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Background: The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.Methods: We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities.Findings: Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities.Interpretation: Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size.Funding: Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. [ABSTRACT FROM AUTHOR]

In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children. [ABSTRACT FROM AUTHOR]

Abstract: Background: BCG vaccine protects against leprosy. Objectives: Estimate BCG protection against leprosy by age by age. Methods: A case control study with 226 cases of leprosy and 857 controls. BCG vaccination was ascertained via examination of BCG scars. Protection is presented for three age groups. Results: BCG protection against leprosy was 86% (95% CI: 77–92%) in the age group 18–29; 54% (95% CI: −37% to 85%) in the age group 30–39 and 32% (95% CI: −3% to 56%) in those aged 40 or more. Conclusions: BCG efficacy against leprosy may well last for three decades and possibly even longer. BCG vaccination must have contributed to worldwide reduction in leprosy incidence. [Copyright &y& Elsevier]

The article discusses the uncertainty related to the effectiveness of Bacillus Calmette Guérin (BCG) vaccine against tuberculosis. It mentions that the doubt about the vaccine's efficiency emerged after some studies revealed the failure of BCG to protect adults in other populations. It suggests clinicians to be fully cautious when recommending BCG vaccination because of the evidence that its protection seems to fall with time. Furthermore, it discourages the administration of BCG to infected individuals and to those who already vaccinated.

Background: A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection.Methods: We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection.Findings: We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0-∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities.Interpretation: The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy.Funding: Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. [ABSTRACT FROM AUTHOR]

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

Background: Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals.Methods: In this retrospective population-based cohort study, we studied Norwegian-born individuals aged 12-50 years who were tuberculin skin test (TST) negative and eligible for BCG vaccination as part of the last round of Norway's mandatory mass tuberculosis screening and BCG vaccination programme between 1962 and 1975. We excluded individuals who had tuberculosis before or in the year of screening and those with unknown TST and BCG status. We obtained TST and BCG information and linked it to the National Tuberculosis Register, population and housing censuses, and the population register for emigrations and deaths. We followed individuals up to their first tuberculosis episode, emigration, death, or Dec 31, 2011. We used Cox regressions to estimate VE against all tuberculosis and just pulmonary tuberculosis by time since vaccination, adjusted for age, time, county-level tuberculosis rates, and demographic and socioeconomic indicators.Findings: Median follow-up was 41 years (IQR 32-49) for 83 421 BCG-unvaccinated and 44 years (41-46) for 297 905 vaccinated individuals, with 260 tuberculosis episodes. Tuberculosis rates were 3·3 per 100 000 person-years in unvaccinated and 1·3 per 100 000 person-years in vaccinated individuals. The adjusted average VE during 40 year follow-up was 49% (95% CI 26-65), although after 20 years, the VE was not significant (up to 9 years VE [excluding tuberculosis episodes in the first 2 years] 61% [95% CI 24-80]; 10-19 years 58% [27-76]; 20-29 years 38% [-32 to 71]; 30-40 years 42% [-24 to 73]). VE against pulmonary tuberculosis up to 9 years (excluding tuberculosis episodes in the first 2 years) was 67% (95% CI 27-85), 10-19 years was 63% (32-80), 20-29 years was 50% (-19 to 79), and 30-40 years was 40% (-46 to 76).Interpretation: Findings are consistent with long-lasting BCG protection, but waning of VE with time. The vaccine could be more cost effective than has been previously estimatedFunding: Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine. [ABSTRACT FROM AUTHOR]

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

Abstract: To estimate the proportion of children in day-care centres with incomplete vaccination and to identify associated risk factors, we conducted a cross-sectional study among 258 children less than 18 months of age attending public and philanthropic day-care centres in the city of Sao Paulo, Brazil. Interviews, blood collection and anthropometry were performed. Unconditional logistic regression was adjusted for incomplete vaccination risk factors. 10.9% of children had incomplete vaccination. Children who were born prematurely (OR=4.27; p =0.004), or were malnourished (OR=4.99; p =0.049), or lived in inadequate housing (OR=2.88; p =0.039), or whose mothers had had poor prenatal care (OR=4.98; p =0.040) were more likely to have incomplete vaccination. Opportunities are being missed to identify children with incomplete vaccination; strategies to enhance vaccination coverage should pay special attention to the needs of families living in inadequate housing; and health promotion actions in primary health facilities and day-care centres should be performed as concomitant activities. [Copyright &y& Elsevier]

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

Abstract: BCG scar has been used as an indicator of vaccination with BCG in the past, but the validity of scar among HIV-positive children is still unknown. The validity of BCG scar reading among such children was estimated, using three different gold standards. The sensitivity ranged from 81.3% (95%-CI: 78.0–84.2) to 91.6% (95%-CI: 88.4–94.0), when the gold standards were, respectively, information from the adult responsible for the child and the vaccination card. The specificity ranged from 90.5% (95% CI: 81.6–95.5) to 94.1% (95% CI: 87.7–97.4), when the gold standards were, respectively, the vaccination card and information from the adult responsible for the child. Reading of BCG scar was shown to be a good indicator for vaccination in the past, among HIV-infected children. [Copyright &y& Elsevier]

Background: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. Methodology and findings: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. Conclusion: Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide. Trial registration: ClinicalTrials.gov: [ABSTRACT FROM AUTHOR]

Background: International migration to middle-income countries is increasing and its health consequences, in particular increasing transmission rates of tuberculosis (TB), deserve consideration. Migration and TB are a matter of concern in high-income countries and targeted screening of migrants for active and latent TB infection is a main strategy to manage risk and minimize transmission. In this paper, we discuss some aspects of TB control and migration in the context of middle-income countries, together with the prospect of responding with equitable and comprehensive policies.Main Body: TB rates in middle-income countries remain disproportionally high among the poorest and most vulnerable groups in large cities where most migrant populations are concentrated. Policies that tackle migrant TB in high-income countries may be inadequate for middle-income countries because of their different socio-economic and cultural scenarios. Strategies to control TB in these settings must take into account the characteristics of middle-income countries and the complexity of TB as a disease of poverty. Intersectoral policies of social protection such as cash-transfer programs help reducing poverty and improving health in vulnerable populations. We address the development of new approaches to improve well-established strategies including contact tracing and active and latent TB screening as an 'add on' to the existing health care guidelines of conditional cash transfer programs. In addition, we discuss how it might improve health and welfare among both poor migrants and locally-born populations. Authorities from middle-income countries should recognise that migrants are a vulnerable social group and promote cooperation efforts between sending and receiving countries for mitigation of poverty and prevention of disease in this group.Conclusions: Middle-income countries have long sent migrants overseas. However, the influx of large migrant populations into their societies is relatively new and a growing phenomenon and it is time to set comprehensive goals to improve health among these communities. Conditional cash transfer policies with TB screening and strengthening of DOTS are some strategies that deserve attention. Reduction of social and health inequality among migrants should be incorporated into concerted actions to meet TB control targets. [ABSTRACT FROM AUTHOR]

Background Helminths are modulators of the host immune system, and infections with these parasites have been associated with protection against allergies and autoimmune diseases. The human host is often infected with multiple helminth parasites and most studies to date have investigated the effects of helminths in the context of infections with single parasite or types of parasites (e.g. geohelminths). In this study, we investigated how co-infections with three nematodes affect markers of allergic inflammation and asthma in children. We selected Ascaris lumbricoides and Trichuris trichiura, two parasites that inhabit the human intestine and Toxocara spp (Toxocara canis and/or T. cati), intestinal roundworms of dogs and cats that cause systemic larval infection in humans. These parasites were selected as the most prevalent helminth parasites in our study population. Results 36.4% of children were infected with one parasite; 12.7% with 2 and 5.2% with 3. Eosinophilia >4% and >10% was present in 74.3% and 25.5% of the children, respectively. Total IgE > 200 IU/mL, sIgE ⩾ 0.70 kU/L and SPT positivity were present in 59.7%, 37.1% and 30% of the children, respectively. 22.7% had recent asthma (12.0% non-atopic and 10.7% atopic). Helminth infections were associated in a dose-dependent way to decrease in the prevalence of SPT and increase in eosinophilia, total IgE, and the production of the regulatory cytokine IL-10 by unstimulated peripheral blood leukocytes. No association with asthma was observed. Conclusions Helminth co-infections in this population were associated with increased markers of the Th2 immune response, and with a host immune regulatory phenotype that may suppress allergic effector responses such as immediate hypersensitivity reactions in the skin. [ABSTRACT FROM AUTHOR]

Background: Social determinants can affect the transmission of leprosy and its progression to disease. Not much is known about the effectiveness of welfare and primary health care policies on the reduction of leprosy occurrence. The aim of this study is to evaluate the impact of the Brazilian cash transfer (Bolsa Família Program-BFP) and primary health care (Family Health Program-FHP) programs on new case detection rate of leprosy. Methodology/Principal Findings: We conducted the study with a mixed ecological design, a combination of an ecological multiple-group and time-trend design in the period 2004–2011 with the Brazilian municipalities as unit of analysis. The main independent variables were the BFP and FHP coverage at the municipal level and the outcome was new case detection rate of leprosy. Leprosy new cases, BFP and FHP coverage, population and other relevant socio-demographic covariates were obtained from national databases. We used fixed-effects negative binomial models for panel data adjusted for relevant socio-demographic covariates. A total of 1,358 municipalities were included in the analysis. In the studied period, while the municipal coverage of BFP and FHP increased, the new case detection rate of leprosy decreased. Leprosy new case detection rate was significantly reduced in municipalities with consolidated BFP coverage (Risk Ratio 0.79; 95% CI = 0.74–0.83) and significantly increased in municipalities with FHP coverage in the medium (72–95%) (Risk Ratio 1.05; 95% CI = 1.02–1.09) and higher coverage tertiles (>95%) (Risk Ratio 1.12; 95% CI = 1.08–1.17). Conclusions: At the same time the Family Health Program had been effective in increasing the new case detection rate of leprosy in Brazil, the Bolsa Família Program was associated with a reduction of the new case detection rate of leprosy that we propose reflects a reduction in leprosy incidence. Author Summary: Leprosy is considered a poverty related disease. Not much is known about the effectiveness of welfare and primary health care policies on reduction of leprosy occurrence. We conducted a study to evaluate the impact of the Brazilian conditional cash transfer (Bolsa Família Program) and the Primary Health Care (Family Health Program) on the new case detection rate of leprosy in the period 2004–2011 in the Brazilian municipalities. All variables were obtained from national databases and a total of 1,358 municipalities were included in the analysis. The new case detection rate of leprosy was significantly reduced in municipalities with intermediate, high, and consolidated BFP coverage. There was a significant increase in new case detection rate of leprosy as Family Health Program coverage increased. We interpret this to mean that at the same time the primary health care had been effective increasing the new case detection rate of leprosy in Brazil, there is an impact of conditional cash transfer in the reduction of the new case detection rate of leprosy due to reduction in leprosy incidence. We expect that these results contribute with arguments to the discussion on the relationship between distributive social policies and health conditions of the population in developing countries worldwide. [ABSTRACT FROM AUTHOR]

Background: Social determinants can affect the transmission of leprosy and its progression to disease. Not much is known about the effectiveness of welfare and primary health care policies on the reduction of leprosy occurrence. The aim of this study is to evaluate the impact of the Brazilian cash transfer (Bolsa Família Program-BFP) and primary health care (Family Health Program-FHP) programs on new case detection rate of leprosy. Methodology/Principal Findings: We conducted the study with a mixed ecological design, a combination of an ecological multiple-group and time-trend design in the period 2004–2011 with the Brazilian municipalities as unit of analysis. The main independent variables were the BFP and FHP coverage at the municipal level and the outcome was new case detection rate of leprosy. Leprosy new cases, BFP and FHP coverage, population and other relevant socio-demographic covariates were obtained from national databases. We used fixed-effects negative binomial models for panel data adjusted for relevant socio-demographic covariates. A total of 1,358 municipalities were included in the analysis. In the studied period, while the municipal coverage of BFP and FHP increased, the new case detection rate of leprosy decreased. Leprosy new case detection rate was significantly reduced in municipalities with consolidated BFP coverage (Risk Ratio 0.79; 95% CI  = 0.74–0.83) and significantly increased in municipalities with FHP coverage in the medium (72–95%) (Risk Ratio 1.05; 95% CI  = 1.02–1.09) and higher coverage tertiles (>95%) (Risk Ratio 1.12; 95% CI  = 1.08–1.17). Conclusions: At the same time the Family Health Program had been effective in increasing the new case detection rate of leprosy in Brazil, the Bolsa Família Program was associated with a reduction of the new case detection rate of leprosy that we propose reflects a reduction in leprosy incidence. [ABSTRACT FROM AUTHOR]

Introduction: Despite the availability of treatment and a vaccine, tuberculosis continues to be a public health problem worldwide. Mental disorders might contribute to the burden of the disease. Objective: The objective of this study was to investigate the association between common mental disorders and tuberculosis. Methods: A matched case-control study was conducted. The study population included symptomatic respiratory patients who attended three referral hospitals and six community clinics in the city of Salvador, Brazil. A doctor’s diagnosis defined potential cases and controls. Cases were newly diagnosed tuberculosis cases, and controls were symptomatic respiratory patients for whom tuberculosis was excluded as a diagnosis by the attending physician. Cases and controls were ascertained in the same clinic. Data collection occurred between August 2008 and April 2010. The study instruments included a structured interview, a self-reporting questionnaire for the identification of common mental disorders, and a questionnaire for alcoholism. An univariate analysis included descriptive procedures (with chi-square statistics), and a multivariate analysis used conditional logistic regression. Results: The mean age of the cases was 38 years, and 61% of the cases were males. After adjusting for potential confounders, the odds of tuberculosis were significantly higher in patients dignosed with a common mental disorder (OR: 1.34; 95% CI 1.05–1.70). Conclusion: There appears to be a positive and independent association between common mental disorders and tuberculosis; further epidemiological studies are required to increase our understanding of the possible biological and social mechanisms responsible for this association. Independent of the direction of the association, this finding has implications for the provision of care for mental disorders and for tuberculosis. [ABSTRACT FROM AUTHOR]

Background: The challenge of diagnosing smear-negative pulmonary TB (tuberculosis) in people living with HIV justifies the use of instruments other than the smear test for diagnosing the disease. Considering the clinical-radiological similarities of TB amongst HIV-infected adults and children, the proposal of this study was to assess the accuracy of a scoring system used to diagnose smear-negative pulmonary TB in children and adolescents, in HIV-infected adults suspected of having smear-negative pulmonary TB. Methods: A Phase III validation study aiming to assess the diagnostic accuracy of a scoring system for diagnosing smear-negative pulmonary TB in HIV-infected adults. The study assessed sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values of the scoring system. Three versions of the scoring system were tested. Results: From a cohort of 2,382 (HIV-infected adults), 1276 were investigated and 128 were diagnosed with pulmonary TB. Variables associated with the diagnosis of TB were: coughing, weight loss, fever, malnutrition, chest X-ray, and positive tuberculin test. The best diagnostic performance occurred with the scoring system with new scores, with sensitivity = 81.2% (95%-CI 74.5% –88%), specificity = 78% (75.6% –80.4%), PPV = 29.2% (24.5% –33.9%) and NPV = 97.4% (96.4% –98.4%), LR+ = 3.7 (3.4–4.0) and LR− = 0.24 (0.2–0.4). Conclusion: The proposed scoring system (with new scores) presented a good capacity for discriminating patients who did not have pulmonary TB, in the studied population. Further studies are necessary in order to validate it, thus permitting the assessment of its use in diagnosing smear-negative pulmonary TB in HIV-infected adults. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the association between food and nutrition insecurity and asthma in children from Latin America.DesignCross-sectional study.SettingSão Francisco do Conde, Bahia, north-eastern Brazil.SubjectsThe study included 1307 children aged 6–12 years from public elementary schools. Asthma symptoms were collected using a questionnaire that was translated and adapted from the International Study of Asthma and Allergies in Childhood, phase III. The diagnosis of asthma was determined based on reports of wheezing in the previous 12 months. The Brazilian Food Insecurity Scale was used to identify food insecurity. We also obtained demographic, socio-economic and anthropometric information for each participant. We used multivariate logistic regression analyses to assess the associations of interest.ResultsOf the children surveyed, 10·4 % had a history of wheezing and 64·5 % had some degree of food and nutrition insecurity. We found a positive dose–response relationship and statistically significant associations of asthma with moderate (OR = 1·71, 95 % CI 1·01, 2·89) and severe (OR = 2·51, 95 % CI 1·28, 4·93) food and nutrition insecurity.ConclusionsThe results show that moderate and severe food and nutrition insecurity are markers of vulnerability to wheezing. It is important to note that the results of studies in this field have potential implications for social policies that promote food security. Further studies to identify the mechanisms involved in the relationship between food and nutrition insecurity and asthma are needed. [ABSTRACT FROM AUTHOR]

Objective: To identify the incidence of and risk factors for tuberculosis in people living with HIV (PLHIV). Design: Observational, prospective cohort study. Methods: A total of 2069 HIV-infected patients was observed between July 2007 and December 2010. The Kaplan-Meier method was used to estimate the probability of survival free of tuberculosis, and Cox regression analysis to identify risk factors associated with the development of tuberculosis. Results: Survival free of tuberculosis (TB) was 91%. The incidence rate of tuberculosis was 2.8 per 100 persons/years. Incidence of tuberculosis was higher when subjects had CD4 cell count <200 cells/mm3; were not on antiretroviral therapy; in those who had, a body mass index <18.5 kg/m2, anemia (or were not tested for it), were illiterate or referred previous tuberculosis treatment at entry into the cohort. Those not treated for latent TB infection had a much higher risk (HR = 7.9) of tuberculosis than those with a negative tuberculin skin test (TST). Having a TST≥5 mm but not being treated for latent TB infection increased the risk of incident tuberculosis even in those with a history of previous tuberculosis. Conclusions: Preventive actions to reduce the risk of TB in people living with HIV should include an appropriate HAART and treatment for latent TB infection in those with TST≥5 mm. The actions towards enabling rigorous implementation of treatment of latent TB infection and targeting of PLHIV drug users both at the individual and in public health level can reduce substantially the incidence of TB in PLHIV. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the relative importance of body mass index (BMI) and abdominal obesity in the prevalence of wheezing in Brazilian children. Materials and methods. This is a cross-sectional study of male and female students, 6-12 years old, from the public elementary schools of São Francisco do Conde, Bahia, Northeast Brazil. Reports of wheezing in the past 12 months were collected using a questionnaire from the International Study of Asthma and Allergies in Childhood Program (ISAAC) phase III, adapted to Portuguese. Anthropometric, demographic, and socioeconomic information was collected. Multivariate logistic regression analyses were used to assess the associations of interest. Results. Of the children surveyed, 10.6% reported wheezing. Excess weight was observed in 16.2%, 10.5%, and 7.9% of the sample, measured by BMI, waist circumference (WC), and the waist-to-height ratio (WHtR), respectively. The percentage of patients with wheezing attributable to BMI ≥ 85th percentile (8.2%) slightly exceeded those identified with abdominal obesity, WC  ≥ 80th percentile (7.3%) and WHtR  > 0.5 (7.1%). Conclusion. The results suggest that an excess of fat deposits, either in the abdominal region or elsewhere in the body, increased the risk of wheezing. Since obesity is an important public health problem worldwide, control of this problem may partially reduce the occurrence of wheezing in youth. [ABSTRACT FROM AUTHOR]

Background: Toxocara canis and T. cati are parasites of dogs and cats, respectively, that infect humans and cause human toxocariasis. Infection may cause asthma-like symptoms but is often asymptomatic and is associated with a marked eosinophilia. Previous epidemiological studies indicate that T. canis infection may be associated with the development of atopy and asthma. Objectives: To investigate possible associations between Toxocara spp. seropositivity and atopy and childhood wheezing in a population of children living in non-affluent areas of a large Latin American city. Methods: The study was conducted in the city of Salvador, Brazil. Data on wheezing symptoms were collected by questionnaire, and atopy was measured by the presence of aeroallergen-specific IgE (sIgE). Skin prick test (SPT), total IgE and peripheral eosinophilia were measured. Toxocara seropositivity was determined by the presence of anti-Toxocara IgG antibodies, and intestinal helminth infections were determined by stool microscopy. Findings: Children aged 4 to 11 years were studied, of whom 47% were seropositive for anti-Toxocara IgG; eosinophilia >4% occurred in 74.2% and >10% in 25.4%; 59.6% had elevated levels of total IgE; 36.8% had sIgE≥0.70 kU/L and 30.4% had SPT for at least one aeroallergen; 22.4% had current wheezing symptoms. Anti-Toxocara IgG was positively associated with elevated eosinophils counts, total IgE and the presence of specific IgE to aeroallergens but was inversely associated with skin prick test reactivity. Conclusion: The prevalence of Toxocara seropositivity was high in the studied population of children living in conditions of poverty in urban Brazil. Toxocara infection, although associated with total IgE, sIgE and eosinophilia, may prevent the development of skin hypersensitivity to aeroallergens, possibly through increased polyclonal IgE and the induction of a modified Th2 immune reaction. [ABSTRACT FROM AUTHOR]

Recent studies have shown that asthma represents a major health issue not only in children of developed countries but also in urban centers in some middle-income countries. Brazil has one of the highest prevalences of asthma worldwide. Recently, interest has grown in the relationship between psychosocial factors and asthma. This article examines the relationship between maternal mental disorders and the prevalence of asthma in low-income children from an inner city area of Salvador in the state of Bahia, Brazil, and is part of the SCAALA program (Social Change, Allergy and Asthma in Latin America). A total of 1,087 children between the ages of 5 and 12 were investigated, together with their mothers. The mothers’ mental health was evaluated using the SRQ-20, an instrument for the psychiatric screening of minor psychiatric disorders (depression, anxiety and somatic complaints). The prevalence of asthma was investigated using the ISAAC survey, a standardized, validated questionnaire for asthma and other allergic diseases. Cases were defined as asthma if the patient reported having had wheezing in the previous 12 months in addition to at least one of the following: having asthma, wheezing while exercising, waking during the night because of wheezing, or having had at least four episodes of wheezing in the previous 12 months. Atopy was defined as a positive skin prick test to allergens. The presence of minor psychiatric disorders in the mothers was significantly associated with the presence of asthma in the children, and this association was consistent with all forms of asthma, irrespective of whether it was atopic or nonatopic. Future studies should be carried out to further investigate this association and the potential biological mechanisms involved. Programs for asthma control should include strategies for stress reduction and psychological support for the families of asthmatic children. [ABSTRACT FROM AUTHOR]

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

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

Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44–3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus. • Childhood asthma is associated with the 17q21 region in admixed populations. • Both, allergic and non-allergic childhood asthma, are associated with the 17q21 region. • The association of childhood asthma with the 17q21 region is independent of sex or ancestry. • Seropositivity for Herpes zoster virus infection modifier the association of childhood asthma with the 17q21 region [ABSTRACT FROM AUTHOR]

Background: Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking.Methods: A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001-2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up.Results: Smoking (OR 2.53, 95% CI 1.23-5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46-8.93) were found to be independently associated with relapse of tuberculosis.Conclusions: Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. [ABSTRACT FROM AUTHOR]