A RETROSPECTIVE STUDY OF SECOND LINE DRUG RESISTANCE AND THEIR MUTATIONAL PATTERNS IN MYCOBACTERIUM TUBERCULOSIS USING GENOTYPE MTBDRSL ASSAY
K. Suresh, Dr. P. V. Ramana* and Dr. P. Satyanarayana Raju
Background: As a persistent global health problem Pulmonary Tuberculosis is causing immeasurable suffering and wreaking havoc in mankind especially in developing countries.[1,2] A notable challenge in control and management of tuberculosis is the drug resistance to anti Tuberculosis drugs leading to Multi Drug Resistant Tuberculosis (MDR-TB) and Extensively Drug Resistant Tuberculosis (XDR-TB). This is further compounded by the expensive treatment regimens, adverse side effects and toxicity in patients undergoing treatment.[5,6] After the approval by WHO there is a great deal of interest evoked worldwide and in India to use Molecular Genotype susceptibility tests for rapid detection of drug resistance (MDR-TB and XDR-TB) in Pulmonary Tuberculosis. At the present moment the Genotype MTBDRsl assay (hain life science, Germany) is the only available commercial assay to detect Drug Resistance to Second Line anti tuberculosis drugs. This test detects and targets resistance to Fluoroquinolones and second line Injectable drugs Amikacin (Am), Kanamycin (Km) and Capreomycin (Cm). Materials and Methods: This study has been done in IRL-Visakhapatnam to know the XDR cases in Diagnosed cases of MDR and INH mono Resistant pulmonary tuberculosis and to know the pattern of mutations in XDR and Pre-XDR cases. The samples received in the IRL lab. between January 2018 and December 2018 which were drug resistant either MDR-TB/RR-TB or Isonaizid resistant were analysed. Results: This study conducted has shown that out of the 2038 sample received 1279 samples were Males (62.70%) and Females were 759 (37.20%). The Sex ratio is 2:1. Among the MDR isolates Fluoroquinolone resistance was 15.25%. and second-line Injectable drugs resistance was 0.9% The combined Fluoroquinolone and second line injectable Aminoglycoside resistance was 0.5%. In this study the Genotype MTBDRsl assay has shown a mutation in Codon 94 for Fluroquinolone’s resistance. Amongst the mutations in codon 94 the most commonly seen mutation was gyr-A MUT3c in 63 samples. In 6 cases we have observed the rare gyr-A MUT3d mutation which has not been reported by other such similar studies making it a unique feature. In 29 samples we found gyr-B WT1 missing which indicates the presence gyr-B mutations in this region. In addition to the above observation, out of the rrs mutations for second line injectable drugs we found that a rrs MUT1 was seen commonly in 12 cases while rrs MUT2 was seen in 11 samples. This study also demonstrated mutations in 5 samples in eis region which were detected by the absence in eis MUT2.
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