Tuberculosis Screening and Case Finding Among Migrants Adriana Hristea University of Medicine and Pharmacy Carol Davila National Institute for Infectious Diseases Prof Dr Matei Bals Bucharest, Romania

Conflict of Interest No conflict of interest to declare

Outline Tuberculosis (TB) risk in migrants in low TB burden countries vs risk of TB in travelers from low to high TB burden countries Methods of TB screening and case finding among migrants Identifying active TB Screening migrants for latent TB infection (LTBI)

TB risk in migrants Migration - not a risk for TB by itself Migrants are not representative for the country TB risk Immigrants from TB endemic countries account for a significant proportion of TB cases in low TB burden countries Stressful living condition in overcrowded conditions Social isolation, Poverty, Malnutrition, Unemployment, Difficulties in accessing health care

TB in migrants in low TB burden countries Country of origin with high TB burden Country of arrival with low TB burden Migrants Emigrants Immigrants Active TB on arrival New TB infection Community transmission/VFR Reactivation of LTBI 55-90% Data on LTBI prevalence (cross-sectional) Few longitudinal data on reactivation Relatively little transmission (genotyping data) Pareek et al. BMC Medicine 2016; Franzetti F, et al Clin Microbiol Infect. 2010; Hernandez-Garduno E, et al CMAJ. 2002

Risk of TB in travelers Travelers Visiting friends and relatives Country with high TB burden Country with low TB burden The absolute risk in most short-term travellers is low Association between country TB incidence and risk of converting a tuberculin skin test (TST) Denholm JT, Thevarajan I. J Trav Med, 2016

Risk of TB in travelers (2) Country with high TB burden Country with low TB burden Travelers largest study of TB risk in travellers in US Peace Corps volunteers: 689 cases of LTBI and 13 cases of active TB, (0.95 cases of LTBI [95%CI 0.88–1.02] and 0.02 cases of active TB (95% CI 0.01–0.03) per 1000 Volunteer-months (1) risk estimates (LTBI and active TB) traveller risk in long-term travel: - TST conversion 4.28 and 5.36 per 1000 person months of travels (2) - Cumulative LTBI incidence of 2% in long-term traveller and military personnel (3) found a general correlation between risk of TST conversion and regional TB incidence, with the highest risk coming from sub-Saharan African settings. In high incidence countries, risk of TST conversion overall was around 1.6% per year, with active TB occurring in approximately 0.1% per year. Brown M, et al J Travel Med. 2015; Cobelens FG, et al Lancet. 2000; Freeman RJ, et al J Travel Med. 2010 .

Outline Tuberculosis (TB) risk in migrants in low TB burden countries vs risk of TB in travelers from low to high TB burden countries Methods of TB screening and case finding among migrants Identifying active TB Screening migrants for LTBI

Screening for TB in migrants in low TB burden countries Active TB on arrival Reactivation of LTBI Community transmission Pre-arrival active TB screening Post-arrival active TB screening Post-arrival LTBI screening Post-arrival Routine identification of active TB and contact tracing (LTBI) Pareek et al. BMC Medicine 2016

Pre-arrival active TB screening People who are applying to travel to certain countries (Australia, Austria, Canada, France, Israel, Jordan, New Zealand, UK, USA) Asylum seekers and irregular migrants are not included in the program (other measures to control TB are needed) Issues: Incidence rate cut off for the need of screening (arbitrary choice) Published information about cost-effectiveness of pre-entry screening is scarce Chest X-ray is not a perfect method; sputum culture Most TB cases in migrants diagnosed > 2 years after entry into the country Pareek M, et al Emerg Infect Dis 2012; MJ van der Werf, P Kramarz Lancet Infect Dis 2016

Pre-arrival active TB screening (2) Useful component of a TB elimination strategy and can add to the control of TB in migrants Host country can save health-care costs (should all European countries implement pre-entry TB screening?) Health-care services accessible and responsive to the needs of all (early TB diagnosis and treatment) Need to consider equity, ethics, risk of stigma and discrimination Pareek M, et al Emerg Infect Dis 2012; Lonnroth K, Eur Respir J 2015; MJ van der Werf, P Kramarz Lancet Infect Dis 2014

Yield of screening for active TB among migrants within the EU/EFTA Systematic review (25 studies active TB screening in migrants) Differences in: Type of screening (mandatory/voluntary) Populations and number of subjects screened (asylum seekers, all migrants, undocumented migrants) Yield of screening according to the strategy: Pre-entry (93 cases/100 000 screened), Port of arrival (29/100 000 screened), Post-arrival (431 cases /100 000 screened) Kunst H et al Int J Tuberc Lung Dis 2017

Yield of screening for active TB among migrants within the EU/EFTA (2) Reported coverage: 85-100% for subject population >10.000 Yield of screening: 26 to 671/100 000 screened Reported coverage: 64-85% for subject population <10.000 Yield of screening: 0 to 5782/100 000 screened Kunst H et al Int J Tuberc Lung Dis 2017

Yield of screening for LTBI among migrants within the EU/EFTA Systematic review (20 studies LTBI screening in migrants) Differences in: Method used: TST+IGRA (Italy, the Netherlands and Norway), IGRA testing only (Switzerland and the UK), TST only (Spain) Coverage for LTBI screening (reported for 3 countries from 6 studies): 15% and 99% Yield for LTBI screening: TST: 28-45% IGRA: 17-29% The highest yield of LTBI was from a study in the Netherlands using TST among migrants from countries with a TB incidence of . 50/100 000 recruited from the mandatory screening programme, with a reported yield of 42.5% Kunst H et al Int J Tuberc Lung Dis 2017

TB and LTBI screening of migrants in Europe Limited information about screening within EU countries Limited progress to systematically collect and evaluate screening data and harmonise screening policies across Europe Different: Screening methodology, Definitions used for coverage and yield Migrant populations Age groups TB incidence in the country of origin making it challenging to compare screening strategies and make valid conclusions on the most cost-effective policy/ approach. Kunst H et al Int J Tuberc Lung Dis 2017

Economic evaluations of LTBI screening (1) Review of 10 research studies, published between 2000 and 2014; 4 in the US, 3 in the UK, and 3 in Canada; Limitations: Age limitations in the study population (4 studies); Defining “immigrants”: at the moment of their entrance/within 5 years/without specification/>5 years Neither quality nor quantitative weights of each study to make a pooled conclusion on cost-effectiveness Zammarchi et al. BMC Health Services Research 2015

Economic evaluations of LTBI screening (2) Detecting and treating LTBI in immigrants was associated with substantial health and economic benefits One-step IGRA-protocol is the most cost-effective strategy for LTBI screening in migrants (in any context?) Targeting young migrants from countries at higher incidence of TB increases the cost-effectiveness of the screening Zammarchi et al. BMC Health Services Research 2015

Migrant screening methods Active TB screening When Pre-arrival, at arrival, post-arrival How Algorithms including: CXR Symptom-based questionnaires, Bacteriology Weaknesses Low yields for active TB Uncertain cost-effectiveness Not identifying LTBI LTBI screening When Post-arrival How Algorithms including different combinations of TST and IGRA Weaknesses Difficult to implement Numbers accepting/completing treatment suboptimal Pareek et al. BMC Medicine 2016

Flowchart for travel evaluations for TB risk If the pre-travel LTBI test was performed (either with low risk of exposure and risk factors for progressing to active TB) it should be repeated and LTBI treatment should be considered if positive test. If the risk of exposure and risk factors for progressing to active TB are low and the pre-travel LTBI test was not performed there is no routine follow up needed unless TB exposure occurs. It is important to consider BCG vaccination if <5 years old. Denholm JT, Thevarajan I. J Trav Med, 2016

Conclusions Screening migrants from high TB incidence countries for active TB or LTBI is a critical component of the TB elimination strategies in low-incidence countries The aim of LTBI screening is the prevention of progression to active TB via preventive therapy Most developed countries screen for active TB, but screening for LTBI is less commonly performed There are discrepancies between policies and implementation of migrant screening

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