Treatment

Tuberculosis (TB), with an estimated incidence of 10 million people every year (range 8.9–11.0 million), is a major cause of ill health and one of the leading causes of death worldwide. Until the coronavirus disease (COVID-19) pandemic, TB was the leading cause of death from a single infectious agent, ranking above HIV, with an estimated 1.2 million TB deaths among people who are HIV-negative (range, 1.1–1.3 million), and an additional 208 000 deaths among people who are HIV-positive (range, 177 000– 242 000).

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).

The production and writing of this document, WHO operational handbook on tuberculosis Module 4: Treatment – drug-susceptible tuberculosis treatment, was coordinated by Fuad Mirzayev, with the support of Medea Gegia and Linh Nguyen, under the guidance of Matteo Zignol and the overall direction of Tereza Kasaeva, Director of the World Health Organization (WHO) Global Tuberculosis Programme (WHO/GTB). Significant input to finalize the document was provided by Giovanni Battista Migliori, WHO Collaborating Centre for Tuberculosis and Lung Diseases; Fondazione S.

This operational handbook was prepared and coordinated by Linh Nguyen and Fuad Mirzayev, with input from Ernesto Jaramillo and Matteo Zignol, and under the overall direction of Tereza Kasaeva, Director, WHO Global Tuberculosis Programme. The WHO Global Tuberculosis Programme gratefully acknowledges the contributions of all experts involved in the production of the latest updates of the WHO guidelines on tuberculosis care and support, on which this handbook is based, as well as other contributors listed below.

Modified all-oral shorter MDR-TB regimens (i.e. regimens that differ from the recommended 9-month shorter regimens) should only be implemented under “operational research conditions”. The main conditions are:

At present, there is little evidence to support modified all-oral shorter MDR-TB regimens that are designed using the hierarchy of TB medicines (Table 6.1). NTPs that intend to pilot such types of shorter MDR-TB regimens are advised to do so under operational research conditions.

The South African NTP implemented the 9-month all-oral MDR/RR-TB regimen as a standardized course of treatment, with little room for variation. Some changes to the prescribed regimen were considered acceptable in the South African context and may be appropriate in other settings (as described in Section 5.2).

Some patients who start treatment with the 9-month all-oral regimen are unable to continue or complete the course of treatment, and may have to restart or switch to a different regimen; for example, in the following situations:

Extensive (or advanced) TB disease in adults is defined as the presence of bilateral cavitary disease or extensive parenchymal damage on chest radiography. In children aged below 15 years, extensive (or advanced) disease is usually defined by the presence of cavities or bilateral disease on chest radiography (see above regarding severe and nonsevere TB disease in children). This highlights the importance of chest radiography as part of the diagnostic work-up for patients, along with the usual patient–clinician interaction.

Dosing and safety data to support the optimal use of second-line TB medicines during pregnancy are generally sparse. There have been case reports and observational data reporting successful treatment and pregnancy outcomes among women who received treatment (including bedaquiline-containing regimens) for MDR/RR-TB during pregnancy and postpartum, but pregnant and breastfeeding women are usually excluded from clinical drug trials and early access programmes.