Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

BACKGROUND: Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. METHODS: We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. CONCLUSION: Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes

The burden of tuberculosis and attributable risk factors in Brazil, 1990-2017: results from the Global Burden of Disease Study 2017.

BACKGROUND: Tuberculosis (TB) continues to be an important cause of fatal and non-fatal burden in Brazil. In this study, we present estimates for TB burden in Brazil from 1990 to 2017 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017). METHODS: This descriptive study used GBD 2017 findings to report years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of TB in Brazil by sex, age group, HIV status, and Brazilian states, from 1990 to 2017. We also present the TB burden attributable to independent risk factors such as smoking, alcohol use, and diabetes. Results are reported in absolute number and age-standardized rates (per 100,000 inhabitants) with 95% uncertainty intervals (UIs). RESULTS: In 2017, the number of DALYs due to TB (HIV-negative and HIV-positive combined) in Brazil was 284,323 (95% UI: 240,269-349,265). Among HIV-negative individuals, the number of DALYs was 196,366 (95% UI: 189,645-202,394), while 87,957 DALYs (95% UI: 50,624-146,870) were estimated among HIV-positive individuals. Between 1990 and 2017, the absolute number and age-standardized rates of DALYs due to TB at the national level decreased by 47.0% and 68.5%, respectively. In 2017, the sex-age-specific TB burden was highest among males and in children under-1 year and the age groups 45-59 years. The Brazilian states with the highest age-standardized DALY rates in 2017 were Rio de Janeiro, Pernambuco, and Amazonas. Age-standardized DALY rates decreased for all 27 Brazilian states between 1990 and 2017. Alcohol use accounted for 47.5% of national DALYs due to TB among HIV-negative individuals in 2017, smoking for 17.9%, and diabetes for 7.7%. CONCLUSIONS: GBD 2017 results show that, despite the remarkable progress in reducing the DALY rates during the period, TB remains as an important and preventable cause of health lost to due premature death and disability in Brazil. The findings reinforce the importance of strengthening TB control strategies in Brazil through integrated and multisectoral actions that enable the access to prevention, early diagnosis, and timely treatment, with emphasis on high-risk groups and populations most vulnerable to the disease in the country

Tuberculosis in Brazil and cash transfer programs: A longitudinal database study of the effect of cash transfer on cure rates.

INTRODUCTION: Tuberculosis incidence is disproportionately high among people in poverty. Cash transfer programs have become an important strategy in Brazil fight inequalities as part of comprehensive poverty alleviation policies. This study was aimed at assessing the effect of being a beneficiary of a governmental cash transfer program on tuberculosis (TB) treatment cure rates. METHODS: We conducted a longitudinal database study including people ≥18 years old with confirmed incident TB in Brazil in 2015. We treated missing data with multiple imputation. Poisson regression models with robust variance were carried out to assess the effect of TB determinants on cure rates. The average effect of being beneficiary of cash transfer was estimated by propensity-score matching. RESULTS: In 2015, 25,084 women and men diagnosed as new tuberculosis case, of whom 1,714 (6.8%) were beneficiaries of a national cash transfer. Among the total population with pulmonary tuberculosis several determinants were associated with cure rates. However, among the cash transfer group, this association was vanished in males, blacks, region of residence, and people not deprived of their freedom and who smoke tobacco. The average treatment effect of cash transfers on TB cure rates, based on propensity score matching, found that being beneficiary of cash transfer improved TB cure rates by 8% [Coefficient 0.08 (95% confidence interval 0.06-0.11) in subjects with pulmonary TB]. CONCLUSION: Our study suggests that, in Brazil, the effect of cash transfer on the outcome of TB treatment may be achieved by the indirect effect of other determinants. Also, these results suggest the direct effect of being beneficiary of cash transfer on improving TB cure rates

Mapping the tuberculosis scientific landscape among BRICS countries: a bibliometric and network analysis

BACKGROUND The five BRICS (Brazil, Russian, Indian, China, and South Africa) countries bear 49% of the world’s tuberculosis (TB) burden and they are committed to ending tuberculosis. OBJECTIVES The aim of this paper is to map the scientific landscape related to TB research in BRICS countries. METHODS Were combined bibliometrics and social network analysis techniques to map the scientific publications related to TB produced by the BRICS. Was made a descriptive statistical data covering the full period of analysis (1993-2016) and the research networks were made for 2007-2016 (8,366 records). The bubble charts were generated by VantagePoint and the networks by the Gephi 0.9.1 software (Gephi Consortium 2010) from co-occurrence matrices produced in VantagePoint. The Fruchterman-Reingold algorithm provided the networks’ layout. FINDINGS During the period 1993-2016, there were 38,315 peer-reviewed, among them, there were 11,018 (28.7%) articles related by one or more authors in a BRICS: India 38.7%; China 23.8%; South Africa 21.1%; Brazil 13.0%; and Russia 4.5% (The total was greater than 100% because our criterion was all papers with at least one author in a BRICS). Among the BRICS, there was greater interaction between India and South Africa and organisations in India and China had the highest productivity; however, South African organisations had more interaction with countries outside the BRICS. Publications by and about BRICS generally covered all research areas, especially those in India and China covered all research areas, although Brazil and South Africa prioritised infectious diseases, microbiology, and the respiratory system. MAIN CONCLUSIONS An overview of BRICS scientific publications and interactions highlighted the necessity to develop a BRICS TB research plan to increase efforts and funding to ensure that basic science research successfully translates into products and policies to help end the TB epidemic

Impact of roll out of rapid molecular test for tuberculosis in Brazil

Introdução: A tuberculose (TB) ainda se apresenta como um grave problema de saúde pública no mundo, com mais de 10 milhões de casos e 1,3 milhão de mortes anualmente. Em 2020, no Brasil, foram notificados 66.819 casos novos de TB, e aproximadamente 913 casos de TB drogarresistente. Cerca de 4.500 pessoas vão a óbito, anualmente, por TB no país. Com as tecnologias atuais, a melhor estratégia para controlar a transmissão e reduzir a incidência da TB é o diagnóstico e tratamento dos casos pulmonares bacilíferos, associados ao diagnóstico e tratamento da infecção latente. O Brasil incorporou, em 2014, o teste rápido molecular (TRM), recomendando-o como estratégia inicial para diagnóstico da TB e detecção da resistência à rifampicina (TB-RR). A presente tese buscou descrever e analisar o impacto da implantação do teste rápido molecular para tuberculose sobre os indicadores programáticos para o controle da tuberculose no Brasil, e o efeito do teste rápido molecular no início do tratamento em casos de tuberculose resistentes à rifampicina e/ou multidrogarresistente. Métodos: foram realizados estudos observacionais, com dados secundários. O primeiro, trata-se de um estudo ecológico cujas unidades de análise foram os municípios que compõe a rede de teste rápido molecular para TB (RTR-TB), e foram analisados os indicadores da TB antes e depois do início de utilização do TRM. Foi utilizada a modelagem de séries temporais interrompidas pela Regressão de Prais-Winsten. O segundo estudo teve como desenho uma coorte retrospectiva, tomando o indivíduo como unidade de análise. Foi utilizado o método de análise de sobrevida para avaliar o efeito do TRM sobre o tempo entre o diagnóstico e o início do tratamento dos casos novos de TB-RR / TB-MDR. A Regressão de Cox foi utilizada para estimação dos riscos proporcionais. Resultados: no período estudado, a RTR-TB consumiu um total de 1.756.358 cartuchos de TRM, sendo 1.734.935 testes realizados. A notificação de casos novos de TB na série histórica trimestral de janeiro de 2010 a junho de 2014 apresentou tendência estacionária. Após a implantação do TRM-TB, verificou-se uma tendência de aumento médio da ordem de 0,5% (IC 95%: 0,13 - 0,87) de casos novos, por trimestre, e em todo o período pós-intervenção, houve um incremento de 8.241 casos novos de TB nos municípios da RTR-TB, um aumento de 15% (IC 95%: 10,71 - 19,46) no nível de confirmação laboratorial dos casos novos de TB, e uma queda de 8,42% (IC 95%: -15,61 - -0,62) na realização de baciloscopia. Entre 2014 e 2019, 2.071 casos de TB-RR / TB-MDR tiveram o diagnóstico da resistência por meio do TRM, e 1.592 por meio do TSA. Após a incorporação do TRM, houve uma redução no tempo médio de início do tratamento da resistência em 89 dias (p-valor < 0,0001), quando comparado ao TSA. Indivíduos diagnosticados pelo TRM apresentam maior probabilidade de iniciar o tratamento da TB-DR mais precocemente quando comparado aos indivíduos diagnosticados pelo TSA, e essa diferença é mais acentuada até os primeiros 60 dias após o diagnóstico. Indivíduos diagnosticados pelo TSA apresentaram probabilidade 78% menor de iniciar o tratamento nos primeiros 30 dias após o diagnóstico da resistência quanto comparado aos indivíduos diagnosticados pelo TRM (HRadj: 0,22; IC95%: 0,13 - 0,36), e 49% menor probabilidade de iniciar o tratamento nos primeiros seis meses após o diagnóstico quando comparado aos indivíduos diagnosticados pelo TRM (HRadj: 0,51; IC95%: 0,39 - 0,62). Conclusões: o TRM apresentou, de forma global, impacto positivo nas estratégias de controle da TB do Brasil, reestruturando a rede de diagnóstico da doença, aumentando a confirmação laboratorial, e diminuindo o tempo entre o diagnóstico e o início do tratamento da TB-RR / TB-MDR. A incorporação do TRM no SUS propiciou um diagnóstico da doença mais rápido e com maior sensibilidade, viabilizando um diagnóstico muito mais oportuno da TB-RR / TB-MDR, e encurtando o tempo para início do tratamento da TB resistente. A ampliação do diagnóstico rápido molecular por TRM para os municípios que ainda não compõe a RTR-TB podem contribuir para um melhor controle da TB no país.Introduction: Tuberculosis (TB) still is as a serious public health problem in the world, with more than 10 million cases and 1.3 million deaths annually. In 2020, in Brazil, 66.819 new cases of TB and approximately 913 cases of drug-resistant TB were notified. About 4,500 persons die annually from TB in the country. With the current technologies available, the best strategies to control the transmission and to reduce the TB incidence is the diagnosis and treatment of the bacilliferous pulmonary cases, associated with the diagnosis and treatment of latent infection. In 2014, Brazil has incorporated the rapid molecular test (TRM), recommending it as an initial strategy for diagnosing TB and detecting rifampicin resistance (TB-RR). The present thesis describes and analyses the impact of the roll out of the TRM for TB on the programmatic indicators for TB control in Brazil, and the effect of the TRM in the beginning of the treatment in cases of tuberculosis resistant to rifampicin and/or multidrugresistent. Methods: observational studies were performed with routine data. The first study was an ecological study whose units of analysis were the municipalities that make up the rapid molecular testing network for TB (RTR-TB), and TB indicators were analyzed before and after the beginning of TRM use. The modeling of time series interrupted by the Prais-Winsten Regression was used. The second study was a retrospective cohort, whose the individual was the unit of analysis. The survival analysis method was used to assess the effect of TRM on the time between diagnosis and initiation of treatment of new cases of RR-TB / MDR-TB. Cox regression was used to estimate proportional hazards. Results: in the period studied, the RTR-TB consumed a total of 1,756,358 TRM cartridges, with 1,734,935 tests performed. The notification of new TB cases in the quarterly historical series from January 2010 to June 2014 showed a stationary trend. After the implementation of the TRM-TB, there was a trend towards an average increase of around 0.5% (95% CI: 0.13 - 0.87) of new cases, per quarter-year, and throughout the post-intervention period, there was an increase of 8,241 new TB cases in the municipalities of RTR-TB, a 15% increase (95% CI: 10.71 - 19.46) in the level of laboratory confirmation of new TB cases, and a decrease of 8.42% (95% CI: -15.61 - -0.62) in performing smear microscopy. Between 2014 and 2019, 2,071 RR-TB/MDR-TB cases were diagnosed with resistance through TRM, and 1,592 through TSA. After the incorporation of TRM, there was a reduction in the mean time of initiation of resistance treatment by 89 days (p-value < 0.0001), when compared to TSA. Individuals diagnosed by TRM are more likely to start DR-TB treatment earlier when compared to individuals diagnosed by TSA, and this difference is more accentuated up to the first 60 days after diagnosis. Persons diagnosed by TSA were 78% less likely to start the treatment in the first 30 days after the diagnosis of resistance when compared to those diagnosed by TRM (HRadj: 0.22; 95% CI: 0.13 - 0.36), and 49% lower probability of starting the treatment in the first six months after the diagnosis when compared to those diagnosed by TRM (HRadj: 0.51; 95%CI: 0.39 - 0.62). Conclusions: Overall, the TRM had a positive impact on TB control strategies in Brazil, restructuring the disease diagnosis network, increasing laboratory confirmation, and reducing the time between diagnosis and initiation of TB-RR / TB-MDR treatment. The incorporation of TRM into the Public Health System in Brazil provided a faster and more sensitive diagnosis of the disease, enabling a much more timely diagnosis of RR-TB / MDR-TB, and shortening the time to start treatment for resistant TB. The expansion of rapid molecular diagnosis by TRM to municipalities that are not yet part of the RTR-TB may contribute to better control of the disease in the country

Tuberculosis burden on AIDS in Brazil: A study using linked databases.

OBJECTIVES:To estimate the burden of tuberculosis (TB) in reported AIDS cases, to compare the characteristics of TB/HIV subjects with those without TB and to evaluate survival with or without TB in Brazil. METHODS:The data source was the linked database between AIDS (2011-2014) and TB (2011-2014) databases from the Notifiable Diseases Information System (SINAN). The sociodemographic, clinical, laboratory results and use of antiretroviral therapy (ART) data were compared by TB occurrence or not. Survival probability was estimated using the Kaplan-Meier method and associated factors were sought using Cox regression. RESULTS:The proportion of TB diagnosed from 2011 to 2014 among AIDS cases reported between 2006 and 2014 was 6.3%. Subjects coinfected with TB were predominantly male, older, with lower schooling, with lower CD4 count, higher viral load, and higher proportion of ART initiation than those without TB. 57.5% were diagnosed with HIV before TB, 38.2% as concurrent TB/HIV and 4.3% with TB before HIV. 16,466 reported TB cases were not found in the AIDS database, although registered as HIV-infected in the SINAN TB database between 2011 and 2014. Median survival for PLHIV was 581 days, with 582 for those without TB, significantly higher than 547 for those with TB (log-rank teste, p = 0,001). In the Cox multivariate analysis, male gender [aHR = 1.27 (CI 95% 1.22-1.33)], older age [aHR = 1.020 (CI 95% 1.019-1.022)] and TB coinfection [aHR = 1.97 (CI 95% 1.88-2.07)] were positively associated with adjusted hazard of death, whereas CD4 count 200-499 cells [aHR = 0.21 (CI 95% 0.20-0.22)] and receiving ART [aHR = 0.2 2(CI 95% 0.21-0.23)] reduced the risk of death. CONCLUSIONS:HIV-infected subjects should be screened for TB at care entry, to minimize diagnosis and treatment delays when active TB is present or to increase the odds of being offered latent TB infection therapy to prevent TB. On the other hand, TB cases should be promptly tested for HIV. All those will contribute to reduce mortality among people living with AIDS