Background
Tuberculosis (TB) is an infectious disease that is a leading cause of morbidity and mortality globally. There were an estimated 1.3 million total deaths caused by TB in 2022.1 Vietnam is one of the 30 highest TB burden countries, with an estimated 172 000 persons developing TB (including people living with HIV) in 2022.2
TB infection continues to be a significant cause of the increasing number of overall infections. After exposure to Mycobacterium tuberculosis (MTB), 5%–10% of people with TB infection will develop active TB, usually within the first 2 years after exposure.3 In 2018, the WHO estimated the global prevalence of TB infection to be 23%, meaning approximately 1.7 billion people were infected worldwide.4 5 A recent re-estimation using mathematical modelling demonstrated that in order to end TB by 2050, at least one-quarter of the global population living with TB infection would require TB preventive therapy.6
The tuberculin skin test (TST) and interferon-gamma (IFN-γ) release assays (IGRA) are currently the two preferred diagnostic tools for detecting TB infection. TST uses Tuberculin PPD RT 23 intradermally, which is affordable and easily performed.7 TST is currently the most frequently used TB infection test in Vietnam. However, TST has low sensitivity and specificity, particularly in people who are immunocompromised or have been BCG vaccinated, and people must return to a health facility to have the induration on their arm interpreted. IGRAs are more expensive and technically more complex, requiring phlebotomy, trained staff and laboratory equipment. Neither method is ideal for accurate and prompt diagnosis of TB infection in a community setting.8 Therefore, it is critical to develop new test methods to achieve the public health goal of preventing progression from TB infection to active TB and thereby reducing transmission.
Cy-Tb (Serum Institute of India, Pune, India) is an M. tuberculosis antigen-based skin test that was endorsed by the WHO in 2022.9 The test uses M. tuberculosis-specific antigens (rdESAT-6 and rCFP-10), which are injected intradermally, providing results after 48–72 hours, similar to the TST. However, a recent study indicated the superior performance of Cy-Tb compared with TST, with results in line with the QuantiFERON-TB Gold Plus (QFT-Plus) assay (QIAGEN, Venlo, The Netherlands).10
Simplified versions of IGRAs are emerging,11 including the lateral flow Standard F TB assay (SD Biosensor, Gyeonggi-do, Republic of Korea). Standard F TB has fewer manual processing steps than current-generation IGRAs. After incubation for 16–24 hours, the results will be available in 15 min. Following the stimulation with ESAT-6 and CFP-10 antigens, the IFN-γ production in whole blood is measured by a fluorescent immunoassay.12 A recent clinical trial comparing the sensitivity and specificity of the Standard F TB versus QIAreach QuantiFERON-TB (QIAGEN, Venlo, The Netherlands), using TST as a reference standard, showed that the Standard F TB has 88.9% sensitivity and 92.5% specificity for TB infection diagnosis.13 However, given the limited accuracy of TST in diagnosing TB infections, further studies comparing to the current gold standard are warranted. Compared with QFT-Plus, the Standard F TB assay may offer important advantages, such as being able to be implemented in low-resource settings, and reducing the financial burden on health systems and people with TB. The Standard F TB assay is currently undergoing Expert Review Panel for Diagnostics and WHO review.14
Currently, there are no studies comparing the accuracy of Standard F TB versus QFT-Plus. In addition, there are also no head-to-head comparisons of the sensitivity and specificity of Cy-Tb and Standard F TB. The studies comparing the accuracy of Cy-Tb test versus QFT-Plus have been conducted in Spain and South Africa,9 15 whereas there are no studies in a high TB burden, Asian population. This study was designed to address these knowledge gaps.
This post was originally published on https://bmjopen.bmj.com