Genetic polymorphism of rare mutations in Mycobacterium tuberculosis-infected patients in Delhi

Abstract

Background: There is a wide variation in existing Mycobacterium tuberculosis strains across the globe, and false results in line probe assay (LPA) can occur due to the presence of unique genetic mutations in different settings. Objectives: An attempt was made to observe uncommon mutations in multidrug-resistant tuberculosis (MDR-TB) strains and determination of genetic diversity by spoligotyping and to study the treatment outcome in patients with uncommon mutations. Materials and Methods: Band pattern analysis of LPA strips was performed as per manufacturer's instructions. DNA sequencing was performed to confirm the presence of uncommon mutations in Intermediate Reference Laboratory in Delhi state. Results: Four uncommon mutations were recognized along with 12 unique spoligotype patterns which serve as an update to worldwide databases. The noteworthy presence of a spoligotype previously rarely seen in India was the SIT53/T1 pattern. Central Asian (CAS) spoligotype was highly associated with MDR followed by Beijing type. During follow-up, the treatment outcomes of cases showing uncommon mutations were considered as cured, after completion of their treatment. Conclusion: The rifampicin resistance appears to be an effective marker of MDR-TB. The presence of uncommon mutations confirms genetic polymorphism that may require treatment targeted at both drug-resistant and drug-susceptible phenotypes for the better management of patients with MDR-TB.

Keywords

• Multidrug resistant
• sequencing
• spoligotyping
• treatment outcome
• uncommon mutations