EMERGING INFECTIOUS DISEASES: A CONTINUOUS CHALLENGE FOR EUROPE

STOA-AVIESAN WORKSHOPJUNE 19TH 2012; EUROPEAN PARLIAMENT; BRUXELLES

A sustainable agenda

for tuberculosis control and research

Robert Loddenkemper

Berlin

German Central Committee against Tuberculosis

European Respiratory Society

Die ZEIT 26.Nov. 2006

1970/80 it was assumed that TB is nearly vanquished

In 1996 WHO declares TB an emergency in the Europe Region

„The return of phthisis“

Estimated number of cases

Estimated number of deaths

1.45 million(range: 1.2–1.6 million)

8.8 million(range: 8.5–9.2 million)

440,000(range: 390,000–510,000)

All forms of TB

Multidrug-resistant TB (MDR-TB)

HIV-associated TB 1.1 million (13%) (range: 1.0–1.2 million)

350,000(range: 320,000–390,000)

The Global Burden of TB -2010

about 150,000

Estimated TB incidence rates, by country, 2010

TB cases per 100 000

0–24

25–49

50–99

100–299

>=300

No estimate

Main causes for the global TB burden

• Demographic factors- population growth, age structure

• Increasing poverty, socioeconomic development- Quality of medical facilities

• Situation in penitentiaries

• HIV epidemic: TB/HIV co-coinfection with TB

• Inefficient treatment:MDR/XDR tuberculosis

• Migration

5

Eradication of Tuberculosis: Problem of LTBI

Active TB disease- 8,8 million new cases per year

- only “peak of iceberg”

Latent TB Infection (LTBI)- the “hidden” epidemic- ~2 billion people

Incidence of tuberculosis in Europe, 2010* Percentage of tuberculosis foreign-born cases among notified tuberculosis patients in Europe* 2010

418.000 (355-496.000) new cases

Incidence 47 (40-55)/100.000

In 18 HPC : 87% of incidence

*2012 ECDC-WHO Annual TB-Report

In several EU/EEA countries >50% foreign-born cases

Percentage of MDR-TB cases among tuberculosis patients with DST results in Europe, 2010

(2012 ECDC-WHO Annual TB-Report)

16.5

19.2

19.3

19.4

20.0

22.3

23.8

27.3

28.3

15.4

14.8

16.0

16.1

0 5 10 15 20 25 30

Tashkent, Uzbekistan (2005)

Estonia (2008)

Donetsk Oblast, Ukraine (2006)

Mary El Republic, Russian Federation (2008)

Dushanbe city and Rudaki district, Tajikistan (2009)

Belgorod Oblast, Russian Federation (2008)

Kaliningrad Oblast, Russian Federation (2008)

Republic of Moldova (2006)

Ivanovo Oblast, Russian Federation (2008)

Baku city, Azerbaijan (2007)

Arkhangelsk Oblast, Russian Federation (2008)

Pskov Oblast, Russian Federation (2008)

Murmansk Oblast, Russian Federation (2008)

13 top settings with highest % of MDR-TB among new cases, 2001-2010 (WHO Report 2011)

EU/EEA: <3% of new cases

Estonia : 18.6%, Latvia: 10.8%

Tadjikistan: 57. 5% of new cases

Ukraine : 79.4% of previously treated cases

XDR-TB: 13.2% in Europe12.2% in EU/EEA

Kazakhstan: in up to 76.6%

Percentage of tuberculosis/HIV co-infected patients in Europe,

2010*

19992000

20012002

20032004

20052006

20072008

20090

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

0

1

2

3

4

5

6

7

absolute number of new casesincidence per 100'000 population

Abso

lute

num

ber o

f new

case

s

Incid

ence

per

100

'000

pop

ulati

on

Russian Federation(new TB/HIV cases 1999-2009)

Frolova OP. AIDS 2010

In the EU >10% prevalence in Estonia , Ireland, Malta, the Netherlands, Portugal

Outside EU high in Russian Federation, Moldova and Ukraine

*2012 ECDC-WHO Annual TB-Report

Treatment success rate of new MDR-TB cases in the EU/EEA,

2008 Estimated tuberculosis mortality in Europe, 2010

<60.000 (40-90.000) deaths

Mortality 6.8 (5.4-8.3)/100.000

In 18 HPC : 94% of mortality

2012 ECDC-WHO Annual TB-Report

Smear-positive sputum: Insufficient for diagnosis of 50% of TB patients, notably HIV/Mtb coinfected individuals.

Vaccination: BCG protects toddlers but not their parents.

Therapy:Rising incidences of MDR-TB and XDR-TB.

Our inability to control TB is due to our neglect over the years. Better measures are needed. If we increase our research efforts today, new measures may become available in a decade.

TB control – where are we today?

Robert Koch

1843 -1910

Albert Calmette 1863-1933

Camille Guérin 1872-

1961

Selman Waksman 1888-1973

Stefan H.E. Kaufmann 2012

Potential effects of new TB vaccines, diagnostics and drugs

Targets of Stop TB Partnership/WHO:

• Reduce prevalence and mortality by half till 2015 as compared to 1990

• Eliminate TB by 2050 (annual incidence < 1/million population

How can this be achieved until 2050?*

• Pre-exposure vaccine: reduction of incidence by 39 – 52%• Drugs with shorter treatment time plus against MDR/XDR-TB:

reduction by 10 – 27% • Rapid diagnosis: reduction by 13 – 42%• Combined: reduction by 70%

• In addition new products targeted at LTBI required*Abu-Raddad et al., PNAS, 2009 ; Kaufmann, Hussey & Lambert, Lancet 2010

12

Time-to-result: 1 h 45 min

GeneXpert

Xpert MTB (Rifampicin)

Courtesy of S. Rüsch-Gerdes

The assay is fully automated with only 3 manual steps at the beginning: Addition of SR to raw sputum and 15 min later, after the sample has been inactivated and liquified, transfer to the Cartridge and in the instrument. All the rest is automated: Sample concentration, removal of inhibitors, ultrasonic lysis of cells and a nested real time PCR.

15

Prevention is Better than Cure: Vaccination

Ottenhoff THM et al. Tuberculosis 2012

Prevention is Better than Cure: Research

Prevention is Better than Cure: Research

TB: cost of research• Available funding for research & development in TB:

ca. 500 million US$

• Required funding for research & development of new intervention measures against TB over the next 10 years: ca. 2 billion US$ annually

(total ca. 20 billion US$ over 10 years)

TB: financial losses • Total direct and indirect cost:

>20 billion US$ annually!!

Stefan H.E. Kaufmann 2012

Prevention is Better than Cure: Research

TB: cost of research• Available funding for research &

development in TB: ca. 500 million US$

• Required funding for research & development of new intervention measures against TB over the next 10 years: ca. 2 billion US$ annually

(total ca. 20 billion US$ over 10 years)

TB: total direct and indirect cost

>20 billion US$ annually!!

Stefan H.E. Kaufmann 2012

How to improve the TB emergency situation in the Europe Region?

• Develop/update National TB control programmes incl. for penitentiary systems

• Commitment of governments!!• Implement Stop TB strategy (DOTS and DOTS-plus)• Adress MDR-/XDR-TB and HIV/TB co-infection• Build up high quality lab capacity (resistance testing)• Concentrate on high risk groups• Research and development of new tools (diagnostics, drugs, vaccines, biomarkers)• Operational research

What may happen in the future?

Investment in effective TB control

incl. research

Poverty,TB neglect,

MDR/XDR, HIV

•Aim of TB Partnership “Elimination of TB in 2050” looks rather utopic!

•In the contrary, TB situation, at least in Eastern Europe, may even worsen!