BACKGROUND:
Tuberculosis (TB) remains a major global health challenge, with approximately 10 million new cases reported each year.¹˒² Clinical outcomes, including infection, progression to active disease, drug resistance, and mortality, result from complex biological, social, and environmental interactions.³˒⁴ Many of these risks are modifiable and can be mitigated through multisectoral public health policies.⁵ Given the vast and heterogeneous evidence base, an overview of systematic reviews is essential to synthesize high quality data and support equitable, context specific interventions.⁶

METHODS:
This overview followed the Cochrane Handbook guidelines⁷ and PRISMA 2020 recommendations.⁸ PubMed, Embase, Cochrane Library, LILACS, and PROSPERO were searched for systematic reviews on TB risk factors. Methodological quality and bias were assessed using ROBIS.

RESULTS:
Of 230 records, 52 reviews met inclusion criteria, covering 1,355 primary studies. Most research occurred in India, South Africa, Brazil, China, and the United States. Progression to active disease was the most frequently investigated endpoint (51.9%). Across risk factor categories, comorbidities and environmental/household exposures were most prevalent (73.1%), followed by demographic and socioeconomic factors (36.5%), TB dynamics and treatment-related factors (28.9%), and behavioral determinants (15.4%). Comorbidities, particularly HIV and diabetes, and environmental exposures (e.g., secondhand smoke) predominated in reviews on infection (69.2%), disease progression (69.2%), and severity or mortality (66.7%). In contrast, drug-resistant TB was primarily linked to treatment-related or disease-dynamic characteristics (57%). High heterogeneity across primary studies was frequently reported, and more than half of the included reviews had a high risk of bias. These findings underscore that, despite substantial documentation of risk factors, the overall quality of synthesized evidence remains insufficient to reliably guide global policymaking.

CONCLUSIONS:
TB disproportionately affects socially and economically vulnerable groups, with research focusing on active disease. Addressing TB’s multifactorial nature requires robust multisectoral policies and highlights the urgent need to confront social determinants and health inequities worldwide.