Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005

South Korea is an intermediate tuberculosis (TB) burden country; in 2019, the annual incidence of TB was reported to be 59 per 100,000 [1]. TB is still an important public health concern in South Korea; for effective TB control, understanding its epidemiology, such as the prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) is important. ARI represents the proportion of newly infected or re-infected people over a 1-year period calculated based on the prevalence of LTBI. LTBI prevalence has steadily decreased in South Korea [2, 3]; however, about one third of the general population in South Korea is still thought to have LTBI [4, 5].

To date, LTBI prevalence studies and analysis of ARI have been conducted mainly using the tuberculin skin test (TST) in South Korea [2, 6, 7]. In previous studies, the annual risk of TB infection in South Korea was estimated using TST results in ages 5–9 years, and the ARI was 0.5–5.3% based on a 10-mm induration between 1958 and 1988 [6]. However, studies on ARI using interferon-gamma release assay (IGRA) results in South Korea are lacking.

In this study, we aimed to identify the prevalence of LTBI and estimate ARI in health care settings based on IGRA results of HCWs. We also aimed at identifying the risk factors of LTBI for HCWs with a particular focus on their age in an intermediate TB burden country.

In this study, using 3233 IGRA results of HCWs between 20 and 68 years of age, the overall prevalence of LTBI was 24.1%, and age was the strongest predictor of LTBI, rather than working in TB-related departments. The annual risk of TB infection ranged from 0.26 to 1.35% between 1986 and 2005, and its risk has gradually decreased over the last two decades.

ARI with Mycobacterium tuberculosis is known to be calculated from an observed prevalence of infection, approximating the incidence of infection. ARI for TB is one of the most important indicators for accessing its epidemiology in a population and is potentially informative about the transmission of TB within a community [12]. The main cause for the decline in ARI was a decreased prevalence of active TB in South Korea over 30 years, estimated from 443 to 167 cases per 100,000 population between 1985 and 2005, owing to economic growth and governmental effort to control TB via Bacillus Calmette–Guérin (BCG) vaccination, a TB notification system, and appropriate treatment through public health systems [3, 13]. Additionally, improvement on infection control at medical institutions is believed to have contributed to reducing ARI among HCWs.

To date, trends for TB prevalence and ARI have been documented in several countries, and most research has been based on national TST surveys [14‐16]. In South Korea, Kim et al. reported that the prevalence of LTBI using TST in persons < 30 years of age decreased from 55.9% in 1965 to 30.8% in 1995. In conjunction with this change, the ARI of TB in persons < 30 years of age decreased from 5.3% in 1965 to 0.5% in 1995 [2]. The use of TST however, has a poor specificity due to its cross-reaction with BCG vaccine strain and nontuberculous mycobacteria. According to a study conducted in South Korea comparing TST and IGRA results according to TB infection risk [4], the agreement between TST and IGRA was not high, and IGRA was a better indicator of the risk of TB infection than TST in a BCG-vaccinated population. There have been attempts to estimate ARI using IGRA [17, 18]. Nishimura et al. used IGRA data from HCWs in a university hospital in Japan and reported estimated ARIs for TB of 0.156% in 1986 and 0.049% in 2004 [19]. In a recent prospective study of a population of 13,580 individuals in China, ARI was estimated by conversion of IGRA and TST [20]. The annual TB infection rate was suggested to be 3.1% based on IGRA conversion and 1.5% based on persistent positive results after IGRA conversion. Meanwhile, however, ARI based on TST conversion was 14.5%, suggesting of limitation of ARI estimation based on TST results. The study concluded that the use of IGRA was more accurate than TST when estimating ARI [20]. However, studies on ARI using IGRA results are lacking in South Korea. Among recent large-scale surveys, a survey of 2051 sample of the 2016 Korea National Health and Nutrition Examination Survey (KNHANES) showed that the overall prevalence of LTBI was 33.2% using TST results [3, 21], which was higher than our study results. Considering the false positivity of TST, we believed that our data using IGRA results would reflect more accurate LTBI prevalence and ARI in South Korea where BCG vaccination is mandatory.

Our study also suggested that LTBI was related to older age, healed TB lesion on chest x-ray, and male gender, and not to current occupation in high-risk TB department. Several previous studies reported that TB-related departments such as respiratory ward or clinic, medical ICU, and emergency department increased the risk of LTBI positivity as compared to other departments [22‐24]. However, the majority of studies reporting such analyses were conducted in low-incidence settings. Contrarily, in countries with a relatively high TB burden, several studies have reported no significant differences in the LTBI positivity in HCWs working in TB-related department and other departments [25, 26]. The possible reasons for our results include a probability of casual contact with active TB patients in Korea, increased age regardless of working department, and adequate infection control in tertiary hospitals in our study setting.

Although the ARI for TB gradually decreased over 20 years in our study, LTBI prevalence and ARI among HCWs in South Korea were still higher than those in developed countries. This study also showed that the prevalence of LTBI was affected more by age-related risk exposure than working in a TB-related department. It is well known that exposure to TB at a young age and recent infection are major risk factors for the progression to active TB [27, 28]. Therefore, in South Korea, approaches to LTBI treatment among HCWs according to age should be differentiated due to a high likelihood of recent infections at a young age regardless of the department in which one is currently working.

This study has several limitations. First, we conducted this study at a single, tertiary hospital; hence, the findings may not be representative of HCWs in other hospital nor general population in South Korea. Second, in calculating ARI in this study, we used cross-sectional data rather than longitudinal data; hence, the accuracy of findings for old age may decrease given that the IGRA test scores wane as the age increases. Despite these limitations, to our knowledge, this is the first study in South Korea to report the estimation of ARI for TB based on IGRA results, and our study included large HCWs of different ages, working department, and working durations. Considering that age has a great impact on LTBI positivity, long-term follow-up studies are needed to identify how the progression from LTBI to active TB differs by age group.

Our study showed that ARI in HCWs in South Korea has gradually decreased over the last two decades, but LTBI was still considerably prevalent. We also suggest that LTBI among HCWs might be greatly affected by age, rather than occupational exposure in intermediate TB burden countries, hence different LTBI treatment strategies by age group should be considered.