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 LoddenkemperBerlin
German Central Committee against TuberculosisEuropean 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
0–2425–4950–99100–299>=300No 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-ReportIn 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 drugsTargets 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
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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!
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