Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program

Tuberculosis (TB) remains a serious global threat to public health. In 2022, an estimated 1.3 million deaths worldwide were attributed to TB.1 Approximately one-fourth of the global population is thought to be infected with Mycobacterium tuberculosis. 2 To achieve elimination of TB by 2050, treatment of latent tuberculosis infection (LTBI) is crucial.3 World Health Organization (WHO) recommends that screening and treatment for LTBI should be performed among contacts of active TB patients or clinical high-risk groups in high-income or middle-income countries with an annual TB incidence rate of less than 100 cases per 100,000 population.4 Additionally, screening and treatment for LTBI should be considered for prisoners, healthcare workers, immigrants from countries with high TB burden and homeless populations.

South Korea is a country with intermediate TB burden, showing a rapid decrease in TB burden since 2010’s. In 2011, annual TB incidence was 100.8 cases per 100,000 population. By 2022, it had decreased to 39.8 cases per 100,000 population.5 South Korean government implemented an LTBI screening program for people living with human immunodeficiency virus (HIV) and household contacts aged under 6 in 2004 and expanded target groups progressively.6 Currently, LTBI screening is widely performed among TB contacts of all ages and various clinical risk groups specified in Korean guidelines for TB.7 However, the current LTBI strategy of South Korea does not cover immigrants due to the lack of evidence.8, 9

The number of foreign TB patients peaked at 2,569 in 2016. It gradually decreased to 1,072 in 2022. However, they still account for more than 5% of total notified TB cases each year.5 Although foreign population accounted for only 3.5% of the total population in South Korea, which was lower than an average of 10.6% in OECD countries in 2022,10 there is a growing argument for expanding immigration to address labor shortages resulting from population aging.11 Considering that TB incidence in native Korean is decreasing rapidly, TB among immigrant population might be emerging as a significant issue in national TB control, as in other countries with a low TB burden.12, 13

With these backgrounds, this study aimed to investigate TB incidence among immigrants who participated in the pilot LTBI screening program and prioritize specific target groups for LTBI screening to mitigate the risk of active TB.

A total of 10,918 foreigners participated in the LTBI screening program. After applying exclusion criteria, a total of 9,517 participants were finally included in this study (Fig. 1). Baseline demographic characteristics of these enrolled participants and results of IGRA test are detailed in Table 1. Prevalence of LTBI among enrolled participants was 26.9%. The prevalence among participants aged under 35 was 14.3%, whereas it was 45.3% in those aged 65 or over. Participants from countries with intermediate TB burden, most of them from China, exhibited the highest prevalence (29.6%). Regarding visa types, those with overseas Korean – work and visit (H2) visa showed a marked high prevalence (31.7%), followed by those on family visit or marriage migrant (F visa) (30.3%). The majority of these two groups were comprised of ethnic Koreans with Chinese nationality.

Fig. 1
Flow chart showing the enrollment of participants.
LTBI = latent tuberculosis infection, TB = tuberculosis, IGRA = interferon-gamma release assay.

• Click for larger image

Table 1
Baseline demographic features of enrolled participants

• Click for larger image
• Click for full table
• Download as Excel file

TB incidence among participants

TB incidence among total participants is presented in Table 2. Out of a total of 9,517 participants, 14 TB cases were identified with a cumulative follow-up of 11984.02 person-years, resulting in an incidence rate of 116.8 per 100,000 person-years. TB incidence among male participants was 149.8 per 100,000 person-years whereas that in females was 64.6 per 100,000 person-years. Incidence among participants aged under 35 was 85.1 per 100,000 person-years, whereas that among those aged 65 or over was 655.1 per 100,000 person-years. Those from countries with an intermediate burden of TB showed the incidence of 119.7 per 100,000 person-years. Participants from high TB burden countries showed incidence of 106.0 per 100,000 person-years. Participants with positive IGRA results who did not initiate LTBI treatment showed a TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed a TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio (IRR) of 9.08 (95% CI, 2.50–32.99).

Table 2
TB incidence among total participants (N = 9,517)

• Click for larger image
• Click for full table
• Download as Excel file

When the same analysis was applied to those with positive IGRA results, TB incidence in those aged under 35 increased the most abruptly among all age groups – from 85.1 per 100,000 person-years in total participants to 444.5 per 100,000 person-years in those with positive IGRA results (Table 3). Participants with positive IGRA results from countries with a high TB burden showed an incidence of 415.2 per 100,000 person-years, whereas that in those from countries from an intermediate TB burden was 304.6 per 100,000 person-years. Participants with positive IGRA results who aged 65 or over from countries with an intermediate TB burden showed the TB incidence of 714.6 per 100,000 person-years. That in those who aged under 35 from countries with a high TB burden and those aged under 35 from countries with an intermediate TB burden was 636.5 per 100,000 person-years and 386.2 per 100,000 person-years, respectively.

Table 3
TB incidence among participants with positive IGRA results (N = 2,564)

• Click for larger image
• Click for full table
• Download as Excel file

SIR of TB

SIR of TB among total participants was 2.60 (95% CI, 1.54–4.38; P < 0.001) (Table 4). Participants aged 65 or over showed the highest SIR among all age group (SIR, 5.38; 95% CI, 1.35–21.52; P = 0.017). Participants with H2 visa demonstrated the highest SIR among all visa type (SIR, 3.13; 95% CI, 1.63–6.01; P = 0.001). The younger age group under 35 from countries with a high TB burden had an SIR of 4.10 (95% CI, 1.02–16.37; P = 0.046) for TB incidence. The older age group over 65 from countries with an intermediate TB burden exhibited the highest SIR (5.41; 95% CI, 1.35–21.65; P = 0.017) among participants, followed by a younger age group under 35 from high TB burdened countries (SIR, 4.10; 95% CI, 1.02–16.37; P = 0.046).

Table 4
Standardized incidence ratio of TB among total participants compared with total population in Korea

• Click for larger image
• Click for full table
• Download as Excel file

SIR among those with positive IGRA results was 5.86 (95% CI, 3.15–10.89; P < 0.001) (Table 5). Young age group under 35 (SIR, 12.91; 95% CI, 4.16–40.03; P < 0.001), participants from countries with high TB burden (SIR, 11.26; 95% CI, 1.59–79.95; P = 0.016), and participants with employment visa (SIR, 10.88; 95% CI, 1.53–77.24; P = 0.017) showed marked high SIR. By analyzing TB burden of countries of origin and age together, participants aged under 35 from countries with a high TB burden (SIR, 18.08; 95% CI, 2.55–128.37; P = 0.004) and those from countries with an intermediate TB burden (SIR, 11.30; 95% CI, 2.82–45.16; P < 0.001) showed prominently high SIRs.

Table 5
Standardized incidence ratio of TB among participants with positive IGRA results compared with total population in South Korea

• Click for larger image
• Click for full table
• Download as Excel file

In this study, we examined TB risk among immigrants who participated in the pilot LTBI screening project by calculating the incidence of TB stratified with age, the TB burden of COO, and LTBI status, and then presenting the SIR compared to the general population in South Korea. We found a high SIR among IGRA-positive immigrants aged under 35 from high or intermediate TB-burden countries. Additionally, a high SIR was observed in immigrants aged 65 or over from intermediate TB-burden countries, regardless of their IGRA results.

As of December 2023, the estimated number of foreign residents in South Korea was 2.51 million.20 Although the current proportion of foreign population among total population in South Korea was relatively low among OECD countries,10 the government is implementing immigration policy drawing more migrants to sustain economic growth, considering the all-time low fertility rate (0.78 children per woman in 2022) and rapid population aging in South Korea.21 For example, to address shortage of labor in various industrial fields, the scale of introduction of non-professional employment (E-9 visa) was significantly expanded from the usual 50,000 to 120,000 in 2023.22 In addition, South Korean government is implementing a pilot program to address the shortage of domestic workers by expanding the eligibility of foreign domestic workers to include a non-professional employment (E-9) category.22 With this background, the number of people with migration backgrounds, which was 2.18 million (4.2% of total population) in 2020, is projected to increase to 3.23 million (6.4% of total population) by 2040.23

The current TB control strategy for immigrants in South Korea primarily focuses on screening for active TB.8, 24 Pre-entry TB screening for long-term visa applicants from 19 Asian countries has been implemented since 2016. Mandatory TB screening is also enforced upon visa changes or extensions after entry. LTBI screening for immigrants has not been implemented so far as TB burden in South Korea is disproportionately high, considering its socio-economic level.25 In addition, unlike other low-incidence countries where TB among foreign-born population accounts for the majority of nationwide TB burden,26 TB among native elderly population rather than foreign-born population has been prioritized in national TB control policy in South Korea.27 However, with a rapid decrease in TB incidence in recent years,5 and a low LTBI prevalence among young population in South Korea,28 LTBI screening for immigrants would be underscored in national TB control program in the near future.

Many countries with a low TB burden have implemented LTBI screening for immigrants in diverse forms.29 The United States (US) has adopted a pre-arrival LTBI screening. All applicants for US visa aged 2 and above from countries with TB incidence over 20 cases per 100,000 population are required to undergo an IGRA test.30 In UK, immigrants aged 16–35 years from countries with TB incidence over 150 cases per 100,000 population or countries in sub-Saharan Africa who arrived in England in the previous 5 years are offered post-arrival LTBI screening with IGRA.18 European guidelines did not universally recommend LTBI screening for immigrants. They suggested that decisions should be made based on the specific epidemiological status of each member state.31 However, many European countries have adopted post-arrival LTBI screening for immigrants.29 In a survey performed in 2016, approximately half (52.7%) of European countries provided LTBI screening for refugees.32

In this study, diagnostic performance of IGRA in stratification of TB risk among immigrants was demonstrated. The diagnostic performance of LTBI test is one of crucial factors in selection of target group for LTBI screening.33 IRR of positive IGRA results compared with negative results among immigrants aged under 35 from countries with high or intermediate TB burden was 17.52 (95% CI, 1.41–919.77). Although verification in further studies with larger sample size is needed, this high IRR suggests that risk stratification with IGRA among young immigrants is efficient. Although a previous cost-effectiveness study has provided evidence for current LTBI screening policy among immigrants in UK,34 subsequent studies on the efficacy of LTBI treatment among immigrants and its cost-effectiveness should be conducted.

IRR among those aged 65 or over from countries with an intermediate TB burden was only 1.13 (95% CI, 0.01–88.71) due to develop of TB in participants with negative IGRA results. In a previous meta-analysis, the predictive performance of IGRA was lower in countries with a high TB incidence than in those with a low TB incidence, which derived from a de novo TB infection among people with initial negative IGRA results and subsequent TB development among them.35 Moreover, in contrast to a result of a previous study reporting that TB risk in elderly population with LTBI was lower than that in younger population with LTBI as the elderly people with LTBI were infected long ago,36 TB incidence in elderly immigrants with positive IGRA results was comparable to that in younger immigrants with positive IGRA results. Among immigrants with positive IGRA results, those aged 65 or over showed the highest TB incidence (714.6 per 100,000 person-years), followed by those aged under 35 (444.5 per 100,000 person-years). We postulate that de novo TB infection would be quite frequent among elderly immigrants, the majority of whom are ethnic Koreans with Chinese nationality. While not confirmed by our data, one possibility is that many elderly immigrants might work as caregivers and thus could have been exposed to TB within hospital settings.37 As of 2020, 46% of caregivers working in domestic nursing hospitals were foreigners, with the majority being ethnic Korean women in their 50s and 60s who had Chinese nationality.38 Although the burden of nosocomial TB exposure in South Korea is still substantial,39 caregivers are excluded from LTBI screening currently as they are not hospital employees. Further research is needed on LTBI prevalence and incidence of TB among elderly immigrants, particularly those working as caregivers.

This study is the first to report the incidence TB based on LTBI status among foreign immigrants in South Korea. As South Korea does not conduct LTBI screening for immigrants, currently, we adopted the rationale from the UK, which actively screens immigrants for LTBI. We classified immigrants based on their age and the COO’s TB burden to investigate the detailed TB risk. However, this study has several limitations. First, as development of TB among participants was rare, adequate statistical power could not be achieved. Due to a relatively short duration of follow-up time (mean follow-up time of 1.26 years), we could not demonstrate the TB incidence from a long-term perspective. Moreover, the lack of access to immigration records for immigrants raises the possibility that some of them might not have resided in Korea during the study period, which could lead to an underestimation of TB incidence. Further research with a larger sample size, extended duration of follow-up period and precise information on in-bound and out-bound immigration office is required. Second, this study was a pilot project and included only a subset of immigrants who underwent mandatory TB screening for visa changes or extensions, which may introduce selection bias. The number of mandatory TB screenings conducted for immigrants in 2018 was 241,322. Among these, 8,811 individuals participated in the pilot LTBI screening project at 12 designated hospitals and 9 public health centers in Gyeonggi Province, with a participation rate of 3.65%. This represents 0.37% of the total 2,367,607 foreign residents in Korea in 2018. However, due to the lack of information about the source population, we could not verify this bias. There is a possibility that immigrants who are more health-conscious and diligent about their health care selectively participated in this pilot project, which could result in an underestimation of TB risk. It is also plausible that some participants had specific reasons for undergoing screening, such as respiratory symptoms like cough or sputum, or recent contact with TB patients. These factors lead to an overestimation of TB risk, thus indicating that selection bias could act in both directions. Third, as this study is an observational study, 316 participants who underwent LTBI treatment, which could affect the natural course of TB infection, were identified, and excluded from the study. There were no cases of TB among them, and if they had been included, the TB risk would have been calculated lower. Though we could not verify on the specific circumstances under which IGRA-positive participants started LTBI treatment, it is possible that they began treatment due to recent contact with TB patients or other risk factors for developing TB. From this perspective, we postulate that if these participants had not received LTBI treatment, the incidence of TB might have been much higher. Fourth, the lack of access to immigration records for immigrants raises the possibility that some of them might not have resided in Korea during the study period, which could lead to an underestimation of TB incidence. Fifth, since less than a half of immigrants were enrolled in NHI, information regarding income levels or comorbidities available from NHID could not be utilized for analysis.

In conclusion, young immigrants with positive IGRA results from countries with a high or intermediate TB burden showed a relatively high risk for TB development compared to general South Korea population. Furthermore, unexpected high TB risk was observed among elderly immigrants with positive IGRA results, warranting further investigation.