WITHDRAWN: Prevalence ofkatGandinhAmutations in genes associated with isoniazid resistance inMycobacterium tuberculosisclinical isolates in Cameroon

Abstract

Purpose: Genetic mutations in the katG and inhA promoter regions are the main drivers of isoniazid resistance. However, the geographical distribution of isoniazid resistance-associated mutations differs. This study investigated the prevalence of katG and inhA mutations in isoniazid-resistant strains of Mycobacterium tuberculosis (MTB) clinical isolates in Cameroon. Methods: A retrospective analysis was conducted on 500 isoniazid-resistant MTB clinical isolates collected from the National Tuberculosis Reference Laboratory in Cameroon (2014 to 2020). Mutations at the katG and inhA genes were screened using the GenoType MTBDRplus assay. Results: A total of 432 culture-positive MTB isolates were obtained. The male-to-female ratio of the patients was 52.8% to 43.1%, with an average age of 36.3+/-13.4 years. Isoniazid resistance was detected in 86.3% of isolates, 26% being isoniazid-monoresistant and 74% multidrug resistant. The katG S315T1 mutation was the most prevalent (69.4%). Mutations in the inhA promoter region were found in 22% of isoniazid-resistant isolates, with C-15T being the most common (16.9%). Co-mutation in both katG and inhA genes was observed in 8.6% of isoniazid-resistant isolates. Additionally, 13.7% of isolates did not exhibit mutations in the katG and inhA promoter regions. Conclusion: The study confirmed the prevalence of the katG S315T substitution as a reliable indicator of isoniazid resistance, with the inhA C-15T mutation providing additional support. However, a notable proportion of isoniazid-resistant isolates exhibited no evidence of the katG S315T and inhA promoter mutations, emphasizing the importance of understanding resistance mechanisms for effective treatment strategies and public health interventions against drug-resistant tuberculosis in the region. Keywords: Mycobacterium tuberculosis, isoniazid resistance, katG, inhA, mutations, Cameroon