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.

Targeting screening and treatment for latent tuberculosis infection towards asylum seekers from high-incidence countries – a model-based cost-effectiveness analysis

Background Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence. Methods We sampled hypothetical cohorts of 30–45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017–2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds. Results We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2–21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7–14.8) QALYs at a cost of €51,000 (€18,000–€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100–€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200–€128,200) and €62,000 (€23,200–€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100. Conclusions LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.

Latent tuberculosis screening and treatment in HIV: highly acceptable in a prospective cohort study

BackgroundPeople living with HIV (PLWH) are at increased risk of reactivation of latent TB infection (LTBI). Although UK and international guidelines identify this group as a priority for LTBI screening and treatment, data on attitudes of PLWH to this policy recommendation are lacking.MethodsA five-point, Likert-style questionnaire was administered to PLWH to assess views and intentions towards accepting LTBI screening and treatment. Subsequent Immune Gamma Release Assay (IGRA) testing was offered, and chemoprophylaxis if required. Influencing demographic and psychological associations with planned, and actual, testing and treatment uptake, were assessed using multivariable logistic regression.Results444/716 (62%) patients responded. 417/437 (95.4%) expressed intention to accept LTBI testing. The only significant association was the perceived importance of testing to the individual (aOR 8.98, 95% CI 2.55–31.67). 390/393 (99·2%) accepted appropriate IGRA screening; 41/390 (10·5%) were positive. 397/431 (92.1%) expressed intention to accept chemoprophylaxis, associated with perceived importance of treatment (aOR 3.52, 95% CI 1.46–8.51), a desire to have treatment for LTBI (aOR 1.77, 95% CI 0.99–3.15), and confidence in taking treatment (aOR 3.77, 95% CI 1.84–7.72). Of those offered chemoprophylaxis, 36/37 (97·3%) accepted and 34/36 (94·4%) completed treatment. There were no correlates with actual screening acceptance.ConclusionsLTBI is common amongst PLWH, highlighting the importance of robust screening and treatment programmes. This study shows that screening and treatment for LTBI is highly acceptable to PLWH and provides strong, objective, evidence for policy-makers developing guidelines in this cohort.

798. Incomplete Contact Investigation and Risk of Developing Tuberculosis Among Healthcare Professionals After Tuberculosis Exposure

Background Tuberculosis (TB) contact investigation is recommended for healthcare professionals (HCPs) after TB exposure. However, association between no participation in or incomplete contact investigation and subsequent TB development has not been well-described. This study aims to determine TB incidences and factors associated with TB development among HCPs requiring contact investigations. Methods We conducted a prospective cohort study among Thai HCPs with TB exposure from January 2013 to December 2017. Contact investigations, including baseline TB and latent tuberculosis infection (LTBI) screening and follow-up at 3 months after TB exposure, were recommended to all HCPs. The two-step tuberculin skin test (TST) was used for LTBI testing. All HCPs were followed for 2 years for TB development. Results Of the 342 HCPs with TB exposure included in the study, 311 (91%) participated in the contact investigations and 252 (74%) completed baseline TB and LTBI screening. Among the 210 HCPs with negative baseline TST, 45 (21%) completed the follow-up tests. The overall incidence of TB was 2.92/100 person-years. HCPs who did not complete follow-up TST had significantly higher TB incidence than those completed baseline and follow-up TST (3.55 vs. 0/100 person-years; P=0.01). No participation in the contact investigation and no chest radiograph performed at baseline were the independent factors associated with TB development among the HCPs [adjusted odds ratio (aOR) 6.69; P&lt; 0.001 and aOR 8.85; P=0.01, respectively]. Contact with an index patient with concomitant TB at extrapulmonary sites (aOR 49.76, 10.03-246.99; P&lt; 0.001) and with negative sputum AFB but positive sputum GeneXpert MTB/RIF (aOR 3.18, 1.35-7.50; P=0.008) were independently associated with no participation in the contact investigation. Conclusion The findings indicate the risk of TB development among the HCPs who did not undergo or complete contact investigations and underscore the need for interventions to improve contact investigation participation and completeness. Disclosures All Authors: No reported disclosures

Systematic review of latent tuberculosis infection research to inform programmatic management in Ireland

The World Health Organisation (WHO) End Tuberculosis (TB) Strategy and the WHO Framework Towards Tuberculosis Elimination in Low Incidence Countries state that latent tuberculosis infection (LTBI) screening and treatment in selected high-risk groups is a priority action to eliminate TB. The European Centre for Disease Prevention and Control (ECDC) advises that this should be done through high-quality programmatic management, which they describe as having six key components. The research aim was to systematically review the literature to identify what is known about the epidemiology of LTBI and the uptake and completion of LTBI screening and treatment in Ireland to inform the programmatic management of LTBI nationally. A systematic literature review was performed according to a review protocol and reported in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Twenty-eight studies were eligible for inclusion and described LTBI screening or treatment performed in one of five contexts, pre-biologic or other immunosuppression screening, people living with HIV, TB case contacts, other vulnerable populations, or healthcare workers. The risk of bias across studies with regard to prevalence of LTBI was generally high. One study reported a complete cascade of LTBI care from screening initiation to treatment completion. This systematic review has described what published research there is on the epidemiology and cascade of LTBI care in Ireland and identified knowledge gaps. A strategy for addressing these knowledge gaps has been proposed.

Fewer losses in the cascade of care for latent tuberculosis with solo interferon-gamma release assay screening compared to sequential screening

Background Refugees are at increased risk of developing tuberculosis (TB) soon after resettlement. Targeting high-risk populations for latent tuberculosis infection (LTBI) screening and treatment is an important measure towards eliminating TB in low incidence countries, however, there are low rates of screening and treatment completion in the LTBI cascade of care. The authors hypothesized that an interferon-gamma release assay (IGRA) screening strategy would lead to a higher proportion of refugees completing LTBI screening and treatment, compared to sequential screening with tuberculin skin test (TST) and confirmatory IGRA. Methods This retrospective cohort study included eligible refugees screened with a sequential strategy versus a solo-IGRA strategy at different time periods from a centralized refugee clinic. The primary outcome was the proportion completing LTBI screening in each cohort. Results A total of 471 subjects were included (240 in sequential screening, 231 in solo-IGRA screening). 54% of refugees completed LTBI screening with sequential testing, compared to 85% of those screened with a solo-IGRA. Time to completing screening was also shorter in the solo-QFT group (difference 16.5 days, p < 0.01, 95% confidence interval 9.3, 23.7). There was a higher incidence of LTBI diagnosis in the solo-IGRA group (41 versus 20, p = 0.002). Screening completion was predicted by solo-IGRA screening (aOR 3.74, 95% confidence interval 2.30, 6.09; p < 0.001) and if refugees were privately-sponsored (aOR 2.81, 95% confidence interval 1.53, 5.15; p = 0.001). Treatment completion rates did not differ between groups. Conclusion This study has identified fewer dropouts in the LTBI cascade of care if a solo-IGRA strategy is used for screening. An IGRA should be strongly considered as the screening method for refugees arriving in low-incidence settings if resources are available.

Tuberculosis infection screening in children with close contact: a hospital-based study

Background Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance. Methods During 2013–2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk. Results A total 6202 children (median age: 4.76 years; interquartile range: 1.0–8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA− /TST+ results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result. Conclusions Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.

Lessons learned from implementation of interferon-gamma release assay to screen for latent tuberculosis infection in a large multicenter observational cohort study in Brazil

Background: Interferon-gamma release assay (IGRA) has emerged as a useful tool in identifying latent tuberculosis infection (LTBI). This assay can be performed through testing platforms, such as QuantiFERON-TB Gold Plus (QFT-Plus). This in vitro test has been incorporated by several guidelines worldwide and has recently been considered for the diagnosis of LTBI by the World Health Organization (WHO). The possibility of systematically implementing IGRAs such as QFT-Plus in centers that perform LTBI screening has been accelerated by the decreased availability of tuberculin skin testing (TST) in several countries. Nevertheless, the process to implement IGRA testing in routine clinical care has many gaps. Methods: The study utilized the expertise acquired by the laboratory teams of the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil consortium during study protocol implementation of LTBI screening of TB close contacts. Results: RePORT-Brazil includes clinical research sites from Brazilian cities and is the largest multicenter cohort of TB close contacts to date in the country. Operational and logistical challenges faced during IGRA implementation in all four study laboratories are described, as well as the solutions that were developed and led to the successful establishment of IGRA testing in RePORT-Brazil. Conclusions: The problems identified and resolved in this study can assist laboratories implementing IGRAs, in addition to manufacturers of IGRAs providing effective technical support. This will facilitate the implementation of IGRA testing in countries with a high TB burden, such as Brazil.

POS1157 CONCORDANCE BETWEEN THE QUANTIFERON-TB GOLD IN-TUBE AND TUBERCULIN TEST FOR THE DIAGNOSIS OF LATENT TUBERCULOSIS INFECTION IN PATIENTS WITH RHEUMATIC DISEASES

Background:Patients with rheumatic diseases (RD) are at higher risk of latent tuberculosis infection (LTBI) reactivation. To detect and treat it before starting treatment, especially with biological therapies, decrease the reactivation risk. Diagnosis is carried out by the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs), IGRAs might be more specific and sensitive.Objectives:We aim to analyze the concordance between QuantiFERON-TB Gold In-Tube (QTF) and TST for the diagnosis of LTBI in patients with rheumatic diseases.Methods:A retrospective observational study was conducted including patients diagnosed with RD screened for LTBI with both TST and QTF (2014-2018). Demographical and clinical variables at screening and at follow-up were collected. The concordance between both tests has been estimated as categorical variables using Cohen´s Kappa test, considering “poor” if it is ≤ 0,20; “low” if 0,20 < k ≤ 0,40, “moderate” if 0,40 < k ≤ 0,60, “substantial” if 0,60 < k ≤ 0,80 and “optimal” if k > 0,80.Results:167 patients were included (57% women) with a mean age of 52±16 years. 42% of them had systemic autoimmune diseases, 22% spondyloarthropathies and 36% other RD. 2 had history of past active tuberculosis (TB). At the time of screening, 46.11% were treated with GC.LTBI was diagnosed in 35 patients: 15 had both QTF and TST positive, 16 only QTF positive and 4 only TST positive. 12 from 31 QTF positive patients were treated with GC at the time of screening. 3 from 19 TST positive patients were treated with GC at the time of screening.After LTBI screening 62 patients received biological treatment, 4 of them had both test positive, 6 only QTF positive and 2 only TST positive. 11 received LTBI treatment according to the hospital protocol (isoniazid for 6 to 9 months). 10 completed treatment, 1 did not because of intolerance and did not receive other treatment. 1 patient with only TST positive was considered a false positive and did not receive treatment. During follow-up no TB reactivation was reported.23 patients with LBTI received treatment other than biological therapy during follow-up, of them 8 received LBTI treatment. There was no TB reactivation during follow up.The Kappa concordance between QTF and TST was estimated: moderated in the whole sample, poor in the patients treated with GC at screening, and substantial when the patients treated with GC at screening were excluded. Results are shown in Table 1.Table 1.Kappa concordance between QTF and TST.Conclusion:QTF seems to be the most appropriate LTBI screening test in patients with RD treated with GC. Screening and treatment of LTBI in patients with RD treated with or without biological agents was effective in reducing TB reactivation.Disclosure of Interests:None declared.

Latent tuberculosis screening before kidney transplantation in the South of Brazil

Background: Tuberculosis (TB) is a prevalent infection after kidney transplantation (KT) in high-burden countries. Latent tuberculosis infection (LTBI) screening includes previous TB history, chest radiograph findings, and tuberculin test (TST) and/or interferon-gamma release assays (IGRAs) results. We aimed to compare our routine LTBI screening of KT candidates and living donors (LD) with their IGRA results, and evaluate if this would improve isoniazid (INH) treatment referral. Methods: We evaluated adult KT candidates and LD with complete routine LTBI screening and QuantiFERON-TB® Gold In-Tube (QFT) testing. Blood samples were collected from April 4th, 2014 to October 31st, 2018, with follow-up until October 31st, 2019. Results: There were 116 KT recipients, with 30% QFT-positive results. Positive QFT was associated with past TB history (p=0.007), positive TST (p<0.0001), residual radiographic lesions (p=0.003), and diabetes (p=0.035). There were 25 LD, 40% had positive QFT. Positive QFT was associated with a positive TST (p=0.002). Positive QFT results increased INH referral in 80%. Post-transplant TB incidence was 2.6% in a median follow-up of 2 (1-33) months. No variables were associated with post-transplant TB. TB patients had inferior, although non-significant, 5-year graft survival (66.7% vs. 76.5%) (p = 0.402). Conclusion: In the present study, the association of QFT to our routine LTBI screening incremented INH treatment referral, but there was still a high incidence of post-transplant TB, possibly related to other forms of infection, such as new exposure and donor transmission.