Associated Risk Drivers of Increased Multidrug-Resistant Tuberculosis (MDR-TB) Cases in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

OBJECTIVES Primary Objective: To identify and synthesize evidence on risk factors significantly associated with increased MDR-TB cases in sub-Saharan Africa. Secondary Objectives: - To estimate pooled effect sizes (odds ratios, risk ratios, or hazard ratios) for each identified risk factor. - To explore heterogeneity across studies by country, setting (urban/rural), population subgroup (e.g., children, PLHIV), and study design. - To assess the strength and quality of evidence for each risk factor. - To identify gaps in literature and propose priorities for future research and policy. 3. Eligibility Criteria (PICOs Framework) Population: Individuals residing in sub-Saharan African countries (as defined by the World Bank or WHO AFRO region). Includes all age groups, genders, and clinical statuses (e.g., HIV-positive, incarcerated, healthcare workers). Intervention/Exposure: Any potential risk factor or driver hypothesized or demonstrated to increase MDR-TB incidence/prevalence. Examples include: Biological: HIV infection, diabetes, malnutrition, genetic susceptibility Behavioral: Smoking, alcohol use, delayed care-seeking Socioeconomic: Poverty, overcrowding, unemployment, low education Health system: Inadequate diagnostic capacity, treatment interruptions, poor infection control Environmental: Indoor air pollution, mining exposure Programmatic: Previous TB treatment, non-adherence, suboptimal drug regimens Comparator: Absence of the risk factor or lower exposure level (e.g., HIV-negative vs. HIV-positive; urban vs. rural residence). Outcomes Primary outcome: Incident prevalent MDR-TB cases Secondary outcomes: Treatment failure, relapse, or default rates Drug resistance patterns (e.g., pre-XDR, XDR-TB) Study Designs: Quantitative observational studies: cohort, case-control, cross-sectional Analytical studies reporting effect estimates (OR, RR, HR, prevalence ratios) with 95% confidence intervals Studies published in peer-reviewed journals or grey literature (e.g., national TB program reports, WHO country profiles) from January 2000 to present Exclusion Criteria: Studies not conducted in SSA Continent Case reports, case series (