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

ABSTRACT

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).[3] 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.[3] 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.[8] 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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