World Health Organization · 2025 consolidated edition · 377 pages
Comprehensive implementation guidance for drug-susceptible and drug-resistant TB treatment regimens, care and support for clinicians and national TB programmes worldwide.
- Issuer
- World Health Organization
- Edition
- 2025 consolidated edition
- Audience
- National TB programme managers, policy-makers, infectious disease specialists, pulmonologists, general clinicians, paediatricians, HIV clinicians, public health professionals, laboratory staff
- Evidence
- GRADE-rated recommendations based on systematic reviews, randomised controlled trials (Study 31, SHINE), individual patient data meta-analyses; good practice statements where evidence-based recommendations not feasible
- Reviewed
- 18 Oct 2026 · GMJ
What this guideline says
GMJ summary
This operational handbook consolidates WHO’s practical guidance on implementing TB treatment and care policies. It covers drug-susceptible TB (DS-TB) treatment with 6-month (2HRZE/4HR) and newer 4-month regimens (2HPMZ/2HPM for adults ≥12 years; 2HRZ(E)/2HR for children 3 months–16 years with non-severe disease), drug-resistant TB treatment including short-course and longer regimens, and patient-centred care and support interventions.
The handbook provides detailed eligibility criteria, dosing schedules, treatment monitoring protocols, adverse event management, and outcome definitions harmonised across DS-TB and DR-TB. Special populations addressed include people living with HIV, pregnant women, children, older adults, and those with diabetes or renal/hepatic impairment. All regimens recommend daily dosing with treatment support tailored to individual patient needs.
The guidance emphasises rapid molecular diagnosis with drug susceptibility testing, patient-centred care models, and comprehensive monitoring including bacteriological assessment at 2 months and end of treatment. The 2020 revised treatment outcome definitions apply uniformly to all TB treatment regimens, facilitating standardised reporting and programme evaluation.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Standard DS-TB treatment: 2HRZE/4HR (6 months) daily for all ages; ethambutol can be omitted in HIV-negative children <10 years in low HIV/isoniazid-resistance settings
- New 4-month rifapentine-moxifloxacin regimen (2HPMZ/2HPM) for adults and children ≥12 years, ≥40 kg: rifapentine 1200 mg, moxifloxacin 400 mg daily with food; excludes pregnant women, CD4 <100 cells/mm³, severe extrapulmonary TB
- Children 3 months–16 years with non-severe TB (non-cavitary, one lobe, no miliary pattern, Xpert negative/trace/very low/low): 2HRZ(E)/2HR (4 months) daily; extend to 6 months if no clinical response
- Tuberculous meningitis: dexamethasone or prednisolone tapered over 6–8 weeks (strong recommendation); children receive 2HRZE/10HR (12 months) or alternative 6HRZEto (6 months intensive)
- People living with HIV: start ART within 2 weeks of TB treatment regardless of CD4 count (delay 4–8 weeks in meningitis); use efavirenz-based regimen or dolutegravir 50 mg twice daily with rifampicin
- Treatment monitoring: sputum smear/culture at 2 months and end of treatment; positive culture at 2 months without clinical/radiological improvement requires DST for rifampicin, isoniazid, fluoroquinolones
- Do not extend intensive phase if smear positive at 2 months (strong recommendation); do not use thrice-weekly dosing in DS-TB (conditional recommendation)
- Drug-resistant TB: BPaLM regimen (bedaquiline 400 mg×2 weeks then 200 mg, pretomanid 200 mg, linezolid 600 mg, moxifloxacin 400 mg) for 6 months in MDR/RR-TB; monthly culture monitoring until two consecutive negative results
Guide for regimen selection for DS-TB by age group
Table extracted from the guideline
| Age group | 0–3 months | 3 months–10 years | 10–12 years | 12–16 years | >16 years |
|---|---|---|---|---|---|
| 2HRZ(E)/4HR | Standard regimen | Add E in high HIV/Hr settings or CLHIV | Add E in high HIV/Hr settings or CALHIV | Independent of severity/HIV | Independent of severity/HIV |
| 2HRZ(E)/2HR | — | Non-severe TB, >3 kg; add E in high HIV/Hr or CALHIV | Non-severe TB; add E in high HIV/Hr or CALHIV | Non-severe TB; add E in high HIV/Hr or CALHIV | — |
| 2HPMZ/2HPM | — | — | — | Independent of severity/HIV | Independent of severity/HIV |
| Additional factors | — | Disease severity, access/cost, patient/family preference | Disease severity, access/cost, patient/family preference | Disease severity, access/cost, patient/family preference | Access/cost, patient preference |
Source: World Health Organization, Operational handbook on tuberculosis: Module 4: treatment and care. Reproduced in summary form.
What changed in this edition
Versus the previous edition
- Introduction of 4-month rifapentine-moxifloxacin regimen (2HPMZ/2HPM) for adults and adolescents ≥12 years based on Study 31 trial results showing non-inferiority to standard 6-month treatment
- Introduction of 4-month regimen (2HRZ(E)/2HR) for children 3 months–16 years with non-severe TB based on SHINE trial, replacing routine 6-month treatment in this population
- Harmonised treatment outcome definitions (2020 revision) applying to both DS-TB and DR-TB: treatment failed, cured, treatment completed, died, lost to follow-up, not evaluated, with optional 'sustained treatment success' for research
- Abolition of former Category II 8-month retreatment regimen (2HRZES/1HRZE/5HRE); retreatment cases require DST to guide regimen selection
- Strong recommendation against thrice-weekly dosing in DS-TB; daily dosing recommended throughout treatment (7 days per week)
- BPaLM and BPaLC regimens introduced for MDR/RR-TB as shorter all-oral options replacing injectable-containing regimens
- Updated ART guidance: start within 2 weeks regardless of CD4 count (except meningitis); dolutegravir 50 mg twice daily with rifampicin
From the guideline
Verbatim
“New patients with pulmonary TB should receive a regimen containing 6 months of rifampicin: 2HRZE/4HR.”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As Chair of Georgia's Public Health Institute and a long-time WHO consultant, I have watched our National TB Programme achieve remarkable DST coverage—over 95% of cases now receive rapid molecular testing—yet Georgia's MDR-TB burden remains among Europe's highest at 11% in new cases and 30% in retreatment. This handbook's emphasis on daily dosing and the new 4-month paediatric regimen for non-severe disease are immediately applicable; our child-friendly FDC procurement already supports 2HRZ(E)/2HR implementation, and shortening treatment from 6 to 4 months in eligible children will reduce family burden and improve adherence, a persistent challenge in our rural regions. The rifapentine-moxifloxacin regimen for adults is appealing but requires honest assessment: rifapentine is not yet in our national supply chain, and the handbook's requirement for administration with food may complicate directly observed therapy in outpatient settings where meal provision is inconsistent. Georgian clinicians should prioritise mastering the radiographic and bacteriological criteria for 'non-severe' TB in children—our 2021 national training did not yet cover these definitions—and ensure that every retreatment case receives DST before empirical regimen selection, as the handbook and our own data demand.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 18 Oct 2026
Applicability
Georgia and the South Caucasus
Georgia’s National TB Programme reports approximately 2,500 new TB cases annually (incidence ~65 per 100,000), with MDR/RR-TB prevalence of 11% in new cases and 30% in retreatment cases—among the highest in the WHO European Region. The country has achieved >95% coverage of rapid molecular testing (Xpert MTB/RIF) and universal DST, positioning it well to implement the regimen-selection algorithms in this handbook. The 4-month rifapentine-moxifloxacin regimen may face barriers due to rifapentine cost and availability until generic supply increases; however, the 4-month paediatric regimen (2HRZ(E)/2HR) is immediately feasible using existing first-line drugs and child-friendly FDCs already procured. Georgia’s TB/HIV coinfection rate (~6% of TB patients) requires robust ART/TB treatment integration as outlined; the dolutegravir dose adjustment recommendation is particularly relevant as Georgia transitioned to dolutegravir-based first-line ART in 2019. National TB Programme adaptation will need to address treatment supporter networks for daily observed therapy, updated clinician training on new eligibility criteria (especially radiographic assessment of ‘non-severe’ disease), and procurement planning for rifapentine and high-quality moxifloxacin if the 4-month adult regimen is to be scaled. Baseline fluoroquinolone resistance in rifampicin-susceptible TB cases in Georgia is approximately 2–3%, supporting empirical use of moxifloxacin-containing regimens without mandatory FQ-DST, though surveillance should continue.
Questions this guideline answers
Quick answers
Can I use the 4-month 2HPMZ/2HPM regimen in a pregnant woman with DS-TB?
No. Pregnant, breastfeeding and postpartum women were excluded from the Study 31 trial, so there is no evidence on safety or efficacy. Use the standard 6-month 2HRZE/4HR regimen, which is safe in pregnancy. Consider adding pyridoxine supplementation.
A 14-year-old with pulmonary TB has bilateral disease with a 3 cm cavity on chest X-ray. Which regimen should I use?
The patient has severe disease (cavitary, bilateral). Do not use the 4-month paediatric regimen (2HRZ(E)/2HR), which is only for non-severe TB. You may use either the 6-month 2HRZE/4HR regimen or, if the patient weighs ≥40 kg, the 4-month rifapentine-moxifloxacin regimen (2HPMZ/2HPM), which has no disease-severity restrictions.
My patient's sputum smear is still positive at the end of 2 months of treatment but he feels better. Should I extend the intensive phase?
No. Do not extend the intensive phase (strong recommendation). A positive smear at 2 months often indicates dead bacilli in patients responding well. Continue to the continuation phase. If there is no clinical or radiological improvement, or if drug resistance or failure is suspected, obtain sputum culture and DST for rifampicin, isoniazid and fluoroquinolones.
When should I start antiretroviral therapy in a TB patient newly diagnosed with HIV?
Start ART as soon as possible within 2 weeks of initiating TB treatment, regardless of CD4 count (strong recommendation). The only exception is tuberculous meningitis: delay ART for 4–8 weeks after starting TB treatment because immediate ART is associated with more serious adverse events in this setting.
Related on GMJ
Interconnected resources
Dictionary of Public Health
Drugs A–Z
Quality & accreditation
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- Issuer
- World Health Organization
- Type
- Handbook
- Edition
- 2025 consolidated edition
- Replaces
- WHO operational handbook on tuberculosis. Module 4: treatment – drug-susceptible tuberculosis treatment, 2022; Module 4: treatment – drug-resistant tuberculosis treatment, 2022; Module 4: treatment – tuberculosis care and support, 2022
- Status
- Current
- Published
- 2025-04-23
- Languages
- English
- Scope
- Global: all WHO Member States, applicable to high-, medium- and low-TB-burden settings; includes guidance for resource-limited contexts
- Audience
- National TB programme managers, policy-makers, infectious disease specialists, pulmonologists, general clinicians, paediatricians, HIV clinicians, public health professionals, laboratory staff
- Pages
- 377
- Licence
- CC BY-NC-SA 3.0 IGO
- ISBN
- 978-92-4-010814-1
- Evidence
- GRADE-rated recommendations based on systematic reviews, randomised controlled trials (Study 31, SHINE), individual patient data meta-analyses; good practice statements where evidence-based recommendations not feasible
- Next review
- Not specified; continuous update cycle as new evidence emerges
- Record history
- Created 18 Oct 2026 · updated 18 Oct 2026 · next check Apr 2027
World Health Organization. WHO operational handbook on tuberculosis. Module 4: treatment and care. Geneva: World Health Organization; 2025. Licence: CC BY-NC-SA 3.0 IGO.GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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