AntiTB drug resistance surveillance in Europe: current status and updated results

1
Anti-TB drug resistance surveillance in Europe
current status and updated results

• A. Infuso, EuroTB, Institut de Veille Sanitaire
• for the network of national correspondents
• 11th Wolfheze Workshops / EuroTB meeting
• Scheveningen, 31 May 2005

2
Current national correspondents

• H. Hafizi (Albania) M.Coll-Armangué (Andorra)
  
• M. Safarian (Armenia) J.P. Klein (Austria)
  
• A. Djabbarov (Azerbaijan) V. Borstchevsky
  (Belarus)
• M. Wanlin and A. Aerts (Belgium) Z.
  Dizdarevic B. Stefanovic (Bosnia Herzegov.)
• S. Alexandrov (Bulgaria) I. Gjenero Margan
  (Croatia)
• P. Constantinou (Cyprus) L. Trnka (Czech
  Republic)
• P. Andersen (Denmark) V. Hollo (Estonia)
  
• P. Ruutu (Finland)
• B. Decludt (France) A. Salakaia (Georgia)
• W. Haas (Germany) G. Spala (Greece)
• J. Mester (Hungary) T. Blöndal (Iceland)
• J. O'Donnell (Ireland) D. Chemtob (Israel)
  
• MG Pompa (Italy) G.B. Rakishev (Kazakhstan)
• A Alisherov (Kyrgyzstan) J. Leimans (Latvia)
• E. Davidaviciené (Lithuania) P. Huberty-Krau
  (Luxembourg)
• L. Simonovska (FYR of Macedonia) A. Pace
  Asciak (Malta)
• D. Sain (Republic of Moldova) A. Nègre
  (Monaco)
• C. Erkens (the Netherlands) E. Heldal and BW.
  Askeland (Norway)
• M. Korzeniewska-Kosela (Poland) A.F.Fonseca
  Antunes (Portugal)

3
Background EuroTB

• Surveillance of tuberculosis in Europe, started
  in 1996
• 52 national TB surveillance institutions in the
  WHO European Region
• WHO collaborating Centre
• Funded by the European Commission
• Coordination team and Advisory Committee
• Work developed from consensus recommendations
• Collection of standardised data on TB cases
  notified in the countries
• common case definition
• description of cases, risk groups, trends
• drug resistance surveillance (1998)
• treatment outcome monitoring (2001)

4
DRS approaches

• 1) Exhaustive surveillance
• Initial diagnostic drug susceptibility testing
  (DST) results collected for all culture positive
  TB cases notified
• 2) Drug resistance surveys
• DST performed for (systematic) samples of new and
  of retreated TB cases diagnosed in (randomly)
  selected clinical Centres, during a defined time
  period
• Repeated over time
• 3) Sentinel surveillance
• Initial diagnostic drug susceptibility testing
  (DST) results collected for all cases diagnosed
  in selected facilities (ongoing)
• 4) Other data
• diagnostic drug susceptibility testing (DST)
  results on undefined or ill defined case series

5
Individual TB case data set
OUTCOME
EuroTB
6
Aggregate DRS data (tables)
EuroTB
7
Data use

• European data bases (project participants)
• Individual data base
• Aggregate data bases (web queries)
• Data dissemination (www.eurotb.org)
• Annual reports
• WHO reports
• Congress communications / papers

EuroTB
8
Presentation of European DRS data

• Group A
• Exhaustive surveillance, if
• culture routinely used and
• Initial DST results available for all / most
  cases
• Drug resistance surveys
• Group B
• Any method if limited geographic coverage
• Sentinel surveillance
• Other data

EuroTB
9
Geographic areas, WHO European Region (52
countries)
East (12)
EU West (32)
Centre (8)
Andorra Malta Monaco
San Marino
EuroTB
10
Laboratories doing culture and DST and DST
methods used, 2003 (41 countries)
(MGIT, MB/BACT)
EuroTB
11
International and national external quality
assurance (EQA)for drug susceptibility testing,
2002-2003
International and national EQA
No or partial national EQA
No EQA
Andorra Malta Monaco
San Marino
EuroTB
12
Drug resistance surveillance data, Europe,
2003(41 countries)
group A (N29) (exhaustive, complete data or
surveys)
group B (N12) (other data)
Survey
Sentinel
Survey
Survey
Andorra Malta Monaco
San Marino
EuroTB
13
Proportion of tuberculosis cases notified with a
positive culture, 2003
cases
100
Centre
EU West
EU West
Centre
80
60
40
20
0
Italy
Israel
Latvia
Ireland
Spain
France
Greece
Poland
Finland
Croatia
Austria
Norway
Sweden
Albania
Slovakia
Estonia
Belgium
Slovenia
Bulgaria
Hungary
Portugal
Romania
Lithuania
Denmark
Germany
Netherlands
Switzerland
Czech Republic
United Kingdom
Macedonia, F.Y.R.
Bosnia Herzegovina (Fed.)
Initial DST available for most cases
Initial DST non available or incomplete
EuroTB
14
Global resistance to isoniazid (INH), rifampicin
(RMP) and multidrug resistance (MDR), 2003
Mean (country range) Austria, Belgium,
Czech Republic, Denmark, Finland, Germany,
Iceland, Ireland, Israel, Luxembourg, Malta,
Netherlands, Norway, Slovakia, Slovenia, Sweden,
Switzerland and United Kingdom Bosnia
Herzegovina (Federation) and Croatia
15
Multidrug resistance by anti-TB treatment
history, Europe, 2003
MDR cases
countries in group A with exhaustive
surveillance, reporting gt 50 cases
16
Primary multi-drug resistance, Europe, 2003(TB
cases never treated)
Data representativeness unknown
of MDR cases
lt 2
2-4.9
5
14
No data
8
9
Andorra Malta Monaco
San Marino
2002 for United Kingdom 2001 for Poland,
Kazakhstan
17
Acquired multi-drug resistance, Europe,
2003(retreated TB cases)
Data representativeness unknown
of MDR cases
lt6
612
13
53
No data / no cases
42
52
Andorra Malta Monaco
San Marino
2002 for United Kingdom 2001 for Poland,
Kazakhstan
18
Total multidrug resistance by geographic origin,
Europe, 2003
MDR cases
countries in group A with exhaustive
surveillance, reporting gt 50 cases
19
Global resistance to isoniazid and MDR by area of
origin, EU West EXCEPT the Baltic States, 2003
INH
Total with
Area of origin
resistance
MDR
DST results
N
()
N
()
EU West
5 648
196
(3.4)
28
(0.5)
(6.2)
(1.0)
Centre
894
55
9
(29.3)
(15.4)
Former Soviet Union
318
93
49
(14.5)
(4.5)
Rest of Asia
1 040
151
47
(9.6)
(1.4)
Africa
1 188
114
16
Other (America Oceania)
122
10
(8.2)
1
(0.8)
Unknown
390
34
(8.7)
8
(2.1)
Total
9 600
653
(6.8)
158
(1.6)
Austria, Belgium, Czech Republic, Denmark,
Finland, Germany, Iceland, Ireland, Luxembourg,
Malta, Netherlands, Norway, Slovakia, Slovenia,
Sweden, Switzerland.
20
Resistance to INH and MDR by anti-TB treatment
history, EU West, 2000-2003 (14 countries)
resistant cases
INH - prev. treated
INH - new
MDR - prev. treated
MDR - new
Austria, Belgium, Czech Reoublic, Denmark,
Finland, Iceland, Ireland, Malta, Netherlands,
Norway, Slovakia, Slovenia, Sweden, Switzerland
21
Resistance to INH and MDR by anti-TB treatment
history, Baltic States, 1999-2003
resistance
INH - prev. treated
MDR - prev. treated
INH - new
MDR - new
22
Treatment outcome by drug-resistance profile
(INH, RMP, EMB), culture positive TB cases with
DST results, EU West, 2002
Andorra, Austria, Belgium, Czech Republic,
Denmark, Estonia, Germany, Iceland, Ireland,
Latvia, Netherlands, Norway, Slovakia, Slovenia,
Sweden (N11,036).
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Summary EU West

• Laboratory practices
• International quality assurance for DST in place
  in most countries
• National EQA incomplete
• New DST methods increasingly used
• Surveillance of drug resistance
• Geographic coverage still incomplete
• Prevailing exhaustive surveillance
• Feasible in countries with strong laboratory
  involvment in surveillance
• Completeness of information an issue in some
  countries
• Baltic States very high levels of global MDR
  20, stable (?)
• Others global MDR lt 2 associated with foreign
  origin

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Summary Centre

• Quality assurance partial
• Exhaustive surveillance hampered by low
  proportions of reported C cases
• Survey in Romania
• Levels of resistance
• Low in Bosnia Fed., Croatia, Belgrade, (Albania)
• Intermediate in Romania (3 primary MDR)

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Summary East

• EQA not implemented in most countries
• Very incomplete drug resistance surveillance data
• Routine reporting of DST not adapted
• Some local and one national survey (Kazakhstan)
• Data from (partial) diagnostic DST on selected
  cases
• Likely hypothesis very high levels of MDR
  widespread

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Conclusions

• In the EU, the main constraint to improved DRS
  remains the insufficient integration of
  laboratories in TB surveillance
• In most countries in the East, lack of drug
  resistance data
• due to weak laboratory capacities
• limits implementation of and advocacy for MDR-TB
  control.
• How could Europe be more efficient in promoting
  all this?