Abstract:

As one of the countries with high burden of tuberculosis worldwide, China possesses a huge number of tuberculosis cases and latent tuberculosis infections (LTBI), which brings great challenges to the prevention and control of tuberculosis. Effective identification of tuberculosis and LTBI is of great significance to control the epidemic situation of tuberculosis. The diagnosis of sputum-negative pulmonary tuberculosis, especially LTBI, depends on the immunological diagnostic method of tuberculosis infection. The current immunological detection methods of tuberculosis infection are mainly tuberculin skin test (TST), interferon-gamma release assays (IGRA) and antigen-antibody detection. On the basis of the current three methods, we have developed new products and techniques for the diagnosis of LTBI and tuberculosis-recombinant Mycobacterium tuberculosis fusion protein (EC) (the product name is the Chinese general name of the drug determined by the State Pharmacopoeia Commission, and “EC” refers to the recombinant fusion protein “Mycobacterium tuberculosis early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10)”) (short for “EC”), featuring simple operation, high sensitivity and specificity. At present, phase Ⅰ, Ⅱ and Ⅲ clinical trials of EC have been completed. In the screening of 1559 healthy people in the phase Ⅲ clinical trial, it was found that the detection results of EC and IGRA had quite high specificity and consistency(88.77%). The clinical study of 791 patients diagnosed with tuberculosis showed that the detection results of EC, tuberculosis infected T lymphocyte spot test (T-SPOT.TB) and tuberculin pure protein derivative (TB-PPD) had good sensitivity and quite high consistency among them. In the study of 479 patients uninfected Mycobacterium tuberculosis, the negative coincidence rate of EC and T-SPOT.TB was high (reaching 88.20% and 93.17%). In the study of the effect of BCG vaccine on the test results, it was found that EC and T-SPOT.TB were basically not affected by BCG. In the clinical study of 394 patients diagnosed with non-tuberculous diseases, it was found that the negative coincidence rate of EC and T-SPOT.TB was quite high, and the consistency was good (87.21%). Based on the fact that EC is safe and effective in the diagnosis of tuberculosis infection, EC has passed the drug examination and approval of the State Drug Administration and is approved to be listed on the market. After extensively soliciting the opinions of experts in the fields of tuberculosis prevention and control, clinical and research and combining with the clinical trial results of EC, the expert consensus on the clinical application of EC has been formed on the basis of systematically summarizing the application characteristics of relevant technologies and methods. This consensus introduces the recommendations for the clinical application of EC, including the target users, method of application, the interpretation of the results, as well as the clinical significance and scope of use.

Key words: Latent tuberculosis, Mycobacterium infections, Diagnosis, differential, Recombinant Mycobacterium tuberculosis fusion protein (EC), Marketing of health services, Consensus development conferences as topic