Introduction
Group A streptococci (S. pyogenes) are Gram-positive facultative anaerobic coccobacilli bacteria that grow as chains. These bacteria are responsible for a collection of different diseases in humans ranging from a mild illness such as pharyngitis (commonly referred to as strep throat) to more severe invasive diseases such as necrotizing fasciitis and toxic shock which are rare in occurrence [Reference Walker1, Reference Brouwer2]. Cases of S. pyogenes pharyngitis tend to occur more frequently in the early stages of life (0–9 years) with some children experiencing multiple episodes of streptococcal pharyngitis [Reference Mponponsuo3, Reference Kline4].
An important virulence factor for S. pyogenes is the M protein which is a long-coiled dimerized protein that projects from the Gram-positive cell wall of the bacteria [Reference Walker1, Reference Fischetti5]. The M protein is encoded by the emm gene of which there are 261 emm types [6, Reference Frost7]. This diversity in emm gene sequence results in multiple M-type proteins with some types more prevalent than others [Reference Frost7, Reference Frost8]. Different emm types occur with greater frequency in low-income regions than in high-income countries where the emm type diversity is much less [Reference Steer9].
In the last 2 years (2022–2023), post-COVID-19 restrictions, the rates of S. pyogenes infections have significantly increased, notably in the UK and Europe as well as the USA and Australia [Reference Alcolea-Medina10-Reference Johannesen16]. Much of this increase has been driven by a small number of S. pyogenes emm types notably emm1 and emm12. Of the emm1 strains, a strain termed the M1UK S. pyogenes strain is more prevalent in both adults and children than the previously more common M1global strain [Reference Davies12, Reference Li17, 18]. The M1UK strain is a hypervirulent S. pyogenes that first appeared in the UK in 2013 and subsequently spread globally [Reference Lynskey19].
The objective of this work was to describe the increase in S. pyogenes infections (pharyngitis and invasive disease) in Alberta, Canada from 2018 to 2023 and provide a genomic analysis of a subset of invasive S. pyogenes isolates identified during the increase in cases post-COVID-19 restrictions, from November 2022 to May 2023.
Methods
Data collection for non-invasive S. pyogenes pharyngitis specimens
Data on the number of pharyngitis swabs submitted to diagnostic microbiology laboratories in Alberta and the number positive for S. pyogenes was collated from 1 January 2018 to 31 December 2023 (72 months). This period was selected to include pre- and post-COVID-19 pandemic dates as well as overlay with the increase in invasive S. pyogenes infections beginning November 2022. The large data set was extracted from three different Laboratory Information Systems (LIS) used by diagnostic microbiology laboratories in Alberta during this 72-month period (LIS systems were Meditech, Cerner Millennium, and EPIC) and collated into Microsoft Excel format for analysis. Data captured included both throat cultures and molecular assays used for the detection of S. pyogenes from throat swabs. Alberta population estimates (used to standardize incidence calculations) were obtained from the Government of Alberta resource; http://www.ahw.gov.ab.ca/IHDA_Retrieval/ihdaData.do (accessed 1 March 2024).
Data collection for invasive S. pyogenes isolates
An invasive infection caused by S. pyogenes is designated as a Public Health Notifiable Disease in Alberta ( https://open.alberta.ca/publications/streptococcal-disease-group-a-invasive ). Therefore, all cases are reported to public health by the laboratory identifying the case. Invasive S. pyogenes disease was defined as the identification of S. pyogenes from any sterile site including blood, brain cerebrospinal fluid, deep tissues, and joints. All invasive S. pyogenes isolates were identified by diagnostic microbiology laboratories in Alberta and were submitted to the APL-Public Health reference laboratory for emm typing and antimicrobial susceptibility assays for trending analysis.
Antibiotic susceptibility assays were performed and interpreted using reference disk diffusion methods as described by the Clinical Laboratory Standards Institute [20]. Antimicrobials assayed were penicillin, erythromycin, clindamycin, and vancomycin. All antimicrobial disks were purchased from BBL, Oxoid, England.
Linkage of invasive S. pyogenes with S. pyogenes pharyngitis
Cases of invasive S. pyogenes that were identified between 1 January 2018 and 31 December 2023, were matched to S. pyogenes pharyngitis specimens using the personal healthcare number of each case. This was done to calculate the percentage of known S. pyogenes pharyngitis cases that progressed to known invasive S. pyogenes disease. S. pyogenes pharyngitis specimens were considered linked to invasive disease if the positive pharyngitis swab was collected within 7 days pre- and 7 days post-initial diagnosis of invasive S. pyogenes disease. This time frame was selected to capture all cases, as S. pyogenes pharyngitis is typically resolves within four to 5 days [Reference Sauve21].
Emm typing and whole genome sequencing
The method used to emm type invasive S. pyogenes isolates was DNA sequencing of the emm gene as previously described [22, 23].
For whole genome sequencing, S. pyogenes DNA was extracted using the MagaZorb DNA Mini-Prep Kit (Promega). Briefly, colonies grown in Todd-Hewitt Broth were centrifuged at 6000 × g for 2 minutes and the supernatant was removed. Cells were washed in 12 mM Tris and then lysed in mutanolysin/hyaluronidase lysis solution (62 ml; 10 ml 3 000 U/mL mutanolysin (Sigma), 2 mL of 30 mg/mL hyaluronidase (Sigma), and 50 mL of 10 mM Tris). Lysozyme (15 μL, 100 mg/mL; Sigma) was added and incubated for 1 h at 37 °C with shaking at 700 rpm (Eppendorf ThermoMixer F1.5). Proteinase K solution (20 μL) and RNase A (20 μL, 20 mg/mL; Qiagen or Invitrogen) were added and the tubes were incubated at room temperature for 5 minutes. ATL lysis buffer (200 μL) was added, and tubes were incubated for 2 h at 56 °C with shaking at 900 rpm (Eppendorf ThermoMixer F1.5). Extracts were centrifuged at 9000 × g for 2 minutes and wash, binding, and elution steps were completed with the KingFisher mL Purification System (Thermo Scientific) with Qiagen Buffer EB. Extracted genomic DNA was prepared using a modified Illumina DNA Prep protocol (https://www.medrxiv.org/content/10.1101/2022.02.07.22269672v1) on an Eppendorf epMotion (APL-Public Health Laboratory) or Illumina Nextera XT (National Microbiology Laboratory). Genomes were sequenced using a High Output Kit on an Illumina MiniSeq (APL-Public Health Laboratory) or an Illumina NextSeq 500/550 (National Microbiology Laboratory).
Bioinformatic analysis
Raw sequence data quality was processed through pathogen-seq 1.0.4 (https://github.com/iaoli-dong/pathogenseq); de novo assemblies were generated with SPAdes v3.15.5 using the wrapper Shovill 1.1.0 (github.com/tseemann/shovill), with a minimum length cutoff of 300 bp [Reference Bankevich24]. In silico emm-typing was performed using emm-typer 0.2.0 (github.com/MDU-PHL/emmtyper), MLST performed with mlst v2.19.0 (github.com/tseemann/mlst), and virulence factor profiling using abricate 1.0.1 (github.com/tseemann/abricate) using the virulence factor database [Reference Liu25]. To check if any emm1.0 isolates were the M1UK variant, assembly_snptyper v0.1.0 (github.com/boasvdp/assembly_snptyper) was used [Reference Lynskey19]. Phylogenetic trees were generated by providing the filtered core genome alignment generated by Panaroo 1.5.0 to IQ-TREE 2.2.2.7, using 1 000 ultra-fast bootstraps, 1 000 Shimodaira-Hasegawa approximate likelihood ratio tests (SH-aLRT), and ModelFinder [Reference Tonkin-Hill26, Reference Hoang27]. The tree was rerooted using the midroot with Gotree 0.4.3, annotated using Arcahaeopteryx 0.9930 beta (sites.google.com/view/archaeopteryx/), metadata management with csvtk 0.30.0 (github.com/shenwei356/csvtk), and ultimately visualized using GraPhlAn 1.1.3 (github.com/biobakery/graphlan) [Reference Lemoine and Gascuel28].
The genomic data reported in this study have been deposited in the NCBI Sequence-based Archive as part of the BioProject PRJNA1182376.
Statistical analysis
The incidence calculation for invasive S. pyogenes was based on the number of isolates submitted for emm typing. A single isolate per case was counted unless the second isolate was collected greater than 30 days post from the first isolate. Data were graphed using OriginLab software 2023 (OriginLab Corporation, https://originlab.com).
Summary data was divided into three time periods for analysis; pre-COVID-19 years (2018–2019), years impacted by COVID-19 restrictions (2020–2022), and years’ post-COVID-19 restrictions (2023). Chi-square tests to compare study indicators between time periods were performed using R, Version 3.4.3 GUI 1.70 (2016) (The R Foundation for Statistical Computing, Vienna, Austria).
Ethics
Ethics approval for this study was obtained from the University of Alberta Research Ethics Board (REB). Study number Pro00140378.
Results
There were 1 041 967 pharyngitis swabs submitted for S. pyogenes detection over the 72-month survey period, of which 182 983 were positive for S. pyogenes (positivity rate of 17.6%). The number of pharyngitis swabs collected monthly varied from a low of 3 929 swabs (December 2020) to a high of 28 662 swabs (March 2023). The month with the greatest number of positive S. pyogenes pharyngitis swabs was March 2023 (10 321 swabs – 36.0% positivity rate) (Figure 1).
Figure 1. Streptococcus pyogenes positive specimens from cases of pharyngitis in Alberta. The columns indicate the number of positive specimens for each month over the six-year period. The line indicates the percent positivity. The horizontal gray bar indicates when Alberta imposed province wide Public Health restrictions (12 March 2020–14 June 2022). All ages are included in the data.
Overall, S. pyogenes positivity for pharyngitis swabs was significantly higher in 2023 vs. 2018–2019 (p < 0.0001). From January 2018 to March 2020 (pre-COVID-19), positive specimens for S. pyogenes pharyngitis for all age groups displayed seasonality peaking during winter months (December, January, and February) (Figure 1). From April 2020 to February 2022, positive S. pyogenes pharyngitis specimen numbers dropped to 1 000/month or fewer. The drop in submissions starting April 2020 coincided with the implementation of Public Health intervention measures mandated by the provincial government due to COVID-19 on 12 March 2020 [Reference Hinshaw29]. These were lifted on 14 June 2022, approximately 2 years later (Figure 1) [30]. The age group with the greatest number of positive S. pyogenes pharyngitis specimens was the 0–9 years age group with 2023 having the highest annual percent positivity (41.5% (28 027/67 511)) (Figure 2a). Ages 30–39 showed the second highest positivity rate in all years except 2021, and in 2023, 30.0% of submitted specimens for this age group were positive for S. pyogenes (Figure 2a). For both the 0–9 and 30–39 age groups, S. pyogenes positivity for pharyngitis swabs was significantly higher vs. the pooled value of all other ages (p < 0.0001). Presenting the data as incidence per 1 000 specimens shows the 0–9-year-old age group most severely affected by S. pyogenes pharyngitis (Figure 2b). During COVID-19 restrictions, the years 2020 and 2021 had the lowest incidence per 1 000.
Figure 2. Streptococcus pyogenes positive pharyngitis specimens based on age and year. (a.) The percent of positive S. pyogenes pharyngitis from 2018 to 2023 by age group. S. pyogenes positivity was significantly higher in the 0–9- and 30–39-year-old age categories vs. the pooled value of all other ages (p < 0.0001). (b.) The incidence per 1 000 cases of S. pyogenes pharyngitis in Alberta from 2018 to 2023 by age group (http://www.ahw.gov.ab.ca/IHDA_Retrieval/ihdaData.do).
The incidence of invasive S. pyogenes based on isolates submitted for emm typing showed a rise in incidence rates beginning in 2014 (4.6/100 000) with rates peaking in 2020 (11.4/100 000) and then dropping in 2021 (Figure 3). This was followed by a large increase in 2023 to 19 cases/100 000. Analysis of invasive cases from January 2018 to March 2020 (pre-pandemic) for all ages showed invasive S. pyogenes case numbers averaged 36.5 cases/month and from April 2020 to October 2022 (pandemic) cases averaged 34.7 cases/month. From November 2022 to December 2023 (upsurge period) this significantly increased to 72.9 cases/month (over 2-fold rise) with the greatest number of cases occurring in April 2023 (95 cases) (Figure 4.). The incidence of invasive S. pyogenes was significantly higher in 2023 vs. 2018–2019 for adults (>14 years of age) and children (≤14 years of age) (p < 0.0001). For children 14 years of age and under, the average number of cases/month was 2.5 from January 2018 to October 2022, and from November 2022 to December 2023, this increased to 12.5/month (a 5-fold increase).
Figure 3. The incidence per 100 000 of invasive Streptococcus pyogenes disease in Alberta from 2003 to 2023 (21 years) for the general population. Incidence is based on the number of invasive S. pyogenes isolates submitted for emm typing as per notifiable disease reporting requirements. The highest incidence occurred in 2023 at 18.9/100 000.
Figure 4. Cases of invasive Streptococcus pyogenes disease from 2018 to 2023 by month. Adult is defined as individuals >14 years of age. Child is defined as individuals ≤14 years of age.
The most frequent emm types in 2022 for adults were emm74, 49, 41, and 82. This changed in 2023 with emm1 and emm12 becoming the predominant emm types followed by emm92, emm41, and emm53 (Figure 5a). The proportion of invasive S. pyogenes that were emm1 or 12 vs. other types was significantly higher in 2023 vs. 2018–2019 (p < 0.0001). For children during both 2022 and 2023, most cases of invasive S. pyogenes were attributed to emm1 and emm12 with other emm types rarely seen (Figure 5b).
Figure 5. emm types of invasive Streptococcus pyogenes cases for adults and children. (a.) The number of invasive S. pyogenes disease by emm type for adults (>14 years of age) in 2022 and 2023. (b.) The emm types of invasive S. pyogenes disease for children (≤14) in 2022 and 2023. In comparison to adults, there are few cases in this age group except for emm1 and emm12.
During the last 2 years of the survey (2022–2023), there were 43 emm types identified (Figure 5a and 5b). As emm1 and 12 cases had increased in comparison to all other emm types, we took a closer look at these emm types over the six-year survey period. Figure 6 presents the number of cases of only emm1 and emm12. From January 2018 to April 2020 (pre-COVID-19 interventions), emm1 and emm12 averaged under five cases per month. Case numbers for emm1 and 12 decreased in April/May 2020 (the start of SARS-CoV-2 restriction period) and then increased sharply starting in October 2022 after the lifting of restrictions (Figure 6.).
Figure 6. The number of cases of invasive emm1 and emm12 Streptococcus pyogenes from 2018 to 2023 by month. All ages are included.
The collection of positive S. pyogenes pharyngitis specimens provided us with the opportunity to identify invasive S. pyogenes cases that also had documented S. pyogenes pharyngitis. Of the 182 983 specimens of laboratory-confirmed S. pyogenes pharyngitis over the six-year period from 2018 to 2023, 111 cases (0.06% (60.7/100 000)) also presented with invasive S. pyogenes disease within 7 days of S. pyogenes pharyngitis diagnosis (Supplemental Table S1). Sixty-five (57.5%) of these cases were male. Thirty-three (29.5%) were associated with emm1 (including subtypes) and sixteen (14.3%) were associated with emm12 (including subtypes). Thirty-five (31.3%) of the cases with S. pyogenes pharyngitis and invasive S. pyogenes disease were 14 years of age and under. Of these 35 cases of S. pyogenes pharyngitis linked to invasive disease in children, 45.7% (16/35) were invasive emm1 (including subtypes) and 20% (7/35) were invasive emm12 (including subtypes) (Supplemental Table S1).
From 1 January 2018 to 31 December 2023, antimicrobial susceptibility assays were performed on 3 179 invasive S. pyogenes isolates (2018–442 isolates, 2019–433, 2020–469, 2021–398, 2022–519, and 2023–918). All isolates were fully susceptible to penicillin and vancomycin. Overall, erythromycin and clindamycin resistance in invasive S. pyogenes cases were significantly higher in 2023 vs. 2018–2019 (p < 0.0001). Antimicrobial resistance to erythromycin ranged from a low of 5.3% in 2021 to a high of 15.1% in 2023 (Table 1). This is similar to clindamycin with a low of 4.0% in 2021 and a high of 13.3% in 2023 (Table 1). The most common emm types associated with clindamycin and erythromycin resistance were emm92, 77, 83, and 53 (Supplemental Table S2). Together, these four emm types accounted for 71.4% of erythromycin-resistant isolates and 69.3% of clindamycin-resistant isolates. Of the 591 isolates of emm1 and 12 over the 6 years surveyed, only five were erythromycin resistant and three clindamycin resistant.
Table 1. Erythromycin and clindamycin resistance (%) 2018–2023
Erythromycin and clindamycin resistance was significantly higher in 2023 vs. 2018–2019 (p < 0.0001).
Genome sequencing was completed for 549 invasive S. pyogenes isolates collected from 1 November 2022 to 31 May 2023 (all emm types) (Figure 7 and Supplemental Table S3). There were 192 speA isolates (35.0%), 301 speC isolates (54∙8%), 80 isolates with both speA and speC (14.6%), and 302 with spd1 (55.0%). Of the 134 emm1 isolates sequenced, the genomic analysis showed 79 isolates belonged to the M1UK lineage based on 27 single nucleotide variants in the core genome (59.0% of emm1 cases) and 54 isolates belonged to the M1global strain (40.3%) with one case as M1intermediate (Figure 7 and Supplemental Table S3). Ninety-eight percent of M1 isolates possessed the speA gene whereas two isolates, (an M1UK and an M1intermediate) did not (Figure 8a and Supplemental Table S3). The speC gene was present in 33.6% of M1 isolates. Interestingly, the speC gene was present in a distinct branch of the M1UK group and absent in all M1global isolates except for one isolate (Figure 8a and Supplemental Table S3). The emm12 S. pyogenes isolates exhibited higher diversity in comparison to the emm1 stains (Figure 8b). Only 19 isolates of the 549 sequenced had all three ssa, speC, and spd1 genes, (three emm12.0, four emm12.4, 11 emm4.0, and one emm58.0) (Supplemental Table S3).
Figure 7. Phylogenetic tree analysis of 549 invasive Streptococcus pyogenes isolates from November 2022 to May 2023. A maximum likelihood phylogenetic tree was constructed from the core genomes using a GTR + F + I + G4 model. Emm types are indicated, sequence types are coloured by nodes, and the M1UK variant is indicated by a star-shaped node. Bars in concentric circles represent the presence of the sic gene followed by 12 different exotoxin genes found in S. pyogenes.
Figure 8. Phylogenetic trees of (a) 134 emm1 invasive Streptococcus pyogenes isolates and (b) 106 invasive emm12 isolates all collected from November 2022 to May 2023. Maximum likelihood phylogenetic trees constructed with core gene alignment using a HYK + F + I model for emm1 and K3Pu + F + I model for emm12. (a). The phylogenetic tree shows 54 M1global and 80 M1UK S. pyogenes isolates. Sequence types are coloured by nodes, and the M1UK variant is indicated by a star-shaped node. Bars in concentric circles represent the presence of sic gene followed by 12 different exotoxin genes found in S. pyogenes. (b). Phylogenetic tree of emm12 isolates in Alberta.
Discussion
The data presented for pharyngitis specimens over the 6 years surveyed showed yearly fluctuating changes in positivity rates for S. pyogenes. Prior to the implementation of Public Health interventions for COVID-19, pharyngeal S. pyogenes positivity rates showed a predictable seasonality trend as previously reported by others with the highest rates occurring in winter months and lower in summer [Reference Kline4, Reference Kennis31, Reference Frenck32]. The implementation of Public Health interventions for COVID-19 reduced these rates significantly starting in 2020 [Reference Hinshaw29]. It was after these restrictions were lifted that pharyngitis S. pyogenes positivity rates sharply increased peaking in March 2023 [30]. This should not be surprising as these interventions were targeted towards the respiratory transmission of SARS-CoV-2, which is also a similar transmission route for S. pyogenes. It is unusual though to have such a large increase in cases as it could have been predicted that case numbers would have returned to pre-COVID-19 levels once restrictions were lifted.
Breaking down S. pyogenes pharyngitis by age group showed specimens were the most prevalent in the 0–9-year-old age group. A study by Mponponsuo et al., analyzed cases of S. pyogenes pharyngitis in Calgary, Alberta from 2010 to 2018 [Reference Mponponsuo3]. This study included 1 074 154 tests, of which 16.6% were positive for S. pyogenes, similar to our study. These investigators found the 5–14 age group had the highest positivity rate (42.2%) [Reference Mponponsuo3]. In a recent study by Kline et al., this group found that the 0–4 and 5–9 age groups also had the most frequent S. pyogenes pharyngitis visits to healthcare providers of all ages [Reference Kline4]. It is concerning that for the 0–9-year-old age group in our study, rates approached nearly 50% positivity, a very high rate of S. pyogenes pharyngitis. A possible reason for this sharp rise in S. pyogenes pharyngitis may include more mixing of this age group as COVID-19 restrictions were lifted and children returned to daycares and schools.
The increase in S. pyogenes pharyngitis specimens was mirrored by increases in S. pyogenes invasive disease. The incidence of invasive disease rose sharply from 9.8/100 000 in 2022 to 19/100 000 in 2023, a significant increase. It should be noted that 2023 was not the first year that the incidence of invasive S. pyogenes disease began to increase. The incidence of invasive S. pyogenes started to rise in 2014, peaking in 2020. However, the magnitude of the increase over this six-year period was not at the same level as the increase in 2023. The increase in 2023 reflects increases in invasive S. pyogenes disease seen elsewhere such as the UK, other countries in Europe, the USA, and Australia [Reference Alcolea-Medina10, Reference Guy14, Reference Rodriguez-Ruiz33, Reference Davies34]. The reasons for this steady climb in invasive disease since 2014 are not completely clear and potentially involve several factors. These may include the introduction of new strains, greater vulnerability in the population, and lifting of COVID-19 restrictions leading to increases in population density. Examples include educational institutions resuming in-class instruction and removal of the requirement for masking in areas such as shopping locations.
Prior to the SARS-CoV-2 pandemic, emm1 and 12 were the most frequent emm types associated with invasive disease in Alberta, along with other emm types [Reference Tyrrell35]. During the COVID-19 restriction period, these two emm types almost disappeared as S. pyogenes bacteria responsible for invasive disease. Once restrictions were lifted, both emm types returned in increased prevalence as the predominant emm types and at higher rates compared to rates pre-COVID-19. Reasons for the emm1 and emm12 resurgence are likely multifactorial including lifting of Public Health interventions thereby allowing the potential for increased respiratory transmission of these emm types. It is interesting that both emm1 and 12 are part of the A-C cluster (emm1:A-C3 and emm12:A-C4), which is considered a cluster associated with the throat as opposed to emm type clusters associated more with cutaneous disease [Reference Sanderson-Smith36]. The only other A-C emm cluster type found in Alberta from cases of invasive S. pyogenes was emm3, however, invasive disease caused by this emm type has not occurred to the same extent as emm1 and emm12 for reasons which are not well understood.
The collection of S. pyogenes pharyngitis data provided an opportunity to determine the rate of S. pyogenes pharyngitis progressing to invasive disease for the Alberta population. For every 100 000 positive S. pyogenes pharyngitis specimens, approximately 61 cases progressed into invasive disease over the six-year period surveyed. This is a crude estimate of the risk of developing invasive disease in patients with pharyngitis as several events occurring during the survey period could have affected the results. A major event was the SARS-CoV-2 pandemic as it is likely individuals may have not sought S. pyogenes pharyngitis testing due to adherence to isolation requirements. This coupled with an apparent decrease in S. pyogenes transmission during pandemic years may have skewed the estimate during the pandemic. Also, physicians may not have collected a specimen for a laboratory diagnosis and alternatively prescribed based on symptoms. It should also be noted that pharmacies in Alberta can perform point-of-care tests for S. pyogenes pharyngitis. Those cases of S. pyogenes pharyngitis diagnosed in pharmacies are not captured in the patient’s provincial health record. While these and other variables may affect our estimate of invasive disease occurring during an episode of pharyngitis, an average of 61 cases of invasive disease per every 100 000 cases of pharyngitis over a six-year period we believe is plausible.
Both erythromycin and clindamycin resistance in Alberta for invasive S. pyogenes ranged from 4–9% from 2018 to 2022 however, in 2023, rates significantly increased to between 14–16%. These rates are higher than what we have previously reported for Canada (2018–2022) and likely reflect regional differences in circulating strains in Alberta [Reference Golden37]. Similar to our Alberta study, predominant resistant emm types, emm11, 53, 77, 83, and 92, also have been reported as significant erythromycin-resistant emm types in Canada and the USA [Reference Golden37, Reference Li38]. It is interesting that emm92 is the most frequently encountered erythromycin/clindamycin resistant emm type as this emm type has been shown to be associated with erythromycin/clindamycin resistant emm92 strains in adult IV drug users in the USA [Reference Powell39]. Efforts are now being made to determine the demographics of the emm92 iStrep A isolates in our survey study.
During the global increase in iStrep A disease, much interest has focused on the M1UK S. pyogenes bacteria as it rapidly expands throughout the world replacing M1global as the predominant M1 type in just a few short years [Reference de Gier11, Reference Li40-Reference Vieira42]. M1UK was first detected in Alberta in 2016 and is now broadly distributed across Canada [Reference Golden37, Reference Demczuk43]. For the S. pyogenes isolates for which we sequenced (November 2022 to May 2023), M1UK accounted for close to 60% of the invasive M1 isolates making it the predominant emm type strain over this period. Past reports have shown that M1UK produces high levels of the SpeA exotoxin in comparison to the M1global strain [Reference Lynskey19]. Both SpeA and SpeC exotoxin have been shown to be associated with increased fitness and virulence of S. pyogenes strains causing disease [Reference Lynskey19, Reference Brouwer44, Reference Kasper45]. All M1 isolates for which genomic sequencing was completed possessed the speA toxin gene except for two M1UK isolates. The speC gene was less frequent in the M1 isolates.
In summary, rates of both S. pyogenes pharyngitis and invasive S. pyogenes disease have substantially increased in Alberta, Canada post-COVID-19. This increase has persisted for over a year since SARS-CoV-2 restrictions were lifted. Invasive disease rates have been driven by predominately two emm types, emm1 and emm12 with M1UK more frequent than M1global.
Supplementary material
The supplementary material for this article can be found at http://doi.org/10.1017/S0950268824001857.
Data availability statement
The data that support the findings of this study are available on request from the corresponding author. Restrictions may apply to the availability of personal data linked to patient information.
Acknowledgements
We thank the clinical diagnostic microbiology laboratories in Alberta for identifying invasive Strep A isolates and submitting these to the Provincial Public Health Laboratory for emm typing.
Author contribution
GJT planned the study, obtained ethics, analyzed the data, and wrote the first draft of the manuscript. EM analyzed the pharyngitis data, provided statistics, and assisted in writing. MC and VL performed the genomic analysis, reviewed the manuscript, and assisted in writing. ARG and IM conducted genome sequencing, reviewed the manuscript, and assisted in writing.
Competing interest
The authors declare none.
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