1. 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

2. Conflict of Interest
No conflict of interest to declare

3. 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)

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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/ screened),
Port of arrival (29/ screened),
Post-arrival (431 cases / screened)
Kunst H et al Int J Tuberc Lung Dis 2017

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

14. 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/ recruited from the mandatory screening programme, with a reported yield of 42.5%
Kunst H et al Int J Tuberc Lung Dis 2017

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. Thank you!