TST (Tuberculin Skin Test) Interpretation Table

Row 1: Induration > 5 mm = Positive

• HIV / severe immunosuppression (e.g., patients on steroids, organ transplant recipients, TNF-alpha inhibitors): The immune system is weakened, so a reduced cellular immune response still likely reflects true TB infection. Waiting for a larger reaction could mean missing the diagnosis.
• Close contacts of TB: These people have had direct, known exposure to an active TB case - so any measurable induration strongly suggests infection.
• History of prior TB: Prior infection already primes the immune system. Even a small reaction is meaningful.

In these patients, the body may NOT mount a big reaction even if infected - so a lower bar is set.

Row 2: Induration > 10 mm = Positive

• Recent immigrants (from high TB-burden countries)
• IVDA (intravenous drug abusers)
• Age < 4 years or adolescents with exposure from high-risk groups
• High-risk occupations: HCW (healthcare workers), care home staff, prison workers

• Recent immigrants from TB-endemic regions (South Asia, Sub-Saharan Africa, etc.) have a much higher background prevalence.
• IVDA: IV drug users have higher rates of TB due to poor health, shared spaces, and often co-existing HIV.
• Children < 4 years: Young children have immature immunity and can rapidly progress from latent to active TB, so earlier detection matters.
• HCW / care homes / prisons: Occupational exposure to patients or populations with high TB rates.

Row 3: Induration > 15 mm = Positive

• Prior BCG vaccination (very common in India)
• Exposure to non-tuberculous mycobacteria (NTM)

Key Concept: What is being measured?

Summary Table (Simplified)

• 1 TU PPD RT23 = 5 TU PPD-S (the Indian standard uses RT23, while WHO uses PPD-S)
• A positive TST means the person is either susceptible to TB or already has TB infection - it does NOT distinguish active from latent disease
• Repeated TST can cause desensitization (booster effect), reducing the wheal in subsequent tests - this is why it should not be done repeatedly without reason

O = Ofloxacin

Context from your image - the Hmono/poly DRTB regimen:

• Intensive phase (3 months): HRZe - Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
• Continuation phase (4 months): HRe - Isoniazid, Rifampicin, Ethambutol

• Intensive phase (4-6 months): CHOBZe - Cycloserine, Ofloxacin, Bedaquiline (or other drugs), Pyrazinamide, Ethambutol
• Continuation phase (5 months): COZe

"O" in the Hmono TB / ZERO regimen = Ofloxacin, a second-line fluoroquinolone antibiotic used in drug-resistant TB treatment.

XDR/Poly DRTB Regimen - Drug Decoding

The subscript numbers (L₂, C₂) denote the dose in hundreds of mg - so L₂ = Linezolid 600 mg (some notes use 600 mg as the standard dose from the ZeNix trial) and C₂ = Clofazimine 200 mg OR they may simply indicate these are Group 2 drugs in the NTEP classification.

About each drug:

• A bacteriostatic oxazolidinone that inhibits protein synthesis (50S ribosomal subunit)
• Standard dose: 600 mg/day (reduced from 1200 mg after ZeNix trial showed equal efficacy with fewer side effects)
• Key side effects: peripheral neuropathy, optic neuritis, myelosuppression (thrombocytopenia)

• Originally an anti-leprosy drug, now a core drug in DR-TB
• Mechanism: binds mycobacterial DNA, also generates reactive oxygen species
• Side effects: skin hyperpigmentation (reddish-brown discoloration), GI upset, QTc prolongation

• A newer drug (FDA approved 2012), first new TB drug in 40 years
• Mechanism: inhibits mycobacterial ATP synthase (unique target, no human ATP synthase cross-reactivity)
• Side effects: QTc prolongation (must monitor ECG), hepatotoxicity, nausea
• Duration: typically used for 24 weeks (6 months), though NTEP India now extends to the full intensive phase

The BPaL Connection

BPaL vs BPaLM for Drug-Resistant TB

Drug Composition

Indications (WHO 2022 Guidelines)

Key Clinical Trial Evidence

Nix-TB & ZeNix Trials (BPaL)

• Nix-TB (2020, NEJM): 109 patients with XDR-TB or treatment-intolerant MDR-TB
  • 90% favorable outcomes at 6 months post-treatment
  • High adverse event rate: 81% peripheral neuropathy, 48% had dose reduction of linezolid
  • Led to FDA approval of Pretomanid in 2019
• ZeNix (2022): Tested different linezolid doses within BPaL
  • Linezolid 600 mg (not 1200 mg) showed similar efficacy with significantly fewer adverse effects
  • Established 600 mg as the preferred linezolid dose in BPaL

TB-PRACTECAL Trial (BPaLM vs BPaL vs Standard Care)

• BPaLM was non-inferior AND superior to standard care
• BPaLM also had fewer serious adverse events than standard care - a remarkable finding
• NEJM interim analysis (2022, PMID 36546625) showed similarly striking results: 11% vs 48% unfavorable outcomes

Efficacy Comparison: BPaL vs BPaLM

Adverse Effects Comparison

Key safety concern in BPaLM: Three QT-prolonging drugs together (Bedaquiline + Moxifloxacin + Linezolid) - rigorous ECG monitoring is mandatory.

Practical Summary

Bottom Line

The Confusion Explained: Why Are There Two Regimens for Each Category?

The Master Framework

The notes are showing you BOTH because NTEP India officially adopted BPaLM/BPaL only in September 2024. Notes written slightly before this will still contain the older regimens, which are still used when BPaLM/BPaL is not eligible.

For MDR-TB: Which to Use?

New (PREFERRED): BPaLM - 6 months

• Bedaquiline + Pretomanid + Linezolid + Moxifloxacin
• Use when: Patient has not been exposed to any of these drugs for more than 1 month and FQ-susceptible
• Success rate: ~91%
• Duration: 6 months only
• WHO recommendation: Strong (2022); NTEP India: Approved Sept 2024

Old (ALTERNATIVE): 9-11 month shorter oral regimen (your 2nd table)

• Patient has had > 1 month prior exposure to Bedaquiline, Pretomanid, or Linezolid
• Children below 14 years (Pretomanid not yet approved for them)
• Pregnant women (Pretomanid safety not established)
• Drug supply unavailability (BPaLM drugs not yet available at all NTEP sites)
• Resistance detected to one of the BPaLM drugs

Even Older: 18-20 month longer oral regimen

• Used when both the above are not feasible
• Contains Group A, B, C drugs built individually based on DST
• Your 2nd table shows this format (Bdq, Lfx/Mfx, Cfz, Lzd, Cs, E, Z...)

For XDR/Pre-XDR TB: Which to Use?

New (PREFERRED): BPaL - 6 months

• Bedaquiline + Pretomanid + Linezolid
• Use when: Fluoroquinolone-resistant (so Moxifloxacin dropped), no prior exposure > 1 month
• Success rate: ~88-90%
• FDA approved: 2019; NTEP India: 2024

Old (ALTERNATIVE): L₂, C₂, B regimen (bottom of 1st table / 18-30 months)

• Children below 14 years
• Pregnant women
• Prior exposure to Bdq, Lzd, or Pa
• Resistance suspected to BPaL drugs
• Sites where Pretomanid is not yet available

Clean Decision Tree

DR-TB confirmed
    │
    ├── DS-TB (H+R sensitive) ──────────────────► 2HRZE / 4HRE (Standard)
    │
    ├── H mono/poly resistant ──────────────────► HRZe (3 months) + HRe (4 months)
    │
    ├── MDR/RR-TB (R resistant ± H resistant)
    │       │
    │       ├── FQ-susceptible + BPaLM eligible? ──► BPaLM (6 months) ← PREFERRED
    │       └── BPaLM not eligible ────────────────► 9-11 month OR 18-20 month regimen
    │
    └── Pre-XDR / XDR-TB (MDR + FQ resistant)
            │
            ├── BPaL eligible? ────────────────────► BPaL (6 months) ← PREFERRED
            └── BPaL not eligible ─────────────────► L₂C₂B / 18-30 month regimen

Simple One-Line Summary