Determinants of delayed diagnosis and treatment of tuberculosis in high-burden countries: a mixed-methods systematic review and meta-analysis

Abstract Background: Globally, 30 countries with the highest tuberculosis (TB) burden bears 87% of the world’s TB cases. Delayed diagnosis and treatment are detrimental to TB prognosis and sustain TB transmission in the community, making TB elimination a great challenge, especially in these countries. Our objective was to elucidate the determinants and duration of delayed diagnosis and treatment of pulmonary TB in high TB burden countries. Methods: We conducted a systematic review and meta-analysis of quantitative and qualitative studies by searching four databases for literature published between 2008 and 2018 following PRISMA guidelines. For quantitative studies, we performed narrative synthesis of the covariates that were significantly associated with patient, health system, treatment, and total delays. The pooled median duration of delay and effect sizes of covariates were estimated using random-effects meta-analyses. We identified key qualitative themes using thematic analysis. Results: We included 124 articles from 14 low-and lower-middle-income countries (LIC and LMIC) and five upper-middle-income countries (UMIC) in this review. The pooled median duration of patient, health system, and treatment delay were 28 days (95%CI 20–30), 11.5 days (95%CI 3.9–24.7), and six days (95%CI 1–28.4), respectively. We found that the duration of delays was consistently shorter among UMIC compared to LIC and LMIC. There was consistent evidence that being female and rural residence was associated with longer patient delay. Furthermore, patient delay was also associated with other individual, interpersonal, and community risk factors such as poor TB knowledge, long chains of care-seeking through private/multiple providers, perceived stigma, financial insecurities, and poor access to healthcare. Health system and treatment delay were mediated by organizational and policy factors. These factors included the lack of resources and complex administrative procedures and systems at the health facilities. We identified data gaps in 11 high burden countries. Conclusions: This review detailed the determinants of delayed TB diagnosis and treatment in high burden countries. The gaps identified at different socio-ecological levels could be addressed through tailored approaches, education, and at a higher level, through health system strengthening and provision of universal health coverage to reduce delays and improve access to TB diagnosis and care.