WHO Announces Updates to its Guidelines on Tests for the Diagnosis of TB Infection

Release time:2022-10-08  |  Click rate:

On September 30, World Health Organization (WHO) published its updated consolidated guidelines on tuberculosis (TB) and the use of tests for the diagnosis of TB infection. Three new Mycobacterium tuberculosis antigen-based skin test (TBST) products worldwide, including the Recombinant Mycobacterium Tuberculosis Fusion Protein (EC®) (C-TST) developed by Anhui Zhifei Longcom Biopharmaceutical Co.,Ltd, a wholly-owned subsidiary of Chongqing Zhifei Biological Products Co., Ltd. were recommended for the diagnosis of TB infection.
In response, WHO announced updates to its guidelines on tests for the diagnosis of TB infection. “The diagnostic options for people with TB infection are increasing thanks to manufacturer engagement and new research. Ensuring that everyone in need can obtain a rapid and accurate diagnosis of TB infection is of critical importance to prevent and finally eliminate TB” said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme.
TB is a chronic infectious disease caused by bacteria (Mycobacterium tuberculosis, M.tb) and it most often affects the lungs. TB is spread through the air when people with lung TB cough, sneeze or spit. A person needs to inhale only a few germs to become infected. Every year, 10 million people fall ill with TB. Despite being a preventable and curable disease, 1.5 million people die from TB each year [1].
According to WHO, an estimated 10.6 million people (95% UI: 9.9–11million) fell ill with TB worldwide in 2021. The TB incidence rate (new cases per 100,000 population per year) is estimated to have increased by 3.6% between 2020 and 2021, following declines of about 2% per year for most of the past 2 decades [2].
About one-quarter of the world’s population is estimated to be infected by TB bacteria, and 5-15% of these people will fall ill with active TB disease [1]. In the face of the slow rate of global TB decline, early screening for latent TB infection and preventive treatment of high-risk populations are important for TB control.
This updated WHO policy is the first to recommend a new TBST and integrates all existing recommendations for the diagnosis of TB infection, including the traditional tuberculin skin test (TST) and the interferon gamma release assay (IGRA).
The TBST is a new test for the diagnosis of TB infection. It is defined as a skin test that uses the M.tb specific antigen (ESAT-6 and CFP-10) to detect TB infection.
WHO convened a Guideline Development Group (GDG) from 31 January to 3 February 2022. The objectives of the meeting were to assess the available data on TBST related to patient-important outcomes, diagnostic accuracy, safety, concordance, and economic and qualitative evidence, in comparison to TST and IGRA. The following technologies were included in the evaluation: C-Tb (Serum Institute of India, India); C-TST (formerly known as ESAT6-CFP10 test, Anhui Zhifei Longcom, China); and Diaskintest (Generium, Russian Federation) [4]. EC®(C-TST)became the only M.tb specific antigen screening reagent for TB infection in China.
As a new class of tests to diagnose TB infection, TBST have been evaluated by WHO and are found to be accurate, acceptable, feasible and cost-effective. These tests represent an alternative to TST and IGRA, a significant advancement to TST which has been used for over half a century [3].
1. TBST were found to be accurate for detection of TB infection compared with IGRA and TST
Study Design:
For sensitivity: 17 studies involving 1,276 participants; for specificity (including difference in specificity): 14 studies involving 3,792 participants; and for agreement: 16 studies involving 3,198 participants [4].
Diagnostic accuracy of TBST was confirmed for detection of TB compared with IGRA and TST. Overall, pooled sensitivity and specificity for TB infection detection were 76.0% (95% confidence interval [CI]: 70.0 to 81.0) and 98.0% (95% CI: 94.0 to 99.0), respectively. Difference in specificity between TBST and TST among those who were BCG vaccinated was 67.4% (95% CI: 24.0 to 110.7) and was higher for TBST. Agreement with TST in people without TB disease was 59.4% (95% CI: 45.4 to 72.1) and in people with TB disease was 88.3% (95% CI: 82.1 to 92.5). Agreement with IGRA in people without TB disease was 89.0% (95% CI: 82.6 to 93.2) and in people with TB disease was 85.7% (95% CI: 79.5 to 90.3) [4].
Results of six studies involving 2,931 patients: The safety profile of novel TBST appears to be similar to that of TST and is associated with mostly mild injection site reactions such as itching and pain. Relative risk for any injection site reaction in comparison with TST amounted to 1.05 (95% CI: 0.70 to 1.58). Relative risk for any systemic reaction in comparison with TST was 0.84 (95% CI: 0.60 to 1.10) [4].
Overall, the new TBST class of tests contain the same ESAT-6 and CFP-10 antigens as IGRA, and are superior to traditional TST (especially in terms of specificity). TBST also provide an accurate, acceptable and cost-effective alternative to IGRA. These make TBST a suitable alternative for the diagnosis of TB infection, particularly in populations with prior BCG vaccination history. This is important to potentially reduce false positive diagnosis of TB infection in settings using TST. Generally, TBST has good feasibility [5].
To end the TB epidemic, Latent TB infection must be controlled. Mycobacterium Vaccae for Injection (Vaccae®) developed by Anhui Zhifei Longcom Biopharmaceutical Co.,Ltd, a wholly-owned subsidiary of Chongqing Zhifei Biological Products Co., was approved in June 2021. It is currently used to prevent TB in people aged 15-65 with latent TB infection. It is the world's first approved immunological agent for the prevention of TB in people with latent TB infection.
We are promoting the advancement of ending the TB epidemic and building a closed loop of "early detection, early intervention and early treatment" for people with latent TB infection.
Let us work together to end TB!
[2]WHO. Global tuberculosis report 2022  [Z]. Global tuberculosis report 2022
[4]Rapid communication: TB antigen-based skin tests for the diagnosis of TB infection
[5]WHO consolidated guidelines on tuberculosis Module 3: Diagnosis Tests for tuberculosis infection