Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

Trends in Untreated Tuberculosis in Large Municipalities, Brazil, 2008-2017.

We adapted a mathematical modeling approach to estimate tuberculosis (TB) incidence and fraction treated for 101 municipalities of Brazil during 2008-2017. We found the average TB incidence rate decreased annually (0.95%), and fraction treated increased (0.30%). We estimated that 9% of persons with TB did not receive treatment in 2017.

Environmental factors associated with the time to tuberculosis diagnosis in prisoners in São Paulo, Brazil.

BACKGROUND: Environmental conditions play an important role in the high incidence of tuberculosis in prisons. We estimated the effect of environmental factors, including measurements based on cell dimensions, on the time to tuberculosis diagnosis in prison population of Brazil. METHODS: This is a retrospective cohort of 2,257 prisoners diagnosed with tuberculosis in 2014 and 2015. We collected environmental data from 105 prisons and linked with routine tuberculosis surveillance and prison data. We estimated tuberculosis-free survival time with Cox risk models, guided by a validated directed acyclic graph. RESULTS: The median disease-free time was 1.71 years (95% confidence interval [95% CI] 1.64-1.78). Each 50% increase in occupancy-rate, increased the tuberculosis speed incidence by 16% (95% CI 8%-25%) in the first 2 years, and 9% (95% CI 3%-16%) up to 5 years. An increase in the cell area per person (ln[m2/person]) reduced the hazard of tuberculosis by 13% (95% CI 3%-23%) for up to 2, and 12% (95% CI 3%-21%) for up to 5 years. DISCUSSION: Most tuberculosis cases were diagnosed within 2 years of incarceration. Prison overcrowding and physical space per person in the cell were associated with the tuberculosis-free disease time. CONCLUSIONS: Interventions to reduce overcrowding or increase physical space are crucial to prevent tuberculosis in prisons.

Excess tuberculosis cases and deaths following an economic recession in Brazil: an analysis of nationally representative disease registry data.

BACKGROUND: In 2019, tuberculosis incidence and mortality in Brazil were 46 and 3·3 per 100 000 population, respectively, and the country has reported rising tuberculosis case rates since 2016, following an economic crisis beginning in mid-2014. We aimed to estimate the number of excess tuberculosis cases and deaths during the recession period, and assessed potential causes. METHODS: In this multi-level regression modelling study, we extracted tuberculosis case notifications from Brazil's National Notifiable Disease Information System (known as SINAN), and tuberculosis deaths from the Mortality Information System (known as SIM), for all ages. We fitted mixed-effects regression models estimating trends in these outcomes-stratified by sex, age group, and state-during the pre-recession period (Jan 1, 2010-Dec 31, 2014). We calculated excess cases and deaths between Jan 1, 2015, and Dec 31, 2019 (the recession period) as the difference between reported values and a counterfactual of continued pre-recession trends. We examined the relationship between excess cases and possible explanatory factors using ordinary least squares regression. We tested the robustness of our findings to alternative model specifications related to the pre-recession period and criteria for defining tuberculosis deaths. FINDINGS: We estimated 22 900 excess tuberculosis cases (95% uncertainty interval 18 100-27 500) during 2015-19. By 2019, reported cases were 12% (10-13) higher than predicted by historical trends. 54% (44-66) of excess cases occurred among 20-29-year-old men. In this group, reported cases in 2019 were 30% (25-36) higher than predicted. Excess cases were positively associated with an increasing fraction of cases among incarcerated individuals (p=0·001) and higher unemployment (p=0·04) at the state level. Estimated excess deaths for 2015-19 were not statistically significant from 0 (-600 [-2100 to 1000]). These results were robust to alternative definitions of the pre-recession period and criteria for defining tuberculosis deaths. INTERPRETATION: Tuberculosis cases in Brazil rose substantially in 2015-19 during the recession, largely affecting young men. This increase seems to be linked to increasing tuberculosis transmission among incarcerated populations. Rising tuberculosis case rates threaten tuberculosis control in Brazil, and highlight the threat posed by prison-based tuberculosis transmission. FUNDING: US National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Bayesian evidence synthesis to estimate subnational TB incidence: An application in Brazil.

BACKGROUND: Evidence on local disease burden and the completeness of case detection represent important information for TB control programs. We present a new method for estimating subnational TB incidence and the fraction of individuals with incident TB who are diagnosed and treated in Brazil. METHODS: We compiled data on TB notifications and TB-related mortality in Brazil and specified an analytic model approximating incidence as the number of individuals exiting untreated active disease (sum of treatment initiation, death before treatment, and self-cure). We employed a Bayesian inference approach to synthesize data and adjust for known sources of bias. We estimated TB incidence and the fraction of cases treated, for each Brazilian state and the Federal District over 2008-2017. FINDINGS: For 2017, TB incidence was estimated as 41.5 (95 % interval: 40.7, 42.5) per 100 000 nationally, and ranged from 11.7-88.3 per 100 000 across states. The fraction of cases treated was estimated as 91.9 % (89.6 %, 93.7 %) nationally and ranged 86.0 %-94.8 % across states, with an estimated 6.9 (5.3, 9.2) thousand cases going untreated in 2017. Over 2008-2017, incidence declined at an average annual rate of 1.4 % (1.1 %, 1.9 %) nationally, and -1.1%-4.2 % across states. Over this period there was a 0.5 % (0.2 %, 0.9 %) average annual increase in the fraction of incident TB cases treated. INTERPRETATION: Time-series estimates of TB burden and the fraction of cases treated can be derived from routinely-collected data and used to understand variation in TB outcomes and trends.

Impact of alcohol disorder and the use of illicit drugs on tuberculosis treatment outcomes: a retrospective cohort study.

BACKGROUND: Alcohol and illicit drugs are associated with the discontinuation of tuberculosis (TB) treatment and can compromise the immune system. We estimated the impact of alcohol disorder and the use of illicit drug on TB treatment outcomes, considering the interaction of both substances in patients from São Paulo state, Brazil. METHODS: This is a retrospective cohort of patients diagnosed with TB from 2011 to 2015. We estimated the relative risk (RR) of an unsuccessful outcome associated with alcohol disorder, use of illicit drugs and their interaction using a multiple regression model. We used the adjusted RR to estimate the population attributable fraction. RESULTS: Out of a total 77,212 TB patients, 22.2% used at least one of the substances of interest during treatment, while 17% presented an unsuccessful outcome of TB treatment. Compared with no exposure to any substance, alcohol disorder alone (adjusted RR: 1.48; 95% CI: 1.4-1.56), drug use alone (adjusted RR: 2.1; 95% CI: 1.98-2.21) and exposure to both substances (adjusted RR: 2.09; 95% CI: 1.97-2.21) were all associated with a higher risk of an unsuccessful outcome. The adjusted RR of an unsuccessful outcome for people exposed to both substances was 32.7% (95% CI: 26.8-38.2%) and 15.8% (95% CI: 11.5-20.1%) lower than expected on the multiplicative and additive scales respectively. Among all TB patients, 15.8% (95% CI: 15-16.5%) of unsuccessful outcomes was attributable to those exposures. CONCLUSIONS: We identified a negative interaction between alcohol disorder and the use of illicit drugs on TB treatment outcomes. Despite this, interventions to reduce substance use in TB patients could have a meaningful contribution to preventing unsuccessful treatment outcomes.

Exposure to magnetic fields and childhood acute lymphocytic leukemia in São Paulo, Brazil.

BACKGROUND: Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil. METHODS: This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines. RESULTS: For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (µT), compared to children exposed to levels below 0.1 µT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44). CONCLUSIONS: Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion.