The impact of undernutrition on tuberculosis prevalence and treatment outcomes in Ethiopia
Introduction: Tuberculosis (TB) is a leading infectious cause of death globally, with an estimated 10.6 million new cases and 1.3 million deaths annually. The emergence of multidrug-resistant tuberculosis (MDR-TB), characterized by resistance to isoniazid and rifampicin, further complicates the global TB control efforts. The progression from latent to active TB is influenced by various factors including undernutrition. While the individual-level association between TB and undernutrition has been documented, there has been a lack of studies exploring their geospatial co-distribution, particularly in high TB-burden countries like Ethiopia. There was also limited evidence on the impacts of undernutrition or failure to gain weight during follow-up on treatment outcomes among patients with TB and MDR-TB in Ethiopia. Furthermore, there was insufficient conclusive evidence to measure the effects of nutritional intervention on improving adherence to TB treatment and outcomes. This PhD thesis aimed to address these knowledge gaps by investigating the geospatial overlap of undernutrition and TB (objective 1), quantifying the effect of undernutrition and weight change on TB and MDR-TB treatment outcomes (objectives 2 and 3), and assessing the impact of nutritional intervention on TB treatment adherence, prognostic markers, and treatment outcomes (objective 4). Various study designs and statistical analyses were used to address the thesis objectives. A Bayesian model-based geostatistics was used to investigate the geospatial overlap of undernutrition and TB prevalence in Ethiopia (objective 1), using data from national prevalence surveys. A Cox proportional hazard model was performed to assess the effect of undernutrition on TB treatment outcomes using data from a retrospective cohort study in northwest Ethiopia (objective 2). Longitudinal data analysis using a joint model was applied to determine the effect of weight variation over time on MDR-TB treatment outcomes in patients with MDR-TB (objective 3). Systematic reviews and meta-analyses were performed to synthesize evidence on the impact of nutritional intervention on improving TB treatment adherence, prognostic markers, and treatment outcomes (objective 4). Results: The results of this thesis showed that spatial co-distribution of undernutrition and TB prevalence was found in some parts of Ethiopia. Population density was positively associated with TB and negatively associated with all forms of undernutrition. The distance to a health facility was positively associated with stunting and adult undernutrition. The overall successful treatment outcomes for patients with TB and MDR-TB in northwest Ethiopia were 89% and 67%, respectively. Undernutrition was positively associated with unsuccessful treatment outcomes, higher mortality, and a longer time to sputum culture conversion in patients with TB and MDR-TB. This thesis also indicated a significant relationship between weight variation over time and early unsuccessful MDR-TB treatment outcomes, suggesting that a one-unit increase in weight corresponds to a nearly 5% reduction in the risk of an unsuccessful outcome. Systematic reviews and meta-analyses demonstrated that the provision of nutritional support, as well as zinc and vitamin A supplementation, can improve adherence to TB treatment, increase early sputum smear conversion, and higher levels of serum zinc, retinol, and hemoglobin among people with TB. Conclusion: This thesis provides evidence that could guide decision-making and shape service delivery strategies for supporting nutritional aspects in the prevention and management of TB. The co-distribution of TB and undernutrition provides important evidence for targeted intervention strategies. This thesis has also made policy suggestions that could contribute to achieving the End-TB targets, emphasizing the relevance of strengthening the integration of nutritional interventions as an integral part of TB care.
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