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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by Fondation Merieux

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Centre Regional Ethics Committee for Human Research of the Ministry of Public Health, Cameroon gave ethical approval for this work

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Data Availability

All data produced in the present study are available upon reasonable request to the authors

List of AbbreviationsA-LysLysis bufferAM-AAmplification mix AAM-BAmplification mix BA-NBNeutralization bufferCON-DConjugate diluent.CPCCentre Pasteur du CamerounDENDenaturation solutionDSTDrug susceptibility testingGCGrowth controlHIVHuman Immunodeficiency VirusHRHeteroresistanceHYBHybridization solutionINHIsoniazidINH-RIsoniazid-resistantLPALine Probe AssayMDRMultidrug-resistantMDR-TBMultidrug-resistant tuberculosisMGITMycobacterial Growth Indicator TubeMTBMycobacterium tuberculosisMUTMutantOADCOleic Albumin Dextrose CatalasePCRPolymerase chain reactionRIFRifampicinRINRinse solutionRR-TBRifampicin-resistant tuberculosisSUB-DSubstrate diluentTBTuberculosisTB-NRLTuberculosis National Reference LaboratoryWHOWorld Health OrganizationWTWild type