Genomic Epidemiology of Childhood Tuberculosis in North West Nigeria: Phylogenetic Analysis of Mycobacterium tuberculosis Transmission Networks and Drug Resistance Determinants

Paediatric tuberculosis (TB) in Nigeria is predominantly caused by transmission from adult sources, yet the molecular epidemiology and transmission network structure of childhood TB in north-western Nigeria remain entirely uncharacterised. This study applies whole-genome sequencing-based phylogenetics to reconstruct Mycobacterium tuberculosis transmission networks and characterise drug resistance determinants in paediatric TB cases across Kano, Kaduna, and Sokoto states. Over 30 months from 2022 to 2024, 186 culture-confirmed TB cases in children aged 0 to 15 years were enrolled from eight tertiary facilities. Mycobacterium tuberculosis isolates underwent whole-genome sequencing on the Illumina NextSeq platform. Phylogenetic reconstruction using Bayesian evolutionary analysis identified transmission clusters. Drug resistance mutations were identified through bioinformatic comparison against the WHO catalogue of mutations. Lineage 4 (Euro-American) dominated (68.3%), with Lineage 2 (Beijing) present in 14.5% of isolates. Phylogenetic clustering suggested household transmission in 61.4% of cases, with 22.4% forming community-level transmission clusters crossing household boundaries. Multi-drug resistant TB was identified in 8.6% of isolates, with mutations in rpoB, katG, and inhA being most prevalent. One pre-extensively drug-resistant case was identified carrying additional mutations in gyrA and eis. The findings reveal active community transmission networks beyond the household in north-western Nigeria, challenging the assumption that paediatric TB reflects purely household exposure. These data support TB contact tracing reform and provide a genomic baseline for transmission interruption programmes. Keywords: genomic epidemiology, paediatric tuberculosis, transmission networks, North West Nigeria, drug resistance.