Analysis of mutational pattern in multidrug resistant tuberculosis (MDR TB) in a geographically isolated northeastern region of India

Abstract

Objectives: To assess the mutational pattern of multidrug resistant tuberculosis and evaluate the performance of MTBDRplus and MTBDRsl in rapid detection of multidrug and second line resistance of tuberculosis in a geographically isolated population. Methods: The assay was performed directly on 375 smear positive sputum specimens from patients referred to a busy routine diagnostic lab in Manipur, northeast India. MTBDRplus andMTBDRsl were performed as per the directions of the manufacturer. Results were compared with BacT/Alert 3D culture and DST system Results: Of the 375 smear positive specimen, 364 (97.1%) gave interpretable results by MTBDRplus assay within 1 - 2 days with an additional 2days for EMB resistance of the MDR strains.Sensitivity, specificity, and positive and negative predictive values were high for rifampicin and multidrug resistant strains with a range of 98 - 100 %. Isoniazid has comparatively lower sensitivity of 81% amongst the drug compared with phenotypic BacT/Alert 3D results.The mutational pattern of this geographically isolated region didn't have much variation as shown by the absence of bands in the rpoB MUT2A/2B and inhA MUT2/3A/3B regions of the gene. Conclusions: The results of this study supports the use of MTBDRplus for rapid diagnosis of TB from smear positive specimens considering the drastic reduction of time in diagnosis and its accuracy being comparable to phenotypic methods while the MTBDRsl's ability to detect rare mutations makes it a potential method for analysing mutational patterns.