Regional overview of virological surveillance 2010/2011

Transcription

Regional overview of virological surveillance 2010/2011
Joint ECDC/WHO Euro Influenza Surveillance Meeting
(3rd EISN/ECDC Annual General Meeting)
Ljubljana, Slovenia, 7-9 June 2011
Global Virological Surveillance (Focus on Europe):
2010/11 Influenza Season
Dr Rod S Daniels
(CNRL co-ordination team)
WHO-CC, Virology Division, NIMR, London, UK.
Review of 2010-11 Northern Hemisphere Influenza Season.
Canada & USA
A (H3=NS>H1p)>>B
West/North Europe
A(H1p>NS>>H3)>B
East Euro/Cent-East Asia
A(H1p>>H3>NS)>>B
Source: FluNet - WER (no
22, 2011, 86, 222-227)
Influenza virus detections, From 2010 week 45 to 2011 week 18
Data source: FluNet (www.who.int/flunet), Global Influenza Surveillance Network (GISN) 17 May 2011.
Percentages of influenza out of all positive influenza detections.
A(H1N1)pdm09
A(H3N2)
Flu A (not subtyped)
Flu B
No activity or no data
1-25%
26-50%
51-75%
76-100%
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion
whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of
its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border
lines for which there may not yet be full agreement. © WHO 2011. All rights reserved.
Data source: WHO, GISN
Map production:
Global Influenza Programme
World Health Organization
The 2010-11 Influenza Season in Europe
Sentinel
Non-sentinel
Sentinel: % Influenza Positive
Sentinel Surveillance: Individual Countries within the ECDC & WHO EURO Regions
Spain
A>B
Slovenia
B=A
England
A>B
Ukraine
B>A
France
A=B
Moldova
A>B
Norway
B>A
Greece
A>B
Denmark
A
Russian Fed
A>B
Germany
A>B
Israel
A>B
Specimens Received 2010-11 Influenza Season: ECDC/WHO EURO Member States
MONTH
A
Country
DECEMBER
Austria
Belgium
Croatia
Denmark
Finland
France
Georgia
Germany
Ireland
Israel
Italy
Latvia
Luxembourg
Malta
Netherlands
Norway
Portugal
Romania
Slovenia
Spain
Sweden
Switzerland
Turkey
Ukraine
United Kingdom
JANUARY
Belgium
Croatia
Czech Republic
Estonia
Germany
France
Georgia
Greece
Ireland
Israel
Italy
Latvia
Malta
Moldova
Netherlands
Portugal
Romania
Russia
Slovenia
Spain
Sweden
Switzerland
Turkey
Ukraine
United Kingdom
FEBRUARY
Czech Republic
Estonia
Ireland
Italy
Greece
Latvia
Malta
Moldova
Russia
Spain
Turkey
Ukraine
MARCH
Estonia
Georgia
Greece
Ireland
Latvia
Malta
Romania
Russia
Spain
Turkey
Ukraine
1
5
1
H1N1pdm
Number
Number
received
antigenically
characterised
6
22
10
5
2
20
1
8
10
6
16
8
5
2
20
1
8
8
8
5
5
6
6
5
3
4
1
5
1
6
23
5
7
1
2
1
6
19
5
7
4
40
0
in process
1
2
13
9
1
0
13
4
H3N2
B
B Victoria lineage
Number
Number
received
antigenically
characterised
Number
antigenically
characterised
2
1
3
3
17
17
1
20
1
12
2
2
2
2
9
9
3
0
4
4
1
7
2
7
2
2
1
2
1
8
9
2
1
9
2
1
7
44
6
22
2
7
2
2
2
6
2
0
49
10
41
8
2
1
1
0
2
3
6
2
3
6
3
23
3
23
8
6
2
3
5
2
3
5
1
1
1
1
2
2
1
0
1
2
1
1
10
1
1
3
3
1
1
5
1
8
30
2
4
54
5
2
11
5
1
2
1
14
31
8
16
in process
4
52
4
2
3
5
0
2
1
13
21
20
3
6
4
20
in process
in process
in process
1
32
2
1
9
1
7
17
8
5
1
26
in process
1
in process
in process
in process
6
8
4
2
in process
15
1
2
6
in process
in process
1
in process
1
1
2
7
8
3
1
1
in process
8
1
in process
13
1
2
1
10
1
1
1
1
1
2
5
4
6
3
5
in process
1
1
2
2
2
2
1
3
4
1
16
1
2
4
3
5
2
3
in process
in process
1
1
1
1
in process
1
1
22
7
2
2
9
3
9
in process
3
3
3
2
1
1
5
1
1
5
1
1
2
2
1
1
259
215
4
1
5
5
8
1
5
1
3
3
2
4
5
6
in process
in process
32
537
354
1
1
APRIL
Malta
Total Received = 1066
B Yamagata lineage
Number
Number
received
antigenically
characterised
Number
received
1
0 = insufficient HA titre for antigenic characterisation
98
55
102
38
30
A(H1N1)pdm09 viruses
Propagated in cell culture - MDCK cells or
others
Recent reports of a reduced frequency of
isolation - not seen in all laboratories
Antigenic analyses of A(H1N1)pdm09 influenza viruses (Turkey RBCs)
Haemagglutination inhibition titre
1
Post infection ferret sera
Viruses
Collection
date
Passage
History
A/Cal
7/09
F05/10
A/Eng A/Auck A/Bayern A/Lviv
A/HK
A/C'church
195/09
3/09
69/09
N6/2009 2212/2010
16/2010
F06/10 F17/09 C4/33/09 C4/34/09 F21/10
F30/10
HA1 amino acid
substitutions
associated with
low HI titre &
changes in
receptor binding
REFERENCE VIRUSES
A/California/7/2009
A/England/195/2009
A/Auckland/3/2009
A/Bayern/69/2009
A/Lviv/N6/2009
A/Hong Kong/2212/2010
A/Christchurch/16/2010
2009-04-09
2009-04-28
2009-04-25
2009-07-01
2009-10-27
2010-07-16
2010-07-12
E2/E4
MDCK1/MDCK4
Ex/E3
MDCK4/MDCK2
MDCK5
E4
E2/E1
5120
5120
5120
320
1280
5120
5120
5120
5120
5120
160
160
5120
2560
5120
5120
5120
160
160
5120
5120
1280
2560
2560
640
1280
5120
2560
2560
2560
2560
640
1280
5120
2560
2560
5120
5120
160
640
5120
5120
2560
2560
2560
160
320
5120
5120
A/Valladolid/53/2010
A/Athens/230/2011
A/Palencia/37/2011
2010-12-10
2011-01-18
2011-02-10
MDCK1/MDCK2
1st/MDCK1
MDCK1/MDCK2
1280
160
1280
2560
160
1280
2560
160
1280
640
1280
640
640
640
1280
2560
320
1280
1280
320
640
A/Ireland/72392/2010
A/Denmark/120/2010
A/Nordrhein-Westfalen/14/2010
A/Estonia/54626/11
A/Ioannina/GR6664/2011
A/Kaluga/1/2011
2010-12-07
2010-12-21
2010-12-22
2011-02-16
2011-02-21
2011-03-14
MDCK3/MDCK1
MDCK6/MDCK1
C2/MDCK1
MDCK 1/MDCK3
MDCK3
E1/E1
1280
640
160
1280
2560
2560
640
160
160
1280
2560
2560
640
80
320
2560
2560
2560
640
640
640
640
640
1280
1280
1280
640
640
1280
2560
640
640
320
1280
2560
2560
A/Baden-Wuttermberg/14/2010
A/Trieste/04/2011
A/Paris/2301/2010
A/Trieste/12/2011
A/Estonia/54086/11
A/St. Petersburg/100/2011
2010-12-27
2010-12-27
2010-12-30
2011-01-13
2011-02-08
2011-03-14
C3/MDCK1
III MDCK/MDCK1
C1/MDCK1
MDCK1/MDCK1
MDCK 2/MDCK3
E1/E1
40
640
160
320
320
1280
80
160
320
160
160
1280
160
160
160
160
80
1280
160
640
160
640
320
640
320
640
1280
640
160
1280
A/PaisVasco/RR6909/10
A/Stockholm/15/2010
A/Trieste/11/2011
A/Larissa/GR190/2011
A/Israe/lL-1227/2011
2010-12-01
2010-12-13
2011-01-11
2011-01-17
2011-01-26
P1 MDCK-SIAT/MDCK1
C3/MDCK1
II MDCK/MDCK1
1st/MDCK2
P1
1280
160
1280
1280
2560
1280
160
640
2560
2560
1280
160
640
2560
2560
640
640
1280
1280
1280
A/Zamora/55/2010
A/Salamanca/63/2010
A/Netherlands/2/2011
2010-12-16
2010-12-28
2011-01-03
MDCK1/MDCK3
MDCK1/MDCK3
xMDCK2/MDCK1
1280
2560
320
1280
2560
160
1280
2560
160
A/Finland/26/2010
A/LaRioja/RR6968/2010
A/La Rioja/RR6966/2010
A/Soria/16/2011
2010-12-09
2010-12-16
2010-12-23
2011-01-13
MDCK1/MDCK1
P1 MDCK-SIAT
SIAT1/MDCK1
MDCK1/MDCK1
640
640
640
640
640
640
640
640
A/Austria/593095/2010
2010-12-23
C2/MDCK1
1280
A/Czech Republic/32/2011
A/Estonia/55236/2011
2011-03-02
MDCK4/MDCK1
MDCK1/MDCK1
A/Limoges/1159/2010
A/Netherlands/219/2011
A/Moldova/448/2011
2010-12-22
2011-01-02
2011-02-07
P2MDCK/MDCK1
xMDCK2
MDCK2
G155E
G155E D222G
D222N
TEST VIRUSES
1
Starting antiserum dilution = 1/40; 2 K119N substitution (+cho).
G155X
S185T
640
160
320
640
1280
1280
G155X
G155X D222G
K153X
S185T D97N
80
320
80
320
320
640
80
320
160
160
160
640
K153X
G155X
1280
1280
2560
2560
2560
1280
320
1280
2560
2560
1280
160
1280
1280
2560
320
1280
640
1280
2560
640
1280
2560
640
640
1280
320
1280
1280
1280
1280
640
320
640
640
1280
640
1280
640
1280
1280
1280
1280
2560
2560
2560
2560
1280
1280
320
1280
1280
640
1280
2560
2560
2560
2560
2560
640
640
2560
2560
2560
2560
1280
1280
640
<
640
320
40
1280
1280
<
320
320
160
640
1280
320
1280
640
80
1280
320
80
640
Vaccine virus
S185T S143G A197T
G155X
Q223R
G155E
G155X
R205K I216V V249L
No defining node
G155X
N125D
D222X
No defining node
N31D S162N(+cho) A186T
D222G
G155E D222N
A134T S183P
Phylogenetic Comparison of A(H1N1)pdm09 HA genes (HA1 coding region)
Amino acid substitutions in H1 HA associated with passage
in tissue culture, resulting in low reactivity in HI assays.
Single amino acid
substitutions
between 153 and
157, often
polymorphic.
Liu Y et al (2010)
J. Virol., 84, 12069-74
Amino acid substitutions in HA in emerging
genetic groups of A(H1N1)pdm09 viruses
6 genetic groups
•
•
•
•
•
•
SH group N125D, e.g. A/Christchurch/16/2010
Stockholm/14 group R205K, I216V, V249L
England/375 group D97N, S185T, e.g. A/England/142/2010
Czech Republic/32 group N31D, S162N (+CHO), A186T
Baden-Wurtemburg/14 group S143G, S185T, A197T
Alborz/5607group A134T, S183P, e.g. A/Wyoming/01/2011
H1 HA amino acid substitutions associated with different genetic groups
125
216
249
185
97
205
SH group
Stockholm/15 group
N125D
R205K, I216V, V249L
186
162
185
England/375 group
D97N, S185T
197
183
143
134
31
Czech Rep/32 group
Baden-Wurt/14 group
Alborz/5607 group
N31D, S162N (+CHO), A186T
S143G, S185T, A197T
A134T, S183P
A(H1N1)pdm09 viruses
Many genetic groups have emerged, some seem to
have died out
Viruses remain very similar antigenically although
variants can be readily selected in MDCK cells
Recent problems with isolation are being examined
H3N2 viruses
Problems with agglutination of red blood cells
• Through the NA glycoprotein (associated with
polymorphism at position 151 of the NA) – Lin YP et al
(2010) J. Virol., 84, 6769-81
• Through poor binding to red blood cells of any species
At the WHO CC in London virus replication in culture is
detected by CPE associated with NA (sialidase) activity
63% of H3N2 viruses isolated through the season were
HA –ve NA +ve
Antigenic analyses of influenza A(H3N2) viruses
(Guinea Pig RBCs + 20nM Oseltamivir)
Haemagglutination inhibition titre
1
Amino acid substitutions compared to A/Perth/16/2009 HA
210/09
F11/10
5/10
F27/10
10/10
F03/11
SpfCk3E3/E11
E2/E4
E3/E3
E2/E3
E3/E2
E2/E3
MK1/M2/S3
E2/E2
1280
5120
40
40
160
160
<
<
640
5120
80
<
160
320
<
<
<
40
1280
640
640
1280
80
160
<
40
640
320
640
1280
40
40
160
320
1280
40
5120
2560
40
40
<
160
1280
160
5120
5120
40
40
<
40
640
640
1280
320
160
160
80
160
2560
320
2560
2560
320
320
Perth/16 clade
T212A
208/09
F7/10
S199A
15/09
F24/09
E280A
16/09
F30/09
I230V
10/07
F29/09
Y94H
67/05
F18/08
D53N
History
N312S
Date
Virus specific
S45N
(+cho)
A/Perth
V223I
A/Ala
N145S
A/Vic
S214I
A/Vic
L183H
A/Wis
R261Q
A/Perth
I260M
A/Bris
V213A
A/Wis
R142G
Passage
N133D
(-cho)
Collection
K144N
Viruses
Defining genetic groups
K62E
Post infection ferret sera
Victoria/208 clade
REFERENCE VIRUSES
A/Wisconsin/67/2005
A/Brisbane/10/2007
A/Perth/16/2009
A/Wisconsin/15/2009
A/Victoria/208/2009
A/Victoria/210/2009
A/Alabama/5/2010
A/Perth/10/2010
TEST VIRUSES
2005-08-31
2007-02-06
2009-07-04
2009-07-06
2009-06-02
2009-06-02
2010-07-13
2010-05-25
*
*
*
*
*
*
*
*
*X
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*V
L194P, V213A
*
*
*
*
*
*
*
*
*
*
*
*
*
G186V, 222X, 227X
R208K, 216X, N225D
2
A/Hmelnizk/ 4175/2010
2010-12-01
C1/SIAT1
640
640
<
<
80
<
160
160
A/Norway/1330/2010
A/Israel/1/2011
2010-12-03
2011-01-10
MDCK1/SIAT1
SIAT1
<
<
<
80
80
320
320
640
80
160
80
320
80
320
ND
640
A/Stockholm/6/2010
A/Stockholm/10/2010
A/Paris/1844/2010
A/Hessen/5/2010
2010-09-29
2010-11-19
2010-11-29
2010-12-13
C2/SIAT1
C1/SIAT1
C1/SIAT1
C3/SIAT1
40
<
40
<
<
<
<
<
1280
640
640
80
160
80
1280
320
160
80
320
80
640
320
640
80
ND
ND
640
80
ND
ND
ND
ND
A/Cote d'Ivoire/GR1542/2010
A/Cote d'Ivoire/GR1728/2010
A/Ghana/FS-10-4723/2010
A/Paris/2120/2010
A/Finland/40/2010
A/Israel/18/2011
2010-10-22
2010-11-08
2010-12-02
2010-12-10
2010-12-22
2011-01-21
SIAT3
SIAT3
SIAT1/SIAT1
C1/SIAT2
MDCK2/SIAT1
C1/SIAT4
<
40
40
<
<
80
<
80
80
80
160
80
80
320
320
80
640
320
160
320
320
160
320
320
80
160
320
160
320
320
40
160
160
160
320
320
320
320
320
640
1280
640
160
640
640
640
1280
640
A/England/270/2010
A/Lyon/1135/2010
A/Israel/5/2011
2010-12-06
2010-12-19
2011-01-15
SIAT1/SIAT1
MDCK2/SIAT1
C1/SIAT4
<
<
40
80
80
40
160
320
640
160
320
320
80
320
320
80
320
320
1280
1280
640
640
1280
1280
A/Bretagne/2248/2010
A/Galati/47519/2011
A/Genoa/01/2010
A/Moldova/378/2011
A/Valladolid/40/2011
A/Moldova/601/2011
A/Romania/55656/2011
2010-12-25
2010-12-29
2010-12-31
2011-02-08
2011-02-16
2011-02-18
2011-03-10
C1/SIAT1
MDCK2/SIAT3
MDCK2/SIAT4
SIAT3
MDCK1/SIAT1
SIAT3
SIAT2
<
<
40
40
40
40
40
40
160
40
80
40
40
40
160
1280
160
320
320
320
320
320
1280
320
320
640
320
640
320
1280
320
320
320
320
320
320
2560
160
160
320
320
320
1280
1280
640
640
1280
640
1280
1280
5120
640
1280
1280
1280
1280
A/Netherlands/34/2010
2010-12-23
xMDCK2/SIAT1
<
40
160
80
80
80
1280
320
Vaccine virus
ND = Not Done
1
*
*
*
2
Starting antiserum dilution = 1/40; Sequences of highlighted viruses are included in the HA phylogeny.
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
D
*
D
D
D
D
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
N8D(-cho), N158K, K189N
*
*
I25V, E50K, P162S
G5E, E50K, P162S
E50K, P162S
E50K, P162S
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
G
G
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
L3I, T481, L164V
T48I, K92R
T48A, Q57H, K92R, K326R
N6D
I192T, N246H(-cho)
A198S
Antigenic analysis of influenza A H3N2 viruses
(Plaque Reduction Neutralisation - MDCK-SIAT)
1
Amino acid substitutions compared to A/Perth/16/2009
Perth/16 clade
T212A
S199A
E280A
I230V
Y94H
D53N
Virus specific
N312S
S45N
V223I
N145S
R261Q
I260M
A/Vic A/Per A/Ala
208/09 10/10
5/10
F07/10 F1777 F27/10
V213A
A/Per
16/09
F30/09
R142G
A/Bris
10/07
F29/09
N133D
Passage
History
K144N
Collection
Date
K62E
Viruses
S214I
Defining genetic groups
Post infection ferret sera
L183H
Neutralisation titre
Victoria/208 clade
REFERENCE VIRUSES
A/Brisbane/10/2007
2007-02-06
E2/E4
5120
160
640
80
80
A/Perth/16/2009
2009-07-04
E3/E4
320
1280
640
320
320
A/Victoria/208/2009
2009-06-02
E3/E2
640
1280
5120
1280
1280
A/Perth/10/2010
2010-05-25
E2/E1
160
640
320
320
320
A/Alabama/5/2010
2010-07-13 MK1/MDCK2/SIAT2
80
320
160
320
640
* *
* *
* *
* *
X
*
* *
* * * *
* * * *
*
*
*
R208K, 216X, N225D
TEST VIRUSES
A/Peleponnese/4043/2010
2010-10-11
SIAT2
320
1280
320
640
1280
A/Hong Kong/6925/2010
2010-11-30
MDCK2/SIAT1
80
1280
160
320
320
A/Ghana/FS-4462/2010
2010-09-28
SIAT1/SIAT1
160
320
160
160
320
A/Ghana/FS-4589/2010
2010-10-22
SIAT1/SIAT1
80
320
160
160
320
A/Johannesburg/34/2010
2010-07-11
MDCK1/SIAT2
80
640
640
ND
ND
A/Cape Town/62/2010
2010-07-20
MDCK2/SIAT2
80
320
320
ND
ND
A/Johannesburg/87/2010
2010-07-26
MDCK1/SIAT2
40
320
320
ND
ND
A/Johannesburg/60/2010
2010-07-16
MDCK3/SIAT1
80
1280
640
ND
ND
A/Rhode Island/1/2010
2010-01-26
E4/E1
320
320
80
160
320
A/Stockholm/2/2010
2010-04-30
C1/MDCK1/SIAT1
80
320
160
ND
ND
A/Madagascar/7142/2010
2010-11-05
MDCK2/SIAT1
80
320
160
320
320
A/Argentina/28342/2010
2010-11-23
SIAT1/SIAT1
160
640
320
640
1280
A/Argentina/28367/2010
2010-11-23
SIAT1/SIAT1
80
640
320
640
1280
A/Madagascar/7184/2010
2010-11-16
MDCK1/SIAT1
80
320
160
320
320
A/Madagascar/7749/2010
SIAT3
MDCK2/SIAT2
40
320
160
320
640
A/Netherlands/9/2010
2010-12-10
2010-04-21
40
160
320
ND
ND
A/Bremen/1/2010
A/Bretagne/2248/2010
2010-12-17
2010-12-25
C2/SIAT1
C1/SIAT1
80
40
640
320
160
160
ND
ND
640
640
A/Hong Kong/6894/2010
2010-11-26
MDCK2/SIAT1
80
320
80
160
320
A/Argentina/28370/2010
2010-11-23
SIAT1/SIAT1
80
640
320
640
640
A/Argentina/28378/2010
2010-11-30
SIAT1/SIAT1
40
320
160
320
640
A/Fes/140/2010
2010-12-30
SIATx/SIAT1
80
640
320
ND
640
ND = Not Done
1
Vaccine virus
Based on 50% plaque reduction compared to serum negative controls
* * *
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
* * *
*
*
*
*
*
* *
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
* * *
*
* * *
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
* * * *
*
*
* * * *
*
*
* * * *
*
*
* * * T
*
*
* * * * * *
*
* * * * * *
*
* * * * * *
E50K, P162S
Q80R, V323I
Q80R, V323I
L59I
L3F, L59I
T48A, K92R, D188Y
F193Y, A198S
T128A
K238R
K238R
N6D
T135A
Phylogenetic Comparison of A(H3N2) HA genes (HA1 coding region)
H3N2 genetic groups
• H3N2 viruses split into two genetic
clades: the Perth/16/2009 clade and the
Victoria/208/2009 clade
• Viruses in both clades are antigenically
similar and distinct from viruses in the
earlier A/Brisbane/10/2007 clade
Perth/16 clade groups
162
213
212
133
260
261
Vic/210
P162S, I260M,
R261Q
Nor/1330
N133D (-CHO)
R142G, A212T,
V213A
142
Vic/208 clade groups
144
145
144
144
230
94
223
62
53
280
62
92
48
312
62
312
Rhode Is/01
Cote d‟Ivoire
K62N, K144N + T48A, K92R, N312S
K62E, K144N + N145S,V223I
Alabama/05
K62E, K144N + D53N, Y94H, I230V, E280A, S312N
H3N2 viruses
Problems with H3N2 viruses• Difficulties with propagation in some cells
• Difficulties in obtaining egg-isolates for vaccines
Genetic groups have emerged but viruses associated with
none of these genetic groups are consistently
antigenically distinct from the current vaccine virus
(A/Perth/16/2009)
• HI assays are unreliable but the addition of oseltamivir
removes NA-mediated agglutination.
• VNT assays are used to back up HI data but involve
much more work for viruses that do not propagate
efficiently.
Influenza B viruses
Vaccine viruses are made in eggs
Egg propagated viruses lose a CHO site
• at residue 197 of HA for B/Victoria-lineage viruses
• at residue 196 of B/Yamagata-lineage viruses
For B/Victoria-lineage viruses, loss of the CHO site
exposes an epitope well-recognised by ferrets
Cell-propagated viruses that are closely related
genetically to the B/Victoria-lineage vaccine virus are
used to define the antigenicity of virus isolates,
being „surrogates‟ for the vaccine virus
Antigenic analyses of influenza B/Victoria-lineage viruses (Turkey RBCs)
Haemagglutination inhibition titre 1
Post infection ferret sera
Viruses
Collection
date
Passage
History
B/Mal B/Eng
B/Bris2
60/08 2506/04 393/08
Sh 524 F28/05 F31/08
B/Bris
60/08
F25/10
B/Paris B/HK B/Odessa
1762/08 514/09
3886/10
F11/09 F3/10
F17/10
REFERENCE VIRUSES
B/Malaysia/2506/2004
B/England/393/2008
B/Brisbane/60/2008
B/Paris/1762/2008
B/Hong Kong/514/2009
B/Odessa/3886/2010
2004-12-06
2008-08-29
2008-08-04
E3/E5
E1/E6
E4/E4
C2/MDCK4
2009-10-11 MDCK1/MDCK1
2010-03-19
C2/MDCK3
1280
640
640
640
640
1280
320
80
80
10
10
10
80
160
160
20
10
20
80
320
320
40
40
40
<
40
80
80
80
80
<
20
20
160
160
160
<
40
40
80
80
160
2010-12-01
2010-12-01
2010-12-02
2010-12-07
2010-12-08
2010-12-09
2010-12-09
2010-12-10
2010-12-14
2010-12-21
2010-12-23
2010-12-27
2010-12-31
2010-12-31
1280
320
5120
1280
1280
640
1280
640
1280
2560
640
640
640
2560
20
10
640
160
20
10
40
20
160
<
20
10
<
640
<
10
320
80
40
<
40
40
1280
160
40
20
20
640
40
10
640
160
40
40
80
40
1280
80
40
20
20
1280
40
20
160
80
80
160
80
80
160
320
80
40
80
160
80
40
320
320
160
160
640
640
320
320
160
160
160
160
80
160
320
160
320
160
320
160
320
320
320
80
80
160
TEST VIRUSES 3
B/Genova/2/2010
B/Zamora/52/2010
B/Lisboa/56/2010
B/Kharkov/4178/2010
B/Lisboa/21/2010
B/Hmelnizk/4273/2010
B/Brussels/G0707/2010
B/Stockholm/10/2010
B/LaRioja/RR6969/2010
B/Ceuta/RR7185/2010
B/Latvia/12-41046/2010
B/Latvia/12-43110/2010
B/Parma/04/2010
B/Ireland/00132/2010
MDCK1/MDCK1
MDCK1/MDCK2
SIAT1/MDCK2
1/MDCK1
MDCK1/MDCK2
1/MDCK1
MDCK2
C0/MDCK1
SIAT1/MDCK1
MDCK1/MDCK1
MDCK1/MDCK1
MDCKx/MDCK2
MDCK1/MDCK1
MDCK1/MDCK1
Vaccine virus
1
< = <10;
2
3
Hyperimmune sheep serum; Sequences of highlighted viruses are included in the HA phylogeny.
Phylogenetic Comparison of B/Victoria-lineage HA genes (HA1 coding region)
Antigenic analyses of influenza B/Yamagata-lineage viruses (Turkey RBCs)
Haemagglutination inhibition titre
Post infection ferret sera
Viruses
REFERENCE VIRUSES
B/Egypt/144/2005
B/Florida/4/2006
B/Brisbane/3/2007
B/England/145/2008
B/Bangladesh/3333/2007
B/Wisconsin/1/2010
Collection
Passage
date
History
B/Fl2 B/Eg1 B/Fl1 B/Bris1 B/Eng1 B/Bang1 B/Wis1
4/06 144/05
4/06
3/07 145/08 3333/07
1/10
Sh 479 F07/05 F20/07 F24/07 F9/08 F25/08 F26/10
2007-08-07
2010-02-20
E3/E6
E3/E4
E2/E3
Ex/E4
E3/E4
E3/E2
5120
5120
5120
640
5120
1280
160
640
320
20
80
40
640
2560
1280
80
640
320
160
640
320
10
40
20
40
320
80
80
40
20
320
1280
640
40
640
80
160
640
320
20
320
320
2010-12-01
2011-01-18
2011-01-18
2011-02-01
2010-12-16
2010-12-28
2011-01-05
2010-12-20
2011-01-19
2010-12-22
2010-12-27
2010-12-16
2011-03-14
2011-03-15
SIAT1/MDCK1
C2/MDCK1
C2/MDCK1
MDCK1/MDCK1
C2/MDCK1
C2/MDCK1
MDCK2/MDCK1
SIAT1/MDCK1
MDCK1/MDCK1
C1/MDCK2
C1/MDCK1
MDCK1/MDCK1
MDCK 2/MDCK1
MDCK 2/MDCK1
5120
5120
5120
5120
1280
5120
5120
5120
1280
5120
1280
2560
2560
2560
320
640
640
160
40
160
320
640
320
160
80
80
40
160
640
320
640
320
80
160
640
1280
160
320
160
160
80
160
80
160
640
<
40
160
160
320
80
640
80
80
<
40
320
160
320
80
80
320
320
320
80
320
160
80
<
80
320
320
320
160
80
160
320
320
80
320
80
40
80
640
320
160
320
160
160
640
320
320
160
1280
320
80
80
320
2005-05-01
2006-12-15
2007-09-03
TEST VIRUSES 3
B/England/170/2010
B/Turkey/93/2011
B/Turkey/97/2011
B/Latvia/2-70/2011
B/Niedersachsen/2/2010
B/Berlin/2/2010
B/Lyon/68/2011
B/England/512/2010
B/Trieste/05/2011
B/Nordrhein-Westfalen/1/2010
B/Bretagne/2278/2010
B/Finland/33/2010
B/Estonia/55669/11
B/Estonia/55763/11
1
2
3
< = <10 ; Hyperimmune sheep serum; Sequences of highlighted viruses are included in the HA phylogeny.
Phylogenetic Comparison of B/Yamagata-lineage HA genes (HA1 coding region)
Influenza B viruses
The majority of viruses have been of the B/Victoria-lineage
(~90%)
B/Yamagata-lineage viruses have been seen in a smaller
number of locations.
The vast majority of B/Victoria-lineage viruses are in the
B/Brisbane/60 genetic clade and react well with ferret
antisera raised against mammalian cell grown viruses
genetically similar to egg-grown B/Brisbane/60/2008
B/Yamagata-lineage viruses most frequently fall into the
B/Bangladesh/3333/2007 genetic clade and are
antigenically similar to recent viruses within the clade
e.g. B/Wisconsin/01/2010
Recent Changes in WHO Influenza Vaccine Recommendations
SH 2009 (Sep 2008)
NH 2009-10 (Feb 2009)
H1N1
H3N2
Flu B
A/Brisbane/59/2007-like
A/Brisbane/10/2007-like
B/Florida/4/2006-like (Yam)
H1N1
H3N2
Flu B
A/California/7/2009-like (pand) A/California/7/2009-like (pand)
A Perth/16/2009-like
A Perth/16/2009-like
B/Brisbane/60/2008-like
B/Brisbane/60/2008-like
NH 2010-11 (Feb 2010)
A/Brisbane/59/2007-like
A/Brisbane/10/2007-like
A/Brisbane/60/2008-like (Vic)
*
SH 2011 (Sep 2010)
SH 2010 (Sep 2009)
A/California/7/2009-like (pand)
A Perth/16/2009-like
B/Brisbane/60/2008-like
A/California/7/2009-like (pand)
A Perth/16/2009-like
B/Brisbane/60/2008-like
NH 2011-12 (Feb 2011)
Individual countries (Member States within GISN) make the decision
whether or not to adopt these recommendations to meet their country
needs (based on local surveillance of circulating influenza viruses)
* Due to the rare detection/confirmation of seasonal A(H1N1) viruses since
March 2009, NO recommendation for inclusion of such viruses has been made
since NH 2009-10.
http://www.nimr.mrc.ac.uk/who-influenza-centre/annual-and-interim-reports/
Summary of antiviral susceptibility surveillance findings
Reported to WHO: September 2010 - March 2011
For A(H1N1)pdm09: oseltamivir
resistance indicated, all viruses
remained sensitive to zanamivir and
all were resistant to adamantanes.
Table 1: Rate (%) of detection of oseltamivir resistance
MMM-YY*
Sep-10
Oct-10
Nov-10
Dec-10
Jan-11
Feb-11
Mar-11
Overall
WHO Collaborating Centre
CDC
CNIC NIMR VIDRIL NIID Overall
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2.2
0
0.4
0.7
0
0
0
1.5
0.9
0.6
0
1.3
1.2
1.5
1.2
1.3
0
0
0
4.8
2.6
1.4
0
0
0
5.8
1.8
1
0
0.7
1.2
2.2
* Month of specimen collection
A(H3N2) viruses sensitive to NI antivirals, resistant to adamantanes
Influenza B viruses sensitive to NI antivirals
Based on Tessy/EuroFlu Reporting: 2.95% A(H1N1)pdm09 viruses oseltamivir
resistant (91/3080) and observations as above for A(H3N2) and influenza B
NIC UK (Eng): A(H1N1)pdm09 resistant viruses from cases with no known exposure to
oseltamivir increased from 11% in 2009-10 season to at least 28% in 2010-11 season
1.5
Acknowledgements
All members of National Reference
Laboraties (largely WHO recognised
National
Influenza
Centres),
WHO,
EISN/ECDC, WHO-EURO, Networks of
Sentinel GPs/MDs……. who provide
clinical specimens, epidemiologic/clinical
data, virus isolates, gene sequences, HI
data, drug sensitivity data…… and form
the fabric of the Global Influenza
Surveillance & Response System (GISRS)
– formerly Global Influenza Surveillance
Network (GISN).
UNSUBTYPEABLE
A**
Ideally send matched
clinical specimens
and virus isolates
** Unsubtypeable A‟s by PCR should be
sent to a WHO CC if circumstances are
unusual
http://www.who.int/csr/disease/influenza/influenzanetwork/en/index.html
((under “Other”)
WHO
Shipment
fund help
WHO CC @ NIMR, London (WIC)
WHO CC
John McCauley
Rod Daniels
Yipu Lin
Vicky Gregory
Lynne Whittaker
Zheng Xiang
Nicholas Cattle
Chandi Halai
Karen Cross
Influenza Group
Alan Hay (retired)
Steven Wharton
Patrick Collins
Haixia Xiao
Nicole Runkler
Ana Luisa Reis
Michael Bennett
John Skehel (retired)
Support Groups
Biological Services
Protein Structure
Physical Biochemistry
Mathematical Biology
HPA (Colindale)
Maria Zambon
Nichola Goddard
Joanna Ellis
Angie Lackenby
Monica Galiano
Catherine Thompson
NIBSC (HPA)
Othmar Engelhardt
Robert Newman
Diane Major
Sanger Centre
Paul Kellam

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