Phenotypic isoniazid resistance and associated mutations in pediatric tuberculosis

Abstract

Background and objectives: Tuberculosis (TB) remains one of the most challenging global health problems as resistance to first-line antimycobacterial drugs continues to rise in many countries worldwide. Isoniazid-resistant TB without MDR-TB poses a serious threat to the management and control of TB across the world. The aim of this study was to investigate the extent of katG315 and inhA-15 mutations in Mycobacterium tuberculosis strains isolated from pediatric TB patients from a tertiary care hospital.

Material and methods: A total of 51 pulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to INH was detected by 1% proportion method. katG315 and inhA-15 genes were amplified by PCR and detection of mutations in katG315 and inhA-15 genes was done by sequencing.

Result: A sample size of only 51 could be achieved due to short duration of the study. 36/51 (70.6%) culture isolates were obtained and put for drug susceptibility test, 5(13.89%) were resistant for isoniazid. M. tuberculosis DNA was found in fifty samples. Mutations in either katG315 or inhA-15 genes were found in 7/50 (14%) samples. Six of seven (85.7%) had mutation in katG315 gene and 1/7 (14.2%) had mutation in inhA-15 gene.

Conclusion: INH resistance not only reduces the probability of treatment success, but may also facilitate the spread of MDR-TB and reduce the effectiveness of INH preventive therapy (IPT) therefore quantification of the magnitude of INH resistant TB and variation in frequency of isoniazid resistance associated mutations is important.

Keywords: Isoniazid resistance; Pediatric; Tuberculosis; inhA; katG.