Frequency, genetic mechanisms and factors associated with pre-extensively drug-resistant tuberculosis in Northern Nigeria

Abstract

<title>Abstract</title> Background Rifampicin-resistant <italic>Mycobacterium tuberculosis</italic> (MTB), a critical priority pathogen, becomes highly complicated when it develops into pre-extensively drug-resistant (pre-XDR) and is an exceptional challenge for global TB control efforts. This study aims to determine the frequency and mutations associated with fluoroquinolone and aminoglycoside resistance in MTB isolates from patients with pulmonary illnesses in Kaduna State, Nigeria. Materials and Methods A total of 144 MDR-TB-positive isolates previously obtained from sputum samples were collected from 360 individuals and were processed using the NaOH-Na-citrate-NALC method. All isolates were tested for MTB complex using TB Ag MPT64 (SD Bioline), and GenoType MTBDR <italic>sl</italic> VER 2.0 was used to identify chromosomal mutations in <italic>gyrA, gyrB, rrs</italic> and <italic>eis</italic> genes. Risk associated with pre-XDR-TB was assessed using a structured questionnaire, and the generated data were statistically analysed. Results The occurrence rate of pre-XDR in MDR-TB was 24.3% (n = 35) among 9.7% of individuals. Fluoroquinolone resistance was detected in 18/35 (51.4%) due to diverse mutations and missing regions WT1 and WT2 in <italic>gyrA</italic> (n = 14) and N538D in <italic>gyrB</italic> (n = 4). The predominant mechanisms of aminoglycoside resistance (41.2%, 7/17) among pre-XDR-TB strains were MUT1 (A1401G) and MUT2 (G1484T) in the <italic>rrs</italic> gene. Moreover, the MUT1 (C-14T) mutation (23.5%, 4/17) was observed in the <italic>eis</italic> promoter region. Histories of contact with TB patients (OR = 8.94, 95% CI: 4.1-19.49, <italic>p</italic> &lt; 0.0001) and prior anti-tuberculosis treatment (OR = 2.36, 95% CI: 1.13–4.94, <italic>p</italic> = 0.00233) were associated with pre-XDR-TB. Conclusion This study revealed a high occurrence of pre-XDR-TB in the study population and among the MDR strains, which could lead to treatment failures and a higher public health threat. To stop pre-XDR-TB from spreading and growing and to improve treatment outcomes in this and other regions where it is more prevalent, it is imperative to diagnose resistance to second-line anti-tuberculosis quickly before beginning treatment and activate pre-XDR-TB surveillance systems.