Use of alternative interferon-gamma release assays for the diagnosis of TB infection

Publication Year 28 Aug 2023

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WHO policy statement

Tuberculosis (TB) infection is a state that is characterized by persistent immune response to stimulation by Mycobacterium tuberculosis (Mtb) antigens with no evidence of clinically manifest TB disease.1 It is estimated that about a quarter of the world’s population is infected with Mtb. Testing for TB infection increases the probability that individuals who are the target for preventive treatment will benefit from such treatment. However, there is no gold standard test to diagnose TB infection. The two currently available classes of tests – tuberculin skin test (TST) and interferon-gamma release assay (IGRA) – are indirect and require a competent immune response to identify people infected with TB. A positive test result by either method is not, by itself, a reliable indicator of the risk of progression to active disease.
In 2011, the World Health Organization (WHO) issued recommendations on the use of IGRAs for the diagnosis of TB infection, including the blood-based Qiagen QuantiFERON-Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and Oxford Immunotec T-SPOT.TB (T-Spot) assays. In recent years, new and updated versions of blood-based IGRAs have been marketed, and WHO has solicited information on these tests directly from manufacturers and from a public call for information. The following products had sufficient independent evidence for consideration: QuantiFERON-TB Gold Plus (QFT-Plus), QIAreach QuantiFERON-TB (QIAreach), Beijing Wantai’s TB-IGRA (Wantai), the Standard E TB-Feron enzyme-linked immunosorbent assay (ELISA) (TBF) and T-SPOT.TB 8 with T-Cell Select (T-Cell Select).
To evaluate these technologies and determine whether one or more of them could be included under the existing WHO recommendations for IGRA testing, WHO convened a Technical Advisory Group (TAG) on TB Diagnostics and Laboratory Strengthening, which met virtually on 27–29 October 2021. This document provides background information, available evidence and subsequent deliberations by the TAG.
Following the TAG’s review of the evidence and provision of advice, WHO makes the following policy statement:

  1. Based on available data, Beijing Wantai’s TB-IGRA and Qiagen QuantiFERON-TB Gold Plus performance is comparable to that of WHO-recommended IGRAs for the detection of TB infection.
  2. Based on available data, Qiagen QIAreach QuantiFERON-TB, SD Biosensor Standard E TB-Feron ELISA and Oxford Immunotec T-SPOT.TB 8 with T-Cell Select could not be adequately compared with WHO-recommended IGRAs for detection of TB infection.
  3. Current WHO recommendations for the use of IGRAs are also valid for Beijing Wantai’s TB-IGRA and Qiagen QuantiFERON-TB Gold Plus.
The guidance provided should facilitate the procurement and uptake of the recommended technologies and improve patient care. The policy statements should be read in the context of the remarks and implementation considerations detailed in this report, which also provides proposed research questions that seek to address data gaps and inform models of effective test implementation. The current WHO recommendations on the use of TST and IGRAs (including T-Spot) are unchanged and remain valid. All products recommended by WHO are automatically eligible to be included in the WHO essential diagnostic list.
The WHO recommendations on diagnostics are based on clinical research evidence; they do not include quality assessments of the products or the manufacturing process involved. Before introducing any new products, countries should ensure that those products fulfil local or internationally recognized regulatory requirements.
Finally, this policy document will be incorporated into updates of existing WHO consolidated guidance.