The burden and predictors of latent tuberculosis infection among immigrants in South Korea: a retrospective cross-sectional study

Background Approximately one-fourth of the global population is latently infected with Mycobacterium tuberculosis. An understanding of the burden of latent tuberculosis infection (LTBI) among immigrants compared with the general Korean population should be the first step in identifying priority groups for LTBI diagnosis and treatment. The study aimed to compute the age-standardized LTBI prevalence and predictors among immigrants with LTBI in South Korea. Methods In 2018, the Korea Disease Control and Prevention Agency implemented a pilot LTBI screening project for immigrants using a chest radiography and the QuantiFERON Gold In-Tube assay. A standardized prevalence ratio (SPR) was computed to compare the LTBI burden in immigrants and the general Korean population. Results During the duration of the project, a total of 8108 immigrants (5134 males and 2974 females) underwent LTBI screening. The SPR of 1.547 (95% confidence interval [CI] 1.468–1.629) in males and 1.261 (95% CI 1.177–1.349) in females were both higher than the Korean reference population. Furthermore, among the immigrants, those aged < 40 years and Korean diaspora visa holders had a higher SPR. Conclusion This study found a higher LTBI prevalence among immigrant population in South Korea compared to that in the general Korean population, and the SPR was higher among those aged < 40 years and the Korean diaspora. The findings can be used as baseline evidence for including immigrants in South Korea in the at-risk group with a priority need for LTBI screening and treatment.

Cross-sectional study of prevalence and risk factors, and a cost-effectiveness evaluation of screening and preventive treatment strategies for latent tuberculosis among migrants in Singapore

ObjectivesWHO recommends that low burden countries consider systematic screening and treatment of latent tuberculosis infection (LTBI) in migrants from high incidence countries. We aimed to determine LTBI prevalence and risk factors and evaluate cost-effectiveness of screening and treating LTBI in migrants to Singapore from a government payer perspective.DesignCross-sectional study and cost-effectiveness analysis.SettingMigrants in Singapore.Participants3618 migrants who were between 20 and 50 years old, have not worked in Singapore previously and stayed in Singapore for less than a year were recruited.Primary and secondary outcome measuresCosts, quality-adjusted life-years (QALYs), threshold length of stay, incremental cost-effectiveness ratios (ICERs), cost per active TB case averted.ResultsOf 3584 migrants surveyed, 20.4% had positive interferon-gamma release assay (IGRA) results, with the highest positivity in Filipinos (33.2%). Higher LTBI prevalence was significantly associated with age, marital status and past TB exposure. The cost-effectiveness model projected an ICER of S$57 116 per QALY and S$12 422 per active TB case averted for screening and treating LTBI with 3 months once weekly isoniazid and rifapentine combination regimen treatment compared with no screening over a 50-year time horizon. ICER was most sensitive to the cohort’s length of stay in Singapore, yearly disease progression rates from LTBI to active TB, followed by the cost of IGRA testing.ConclusionsFor LTBI screening and treatment of migrants to be cost-effective, migrants from high burden countries would have to stay in Singapore for ~50 years. Risk-stratified approaches based on projected length of stay and country of origin and/or age group can be considered.

Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study

Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

Prevalence of Mycobacterium tuberculosis infection as measured by the QuantiFERON-TB Gold assay and ESAT-6 free IGRA among adolescents in Mwanza, Tanzania

Background The prevalence of latent tuberculosis infection (LTBI) is vastly higher than that of tuberculosis (TB) disease and this enormous reservoir of individuals with LTBI impacts the global TB control strategy. Adolescents are at greatest risk of TB infection and are thus an ideal target population for a potential effective TB vaccine to be added to the current BCG programme as it could reduce the number of latent infections and consequently the number of adults with TB disease. However, LTBI rates are often unknown for this population. This study aims to estimate the magnitude of LTBI and to determine if Tanzanian adolescents would be a good population for a prevention of TB infection trial. Methods This was a descriptive cross-sectional study that recruited 193 adolescents aged 12 and 16 years from government schools and directly from the community in Mwanza Region, Tanzania. Socio-demographic characteristics were collected for all enrolled participants. Blood was drawn and tested using QuantiFERON-TB Gold In-Tube (QFT-GIT), and Early Secretory Antigenic Target-6–Free Interferon-gamma Release Assay (ESAT-6 free IGRA). Concordance between QFT-GIT and ESAT-6 free IGRA was evaluated using the McNemar’s test. Results Overall estimates of LTBI prevalence were 19.2% [95%CI, 14.1; 25.2] and 18.6% [95%CI, 13.6; 24.6] as measured by QFT-GIT IGRA and ESAT-6 free IGRA, respectively. The 16-year-old cohort had a higher LTBI prevalence (23.7% [95%CI, 16.1; 32.9]) as compared to 12-year-old cohort (14.6% [95%CI, 8.6; 22.7]) as measured by QFT-GIT IGRA. When measured by ESAT-6 Free IGRA, LTBI prevalence was 24.7% (95%CI, 16.9; 34.0) for the 16-year-old cohort and 12.5% (95%CI, 7.0; 20.3) among the 12-year-old cohort. According to both tests the prevalence of TB infection and the corresponding annual risk of tuberculosis infection (ARTI) and force of infection were high and increased with age. Of all enrolled participants, 97.4% had concordant results for QFT-GIT IGRA and ESAT-6 free IGRA (p = 0.65). Conclusions The prevalence of LTBI and the associated ARTI and force of infection among adolescents is high and increases with age in Mwanza Region. There was a high concordance between the QFT-GIT and the novel ESAT-6 free IGRA assays. These findings suggest Mwanza is a promising area to conduct novel TB vaccine research prevention of infection (POI) studies targeting adolescents.

POS1436 EPIDEMIOLOGY OF LATENT TUBERCULOSIS INFECTION IN PATIENTS WITH RHEUMATIC IMMUNE-MEDIATED DISEASES. SINGLE UNIVERSITY STUDY OF 1117 PATIENTS

Background:Patients with rheumatologic immune-mediated diseases (R-IMID) with Latent tuberculosis infection (LTBI) requiring biologic therapy (BT) are at an increased risk of active tuberculosis (TB). Screening of LTBI with tuberculin skin test (TST) and/or Interferon (IFN)-γ release assays (IGRA) is recommended before starting of BT.Objectives:In patients with R-IMID previously to BT our aim was to assess a) prevalence of LTBI, b) importance of using a booster test in negative TST and c) to compare TST with the IGRA test.Methods:Cross-sectional single University Hospital study including all patients diagnosed with R-IMID who underwent a TST and/or IGRA in the last five years (2016-2020).TST was performed by a subcutaneous injection of 0.1 ml of purified protein derivative (PPD) with a reading after 72 hours. TST was considered positive with an induration of more than 5 mm of diameter. If the first TST was negative, a new TST (Booster) was performed between 1 and 2 weeks after the first TST.LTBI was diagnosed by a positive IGRA and/or TST and absence of active TB (Chest radiograph). Diagnosis with IGRA vs TST was compared (Cohen’s kappa coefficient).Results:We included 1117 patients (741 women/376 men), mean age 53±15 years with LTBI. Chest radiograph was normal in most of the patients, only 39 patients (3.5%) presented signs of previous TB infection, mostly granuloma. Total LTBI prevalence was 31.7% (354/1117). LTBI prevalence in different underlying R-IMID ranges from 35% in vasculitis up to 26.5% in conectivopathies (Figure 1).Booster was positive in 66 patients (7.7%) out of 859 patients with a negative simple TST. Results of TST (+booster) and IGRA tests are shown in Table 1. TST (+booster) was positive in 187 patients (22.9%) out of 817 with a negative or indeterminate IGRA test. IGRA test was positive in 30 (3.8%) out of 793 patients with a negative TST (+booster). Cohen’s Kappa coefficient between TST (+booster) and IGRA (QFT-plus), was 0.381.Conclusion:LTBI is frequent between patients with R-IMID. Booster after negative simple TST may be useful, since it can detect false negatives for LTBI. IGRA and TST(+booster) show a low grade of agreement. Therefore, performing both tests before BT may be recommendable.Table 1.Results of TST (+booster) and IGRA testIGRA (QFT-Plus)PositiveNegativeIndeterminateUnavailableTotalTST(+Booster)Positive891424548324Negative30500130133793Total1196421751811117* Cohen’s kappa coefficient: 0.381Figure 1.Prevalence of LTBI in different underlying R-IMIDLTBI: Latent tuberculosis infection, PsA: Psoriatic arthritis, RA: Rheumatoid arthritis, SpA: Axial spondyloarthritis.Diagnosis of LTBI: Positive TST(+booster) and/or IGRA test.Disclosure of Interests:David Martínez-López: None declared, Joy Osorio-Chavez: None declared, Carmen Álvarez-Reguera: None declared, Virginia Portilla: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD, Consultant of: Abbvie, Pfizer, Roche, Sanofi and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Grant/research support from: Abbvie, MSD, and Roche

State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity

Introduction Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. Methods We created a mathematical model using all incident TB disease cases during 2013–2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. Results We estimated that 2.7% (CI: 2.6%–2.8%) of the U.S. population, or 8.6 (CI: 8.3–8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%–1.1%) and among non-US-born persons was 13.9% (CI: 13.5%–14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45–64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). Conclusions Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.

Prevalence of Latent Tuberculosis Infection among Non-U.S.–Born Persons by Country of Birth — United States, 2012-2017

Background Most tuberculosis (TB) disease in the U.S. is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-U.S.–born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress towards TB elimination. Methods 13 805 non-U.S.–born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON ® Gold In-Tube test, and T-SPOT ®.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CRI) for each country or world region of birth. Results Among the study population, the estimated LTBI prevalence was 31% (95% CRI 26% – 35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42%-55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8%-13%. Conclusions LTBI prevalence in persons born outside the United States varies widely by country. These estimates can help target community outreach efforts to the highest risk groups.

Optimal Testing Choice and Diagnostic Strategies for Latent Tuberculosis Infection Among US-Born People Living with Human Immunodeficiency Virus (HIV)

Background Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. Methods We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. Results Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. Conclusions LTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT’s higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.

Latent tuberculosis infection prevalence in rural Madagascar

Background Understanding latent Mycobacterium tuberculosis infection (LTBI) prevalence is crucial for the design of TB control strategies. There are no data on LTBI in rural Madagascar. Methods Tuberculin skin tests were performed in 98 adults aged &gt;15 y in five rural villages in the Ifanadiana district, Madagascar. Results Of adults, 78.6% were positive for LTBI, ranging between 28.6% and 95.0% among villages. The majority (65.3%) showed an induration reaction of &gt;15 mm. Conclusions LTBI prevalence is high in rural Madagascar. Long-term TB control strategies including LTBI testing and treatment must account for high and heterogeneous prevalence in remote, underdeveloped areas.

Duration of Exposure Among Close Contacts of Patients With Infectious Tuberculosis and Risk of Latent Tuberculosis Infection

Background Predictors of latent tuberculosis infection (LTBI) among close contacts of persons with infectious tuberculosis (TB) are incompletely understood, particularly the number of exposure hours. Methods We prospectively enrolled adult patients with culture-confirmed pulmonary TB and their close contacts at 9 health departments in the United States and Canada. Patients with TB were interviewed and close contacts were interviewed and screened for TB and LTBI during contact investigations. Results LTBI was diagnosed in 1390 (46%) of 3040 contacts, including 624 (31%) of 2027 US/Canadian-born and 766 (76%) of 1013 non-US/Canadian-born contacts. In multivariable analysis, age ≥5 years, male sex, non-US/Canadian birth, smear-positive index patient, and shared bedroom with an index patient (P &lt; .001 for each), as well as exposure to &gt;1 index patient (P &lt; .05), were associated with LTBI diagnosis. LTBI prevalence increased with increasing exposure duration, with an incremental prevalence increase of 8.2% per 250 exposure hours (P &lt; .0001). For contacts with &lt;250 exposure hours, no difference in prevalence was observed per 50 exposure hours (P = .63). Conclusions Hours of exposure to a patient with infectious TB is an important LTBI predictor, with a possible risk threshold of 250 hours. More exposures, closer exposure proximity, and more extensive index patient disease were additional LTBI predictors.