Drug resistance pattern and mutation pattern in pediatric tuberculosis: Study from north India

Area of Science:

• Microbiology
• Genetics
• Pediatric Infectious Diseases

Background:

• Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) pose global health threats.
• Molecular diagnostics like GenoType MTBDRplus enable rapid detection of resistance, facilitating timely management of DR-TB.
• Understanding regional mutation patterns for isoniazid (INH) and rifampicin (RIF) resistance is crucial for epidemiology.

Purpose of the Study:

• To investigate genetic mutations associated with drug-resistant tuberculosis in children under 12 years old.
• To analyze resistance patterns in pediatric pulmonary and extrapulmonary tuberculosis cases.

Main Methods:

• Retrospective analysis of 3461 suspected TB cases over 54 months (January 2015 - June 2019).
• Utilized Hain's GenoType MTBDRplus VER 2.0 for drug resistance testing on 250 Mycobacterium tuberculosis isolates.
• Compared GenoType MTBDRplus results with Xpert MTB/Rif Assay.

Main Results:

• 15.2% of tested isolates (38/250) were drug-resistant tuberculosis (DR-TB).
• MDR-TB accounted for 22 cases, with 13 isoniazid monoresistant and 3 rifampicin monoresistant.
• Common RIF resistance mutations involved absence of rpoB WT8 and presence of rpoB MUT 3 (88%). Isoniazid resistance was linked to katG MUT 1.
• GenoType MTBDRplus identified mutations missed by Xpert MTB/Rif Assay, including those outside the S531L locus.

Conclusions:

• Xpert MTB/Rif Assay alone may miss isoniazid monoresistance, highlighting the need for comprehensive testing.
• GenoType MTBDRplus significantly reduces turnaround time for DR-TB diagnosis, enabling earlier patient management.
• Molecular testing is essential for accurate and timely diagnosis of drug-resistant tuberculosis in children.