What
Tuberculosis (TB) is widely recognized as a treatable and curable disease, yet this study shows that its consequences extend far beyond the active infection phase. Individuals who survive TB continue to face a significantly elevated risk of death for many years after diagnosis and even after completing treatment. This long-term mortality burden is largely overlooked in public health frameworks, with no dedicated guidance from global authorities such as the WHO to address post-TB health risks. The persistence of this risk is thought to arise from a combination of biological damage—such as permanent lung impairment and chronic inflammation—as well as ongoing social and health vulnerabilities, including comorbid conditions and poverty.
The magnitude and duration of excess mortality are substantial. Immediately after TB diagnosis, mortality risk is extremely high, particularly within the first month, and although it declines over time, it remains elevated even 14 years later. Individuals who complete treatment fare better than those newly diagnosed, but still experience roughly double the mortality risk of comparable TB-free individuals over the long term. Importantly, this is not just a relative effect; the absolute number of excess deaths is large, indicating a significant population-level burden that persists well beyond clinical recovery.
This increased mortality risk spans multiple causes of death rather than being limited to TB-related complications. Elevated risks are observed for cardiovascular disease, respiratory conditions, cancer, and metabolic disorders. Certain patterns stand out: respiratory and cancer-related deaths are particularly high shortly after diagnosis or treatment, while cardiovascular mortality becomes more prominent over time. Additionally, deaths from external causes—especially assaults—are also higher among TB-affected individuals, suggesting that social determinants and environmental risks play a meaningful role alongside biological factors.
The impact of TB on mortality is not uniform across populations. Younger adults show higher relative risks, whereas older individuals bear a greater absolute burden of excess deaths. Differences by sex are modest, though slightly higher risks are observed among women in some contexts. Disease severity also matters: individuals with extrapulmonary or mixed forms of TB tend to have worse outcomes than those with pulmonary TB alone. Comorbidities further amplify risk, with diabetes emerging as a particularly important factor—associated with even greater absolute excess mortality than HIV in this study. Notably, household contacts of TB patients also exhibit modestly increased mortality, reinforcing the role of shared socioeconomic and environmental exposures.
How
This study was designed as a large-scale retrospective cohort analysis using nationwide administrative data from Brazil. It leveraged the “100 Million Brazilian Cohort,” which captures over 130 million individuals enrolled in social welfare programs and represents predominantly low-income populations. These data were linked to national TB notification records and mortality registries, allowing researchers to follow individuals over time and assess long-term outcomes with high completeness and reliability. The study period spanned from 2004 to 2018, providing sufficient duration to evaluate long-term mortality trends.
Two main exposure groups were defined: individuals at the time of TB diagnosis and individuals who had successfully completed TB treatment. Each exposed individual was matched to a TB-free control using exact matching on a wide range of demographic and socioeconomic variables, including age, sex, race or ethnicity, geographic location, housing conditions, and household characteristics. This matching approach was designed to minimize confounding by ensuring that exposed and unexposed groups were highly comparable at baseline, particularly with respect to social determinants of health.
The study focused primarily on “natural deaths,” defined as deaths excluding TB, HIV, and external causes, in order to isolate the indirect and longer-term physiological consequences of TB. Secondary outcomes included all-cause mortality and specific causes of death, such as cardiovascular disease, cancer, respiratory illness, metabolic disorders, and external causes like accidents and assaults. Mortality outcomes were classified using standardized ICD-10 codes, enabling consistent categorization across the dataset.
Participants were followed from the point of TB diagnosis or treatment completion until death, the end of the study period, or (for controls) a subsequent TB diagnosis. Statistical analysis used the Aalen–Johansen estimator to calculate cumulative incidence while accounting for competing risks from different causes of death. Key measures included risk ratios, incidence rate ratios, and absolute risk differences, providing both relative and population-level perspectives on mortality risk over time.
To ensure data quality and interpretability, several exclusion criteria were applied, including removal of individuals with missing key variables, implausible dates, prior TB diagnoses before cohort entry, or extreme ages. Additional subgroup analyses were conducted to examine variation in mortality risk by age, sex, comorbidities, TB type, and household exposure. The study also incorporated analyses of household contacts, allowing for comparison between TB patients and individuals sharing similar living environments, further strengthening the interpretation of both biological and social drivers of long-term mortality.
Source: Cerqueira-Silva, T., Boaventura, V.S., Paixão, E.S., Sanchez, M., Leyrat, C., Ranzani, O., Barreto, M.L. and Pescarini, J.M., 2026. Long-term risk of death after tuberculosis diagnosis and treatment. Nature Medicine, pp.1-8.
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