Обратная связьGlobally, tuberculosis (TB) continues to be a significant public health problem. It has been estimated that about a quarter of the world’s population was infected with Mycobacterium tuberculosis (Mtb) bacteria (1). In 2023, an estimated 10.8 million infected individuals went on to develop TB disease, while 8.2 million were diagnosed and reported to the World Health Organization (WHO) (2). Of those 8.2 million, an estimated 1 million people developed drug-resistant TB (DR-TB) – specifically, the form of DR-TB that is resistant to the first-line antibiotic isoniazid (INH) but susceptible to rifampicin (RIF) (i.e. Hr-TB) – and an additional 410 000 people developed TB disease resistant to both INH and RIF (i.e. multidrug-resistant TB [MDR-TB]), or to RIF alone (i.e. RIF-resistant TB [RR-TB]) (3). Only two in five of the people estimated to have MDR-TB or RR-TB (MDR/RR-TB) were found and initiated on treatment, and only 55% of RR-TB patients received follow-on testing for resistance to the fluoroquinolones (FQs) as essential for diagnosis of pre-extensively drug-resistant TB (pre-XDR-TB). In addition, although the total number of deaths caused by TB fell from 1.32 million in 2022 to 1.25 million in 2023, the disease still probably overtook coronavirus disease (COVID-19) as the world’s leading cause of death due to a single infectious agent (2).
In support of addressing these gaps, WHO’s global strategy for TB prevention, care and control for 2015–2035 – known as the End TB Strategy (4) – calls for the early detection of TB infection, diagnosis of TB and universal access to drug susceptibility testing (DST). To meet the End TB Strategy targets:
- individuals living with TB infection who are at higher risk of progression to active TB should receive TB infection testing to identify those who will benefit most from TB preventive treatment (TPT);
- WHO-recommended rapid diagnostic tests (WRDs) should be made available to all individuals with signs or symptoms of, or who screen positive for, TB;
- individuals with bacteriologically confirmed TB should receive testing for resistance to RIF;
- people with RR-TB should receive testing for resistance to the FQs; and
- individuals with pre-XDR-TB should receive testing for resistance to bedaquiline (BDQ) and linezolid (LZD), and to all other drugs that might be included in their treatment regimen (3).¹
Section 2 of this handbook outlines TB tests, with WHO recommendations for the detection of TB infection, disease and drug resistance; Section 3 outlines considerations for the implementation of these tests.
In addition, the first WHO standard on universal access to rapid TB diagnostics was issued in 2023 (3). The standard emphasizes the need to undertake a comprehensive approach to diagnostics while following the care cascade and closing all gaps; for example, availability and access to quality-assured testing and DST, testing capacity, rapid turnaround time for results and monitoring of indicators. Furthermore, the framework of indicators and targets for laboratory strengthening under the End TB Strategy (4) highlights that all national TB programmes (NTPs) should prioritize the development of a network of TB laboratories that use modern methods of diagnosis (e.g. molecular methods and liquid culture), have efficient referral systems, use electronic data and diagnostics connectivity, use standard operating procedures (SOPs) and appropriate quality assurance (QA) processes, adhere to biosafety principles for all testing and have sufficient human resources. These priorities should be comprehensively addressed in national strategic plans and should be adequately funded. Practical considerations for implementing and strengthening these essential testing programme elements are further detailed in Section 3 and Section 4, respectively.
In addition to universal access to TB diagnostic testing services, both the WHO standard and recent guidelines on TB diagnosis continue to highlight the need for universal DST, especially for the medicines for which mWRDs are available (ideally, performed before treatment is started while not delaying treatment initiation when waiting for results) (5). WHO recently approved the use of targeted next-generation sequencing (NGS) as a follow-on technology for the detection of drug resistance (Section 2) (6). Targeted NGS solutions couple the amplification of selected genes with NGS technology, and can detect resistance to many drugs using a single processed sputum sample (6). Because these tests can interrogate entire genes to identify specific mutations associated with resistance, targeted NGS may be more accurate than other mWRDs. In addition to detection of resistance to first-line TB drugs, current recommendations support the use of this technology for the rapid detection of resistance to three of the drugs used in the BPaLM regimen (i.e. BDQ, LZD and moxifloxacin [MFX]); therefore, this handbook includes further implementation considerations and algorithms using this technology. Of note, the fourth BPaL/M drug – pretomanid (Pa) – has recently had criteria established for DST, and these details are also included in this document (Web Annex B). Based on current treatment recommendations, countries embarking on interventions to detect and treat DR-TB should, in addition, establish laboratory capacity to perform culture-based phenotypic DST for drugs that are recommended for use in MDR-TB regimens (7) and for which there are reliable phenotypic DST methods (e.g. BDQ, LZD, Pa, cycloserine [Cs], clofazimine [CFZ] and delamanid [DLM]). Lastly, countries should expand their capacity to monitor the culture conversion of people being treated for DR-TB.
1 The original End TB Strategy called for the testing of all people with RR-TB for susceptibility to second-line injectable agents (kanamycin, capreomycin and amikacin). However, WHO currently recommends that injectable medicines be phased out of all treatment regimens as a priority and replaced by BDQ; this makes rapid DST for amikacin unnecessary.