Date of Award

Spring 1-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Public Health

First Advisor

Cohen, Theodore

Abstract

Tuberculosis (TB) is a leading cause of death from infectious disease globally, despite the availability of effective antibiotic treatment. Control efforts focus on the rapid diagnosis and treatment of individuals with TB, which reduces both disease-related morbidity and mortality and onward transmission. In addition to passive case finding, the World Health Organization recommends active case finding for high-risk individuals and their contacts. Expanding these activities to populations in which there is evidence of recent transmission may be a suitable strategy to reduce TB burden, but identifying these populations is a persistent challenge. Statistical analyses, informed by high quality surveillance data, can enable the detailed study of TB epidemics, revealing biological and epidemiological drivers of transmission. In Chapter 1, I use whole genome sequencing data to investigate high levels of multidrug resistant (MDR) M. tuberculosis (Mtb) transmission in the Republic of Moldova. Through several phylogenetic approaches, I identify a strain of MDR Mtb (“Ural A”) which appears to be expanding rapidly within Moldova. The Ural A strain is estimated to have a reproduction number more than twice that of drug susceptible strains belonging to the same lineage. I also identify several candidate mutations which are associated with this highly transmissible strain and provide preliminary evidence to suggest that this strain is present outside of Moldova. In Chapter 2, I use whole genome sequencing data, patient home location data, and additional demographic information to describe TB transmission networks in Blantyre, Malawi. In this HIV co-endemic setting, I found evidence of a complex TB epidemic where there are both localized, within-neighborhood transmission networks and more generalized networks spanning the entire city. These findings point towards a two-pronged TB control strategy of generalized improvements to primary care access and targeted case finding activities to reduce Mtb transmission within Blantyre. In Chapter 3, I use case notification and TB mortality data to estimate the impact of the COVID-19 pandemic on TB detection in Brazilian states. I estimate that approximately 20,000 individuals with active disease did not receive a diagnosis or treatment during the first 21 months of the pandemic (April 2020 – December 2021). These individuals likely spread disease within their homes and communities, and I estimate increases in TB incidence in 2021. I also estimate a negative association between the number of filled physician contracts and the number of individuals who did not receive a TB diagnosis over the study period, suggesting a link between health system resiliency and recovery of essential TB services after COVID-19-related disruptions.

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