ECDC presentation at the Union Conference, Liverpool, 27 October 2016. Marieke van der Werf, ECDC.

1. Guidance on programmatic management of
latent TB infection: applicability for TB control
in migrants
Marieke J. van der Werf, Netta Beer, Sake J. de Vlas, Teymur Noori, Marije
Vonk Noordegraaf-Schouten
Liverpool, 27 October 2016

2. Background
TB notifications by country, EU/EEA, 2014
58 008 TB cases in 29 EU/EEA countries
12.8 per 100 000 population (range 2.5–79.7)
2
Not reporting
20 to 49 per 100 000
10 to 19 per 100 000
5 to 9 per 100 000
< 5 per 100 000
≥ 50 per 100 000

3. Background
Towards TB elimination in EU/EEA
With current mean annual change in the TB notification rate (-6%), the
EU/EEA will achieve TB elimination by 2092.
To reach elimination by 2050, TB rates need to decline by 12% annually.
3
1
10
100
1000
2010 2020 2030 2040 2050 2060 2070 2080 2090
TBnotificationsper1million
Decline needed to reach TB elimination by 2050 Current mean annual decline

4. Towards TB elimination: An action
framework for low-incidence countries
Priority action area
1. Ensure political commitment, funding and stewardship
for planning and essential services of high quality.
2. Address the most vulnerable and hard-to-reach
groups.
3. Address special needs of migrants and cross-border
issues.
4. Undertake screening for active TB and LTBI in TB
contacts and selected high-risk groups, and provide
appropriate treatment.
5. Optimize the prevention and care of drug-resistant TB.
6. Ensure continued surveillance, programme monitoring
and evaluation and case based-data management.
7. Invest in research and new tools.
8. Support global TB prevention, care and control.
4

5. Towards TB elimination: An action
framework for low-incidence countries
Priority action area
1. Ensure political commitment, funding and stewardship
for planning and essential services of high quality.
2. Address the most vulnerable and hard-to-reach
groups.
3. Address special needs of migrants and cross-border
issues.
4. Undertake screening for active TB and LTBI in TB
contacts and selected high-risk groups, and provide
appropriate treatment.
5. Optimize the prevention and care of drug-resistant TB.
6. Ensure continued surveillance, programme monitoring
and evaluation and case based-data management.
7. Invest in research and new tools.
8. Support global TB prevention, care and control.
5

6. ECDC guidance document on programmatic
management of latent TB infection: PROCESS
Expert
meeting
• Inventory of expert opinions on components of LTBI control
collected through a questionnaire and two interactive rounds
Systematic
reviews
• Systematic literature reviews on scientific evidence for relevant
components of LTBI control
Modelling
• Mathematical modelling and cost-effectiveness studies on LTBI
control
Expert panel
meeting
• Expert panel meeting to discuss the results of the systematic
reviews and modelling
Guidance
• Development of guidance with options for introducing
programmatic LTBI control in the European Union
6

7. Step 1: Expert meeting
Components identified for guidance
• diagnostic tests for LTBI
• preventive treatment regimens
• risk group specific interventions
• combining LTBI control with other health programmes
7Sandgren et al. Euro Surveill. 2016 Aug 25;21(34).

8. Step 2: Systematic literature reviews
8

9. Step 2: Systematic literature reviews
1. What is the prevalence of LTBI among risk groups?
2. What is the risk of progression of LTBI to active TB disease among risk groups?
3. What is the incidence of active TB among risk groups?
4. Among individuals at risk of LTBI, which investigations and clinical parameters are most
predictive of the absence of active TB?
5. Among persons at high risk of latent tuberculosis infection (LTBI) who are not on tuberculosis
preventive therapy, which test(s) alone or in combination with other proxies for LTBI, when
positive, can best identify individuals most at risk of progression to incident tuberculosis (TB)
disease?
6. Systematic literature review and meta-analysis on the best treatment options for latent
tuberculosis infection
7. What is the best way to monitor and manage hepatic toxicity and other adverse events in
individuals receiving treatment for LTBI?
8. Does treatment for LTBI lead to significant development of resistance against the drugs used?
9. What is the effectiveness of anti-tuberculosis drugs (any regimen) in preventing active TB in
contacts of MDR-TB patients?
10. For each recommended LTBI treatment regimen, what are the initiation and completion rates?
11. For each recommended LTBI treatment regimen, what are the determinants of treatment
initiation, adherence and completion?
12. In individuals who are eligible for LTBI treatment, what are the interventions with demonstrated
efficacy to improve LTBI treatment initiation, adherence and completion?
13. Will duration of protection from LTBI treatment be a barrier to LTBI management
implementation?
14. What is the cost-effectiveness of LTBI management interventions?
9

10. Step 2: Systematic literature reviews
1. What is the prevalence of LTBI among risk groups?
2. What is the risk of progression of LTBI to active TB disease among risk groups?
3. What is the incidence of active TB among risk groups?
4. Among individuals at risk of LTBI, which investigations and clinical parameters are most
predictive of the absence of active TB?
5. Among persons at high risk of latent tuberculosis infection (LTBI) who are not on
tuberculosis preventive therapy, which test(s) alone or in combination with other
proxies for LTBI, when positive, can best identify individuals most at risk of
progression to incident tuberculosis (TB) disease?
6. Systematic literature review and meta-analysis on the best treatment options for
latent tuberculosis infection
7. What is the best way to monitor and manage hepatic toxicity and other adverse events in
individuals receiving treatment for LTBI?
8. Does treatment for LTBI lead to significant development of resistance against the drugs used?
9. What is the effectiveness of anti-tuberculosis drugs (any regimen) in preventing active TB in
contacts of MDR-TB patients?
10. For each recommended LTBI treatment regimen, what are the initiation and completion rates?
11. For each recommended LTBI treatment regimen, what are the determinants of treatment
initiation, adherence and completion?
12. In individuals who are eligible for LTBI treatment, what are the interventions with demonstrated
efficacy to improve LTBI treatment initiation, adherence and completion?
13. Will duration of protection from LTBI treatment be a barrier to LTBI management
implementation?
14. What is the cost-effectiveness of LTBI management interventions?
10

11. Mathematical modelling and cost-
effectiveness studies
11
Erasmus MC. Report: Assessment of introducing programmatic latent tuberculosis control in the European Union and
candidate countries. Work package 5: Cost-effectiveness analysis
BRHR = behaviour-related high-risk individuals

12. ECDC guidance document on programmatic
management of latent TB infection: PROCESS
Expert
meeting
• Inventory of expert opinions on components of LTBI control
collected through a questionnaire and two interactive rounds
Systematic
reviews
• Systematic literature reviews on scientific evidence for
relevant components of LTBI control
Modelling
• Mathematical modelling and cost-effectiveness studies on
LTBI control
Expert panel
meeting
• Expert panel meeting to discuss the results of the systematic reviews
and modelling
Guidance
• Development of guidance with options for introducing programmatic
LTBI control in the European Union
12

13. ECDC guidance: Applicability for TB control
in migrants
13
Total population
Infectious diseases
LTBI
Migrants

14. ECDC guidance: Applicability for TB control
in migrants
14
Total population
Infectious diseases
LTBI
Migrants

15. ECDC guidance: Applicability for TB control
in migrants
15
Total population
Infectious diseases
LTBI
Migrants

16. Acknowledgements
Erasmus MC
Jan A.C. Hontelez
Joost Vanhommerig
Suzanne Verver
Rui Cai
Rinke Hoekstra
Jan Hendrik Richardus
Sake J. de Vlas
ECDC
Andreas Sandgren
Netta Beer
Teymur Noori
16
Pallas, Health research and
consultancy B.V.
Marije Vonk Noordegraaf-Schouten
Femke van Kessel
Anke Stuurman
Anouk Oordt-Speets
Radbout UMC
Rob Baltussen

17. Trend in origin of TB cases in the EU/EEA,
2007-2013
17
0.0
5.0
10.0
15.0
20.0
25.0
0
10000
20000
30000
40000
50000
60000
70000
2007 2008 2009 2010 2011 2012 2013
Percentage
No.ofcases
Year
TB cases of non-EU/EEA origin TB cases of EU/EEA origin
TB cases of unknown/not specified origin % of non-EU/EEA TB cases among all TB
Ködmön et al. Eurosurveillance March 2016

18. Conflict of interest disclosure
X I have no, real or perceived, direct or indirect conflicts of interest that relate to this
presentation.
 I have the following, real or perceived direct or indirect conflicts of interest that relate to
this presentation:
Affiliation / financial interest Nature of conflict / commercial company name
Tobacco-industry and tobacco corporate affiliate
related conflict of interest
Grants/research support (to myself, my institution or
department):
Honoraria or consultation fees:
Participation in a company sponsored bureau:
Stock shareholder:
Spouse/partner:
Other support or other potential conflict of interest:
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