Genetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis in Mongolia

Abstract

Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al. analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations (B. Buyankhishig, T. Oyuntuya, B. Tserelmaa, J. Sarantuya, et al., Int J Mycobacteriol 1:40–44, 2012, https://doi.org/10.1016/j.ijmyco.2012.01.007). The GenoType MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType MTBDRplus assay, 127 (31.1%) were resistant to rifampin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and 2 (0.5%) had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 strains with any inhA mutation, 290 (98.0%) had a C15T mutation. The proportions of isoniazid-resistant strains with katG mutations were 25.3% among new cases and 36.2% among retreatment cases (P = 0.03) and 17.0% among rifampin-susceptible strains and 52.8% among rifampin-resistant strains (P < 0.01). Rifampin resistance was significantly associated with the katG mutation (adjusted odds ratio, 5.36; 95% confidence interval [CI], 3.3 to 8.67, P < 0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than in those from new cases, and the proportion in cases with rifampin resistance was higher than in cases without rifampin resistance.

Mutaciones genéticas que confieren resistencia a Isoniacida en pacientes con tuberculosis en Lima Centro, Perú 2017-2018

“…Prevalencia del Gen inh A detectada mediante Genotype MTBDRplus, Lima Centro, Perú 2017-2018 N=357(46% de 777 casos) etionamida en un 68,1 % (p<0.05) seguido de rifampicina en un 47,2 % (p<0.05) y estreptomicina en un 33 % (p<0.05). Un estudio en Mongolia encontró que la resistencia a la rifampicina se asoció significativamente (p<0.001) con la mutación katG concluyendo que las cepas resistentes a isoniacida con mutaciones en el gen katG, tenían más probabilidades de haber adquirido resistencia a rifampicina que las cepas con mutaciones en el gen inhA [8] , asimismo diferentes estudios revelan que la mutación en el gen katG se asocia con una mayor proporción de resistencia a rifampicina y las mutaciones en el promotor inhA con monorresistencia a isoniacida [9,10] .…”

Evaluating the Sensitivity of Different Molecular Techniques for Detecting Mycobacterium tuberculosis Complex in Patients with Pulmonary Infection

“…Resistance to RIF occurs because of mutations in the region between amino acid codons 507–533 within the rpo B gene ( Jagielski et al 2018 ). However, resistance to INH occurs because of more complicated genetic mutations involving two genes, codon 315 of the kat G gene and the regulatory region within the inh A gene ( Narmandakh et al 2020 ).…”

Childhood Tuberculosis in Mongolia: Trends and Estimates, 2010-2030

“…To reduce this high childhood TB burden and achieve the global goals detailed above, it is fundamental to improve the efforts to understand the current characteristics of childhood TB. Over the years, studies in Mongolia have been conducted with a focus on adult TB (Naranbat et al 2009;Dobler et al 2018), multidrug-resistant TB (Ganzaya et al 2013;Narmandakh et al 2020), and prevalence of TB among prisoners (Yanjindulam et al 2012) and little is known about childhood TB. Understanding current trends and future estimates of TB will have a greater impact on planning, efficient allocation of available resources, and the development of specific strategies and public health interventions to control this disease better (Cole et al 2020).…”