Genotypic distribution of multidrug-resistant and extensively drug-resistant tuberculosis in northern Thailand

Abstract

BackgroundMultidrug/extensively drug-resistant tuberculosis (M/XDR-TB) is a major public health problem, and early detection is important for preventing its spread. This study aimed to demonstrate the distribution of genetic site mutation associated with drug resistance in M/XDR-TB in the northern Thai population.MethodsThirty-four clinical MTB isolates from M/XDR-TB patients in the upper northern region of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005 to 2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance and rpoB for rifampicin (RIF) drug resistance. The variables included the baseline characteristics of the resistant gene, genetic site mutations, and drug susceptibility test results.ResultsAll 34 isolates resisted both INH and RIF. Thirty-two isolates (94.1%) showed a mutation of at least 1 codon for katG, inhA, and ahpC genes. Twenty-eight isolates (82.4%) had a mutation of at least 1 codon of rpoB gene. The katG, inhA, ahpC, and rpoB mutations were detected in 20 (58.7%), 27 (79.4%), 13 (38.2%), and 28 (82.3%) of 34 isolates. The 3 most common mutation codons were katG 315 (11/34, 35.3%), inhA 14 (11/34, 32.4%), and inhA 114 (11/34, 32.4%). For this population, the best genetic mutation test panels for INH resistance included 8 codons (katG 310, katG 340, katG 343, inhA 14, inhA 84, inhA 86, inhA 114, and ahpC 75), and for RIF resistance included 6 codons (rpoB 445, rpoB 450, rpoB 464, rpoB 490, rpoB 507, and rpoB 508) with a sensitivity of 94.1% and 82.4%, respectively.ConclusionThe genetic mutation sites for drug resistance in M/XDR-TB are quite variable. The distribution of these mutations in a certain population must be studied before developing the specific mutation test panels for each area. The results of this study can be applied for further molecular M/XDR-TB diagnosis in the upper northern region of Thailand.

<p>Genotypic Distribution and a Potential Diagnostic Assay of Multidrug-Resistant Tuberculosis in Northern Thailand</p>

“…27 However, a retrospective investigation during 2008-2011 found only 35.3% of 34 MDR and XDR-TB isolates from northern Thailand carrying the katG mutation at codon 315, together with others 10 loci. 4 Four mutation patterns within the fabG1-inhA promoter were confirmed in this study. The rate of 20.6% for the most common genotypes, −15 (C>T), was comparable to the global frequencies: −15 (C>T) accounted for 19.2% of inhA promoter mutation.…”

“…24 However, the study of 34 MDR and XDR-TB isolates in 2005-2012 in northern Thailand reported eight rpoB mutations with no predominant codon including 588 (26.5%), 589 (26.5%), 526 (23.5%), 571 (20.6%), 531 (17.7%), 545 (17.7%), 564 (11.8%), and 574 (11.8%). 4 Here, the S522L rarely found in rpoB mutant strains was discovered in an MDR-TB isolate. The S522L was found to involve in RIF resistance and rifabutin susceptibility.…”

“…3 However, data on MDR-TB genotypes and their distribution in this area have rarely been described. 4 MDR-TB caused by Mycobacterium tuberculosis (Mtb) that resistant to rifampicin (RIF) and isoniazid (INH) is difficult to diagnose by culture method. Its treatment relies on the second-line drugs, which are difficult to procure and much more toxic and expensive than the first-line drugs.…”

<p>Association Between the Phenotype and Genotype of Isoniazid Resistance Among <em>Mycobacterium tuberculosis</em> Isolates in Thailand</p>

“…A previous report found a high prevalence of the katG S315T gene mutation among HR-TB/MDR-TB/XDR-TB strains (58.7%-68.6%) in Thailand. 16,17 The prevalence of katG S315T varied according to the geographic region: Southeast Asia (78.4%), 18 Vietnam (85.3%), 19 Myanmar (61.2%), 20 Taiwan (29.3%), 6 Japan (25%), 10 India (67.6%), 21 Sri Lanka (67.8%), 22 Romania (52.8%), 23 Cameroon (64%), 24 and the United States (38%). 8 The different ranges of MIC found for each mutation gene can be explained by gene variation.…”

Correlations between Gene Resistant Markers and Second-Line Anti-TB Drug Resistance in Pre-XDR and XDR-TB Patients

“…Related studies have shown specificities of gene mutations in predicting kanamycin [9] [10] [11] and ofloxacin resistance [11] [12] [13] [14]. Many studies have been conducted on genotypic and phenotypic characteristics of drug resistant M. tuberculosis; however, this kind of study is rare in Thailand [15]. Better understanding of the molecular mechanisms of drug resistance in pre-XDR-TB and XDR-TB strains can contribute to the improvement of existing techniques in detecting drug resistance and help to explore new target sites and develop new diagnostic tools.…”