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  • Study subjects and screening protocol: This study was conducted at Severance Hospital (Seoul, Republic of Korea), a tertiary referral hospital with approximately 2400 beds. About 600 culture- or smear-positive pulmonary TB patients are managed annually at this institution. According to the institution’s policy, all high-risk HCWs were recommended to undergo an annual TB screening from October 2009. High-risk HCWs were defined as those who are working at TB-related departments, such as medical intensive care unit, respiratory department of ward and outpatient clinic, emergency department, microbiology laboratory, and radiology department. Each subject underwent a TST, a simple chest radiography, and a medical interview of comorbidities, previous TB history, work duration, and occupational category (i.e., physician, nurse, health aide, technician, and others). We analyzed the screening data of high-risk HCWs who underwent TST at least once between 2009 and 2013. Four TSTs were performed during the study period because only chest radiograph was conducted in 2010. In 2009 (T1), 286 high-risk HCWs participated in the screening. In 2011 (T2), 2012 (T3), and 2013 (T4), 83, 46, and 43 additional high-risk HCWs newly joined the program, respectively, because of movement from other departments or new recruitment. (Fig 1A) Figure data removed from full text. Figure identifier and caption: 10.1371/journal.pone.0204035.g001 Study population of (A) total HCWs and (B) HCWs with two-step baseline TSTs. HCWs, healthcare workers; TST, tuberculin skin test; T1, annual screening in 2009; T2, in 2011; T3, in 2012; T4, in 2013. QFT-GIT was tested for the TST-converted subjects. Those who showed TST-converted and QFT-GIT-positive results were strongly recommended to take treatment for latent TB infection with either 3 months of isoniazid and rifampicin, 4 months of rifampicin, or 9 months of isoniazid. High-risk HCWs were followed for the development of active pulmonary TB after 2013 based on the medical records and the results of regular medical exam for all employees. The study protocol was reviewed and approved by the Institutional Review Board of Severance Hospital, and informed consent was waived by the committee. (4-2017-1055) A TST was performed on the forearm in accordance with the Mantoux method using a 0.1mL of 2 TU of purified protein derivative RT 23 (Statens Serum Institute, Copenhagen, Denmark). The transverse diameter of the induration was measured in millimeters 48 to 72 hours later. A positive TST was defined as an induration ≥ 10 mm in diameter. TST conversion was defined as a baseline TST induration < 10 mm and a follow-up TST induration ≥ 10 mm with an increment of ≥ 6 mm relative to baseline. [13] Follow-up TST was repeated for subjects with previous negative TST. In addition, for the all new employees from October2011, two-step baseline TSTs were carried out as a medical check-up at the time of employment. QFT-GIT was performed according to the manufacturer’s instructions. A positive QFT-GIT result was defined as the interferon-γ response of TB antigen minus the negative control of ≥ 0.35 IU/mL and 25% of the negative control value. Data are presented as numbers (percentage) or medians (range or interquartile range, IQR). Pearson’s chi-squared test or Fisher’s exact test was used to comparing categorical variables, and the Mann-Whitney U-test was used to comparing continuous variables. We used SPSS (v. 18.0; SPSS Inc., Chicago, IL, USA) in data analyzing. In all analyses, P < 0.05 (two-tailed) was taken to indicate statistical significance.
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