Abstract / Summary
Abstract Background Tuberculosis (TB) remains a major global public health challenge despite substantial advances in diagnosis, treatment, and disease control. Although the World Health Organization (WHO) End TB Strategy has established a global treatment success target of at least 90% for drug-susceptible tuberculosis, treatment outcomes remain suboptimal in many settings. Numerous demographic, clinical, behavioral, socioeconomic, and health system-related factors have been reported to influence unsuccessful treatment outcomes; however, the available evidence remains heterogeneous and dispersed across different populations and healthcare settings. This systematic review aimed to synthesize the available evidence regarding factors associated with unsuccessful tuberculosis treatment outcomes and to identify the principal determinants reported across the published literature. Methods This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement. A comprehensive search of PubMed, Scopus, Web of Science, SID, Magiran, and IranDoc was performed for studies published between January 2000 and January 2026. Observational studies evaluating factors associated with tuberculosis treatment outcomes were eligible for inclusion. Two reviewers independently performed study selection, data extraction, and methodological quality assessment using design-appropriate Critical Appraisal Skills Programmed (CASP) checklists. Owing to substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively. Results Thirty-seven studies met the eligibility criteria and were included in the qualitative synthesis. The included evidence comprised cohort, case–control, cross-sectional, and program evaluation studies conducted across multiple geographical settings. Advanced age, HIV co-infection, diabetes mellitus, previous tuberculosis treatment, drug-resistant tuberculosis, delayed diagnosis, poor treatment adherence, and unfavorable socioeconomic conditions were the factors most consistently associated with unsuccessful treatment outcomes. Additional factors reported across several studies included limited access to healthcare services, financial hardship, food insecurity, migration, inadequate patient follow-up, and weaknesses in tuberculosis control programs. Considerable heterogeneity was observed in study populations, outcome definitions, exposure measurements, adjustment strategies, and risk of bias, precluding quantitative meta-analysis. Conclusion Available evidence indicates that unsuccessful tuberculosis treatment outcomes are associated with multiple interacting demographic, clinical, behavioral, socioeconomic, and health system-related factors. However, interpretation of these associations should consider substantial heterogeneity in study design, outcome definitions, confounder adjustment, and methodological quality. Future tuberculosis control strategies should prioritize context-specific interventions targeting modifiable determinants while high-quality comparative studies are needed to strengthen the evidence base.