Meeting report of the WHO expert consultation on the definition of XDR-TB

Overview

The World Health Organization (WHO) consultation meeting on the definition of extensively drug-resistant tuberculosis (XDR-TB) was held on 27, 28 and 29 October 2020 as an online meeting, organized by the Global TB Programme, WHO, Geneva, Switzerland. Over 70 participants attended the meeting, representing countries, bilateral and multilateral agencies, international organizations, nongovernmental organizations, civil society and academia.

The overall goal of the meeting was to discuss recent changes in treatment regimens and diagnostics for drug-resistant TB and to determine how these impact on the definition of XDR-TB, with a view to revising this definition. The pre-existing definition of XDR-TB was formulated in 2006 at a meeting of the Global Taskforce on XDR-TB, convened by WHO, and has been in use for clinical and surveillance purposes, since this time.

The specific meeting objectives were to:

1. Discuss recent changes in treatment regimens and diagnostics for drug-resistant TB and to determine how these impact on the definition of XDR-TB;
2. Discuss options for changing the definition of XDR-TB, including the pros and cons of these options with various perspectives and stakeholders in mind (including clinical, programmatic and surveillance perspectives);
3. Discuss overarching principles that need to be borne in mind when thinking about a new definition of XDR-TB; and
4. Discuss a proposal for a new definition of XDR-TB that has global application and which can be used for clinical, surveillance and programmatic purposes.

Updated definitions

Meeting participants discussed recent developments in the areas of TB diagnosis, treatment and programming, potential future developments in these areas based on the research pipelines and suggested some overarching principles that should guide the development of a revised definition of XDR-TB, including that it should be:

• Simple
• Measurable
• Relevant to national TB programmes, including surveillance and clinical management, and
• Future-proof (i.e., that could be used for a certain period of time despite foreseen changes in practice).

Bearing these principles in mind, and cognizant of the current strategic and operational issues as described by meeting participants, the WHO proposes a definition of pre-XDR-TB as well as a revised definition of XDR-TB. The definition of MDR-TB will remain the same. These definitions are:

Pre-XDR-TB: TB caused by Mycobacterium tuberculosis (M.tuberculosis) strains that fulfil the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone*

XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfil the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone and at least one additional Group A drug*

*The fluoroquinolones include levofloxacin and moxifloxacin as they are the fluoroquinolones currently recommended by WHO for inclusion in longer regimens. The Group A drugs are currently levofloxacin or moxifloxacin, bedaquiline and linezolid, therefore XDR-TB is MDR/RR-TB that is resistant to a fluoroquinolone and at least one of bedaquiline or linezolid (or both). The Group A drugs may change in the future; therefore the terminology Group A is appropriate here and it will apply to any Group A drugs in the future.

These definitions should be applied from January 2021. They will define the group of TB patients who can be rapidly identified and who will require a significantly different treatment approach in order to attain better treatment outcomes without major delays in accessing the treatment. The definitions will also need to be adopted for use in surveillance and epidemiological reporting, to flag both the seriousness of the situation and as a measure of progress against national and global epidemiological indicators to end TB as a public health problem. This meeting report describes background information relevant to the definition of XDR-TB, a rationale for changing this definition and describes the meeting discussions.

The report can be accessed here.

Source: WHO