Invasive group A streptococcal disease surveillance in Canada, 2023

Abstract

Background: Invasive group A streptococcal (iGAS, Streptococcus pyogenes) disease has been a nationally notifiable disease in Canada since 2000.

Objective: To summarize the demographics, emm types and antimicrobial resistance of iGAS isolates collected in Canada in 2023.

Methods: The Public Health Agency of Canada's National Microbiology Laboratory (Winnipeg, Manitoba) collaborates with provincial and territorial public health laboratories to conduct national surveillance of invasive Streptococcus pyogenes. Emm types were extracted from whole genome sequencing data and antimicrobial susceptibilities were predicted from the sequencing data based on the presence of resistance determinants.

Results: Overall, the incidence of iGAS disease in Canada was 6.53 cases per 100,000 population in 2022; an increase from the rate of 5.56 cases per 100,000 population in 2021. A total of 5,201 iGAS isolates were collected during 2023, representing a stark increase in comparison to pre-SARS-CoV-2 pandemic disease activity. Of note during 2023 was the increased number of isolates collected from children younger than 15 years of age (n=577), over double the total in 2019 (pre-pandemic, n=254). The most common emm types overall in 2023 were emm1 (24.2%, n=1,260) and emm12 (16.6%, n=864), representing significant increases in prevalence since 2019 (p<0.0001); these types were also the most common within all Canadian regions and for both adults and children. Antimicrobial resistance rates in 2023 included 11.0% erythromycin resistance, 2.3% clindamycin resistance and 15.2% tetracycline resistance.

Conclusion: The 5,201 isolates of iGAS collected in Canada in 2023 represent the highest annual total to date. The increase of iGAS experienced in 2023 was a critical public health concern, particularly due to the significant burden of pediatric invasive disease. Continued surveillance is vital to understanding the changing landscape of iGAS disease in Canada, particularly emm types and antimicrobial resistance patterns in the post-pandemic period.

Introduction

Group A Streptococcus (GAS, Streptococcus pyogenes) is responsible for a wide range of human diseases, the most serious of which include bacteraemia, streptococcal toxic shock syndrome, necrotizing fasciitis and endocarditis ^{Footnote 1}. After steadily increasing in incidence up to 2019, invasive group A streptococcal (iGAS) infections declined considerably in Canada during the SARS-CoV-2 pandemic (COVID-19). In 2022, it was reported an increased number of iGAS isolates submitted to Canada's National Microbiology Laboratory (NML) in comparison to COVID-19 years, particularly in November and December 2022 ^{Footnote 2}. This coincided with several alerts of increased iGAS disease activity in late 2022 by the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and Pan American Health Organization (PAHO) ^{Footnote 3Footnote 4Footnote 5}. This rapid increase in iGAS disease was accompanied by an abrupt shift in the emm types associated with infections in Canada, from emm49 to emm1 and emm12 ^{Footnote 2}. This report provides a summary of iGAS isolates collected in Canada in 2023.

Methods

Surveillance program

As previously described, surveillance of iGAS in Canada consists of a passive, laboratory-based system where invasive S. pyogenes isolates from all provincial and territorial public health laboratories (except Alberta) are forwarded to NML in Winnipeg for further testing ^{Footnote 2}. In 2023, a total of 5,201 iGAS isolates were reported, including 4,308 submitted directly to NML by provincial and territorial public health laboratories and data for a further 893 isolates collected and tested by the Alberta Provincial Laboratory for Public Health (Table 1). Sterile clinical isolation sites include blood, cerebrospinal fluid, deep tissue, biopsy and surgical samples, bone and any clinical sources associated with necrotizing fasciitis or toxic shock syndrome.

Population-based incidence of iGAS disease up to 2022 were obtained through the Canadian Notifiable Disease Surveillance System (CNDSS). Population data for incidence rates were obtained from Statistics Canada's July 1^st annual population estimates.

Isolate testing

All iGAS isolates submitted to NML in 2023 were whole genome sequenced using the Illumina platform. Isolates were confirmed as S. pyogenes using 16S ribosomal RNA gene sequence analysis. Emm type was identified directly using the WGS Analysis and Detection of Molecular Markers (WADE) pipeline (https://github.com/phac-nml/wade) and CDC emm database. Antimicrobial resistance interpretation (susceptible, resistant/inducibly-resistant) was also predicted using WADE, based on the presence/absence of resistance markers for macrolides/lincosamides (ermA, ermB, ermT, mefA/E), tetracycline (tetA, tetB, tetM, tetO, tetT) and β-lactams (pbp2x).

Supplementary testing was performed on all emm1 isolates submitted to NML in 2023 to determine the prevalence of the novel M1_UK lineage. The M1_UK genotypes were determined by mapping whole genome sequencing reads against reference strain MGAS5005 and identifying 27 characteristic genomic single nucleotide variants, as previously described ^{Footnote 6Footnote 7}.

Data analysis

Demographic data submitted with bacterial isolates included patient age, sex, clinical source, province and date of collection. Multiple isolates with the same emm type and collected from the same patient within 21 days were counted once with the most invasive isolation site assigned. Meningitis-related isolates were regarded as most invasive, followed by blood and then other sterile sites. The laboratory data were aggregated by age into younger than two years, 2–4, 5–14, 15–49, 50–64 and 65 years and older old age groups and regionally into Western (British Columbia, Alberta, Saskatchewan, Manitoba), Central (Ontario and Québec), Eastern (New Brunswick, Nova Scotia, Prince Edward Island, Newfoundland and Labrador) and Northern (Yukon Territories, Northwest Territories and Nunavut) regions of Canada. Statistical significance of trends was assessed using the Cochran Armitage test for trend, with a p-value of <0.05 considered significant.

Results

The overall incidence of iGAS disease in Canada was 6.53 cases per 100,000 population in 2022. Though this represents a decrease from the peak of 8.60 cases per 100,000 population in 2018, it is an increase over the low rate of 5.56 cases per 100,000 population seen during the COVID-19 pandemic in 2021 (Figure 1). There was a startling increase in the number of iGAS isolates submitted in 2023 (n=5,201), almost double the submissions received 2022 (n=2,634) and the highest annual total in Canada to date. After a sharp increase in isolates collected during 2022–Q4 (October to December), totals continued to increase into 2023 with a peak in 2023–Q2 (April to June) (Figure 2). All quarterly isolate totals in 2023 were considerably higher than the corresponding quarter in 2019 (pre-pandemic iGAS disease activity). Of note during 2023 was the increased number of isolates collected from children less than 15 years of age (n=577); over double the total in 2019 (pre-pandemic, n=254). Paediatric isolate submissions also peaked in 2023–Q2 (Figure 2).

Figure 1 - Text description

This figure is a bar graph displaying the incidence of invasive Streptococcus pyogenes cases per 100,000 population in Canada from 2013 to 2022, by age group.

Age group (years)	2013	2014	2015	2016	2017	2018	2019	2020	2021	2022
<1	9.70	9.17	13.86	7.30	8.68	10.61	8.57	7.55	7.72	7.42
1–4	4.59	5.23	4.39	6.41	6.18	6.54	6.41	3.64	1.88	4.85
5–9	3.28	3.63	3.61	3.64	3.11	4.35	4.04	1.64	0.63	2.96
10–14	2.01	1.37	1.05	1.77	1.74	1.30	1.12	0.67	0.71	1.40
15–19	1.02	1.27	1.52	1.34	1.78	2.26	1.82	1.87	0.87	1.07
20–24	2.19	2.47	2.71	2.80	3.51	3.91	3.66	3.72	2.87	2.26
25–29	3.30	3.69	3.99	5.06	5.04	6.91	6.86	5.67	3.66	4.24
30–39	5.27	5.30	5.57	7.55	8.35	9.35	9.42	8.71	7.26	7.18
40–59	5.06	5.05	5.39	6.18	7.83	9.90	9.58	9.33	8.44	8.77
60+	7.20	8.73	8.36	8.70	9.49	12.71	11.98	8.37	6.51	8.85
All ages	4.75	5.17	5.30	6.00	6.82	8.60	8.22	6.87	5.60	6.53

Figure 2 - Text description

This figure is a stacked bar graph displaying the number of invasive Streptococcus pyogenes isolates collected from patients less than 15 years of age and patients 15 years of age and older from 2019 to 2023, by quarter.

Isolate date	Quater	<15 years	≥15 years	Total
2019 (n=3,234)	Qtr1	88	857	947
	Qtr2	62	732	796
	Qtr3	37	639	677
	Qtr4	67	744	814
2020 (n=2,865)	Qtr1	80	852	932
	Qtr2	18	603	623
	Qtr3	25	629	657
	Qtr4	24	628	653
2021 (n=2,180)	Qtr1	27	509	539
	Qtr2	18	494	517
	Qtr3	22	485	509
	Qtr4	18	593	615
2022 (n=2,634)	Qtr1	24	580	607
	Qtr2	24	526	552
	Qtr3	32	516	552
	Qtr4	110	811	923
2023 (n=5,201)	Qtr1	142	1,004	1,153
	Qtr2	190	1,261	1,456
	Qtr3	85	1,046	1,138
	Qtr4	160	1,289	1,454

Of the 5,201 iGAS isolates tested in 2023, 5,177 (99.5%) had patient ages. Infants younger than two years of age accounted for 2.6% (n=135), toddlers aged 2–4 years for 3.0% (n=156), children aged 5–14 years for 5.5% (n=286), teens/adults aged 15–49 years for 36.3% (n=1,886), adults aged 50–64 years for 24.3% (n=1,262) and seniors aged 65 years and older for 27.9% (n=1,452). Of the isolates for which sex information was available, isolates from male patients represented 58.3% (n=2,718) of isolates. Blood was the main clinical isolation site, accounting for 66.0% (n=3,434) of isolates collected.

The most predominant emm types overall in 2023 were emm1 (24.2%, n=1,260) and emm12 (16.6%, n=864), representing significant increases in prevalence since 2019 (from 11.9%, n=385, p<0.0001 and from 4.2%, n=136, p<0.0001, respectively) (Figure 3). After initially increasing in 2022–Q4, emm12 counts peaked in 2023–Q1. At 22.1% of isolates (n=255), emm12 was the most common type during Q1 before declining in prevalence throughout the remainder of 2023 (Appendix, Figure S1). Emm1 increased steadily in prevalence throughout 2023, peaking at 30.7% of isolates (n=446) collected during 2023–Q4 (Appendix, Figure S1). Of note, 60.3% (n=693) of emm1 isolates sequenced in 2023 were the novel M1_UK lineage, roughly double the prevalence seen in 2019 (30.8%, n=106, p<0.0001) (Figure 4). Other emm types that demonstrated significantly increasing trends from 2019 to 2023 include emm41 (2.0%–3.6%, p<0.0001), emm59 (1.5%–3.5%, p<0.0001), emm80 (0.8%–2.7%, p<0.0001), emm82 (1.1%–4.3%, p=0.0097), emm83 (1.5%–3.0%, p<0.0001) and emm92 (1.1%–3.7%, p<0.0001). Many emm types demonstrated significantly decreasing trends (Figure 3).

Figure 3 - Text description

This figure is a bar graph displaying the percentage of Streptococcus pyogenes emm types from all age groups from 2019 to 2023, based on the total number of isolates tested annually.

emm type	2019 (n=3,234)	2020 (n=2,865)	2021 (n=2,180)	2022 (n=2,634)	2023 (n=5,201)
emm1 (385,216,11,126,1260)Footnote a	11.9%	7.5%	0.5%	4.8%	24.2%
emm2 (34,30,9,7,72)	1.1%	1.0%	0.4%	0.3%	1.4%
emm3 (115,31,1,0,6)	3.6%	1.1%	0.0%	0.0%	0.1%
emm4 (95,46,11,19,118)	2.9%	1.6%	0.5%	0.7%	2.3%
emm5 (15,2,0,4,5)	0.5%	0.1%	0.0%	0.2%	0.1%
emm6 (86,72,11,27,29)	2.7%	2.5%	0.5%	1.0%	0.6%
emm8 (2,3,2,0,4)	0.1%	0.1%	0.1%	0.0%	0.1%
emm9 (21,11,14,7,7)	0.6%	0.4%	0.6%	0.3%	0.1%
emm11 (78,68,54,52,73)	2.4%	2.4%	2.5%	2.0%	1.4%
emm12 (136,61,22,151,864)	4.2%	2.1%	1.0%	5.7%	16.6%
emm22 (34,24,21,44,53)	1.1%	0.8%	1.0%	1.7%	1.0%
emm25 (2,0,2,6,5)	0.1%	0.0%	0.1%	0.2%	0.1%
emm27 (2,0,7,3,6)	0.1%	0.0%	0.3%	0.1%	0.1%
emm28 (159,81,43,49,119)	4.9%	2.8%	2.0%	1.9%	2.3%
emm31 (0,2,1,0,2)	0.0%	0.1%	0.0%	0.0%	0.0%
emm33 (2,1,0,1,0)	0.1%	0.0%	0.0%	0.0%	0.0%
emm41 (64,60,42,89,185)	2.0%	2.1%	1.9%	3.4%	3.6%
emm43 (1,0,2,9,10)	0.0%	0.0%	0.1%	0.3%	0.2%
emm44 (6,5,1,4,2)	0.2%	0.2%	0.0%	0.2%	0.0%
emm48 (6,0,1,7,4)	0.2%	0.0%	0.0%	0.3%	0.1%
emm49 (279,487,468,445,402)	8.6%	17.0%	21.5%	16.9%	7.7%
emm53 (142,59,91,100,158)	4.4%	2.1%	4.2%	3.8%	3.0%
emm54 (1,0,1,0,2)	0.0%	0.0%	0.0%	0.0%	0.0%
emm58 (6,4,9,2,20)	0.2%	0.1%	0.4%	0.1%	0.4%
emm59 (48,66,115,111,183)	1.5%	2.3%	5.3%	4.2%	3.5%
emm63 (1,0,1,2,2)	0.0%	0.0%	0.0%	0.1%	0.0%
emm66 (0,0,1,1,2)	0.0%	0.0%	0.0%	0.0%	0.0%
emm68 (7,10,6,3,20)	0.2%	0.3%	0.3%	0.1%	0.4%
emm73 (9,6,8,3,5)	0.3%	0.2%	0.4%	0.1%	0.1%
emm74 (249,190,161,239,203)	7.7%	6.6%	7.4%	9.1%	3.9%
emm75 (59,46,25,23,39)	1.8%	1.6%	1.1%	0.9%	0.7%
emm76 (395,428,213,117,111)	12.2%	14.9%	9.8%	4.4%	2.1%
emm77 (75,68,59,68,84)	2.3%	2.4%	2.7%	2.6%	1.6%
emm78 (3,4,1,0,1)	0.1%	0.1%	0.0%	0.0%	0.0%
emm80 (27,96,107,106,143)	0.8%	3.4%	4.9%	4.0%	2.7%
emm81 (191,204,138,91,88)	5.9%	7.1%	6.3%	3.5%	1.7%
emm82 (35,74,159,235,224)	1.1%	2.6%	7.3%	8.9%	4.3%
emm83 (49,50,69,120,156)	1.5%	1.7%	3.2%	4.6%	3.0%
emm87 (40,29,20,28,43)	1.2%	1.0%	0.9%	1.1%	0.8%
emm88 (0,5,6,7,7)	0.0%	0.2%	0.3%	0.3%	0.1%
emm89 (169,106,72,76,138)	5.2%	3.7%	3.3%	2.9%	2.7%
emm90 (2,0,2,2,1)	0.1%	0.0%	0.1%	0.1%	0.0%
emm91 (39,60,61,48,48)	1.2%	2.1%	2.8%	1.8%	0.9%
emm92 (36,81,63,99,195)	1.1%	2.8%	2.9%	3.8%	3.7%
emm93 (1,1,1,0,2)	0.0%	0.0%	0.0%	0.0%	0.0%
emm94 (22,11,9,10,8)	0.7%	0.4%	0.4%	0.4%	0.2%
emm101 (49,12,7,5,7)	1.5%	0.4%	0.3%	0.2%	0.1%
emm102 (11,14,5,7,8)	0.3%	0.5%	0.2%	0.3%	0.2%
emm106 (1,1,0,3,1)	0.0%	0.0%	0.0%	0.1%	0.0%
emm112 (2,1,0,0,3)	0.1%	0.0%	0.0%	0.0%	0.1%
emm114 (3,4,3,7,6)	0.1%	0.1%	0.1%	0.3%	0.1%
emm118 (7,2,7,4,1)	0.2%	0.1%	0.3%	0.2%	0.0%
emm122 (0,0,0,14,13)	0.0%	0.0%	0.0%	0.5%	0.2%
emm151 (1,0,1,2,3)	0.0%	0.0%	0.0%	0.1%	0.1%
emm161 (2,6,3,0,0)	0.1%	0.2%	0.1%	0.0%	0.0%
emm169 (2,7,16,15,18)	0.1%	0.2%	0.7%	0.6%	0.3%
emm183 (3,3,0,1,1)	0.1%	0.1%	0.0%	0.0%	0.0%
emm265 (0,0,11,4,4)	0.0%	0.0%	0.5%	0.2%	0.1%
Other (25,17,6,31,27)	0.8%	0.6%	0.3%	1.2%	0.5%

Figure 4 - Text description

This figure is a combination line and stacked bar graph. The bars depict the number of invasive Streptococcus pyogenes emm1 isolates from 2019 to 2023 that are M1_UK, intermediate, global, or not tested for emm1 lineage. The line depicts the annual percent prevalence of the M1_UK lineage, from 2019 to 2023.

Genotype	2019 (n=385)	2020 (n=216)	2021 (n=11)	2022 (n=126)	2023 (n=1,260)
M1UK	106	92	4	47	693
Intermediate	15	8	1	2	18
Global	223	88	4	48	438
Not tested	41	28	2	29	111
% M1UK	30.8%	48.9%	44.4%	48.5%	60.3%

Emm1 and emm12 were also the most common types across different age groups and regions. From children younger than 15 years of age, emm1 and emm12 represented 49.0% (n=283) and 25.8% (n=149) of isolates, respectively (Appendix, Figure S2). These types were less dominant for patients 15 years of age and older, representing 21.2% (n=974) and 15.5% (n=713) of isolates, respectively (Appendix, Figure S3). Regionally emm1 and emm12 represented 17.8% (n=360) and 14.8% (n=299), respectively, of isolates collected from Western Canada, 28.6% (n=816) and 16.6% (n=474) from Central Canada and 27.0% (n=84) (of each type) from Eastern Canada (Figure 5). Isolates from Northern Canada were highly represented by emm12 in 2023 at 53.8% (n=7), though only 13 isolates were submitted from this region.

Figure 5 - Text description

This figure is a stacked bar graph displaying the number of invasive Streptococcus pyogenes isolates collected from each Canadian region in 2023, by emm type.

emm type	Western (n=2,027)	Central (n=2,850)	Eastern (n=311)	Northern (n=13)
emm1 (360,816,84,0)Footnote a	360	816	84	0
emm2 (23,45,4,0)	23	45	4	0
emm4 (34,70,14,0)	34	70	14	0
emm6 (23,4,2,0)	23	4	2	0
emm9 (0,7,0,0)	0	7	0	0
emm11 (26,41,6,0)	26	41	6	0
emm12 (299,474,84,7)	299	474	84	7
emm22 (26,22,4,1)	26	22	4	1
emm28 (59,53,7,0)	59	53	7	0
emm41 (99,85,1,0)	99	85	1	0
emm43 (6,4,0,0)	6	4	0	0
emm49 (173,200,27,2)	173	200	27	2
emm53 (64,89,5,0)	64	89	5	0
emm58 (3,13,4,0)	3	13	4	0
emm59 (115,67,1,0)	115	67	1	0
emm68 (4,16,0,0)	4	16	0	0
emm74 (113,89,1,0)	113	89	1	0
emm75 (23,11,5,0)	23	11	5	0
emm76 (61,48,0,2)	61	48	0	2
emm77 (25,43,16,0)	25	43	16	0
emm80 (38,105,0,0)	38	105	0	0
emm81 (52,35,1,0)	52	35	1	0
emm82 (89,130,4,1)	89	130	4	1
emm83 (73,83,0,0)	73	83	0	0
emm87 (4,34,5,0)	4	34	5	0
emm88 (3,4,0,0)	3	4	0	0
emm89 (36,80,22,0)	36	80	22	0
emm91 (36,12,0,0)	36	12	0	0
emm92 (127,57,11,0)	127	57	11	0
emm94 (0,8,0,0)	0	8	0	0
emm101 (7,0,0,0)	7	0	0	0
emm102 (2,5,1,0)	2	5	1	0
emm122 (0,13,0,0)	0	13	0	0
emm169 (3,15,0,0)	3	15	0	0
Other (21,72,2,0)	21	72	2	0

Upon request, NML provides assistance to provincial and territorial public health laboratories for iGAS outbreak/case cluster investigations (including non-invasive isolates from screening) and jurisdictional emm increases. During 2023, NML assisted with a jurisdictional increase (emm12) and 11 outbreak investigations from various jurisdictions, including emm1 (two outbreaks of n=3 cases), emm12 (two outbreaks of n=2, two of n=4), emm49 (two outbreaks of n=2 and n=14), emm53 (n=14), emm80 (n=6), emm82 (n=4) and one multi-emm type outbreak (emm49.2, emm83.1 and emm87, n=14). This represents an increase from the number of requests in previous years.

Antimicrobial resistance among iGAS isolates is presented in Figure 6. Erythromycin resistance increased significantly from 7.0% in 2019 to 11.0% in 2023 (p<0.0001), while tetracycline resistance decreased significantly from 25.1% to 15.2% (p<0.0001). Clindamycin resistance remained relatively stable over the study period (2.3%–4.3%). There was no resistance observed to penicillin. The emm types associated with erythromycin resistance and constitutive and inducible clindamycin resistance included emm11 (95.7% erythromycin resistance, n=67; 27.1% constitutive clindamycin resistance, n=19; 45.7% inducible clindamycin resistance, n=32), emm53 (13.4%, n=18; 12.7%, n=17; 0.7%, n=1), emm77 (91.0%, n=71; 2.6%, n=2; 88.5%, n=69), emm83 (43.9%, n=65; 1.4%, n=2; 42.6%, n=63) and emm92 (97.5%, n=153; 1.9%, n=3; 94.9%, n=149) (Appendix, Table S1).

Figure 6 - Text description

This figure is a line graph displaying the percentage of all invasive Streptococcus pyogenes isolates determined to be erythromycin-resistant, clindamycin-resistant and tetracycline-resistant each year, from 2019 to 2023.

Isolates	2019	2020	2021	2022	2023
ERY-R	7.0%	11.2%	14.6%	14.1%	11.0%
CLI-R	2.5%	3.1%	4.3%	3.0%	2.3%
TET-R	25.1%	29.1%	34.8%	20.8%	15.2%

Discussion

In 2022, 2,544 cases of iGAS disease were reported to the CNDSS, with a national incidence rate of 6.53 cases per 100,000 population. This represents a slightly higher rate than was seen in 2021 (5.56 cases per 100,000 population), where COVID-19 pandemic containment measures had a marked effect on the spread of pathogens with respiratory transmission routes, including S. pyogenes. Beginning in late 2022, Canada began to see a surge in the number of iGAS isolates submitted for testing, mirroring the concerning worldwide increases noted by WHO, CDC and PAHO ^{Footnote 3Footnote 4Footnote 5}. Isolate submissions continued to increase going into 2023, peaking in Q2 but remaining much higher than pre-pandemic totals. Though 2023 incidence was not available at the time of writing, the sharp increase in the number of isolates submitted for testing in 2023 (n=5,201) in comparison to the previous highest annual count reported to the CNDSS in 2018 (n=3,190) suggests that 2023 was a record year for iGAS incidence in Canada.

Initial reports on the worldwide iGAS disease increase of late 2022 noted emm1 and emm12 as the predominant cause of iGAS infections, a trend which continued into 2023 ^{Footnote 8Footnote 9Footnote 10Footnote 11}. In Canada, emm12 increased significantly in prevalence at the end of 2022, continuing into early 2023 before decreasing again by the end of the year. Emm1 also increased in prevalence at the end of 2022; in contrast, it continued to increase into the 2023–2024 respiratory virus season. Recent studies indicate an overrepresentation of emm1 in critically ill patients, particularly of the hypervirulent M1_UK lineage ^{Footnote 12Footnote 13}. A study of patients with S. pyogenes infections admitted to Belgian intensive care units found that 73% of isolates collected were emm1, of which 83% were M1_UK ^{Footnote 12}. A second study of iGAS meningitis in the Netherlands noted 86% emm1 during the 2022–2023 season, of which 79% were M1_UK ^{Footnote 13}. The accumulation of single nucleotide variants within M1_UK has been suggested to confer a fitness advantage in pathogenicity, transmission and persistence, and the lineage demonstrates higher genome stability than the ancestral M1_global lineage ^{Footnote 7Footnote 14}. The M1_UK genotype has expanded considerably in Canada, increasing from 48.5% in 2022 to 60.3% in 2023, which is now close to double the pre-COVID-19 pandemic prevalence. The rapid increase over time suggests that the M1_UK lineage will soon replace the M1_global lineage in Canada. Though the Canadian prevalence is much higher than the most recent published value from the United States (11%) ^{Footnote 15}, a number of European countries have published M1_UK rates ranging from 70% up to 95% ^{Footnote 11Footnote 14Footnote 16}.

The rapid increase of emm1 and emm12 resulted in a substantial displacement of other emm types that were recently common in Canada. In particular, prevalence of emm49 had been rapidly increasing, peaking in 2021 when emm1 had all but disappeared. In 2023, NML assisted with three outbreak analyses involving emm49; overall, it was found that emm49 isolates were highly genetically similar across the country. A recent genomic surveillance study of iGAS disease in Arizona noted a similar clonal expansion of emm49, with limited genomic diversity ^{Footnote 17}. As emm types tend to fluctuate with "epidemic behaviour" as populations develop immunity ^{Footnote 1}, and as emm49 is so genetically homogenous across Canada, it is likely that it was very easily replaced by emm1 and emm12.

As expected, S. pyogenes remained fully susceptible to first-line treatment penicillin. Resistance rates remained high to second-line therapy erythromycin, and commonly collected emm types in Canada with high levels (greater than 40%) of resistance were similar to those described in previous 2020 and 2021/2022 reports ^{Footnote 2Footnote 18}. Clindamycin resistance in Canada remained low in 2023 at 2.3%. This is in contrast to reports out of Europe describing rising clindamycin resistance rates following the COVID-19 pandemic, including 17.5% in Spain and 28.2% in Ireland ^{Footnote 19Footnote 20}. The current report also represents the first publication for this surveillance system of resistance data for tetracycline, a Tier 2 antimicrobial agent as defined by the Clinical and Laboratory Standards Institute ^{Footnote 21}. Though NML did not test tetracycline by the previously utilized disc diffusion method, it is now included in whole genome sequencing-based resistance predictions. The variable number of isolates tested prior to 2023 may have affected the resistance rates presented in Figure 6; however, 2023 represents a complete year of data and a 15.2% rate of resistance. Recent tetracycline resistance rates were variable across different countries, including 43% and 8.3% resistance in Ireland and South Africa, respectively ^{Footnote 20Footnote 22}.

Strengths and limitations

Caution should be exercised when interpreting the data presented in this report as the overall interpretation of the results is limited to only isolates available for testing; provinces and territories may submit only a subset of their isolates to NML for testing. The laboratory-based surveillance system is also limited in that it does not collect enhanced epidemiological data to stratify emm typing data by outcome, manifestation or risk factor, which is critical information to help understand the changing landscape of iGAS disease in Canada. To address these surveillance gaps, the Public Health Agency of Canada, in collaboration with provincial and territorial partners, plan to implement a national enhanced iGAS surveillance system as early as 2024.

Conclusion

After several years of below normal iGAS cases due to the COVID-19 pandemic, isolate counts rebounded significantly in 2023, reaching the highest annual Canadian total to date. Of particular concern was the drastic increase in isolates collected from children younger than 15 years of age. Emm1 and emm12 represented the most common types overall, by age group and by geographic region, far surpassing the previous most common type, emm49. It is unclear whether these emm types will continue to dominate moving forward, or if the distribution will level out as Canada moves further into the post-COVID-19 period. It will be critical to maintain comprehensive surveillance, including integration of epidemiological data through the planned national enhanced iGAS surveillance system, to understand the changing landscape of iGAS disease in Canada.

Authors' statement

ARG — Formal analysis, data curation, visualization, writing−original draft, review & editing of final version
AG — Formal analysis, validation, investigation, data curation, visualization, writing−review & editing
GJT — Resources, methodology, writing−review & editing
JVK — Resources, methodology, writing−review & editing
AM — Resources, methodology, writing−review & editing
M-CD — Resources, methodology, writing−review & editing
JMG — Resources, methodology, writing−review & editing
JMinion — Resources, methodology, writing−review & editing
PV — Resources, methodology, writing−review & editing
CB — Resources, methodology, writing−review & editing
DH — Resources, methodology, writing−review & editing
YY — Resources, methodology, writing−review & editing
XD — Resources, methodology, writing−review & editing
LS — Resources, methodology, writing−review & editing
JMcFadzen — Resources, methodology, writing−review & editing
CP — Writing−review & editing
IM — Conceptualization, validation, methodology, supervision, project administration, writing−review & editing

Competing interests

None.

ORCID numbers

Alyssa R Golden — 0000-0002-1788-1794
Gregory J Tyrrell — 0000-0002-5276-2416
Julianne V Kus — 0000-0001-6033-7244
Allison McGeer — 0000-0001-5647-6137

Acknowledgements

We thank Angela Yuen, Rachel Hink and Anastasia Anistratov from the Invasive Bacterial Diseases Section at the National Microbiology Laboratory for their laboratory technical assistance, and the staff of provincial and public health laboratories in Canada for participating in the national laboratory surveillance program.

Funding

This project was supported by internal funding from the Public Health Agency of Canada.

Appendix

Supplemental material is available upon request to the author: alyssa.golden@phac-aspc.gc.ca

Emm data can also be viewed in interactive format on the National Laboratory Surveillance of Invasive Streptococcal Disease in Canada (eSTREP) Health Infobase page.

Figure S1: Number of invasive Streptococcus pyogenes isolates collected each quarter for emm1, emm12 and all other emm types, 2019–2023

Figure S2: Prevalence of invasive Streptococcus pyogenes emm types isolated from patients less than 15 years old in 2023 (n=577)

Figure S3: Prevalence of invasive Streptococcus pyogenes emm types isolated from patients 15 years and older in 2023 (n=4,600)

Table S1: Percentage of macrolide and lincosamide resistant Streptococcus pyogenes isolates collected in 2023, by emm type

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