A Systems Biology Approach to Characterising Multidrug-Resistant Tuberculosis Transmission Networks in Kano and Kaduna States, North West Nigeria

Multidrug-resistant tuberculosis represents a growing public health emergency in North West Nigeria, where transmission dynamics, acquisition pathways, and the relative contribution of recent transmission versus endogenous reactivation are not characterised at the molecular level. This study applies a systems biology approach integrating whole-genome sequencing, spatial epidemiology, and contact network analysis to characterise multidrug-resistant TB transmission networks in Kano and Kaduna States. A prospective molecular epidemiological design is applied over 36 months, enrolling 600 MDR-TB patients from 15 designated treatment centres. M. tuberculosis isolates undergo whole-genome sequencing using Illumina MiSeq, with genomic clustering and phylogenetic analysis performed using BEAST2 and SNP-distance matrices. Spatial mapping of transmission clusters is conducted in ArcGIS. Contact network data are collected through structured epidemiological interviews, and network analysis is performed using Gephi to identify superspreader nodes. The Evolutionary Epidemiology Theory and One Health Systems Framework guide the theoretical integration. Original contributions include the first molecular characterisation of MDR-TB transmission architecture in North West Nigeria and the identification of high-transmission community nodes for targeted contact tracing. Findings will directly inform the North West Regional TB Control Programme on evidence-based molecular surveillance and outbreak response. Keywords: multidrug-resistant tuberculosis, whole-genome sequencing, transmission networks, North West Nigeria, molecular epidemiology.