Chitra Alagappan1, Smita Sunil Shivekar1, Usharani Brammacharry2, Vidya Raj Cuppusamy Kapalamurthy1, Anbazhagi Sakkaravarthy3, Rathinasamy Subashkumar4, Muthuraj Muthaiah5. 1. State TB Training and Demonstration Centre, Intermediate Reference Laboratory, Government Hospital for Chest Diseases, Gorimedu, Puducherry, India. 2. Department of Biomedical Genetics, Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India. 3. Department of Environment Science, Central University of Kerala, Kasaragod, Kerala, India. 4. Department of Biotechnology, Sri Ramakrishna College of Arts and Science (Formerly SNR Sons College), Coimbatore, Tamil Nadu, India. 5. State TB Training and Demonstration Centre, Intermediate Reference Laboratory, Government Hospital for Chest Diseases, Gorimedu, Puducherry, India. Electronic address: muthuraj1970@gmail.com.
Abstract
OBJECTIVES: The prevalence of isoniazid (INH) monoresistance is high in India. In this study, molecular epidemiological characteristics associated with INH resistance mutations in Mycobacterium tuberculosis in codon katG315 and in the promoter region of the inhA gene were investigated. METHODS: Sputum specimens of smear-positive tuberculosis (TB) patients were subjected to GenoType MTBDRplus assay to identify katG and inhA mutations in M. tuberculosis. In addition to the current study, 17 publications assessed 14100 genotypically resistant M. tuberculosis isolates for mutations in katG inclusive of codon 315. RESULTS: In total, 1821 (11.8%) of 15438 INH-resistant strains had detectable mutations: 71.0% in katG315 and 29.0% in the inhA promoter region. The prevalence of IHN monoresistance was 89.1% in the economically-active age group, 0.4% in the paediatric age group and 10.5% in those aged >60years; the rate in males and females was 12.0% and 10.8%, respectively. Meta-analysis derived a pooled katGS315T resistant TB prevalence of 67.3% (95% CI 59.3-75.4%) with Q=732.19, I2=98.35% and P=0.000 for treated TB cases. CONCLUSION: INH resistance was spread widely and transmission of INH-resistant isolates, especially with katG315T mutation, was confirmed. Therefore, it is important to diagnose katG315T mutants among INH-resistant strains as it may be a risk factor for subsequent development of multidrug-resistant TB (MDR-TB). Prompt detection of patients with INH-resistant strains would expedite modification of treatment regimens, and appropriate infection control measures could be taken in time to diminish the risk of further development and transmission of MDR-TB.
OBJECTIVES: The prevalence of isoniazid (INH) monoresistance is high in India. In this study, molecular epidemiological characteristics associated with INH resistance mutations in Mycobacterium tuberculosis in codon katG315 and in the promoter region of the inhA gene were investigated. METHODS: Sputum specimens of smear-positive tuberculosis (TB) patients were subjected to GenoType MTBDRplus assay to identify katG and inhA mutations in M. tuberculosis. In addition to the current study, 17 publications assessed 14100 genotypically resistant M. tuberculosis isolates for mutations in katG inclusive of codon 315. RESULTS: In total, 1821 (11.8%) of 15438 INH-resistant strains had detectable mutations: 71.0% in katG315 and 29.0% in the inhA promoter region. The prevalence of IHN monoresistance was 89.1% in the economically-active age group, 0.4% in the paediatric age group and 10.5% in those aged >60years; the rate in males and females was 12.0% and 10.8%, respectively. Meta-analysis derived a pooled katGS315T resistant TB prevalence of 67.3% (95% CI 59.3-75.4%) with Q=732.19, I2=98.35% and P=0.000 for treated TB cases. CONCLUSION: INH resistance was spread widely and transmission of INH-resistant isolates, especially with katG315T mutation, was confirmed. Therefore, it is important to diagnose katG315T mutants among INH-resistant strains as it may be a risk factor for subsequent development of multidrug-resistant TB (MDR-TB). Prompt detection of patients with INH-resistant strains would expedite modification of treatment regimens, and appropriate infection control measures could be taken in time to diminish the risk of further development and transmission of MDR-TB.