National Centre for Streptococcus C A N A D A Invasive Group A Streptococci in Canada with a focus on emm59 Gregory J. Tyrrell, PhD, FCCM, D(ABMM) National

NationalCentre forStreptococcusC A N A D A

Invasive Group A Streptococci in Canadawith a focus on emm59

Gregory J. Tyrrell, PhD, FCCM, D(ABMM)

National Centre For StreptococcusC A N A D A

Members of NCS:Marg LovgrenJocelyne KakulphimpDonna FernandesConnie TsangJean WeekesKaren BeheytBetty Forwick


Deadly strep outbreak in northern Ont. largely impacting homeless, drug usersOct 9, 2008TORONTO — 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.


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 minorAbout 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.

Strep strain not a widespread threat: health officialsLast Updated: Friday, October 10, 2008 | 1:39 PM ET Comments10Recommend13CBC 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.


National Centre for Streptococcus(NCS)

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 StreptococcusC A N A D A


Passive Surveillance System:Passive Surveillance System:not the best systemnot the best system

Data collected:Data collected:M typeM typegeographic locationgeographic locationageagesexsexclinical diagnosis if supplied (rarely)clinical diagnosis if supplied (rarely)site of isolationsite of isolationdate of collectiondate of collectionantimicrobial susceptibility for trending antimicrobial susceptibility for trending

What do we (the NCS) collect/report??


iGAS submissions 2004 to September 20084316 cases

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GAS submission to NCS from Ontario by case. 2004-Sep 2008

Mount Sinai Hospital 1153Laboratory Services Branch 296Children’s Hospital of Eastern Ontario 6Kingston General Hospital 1


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iGAS in Alberta 2004 to September 2008


Group A SerotypingLancefield 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.


Group A Streptococci typing

Anti-OF typingopacity factor – fibronectin binding protein.production of OF is associated with M typethe OF type is concordant with M type about 27 different OF types

emm sequencing of region in gene that encodes the M protein.

T typingevidence suggests the T type is a Group A streptococcus pilus.about 20 different T typesone 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)


M types (emm types) in Canada 2004 to Sept 2008.

M1M2M3M4M5M6M8M9M11M12M14M18M22M26M27M28M29M33M34M41M43M48

M49M50M53M58M59M60M61M62M63M66M68M69M70M71M72M73M74M75M76M77M78M79

M80M81M82M83M85M87M89M90M91M92M94M98M101M102M103M104M111M113M114M115M118

65 DIFFERENT TYPES SEEN.

Worldwide there are 114 different M types and 43 sequence types for a total of 157 unique M types (CDC Strep lab database).


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M1 all other M types

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iGAS cases by year with M1 split out from all other M types in Canada


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iGAS cases by year with M59 split out from all other M types in Canada


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M1 M2 M3 M4 M5 M6 M11 M12 M28 M41 M49 M59 M61 M75 M77 M82 M83 M89 M91 M92

Top 20 M types in Canada – 2004 to Sept 2008


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Top 18 M Types in Canada – 2004 to Sept 2008 EXCLUDING M1 and M59


M1 M59 M28 M12 M3 M89 M4 M11 M92 M910

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1 12 28 89 6 49 44 75 77 4 22 11 2 5 92 18 27 73 82 58114 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 2003isolates and 49 emm types among year 2004 isolates. Note that the numbers reflect emm typed isolates only, and not the total numbers of ABCs GAS cases.

2003, N = 1042 GAS isolates2004, N = 768 GAS isolates

emm types

USA Surveillance (slide taken from CDC Streptococcus lab website)


M1 M59 M28 M12 M3 M89 M4 M11 M92 M910

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Male:female313:291

1.1:1 Male:female177:142

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iGAS 2004 to September 2008 Top 4 M types


emm59 cases in Canada by date of isolate collection

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365 cases to October 2, 2008


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14yo femaleConklin ABknee

46 yo maleThompson, MBNF-leg

Mt Sinai 26059, 70 yo

33yo maleThompson, MBRt arm



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58 yo maleWinnipeg, MBAspirate Rt arm

Mt Sinai3 yo-26172

39 yo maleBC-No addressSkin, Rt arm


Conklin, Alberta

Thompson, Manitoba


Thunder BayBaseline yearly rate was 3.6 per 100,000July 2007 to June 2008 36.3 per 100,000

10X

emm types for 41 isolates

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%

Total number of cases from Aug 1, 2007 to Oct 14, 2008 = 75


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emm59 cases by age and sex for Canada 2004 to Sept 2008

male vs female177:1421.24:1

319 cases with gender information


M59 cases in children under 1 year of age

15 cases12 female:3 maleAges: 8D, 9D, 30D, 5W, 5W, 5W, 6W, 7W, 3M, 4M, 5M, 6M, 6M, 7M, 9M

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Table. Source of iGAS emm59 isolates

number of cases

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

Anatomical source of emm59 GAS isolates in Canada for which source information is provided.


Clinical Illness Alberta January 2007 to May 31, 2008.

Manifestation M1 M59

cellulitisjointnecrotizing fasciitispneumoniasepticemia/bacteremiasoft tissue infectiontoxic shock syndrome

total

23362746

51

24442421

41

From Alberta Health and Wellness


M59 elsewhere in the world.

CDC Streptococcus laboratory website: 1995-2001 = 1.1%

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).

Communications with other Streptococcal researchers at Lancefield Streptococcal meeting in Greece June 2008 suggests we arecurrently the only country with this problem.

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.


Original descriptions of M59. Dillon in Alabama.

Nephritic ???


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.

M59 in CanadaT11 or T11/12


Pilus-like structures observed by electron microscopy

Mora M. et.al. PNAS 2005;102:15641-15646

©2005 by National Academy of Sciences

M6 M1 M5 M12


T5/27/44

M59 outbreak in England in 1999slaughterhouse workers8 casesskin infections


Antimicrobial susceptibility

All 365 M59 isolates assayed are fully susceptible to:

PenicillinErythromycinClindamycinVancomycinChloramphenicol


StreptAvax™ 26-Valent M Protein-Based

Vaccine

M24 M5 M6 M19 M29 M14 M24

M89 M101 M77 M114 M75 M76 M92 M89

Hexa A.1Hexa A.1

Septa B.2Septa B.2

Septa C.2Septa C.2

Septa D.1Septa D.1

M1.0 M12 Spa M28 M3 M1.2 M18 M1.0

M2 M43 M13 M22 M11 M59 M33 M2

From Johnathan Carapetis, Menzies School of Health Research, Australia



Genomic sequencing of GAS

M1 Ferretti 2001M18 Musser 2002M3 Nakagawa 2003M6 Musser 2004M1 Musser 2005M28 Musser 2005M3 Musser 2006M2 Musser 2006M4 Musser 2006M12 Musser 2006M5 Parkhill 2007M49 Savic 2008

GAS genomes sequenced to date:

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 isolatesfrom 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.


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

Documents

National Centre for Streptococcus C A N A D A Invasive Group A Streptococci in Canada with a focus on emm59 Gregory J. Tyrrell, PhD, FCCM, D(ABMM) National