Safety of a Novel ESAT6-CFP10 skin test compared with tuberculin skin test in a double-blind, randomized, controlled study

Abstract

Background ESAT6-CFP10 (EC) skin test has been reported accurate and safe in identifying tuberculosis infection. We aimed to demonstrate the safety of EC skin test compared with tuberculin skin test (TST) in university freshmen. Methods We conducted a double-blind, randomized, controlled clinical study in a university freshmen population with 16,680 participates in China, and finally 14,579 completed the study. About a half received an EC skin test and the others received TST. Adverse reactions were evaluated. Results Out of the 14,579 participants, 48.2% (7029/14,579) were males. The average age was 18.1 ± 0.8 years and the average BMI was 20.9 ± 3.1 kg/m2. 50.4% (7351/14,579) participants received EC skin test and 49.6% (7228/14,579) received TST. The EC group had significantly less adverse reactions compared with the TST group (21.3%, 1565/7351 vs. 34.6%, 2499/7228, P = 0.000). The most common adverse reactions for EC were bleeding (5.63%, 414), dermatodyschroia (4.27%, 314), induration (3.90%, 287), swelling (2.49%, 183), pain (1.59%, 117) and pruritus (1.48%, 109). Bleeding, dermatodyschroia, swelling and erythema were significantly less in EC group (P < 0.05), while others were similar to those of TST. Conclusion the EC skin test was safe in our cohort. And its incidence of total adverse drug reactions (ADRs) is less than that of TST. Most adverse reactions were mild or moderate, lasting less than 48 h and self-limiting. Considering the satisfactory diagnostic accuracy in identifying tuberculosis infection, the cost and safety, the EC skin test might be a potential candidate for replacing TST in high burden countries or those with routine BCG vaccination. Clinical Trials Registration. ChiCTR2000038622, Safety of the EC skin test to screen tuberculosis infection in two universities, compared with the tuberculin skin test: a double-blind, randomized, controlled trial. registered on 26/09/2020 at http://www.chictr.org.cn.

A Systematic Review on the Safety of Mycobacterium tuberculosis–Specific Antigen–Based Skin Tests for Tuberculosis Infection Compared With Tuberculin Skin Tests

“…Among those, 7 studies reported on Cy-Tb [ 8–13 ], 5 on C-TST [ 14–16 ], and 11 on Diaskintest [ 17–27 ]. The updated search identified 2 additional C-TST studies [ 28 , 29 ]. We also found studies of early products that were not translated into the final products ( Supplementary Table 1 ) [ 30–35 ].…”

“…In these studies, 2 tests were administered ≥30 minutes apart. The updated search also found a study that randomly administered C-TST in 1 group and TST in the other group while blinding the allocation [ 29 ]. Two studies did not compare C-TST and TST.…”

“…In the first study [ 15 ], a subset of the participants received C-TST in one arm and placebo in the other, and in the second [ 14 ], participants received only C-TST. Only 1 study provided data for the comparison of systemic adverse events [ 29 ].…”

“…Studies of C-TST were conducted as clinical trials and safety events were included as predefined outcomes. In 5 studies that allowed a comparison of C-TST versus TST, 2 were considered at low risk of bias [ 28 , 29 ] while the rest were considered at serious risk of bias in the measurement of outcomes because of the lack of blinding [ 15 , 16 ] ( Supplementary Materials ). While four of the C-TST studies did not randomize allocation of the tests, we did not rate down the risk of bias due to confounding in the ROBINS-I since the same participants received both tests.…”

“… Abbreviations: ISRs, injection site reactions; NA, not available; TST, tuberculin skin test. a In all studies but that of Yang et al [ 29 ], participants received both tests. b Data represent no.…”