Genomic Epidemiology of Multidrug-Resistant Tuberculosis Transmission Networks in North East Nigeria: A Whole Genome Sequencing Approach

Multidrug-resistant tuberculosis (MDR-TB) represents a critical public health emergency, particularly in post-conflict settings where healthcare disruption has reduced treatment completion rates. North East Nigeria, severely affected by the Boko Haram insurgency, has experienced healthcare collapse that may have facilitated MDR-TB transmission. Whole genome sequencing (WGS) provides maximum resolution for reconstructing TB transmission networks and identifying outbreak clusters. This dissertation applied WGS-based genomic epidemiology to characterise MDR-TB transmission networks in North East Nigeria, spanning Borno, Yobe, and Adamawa States. Three hundred and fifty culture-confirmed MDR-TB isolates from two consecutive years of surveillance were subjected to Illumina whole genome sequencing. Transmission cluster reconstruction used a single nucleotide polymorphism (SNP) threshold of 12 SNPs for cluster definition based on within-host diversity modelling. Bayesian phylogenetic analysis in BEAST2 estimated cluster origin times. Geospatial mapping of transmission clusters was conducted using ArcGIS, integrating conflict intensity data. Patient-level risk factors including displacement camp residence, HIV status, and treatment history were examined as predictors of cluster membership. The majority of MDR-TB cases were attributable to ongoing recent transmission rather than reactivation, implicating active nosocomial and household transmission chains. Displaced persons camp clustering was a significant transmission risk factor. These findings demand urgent targeted MDR-TB intervention in North East Nigeria. Keywords: MDR-TB, whole genome sequencing, transmission networks, North East Nigeria, genomic epidemiology