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

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/m. 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 .