Towards TB elimination - Giovanni Battista Migliori

MOVING TOWARDS TB ELIMINATION: EXPERIENCE AND LESSON LEARNED

THROUGH ERS ENGAGEMENT IN EUROPE

G. B. MiglioriWHO Collaborating Centre for TB and Lung Disease,

Fondazione S. Maugeri, Care and Research Institute

Tradate, Italy

Faculty disclosure

NO COI !!!

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.

Sotgiu et al, NEJM 2013

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 Managementscreening

BCG vaccination

drug therapy

Socio-economic improvement

Pneumotorax, Italy, 1907

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

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

Introduction

AIMS: to describe





Core additional interventions to pursueelimination

• 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

Core additional interventions to pursueelimination

• 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)

Elimination programmaticpre-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

Elimination programmaticpre-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

Introduction

AIMS: to describe





WORLD HEALTH ASSEMBLY APPROVES POST-2015 GLOBAL TB STRATEGY AND TARGETS –

WHA TB RESOLUTION

ZERO

TB DEATHS

A WORLD FREE OF TB

Vision

ZERO

TB CASES

ZERO

TB SUFFERING

GLOBAL TB

PROGRAMME

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

TARGETS

• 35% reduction in TB deaths

• <85/100 000 TB incidence rate

• No affected families with catastrophic costs due to TB

TARGETS




TARGETS




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

High-

quality,

integrated

TB care

and

prevention

Bold

policies and

supportive

systems

Intensified

research

and

innovation

Post-2015 TB StrategyProposed Pillars and Principles

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 TB4

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

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

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

-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:




W Europe after WWII

-10%/yr

China, Cambodia

-4%/yr


-20%/yr

W Europe after WWII

-10%/yr

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:





10%/yr

China, Cambodia

-4%/yr


-20%/yr

Eskimos> 10 ; < 20

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

Can TB control among Eskimos be generalised to

the world?





10%/yr

China, Cambodia

-4%/yr


-20%/yr

Elimination target:<1 /million/yr-20%/yr

DEFINITIONS

• Low-incidence countries: TB notification rate of <10 cases (all forms) per 100,000 population and year. Previous al ternative 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 b y 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 fo rms of TB. US CDC defines elimination in the USA as < 1 case of T B, all forms, per million population.

TARGETS

<100 cases per millionCurrent TB burden-2012

in low-incidence countries

<10 cases per millionPre-elimination: 2035

in low-incidence countries

<1 case per millionElimination: 2050

� 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"?

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

Introduction

AIMS: to describe





7 Core areas:

1. TB control commitment, TB awareness, and capacity of health systems

2. Surveillance3. Laboratory services4. Prompt, quality TB care for all5. M/XDR-TB and TB/HIV co-

infection6. New tools7. Partnership and collaboration

ACKNOWLEDGMENTSCOUNTRY 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 MehmetiLATVIA 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

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

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

Introduction

AIMS: to describe





TB Elimination: from Wolfheze to Rome

THANK Rome 4-5 July 2014

Wolfheze, May 1990

WHO/ERS SUMMIT ON TBRome July 4 th-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

� 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

ACTION FRAMEWORK8 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 continuedsurveillance, 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

OBSERVED VS. REQUIRED ANNUAL RATE OF CHANGE TO REACH TB ELIMINATION BY 2035

IN LOW-INCIDENCE COUNTRIES.

OBSERVED VS. REQUIRED ANNUAL RATE OF CHANGE TO REACH TB ELIMINATION BY 2050

IN LOW-INCIDENCE COUNTRIES.

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

-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+ ForeignBorn

All TB per1,000,000 pop

1 Caseper million

TB Elimination is possible: the case of Cyprus (ERJ 2014)

Introduction

AIMS: to describe





L’UNDICENNE È IN ISOLAMENTO ALLA CLINICA DE MARCHI

Casi di Tbc a Milano, iniziata la terapiasul ragazzino con forma multiresistenteEsposito (Sitip): casi pediatrici del genere mai riscontrati negli ultimi 30 anni.

Terapia sperimentale con 5 farmaciPreoccupano 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

Index caseFAMILY

Male, 12 yearsLaryngeal + PTBLong diagnostic delayDirect Sputun examination +++Resistant to SHREZ+FQ+Inj+EtoHaarlem 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

TREATING M/XDR-TB IS DIFFICULT

www.tbconsilium.org

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

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 implementationo Expert opinion for compassionate useo Patient’s tracko LTBI management

• Next steps: « Drug-O-Gram » plug in

www.tbconsilium.org

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 e limination thereafter

• 3. Among the conditions to reach TB elimination: - new vaccine, new point-of-care/rapid test, new effe ctive short

regimens to treat TB and LTBI- Sound health policies beyond NTP

ERS Conference, Munich, September 2014: the launch

THANKYOU !

Towards TB elimination - Giovanni Battista Migliori

Health & Medicine

Transcript of Towards TB elimination - Giovanni Battista Migliori