Abstract
Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a marker to predict Pre-XDR and XDR-TB is rare. Methods: Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN). Associations between resistant genes and Pre-XDR and XDR-TB in the MDR patients were performed using exact probability tests. Univariable logistic regression was used to quantify the strength of association between the gene mutation with Mycobacterium tuberculosis and the prevalence of Pre-XDR and XDR-TB in the MDR patients. Results: The mutations in the region of the rpoB gene at codon 445 (C445T) in the Pre-XDR or XDR-TB patients were significantly 20.6 times more prevalent among the MDR-TB patients. The inhA gene mutation at codon 114 (T114G) was also significantly 8.1 times more prevalent. Conclusion: The findings can be used to predict the odds of Pre-XDR and XDR-TB in MDR-TB patients, as a guide for prevention and treatments.
Highlights
Drug-resistant (XDR) tuberculosis (TB) has emerged as a major threat to global TB control
Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN)
Our study found that Pre-XDR/XDR-TB patients significantly presented a mutation in the region of the rpoB gene at codon 445 (C445T) 20.6 times than the MDR-TB patients (P = 0.026) (Table 7)
Summary
Drug-resistant (XDR) tuberculosis (TB) has emerged as a major threat to global TB control. The low rate of diagnosis and diagnostic delay, the limited access to second-line drugs, and the poor adherence of MDR-TB patients have mainly led to the emergence of XDR-TB [4]. Most of the XDR-TB and Pre-XDR-TB patients in China were new cases, indicating the transmission of resistant strains [5] [6]. In 2016, Thailand had 80 MDR-TB patients Of these cases, 20 were on treatment for XDR-TB and 60 were on MDR-TB and Pre-XDR-TB medication [7]. The emergence of XDR-TB strains is a reflection of poor tuberculosis management and control, and this situation should be considered as an urgent global health problem, especially in developing countries and those lacking resources [10]. Molecular diagnosis will involve MDR-TB and XDR-TB detection, which is useful for predicting Pre-XDR and XDR-TB and for monitoring treatment
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