Income determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians.

Living with extremely low-income is an important risk factor for HIV/AIDS and can be mitigated by conditional cash transfers. Using a cohort of 22.7 million low-income individuals during 9 years, we evaluated the effects of the world's largest conditional cash transfer, the Programa Bolsa Família, on HIV/AIDS-related outcomes. Exposure to Programa Bolsa Família was associated with reduced AIDS incidence by 41% (RR:0.59; 95%CI:0.57-0.61), mortality by 39% (RR:0.61; 95%CI:0.57-0.64), and case fatality rates by 25% (RR:0.75; 95%CI:0.66-0.85) in the cohort, and Programa Bolsa Família effects were considerably stronger among individuals of extremely low-income [reduction of 55% for incidence (RR:0.45, 95% CI:0.42-0.47), 54% mortality (RR:0.46, 95% CI:0.42-0.49), and 37% case-fatality (RR:0.63, 95% CI:0.51 -0.76)], decreasing gradually until having no effect in individuals with higher incomes. Similar effects were observed on HIV notification. Programa Bolsa Família impact was also stronger among women and adolescents. Several sensitivity and triangulation analyses demonstrated the robustness of the results. Conditional cash transfers can significantly reduce AIDS morbidity and mortality in extremely vulnerable populations and should be considered an essential intervention to achieve AIDS-related sustainable development goals by 2030.

Subsidised housing and diabetes mortality: a retrospective cohort study of 10 million low-income adults in Brazil.

INTRODUCTION: Housing-related factors can be predictors of health, including of diabetes outcomes. We analysed the association between subsidised housing residency and diabetes mortality among a large cohort of low-income adults in Brazil. RESEARCH DESIGN AND METHODS: A cohort of 9 961 271 low-income adults, observed from January 2010 to December 2015, was created from Brazilian administrative records of social programmes and death certificates. We analysed the association between subsidised housing residency and time to diabetes mortality using a Cox model with inverse probability of treatment weighting and regression adjustment. We assessed inequalities in this association by groups of municipality Human Development Index. Diabetes mortality included diabetes both as the underlying or a contributory cause of death. RESULTS: At baseline, the mean age of the cohort was 40.3 years (SD 15.6 years), with a majority of women (58.4%). During 29 238 920 person-years of follow-up, there were 18 775 deaths with diabetes as the underlying or a contributory cause. 340 683 participants (3.4% of the cohort) received subsidised housing. Subsidised housing residents had a higher hazard of diabetes mortality compared with non-residents (HR 1.17; 95% CI 1.05 to 1.31). The magnitude of this association was more pronounced among participants living in municipalities with lower Human Development Index (HR 1.30; 95% CI 1.04 to 1.62). CONCLUSIONS: Subsidised housing residents had a greater risk of diabetes mortality, particularly those living in low socioeconomic status municipalities. This finding suggests the need to intensify diabetes prevention and control actions and prompt treatment of the diabetes complications among subsidised housing residents, particularly among those living in low socioeconomic status municipalities.

The effect of primary health care on tuberculosis in a nationwide cohort of 7·3 million Brazilian people: a quasi-experimental study.

BACKGROUND: Universal health coverage is one of the WHO End TB Strategy priority interventions and could be achieved-particularly in low-income and middle-income countries-through the expansion of primary health care. We evaluated the effects of one of the largest primary health-care programmes in the world, the Brazilian Family Health Strategy (FHS), on tuberculosis morbidity and mortality using a nationwide cohort of 7·3 million individuals over a 10-year study period. METHODS: We analysed individuals who entered the 100 Million Brazilians Cohort during the period Jan 1, 2004, to Dec 31, 2013, and compared residents in municipalities with no FHS coverage with residents in municipalities with full FHS coverage. We used a cohort design with multivariable Poisson regressions, adjusted for all relevant demographic and socioeconomic variables and weighted with inverse probability of treatment weighting, to estimate the effect of FHS on tuberculosis incidence, mortality, cure, and case fatality. We also performed a range of stratifications and sensitivity analyses. FINDINGS: FHS exposure was associated with lower tuberculosis incidence (rate ratio [RR] 0·78, 95% CI 0·72-0·84) and mortality (0·72, 0·55-0·94), and was positively associated with tuberculosis cure rates (1·04, 1·00-1·08). FHS was also associated with a decrease in tuberculosis case-fatality rates, although this was not statistically significant (RR 0·84, 95% CI 0·55-1·30). FHS associations were stronger among the poorest individuals for all the tuberculosis indicators. INTERPRETATION: Community-based primary health care could strongly reduce tuberculosis morbidity and mortality and decrease the unequal distribution of the tuberculosis burden in the most vulnerable populations. During the current marked rise in global poverty due to the COVID-19 pandemic, investments in primary health care could help protect against the expected increases in tuberculosis incidence worldwide and contribute to the attainment of the End TB Strategy goals. FUNDING: TB Modelling and Analysis Consortium (Bill & Melinda Gates Foundation), Wellcome Trust, and Brazilian Ministry of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Estimating underreporting of leprosy in Brazil using a Bayesian approach.

BACKGROUND: Leprosy remains concentrated among the poorest communities in low-and middle-income countries and it is one of the primary infectious causes of disability. Although there have been increasing advances in leprosy surveillance worldwide, leprosy underreporting is still common and can hinder decision-making regarding the distribution of financial and health resources and thereby limit the effectiveness of interventions. In this study, we estimated the proportion of unreported cases of leprosy in Brazilian microregions. METHODOLOGY/PRINCIPAL FINDINGS: Using data collected between 2007 to 2015 from each of the 557 Brazilian microregions, we applied a Bayesian hierarchical model that used the presence of grade 2 leprosy-related physical disabilities as a direct indicator of delayed diagnosis and a proxy for the effectiveness of local leprosy surveillance program. We also analyzed some relevant factors that influence spatial variability in the observed mean incidence rate in the Brazilian microregions, highlighting the importance of socioeconomic factors and how they affect the levels of underreporting. We corrected leprosy incidence rates for each Brazilian microregion and estimated that, on average, 33,252 (9.6%) new leprosy cases went unreported in the country between 2007 to 2015, with this proportion varying from 8.4% to 14.1% across the Brazilian States. CONCLUSIONS/SIGNIFICANCE: The magnitude and distribution of leprosy underreporting were adequately explained by a model using Grade 2 disability as a marker for the ability of the system to detect new missing cases. The percentage of missed cases was significant, and efforts are warranted to improve leprosy case detection. Our estimates in Brazilian microregions can be used to guide effective interventions, efficient resource allocation, and target actions to mitigate transmission.

CIDACS-RL: a novel indexing search and scoring-based record linkage system for huge datasets with high accuracy and scalability.

BACKGROUND: Record linkage is the process of identifying and combining records about the same individual from two or more different datasets. While there are many open source and commercial data linkage tools, the volume and complexity of currently available datasets for linkage pose a huge challenge; hence, designing an efficient linkage tool with reasonable accuracy and scalability is required. METHODS: We developed CIDACS-RL (Centre for Data and Knowledge Integration for Health - Record Linkage), a novel iterative deterministic record linkage algorithm based on a combination of indexing search and scoring algorithms (provided by Apache Lucene). We described how the algorithm works and compared its performance with four open source linkage tools (AtyImo, Febrl, FRIL and RecLink) in terms of sensitivity and positive predictive value using gold standard dataset. We also evaluated its accuracy and scalability using a case-study and its scalability and execution time using a simulated cohort in serial (single core) and multi-core (eight core) computation settings. RESULTS: Overall, CIDACS-RL algorithm had a superior performance: positive predictive value (99.93% versus AtyImo 99.30%, RecLink 99.5%, Febrl 98.86%, and FRIL 96.17%) and sensitivity (99.87% versus AtyImo 98.91%, RecLink 73.75%, Febrl 90.58%, and FRIL 74.66%). In the case study, using a ROC curve to choose the most appropriate cut-off value (0.896), the obtained metrics were: sensitivity = 92.5% (95% CI 92.07-92.99), specificity = 93.5% (95% CI 93.08-93.8) and area under the curve (AUC) = 97% (95% CI 96.97-97.35). The multi-core computation was about four times faster (150 seconds) than the serial setting (550 seconds) when using a dataset of 20 million records. CONCLUSION: CIDACS-RL algorithm is an innovative linkage tool for huge datasets, with higher accuracy, improved scalability, and substantially shorter execution time compared to other existing linkage tools. In addition, CIDACS-RL can be deployed on standard computers without the need for high-speed processors and distributed infrastructures.

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

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

Propensity Score Methods in Health Technology Assessment: Principles, Extended Applications, and Recent Advances.

Randomized clinical trials (RCT) are accepted as the gold-standard approaches to measure effects of intervention or treatment on outcomes. They are also the designs of choice for health technology assessment (HTA). Randomization ensures comparability, in both measured and unmeasured pretreatment characteristics, of individuals assigned to treatment and control or comparator. However, even adequately powered RCTs are not always feasible for several reasons such as cost, time, practical and ethical constraints, and limited generalizability. RCTs rely on data collected on selected, homogeneous population under highly controlled conditions; hence, they provide evidence on efficacy of interventions rather than on effectiveness. Alternatively, observational studies can provide evidence on the relative effectiveness or safety of a health technology compared to one or more alternatives when provided under the setting of routine health care practice. In observational studies, however, treatment assignment is a non-random process based on an individual's baseline characteristics; hence, treatment groups may not be comparable in their pretreatment characteristics. As a result, direct comparison of outcomes between treatment groups might lead to biased estimate of the treatment effect. Propensity score approaches have been used to achieve balance or comparability of treatment groups in terms of their measured pretreatment covariates thereby controlling for confounding bias in estimating treatment effects. Despite the popularity of propensity scores methods and recent important methodological advances, misunderstandings on their applications and limitations are all too common. In this article, we present a review of the propensity scores methods, extended applications, recent advances, and their strengths and limitations.

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective.

Effectiveness of rotavirus vaccine against hospitalized rotavirus diarrhea: A case-control study.

Rotavirus is one of the leading cause of hospitalization and outpatients visits among children under five years. This study evaluated overall and genotype-specific vaccine effectiveness of oral monovalent rotavirus vaccine (G1P[8] strain) in preventing hospital admission of Brazilian children with rotavirus acute diarrhea. A hospital based case-control study was conducted in five Regions of Brazil using the National Rotavirus Acute Diarrhea Surveillance System from July 2008 to August 2011. A total of 215 cases (aged 4-24 months) admitted with confirmed rotavirus diarrhea were recruited and 1961 controls hospitalized without diarrhea were frequency matched by sex and age group to cases. Two-dose adjusted vaccine effectiveness (adjusted by year of birth and the frequency matching variables) was 76% (95%CI: 58-86) lasting for two years. Effectiveness controlled by the available potential confounders was 72% (95%CI: 44-85), suggesting no appreciable confounding by those factors for which adjustment was made. In a half of the cases the rotavirus genotype was G2P[4] and in 15% G1P[8]. Genotype-specific VE (two doses) was 89% (95%CI: 78-95), for G1P[8] and 76% (95%CI: 64-84) for G2P[4]. For all G1, it was 74% (95%CI: 35-90), for all G2, 76% (95%CI: 63-84), and for all non G1/G2 genotypes, 63% (95%CI: -27-99). Effectiveness for one dose was 62% (95%CI: 39-97). Effectiveness of two-dose monovalent rotavirus vaccine in preventing hospital admission with rotavirus diarrhea was high, lasted for two years and it was similar against both G1P[8] and G2P[4]. Based on the findings of the study we recommend the continued use of rotavirus in the Brazilian National Immunization Program and the monitoring of the early emergence of unusual and novel rotavirus genotypes.

Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial.

BACKGROUND: Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. METHODS: We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. FINDINGS: We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3-66·7) per 100,000 person-years in the BCG vaccination group and 72·7 (62·8-86·8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3-43%). In Salvador, where vaccine effectiveness was 34% (8-53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11,980 BCG vaccinations. INTERPRETATION: Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. FUNDING: UK Department for International Development, National Health Foundation.

Evidence of an effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: second report of the BCG-REVAC cluster-randomised trial.

BCG revaccination is still used in some tuberculosis endemic countries. Until now, the little evidence available suggested that BCG revaccination confers very limited additional protection, although there was no information on whether protection depends on the setting and age of revaccination, or if protection increases with time since vaccination. Here we report on an extended follow up of the BCG-REVAC trial, a cluster randomised trial conducted in the Brazilian cities Salvador and Manaus including over 200,000 children aged 7-14 years aimed to evaluate the efficacy of BCG revaccination in children who had received neonatal BCG vaccination. With the extended follow-up (9 years) and the additional cases accrued we now have enough power to report vaccine efficacy separately for the two cities (with different distances from Equator and presumably different prevalence of non-tuberculosis mycobacteria), and by age at vaccination and clinical form. The overall vaccine efficacy was 12% (-2 to 24%) as compared to 9% (-16 to 29%) for the 5-year follow up. Vaccine efficacy was higher in Salvador (19%, 3 to 33%) than in Manaus (1%, -27 to 27%) with the highest vaccine efficacy in children from Salvador aged <11 years at revaccination (33%, 3 to 54%). The findings are in line with the hypothesis that BCG vaccination offers higher efficacy in low NTMb prevalence, and show that revaccination with BCG can offer weak protection in selected subgroups.

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > 5 mm, > 10 mm, and > 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > 10 mm was 14.2 percent (95 percent confidence interval (CI) = 8.0 percent-20.3 percent) for children with no BCG scar, 21.3 percent (95 percent CI = 18.5 percent-24.1 percent) for children with one BCG scar, and 45.0 percent (95 percent CI = 32.0 percent-58.0 percent) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > 5 mm and > 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > 5 mm and > 10 mm did not vary with age. There was no evidence for BCG effect on the results > 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage