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High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada

High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in... Open Forum Infectious Diseases MAJOR ARTICLE High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada 1 1 2 3 3 1 3,4 Natalie Bocking, Cai-lei Matsumoto, Kassandra Loewen, Sarah Teatero, Alex Marchand-Austin, Janet Gordon, Nahuel Fittipaldi, and Allison McGeer 1 2 3 4 Sioux Lookout First Nations Health Authority, Canada; Anishinaabe Bimaadiziwin Research Program, Sioux Lookout, Canada; Public Health Ontario, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Canada Background. Worldwide, indigenous populations appear to be at increased risk for invasive group A streptococcal (iGAS) infec- tions. Although there is empirical evidence that the burden of iGAS disease is significant among remote First Nations communities in Northwestern Ontario, Canada, the epidemiology of iGAS infections in the area remains poorly characterized. Methods. Individuals that met case definition for iGAS disease and whose laboratory specimens were processed by Meno Ya Win Health Centre in Sioux Lookout, Canada or who were reported to Thunder Bay District Health Unit, Canada were identified for the period 2009 to 2014. Case demographics, clinical severity, comorbidities, and risk factors were collected through chart review. Strain typing and antibiotic susceptibility were determined when possible. Basic descriptive statistics were calculated. Results. Sixty-five cases of iGAS disease were identified, for an annualized incidence of 56.2 per 100 000. Primary bacteremia was present in 26.2% of cases, and cellulitis was identified in 55.4% of cases. e Th most common comorbidities identified were diabetes (38.5%) and skin conditions (38.5%). Prevalent risk factors included alcohol dependence (25%). Fourteen different emm types were identified among 42 isolates, with the most common being emm114 (17.4%), emm11 (15.2%), and emm118 (13.0%). Resistance to erythromycin and clindamycin was found in 24.6% of isolates. Conclusions. Rural and remote First Nations communities in Northwestern Ontario experience iGAS infections at a rate 10 times the provincial and national average. Compared with other North American series, a lower proportion of isolates causing infection were of emm types included in candidate GAS vaccines. Keywords. health equity; indigenous health; invasive group A Streptococcus. β-hemolytic group A  Streptococcus (GAS) (also known as incidence of iGAS among First Nations, Inuit or Metis (collec- Streptococcus pyogenes) is a Gram-positive bacteria that causes a tively referred to as the indigenous population of Canada). range of human illness and contributes to significant morbidity and Northwestern Ontario, Canada, is home to 26 remote on-re- mortality worldwide. Severe manifestations of invasive GAS include serve First Nations communities, comprising approximately streptococcal toxic shock syndrome and necrotizing fasciitis [1]. 22 000 people (approximately 12% of registered First Nations High rates of invasive bacterial diseases, including invasive in Ontario), who occupy a geographic area the size of France. GAS (iGAS) disease, are frequently reported among indig- Primary care, acute care, and public health services are fragmented enous populations in different countries, including Canada, and complicated by historical and political jurisdictional barriers. the United States, Australia, and New Zealand [2–5]. A recent Sioux Lookout Meno Ya Win Health Centre (SLMHC) is the pri- publication by the Public Health Agency of Canada from the mary referral hospital for all 26 communities; however, critically International Circumpolar Surveillance system reported a ill patients may be transferred directly from their home commu- rate of iGAS among indigenous peoples in Northern Canada nity to tertiary centers in Thunder Bay, Ontario or Winnipeg, approximately 2.5-fold higher than that of other Canadians [2]. Manitoba. The First Nations and Inuit Health Branch of Health No other peer-reviewed publications have characterized the Canada is primarily responsible for surveillance and communica- ble disease control for on-reserve First Nations in Canada. Recent publications have reported high rates of invasive Received 18 August 2016; editorial decision 7 November 2016; accepted 15 November 2016. Correspondence: N. Bocking, MD, MIPH, 3rd Floor - 54 Front Street, P.O. Box 1300, Sioux bacterial diseases among remote on-reserve First Nations in Lookout, Ontario, P8T 1B8, Canada (natalie.bocking@slfnha.com). Northwestern Ontario [6, 7]. We hypothesized that the burden of Open Forum Infectious Diseases illness related to iGAS infections is particularly high in this region. © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ METHODS by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work All GAS-positive cultures processed by SLMHC between is properly cited. For commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofw243 January 1, 2009 and December 31, 2014 were extracted from Invasive Group A Strep in Northern Ontario • OFID • 1 hospital electronic laboratory archives. Possible iGAS cases Sanger sequencing using previously described primers and con- were identified if (1) the isolate was recovered from a normally ditions [11]. sterile site (defined below), (2) the patient was admitted to hos- Data were stored within Excel (Microsoft Office 2010; pital, or (3) the specimen was obtained in the operating room. Microsoft, Redmond, WA) and analyzed using SPSS version Chart reviews were completed on all possible cases to determine 21 (IBM, Armank, NY). Basic descriptive statistics were com- whether patients met the Ontario Provincial Case Definition pleted with confidence intervals (CIs) where appropriate. for iGAS [8]. The case definition included GAS isolated from Denominator data for the 26 communities were obtained normally sterile sites (blood, joint [excluding bursa], cerebro- from First Nations Inuit Health Branch, extracted from the spinal, pleural, peritoneal, pericardial, and deep tissue/abscess Indian Registry System. Overall incidence was determined specimens obtained during surgery) or GAS isolated from a from an average of the crude rates each year and calcu- nonsterile site with evidence of clinical severity (toxic shock lated per 100 000 population. Ethics approval was obtained syndrome, necrotizing fasciitis, pyomyositis, gangrene, men- through the SLMHC Research Review and Ethics Committee ingitis, GAS pneumonia, or death directly attributed to iGAS). as well as the Research Ethics Board from the University of In order to capture iGAS cases transferred directly from Toronto, Canada. Sioux Lookout to Thunder Bay, cases reported to Thunder Bay RESULTS District Health Unit (TBDHU) with a primary residence from one of the 26 communities were identified. As one of 36 public Overall, 6674 specimens processed between 2009 and 2014 health units in Ontario, TBDHU has undertaken active surveil- yielded GAS, and 65 cases of iGAS disease were identified. The lance for iGAS since an outbreak of emm59 iGAS in 2008 [9]. number of cases per year ranged from 9 to 18. The annualized Duplicates of cases already identified through SLMHC were incidence of iGAS was 56.2 per 100 000 (95% CI, 35.4–76.9). The removed. Details on cases transferred directly to Winnipeg mean age of cases was 40 years, with a range of <1 to 87 years. were unavailable. There was a bimodal distribution of age-specific incidence with Information collected by chart review included basic demo- peaks in the 0–19 and 40–59 age groups (Figure 1). Eleven cases graphics, specimen details, clinical severity, comorbidities, risk (17%) occurred among infants less than 1 year of age. factors, and antibiotic sensitivity profiles. Streptococcal toxic e m Th ajority of iGAS cases occurred during the months of shock syndrome was defined as previously described [10]. October to March; however, there was no statistically signifi- History of skin condition included chronic dermatitis/wound cant seasonal trend (Figure 2). The annual proportion of wound causing breaks in skin integrity. Cases identified as nosocomial swabs positive for GAS ranged from 40% to 48%. The average were excluded. In addition, the number of throat and wound annual rate of wound swabs positive for GAS was 61 episodes swabs that yielded GAS and were submitted to SLMHC from per 1000 population. Rates increased between 2009 and 2013 the 26 communities was obtained for each year of the study. and decreased in 2014. e Th average annual rate of throat swabs Crude incidence (removing duplicate isolates occurring within positive for GAS was 46.6 episodes per 1000 population. Rates a 14-day period) and temporal trends of positive throat and increased between 2010 and 2014. Wound swabs positive for wound swabs were assessed. The emm types of isolates from GAS were more prevalent during the summer months, whereas confirmed iGAS cases were determined through traditional GAS-positive throat swabs did not demonstrate a seasonal 30 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0 0.0 <1 1-19 20 - 39 40 - 59 60+ Age Range of Cases Figure 1. Incidence of invasive group A streptococcal cases in 26 rural and remote First Nations communities in Sioux Lookout area between 2009 and 2014 by age. 2 • OFID • Bocking et al Number of Cases Average annual incidence (cases per 100,000 population 12 600 10 500 8 400 Cases of iGAS 6 300 Throat Swab Rate 4 200 Wound Swab Rate 2 100 0 0 Month Case Occurred Figure 2. Temporal distribution of invasive group A streptococcal (iGAS) cases compared with group A streptococcal (GAS)-positive throat swabs and GAS-positive wound swabs submitted from 26 rural and remote First Nations communities in Northwestern Ontario between 2009 and 2014. trend. There was no detectable association between trends of alcohol dependence also had skin conditions, and 5 of 7 persons iGAS incidence and either positive wound swab or positive reporting intravenous drug use were also dependent on alcohol. throat swab rates. Overall, 49 (75.4%) cases had positive blood cultures; among e 2 m Th ost common comorbidities identified were diabetes the 13 with blood cultures that were negative or not done, 9 mellitus (38.5%) and skin conditions (38.5%) (Table  1). The (13.8%) had positive deep tissue/abscess specimens (taken most prominent other potential risk factor was alcohol depend- aseptically in the operating room), 5 (7.7%) had positive syn- ence (25%). There was significant overlap in underlying condi- ovial fluid, and 1 (1.5%) had positive peritoneal fluid cultures. tions: among the 25 patients with underlying diabetes, 10 had One case had a nonsterile specimen positive for GAS with evi- skin conditions, 3 had alcohol dependence, and 2 had both skin dence of clinical severity. Primary bacteremia was present in 17 conditions and alcohol dependence. Seven of 16 persons with (26.2%) cases (Table  2); 1 postpartum bacteremia was identi- fied. Cellulitis was identified at the time of presentation in 36 (55.4%) cases, and septic arthritis was present in 6 (9.2%) cases. Table  1. Characteristics of 65 iGAS Cases Identified From 26 Rural and Streptococcal toxic shock syndrome and necrotizing fasciitis Remote First Nations Communities in Northwestern Ontario Between 2009 each occurred in 6 (9.2%) cases, and the crude 28-day case-fa- and 2014 tality rate for all iGAS was 6.2%. No cases of nosocomial infec- Case Characteristics Number (%) tion were identified. Antibiotic susceptibility profiles were available for 59 iso- Chronic underlying medical conditions Diabetes 25 (38.5) lates. All isolates were sensitive to penicillin. Sixteen isolates Skin conditions 25 (38.5) (24.6%) were resistant to both erythromycin and clindamy- Coronary artery disease 6 (9.2) cin. Of the 65 iGAS cases, 46 isolates were available for emm Active cancer 3 (4.6) typing. Among these, 14 different emm types were identified Peritoneal dialysis* 3 (4.6) (Table 3). The most common emm types were emm114 (17.4%), Hepatitis C 3 (4.6) Liver failure 3 (4.6) emm11 (15.2%), emm118 (13.0%), emm68 (10.9%), and emm82 Connective tissue disorder 3 (4.6) (10.9%). emm type variability over time was observed. Of the Other potential risk factors 16 isolates demonstrating resistance to erythromycin and clin- Alcohol dependence 16 (24.6) damycin, 7 were identified as emm11 and 5 were identified as Previous positive wound swab for GAS 16 (24.6) emm114. The cases associated with these isolates were from dif- Regular use of nonsteroidal anti-inflammatory drug 11 (16.9) ferent communities and temporally unrelated. Injection drug use 8 (12.3) Other substance use 6 (9.2) Underhoused/homeless/living in shelter system 5 (7.7) DISCUSSION Varicella within the previous month 1 (1.5) Abbreviations: GAS, group A streptococcal; iGAS, invasive group A streptococcal.  The incidence of iGAS in Canada increased significantly over *Patients must move from their rural or remote community to a larger center (primarily the last decade (from 2.81 to 4.03 per 100 000 between 2000 Thunder Bay) to receive hemodialysis. Only peritoneal dialysis is available at community level. and 2009)  [12]. In 2013, the Canadian and Ontario rates for Invasive Group A Strep in Northern Ontario • OFID • 3 Number of Cases Avergae annual rate per 100,000 population Table 2. Clinical Features of 65 iGAS Cases Identified From 26 Rural and Northwestern Ontario [9]. The high burden of substance use Remote First Nations Communities in Northwestern Ontario Between 2009 among indigenous peoples in Canada is recognized nation- and 2014 ally as a legacy of historical assimilation policies, multigen- erational trauma, and systemic racism [16]. The prevalence Clinical Features Number (%) of alcohol dependence among iGAS cases in this study (25%) Culture source was consistent with iGAS epidemiology for both indigenous Blood 49 (75.4) Other sterile source 15 (23.1) and non-indigenous populations in Northern Australia [17]. Nonsterile source 1 (1.5) Prescription drug abuse, particularly injection drug use (IDU), Clinical presentation is a significant issue facing many of the communities included Cellulitis 36 (55.4) in this study [18, 19]. However, only 12.3% of cases in this study Primary bacteremia 17 (26.2) were identified as having a history of IDU. Although it is likely Septic arthritis 6 (9.2) underreported, this proportion is consistent with iGAS epide- Pyomyositis 2 (3.1) Peritonitis 2 (3.1) miology reported in non-indigenous populations [20–22]. Meningitis 1 (1.5) Diabetes and skin conditions were found to be common comor- Pneumonia 1 (1.5) bidities among iGAS cases in this review. The prevalence of dia- Disease severity betes among First Nations in Canada is disproportionately high Streptococcal toxic shock syndrome 6 (9.2) compared with the non-indigenous population [23]. Given the Necrotizing fasciitis 6 (9.2) increased risk of iGAS associated with underlying diabetes, this Deceased 4 (6.2) contributes to increased risk for First Nation communities [24]. Abbreviations: iGAS, invasive group A streptococcal. In addition, high prevalence of skin conditions such as eczema and impetigo has been observed in many remote iGAS were 4.72 and 4.6 per 100 000 population, respectively First Nations communities [25]. It has been hypothesized [12, 13]. In contrast, the crude incidence rate of iGAS calculated in Northern Australia that a major risk factor for GAS bac- in this study among 26 rural and remote First Nations com- teremia in Aboriginal people is exposure to an overall high munities in Northwestern Ontario between 2009 and 2014 was burden of GAS infections, primarily skin infections such as more than 10 times higher at a rate of 56.2 per 100 000 popula- impetigo and pyoderma [3, 26]. These populations also expe- tion. Although significantly higher than the incidence of iGAS rience high prevalence of nonsuppurative sequelae to GAS among indigenous peoples in Northern Canada (2.25–20.44 per infection including acute rheumatic fever and poststreptococ- 100 000 population) [2], it is comparable to indigenous popula- cal glomerulonephritis [27, 28]. Although largely eliminated tions in Australia and New Zealand [3, 4, 14, 15]. from Canada, rheumatic fever in First Nations communities High prevalence of substance use has been thought to in Northwestern Ontario has been documented at rates con- be a contributing factor to overall higher rates of iGAS in sistent with Northern Australia (21.3 and 26 per 100 000, respectively) [29]. In Australia, the burden of GAS associated with skin and soft-tissue infections has been primarily related Table 3. emm types of 46 Cases of iGAS Identified From 26 Rural and Re- to inadequate and overcrowded housing [30, 31]. Disparities mote First Nations Communities in Northwestern Ontario Between 2009 in the social determinants of health, including inadequate and 2014 and overcrowded housing, are well documented public health issues facing First Nations communities in Northwestern emm types (N = 46) 2009 2010 2011 2012 2013 2014 Total No. Ontario [32–34]. 1 0 0 0 0 2 1 3 3 0 1 0 0 0 0 1 e p Th roportion of iGAS isolates that demonstrated resistance to 11 0 0 0 1 3 3 7 erythromycin (24.6%) and clindamycin (24.6%) was higher than 53 0 0 0 0 1 0 1 reported in other regions in Canada. A recent analysis of iGAS 59 0 0 0 0 1 1 2 cases from Peel and Toronto regions in Ontario demonstrated an 68 0 0 0 1 1 3 5 increase in erythromycin resistance from 2.2% in 1992–1995 to 80 0 0 0 1 0 0 1 19.5% in 2008–2010 and then to 7.5% in 2013 [35]. A 2011 publi- 82 0 0 2 3 0 0 5 83 0 0 0 1 0 0 1 cation from the Canadian province of British Columbia reported 87 0 0 0 0 0 1 1 resistance in all GAS isolates in 2011 to be 14.5% and 11.9% for 101 0 1 1 0 1 0 3 erythromycin and clindamycin, respectively [36]. 114 1 3 2 1 1 0 8 115 0 0 0 0 2 0 2 LIMITATIONS 118 0 0 0 1 4 1 6 Total 1 5 5 9 16 10 46 Data from Winnipeg could not be accessed; therefore, our data likely underestimates iGAS infection acquired in some Abbreviations: iGAS, invasive group A Streptococcus. 4 • OFID • Bocking et al 9. Athey TB, Teatero S, Sieswerda LE, et  al. High incidence of invasive group a communities. Given the small population size and reported case Streptococcus disease caused by strains of uncommon emm types in Thunder Bay, numbers, rates should be interpreted with caution. Risk factors Ontario, Canada. J Clin Microbiol 2016; 54:83–92. 10. Breiman RF, Davis JP, Facklam RR, et al. Defining the group A streptococcal toxic were self-identified in patient charts and may therefore be under- shock syndrome: rationale and consensus definitions. JAMA 1993; 269:390–91. estimated. Community population statistics from the Indian 11. Beall B, Gherardi G, Lovgren M, et al. emm and sof gene sequence variation in Registry System relies on individuals to register for “Indian sta- relation to serological typing of opacity-factor-positive group A  streptococci. Microbiology 2000; 146:1195–209. tus” and may thus underrepresent the true population of com- 12. Public Health Agency of Canada. Notifiable diseases on-line: invasive group munities, which would result in an overestimation of iGAS rates. A  streptococcal disease. Available at: http://dsol-smed.phac-aspc.gc.ca/dsol- smed/ndis/charts.php?c=pl. Accessed April 21, 2016. 13. Ontario Agency for Health Protection and Promotion (Public Health Ontario). CONCLUSIONS Reportable Disease Trends in Ontario, 2013. 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Available at: http://www.bccdc.ca/resource-gal- in group A  beta-haemolytic streptococci in two remote Northern Territory lery/Documents/Statistics%20and%20Research/Statistics%20and%20Reports/Epid/ Indigenous communities: implications for vaccine development. Vaccine 2010; AntimicrobialResistanceTrendsinBC_2011.pdf. Accessed 21 April 2016. 28:5301–5. 6 • OFID • Bocking et al http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada

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Oxford University Press
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© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
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10.1093/ofid/ofw243
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Abstract

Open Forum Infectious Diseases MAJOR ARTICLE High Incidence of Invasive Group A Streptococcal Infections in Remote Indigenous Communities in Northwestern Ontario, Canada 1 1 2 3 3 1 3,4 Natalie Bocking, Cai-lei Matsumoto, Kassandra Loewen, Sarah Teatero, Alex Marchand-Austin, Janet Gordon, Nahuel Fittipaldi, and Allison McGeer 1 2 3 4 Sioux Lookout First Nations Health Authority, Canada; Anishinaabe Bimaadiziwin Research Program, Sioux Lookout, Canada; Public Health Ontario, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Canada Background. Worldwide, indigenous populations appear to be at increased risk for invasive group A streptococcal (iGAS) infec- tions. Although there is empirical evidence that the burden of iGAS disease is significant among remote First Nations communities in Northwestern Ontario, Canada, the epidemiology of iGAS infections in the area remains poorly characterized. Methods. Individuals that met case definition for iGAS disease and whose laboratory specimens were processed by Meno Ya Win Health Centre in Sioux Lookout, Canada or who were reported to Thunder Bay District Health Unit, Canada were identified for the period 2009 to 2014. Case demographics, clinical severity, comorbidities, and risk factors were collected through chart review. Strain typing and antibiotic susceptibility were determined when possible. Basic descriptive statistics were calculated. Results. Sixty-five cases of iGAS disease were identified, for an annualized incidence of 56.2 per 100 000. Primary bacteremia was present in 26.2% of cases, and cellulitis was identified in 55.4% of cases. e Th most common comorbidities identified were diabetes (38.5%) and skin conditions (38.5%). Prevalent risk factors included alcohol dependence (25%). Fourteen different emm types were identified among 42 isolates, with the most common being emm114 (17.4%), emm11 (15.2%), and emm118 (13.0%). Resistance to erythromycin and clindamycin was found in 24.6% of isolates. Conclusions. Rural and remote First Nations communities in Northwestern Ontario experience iGAS infections at a rate 10 times the provincial and national average. Compared with other North American series, a lower proportion of isolates causing infection were of emm types included in candidate GAS vaccines. Keywords. health equity; indigenous health; invasive group A Streptococcus. β-hemolytic group A  Streptococcus (GAS) (also known as incidence of iGAS among First Nations, Inuit or Metis (collec- Streptococcus pyogenes) is a Gram-positive bacteria that causes a tively referred to as the indigenous population of Canada). range of human illness and contributes to significant morbidity and Northwestern Ontario, Canada, is home to 26 remote on-re- mortality worldwide. Severe manifestations of invasive GAS include serve First Nations communities, comprising approximately streptococcal toxic shock syndrome and necrotizing fasciitis [1]. 22 000 people (approximately 12% of registered First Nations High rates of invasive bacterial diseases, including invasive in Ontario), who occupy a geographic area the size of France. GAS (iGAS) disease, are frequently reported among indig- Primary care, acute care, and public health services are fragmented enous populations in different countries, including Canada, and complicated by historical and political jurisdictional barriers. the United States, Australia, and New Zealand [2–5]. A recent Sioux Lookout Meno Ya Win Health Centre (SLMHC) is the pri- publication by the Public Health Agency of Canada from the mary referral hospital for all 26 communities; however, critically International Circumpolar Surveillance system reported a ill patients may be transferred directly from their home commu- rate of iGAS among indigenous peoples in Northern Canada nity to tertiary centers in Thunder Bay, Ontario or Winnipeg, approximately 2.5-fold higher than that of other Canadians [2]. Manitoba. The First Nations and Inuit Health Branch of Health No other peer-reviewed publications have characterized the Canada is primarily responsible for surveillance and communica- ble disease control for on-reserve First Nations in Canada. Recent publications have reported high rates of invasive Received 18 August 2016; editorial decision 7 November 2016; accepted 15 November 2016. Correspondence: N. Bocking, MD, MIPH, 3rd Floor - 54 Front Street, P.O. Box 1300, Sioux bacterial diseases among remote on-reserve First Nations in Lookout, Ontario, P8T 1B8, Canada (natalie.bocking@slfnha.com). Northwestern Ontario [6, 7]. We hypothesized that the burden of Open Forum Infectious Diseases illness related to iGAS infections is particularly high in this region. © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ METHODS by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work All GAS-positive cultures processed by SLMHC between is properly cited. For commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofw243 January 1, 2009 and December 31, 2014 were extracted from Invasive Group A Strep in Northern Ontario • OFID • 1 hospital electronic laboratory archives. Possible iGAS cases Sanger sequencing using previously described primers and con- were identified if (1) the isolate was recovered from a normally ditions [11]. sterile site (defined below), (2) the patient was admitted to hos- Data were stored within Excel (Microsoft Office 2010; pital, or (3) the specimen was obtained in the operating room. Microsoft, Redmond, WA) and analyzed using SPSS version Chart reviews were completed on all possible cases to determine 21 (IBM, Armank, NY). Basic descriptive statistics were com- whether patients met the Ontario Provincial Case Definition pleted with confidence intervals (CIs) where appropriate. for iGAS [8]. The case definition included GAS isolated from Denominator data for the 26 communities were obtained normally sterile sites (blood, joint [excluding bursa], cerebro- from First Nations Inuit Health Branch, extracted from the spinal, pleural, peritoneal, pericardial, and deep tissue/abscess Indian Registry System. Overall incidence was determined specimens obtained during surgery) or GAS isolated from a from an average of the crude rates each year and calcu- nonsterile site with evidence of clinical severity (toxic shock lated per 100 000 population. Ethics approval was obtained syndrome, necrotizing fasciitis, pyomyositis, gangrene, men- through the SLMHC Research Review and Ethics Committee ingitis, GAS pneumonia, or death directly attributed to iGAS). as well as the Research Ethics Board from the University of In order to capture iGAS cases transferred directly from Toronto, Canada. Sioux Lookout to Thunder Bay, cases reported to Thunder Bay RESULTS District Health Unit (TBDHU) with a primary residence from one of the 26 communities were identified. As one of 36 public Overall, 6674 specimens processed between 2009 and 2014 health units in Ontario, TBDHU has undertaken active surveil- yielded GAS, and 65 cases of iGAS disease were identified. The lance for iGAS since an outbreak of emm59 iGAS in 2008 [9]. number of cases per year ranged from 9 to 18. The annualized Duplicates of cases already identified through SLMHC were incidence of iGAS was 56.2 per 100 000 (95% CI, 35.4–76.9). The removed. Details on cases transferred directly to Winnipeg mean age of cases was 40 years, with a range of <1 to 87 years. were unavailable. There was a bimodal distribution of age-specific incidence with Information collected by chart review included basic demo- peaks in the 0–19 and 40–59 age groups (Figure 1). Eleven cases graphics, specimen details, clinical severity, comorbidities, risk (17%) occurred among infants less than 1 year of age. factors, and antibiotic sensitivity profiles. Streptococcal toxic e m Th ajority of iGAS cases occurred during the months of shock syndrome was defined as previously described [10]. October to March; however, there was no statistically signifi- History of skin condition included chronic dermatitis/wound cant seasonal trend (Figure 2). The annual proportion of wound causing breaks in skin integrity. Cases identified as nosocomial swabs positive for GAS ranged from 40% to 48%. The average were excluded. In addition, the number of throat and wound annual rate of wound swabs positive for GAS was 61 episodes swabs that yielded GAS and were submitted to SLMHC from per 1000 population. Rates increased between 2009 and 2013 the 26 communities was obtained for each year of the study. and decreased in 2014. e Th average annual rate of throat swabs Crude incidence (removing duplicate isolates occurring within positive for GAS was 46.6 episodes per 1000 population. Rates a 14-day period) and temporal trends of positive throat and increased between 2010 and 2014. Wound swabs positive for wound swabs were assessed. The emm types of isolates from GAS were more prevalent during the summer months, whereas confirmed iGAS cases were determined through traditional GAS-positive throat swabs did not demonstrate a seasonal 30 140.0 120.0 100.0 80.0 60.0 40.0 20.0 0 0.0 <1 1-19 20 - 39 40 - 59 60+ Age Range of Cases Figure 1. Incidence of invasive group A streptococcal cases in 26 rural and remote First Nations communities in Sioux Lookout area between 2009 and 2014 by age. 2 • OFID • Bocking et al Number of Cases Average annual incidence (cases per 100,000 population 12 600 10 500 8 400 Cases of iGAS 6 300 Throat Swab Rate 4 200 Wound Swab Rate 2 100 0 0 Month Case Occurred Figure 2. Temporal distribution of invasive group A streptococcal (iGAS) cases compared with group A streptococcal (GAS)-positive throat swabs and GAS-positive wound swabs submitted from 26 rural and remote First Nations communities in Northwestern Ontario between 2009 and 2014. trend. There was no detectable association between trends of alcohol dependence also had skin conditions, and 5 of 7 persons iGAS incidence and either positive wound swab or positive reporting intravenous drug use were also dependent on alcohol. throat swab rates. Overall, 49 (75.4%) cases had positive blood cultures; among e 2 m Th ost common comorbidities identified were diabetes the 13 with blood cultures that were negative or not done, 9 mellitus (38.5%) and skin conditions (38.5%) (Table  1). The (13.8%) had positive deep tissue/abscess specimens (taken most prominent other potential risk factor was alcohol depend- aseptically in the operating room), 5 (7.7%) had positive syn- ence (25%). There was significant overlap in underlying condi- ovial fluid, and 1 (1.5%) had positive peritoneal fluid cultures. tions: among the 25 patients with underlying diabetes, 10 had One case had a nonsterile specimen positive for GAS with evi- skin conditions, 3 had alcohol dependence, and 2 had both skin dence of clinical severity. Primary bacteremia was present in 17 conditions and alcohol dependence. Seven of 16 persons with (26.2%) cases (Table  2); 1 postpartum bacteremia was identi- fied. Cellulitis was identified at the time of presentation in 36 (55.4%) cases, and septic arthritis was present in 6 (9.2%) cases. Table  1. Characteristics of 65 iGAS Cases Identified From 26 Rural and Streptococcal toxic shock syndrome and necrotizing fasciitis Remote First Nations Communities in Northwestern Ontario Between 2009 each occurred in 6 (9.2%) cases, and the crude 28-day case-fa- and 2014 tality rate for all iGAS was 6.2%. No cases of nosocomial infec- Case Characteristics Number (%) tion were identified. Antibiotic susceptibility profiles were available for 59 iso- Chronic underlying medical conditions Diabetes 25 (38.5) lates. All isolates were sensitive to penicillin. Sixteen isolates Skin conditions 25 (38.5) (24.6%) were resistant to both erythromycin and clindamy- Coronary artery disease 6 (9.2) cin. Of the 65 iGAS cases, 46 isolates were available for emm Active cancer 3 (4.6) typing. Among these, 14 different emm types were identified Peritoneal dialysis* 3 (4.6) (Table 3). The most common emm types were emm114 (17.4%), Hepatitis C 3 (4.6) Liver failure 3 (4.6) emm11 (15.2%), emm118 (13.0%), emm68 (10.9%), and emm82 Connective tissue disorder 3 (4.6) (10.9%). emm type variability over time was observed. Of the Other potential risk factors 16 isolates demonstrating resistance to erythromycin and clin- Alcohol dependence 16 (24.6) damycin, 7 were identified as emm11 and 5 were identified as Previous positive wound swab for GAS 16 (24.6) emm114. The cases associated with these isolates were from dif- Regular use of nonsteroidal anti-inflammatory drug 11 (16.9) ferent communities and temporally unrelated. Injection drug use 8 (12.3) Other substance use 6 (9.2) Underhoused/homeless/living in shelter system 5 (7.7) DISCUSSION Varicella within the previous month 1 (1.5) Abbreviations: GAS, group A streptococcal; iGAS, invasive group A streptococcal.  The incidence of iGAS in Canada increased significantly over *Patients must move from their rural or remote community to a larger center (primarily the last decade (from 2.81 to 4.03 per 100 000 between 2000 Thunder Bay) to receive hemodialysis. Only peritoneal dialysis is available at community level. and 2009)  [12]. In 2013, the Canadian and Ontario rates for Invasive Group A Strep in Northern Ontario • OFID • 3 Number of Cases Avergae annual rate per 100,000 population Table 2. Clinical Features of 65 iGAS Cases Identified From 26 Rural and Northwestern Ontario [9]. The high burden of substance use Remote First Nations Communities in Northwestern Ontario Between 2009 among indigenous peoples in Canada is recognized nation- and 2014 ally as a legacy of historical assimilation policies, multigen- erational trauma, and systemic racism [16]. The prevalence Clinical Features Number (%) of alcohol dependence among iGAS cases in this study (25%) Culture source was consistent with iGAS epidemiology for both indigenous Blood 49 (75.4) Other sterile source 15 (23.1) and non-indigenous populations in Northern Australia [17]. Nonsterile source 1 (1.5) Prescription drug abuse, particularly injection drug use (IDU), Clinical presentation is a significant issue facing many of the communities included Cellulitis 36 (55.4) in this study [18, 19]. However, only 12.3% of cases in this study Primary bacteremia 17 (26.2) were identified as having a history of IDU. Although it is likely Septic arthritis 6 (9.2) underreported, this proportion is consistent with iGAS epide- Pyomyositis 2 (3.1) Peritonitis 2 (3.1) miology reported in non-indigenous populations [20–22]. Meningitis 1 (1.5) Diabetes and skin conditions were found to be common comor- Pneumonia 1 (1.5) bidities among iGAS cases in this review. The prevalence of dia- Disease severity betes among First Nations in Canada is disproportionately high Streptococcal toxic shock syndrome 6 (9.2) compared with the non-indigenous population [23]. Given the Necrotizing fasciitis 6 (9.2) increased risk of iGAS associated with underlying diabetes, this Deceased 4 (6.2) contributes to increased risk for First Nation communities [24]. Abbreviations: iGAS, invasive group A streptococcal. In addition, high prevalence of skin conditions such as eczema and impetigo has been observed in many remote iGAS were 4.72 and 4.6 per 100 000 population, respectively First Nations communities [25]. It has been hypothesized [12, 13]. In contrast, the crude incidence rate of iGAS calculated in Northern Australia that a major risk factor for GAS bac- in this study among 26 rural and remote First Nations com- teremia in Aboriginal people is exposure to an overall high munities in Northwestern Ontario between 2009 and 2014 was burden of GAS infections, primarily skin infections such as more than 10 times higher at a rate of 56.2 per 100 000 popula- impetigo and pyoderma [3, 26]. These populations also expe- tion. Although significantly higher than the incidence of iGAS rience high prevalence of nonsuppurative sequelae to GAS among indigenous peoples in Northern Canada (2.25–20.44 per infection including acute rheumatic fever and poststreptococ- 100 000 population) [2], it is comparable to indigenous popula- cal glomerulonephritis [27, 28]. Although largely eliminated tions in Australia and New Zealand [3, 4, 14, 15]. from Canada, rheumatic fever in First Nations communities High prevalence of substance use has been thought to in Northwestern Ontario has been documented at rates con- be a contributing factor to overall higher rates of iGAS in sistent with Northern Australia (21.3 and 26 per 100 000, respectively) [29]. In Australia, the burden of GAS associated with skin and soft-tissue infections has been primarily related Table 3. emm types of 46 Cases of iGAS Identified From 26 Rural and Re- to inadequate and overcrowded housing [30, 31]. Disparities mote First Nations Communities in Northwestern Ontario Between 2009 in the social determinants of health, including inadequate and 2014 and overcrowded housing, are well documented public health issues facing First Nations communities in Northwestern emm types (N = 46) 2009 2010 2011 2012 2013 2014 Total No. Ontario [32–34]. 1 0 0 0 0 2 1 3 3 0 1 0 0 0 0 1 e p Th roportion of iGAS isolates that demonstrated resistance to 11 0 0 0 1 3 3 7 erythromycin (24.6%) and clindamycin (24.6%) was higher than 53 0 0 0 0 1 0 1 reported in other regions in Canada. A recent analysis of iGAS 59 0 0 0 0 1 1 2 cases from Peel and Toronto regions in Ontario demonstrated an 68 0 0 0 1 1 3 5 increase in erythromycin resistance from 2.2% in 1992–1995 to 80 0 0 0 1 0 0 1 19.5% in 2008–2010 and then to 7.5% in 2013 [35]. A 2011 publi- 82 0 0 2 3 0 0 5 83 0 0 0 1 0 0 1 cation from the Canadian province of British Columbia reported 87 0 0 0 0 0 1 1 resistance in all GAS isolates in 2011 to be 14.5% and 11.9% for 101 0 1 1 0 1 0 3 erythromycin and clindamycin, respectively [36]. 114 1 3 2 1 1 0 8 115 0 0 0 0 2 0 2 LIMITATIONS 118 0 0 0 1 4 1 6 Total 1 5 5 9 16 10 46 Data from Winnipeg could not be accessed; therefore, our data likely underestimates iGAS infection acquired in some Abbreviations: iGAS, invasive group A Streptococcus. 4 • OFID • Bocking et al 9. Athey TB, Teatero S, Sieswerda LE, et  al. High incidence of invasive group a communities. Given the small population size and reported case Streptococcus disease caused by strains of uncommon emm types in Thunder Bay, numbers, rates should be interpreted with caution. Risk factors Ontario, Canada. J Clin Microbiol 2016; 54:83–92. 10. Breiman RF, Davis JP, Facklam RR, et al. 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