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Tuberculosis Preventive Therapy (TPT)
What is TPT?
TPT (also called latent TB treatment) refers to treatment given to people with latent TB infection (LTBI) - a state of persistent immune response to M. tuberculosis antigens with no evidence of clinically manifest active TB. The goal is to prevent progression from latent infection to active TB disease. About 5-10% of infected individuals develop TB disease over their lifetime; this risk is dramatically higher in immunocompromised individuals.
TPT is not the same as treating active TB disease. Active TB must always be excluded before starting any TPT regimen.
Mechanism of Action
Preventive therapy reduces the viable bacilli population in inactive or radiographically invisible lesions in the lungs and elsewhere. It may also prevent the establishment of new infection with M. tuberculosis in recently exposed individuals ("primary prophylaxis"). Isoniazid reduces TB incidence by approximately 80% in the year of treatment, with a residual 50% protection visible for up to 10-12 years post-treatment and ~60% overall reduction in cumulative incidence.
- Murray & Nadel's Textbook of Respiratory Medicine, p. 1167
Who Gets TPT? (Indications, in order of priority)
| Group | Risk / Rationale |
|---|---|
| People living with HIV (PLHIV) | 21x higher risk of active TB; 3-16% per year incidence if co-infected; WHO recommends TPT for ALL PLHIV without active TB, regardless of TST/IGRA result |
| Close contacts of new TB cases | 2-4% develop TB in the first year; children/adolescents have ~twice the risk |
| Recent tuberculin converters | Skin test conversion (≥10 mm increase in 2 years) = newly infected; highest risk in first 1-2 years |
| Stable radiographic findings of old TB | History of TB never treated, or inadequately treated; risk 0.4-3.5%/year |
| Children <5 years with positive TST | High priority - recent infection very likely, risk of severe disease high |
| Immunosuppressed individuals | Prolonged steroids (≥15-20 mg prednisone >2-3 weeks), immunosuppressive therapy, hematologic malignancies, end-stage renal disease |
| Before TNF antagonist therapy | Biologic agents dramatically reactivate LTBI |
| Silicosis / coal worker's pneumoconiosis | Occupational risk greatly augments TB progression |
| Contacts of MDR/RR-TB | New strong recommendation in the 2nd edition of WHO TPT guidelines (2023) |
Murray & Nadel's Textbook of Respiratory Medicine, p. 1167-1168
Recommended TPT Regimens
Preferred Shorter Regimens (WHO & CDC-recommended as of 2025-2026)
| Regimen | Duration | Dosing | Notes |
|---|---|---|---|
| 3HP | 3 months | Isoniazid 900 mg + Rifapentine 900 mg once weekly | Preferred short regimen; suitable for adults and children ≥2 years; can be self-administered |
| 1HP | 1 month | Isoniazid 300 mg + Rifapentine 600 mg once daily | Newest regimen; extremely short; evidence growing |
| 3HR | 3 months | Isoniazid + Rifampicin daily | Suitable for children; good alternative |
| 4R | 4 months | Rifampicin alone daily | No isoniazid resistance concern; preferred if INH-resistant source case |
Longer Isoniazid-based Regimens
| Regimen | Duration | Notes |
|---|---|---|
| 6H | 6 months daily isoniazid | Classic regimen; lower completion rates |
| 9H | 9 months daily isoniazid | Higher efficacy than 6H; still used in some settings |
| 36H | 36 months daily isoniazid | Recommended by WHO for PLHIV in high-TB-burden countries to reduce reinfection risk (conditional recommendation) |
Given low completion rates with 6-9 month isoniazid, shorter rifamycin-based regimens are now preferred where feasible. - CDC Yellow Book 2026
Special Considerations
PLHIV
- All PLHIV without active TB should receive TPT as part of a comprehensive HIV care package, regardless of TST/IGRA results.
- In high-TB-transmission settings, 36-month daily isoniazid is conditionally recommended (to mitigate reinfection).
- Benefit persists even in those receiving antiretroviral therapy.
Children
- After ruling out active TB in a newborn born to a TB mother: 6 months of isoniazid preventive therapy, followed by BCG vaccination.
- 3HR is preferred for younger children.
- Park's Textbook of Preventive and Social Medicine
Pregnancy
- TPT is not generally withheld if the indication is strong (e.g., HIV-positive pregnant women).
- Pyridoxine (vitamin B6) should be co-administered with isoniazid to prevent neuropathy.
- Murray & Nadel's Textbook of Respiratory Medicine
TNF Antagonist Therapy / Biologics
- Screen for LTBI before starting anti-TNF therapy (and other targeted biologics).
- Complete at least 1 month (preferably the full course) of TPT before starting immunosuppressive biologics when possible.
- SPIN-FRT Expert Consensus (PMID 39149807) provides specific guidance for psoriasis patients on biologics.
Contacts of MDR/RR-TB
- The 2nd edition WHO consolidated TPT guidelines introduced a new strong recommendation for contacts of MDR/RR-TB to receive preventive treatment - a major update from earlier guidance.
Key Steps Before Starting TPT
- Rule out active TB disease (history, symptoms, CXR, sputum if indicated)
- Test for LTBI (TST or IGRA) - though in PLHIV, TPT is given regardless of test result
- Check baseline LFTs (especially if using rifamycin-based regimens or known hepatic disease)
- Assess drug interactions (especially antiretrovirals with rifampicin/rifapentine)
- Ensure pyridoxine supplementation with isoniazid-containing regimens
Adverse Effects and Monitoring
| Drug | Main Concerns |
|---|---|
| Isoniazid | Hepatotoxicity, peripheral neuropathy (give pyridoxine 25-50 mg/day), pellagra-like syndrome |
| Rifampicin / Rifapentine | Hepatotoxicity, drug interactions (CYP450 inducers), orange discoloration of secretions, flu-like syndrome (rifapentine) |
| Combined regimens | Monitor LFTs; stop if ALT >3x ULN with symptoms or >5x ULN asymptomatic |
WHO End-TB Strategy Context
About one-fourth of the world's population has LTBI. With 5-10% lifetime progression risk, targeted TPT at high-risk groups is a cornerstone of the WHO End TB Strategy and the 2023 UN High Level Meeting on TB targets. The 2nd edition of the WHO consolidated TPT guidelines (2023) contains 21 recommendations covering the full cascade of care: identifying high-risk individuals, screening, testing, choosing the right regimen, managing adverse events, and programmatic monitoring.
Recent Evidence (PubMed, 2024-2026)
- PMID 37991008 (Meta-Analysis, 2024): Screening and effectiveness of preventive treatment in PLHIV in low-incidence settings - confirms efficacy of TPT in HIV-positive populations.
- PMID 39149807 (Practice Guideline, 2025): Expert consensus on TPT before biologics in psoriasis patients - guides practical management of LTBI in immunosuppressed patients.
- PMID 40898127 (Meta-Analysis, 2025): LTBI prevalence and risk factors in rheumatic disease patients - highlights an important high-risk group often encountered in clinical practice.
- WHO, December 2025: Released guidance on evidence generation for novel TPT regimens, signaling ongoing research into even shorter or more effective preventive treatments beyond the current options.
Find latest WHO TPT guidelines PDF or clinical practice algorithms
Searching the Web
WHO consolidated guidelines tuberculosis preventive treatment second edition 2023 PDF download
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WHO TB preventive therapy clinical algorithm flowchart 2024 2025
Here are all the key WHO TPT guideline documents and clinical algorithms I found:
WHO TB Preventive Therapy - Official Documents & PDFs
1. WHO Consolidated Guidelines on TB - Module 1: Prevention (2nd Edition, 2024)
This is the primary, most current WHO TPT guideline document.
- Official WHO page: WHO Module 1 Prevention - TPT 2nd Edition
- Direct PDF download (via IRIS/mirror):
What it contains (21 recommendations covering):
- New strong recommendation: TPT for contacts of MDR/RR-TB (6 months levofloxacin = 6Lfx, based on TB CHAMP and V-QUIN RCTs)
- Integrated screening algorithms from the 2021 WHO TB screening and 2022 TB infection testing guidelines
- Revised regimen recommendations (3HP, 1HP, 3HR, 4R, 6H, 9H)
- Monitoring, adherence support, and programmatic performance frameworks
2. WHO Operational Handbook on TB - Module 1: Prevention (2nd Edition, 2024)
The practical companion - contains actual clinical flowcharts and implementation tools.
- Direct PDF download:
Key clinical algorithm inside (PLHIV):
Screen for symptoms (cough, fever, weight loss, night sweats)
- No symptoms → TB unlikely → Initiate TPT immediately
- Any symptom → Chest X-ray + Xpert MTB/RIF/Ultra + culture → If TB excluded → Initiate TPT; If TB confirmed → Treat for TB
3. Clinical Handbook of TB Management Protocols (2024)
A widely-used practical reference with multiple decision flowcharts:
Contains algorithms for:
- TB screening in ambulatory PLHIV
- TPT initiation pathways
- DR-TB decision trees
4. NCBI Bookshelf - WHO TPT Recommendations (Full Text, Free)
Searchable online version of the 2024 WHO TPT guidelines with all 21 recommendations:
Summary of the WHO Clinical Algorithm for TPT (PLHIV)
Person with HIV
│
▼
Screen for 4 symptoms:
Cough | Fever | Weight loss | Night sweats
│
┌───┴───┐
None Any
│ │
▼ ▼
TPT now Further evaluation
(CXR ± Xpert MTB/RIF/Ultra)
│
┌────┴────┐
TB ruled TB found
out │
│ ▼
▼ Treat TB
TPT now
For non-HIV household contacts and other high-risk groups, the cascade is:
- Identify high-risk individual
- Rule out active TB (symptom screen + CXR if indicated)
- Test for TB infection (TST or IGRA; skipped in children <5 and PLHIV)
- Select TPT regimen based on age, drug susceptibility of source case, and drug availability
- Start TPT, monitor for adverse effects, support adherence
- Record and report outcomes
Key 2024 Updates vs. 2020 (1st Edition)
| Change | Detail |
|---|---|
| New strong recommendation | 6Lfx (levofloxacin x 6 months) for MDR/RR-TB contacts |
| Merged recommendations | HIV screening algorithm recs 11+12 consolidated into one pathway |
| Withdrawn recommendations | 2 older recommendations removed due to implementation issues |
| Terminology update | Aligned with current WHO TB terminology standards |
| Research gaps updated | WHO released further guidance on novel regimen evidence generation (Dec 2025) |
December 2025 Update
WHO released a guidance document on evidence generation for novel TPT regimens (Dec 21, 2025), signaling active pipeline work on regimens even shorter than 1HP - though no new regimens have been formally recommended yet as of mid-2026.
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