Genotypic study of isolated resistance to isoniazid in the Mycobacterium tuberculosis  complex in  a Moroccan hospital

Introduction: Despite the availability of effective and low-cost treatment for tuberculosis (TB) for over four decades, the disease continues to pose a major global health challenge. According to the World Health Organization (WHO), TB was the leading cause of death from a single infectious agent in 2023, surpassing COVID-19, with approximately 1.25 million deaths worldwide. In Morocco, the number of new TB cases rose from 30,897 in 2017 to 35,000 in 2019, reflecting a concerning trend and highlighting the burden TB places on the national health system. A growing concern is the emergence of drug-resistant forms of TB, particularly resistance to isoniazid (INH), a key component of first-line TB therapy. Even in the absence of rifampicin (RIF) resistance, INH resistance is linked to delayed treatment response, increased risk of failure or relapse, and potential progression to (MDR-TB). Unfortunately, current diagnostic strategies in many settings, including Morocco, focus primarily on detecting RIF resistance, often overlooking INH monoresistance. National data on INH resistance are limited, further complicating control efforts. This study aims to investigate the prevalence and genetic patterns of INH resistance in TB cases pulmonary and extrapulmonary, new and previously treated over a three-year period.

A retrospective study was conducted at the Bacteriology Department of Mohammed V Military Instruction Hospital over three years. Data were obtained from the laboratory information system. Clinical samples were processed using conventional bacteriological methods and molecular techniques. Drug resistance was assessed using the HAIN reverse hybridization method (GenoType® MTBDRplus). Statistical analysis was carried out using IBM SPSS Statistics 19 and Microsoft Excel 2019.

The study included 464 TB patients with positive cultures, comprising both new and previously treated cases. The average age was 42.2 years (range: 8–88 years), with a male predominance (74%) and a sex ratio of 2.8. Pulmonary TB cases represented the majority of samples (84.8%), while extrapulmonary cases accounted for 15.2%. Direct microscopy was positive in 74% of cases, and cultures were positive in 100%. INH resistance was observed in 9% of patients (43 out of 464). Molecular characterization of resistance revealed that 63% of the INH-resistant isolates carried mutations in the katG gene, while 37% had mutations in the inhA promoter region.

This study reveals a 9% prevalence of INH resistance among TB cases over a three-year period, emphasizing a significant but underrecognized threat to TB control in Morocco. The majority of INH-resistant strains were associated with katG mutations, while a smaller proportion carried inhA mutations. These findings highlight the limitations of diagnostic tools that focus only on RIF resistance and stress the need for broader molecular testing to detect INH resistance. Enhancing diagnostic capabilities and updating treatment guidelines to include INH resistance detection are critical steps toward improving TB control and preventing the spread of MDR-TB in Morocco. - Received: - Version Posted: