Isoniazid prophylaxis (IPT) is given to a child who is a close contact of an active TB case. The child has a positive Mantoux test (>10 mm) but a normal chest X-ray. After 6 months of isoniazid, the mechanism by which latent TB infection is prevented from progressing is:
- A Isoniazid stimulates macrophage bactericidal activity via reactive oxygen species production
- B Isoniazid is bactericidal against slowly replicating bacilli in granulomas by inhibiting mycolic acid synthesis via InhA and KasA, clearing the bacterial load below the threshold for disease reactivation ✓
- C Isoniazid prevents granuloma formation, allowing cell-mediated immunity to clear bacilli
- D Isoniazid prevents dormancy conversion by blocking mycobacterial sigma factor sigH
Correct answer: B. Isoniazid is bactericidal against slowly replicating bacilli in granulomas by inhibiting mycolic acid synthesis via InhA and KasA, clearing the bacterial load below the threshold for disease reactivation
Explanation
Isoniazid (INH) is a prodrug activated by the mycobacterial catalase-peroxidase (KatG) to reactive intermediates that inhibit the fatty acid synthase II enzymes InhA and KasA, blocking mycolic acid synthesis in the bacterial cell wall. This is bactericidal for actively dividing bacilli. In latent TB, some bacilli are slowly replicating within granulomas; INH's activity against this population reduces the bacillary burden sufficiently to prevent reactivation. INH prophylaxis reduces TB reactivation risk by approximately 60–90%.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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