Predictors and dynamics of household Mtb transmission in high tuberculosis incidence settings

Marambire, Edson Tawanda (2025): Predictors and dynamics of household Mtb transmission in high tuberculosis incidence settings. Dissertation, LMU München: Medizinische Fakultät

Abstract

Introduction: Tuberculosis (TB) remains a critical global health challenge, disproportionately affecting high-burden regions in Southern Africa. Household contacts of people with TB (PWTB) face elevated risks of Mycobacterium tuberculosis (Mtb) infection, yet gaps persist in understanding predictors of transmission and the role of multimorbidity (e.g., HIV, malnutrition, non-communicable diseases). This PhD research investigated predictors and transmission dynamics of household Mtb in high TB incidence settings. Methods: The research was nested within the multinational ERASE-TB cohort study in which household contacts (≥10 years) of adult microbiologically confirmed (medium-high) PWTB were recruited from Zimbabwe, Mozambique and Tanzania. Three interrelated studies were conducted. The first characterised multimorbidity and socioeconomic disparities in TB-affected households. The second developed and evaluated predictive models for Mtb infection (IGRA positivity) among household contacts using multivariable regression with cross-validation and decision curve analysis. The third employed mixed-effects logistic regression to assess influence of HIV/ART status of PWTB on household transmission dynamics. Results: Findings from the first study reveal a substantial burden of chronic conditions and socioeconomic disparities that amplify TB risk. Multimorbidity affected 61% of adults, with high prevalence of HIV (15%), malnutrition (18%), and diabetes (9.4%). Predictive models demonstrated limited utility (AUROC: 0.59–0.60), reflecting challenges in using individual- and household-level factors for Mtb infection risk stratification in settings with high community transmission. The third study demonstrated that HIV-positive PWTB not on ART exhibited 55% lower odds of household Mtb transmission (aOR: 0.45, 95% CI: 0.29–0.69) compared to HIV-negative PWTB and those on ART, even after controlling for bacterial burden and symptom duration. Conclusion: Household Mtb transmission in high-burden settings is shaped by intersecting biological, socioeconomic, and structural factors. Findings emphasize the importance of integrated health screening as a means to improve household health and potentially reduce risk of progression to TB among household members. While predictive models showed limited clinical utility, this underscores the dominance of community transmission. The reduction in transmission among untreated HIV-positive PWTB challenges conventional assumptions, suggesting unmeasured behavioural or healthcare access mediators. Policies must prioritize integrated health screening among TB-affected households, context-adapted Mtb diagnostics, and innovative TB/HIV program integration. Future research should explore feasibility of integrated health screening, develop effective and affordable diagnostic tools and explore mechanisms underlying HIV/ART-related transmission dynamics to optimize prevention strategies.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Mycobacterium tuberculosis, Household transmission, Predictive modelling, High TB incidence settings, Multimorbidity
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 5. November 2025
• 1. Bericht­erstatter:in: Heinrich, Norbert