Tuberculosis Treatment Pathway (NTEP)

Undernutrition is the single leading driver of TB mortality in India. The RATIONS trial (Bhargava et al., Lancet 2023) demonstrated that targeted nutritional supplementation reduces TB incidence among household contacts by 40 to 50%, and that a BMI below 16 is independently associated with a 4 to 5 fold increase in early mortality. Providing specific macro- and micro-nutritional targets alongside ATT is a critical standard of care, not optional supportive therapy.

• R - Rifampicin: Red/Orange secretions, Rapid CYP450 induction (most potent inducer in clinical medicine).
• I - Isoniazid (INH): Injures Nerves (peripheral neuropathy - always give B6), Injures Hepatocytes (hepatitis).
• P - Pyrazinamide: Polyarthralgia (hyperuricaemia), most Potent hepatotoxin of the four.
• E - Ethambutol: Eye issues (retrobulbar optic neuritis, red-green colour blindness). Baseline visual acuity is mandatory.

• When to stop ALL ATT: AST/ALT exceeds 5x ULN (asymptomatic) or exceeds 3x ULN with hepatitis symptoms (nausea, vomiting, anorexia, jaundice).
• Wait: Observe until LFTs normalise or fall below 2x ULN and symptoms resolve completely.
• Rechallenge order: Reintroduce drugs sequentially, one at a time, with 3 to 7 days between each: R first (least hepatotoxic), then H, then Z last (most hepatotoxic). If hepatitis recurs with a specific agent, omit it permanently and substitute.
• Never rechallenge Pyrazinamide if it was the identified culprit. Extend treatment duration instead.

Working through an actual case? The ATT-Induced Liver Injury & Rechallenge pathway carries the bridging regimen and the sequential rechallenge schedule.

• DS-TB: Pan-susceptible to all first-line drugs.
• H-Mono/Poly DR-TB: Resistant to Isoniazid (H), but definitively susceptible to Rifampicin (R). Requires FL-LPA for confirmation.
• MDR/RR-TB: Resistant to Rifampicin (with or without H resistance), but susceptible to Fluoroquinolones (FQ).
• Pre-XDR TB: MDR/RR-TB with additional resistance to any Fluoroquinolone.
• XDR TB: Pre-XDR TB with additional resistance to Bedaquiline (Bdq) and/or Linezolid (Lzd).

NTEP strictly prioritises shorter all-oral regimens (BPaLM for MDR, BPaL for Pre-XDR). However, BPaLM/BPaL are strictly contraindicated in patients below 14 years or those with severe EPTB. The engine reroutes these phenotypes to the 18 to 20 month Longer Oral Regimen.

Drug absorption is highly variable based on gastric contents. Rifampicin Cmax is severely blunted by food, risking acquired resistance. Conversely, Bedaquiline absorption increases nearly two-fold when administered with a high-fat meal. This module dictates specific food timing instructions for every drug to prevent therapeutic failure.

This engine uses the official NTEP 2024 adult weight bands: 25 to 39 kg (2 FDCs), 40 to 54 kg (3 FDCs), 55 to 69 kg (4 FDCs), and 70 kg and above (5 FDCs). Paediatric bands: 4 to 7 kg (1 FDC), 8 to 11 kg (2 FDCs), 12 to 15 kg (3 FDCs), 16 to 24 kg (4 FDCs). These are NOT arbitrary - they are calibrated to deliver therapeutic mg/kg doses across the population range.