This was a retrospective review of medical records of all HCWs being tested for LTBI. LTBI screening in HCWs was conducted from April 2017 to August 2017 at a tertiary hospital (hospital A) with 969 beds and a secondary hospital (hospital B) with 450 beds in South Korea based on the guideline. The HCWs included all employees (e.g., physicians, nurses, nursing assistants, paramedics, clerical staff, laboratory workers, food service workers) working in the hospital. After being advised to undergo LTBI examination through official communication by a section chief, HCWs decided to undergo the examination or not voluntarily. All HCWs who underwent the LTBI examination were enrolled in this study. According to the Manual for TB Management in Medical Institutions, HCWs were classified by the degree of risk into four groups based on two factors: possibility of exposure to MTB; and impact on patients at the time of TB onset in the HCWs (Table 1).

We excluded HCWs who either completed treatment of TB or LTBI in the past or were currently being treated. But there was no baseline data of LTBI for all staff. We obtained information regarding working healthcare facility, age, sex, number of years of service, department of work (doctors, nurses, nursing assiatants, lab workers, and others including clerks) for all participants via analyzing the medical records. To rule out active TB while screening for LTBI, all participants underwent a chest X-ray examination.

LTBI testing was performed with the IGRA test using the QuantiFERON^®-TB Gold in-Tube blood test (QFT-GIT; Cellestis Ltd., Carnegie, VIC, Australia). The cost of the examination for LTBI was reimbursed as per national policy. The QFT-GIT assay was performed according to the manufacturer’s instructions. Briefly, whole blood is drawn into 3 evacuated blood collection tubes: one containing heparin alone (negative control), one containing T cell mitogen (positive

TB: Tuberculosis; ICU: Intensive Care Unit; HCW: health care worker.

control), and one containing M. tuberculosis-specific antigens, including early secreted antigenic target 6, culture filtrate protein 10, and TB7.7 (TB-antigen tube). Following 16 - 24 hours of incubation, the concentration of interferon-gamma (IFN-γ) was determined by enzyme-linked immunosorbent assay. The QFT-GIT test result is considered positive if the IFN-γ response level is at least 0.35 IU/ml.

HCWs with positive results in the LTBI screening test visited outpatient clinics, and had their medical records reviewed by internal medicine doctors. After receiving explanation in outpatient clinics about LTBI, including the criteria for diagnosis, risks, and benefits of treatment, each HCWs were given the options of treatment. Four treatment options were offered: isoniazid (INH) 300 mg orally/rifampin (RIF) 600 mg (450 mg if body weight was <50 kg) orally daily for 3 months; RIF 600 mg (450 mg if body weight was <50 kg) orally daily for 4 months; INH 300 mg orally daily for 9 months; and no treatment. The INH/RIF regimen was recommended as the preferred option. According to the guidelines of the National Institutes for Health and Clinical Excellence (NICE), the regimen had the highest compliance rate in a short period, and treatment results were better than those of other regimens. Treatment costs and related examination expenses were covered by the government. Basal complete blood count, aspartate aminotransferase/alanine aminotransferase, bilirubin, blood urea nitrogen and creatinine were measured prior to treatment. Follow-up examinations were performed at 2, 4, 8 and 12 weeks after the start of treatment. HCWs visited outpatient clinics and were examined for side effects, such as skin disease and so on.

Comparisons between groups were made using the x² test for categorical variables and the Student’s t-test for continuous variables. Independent variables were analyzed using the logistic regression analysis, and a P-value of <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA).

The study was approved by the Institutional Review Board of each participating institution.

In this study, 45.2% (810/1790) of HCWs at hospital A and 74.4% (526/707) of HCWs at hospital B underwent the LTBI examination. Among them, 10 HCWs who had been previously treated with active TB or LTBI were excluded. A total of 1326 HCWs were included in the study, with an average age of 40.99 ± 10.86 years. The clinical characteristics are followed by Table 2. Of the total, 801 HCWs (60.4%) worked at hospital A and 525 HCWs (39.6%) worked at hospital B. The average age of the HCWs at hospital A was 41.29 ± 11.25 years, and at hospital B was 40.47 ± 10.21 years, with no significant difference (P = 0.577). The most populous age group when divided into ten-year intervals was that with individuals 20 - 29 years of age, with 606 HCWs (45.7%). The proportion of

HCWs who had worked less than 11 years was highest, at 68.5% (908). In terms of the classification of HCWs according to the degree of risk, the most populous was group 3, with 633 HCWs (47.7%). Nurses were the largest occupational category, with 801 members (60.4%).

The risk factors for LTBIs are followed by Table 3. Of the 1326 HCWs, 235 (17.7%) were diagnosed with LTBI. The rate of HCWs diagnosed with LTBI at hospital A

LTBI: latent tuberculosis infection.

was 18.6% (149/801) and at hospital B was 16.4% (86/525) (P = 0.30). The average age of HCWs diagnosed with LTBI was 32.32 ± 9.30 years and that of non LTBI HCWs was 40.99 ± 10.86 years (P < 0.001). Of the HCWs diagnosed with LTBI, 44.6% (62/139) were 50 years or older, and the higher the age, the higher was the LTBI rate (P < 0.001). Of those with more than 30 years of work in the hospitals, 32 (49.2%) were positive, with the LTBI rate increasing with the number of years of medical service (P < 0.001). The rate of LTBI was higher in males, with 85 cases (24.6%) (P < 0.001). According to the occupational classification, the LTBI rate was significantly higher in lab workers, with 15 cases (27.3%), compared with doctors and nurses (P < 0.001). According to the classification by the degree of risk, there were no significant differences (P = 0.24). In multivariate analysis, only age was independently associated with increased risk for LTBI (P < 0.001).

Of the 235 HCWs diagnosed with LTBI, 142 (60.4%) started treatment for LTBI. The determinants associated with acceptance rate for LTBI treatment are shown in Table 4. The acceptance rate of HCWs at hospital B was 70.9% (61/86), higher than that at hospital A (54.4%, 81/149) (P = 0.01). In terms of age, the acceptance rate of the 20-29 years group was the highest (P < 0.001). The acceptance rate was 66.0% (99/150) in females and 50.6% (43/85) in males (P = 0.02). In terms of years of work in the hospitals, the acceptance rate was the highest in those with less than 11 years of work, at 70.6% (P = 0.02). In terms of the classification according to the degree of risk, the acceptance rate was the highest in group 1 with 68.6% (P = 0.04). In multivariate analysis, there were no independently associated factors.

Of the 142 HCWs who started LTBI treatment, 125 (88.7%) chose INH/RIF, 9 (6.4%) chose RIF and 7 (5%) chose INH. Overall, 9 of 142 (6.3%) HCWs who started treatment with INH/RIF interrupted the treatment due to adverse effects. Four HCWs interrupted it with hepatotoxicity, 3 HCWs with dizziness, and 2 HCWs with skin rash. HCWs diagnosed as LTBI have been screened annually with chest X-rays to confirm whether LTBI transit to active tuberculosis.