Invasive group A streptococcal (iGAS) surveillance in Island Health, British Columbia, 2022

Background Invasive group A streptococcal disease (iGAS) is caused by Streptococcus pyogenes group A bacteria. In 2022, multiple disease alerts for iGAS in the Island Health region, in the context of increased infections in the paediatric population in Europe and the United States, prompted further investigation into local trends. This surveillance study summarizes epidemiological trends of iGAS in the region covered by Island Health, a regional health authority in British Columbia, in 2022. Methods In British Columbia, iGAS is a reportable disease; all confirmed cases are reported to the regional authority and the provincial health authority (BC Centre for Disease Control). Island Health’s iGAS surveillance system is passive and collects information on cases that are identified through laboratory testing. Surveillance data were summarized for 2022 and compared with historical data from 2017–2021. Results In 2022, the incidence rate was 11.4 cases per 100,000 population (n=101), the highest observed rate in the last six years. The median age of cases was 53 years, with a range of 0–96 years, and 64% of cases were male. The highest risk of infection was reported in men 40–59 years of age, with an incidence rate of 21.3 cases per 100,000 population. The most common emm types were emm92 (n=14), emm49 (n=13), and emm83 (n=12). Overall, 85% (n=86) of cases were hospitalized, 21% (n=21) were admitted to the intensive care unit, and 6% (n=6) died. Conclusion This study highlights that the incidence of iGAS in the Island Health region continued to increase throughout the coronavirus disease 2019 (COVID-19) pandemic, reaching its highest annual rate in 2022. In contrast to reports from Europe and the United States, there was no notable increase in infections in the paediatric population. Given the sustained increase in iGAS activity, continued monitoring and description of the epidemiology of these cases on a regular basis is imperative.


Introduction
Group A streptococcal disease (GAS) is caused by Streptococcus pyogenes group A bacteria (1). A GAS infection is considered invasive when bacteria is detected at a sterile site within the body (1). Invasive group A streptococcus (iGAS) causes severe and in some cases life-threatening illness (1). In 2022, multiple disease alerts for iGAS in Island Health, a regional health authority in British Columbia, in the context of reports of increased infections in the pediatric population in Europe and the United States, prompted further investigation into local trends (2,3). The following surveillance report summarizes epidemiological trends of iGAS in Island Health, British Columbia in 2022.

Methods Population
Island Health is one of five regional health authorities in British Columbia. The Island Health region has a population of about 860,000 people, which includes residents of Vancouver Island, the Islands in the Salish Sea and the Johnstone Straight, and the mainland communities north of Powell River and south of Rivers Inlet ( Figure 1) (4). The region is divided into three health service delivery areas (HSDAs): North, Central and South Island.

Case definitions Confirmed case
Laboratory confirmation of infection with or without clinical evidence of invasive disease: isolation of group A streptococcus (S. pyogenes) from a normally sterile site, or demonstration of S. pyogenes DNA by an appropriately validated nucleic acid test from a normally sterile site (5).

Probable case
Clinical evidence of invasive disease in the absence of another identified etiology and with non-confirmatory laboratory evidence of infection: isolation of group A streptococcus from a non-sterile site, or positive group A streptococcus antigen detection (5).

Surveillance methods
In British Columbia, iGAS is a reportable disease; all confirmed cases are reported to the regional health authority and then to the BC Centre for Disease Control (BCCDC). Island Health's iGAS surveillance system is a passive case-based system that relies on the collection of information about cases that are identified through laboratory testing. Laboratory testing of iGAS is conducted locally at Island Health laboratories. Positive bacterial cultures are then sent to the BCCDC Public Health Laboratory for confirmatory testing. Subtyping (emm typing) of all isolates is conducted by the Canadian National Microbiology Laboratory (NML). Information on case demographics, clinical progression of illness, and risk factors are collected using a standardized surveillance form.
Island Health case-level data were extracted from BCCDC's Public Health Reporting Data Warehouse on February 1, 2023, at 12:00 p.m. PST. The case line list included episode date and information on age, sex, risk factors, and outcomes. The episode date is equal to the onset date if available. If the onset date is not available, then the clinical diagnosis date is used, followed by the earliest of specimen collection date, laboratory result date, or report date.

Data analysis
All analyses were performed using R version 4.1.1 and RStudio version 1.4.1717. Trends in case counts, incidence rates, geographic distribution, demographics, severity, and risk factors were summarized for 2022 and compared with historical data from 2017-2021. Population denominators were used to calculate rates.

Trends in case counts and rates
Incidence rates of iGAS in the Island Health region have been increasing since 2019 ( Figure 2). From 2017 to 2022, incidence rates ranged from 6.7 cases to 11.4 cases per 100,000 population. In 2022, 101 confirmed cases of iGAS were reported in the Island Health region. The incidence rate was 11.4 cases per 100,000 population, which was  The number of reported cases ranged from 3-15 cases per month (incidence range: 0.3 cases to 1.7 cases per 100,000 population) ( Figure 3). The highest observed cases and monthly incidence rates were in January, November, and December (15 cases, incidence rate: 1.7 cases per 100,000 population). In January and November, the number of cases and incidence rate exceeded the maximum cases and incidence seen in the previous five years. The number of cases in these months were 2.5 times and 1.9 times the maximum number of cases reported in the previous five years.

Geographic distribution
The incidence rates in 2022 ranged from 7.9 to 16.0 cases per 100,000 population in the three HSDAs ( Figure 4). The incidence rates in both North and Central Island exceeded the rates for the entire Island Health Region. Since 2019, the incidence rates in Central Island have been increasing. In North Island, the incidence rates increased from 2019 to 2021 and decreased in 2022. In South Island, the incidence rates decreased from 2019 to 2021 and increased in 2022. In 2022, the highest incidence rate occurred in Central Island at 16.0 cases per 100,000 population. Forty-nine cases were reported from Central Island, which is an increase of 19 cases (63% increase) compared to the number reported in the previous year.     Note: There is an issue of small numbers when breaking down cases by the health service delivery areas (HSDA), specifically for North Vancouver Island. Calculated rates in this HSDA are based on numerators with fewer than 20 cases. Therefore, these rates are unstable and should be interpreted with caution. Fluctuations in these values may indicate random variation rather than significant change in the rate

Demographic distribution
The median age of cases was 53 years, with a range of 0-96 years and 64% of cases were male. The distribution and risk of infection were the highest in men (distribution: 64%, incidence: 15.0 cases per 100,000 population) and individuals 40 years of age and older (distribution: 76%, incidence: 14.7 cases per 100,000 population) ( Table 1). The highest incidence was reported in men 40-59 years of age (21.3 cases per 100,000 population) ( Figure 5).

Severity
Twenty-seven percent of cases reported in 2022 were clinically classified as severe ( Table 3). Severe cases are defined as cases of streptococcal toxic shock syndrome (STSS), soft-tissue necrosis (including necrotizing fasciitis, myositis, or gangrene), meningitis, GAS pneumonia, or death directly attributable to GAS infection (6). Overall, 85% of cases were hospitalized, 21% were admitted to the intensive care unit (ICU), and 6% died ( Table 4). The proportion of cases admitted to the hospital and ICU was below the average number admitted in the previous five years (hospitalizations: average=90%, range=85%-93%; ICU admissions: average=23%, range=15%-32%). The case fatality rate was the same as the average case fatality rate reported in the previous five years (average=6%, range=4%-8%). The deaths reported in 2022 occurred in men and women 52-89 years of age (median age=73 years, 67% female). All cases had multiple risk factors reported (median number of reported risk factors=4, range=2-5). Five different emm types were prevalent amongst these fatal cases: 74, 81, 83, 92, and 43.
There was no dominant emm type reported among severe cases. For both severe and non-severe cases, the most common emm types were the same ( Figure 6).

Risk factors
The most common reported risk factors among cases were having a skin infection, 47% (n=47) and having a wound, 46% (n=46) ( Table 5). Compared to the previous five years, skin infections, wounds, alcohol use disorder, unstable housing, chronic cardiac conditions, chronic respiratory conditions, and immunocompromised conditions were reported more frequently in 2022, while injection drug use was reported less frequently. Among severe cases (n=27), the most common reported risk factors were having a wound, 52% (n=14); using substances, 52% (n=14); or having a skin infection, 44% (n=12) ( Table 6). For non-severe cases (n=74), the most common reported risk factors were having a skin infection, 47% (n=35) or having a wound, 43% (n=32).  Note: There is an issue of small numbers when breaking down cases by age group and sex. Calculated rates where the numerator is less than 20 are unstable and should be interpreted with caution. Fluctuations in these values may indicate random variation rather than significant change in the rate  Figure 6: Distribution of streptococcal pyogenes emm types by severity, Island Health, 2022

Discussion
In 2022, 101 confirmed cases of iGAS were reported in the Island Health region, corresponding to an incidence rate of 11.4 cases per 100,000 population; the highest rate reported in the last six years and above the preliminary annual provincial rate (8.5 cases per 100,000 population). Since 2019, the incidence of iGAS has been increasing in the Island Health region. This includes throughout the pandemic period when implemented non-pharmaceutical containment measures were also associated with a decrease in invasive respiratory diseases worldwide (7). Provincially, in British Columbia, rates of iGAS have been higher than expected since 2017, with the incidence in the last six years remaining stable (8). Globally, an increase in the incidence of iGAS over time has also been observed in many countries, including Canada (9-12). Previous analyses have hypothesized that the observed increase is linked to both the increase in genetic diversity of circulating emm types and compounding societal risk factors, such as homelessness and substance use (10,(13)(14)(15)(16)(17). Although the factors associated with the increased incidence seen in the Island Health region since 2019, and particularly in 2022, are not completely clear, it is likely that multiple factors have contributed to the observed trends. This includes increased circulation of respiratory viruses, an increase in the diversity in circulating emm types, and the impact of the coronavirus disease 2019 (COVID-19) pandemic on community services, specifically an increased demand paired with reduced capacity and availability.
In December 2022, several European countries and the United States reported recent increases in infections of iGAS in children (2,3). Similar to the provincial picture in British Columbia, demographic analysis of Island Health cases showed no notable increase in infections among the paediatric population (8). The highest risk of infection was observed in men 40 years of age and older. While men 40 years of age and older appear to be at a higher risk for iGAS in 2022, further analysis on iGAS in this demographic group would contribute to understanding whether this is a confounding factor, since other risk factors, such as substance use, are known to be higher in this population (18)(19)(20).

Limitations
When breaking down case numbers by subgroups, cell sizes become small. Calculated rates where the numerator is less than 20 are unstable and should be interpreted with caution. The descriptive analyses where cases are broken down by month, by HSDA (applies to North Island), by age (applies to age categories younger than 20 years of age), and by age and sex are affected by small cell sizes. Fluctuations in these values may indicate random variation rather than significant change in the rate. As well, information on risk factors is predominantly collected through chart reviews. These reviews may not capture the full medical or social history of each case, therefore risk factors among iGAS cases may be under-reported. The regional data presented in this report have undergone data quality assessment by Island Health, but data reconciliation processes for the provincial data are underway for cases reported for 2019 through 2022. The provincial rates shown are based on preliminary numbers, and final numbers and rates for the province may change. Lastly, this report includes data from pandemic response years and an analysis on the impact of the response on the completeness and trends of respiratory surveillance data in the Island Health region has not yet been conducted. It is likely that due to the response, both burden of disease and data completeness decreased, therefore, observed trends during these years might have been higher than reported in this publication. This would affect the interpretation of observed trends in 2022 in comparison to the previous five years. Despite these limitations, this summary contributes descriptive epidemiology that is important for understanding iGAS in the Canadian context.

Conclusion
Overall, this surveillance study characterizes cases of iGAS in the Island Health region in 2022 and compares these cases to those reported over the last five years. The study highlights that incidence of iGAS in the Island Health region continued to increase throughout the COVID-19 pandemic, reaching its highest annual rate in 2022. In contrast to reports from Europe and the United States, there was no notable increase in infections in the paediatric population. The findings of this report contribute to the epidemiological characterization of iGAS in Canada. Given the continued local, provincial, and national increase in incidence of iGAS, it is imperative that the epidemiology of these cases continues to be monitored and described annually.