Prevalence of isoniazid resistance-conferring mutations associated with multidrug-resistant tuberculosis in Free State Province, South Africa

Abstract

Background. Multidrug-and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB) threaten local and global control of the disease. The molecular line-probe assay (LPA) provides rapid diagnosis and early management of MDR-TB. The LPA detects mutations of katG and inhA genes associated with isoniazid (INH) resistance in Mycobacterium tuberculosis isolates. The katG and inhA genes are associated with high-and low-level INH resistance, respectively, as well as cross-resistance to ethionamide in the case of inhA gene mutations. Patients with MDR-TB due to an inhA mutation could benefit from the use of high-dose INH -instead of ethionamide -in their MDR-TB regimen. Objectives. To determine the frequencies of katG and inhA mutations that conferred INH resistance among MDR-TB isolates during 2014 -2016 in Free State (FS) Province of South Africa. Methods. We retrospectively reviewed MDR-TB isolates assayed with GenoType MTBDRplus (Hain Lifescience, Germany) (LPA) at the central TB laboratory of Universitas Academic Hospital, Bloemfontein, FS, and calculated the frequencies of katG and inhA mutations. Results. Among 918 MDR-TB isolates, the prevalence of katG, inhA and katG plus inhA mutations was 63.9%, 13.4% and 22.7%, respectively. Approximately 60% (n=536; 58.4%) of the isolates were obtained from male patients. The patients' ages ranged from 1 to 89 (median 37) years. The Xhariep district had the highest incidence of INH resistance-conferring mutations in the province. Conclusions. katG-associated mutations are the predominant INH resistance-conferring mechanism among MDR-TB isolates in the FS. Patients infected with isolates that harbour the katG mutation are unlikely to benefit from high-dose INH therapy in the bedaquiline (BDQ)-containing modified short MDR-TB regimen. They may, however, benefit from the inclusion of ethionamide in the regimen. Dual katG and inhA gene mutations make these patients unlikely to respond to either high-dose INH or ethionamide and should now be considered for either the BDQ-containing long MDR-TB regimen or an individualised treatment regimen, depending on fluoroquinolone susceptibility. Clinicians should familiarise themselves with interpreting various INH resistance-conferring mutation results and their implications for management of MDR-TB treatment.S Afr Med J 2019;109(9):659-664. https://doi.

Magnitude of Phenotypic and MTBDRplus Line Probe Assay First-Line Anti-Tuberculosis Drug Resistance Among Tuberculosis Patients; Northwest Ethiopia

“…Tuberculosis (TB) is among the primary health problems, 1,2 particularly in lowincome countries, and is considered as the leading cause of death from a single infectious disease ranking above HIV/AIDS. [3][4][5][6][7][8][9] Worldwide, an estimated 10.0 million people felt ill with an estimated 1.4 million deaths in 2019.…”

Rapid and Simple Detection of Isoniazid-Resistant <i>Mycobacterium tuberculosis</i> Utilizing a DNA Chromatography-Based Technique

“…resistant MTB strains that are often resistant even to other drugs (5,21). Furthermore, studies have indicated a high prevalence of MDR-MTB carrying this mutation of katG 315 (AGC > ACC) from some high TB burden countries such as Bangladesh (80%) (22), Russian Federation (93%) (23), South Africa (87%) (24), and Zambia (91%) (25).…”

TB or not TB? Definitive determination of species within the Mycobacterium tuberculosis complex in unprocessed sputum from adults with presumed multidrug‐resistant tuberculosis

“…Isoniazid resistance in patients with rifampicin resistant was uncommon, accounting for about 29% compared to over 64% in South Africa [ 48 ] and 78% in China [ 49 ]. In the present study, isoniazid monoresistance was categorised from direct sputum samples which was negative in a large number of patients [ 30 ], as compared to MTC isolates in two studies [ 48 , 49 ].…”