WHO operational handbook on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment

With the availability of new evidence on the treatment of drug susceptible TB (DS-TB), WHO has recently updated the DS-TB treatment guidelines by convening a guideline development group meeting in April 2021 and then by releasing the WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment - Drug- Susceptible Tuberculosis Treatment in 2022. These guidelines include a comprehensive set of WHO recommendations, grouping all the new and existing recommendations on the treatment of DS-TB into one document. 

The consolidated guidelines are complemented by this operational handbook which is designed to assist with implementation of the WHO recommendations by Member States, technical partners and others who are involved in the management of patients with DS-TB. The WHO Operational Handbook on Tuberculosis, Module 4: Treatment - Drug-Susceptible Tuberculosis Treatment provides practical guidance on how to put in place the recommendations at the scale needed to achieve national and global impact. 

The operational handbook provides practical information and tools that complement the recommendations in the guidelines based on best practices and knowledge from the field such as microbiology, clinical and programmatic management. The strategies described in the operational handbook are based on the latest WHO recommendations which were formulated following Guideline Development Group meetings using the GRADE approach.  

The operational handbook provides information on different aspects of treatment and care of DS-TB. In particular, the handbook provides practical guidance on the implementation of the new recommendation on the use of a shorter 4-month regimens for the treatment and care of DS-TB. In addition, the handbook includes key considerations for implementation of the standard 6-month regimen, considered as alternative option for the treatment of drug susceptible pulmonary tuberculosis. 

This practical guidance includes important information on drug dosages, drug-drug interactions, treatment peculiarities in special situations, options for treatment of patients with extrapulmonary TB, and monitoring treatment response together with the updated treatment outcome definitions.  

The operational handbook is accompanied with two web annexes, summarizing the results of a series of the systematic reviews on the dosages of the first-line medicines (rifampicin, isoniazid, ethambutol, and pyrazinamide) used in the treatment of drug-susceptible tuberculosis in adults and children. These web annexes are results of the systematic reviews conducted in close collaboration with the University of California San Francisco (UCSF), Center for Tuberculosis, and the University of Liverpool.  

The reviews access all the available evidence on the efficacy of doses higher than currently recommended in the WHO policy documents and either identify the areas where changes are warranted or establish a reliable baseline for the new evidence that will be generated. The reviews looked at both the efficacy and safety outcomes of treatment.  

The findings from both reviews concluded that the WHO-recommended doses for rifampicin, isoniazid, ethambutol, and pyrazinamide remain valid in adults and children. 

There is a need for more robust methods and new, reliable evidence, including in specific subgroups of patients where evidence is particularly scarce - younger children and patients with comorbidities. 

WHO will continue to monitor several ongoing developments in this regard and engage TB community and researchers as the new evidence emerges.