Consolidated Guidelines

The following technologies were included in the evaluation:

The Guideline Development Group concluded that both the sensitivity and specificity of IGRAs in detecting active TB among individuals presumed of having TB were suboptimal and the quality of evidence was low. They also recommended that these tests not be used as a replacement for conventional microbiological diagnosis of pulmonary and extrapulmonary TB.

As explained in Chapter 1, TB infection is a state that is characterized by persistent immune response to stimulation by Mtb antigens with no evidence of clinically manifest TB disease (1). Initially, the TST was the only tool available for TB infection detection.

The preferences of people to be tested and programmes depend on several factors, such as the requirement for an adequately equipped laboratory (e.g. for IGRAs) and possible additional costs for people being tested (e.g. for travel) and programmes (e.g. for infrastructure and testing).

IGRA testing is more costly than the TST and requires appropriate laboratory services. TST testing is less costly and can be performed in the field, but it requires a cold chain, two health care visits and training in intradermal injection, reading and interpretation. The incremental cost–effectiveness of IGRAs and the TST appears to be influenced mainly by their accuracy.

Five prospective cohort studies were identified, with a total of 7769 participants; four of the studies were newly identified. Three of the studies were conducted in South Africa and two in India (14–18). The studies included People with HIV, pregnant women, adolescents, health care workers and household contacts. The pooled risk ratio estimate for the TST was 1.49 (95% CI: 0.79– 2.80), and for IGRAs was 2.03 (95% CI: 1.18–3.50).

Could IGRA be used as an alternative to the TST, to identify individuals most at risk of progression from TB infection to active TB in high TB incidence settings?

There is a critical need for diagnostic tests with improved performance and predictive value for progression to active TB. In addition, the performance of TB infection tests should be evaluated in various risk groups, to assess reinfection and to understand how best to use available tools in each population (e.g. in combination, or sequential use of the TST and IGRAs).

Data synthesis was structured around the preset PICO question, as outlined above. See Web Annex H for additional information on evidence synthesis and analysis.

Where it is feasible, TB infection testing is desirable to identify individuals at highest risk for developing active TB. However, it is not required in People with HIV or in household contacts aged under 5 years. In HIV-negative household contacts aged 5 years and older, and in other risk groups, TB infection tests are recommended, but their unavailability should not be a barrier to treating people who are judged to be at higher risk. The GDG noted that the availability and affordability of the tests could determine which TB infection test is used.