Professor G. B. Migliori - WHO Collaborating Centre for TB and Lung Disease, Fondazione S. Maugeri, Care and Research Institute Tradate, Italy Find out more on http://goo.gl/8GUwwL

1. MOVING TOWARDS TB ELIMINATION:
EXPERIENCE AND LESSON LEARNED
THROUGH ERS ENGAGEMENT IN
EUROPE
G. B. Migliori
WHO Collaborating Centre for TB and Lung Disease,
Fondazione S. Maugeri, Care and Research Institute
Tradate, Italy

2. Faculty disclosure
NO COI !!!

3. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

4. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

5. Sotgiu et al, NEJM 2013

6. 6
INTERVENTIONS TO PREVENT AND MANAGE TB
First sanatorium
Germany, 1857 First Dispensary,
Scotland, 1897
Koch, Mtb,
1882
Drugs, 1945-1962
MMR,1950-1980
Fox:Ambulatory treatment, 1968
Styblo model, 1978
DOTS, 1991
sanatoria Outbreak Management,
Risk Group Management
screening
BCG vaccination
drug therapy
Socio-economic improvement
Pneumotorax, Italy, 1907

7. 7
DOTS
• Government commitment
• Case detection by SS microscopy among self-
reporting symptomatic patients
• Standardised short-course chemotherapy for at
least all confirmed smear positive cases, DOT
during the intensive phase for all new SS+ cases,
continuation phase of RMP-containing regimens
and the whole re-treatment regimen.
• A regular, uninterrupted supply of all essential anti-
TB drugs
• A standardised R&R system allowing assessment of
case-finding and treatment results and of NTP
performances
Int J Tuberc Lung Dis 2001; 5(3):213-215

8. STOP TB STRATEGY (WHO)
1. Pursue high-quality DOTS expansion and enhancement
• Political commitment with increased and sustained financing
• Case detection through quality-assured bacteriology
• Standardised treatment, with supervision and patient support
• An effective drug supply and management system
• Monitoring & evaluation system, and impact measurement
2 Address TB/HIV, MDR-TB and other challenges
3. Contribute to health system strengthening
4. Engage all care providers
5. Empower people with TB and communities
6. Enable and promote research

9. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

11. Core additional interventions to pursue
elimination
• 1) Ensuring early detection of TB patients and their
treatment until cure and preventing avoidable death
from TB
• 2) Reducing the incidence of infection by risk group
management and prevention of transmission of
infection in institutional settings
• 3) Reducing the prevalence of tuberculosis
infection through outbreak management and
provision of preventive therapy for specified groups
and individuals

12. Core additional interventions to pursue
elimination
• 1) Ensuring early detection of TB patients and their
treatment until cure and preventing avoidable death
from TB (C);
• 2) Reducing the incidence of infection by risk group
management and prevention of transmission of
infection in institutional settings (C,E)
• 3) Reducing the prevalence of tuberculosis
infection through outbreak management and
provision of preventive therapy for specified groups
and individuals (E)

13. Elimination programmatic
pre-requirements (1)
• Government and private-sector commitment towards
elimination
• National schemes for TB control and elimination
• National TB policy
• National TB network
• Legal framework
• Human resources development and health
education
• Research
• International and European collaboration

14. Elimination programmatic
pre-requirements (2)
• Case detection through case-finding among
symptomatic individuals presenting to health
services and
• Active case-finding in special groups
• Standard approach to treatment of disease and
TB infection
• Accessibility to TB diagnostic and treatment
services
• Surveillance and treatment outcome monitoring
for TB diseases and TB infection

16. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

17. WORLD HEALTH ASSEMBLY APPROVES POST-2015
GLOBAL TB STRATEGY AND TARGETS –
WHA TB RESOLUTION

18. ZERO
TB DEATHS
A WORLD FREE OF TB
Vision
ZERO
TB CASES
ZERO
TB SUFFERINGGLOBALTB
PROGRAMME

19. Goal and Targets
Target 1
95% reduction in
TB deaths (compared
with 2015)
Target 2
<10/100 000
TB incidence rate
2035
GOAL: End the Global TB Epidemic
GLOBAL TB
PROGRAMME

20. TARGETS
• 35% reduction in
TB deaths
• <85/100 000 TB
incidence rate
• No affected
families with
catastrophic
costs due to TB
TARGETS
• 75% reduction in
TB deaths
• <55/100 000 TB
incidence rate
• No affected
families with
catastrophic
costs due to TB
TARGETS
• 90% reduction in
TB deaths
• <20/100 000 TB
incidence rate
• No affected
families with
catastrophic costs
due to TB
GOAL
• 95% reduction
in TB deaths
• <10/100 000 TB
incidence rate
• No affected
families with
catastrophic
costs due to TB
20352020 20302025
Getting there: Milestones

21. High-
quality,
integrated
TB care
and
prevention
Bold
policies and
supportive
systems
Intensified
research
and
innovation
Post-2015 TB Strategy
Proposed Pillars and Principles

22. POST-2015 TB STRATEGY: PILLAR 1
Treatment of all people with
TB including drug-resistant
TB, with patient-centered
support
3
Preventive treatment of
people at high-risk and
vaccination for TB
4
Early diagnosis of TB
including universal
drug susceptibility
testing; systematic
screening of contacts
and high-risk groups
1 2
Collaborative TB/HIV
activities and management
of co-morbidities
High-
quality,
integrated
TB care
and
prevention
GLOBAL TB
PROGRAMME

23. Integrated, patient-
centered TB Care and
Prevention
Early diagnosis of TB including
universal drug-susceptibility
testing ; systematic screening of
contacts and high-risk groups
Treatment of all people with TB
including drug -resistant TB; and
patient support
Collaborative TB/HIV activities
and management of co-
morbidities
Preventive treatment for persons
at high-risk; and vaccination
against tuberculosis
Bold policies and
supportive systems
Political commitment with adequate
resources for TB care and prevention
Engagement of communities , civil
society organizations, and all public
and private care providers
Universal health coverage policy; and
regulatory framework for case
notification, vital registration, quality
and rational use of medicines, and
infection control
Social protection, poverty alleviation,
and actions on other determinants of
TB
Intensified Research and
Innovation
Discovery, development and rapid
uptake of new tools,
interventions and strategies
Research to optimize
implementation and impact, and
promote innovations
Targets: 95% reduction in deaths and 90% reduction in
incidence (< 10 cases / 100,000 population) by 2035
Post-2015 Global TB Strategy: Pillars

24. Full implementation of Global Plan: 2015 MDG
target reached but TB not eliminated by 2050
Current rate of
decline -2%/yr
W Europe after WWII -
10%/yr
China, Cambodia
-4%/yr
Elimination target:<1 / million / yr
-20%/yr
China, Cambodia
-4%/yr

25. -3.4%/yr
-5%/yr
Incidence Prevalence
-3%/yr
-7%/yr
China
Cambodia
Sustained socio-
economic development
Stop TB Strategy with
adequate resources
TB care subsidized and
decentralised
BCG vaccination in
infants
Decline in TB burden in China and Cambodia
Recipe:

26. Full implementation of Global Plan: 2015 MDG
target reached but TB not eliminated by 2050
Current rate of
decline -2%/yr
W Europe after WWII
-10%/yr
China, Cambodia
-4%/yr
Elimination target:<1 / million / yr
-20%/yr
W Europe after WWII
-10%/yr

27. Nat Rev Microbiol 2012; 10: 407–16.
-10%/year Sustained socio-economic
development
Universal health coverage &
social protection
TB care widely accessible
BCG vaccination in children
Screening of high-risk groups (but
limited impact)
Infection control practices (?)
TB incidence declined 10%/year
after WWII in Europe (the Netherlands)
Recipe:

28. Full implementation of Global Plan: 2015 MDG
target reached but TB not eliminated by 2050
Current rate of
decline -2%/yr
W Europe after WWII -
10%/yr
China, Cambodia
-4%/yr
Elimination target:<1 / million / yr
-20%/yr
Eskimos
> 10 ; < 20

29. Eskimos in Alaska, NW Canada and Greenland:
15% per year incidence decline
Highly focused & high
intensity interventions
Screening and massive TLTBI
TB care decentralised
BCG vaccination
Improved health access &
social protection
Economic development (?)
Recipe:
-17%/year
(1955-74) -8.7%/year
(1972-74)
Grzybowski S, Styblo K, Dorken E. Tuberculosis in Eskimos. Tubercle
1976; (suppl.) 57: 1-58

30. Can TB control among Eskimos be generalised to
the world?

31. Full implementation of Global Plan: 2015 MDG
target reached but TB not eliminated by 2050
Current rate of
decline -2%/yr
W Europe after WWII -
10%/yr
China, Cambodia
-4%/yr
Elimination target:<1 / million / yr
-20%/yr
Elimination target:<1 /million/yr
-20%/yr

32. DEFINITIONS
• Low-incidence countries: TB notification rate of <10 cases (all
forms) per 100,000 population and year. Previous alternative
thresholds: <20/100,000, or <16/100,000.
• Pre-elimination: <10 notified TB cases (all forms) per million
population per year. This is the same as proposed by Clancy et al
in 1991.
• TB elimination: <1 notified TB case (all forms) per million
population and year.
• Alternative definitions: European region, <1 sputum-smear
positive case per million; ECDC has proposed all forms of TB. US
CDC defines elimination in the USA as < 1 case of TB, all forms,
per million population.

33. TARGETS
<100 cases per million
Current TB burden-2012
in low-incidence countries
<10 cases per million
Pre-elimination: 2035
in low-incidence countries
<1 case per million
Elimination: 2050

34. Economic development: better nutrition & housing
Universal health coverage & social protection
TB care widely accessible to all and of high-standards
Focused, high-intensity interventions, including BCG in children
Screening of high-risk groups and mass TLTBI
Infection control practices
However… while incidence decline can accelerate, “elimination” is
another story, as it requires major reduction of:
In turn, this requires…new tools and increased financing
(i) transmission rate, and
(ii) reactivation of latent infection among the already infected
What is needed to accelerate incidence decline and
target "elimination"?

35. What is in the pipelines for new diagnostics,
drugs and vaccines in 2013?
Diagnostics:
₋7 new diagnostics or diagnostic methods
endorsed by WHO since 2007;
₋6 in development;
₋yet no PoC test envisaged
Drugs:
-2 new drugs approved in 2012 & 2013 for
MDR-TB : little impact on epidemiology;
-a regimen and other 2-3 drugs likely to be
introduced in the next 4-7 years
Vaccines:
₋11 vaccines in advanced phases of
₋development;
₋1 reported in 2012 with no detectable
efficacy

36. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

37. 7 Core areas:
1. TB control commitment, TB
awareness, and capacity of
health systems
2. Surveillance
3. Laboratory services
4. Prompt, quality TB care for all
5. M/XDR-TB and TB/HIV co-
infection
6. New tools
7. Partnership and collaboration

38. ACKNOWLEDGMENTS
COUNTRY RESPONDENTS
ALBANIA Hasan Hafizi
BELGIUM Maryse Wanlin, Wouter Arrazola de Onate, Guido Groenen
CROATIA Vera Katalinić Janković, Alexander Simunovic
CZECH REPUBLIC Jiri Wallenfels
DENMARK Peter Henrik Andersen
ESTONIA Piret Viiklepp, Manfred Danilovits, Tiina Kummik
FINLAND Petri Ruutu
FRANCE Thierry. M. Comolet
GERMANY Walter Haas
GREECE Mina Gaga
HUNGARY Zsofia Pusztai
IRELAND Joan O Donnell
ISRAEL Daniel Chemtob
ITALY Enrico Girardi
KOSOVO-UNIMIK Rukije Mehmeti
LATVIA Vija Riekstina
MALTA Analita Pace Asciak
NORWAY Trude M Arnesen
POLAND Ewa Augustynowicz-Kopeć
PORTUGAL Raquel Duarte, Ana Maria Correia
R. OF MACEDONIA Stefan Talevski
ROMANIA Gilda Popescu, Domnica Chiotan
SERBIA Gordana Radosavljevic Asic
SLOVAKIA Ivan Solovic
SLOVENIA Marijan Ivanuša
SPAIN Elena Rodríguez Valín
SWEDEN Jerker Jonsson
SWITZERLAND Peter Helbling, Jean Pierre Zellweger
THE NETHERLANDS Gerard de Vries, Connie Erkens
UK Laura Anderson,Ian Laurenson

39. EUROPE HOW FAR TO REACH ELIMINATION?
EU LOW / MIDDLE TB INCIDENCE COUNTRIES ITALY
10 (33%) No TB Elimination plan NO
7 (23%) No TB elimination guideline NO
15 (50%) No HRD plan NO
10 (33%) No TB Reference centres YES
16 (53%) No TB budget NO
11 (37%) No supervision NO
25 (87%) No modelling NO
5 (17%) No NRL performing all F/SLD DST YES
4 (13%) No free access for all TB cases YES
20 (67%) No all F/SLD NO
10 (33%) Drugs stock-outs NO
10 (33%) No TB/HIV collab. activities NO
13 (43%) Hospital-based MDR-TB care YES
21 (70%) No strategy to introduce new tools NO
21 (70%) No international collaboration for TB
control/elimination
NO
10 (33%) No TB Consilium NO

40. INCIDENCE DECLINE: TECHNOLOGICAL BREAKTHROUGH BY 2025
ADDRESSING THE POOL OF LATENT INFECTION
Business as usual
Optimize current tools,
ensure UHC and SP
New tools: vaccine, prophylaxis
Average -10%/year
-5%/year
-2%/year
Average -
17%/year
GLOBAL TB
PROGRAMME

41. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

42. TB Elimination: from Wolfheze to Rome
THANK Rome 4-5 July 2014
Wolfheze, May 1990

43. WHO/ERS SUMMIT ON TB
Rome July 4th-5th 2014
Elimination of TB in low incidence countries
• New WHO/ERS Framework launched on Sunday (Room AZ-4 h. 12.45)
• Summary report published in the ERJ
• Unprecedent media coverage:187 cuttings, in 11 countries, > 500,000 page
views every months

44. Generalised (with social gradient)
Important community transmission
Many incident cases from recent transmission
Relatively high burden among young people
Dominant public health problem
Poorly resourced health systems
Low incidence
High incidence
Epidemiological characteristics
Highly concentrated to risk groups
Close to elimination in large parts of the population
Low transmission
Outbreaks in special groups
LTBI relatively more important
Migration impact
Stronger health system but less TB visibility

45. ACTION FRAMEWORK
8 PRIORITY ACTIONS FOR ELIMINATION IN LOW-INCIDENCE COUNTRIES
Invest in
research
and new tools
Optimize the
prevention and care
of drug-resistant TB
Address special
needs of migrants
and cross-border
issues
Address the most
vulnerable and hard-
to-reach groups
Support global
TB prevention, care
and control
Ensure continued
surveillance,
programme
monitoring &
evaluation , and
case-based data
management
Undertake
screening for active
TB and latent TB infection
in TB contacts and
selected high-risk groups,
and provide appropriate
treatment
Ensure political
commitment, funding
and stewardship for
planning and
essential services
of high quality

46. OBSERVED VS. REQUIRED ANNUAL RATE OF
CHANGE TO REACH TB ELIMINATION BY 2035
IN LOW-INCIDENCE COUNTRIES.

47. OBSERVED VS. REQUIRED ANNUAL RATE OF
CHANGE TO REACH TB ELIMINATION BY 2050
IN LOW-INCIDENCE COUNTRIES.

48. PROJECTED INCIDENCE RATES IN LOW-
INCIDENCE COUNTRIES IN 2035 CONSIDERING
A DECLINE OF 90% BETWEEN 2015 AND 2035.

49. -5
5
15
25
35
45
55
65
75
85
95
105
115
125
135
145
155
1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014
All SS+ cases
SS+ Cypriots
SS+ Foreign
Born
All TB per
1,000,000 pop
1 Case
per million
TB Elimination is possible: the case of Cyprus (ERJ 2014)

50. Introduction
AIMS: to describe
• The evolution of the strategies to prevent and manage TB
• The evolution of the concept of TB elimination
• The new WHO Post-2015 Strategy and the concept of pre-elimination
• The outcomes of a European ERS, WHO and ECDC survey evaluating
European preparedness to reach elimination
• The strategies to prevent and manage TB within the new TB Elimination
framework for low TB incidence countries
• An example of epidemic of XDR-TB in a major city, which summarizes the
different issues discussed above.

51. L’UNDICENNE È IN ISOLAMENTO ALLA CLINICA DE MARCHI
Casi di Tbc a Milano, iniziata la terapia
sul ragazzino con forma multiresistente
Esposito (Sitip): casi pediatrici del genere mai riscontrati negli ultimi 30 anni.
Terapia sperimentale con 5 farmaci
Preoccupano i casi di tubercolosi a Milano. Sette quelli resi noti negli ultimi giorni: tre bambini di una scuola
media, due di una scuola elementare della zona nord-est (asintomatici) e due studenti stranieri della facoltà di
Scienze politiche dell’Università Statale. A far scattare l’allarme è stato un bambino italiano di 11 anni che
frequenta la scuola media. «È arrivato da noi per un problema apparentemente di otorinolaringoiatra, ma le sue
condizioni generali e il quadro respiratorio ci hanno insospettito. Subito abbiamo pensato alla tubercolosi e la
diagnosi è stata confermata» spiega Susanna Esposito, direttore della Clinica Pediatrica I dell’Ospedale Maggiore
Policlinico di Milano e presidente della Società Italiana di Infettivologia Pediatrica (SITIP). Il bambino, ricoverato
nella clinica De Marchi, «è affetto da un ceppo multiresistente, chiamato XDR, caratterizzato da una resistenza
allargata a un vasto numero di farmaci - chiarisce Esposito -. Si tratta di un ceppo molto raro e difficile da trattare
che abitualmente non colpisce soggetti in età pediatrica, né quelli perfettamente immunocompetenti o senza
patologie di base
Corriere
della Sera
31/10/2011

52. Index case
FAMILY
Male, 12 years
Laryngeal + PTB
Long diagnostic delay
Direct Sputun examination +++
Resistant to SHREZ+FQ+Inj+Eto
Haarlem strain Mother, TST+, QF+
PTB, immigrant,
histopathology+,
CXR improved Cat 1
21 classmates tested:
1 monolateral pleurisy (immigrant)
10 TST+, QF+ (7 native, 3 immigrant)
2 dental hygienists tested:
2TST+, QF+
56 playmates tested:
3 TST+, QF-
(BCG vaccinated)
24 students tested in parallel class
performing common activities:
1 TST+, QF+
1TST+, QF-
57 students tested in other classes:
1TST+, QF+
13 TST+, QF-
TB disease TST+, QF+ TST+, QF -
18 school staff tested:
4TST+, QF+
5TST+, QF-
Sister 6 yrs, PTB
Brother 10 yrs, PTB
Father, TST-, QF-
19 school canteen staff
tested:
3 TST+, QF -
37 educators tested:
1 TST+, QF-
Summer camp circle
27 tested:
All TST-, QF-
Sport related circle
Catechism related circle
50 tested:
1 TST+, QF+
4 TST+, QF-
Other contacts

53. TREATING M/XDR-TB IS DIFFICULT
www.tbconsilium.org

54. ERS/WHO Consilium for M/XDR-TB
Objectives:
To allow a European clinician, free
cost, to load patient’s data and
receive in 1 working day suggestions
by 2 experts on how to manage a
difficult-to treat TB case
To support follow-up of TB patients
travelling within Europe
Web-based regional platform
Specialized team able to cover several
perspectives:(clinical for both adults and
children, surgical, radiological, public
health, psychological, nursing, etc.
Managed by ERS, in collaboration with
WHO Europe (formal agreement) and
ECDC

55. The web platform www.tbconsilium.org
• Now in ENG. RUS, SPA, PORT (FREN)
• Hosted in Switzerland (-> Swiss regulation)
• 4 processes supported + 2 in preparation:
o “Consilium” (get experts advice on cases in24-36 hrs)
o Trans border cases (send a case to a National TB Project
Representative)
o M&E of guidelines implementation
o Expert opinion for compassionate use
o Patient’s track
o LTBI management
• Next steps: « Drug-O-Gram » plug in

56. www.tbconsilium.org

58. Conclusions
• 1. While TB Elimination was considered an advocacy tool for
>20 years, there is epidimiological plausibility
• 2. The majority of low TB incidence counries is on track to
reach pre-elimination by 2035 (2050) and scale-up elimination
thereafter
• 3. Among the conditions to reach TB elimination:
- new vaccine, new point-of-care/rapid test, new effective short
regimens to treat TB and LTBI
- Sound health policies beyond NTP

59. ERS Conference, Munich, September 2014:
the launch

60. THANK
YOU !