Evaluation of Whole-Genome Sequencing as a Surveillance Tool for Multi-Drug-Resistant Tuberculosis in Kano, Kano State

Whole-genome sequencing (WGS) of Mycobacterium tuberculosis has transformed TB surveillance globally by enabling rapid resistance prediction, transmission cluster identification, and lineage classification with unprecedented resolution. However, its application in Nigeria's high-burden TB context is nascent, with most surveillance relying on conventional phenotypic drug susceptibility testing. This study evaluated the concordance, feasibility, and added value of WGS compared to conventional drug susceptibility testing for MDR-TB surveillance at the TB reference laboratory serving Kano State, North West Nigeria. Fifty M. tuberculosis complex isolates from culture-confirmed pulmonary TB patients were subjected to parallel conventional proportion method DST (for isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin) and Illumina-based WGS with bioinformatic resistance prediction using the TBprofiler and Mykrobe tools. Results showed 94 percent concordance between WGS-predicted resistance and conventional DST results. WGS additionally detected heteroresistance in 8 percent of isolates not apparent by conventional DST. Phylogeographic analysis classified 62 percent of isolates as M. tuberculosis lineage 4 (Euro-American) and 34 percent as lineage 1 (Indo-Oceanic). Transmission cluster analysis identified two active transmission clusters of 4 to 6 patients each, previously undetected by conventional epidemiological investigation. TAT for WGS-based resistance prediction was 7 days versus 28 days for conventional DST. These findings affirm WGS as a superior surveillance tool and support phased implementation of WGS in Nigerian national TB programs beginning with reference laboratories. Keywords: whole-genome sequencing, MDR-TB, drug susceptibility testing, Mycobacterium tuberculosis, Kano.