weeks' gestation), low birth weight (<2500 g) and small for gestational age (<10thcentile). We also investigated the effect of time between the onset of the disease and each outcome.

Results: We included 16 738 000 live births. Dengue haemorrhagic fever was associated with preterm birth (OR=2.4; 95% CI 1.3 to 4.4) and low birth weight (OR=2.1; 95% CI 1.1 to 4.0), but there was no evidence of effect for small for gestational age (OR=2.1; 95% CI 0.4 to 12.2). The magnitude of the effects was higher in the acute disease period.

Conclusion: This study showed an increased risk of adverse birth outcomes in women with severe dengue during pregnancy. Medical intervention to mitigate maternal risk during severe acute dengue episodes may improve outcomes for infants born to exposed mothers.
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http://dx.doi.org/10.1136/bmjopen-2018-023529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661644PMC
July 2019

Socioeconomic determinants of leprosy new case detection in the 100 Million Brazilian Cohort: a population-based linkage study.

Lancet Glob Health 2019 09 19;7(9):e1226-e1236. Epub 2019 Jul 19.

Tropical Medicine Centre, University of Brasília, Fiocruz School of Goverment Brasília, Brazil.

Background: Although leprosy is recognised as a disease of poverty, there is little evidence on the specific socioeconomic factors associated with disease risk. To inform targeted strategies for disease elimination, we investigated socioeconomic markers of leprosy risk in Brazil.

Methods: Socioeconomic data from the 100 Million Brazilian Cohort were linked to the Brazilian national disease registry (Sistema de Informação de Agravos de Notificação) for leprosy from Jan 1, 2007, to Dec 31, 2014. Using Poisson regression, we assessed the association of socioeconomic factors with risk of incident leprosy in the full cohort and in children (aged 0-15 years), by leprosy subtype and region of residence.

Findings: In an analysis of 23 899 942 individuals including 18 518 patients with leprosy, increased levels of deprivation were associated with an increased risk of leprosy in Brazil. Directions of effect were consistent in children younger than 15 years and across disease subtypes. Individuals residing in regions with the highest poverty in the country (central-west, north, and northeast regions) had a risk of leprosy incidence five-to-eight times greater than did other individuals. Decreased levels of income and education and factors reflecting unfavourable living conditions were associated with an up to two-times increase in leprosy incidence (incidence rate ratio 1·46, 95% CI 1·32-1·62, for lowest vs highest quartile of income per capita; 2·09, 95% CI 1·62-2·72, for lowest vs highest level of education).

Interpretation: Within the poorest half of the Brazilian population, the most deprived individuals have the greatest risk of leprosy. Strategies focusing on early detection and treatment in the poorest populations could contribute substantially to global disease control.

Funding: Medical Research Council, Wellcome Trust, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazil), the Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa, Economic and Social Research Council, Biotechnology and Biological Sciences Research Council, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação de Apoio à Pesquisa do Distrito Federal.
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http://dx.doi.org/10.1016/S2214-109X(19)30260-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688099PMC
September 2019

Investigation of an outbreak of acute respiratory disease in an indigenous village in Brazil: Contribution of Influenza A(H1N1)pdm09 and human respiratory syncytial viruses.

PLoS One 2019 8;14(7):e0218925. Epub 2019 Jul 8.

Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brazil.

Analyses of the 2009 H1N1 influenza pandemic and post-pandemic years showed high attack rates and severity among indigenous populations. This study presents the characteristics of the first documented influenza outbreak in indigenous peoples in Brazil, that occurred from 30th March to 14th April 2016 in a Guarani village in Southeast Region. Acute respiratory infections were prospectively investigated. The majority of the 73 cases were influenza-like illness (ILI) (63.0%) or severe acute respiratory infection (SARI) (20.5%). The ILI+SARI attack rate (35.9%) decreased with increasing age. There was a high influenza vaccination rate (86.3%), but no statistically significant difference in vaccination rates between severe and non-severe cases was seen (p = 0.334). Molecular analyses of 19.2% of the cases showed 100% positivity for influenza A(H1N1)pdm09 and/or hRSV. Influenza A(H1N1)pdm09 was included in the 6B.1 genetic group, a distinct cluster with 13 amino acid substitutions of A/California/07/2009-like. The hRSV were clustered in the BA-like genetic group. The early arrival of the influenza season overlapping usual hRSV season, the circulation of a drifted influenza virus not covered by vaccine and the high prevalence of risk factors for infection and severity in the village jointly can explain the high attack rate of ARI, even with a high rate of influenza vaccination. The results reinforce the importance of surveillance of respiratory viruses, timely vaccination and controlling risk factors for infection and severity of in the indigenous populations in order to preventing disease and related deaths, particularly in children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613774PMC
February 2020

Validating linkage of multiple population-based administrative databases in Brazil.

PLoS One 2019 28;14(3):e0214050. Epub 2019 Mar 28.

London School of Hygiene and Tropical Medicine, Bloomsbury, London, United Kingdom.

Background: Linking routinely-collected data provides an opportunity to measure the effects of exposures that occur before birth on maternal, fetal and infant outcomes. High quality linkage is a prerequisite for producing reliable results, and there are specific challenges in mother-baby linkage. Using population-based administrative databases from Brazil, this study aimed to estimate the accuracy of linkage between maternal deaths and birth outcomes and dengue notifications, and to identify potential sources of bias when assessing the risk of maternal death due to dengue in pregnancy.

Methods: We identified women with dengue during pregnancy in a previously linked dataset of dengue notifications in women who had experienced a live birth or stillbirth during 2007-2012. We then linked this dataset with maternal death records probabilistically using maternal name, age and municipality. We estimated the accuracy of the linkage, and examined the characteristics of false-matches and missed-matches to identify any sources of bias.

Results: Of the 10,259 maternal deaths recorded in 2007-2012, 6717 were linked: 5444 to a live birth record, 1306 to a stillbirth record, and 33 to both a live and stillbirth record. After identifying 2620 missed-matches and 124 false-matches, our estimated sensitivity was 72%, specificity was 88%, and positive predictive value was 98%. Linkage errors were associated with maternal education and self-identified race; women with more than 7 years of education or who self-declared as Caucasian were more likely to link. Dengue status was not associated with linkage error.

Conclusion: Despite not having unique identifiers to link mothers and birth outcomes, we demonstrated a high standard of linkage, with sensitivity and specificity values comparable to previous literature. Although there were no differences in the characteristics of dengue cases missed or included in our linked dataset, linkage error occurred disproportionally by some social-demographic characteristics, which should be taken into account in future analyses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214050PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438533PMC
December 2019

Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil.

PLoS Negl Trop Dis 2019 03 11;13(3):e0007246. Epub 2019 Mar 11.

Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, Pernambuco, Brazil.

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.
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http://dx.doi.org/10.1371/journal.pntd.0007246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428350PMC
March 2019

The impact of a cash transfer programme on tuberculosis treatment success rate: a quasi-experimental study in Brazil.

BMJ Glob Health 2019 24;4(1):e001029. Epub 2019 Jan 24.

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

Background: Evidence suggests that social protection policies such as Brazil's Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in tuberculosis (TB) elimination. However, study limitations hamper conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB treatment success rate.

Methods: Propensity scores were estimated from a complete-case logistic regression using covariates from a linked data set, including the Brazil's TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll.

Results: The average effect of treatment on the treated was estimated as the difference in TB treatment success rate between matched groups (ie, the control and exposed patients, n=2167). Patients with TB receiving BFP showed a treatment success rate of 10.58 percentage points higher (95% CI 4.39 to 16.77) than patients with TB not receiving BFP. This association was robust to sensitivity analyses.

Conclusions: This study further confirms a positive relationship between the provision of conditional cash transfers and TB treatment success rate. Further research is needed to understand how to enhance access to social protection so to optimise public health impact.
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http://dx.doi.org/10.1136/bmjgh-2018-001029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347926PMC
January 2019

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

PLoS One 2018 31;13(12):e0208925. Epub 2018 Dec 31.

King's College London, London, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312285PMC
May 2019

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

Int J Environ Res Public Health 2018 12 19;15(12). Epub 2018 Dec 19.

Center for Data and Knowledge Integration for Health (CIDACS), Institute Gonçalo Moniz (IGM), Oswaldo Cruz Foundation (FIOCRUZ), Salvador 41.745-715, Brazil.

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 ( = 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.
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http://dx.doi.org/10.3390/ijerph15122904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313389PMC
December 2018

African biogeographical ancestry, atopic and non-atopic asthma and atopy: A study in Latin American children.

Pediatr Pulmonol 2019 02 11;54(2):125-132. Epub 2018 Dec 11.

Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil.

Background: Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies.

Objectives: To investigate the association between individual African ancestry and asthma symptoms, atopic and non-atopic asthma, and atopy in children.

Methods: A cross-sectional study encompassing 1190 individuals was conducted. African biogeographic ancestry was estimated using 370 539 genome-wide SNPs. Serum levels of specific IgE were measured, and skin prick test (SPT) performed for the most common local aeroallergens. Information on asthma symptoms was obtained by applying the International Study of Allergy and Asthma in Childhood questionnaire. The associations between the proportion of individual African ancestry and the outcomes investigated were analyzed through multivariate models adjusted for socio-environmental variables, infections markers, and psychosocial factors.

Results: Each 20% increase in the proportion of African ancestry was negatively associated with SPT reactivity (OR: 0.79, 95%CI: 0.66-0.96) and positively associated with asthma symptoms in non-atopic individuals (OR: 1.40, 95%CI: 1.03-1.89). We estimated that socioeconomic status and number of infections mediated 28.4% of the effect of African ancestry on SPT reactivity, while 20.2% of the effect on non-atopic asthma was explained by socioeconomic status and behavioral problems in children.

Conclusions: The negative association observed between African ancestry and atopy is most probably explained by unobserved environmental or social factors that covariate with ancestry. For non-atopic asthma, in turn, putative genetic variants of risk underlying African ancestry may play some role.
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http://dx.doi.org/10.1002/ppul.24213DOI Listing
February 2019

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis.

BMC Med 2018 10 3;16(1):180. Epub 2018 Oct 3.

Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK.

Background: Zika virus (ZIKV) emerged in Latin America and the Caribbean (LAC) region in 2013, with serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and the lack of a comprehensive collation of data from affected countries.

Methods: Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 90 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vectorial capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.

Results: There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 would present within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p < 0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.

Conclusions: The findings suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.
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http://dx.doi.org/10.1186/s12916-018-1158-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169075PMC
October 2018

Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America.

Sci Rep 2018 09 27;8(1):14475. Epub 2018 Sep 27.

Institute of Collective Health, Federal University of Bahia, 40110-040, Salvador, Bahia, Brazil.

The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk.
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http://dx.doi.org/10.1038/s41598-018-32837-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160443PMC
September 2018

Further pieces of evidence in the Zika virus and microcephaly puzzle.

Lancet Child Adolesc Health 2018 03 12;2(3):162-164. Epub 2018 Jan 12.

Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK. Electronic address:

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http://dx.doi.org/10.1016/S2352-4642(18)30021-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522374PMC
March 2018

Symptomatic Dengue during Pregnancy and Congenital Neurologic Malformations.

Emerg Infect Dis 2018 09;24(9):1748-1750

Dengue virus infection during pregnancy increased the risk for any neurologic congenital anomaly in the infant by roughly 50% and for other congenital malformations of brain 4-fold. Our results show an association between dengue during pregnancy and congenital anomalies of the brain, suggesting that flaviviruses other than Zika virus are associated with such malformations.
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http://dx.doi.org/10.3201/eid2409.170361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106414PMC
September 2018

Chikungunya chronic disease: a systematic review and meta-analysis.

Trans R Soc Trop Med Hyg 2018 07;112(7):301-316

Instituto de Saúde Coletiva. Rua Basílio da Gama, s/n. Canela. CEP 40110040. Salvador, Bahia, Brasil.

Background: Chikungunya is a mosquito-borne disease caused by an arthritogenic alphavirus, with four genotypes: East Central South African (ECSA), West African, ECSA-diverged or Indian Ocean Lineage (IOL) and Asian lineage. Overall, the disease is self-limited; however, in some patients, joint pain and other non-specific symptoms can last for months or years. This systematic review and meta-analysis aims to estimate the proportion of people that self-report chikungunya-related chronic non-specific symptoms.

Methods: Medline, EMBASE, Global Health Library and Scopus were searched for articles published before March 2017. Case-control, cohort, cross-sectional, clinical trials studies and outcome-independent case series were eligible. It was estimated that the proportion of patients who did not recover, by virus genotype, and by the time between disease onset and assessment of chronic symptoms.

Results: A total of 38 studies were included in the review and 34 in the meta-analysis. Of 6532 chikungunya patients, 3157 did not recover fully after 3 months. The overall no recovery rate associated with chikungunya was 43% (95% CI, 35-52%); Inter-genotype group heterogeneity was observed, the highest prevalence in the ECSA-diverged genotype: 50% (95% CI; 40-60%), followed by the Asian lineage genotype: 36% (95% CI; 20-52%). After 12 months follow-up, the overall no-recovery rate was 21% (95% CI; 19-22%).

Conclusion: The evidence suggests that the prevalence of chronic discomfort associated with chikungunya illness varies by virus lineage. The proportion of people that do not fully recovered after chikungunya was high and, therefore, health authorities must prepare to treat patients with symptoms of long-lasting chikungunya adequately addressing the physical, psychological and social needs.
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http://dx.doi.org/10.1093/trstmh/try063DOI Listing
July 2018
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