Consolidated Guidelines

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).

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 Loopamp^ᵀᴹ 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.

Methods used to develop World Health Organization guidelines

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.

The second edition of the WHO guidelines on TPT provides a comprehensive set of recommendations for PMTPT for implementers of the WHO End TB Strategy and also for countries working towards TB elimination (8,9). The guidelines are to be used primarily in national TB and HIV and maternal and child health programmes or their equivalents in ministries of health and by other policy-makers working on TB, HIV, infectious diseases and maternal and child health.

Advanced HIV disease: for adults, adolescents, and children aged 5 years or more, “advanced HIV disease” is defined as a CD4 cell count of less than 200 cells/mm³ or a WHO clinical stage 3 or 4 event at presentation for care. All children with HIV aged under 5 years should be considered as having advanced disease at presentation.

Age groups: the following definitions for adults and children are used in these guidelines for the purpose of implementing recommendations (countries may have other definitions under their national regulations)² :

Before being considered for group membership, each Guideline Development Group (GDG) and External Review Group candidate was required to submit a completed declaration of interest (DOI) form. In addition, a preliminary internet search was performed to identify any obvious public controversies or interests that may lead to compromising situations for the World Health Organization (WHO) and the expert concerned.

Current recommendations on the various methods and tools should not prevent or restrict further research on new, rapid molecular drug-susceptibility tests, especially for assays that can be used as close as possible to where patients with a presumptive diagnosis of TB are identified and where treatment can be initiated. Priorities for further operational research on diagnostics are listed below, grouped for each technology.

Molecular assays intended as initial tests