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New molecular assays – the Truenat MTB, MTB Plus and MTB-RIF Dx assays (Molbio Diagnostics, Goa, India), hereafter referred to as Truenat – were developed in India, and may be used at the same health system level as Xpert MTB/RIF. Of the above-mentioned assays, MTB and MTB Plus are used as initial diagnostic tests for TB, whereas MTB-RIF Dx is used as a reflex test to detect rifampicin resistance for those with positive results on the initial Truenat tests.
The development of the Xpert MTB/RIF assay (Cepheid, Sunnyvale, United States of America [USA]) was a significant step forward for improving the diagnosis of TB and the detection of rifampicin resistance globally. However, Xpert MTB/RIF sensitivity is suboptimal, particularly in smear-negative and HIV-associated TB patients. The Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, USA), hereafter referred to as Xpert Ultra, was developed by Cepheid as the next-generation assay to overcome these limitations. It uses the same GeneXpert® platform as the Xpert MTB/RIF.
The political declaration at the first United Nations (UN) high-level meeting on tuberculosis (TB) held on 26 September 2018 included commitments by Member States to four new global targets (1), which were subsequently renewed at the second UN high-level meeting on TB on 22 September 2023 (2). One of these targets is that at least 90 per cent of the estimated number of people who develop TB are reached with quality-assured diagnosis and treatment in the 5-year period 2023–2027 (2).
Among 105 countries possessing representative data on resistance to fluoroquinolones from the past 15 years, the proportion of MDR/RR-TB cases with resistance to any fluoroquinolone for which testing was done was 20.1% (95% CI: 15.5–25.0%). Thus, rapid and early testing for the detection of fluoroquinolone resistance is essential for determining eligibility for treatment with the all-oral 9–12 month standardized shorter regimen for MDR/RR-TB.
Rapid detection of TB and rifampicin resistance is increasingly available as new technologies are developed and adopted by countries. However, what has also emerged is the relatively high burden of isoniazid-resistant, rifampicin-susceptible TB that is often undiagnosed. Globally, isoniazid-resistant, rifampicin-susceptible TB is estimated to occur in 13.1% (95% CI: 9.9–16.9%) of new cases and 17.4% (95% CI: 0.5–54.0%) of previously treated cases (14).
Genotypic (molecular) methods have considerable advantages for scaling up programmatic management and surveillance of DR-TB, offering rapid diagnosis, standardized testing, potential for high throughput and fewer requirements for laboratory biosafety. Molecular tests for detecting drug resistance – for example, the GenoType MTBDRsl assay (Hain Lifescience, Nehren, Germany), hereafter referred to as MTBDRsl (17) – have shown promise for the diagnosis of DR-TB.
In 2008, WHO approved the use of commercial LPAs for detecting MTBC in combination with resistance to rifampicin and isoniazid in sputum smear-positive specimens (direct testing) and in cultured isolates of MTBC (indirect testing). A systematic review at that time evaluated the diagnostic accuracy of two commercially available LPAs – the INNO-LiPA Rif.TB assay (Innogenetics, Ghent, Belgium), and the GenoType® MTBDRplus (version 1), hereafter referred to as Hain version 1 – and provided evidence for WHO’s endorsement (37, 38).
A commercial molecular assay, the Loopampᵀᴹ Mycobacterium tuberculosis complex (MTBC) detection kit (Eiken Chemical Company, Tokyo, Japan), is based on loop-mediated isothermal amplification (LAMP) reaction. Referred to as TB-LAMP, this is a manual assay that requires less than 1 hour to perform and can be read with the naked eye under UV light. Because it requires little infrastructure and is relatively easy to use, TB-LAMP is being explored for use as a rapid diagnostic test that would be an alternative to smear microscopy in resource-limited settings.
To develop new or update existing guidelines for methods and tools to diagnose tuberculosis (TB), the World Health Organization (WHO) Global TB Programme commissions systematic reviews on the performance or use of the tool or method in question. A systematic review provides a summary of the current literature on diagnostic accuracy or user aspects, for the diagnosis of TB or the detection of anti-TB drug resistance in adults or children (or both) with signs and symptoms of TB.