Operational Handbooks

Three Phase III trials (i.e. REMoxTB, OFLOTUB and RIFAQUIN) failed to demonstrate non-inferiority of shorter regimens used to treat DS-TB (25–27). The recent Phase III trial Study 31 (1) assessed the safety and efficacy of two 4-month regimens for the treatment of DS-TB (28). Patients from 13 countries were recruited for this multicentre, open-label, three-arm non-inferiority RCT, which was carried out in adolescents and adults (aged ≥12 years) with smear and culture positive pulmonary DS-TB (28).

All patients with DS-TB without documented resistance to isoniazid and rifampicin may be treated using the 6-month rifampicin-containing regimen 2HRZ(E)/4HR, which comprises isoniazid, rifampicin, pyrazinamide and ethambutol, for 2 months followed by isoniazid and rifampicin for 4 months (1).

2.1 TB diagnostics and DST

Innovative rapid molecular tests to diagnose both pulmonary and extrapulmonary TB in all populations are strongly recommended over sputum smear microscopy and culture methods, because rapid tests can provide same day results (3). Some of the innovative tests also provide drug susceptibility results for rifampicin (R), isoniazid (H) and fluoroquinolones (FQ), allowing rapid confirmation of diagnosis, and timely and effective treatment allocation.

This chapter on the treatment of drug-susceptible tuberculosis (DS-TB) complements the chapter on drug-susceptible tuberculosis treatment of the WHO consolidated guidelines on tuberculosis Module 4: Treatment and care (1). It provides practical advice based on best practices and knowledge from fields such as pharmacokinetics, pharmacodynamics, microbiology, pharmacovigilance, and clinical and programmatic management.

The WHO operational handbook on tuberculosis, Module 4: treatment and care provides practical guidance on implementing recommendations to achieve national and global impact in tuberculosis (TB) management. It consolidates three key components of the WHO consolidated guidelines on tuberculosis treatment: drug-susceptible TB (DS-TB) treatment, drug-resistant TB (DR-TB) treatment, and tuberculosis care and support. This consolidated operational handbook complements the WHO consolidated guidelines on TB treatment, assisting Member States, technical partners and other stakeholders who

Adverse event: Any untoward medical occurrence that may present in a person with tuberculosis (TB) during treatment with a pharmaceutical product but that does not necessarily have a causal relationship with the treatment.

Bacteriologically confirmed TB case: A case from whom a biological specimen is positive by smear microscopy, culture or a World Health Organization (WHO) recommended rapid diagnostic (e.g. Xpert^® MTB/RIF).

Consolidation of the operational handbook (2025)

Consolidation of the operational handbook was carried out by Medea Gegia, Fuad Mirzayev, and Linh Nguyen under the overall direction of Matteo Zignol and Tereza Kasaeva.