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-SchoutenLiverpool, 27 October 2016

BackgroundTB notifications by country, EU/EEA, 201458 008 TB cases in 29 EU/EEA countries12.8 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

BackgroundTowards 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

2010

2016

2022

2028

2034

2040

2046

2052

2058

2064

2070

2076

2082

2088

1

10

100

1000

Decline needed to reach TB elimination by 2050Current mean annual decline

TB n

otifi

catio

ns p

er 1

milli

on

Towards TB elimination: An action framework for low-incidence countriesPriority action area1. 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

Towards TB elimination: An action framework for low-incidence countriesPriority action area1. 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

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

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).

Step 2: Systematic literature reviews

8

Step 2: Systematic literature reviews1. 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

Step 2: Systematic literature reviews1. 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

Mathematical modelling and cost-effectiveness studies

11Erasmus 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

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

ECDC guidance: Applicability for TB control in migrants

13

Total population

Infectious diseases

LTBI

Migrants

ECDC guidance: Applicability for TB control in migrants

14

Total population

Infectious diseases

LTBI

Migrants

Guidance on

programmatic

management of LTBI

ECDC guidance: Applicability for TB control in migrants

15

Total population

Infectious diseases

LTBI

Migrants

Guidance on prevention

of infectio

us diseases

among newly arrived

migrants in the EU/EEA

Acknowledgements

Erasmus MCJan A.C. HontelezJoost VanhommerigSuzanne VerverRui Cai Rinke HoekstraJan Hendrik RichardusSake J. de Vlas

ECDCAndreas SandgrenNetta BeerTeymur Noori

16

Pallas, Health research and consultancy B.V.

Marije Vonk Noordegraaf-Schouten

Femke van KesselAnke StuurmanAnouk Oordt-Speets

Radbout UMCRob Baltussen

Trend in origin of TB cases in the EU/EEA, 2007-2013

17

2007 2008 2009 2010 2011 2012 20130

10000

20000

30000

40000

50000

60000

70000

0.0

5.0

10.0

15.0

20.0

25.0

TB cases of non-EU/EEA origin TB cases of EU/EEA originTB cases of unknown/not specified origin % of non-EU/EEA TB cases among all TB

Year

No.

of

case

s Percentage

Ködmön et al. Eurosurveillance March 2016

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