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The Prediction Factors of Pre-XDR and XDR-TB among MDR-TB Patients in Northern Thailand

Journal of Tuberculosis Research 2018年第1期6卷 36-48页

作者： Risara Jaksuwan Jayanton Patumanond Prasit Tharavichikul Charoen Chuchottaworn Pattana Pokeaw jongkolnee settakorn Clinical Epidemiology Unit Faculty of Medicine Chiang Mai University Chiang Mai Thailand Faculty of Medicine Thammasat University Bangkok Thailand Department of Microbiology Faculty of Medicine Chiang Mai University Chiang Mai Thailand Division of Respiratory Medicine Chest Disease Institute Nonthaburi Thailand Office of Disease Prevention and Control 10 Chiang Mai Thailand Department of Pathology Faculty of Medicine Chiang Mai University Chiang Mai Thailand

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.

关键词： Prediction Tuberculosis Drug Resistance MDR-TB XDR-TB

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

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Journal of Tuberculosis Research 2017年第3期5卷 178-188页

作者： Risara Jaksuwan Prasit Tharavichikul Charoen Chuchottaworn Jayanton Patumanond Piyada Kunawararak jongkolnee settakorn Clinical Epidemiology Unit Faculty of Medicine Chiang Mai University Chiang Mai Thailand Department of Microbiology Faculty of Medicine Chiang Mai University Chiang Mai Thailand Division of Respiratory Medicine Chest Disease Institute Nonthaburi Thailand Faculty of Medicine Thammasat University Bangkok Thailand Office of Disease Prevention and Control 10 Chiang Mai Thailand Department of Pathology Faculty of Medicine Chiang Mai University Chiang Mai Thailand

Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper north of Thailand.

关键词： XDR-TB Pre-XDR-TB Ofloxacin gyrA Kanamycin rrs

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