<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">Genotypic study of isolated resistance to isoniazid in the Mycobacterium tuberculosis&#160; complex in&#160; a Moroccan hospital </xhtml:span>

Introduction: Despite the introduction 40 years ago of effective and low-cost treatment for tuberculosis, morbidity and mortality from this disease remain substantial worldwide. According to the WHO, tuberculosis is once again the leading cause of death worldwide from a single infectious agent. In 2023, TB caused approximately 1.25 million deaths. In Morocco, the number of new tuberculosis cases rose from 30,897 in 2017 to 35,000 in 2019.The incidence of multidrug-resistant or rifampicin-resistant tuberculosis was estimated at 1.7 per 100,000 inhabitants, Isoniazid is a cornerstone of first-line TB treatment, and resistance to it even in the absence of rifampicin resistance is associated with delayed treatment response, higher rates of treatment failure or relapse,and increased risk of progression to MDR-TB if not promptly identified and appropriately managed. Moreover, current diagnostic algorithms in many settings, including Morocco, may miss INH monoresistance due to their reliance on rapid molecular tests that primarily detect rifampicin resistance. further emphasizing the emerging threat of drug-resistant TB. Despite this, national data on isoniazid monoresistance remain scarce. Given the increasing burden of TB and the critical importance of early detection of drug resistance, it is essential to better understand patterns of resistance beyond rifampicin. It is within this context that we conducted the present study, which aims to investigate isoniazid resistance in tuberculosis cases over a period of three years.     Materials and Methods This is a retrospective study conducted at the Bacteriology Department of Mohammed V Military Instruction Hospital over a period of 3 years. Data were collected via the laboratory information system. Clinical samples underwent treatment using both conventional bacteriological methods and molecular techniques. The study of resistance to major anti-tuberculosis drugs was performed using the reverse hybridization technique, specifically the HAIN method (GenoType® MTBDRplus by Hain Lifescience. Statistical analysis was performed using IBM SPSS Statistics19 and Microsoft Excel 2019                                       Results: The study involved 464 patients treated for pulmonary and extrapulmonary tuberculosis, including both new cases and those previously treated with positive cultures. The mean age of the patients was 42.2 years, with a range from 8 to 88 years. There was a predominance of males at 74%, with a sex ratio of 2.8.                                                                                    Pulmonary sputum samples accounted for 84.8% of the cases, where as extrapulmonary samples representedonly15.2%,the positivity rates for direct examination and culture across all samples were74%and100%, respectively. Isoniazid resistance had a prevalence of 9% (43/464). Genetic mutations observed indicated that 63% of the clinical isolates resistant to INH had mutations in the katG gene, while 37% had mutations in the inhA gene. Conclusion The increasing prevalence of Mycobacterium tuberculosis complex strains resistant to one or more first-line anti-tuberculosis drugs highlights the urgent need for targeted and ongoing epidemiological surveillance. In this study, we found that isoniazid resistance affected 9% of tuberculosis cases over the three-year period, underscoring a significant yet under recognized threat to TB control efforts in Morocco. Molecular analysis revealed that the majority of resistant strains carried mutations in the katG gene, with a smaller proportion exhibiting mutations in the inhA promoter region.