Invasive Group A Streptococci in Canada
with a focus on emm59
Gregory J. Tyrrell, PhD, FCCM, D(ABMM)
National Centre
For Streptococcus
C A N A D A
National
Centre for
Streptococcus
C A N A D A
Members of NCS:
Marg Lovgren
Jocelyne Kakulphimp
Donna Fernandes
Connie Tsang
Jean Weekes
Karen Beheyt
Betty Forwick
Deadly strep outbreak in northern Ont. largely impacting homeless, drug users
Oct 9, 2008
TORONTO — A deadly outbreak of streptococcal infections that's killed 10 people in northern Ontario is
likely to spread but doesn't pose a widespread threat because it appears to be clustered around distinct
groups of people, the province's chief medical officer of health said Thursday.
"It doesn't seem to be showing and spreading throughout the community there but spreading within a
very specific subgroup of the community," Dr. David Williams said a day after Thunder Bay's public
health unit announced the deaths.
"It seems to be a very limited part of the community... Some related with homeless, some with an
intravenous drug user group, some related with some urban populations we're trying to follow-up on.
"For the province at wide, I would say no, it's not a big concern."
The city's health officials also said they've treated another 75 people with invasive Group A
streptococcal infections over the past year.
"We are obviously interested - I am, as the chief medical officer of health - of how well they're doing up
there on this one, and with the uniqueness of the situation, with the unique community issues," Williams
said. "I'll be interested to hear how they'll approach it as a community action."
Cases of Group A strep began surfacing in the Thunder Bay area in late summer 2007, which wasn't
particularly unusual for an infectious disease that's known as the cause of strep throat.
But cases continued to rise, growing beyond the normal six cases and one death per year.
When the local health unit recognized an influx of more severe cases in February, officials began their
probe and found about half of the cases belonged to a strain never seen before in the province, said
health unit epidemiologist Lee Sieswerda.
Called emm-59, the strain was already known in the western provinces. Starting in 2006, a smattering
of victims across the West became infected with the bug that's now linked to more than 300 cases in
the region, said Greg Tyrrell, director of Edmonton's National Centre for Streptococcus.
"This is a type we really haven't seen much in Canada in the past. We don't know why," Tyrrell said,
adding the centre is conducting studies to learn more.
National
Centre for
Streptococcus
C A N A D A
Strep strain not a widespread threat: health officials
Last Updated: Friday, October 10, 2008 | 1:39 PM ET Comments10Recommend13
CBC News
A potentially deadly strain of streptococcal infections that contributed to the deaths of 10 people in northwestern Ontario doesn't pose a
widespread threat, the province's chief medical officer of health says.
"It doesn't seem to be showing and spreading throughout the community [in Thunder Bay], but spreading within a very specific subgroup of the
community," Dr. David Williams said.
Doctors have treated 75 people with Group A streptococcal infection in the Thunder Bay area since August 2007.
The outbreak seems to be concentrated in a group of homeless people and intravenous drug users, Williams said Thursday.
"For the province [at large], I would say no, it's not a big concern."
Most infections minor
About half of the cases involved the M-59 strain, which has been moving east from British Columbia since 2006.
The strain is linked to more than 300 cases across Canada, said Greg Tyrrell, director of Edmonton's National Centre for Streptococcus.
Both Tyrrell and Dr. Don Low, microbiologist in chief at Toronto's Mount Sinai Hospital, said they expect the M-59 strain to keep spreading across
the country.
"We've seen it out now for a couple of years out west and now in Thunder Bay, so it wouldn't be surprising that it eventually shows up in southern
Ontario and the other eastern provinces," said Low.
This is strep season, but for most people there is no reason to be worried about this strain, the health officials said.
"Most of these infections are going to be minor infections that just cause sore throat or a skin infection, where antibiotics will treat them quite
effectively," Low added.
Meanwhile, the widow of Daniel MacMaster, 37, who died in a Thunder Bay hospital with invasive group A streptococcal disease in March, said he
showed flu-like symptoms when he first became sick.
"He went to emergency because he really wasn't feeling good at all," recalled Tina McCallum, MacMaster's common-law partner. "They gave him
puffers and a note to take some time off work."
MacMaster was one of the 10 who died over the past year.
Health officials in Thunder Bay are working on tracing the close contacts of those infected.
National
Centre for
Streptococcus
C A N A D A
National Centre for Streptococcus
(NCS)
National Centre
For Streptococcus
C A N A D A
Operated in partnership with the National Microbiology Laboratory in Winnipeg
and Provincial Laboratory for Public Health (Alberta Health Services)
in Edmonton since 1992.
National Streptococcal Reference Laboratory.
Group A streptococcus serotyping.
Group B streptococcus serotyping.
Streptococcus pneumoniae serotyping.
Gram positive, catalase negative cocci identification.
Antimicrobial susceptibility assays for trending analysis.
Laboratory support for Streptococcal outbreak investigation.
Provide consultative services on streptococci and streptococcal
related issues where requested.
Streptococcal research, both basic and clinical.
Assess new technology for any of the above.
National
Centre for
Streptococcus
C A N A D A
What do we (the NCS) collect/report??
Passive Surveillance System:
not the best system
Data collected:
M type
geographic location
age
sex
clinical diagnosis if supplied (rarely)
site of isolation
date of collection
antimicrobial susceptibility for trending
National
Centre for
Streptococcus
C A N A D A
iGAS submissions 2004 to September 2008
4316 cases
1600
1400
1200
number of cases
1000
800
600
400
200
0
BC
AB
SK
MB
ON
PQ
NB
NS
PEI NFLD YK
province or territory
National
Centre for
Streptococcus
C A N A D A
NWT
NU
GAS submission to NCS from Ontario by case. 2004-Sep 2008
110
100
90
80
number of cases
70
60
50
40
30
20
10
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
0
2004
2005
2006
date
Mount Sinai Hospital
Laboratory Services Branch
Children’s Hospital of Eastern Ontario
Kingston General Hospital
National
Centre for
Streptococcus
C A N A D A
1153
296
6
1
2007
2008
iGAS cases in Canada by month and year
2004 to September 2008
160
140
120
80
60
40
20
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
100
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
iGAS in Canada 2004 to September 2008
160
140
100
80
60
40
20
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
number of cases
120
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
iGAS in Alberta 2004 to September 2008
36
34
32
30
28
24
22
20
18
16
14
12
10
8
6
4
2
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
number of cases
26
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
Group A Serotyping
Lancefield Typing System
•
M type
– protein antigen
– virulence factor
– non-helical region at N
terminus confers
serological specificity of M
protein
– 86 M types (Facklam et al.
1999. EID;5:247-253)
– emm gene = M protein
– 124 emm types (Facklam
et al. 2002. CID:34;28-38)
– 2008 - more emm types
now known.
National
Centre for
Streptococcus
C A N A D A
Group A Streptococci typing
Anti-OF typing
opacity factor – fibronectin binding protein.
production of OF is associated with M type
the OF type is concordant with M type
about 27 different OF types
T typing
evidence suggests the T type is a Group A streptococcus pilus.
about 20 different T types
one strain can carry more than one T type (e.g. 3/13/B3264)
T type (pattern) is associated with M type (e.g. M1 T1)
emm sequencing of region in gene that encodes the M protein.
National
Centre for
Streptococcus
C A N A D A
Worldwide there are 114 different M types and
43 sequence types for a total of 157 unique M types
(CDC Strep lab database).
M1
M2
M3
M4
M5
M6
M8
M9
M11
M12
M14
M18
M22
M26
M27
M28
M29
M33
M34
M41
M43
M48
M80
M49
M81
M50
M82
M53
M83
M58
M85
M59
M87
M60
M89
M61
M90
M62
M91
M63
M92
M66
M94
M68
M98
M69
M101
M70
M102
M71
M103
M72
M104
M73
M111
M74
M113
M75
M114
M76
M115
M77
M118
M78
M79
National
Centre for
Streptococcus
C A N A D A
M types (emm types) in Canada 2004 to Sept 2008.
65 DIFFERENT TYPES SEEN.
iGAS cases in Canada by month and year
2004 to September 2008
160
140
120
80
60
40
20
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
100
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
iGAS cases by year with M1 split out from all other M types in Canada
160
M1
all other M types
140
120
80
60
40
20
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
number of cases
100
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
iGAS cases by year with M59 split out from all other M types in Canada
160
M59
all other M types
140
120
80
60
40
20
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
100
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
Top 20 M types in Canada – 2004 to Sept 2008
200
180
160
number of cases
140
120
100
80
60
40
20
0
2003
2004
2005
2006
year
National
Centre for
Streptococcus
C A N A D A
2007
2008
2009
M1
M2
M3
M4
M5
M6
M11
M12
M28
M41
M49
M59
M61
M75
M77
M82
M83
M89
M91
M92
Top 18 M Types in Canada – 2004 to Sept 2008
EXCLUDING M1 and M59
90
80
70
number of cases
60
50
40
30
20
10
0
2003
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
2009
M2
M3
M4
M5
M6
M11
M12
M28
M41
M49
M61
M75
M77
M82
M83
M89
M91
M92
28
Top ten M types in Canada by percentage based on
overall number of cases
26
24
2004
2005
2006
2007
2008
percentage of total/year
22
20
18
16
14
12
10
8
6
4
2
0
M1
M59 M28 M12
M3
M89
M type
National
Centre for
Streptococcus
C A N A D A
M4
M11 M92 M91
USA Surveillance (slide taken from CDC Streptococcus lab website)
25%
2003, N = 1042 GAS isolates
2004, N = 768 GAS isolates
20%
15%
10%
5%
emm types 1 12 28 89 6 49 44 75 77 4 22 11 2 5 92 18 27 73 82 58 114 94
Distribution of invasive isolates from Active Bacterial Core surveillance
(ABCs) among the 22 most common emm types found during 2003. These
22 types accounted for 870/1042 (83.5%) of year 2003 isolates and 604 (78.6%)
of year 2004 isolates. There was a total of 51 emm types among year 2003
isolates and 49 emm types among year 2004 isolates. Note that the numbers
National
reflect emm typed isolates only, and not the total numbers of ABCs GAS cases.
Centre for
Streptococcus
C A N A D A
28
Top ten M types in Canada by percentage based on
overall number of cases
26
24
2004
2005
2006
2007
2008
percentage of total/year
22
20
18
16
14
12
10
8
6
4
2
0
M1
M59 M28 M12
M3
M89
M type
National
Centre for
Streptococcus
C A N A D A
M4
M11 M92 M91
iGAS 2004 to September 2008 Top 4 M types
Male:female
313:291
1.1:1
22
20
22
20
M1
16
16
14
14
12
10
8
6
4
Male:female
177:142
1.2:1
18
number of cases
number of cases
18
2
12
10
8
6
4
2
0
0
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
age
40
50
60
70
80
90
100
age
22
22
Male:female
58:76
1:1.3
20
18
Male:female
94:85
1.1:1
20
18
M28
number of cases
16
number of cases
M59
14
12
10
8
6
4
2
M12
16
14
12
10
8
6
4
2
0
0
0
10
20
30
40
50
age
National
Centre for
Streptococcus
C A N A D A
60
70
80
90
100
0
10
20
30
40
50
age
60
70
80
90 100
34
emm59 cases in Canada by date of isolate collection
365 cases to October 2, 2008
32
30
28
26
24
20
18
16
14
12
10
8
6
4
2
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
22
2004
National
Centre for
Streptococcus
C A N A D A
2005
2006
date
2007
2008
emm59 cases in Canada by date of isolate collection
and province
34
32
PQ
ON
MB
SK
AB
BC
30
28
26
22
20
18
16
14
12
10
8
6
4
2
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
24
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
emm59 cases in Canada by date of isolate collection
and province
34
32
PQ
ON
MB
SK
AB
BC
30
28
26
22
20
18
16
14
33yo male
Thompson, MB
Rt arm
12
10
Mt Sinai
46 yo male
26059, 70 yo
Thompson, MB
NF-leg
8
6
4
14yo female
Conklin AB
knee
2
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
24
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
emm59 cases in Canada by date of isolate collection
and province
34
32
PQ
ON
MB
SK
AB
BC
30
28
26
22
20
18
16
14
12
39 yo male
BC-No address
Skin, Rt arm
10
8
Mt Sinai
3 yo-26172
6
4
58 yo male
Winnipeg, MB
Aspirate Rt arm
2
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
number of cases
24
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
Conklin,
Alberta
Thompson,
Manitoba
National
Centre for
Streptococcus
C A N A D A
Thunder Bay
Baseline yearly rate was 3.6 per 100,000
July 2007 to June 2008 36.3 per 100,000
10X
Total number of cases from
Aug 1, 2007 to Oct 14, 2008 = 75
emm types for 41 isolates
National
Centre for
Streptococcus
C A N A D A
emm type
# of cases
Percent
1
7
17%
3
1
2%
6
1
2%
12
1
2%
44
5
12%
49
2
5%
53
1
2%
59
18
44%
68
1
2%
82
1
2%
115
1
2%
st7406
2
5%
total
41
100%
emm59 cases by age and sex for Canada 2004 to Sept 2008
16
319 cases with gender information
14
male vs female
177:142
1.24:1
number of cases
12
10
female
male
8
6
4
2
0
0
10
20
30
40
50
age
National
Centre for
Streptococcus
C A N A D A
60
70
80
90
100
M59 cases in children under 1 year of age
15 cases
12 female:3 male
Ages: 8D, 9D, 30D, 5W, 5W, 5W, 6W, 7W, 3M, 4M, 5M, 6M, 6M, 7M, 9M
PQ
ON
MB
SK
AB
BC
2
1
0
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
Feb
Apr
Jun
Aug
Oct
Dec
number of cases
3
2004
2005
2006
date
National
Centre for
Streptococcus
C A N A D A
2007
2008
Anatomical source of emm59 GAS isolates in Canada
for which source information is provided.
Table. Source of iGAS emm59 isolates
number of cases
National
Centre for
Streptococcus
C A N A D A
blood
214
aspirate elbow/knee
42
abscess arm/hand
40
abscess leg/foot
24
abscess other
16
pleural/lung
7
abdominal wound
3
bone
2
other
18
Clinical Illness Alberta
January 2007 to May 31, 2008.
Manifestation
M1
M59
cellulitis
joint
necrotizing fasciitis
pneumonia
septicemia/bacteremia
soft tissue infection
toxic shock syndrome
2
3
3
6
27
4
6
2
4
4
4
24
2
1
total
51
41
From Alberta Health and Wellness
National
Centre for
Streptococcus
C A N A D A
M59 elsewhere in the world.
Communications with other Streptococcal researchers at
Lancefield Streptococcal meeting in Greece June 2008 suggests we are
currently the only country with this problem.
CDC Streptococcus laboratory website: 1995-2001 = 1.1%
Bernie Beall –CDC Strep lab Nov 7, 2008; last 5 mo in USA – 1 isolate.
In 2007 there were 10 isolates in San Francisco – very low.
New Zealand : 250-300 isolates/year.
~5-7 isolates are M59 (2%)
come from cases of nephritis, abcesses,
blood cultures, or throat (RF)
In Canada 2008: 23.4% (195 isolates).
National
Centre for
Streptococcus
C A N A D A
Original descriptions of M59.
Dillon in Alabama.
Nephritic ???
National
Centre for
Streptococcus
C A N A D A
T-type
T antigen is a pilus protein
Most M59’s (if not all)
from elsewhere in the
world seem to be T11
or T11/12.
National
Centre for
Streptococcus
C A N A D A
M59 in Canada
T11 or T11/12
Pilus-like structures observed by electron microscopy
Mora M. et.al. PNAS 2005;102:15641-15646
M6
National
Centre for
Streptococcus
©2005 by National Academy of Sciences
C A N A D A
M1
M5
M12
M59 outbreak in England in 1999
slaughterhouse workers
8 cases
skin infections
T5/27/44
National
Centre for
Streptococcus
C A N A D A
Antimicrobial susceptibility
All 365 M59 isolates assayed are fully
susceptible to:
Penicillin
Erythromycin
Clindamycin
Vancomycin
Chloramphenicol
National
Centre for
Streptococcus
C A N A D A
StreptAvax™
26-Valent M Protein-Based
Vaccine
Hexa A.1
M24
M5
M6
M19
M29
M14
M24
Septa B.2
M1.0
M12
Spa
M28
M3
M1.2
M18
M1.0
M43
M13
M22
M11
M59
M33
M2
M101
M77
M114
M75
M76
M92
M89
Septa C.2
M2
Septa D.1
M89
National
From
Johnathan Carapetis, Menzies School of Health Research, Australia
Centre for
Streptococcus
C A N A D A
National
Centre for
Streptococcus
C A N A D A
Genomic sequencing of GAS
GAS genomes sequenced to date:
M1
M18
M3
M6
M1
M28
M3
M2
M4
M12
M5
M49
Ferretti
Musser
Nakagawa
Musser
Musser
Musser
Musser
Musser
Musser
Musser
Parkhill
Savic
National
Centre for
Streptococcus
C A N A D A
2001
2002
2003
2004
2005
2005
2006
2006
2006
2006
2007
2008
Canadian M59 strain
being sequenced.
Summary:
1. NCS – National Reference Centre for emm typing
Group A streptococci.
2. Ontario has submitted approximately 1/3 of iGAS isolates
from 2004 to 2008.
3. iGAS case numbers appear to be increasing.
4. M typing = emm type.
5. 157 unique M types worldwide.
6. Canada has seen 65 M types 2004-2008.
7. Increase in M59 started 2006 (January?) More common than
M1 in 2008 – now ~24% of cases.
8. Not seen elsewhere in world including USA to any
appreciable extent.
9. Distribution primarily middle age adults with
average age 40/41 years.
National
Centre for
Streptococcus
C A N A D A
Summary continued:
10. 15 cases out of 365 in children under 1 year of age.
11. M59 increase focused in Western Canada with cases
in Thunder Bay.
12. Primary source of isolate – blood followed by joint aspirates
and abscesses.
13. Clinical presentation in Alberta – septicemia/bacteremia.
14. T type is T11 or T11/12 (pilus).
15. Susceptible to penicillin, erythromycin, clindamycin,
vancomycin and chloramphenicol.
16. Included in GSK’s StreptVax vaccine.
17. M59 genome sequenced and undergoing analysis.
Outbreak/Epidemic wave of M59 in Canada
National
Centre for
Streptococcus
C A N A D A