Introduction
Group A streptococci (GAS) cause infections ranging from uncomplicated pharyngitis to severe invasive GAS (iGAS) such as necrotizing fasciitis. Reference Cunningham1 Rates of iGAS infections have been rising in recent years. Reference Tyrrell, Fathima, Kakulphimp and Bell2 Puerperal sepsis (PS) is a potentially life-threatening infection in mothers following childbirth, with GAS being a common cause. Reference Knowles, O’Sullivan, Meenan, Hanniffy and Robson3 Although rare in developed countries, it is a well-recognized postpartum complication with potentially devastating consequences including maternal death. Reference Riad, Thottacherry, Crawley, Phillip-Abraham and Ibrahim4
GAS commonly colonize the throat or skin and are primarily transmitted by contact of mucosal membranes with infectious droplets. Reference Cunningham1 Mothers are vulnerable to peripartum GAS infections due to disrupted vaginal mucosal and/or perineal cutaneous barriers. Reference Cunningham1,Reference Knowles, O’Sullivan, Meenan, Hanniffy and Robson3,Reference Deutscher, Lewis, Zell, Taylor, Van Beneden and Schrag5 Outbreaks of nosocomial postpartum iGAS infections continue to be reported. Reference Haden, Liscynesky and Colburn6 Case clustering of infections due to identical strains of GAS implies a common source in some instances, with health care workers (HCWs) who were asymptomatic carriers identified in several outbreaks. Reference Knowles, O’Sullivan, Meenan, Hanniffy and Robson3,Reference Deutscher, Lewis, Zell, Taylor, Van Beneden and Schrag5,Reference Haden, Liscynesky and Colburn6 This clustering suggests that these infections are potentially preventable. Reference Haden, Liscynesky and Colburn6,Reference Steer, Lamagni and Healy7
With a perceived increase in hospital-associated PS cases, we sought to comprehensively analyze iGAS-PS cases within the Calgary Zone health region in Alberta, Canada using epidemiologic and molecular techniques. We incorporated items as outlined in the STROBE template (https://www.strobe-statement.org/checklists/) for the reporting of cohort studies.
Methods
Data sources
All cases occurred in the Calgary Zone between January 1, 2013 and December 31, 2022. In Alberta, iGAS infections are a notifiable disease to Public Health (PH). 8,9 GAS isolates were identified by the microbiology laboratory and reported to PH. Clinical case data were collected by trained PH staff using a standardized notifiable disease reporting form with the data stored centrally at the Ministry of Health. 8 Clinical data were then linked to laboratory data from Alberta Precision Laboratories for each patient. Live-birth data and population census were obtained from the Government of Alberta Open Data. 10
Case definitions
PS cases were defined as iGAS infections of the genital tract occurring from parturition to 6-weeks postpartum with two or more of the following: pelvic pain, fever, abnormal vaginal discharge and/or odor, or delay in uterine involution. Confirmed iGAS infections were defined as PS with identification of GAS from a normally sterile site (such as blood). 8 Probable cases of iGAS infection were defined as severe disease using clinical and laboratory criteria (without another etiology/explanation) with isolation of GAS from a nonsterile site. 8
Cases were further adjudicated as hospital/delivery-acquired or community-acquired using a 48-hour timeline from time of delivery to symptom onset. All cases were independently adjudicated by Infection Prevention and Control (IPC) personnel and PH officials, with further review by IPC physicians and Medical Officers of Health. Hand hygiene and personal protective equipment (PPE) use information was also collected from delivery records.
Molecular analysis and isolate similarity
Isolates of GAS from patients and, where available, HCWs, were analyzed using molecular techniques, including whole genome sequencing (Supplemental files). Temporo-spatially related cases and clusters were also similarly analyzed.
Research ethics and policy development
Cases of iGAS infection are notifiable under the Alberta Public Health Act, requiring investigation by PH. The data obtained from this study were used to facilitate the development of policy interventions with the aim to reduce the incidence of PS (Supplemental files).
Results
Descriptive epidemiologic data
The rates of all iGAS infections in Alberta were increasing throughout the study period (Figure 1). Twenty-one iGAS-PS cases were identified between 2013 and 2022 in the Calgary Zone, representing a crude incidence of 1.35/10,000 live births. Of the 21 cases, there was one maternal death, nine adult intensive care unit (ICU) admissions, and six emergency hysterectomies (Supplemental Table).
Figure 1. Rates of all iGAS infections (isolate based, counting one isolate per patient) in the province of Alberta (total population, adjusted by year, all age groups) 2013–2022 (ranging from 267 to 439 cases per year).
Of the 21 cases, 18 (85.7%) were adjudicated as hospital/delivery-acquired, while three were community-acquired. Nineteen cases had iGAS isolates recovered, with 12 emm types identified (Table 1). The emm type could not be ascertained for two cases due to isolates not being submitted to the PH laboratory. Masks were not used during delivery for 14 (66.7%) cases, while information about PPE use was not available for six cases, and surgical mask use was confirmed for one case.
Table 1. iGAS-PS cases, year of occurrence, emm type, MLST, and presence or absence of streptococcal toxin genes
C or P, confirmed or probable case of iGAS-PS; HCW, healthcare worker; HDA or CA, hospital/delivery-acquired or community-acquired; iGAS-PS, invasive Group A streptococcus puerperal sepsis; MLST, multilocus sequence typing; NI, no isolate.
Cluster and molecular analysis
Four cases were identified as emm1 (cases 1–4, Table 1), with cases 1 and 2 occurring in spring 2013 at the same hospital. For cases 1 and 2, core single nucleotide variant (SNV) analysis showed the isolates to be identical to an isolate obtained from a pharyngeal swab of an unmasked HCW directly engaged in both deliveries. Cases 3 and 4 were not temporo-spatially linked to cases 1 and 2.
Cases 7 and 8 were typed as emm11 (Table 1). Both cases occurred in spring of 2014 at the same hospital and had the same healthcare team. The isolates matched through core SNV analysis. In addition, these cases were among those in which masking was not used. Case 18 was temporo-spatially linked to cases 7 and 8 (same month/same hospital/same healthcare team) but typed as emm89.
Policy development
Policy changes addressing the rising rates of PS included multiple interventions, including masking, focused point-of-care risk assessment, and appropriate PPE for delivery personnel.
Discussion
Our study identified 21 iGAS-PS cases between 2013 and 2022 which represented 1.35 cases/10,000 live births in the Calgary Zone health region and had unfortunate consequences including mortality, ICU admissions, and emergency hysterectomies. Most cases (85.7%) were adjudicated as healthcare/delivery-acquired. The clustering and identical match of cases 1 and 2 to an isolate from an unmasked delivering HCW supports that transmission occurred from the delivering HCW. Other results to highlight involved cases 7, 8, and 18. Although cases 7 and 8 had emm11 and were matched molecularly, the emm89 for case 18 did not match. However, it suggested a potential breakdown in IPC standards including non-masking that could have contributed to these cases.
Our data suggest that PS secondary to hospital/delivery-acquired iGAS may be preventable given the molecular matches, suggesting transmission from a common source. These data were used to inform a multidisciplinary task force to implement recommendations and practice policy changes across the entire province to prevent iGAS-PS (Supplemental files).
Adherence with these policies was overshadowed by the COVID-19 pandemic, which required masking and eye protection during all patient interactions. Although the incidence of PS declined dramatically after 2019, interpreting the reasons for this is difficult given the pandemic.
Our study has recognized limitations. The detection of all iGAS infections in a health region is challenging. Our surveillance methods likely underestimate the total number of infections. Early antimicrobial administration prior to culture collection can render cultures negative in otherwise positive cases. Furthermore, bacterial cultures are not always collected in cases of invasive postpartum infections since the most likely micro-organisms are well-defined with several acceptable empiric antimicrobial options. Reference Cunningham1,Reference Riad, Thottacherry, Crawley, Phillip-Abraham and Ibrahim4,Reference Steer, Lamagni and Healy7 We were also conservative in our definition for confirmed iGAS infection as it had to be isolated from a normally sterile site. The limited availability of GAS isolates from HCWs further limited the analysis. These factors together contribute to underestimating the total number of cases. Our study was also retrospective and did not allow for additional collection of information. Despite these limitations, the available data including the molecular analysis provides compelling evidence for the hospital/delivery-associated transmission of iGAS.
In summary, PS secondary to hospital/delivery-acquired iGAS is a potentially preventable infection. Our study found that most cases were hospital/delivery-acquired and highlights the need for ongoing surveillance and provides strong rationale for developing policies to prevent iGAS-PS, with ongoing evaluation to assess whether policy interventions reduce the burden of iGAS-PS.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ice.2024.154.
Acknowledgments
We thank the clinical diagnostic microbiology laboratory in Calgary for identifying iGAS isolates and submitting these to the Provincial Public Health Laboratory for emm typing.
Financial support
None.
Competing interests
This work was presented in part as an accepted abstract in poster format at the Association of Medical Microbiology and Infectious Disease Canada – Canadian Association for Clinical Microbiology and Infectious Diseases Annual Conference held virtually in Vancouver, BC April 29 – May 1, 2020.
John Conly has held grants from the Canadian Institutes for Health Research on acute and primary care preparedness for COVID-19 in Alberta, Canada, and was the primary local Investigator for a Staphylococcus aureus vaccine study funded by Pfizer for which all funding was provided only to the University of Calgary. He was a co-investigator on a WHO-funded study using integrated human factors and ethnography approaches to identify and scale innovative IPC guidance implementation supports in primary care with a focus on low-resource settings and using drone aerial systems to deliver medical supplies and PPE to remote First Nations communities during the COVID-19 pandemic. He also holds grants from the Synder Institute and a Catalyst Grant from the VPR Office at the University of Calgary for studies on the transmission of SARS-CoV-2 in K18-mice and received funding from BioMérieux Canada for accommodations and travel expenses to attend a meeting on Antimicrobial Resistance in 2022 and accommodations and travel expenses from the 2023 International Consortium for Prevention & Infection Control meeting to attend an IPC Think Tank meeting outside the scope of the submitted work. He is a member and Chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19 and a member of the WHO Health Emergencies Programme (WHE) Ad-hoc COVID-19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO and for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants. He is also a member of the Cochrane Acute Respiratory Infections Working Group.
Gregory Tyrrell – Canadian Institutes of Health Research operating grant co-investigator (2023) for a phase 1 clinical trial of a peptide-based group A streptococcal vaccine. Also has stock options for AVIGASVAX (vaccine for group A streptococci).
Judy MacDonald is a Director on the Board of the Alexandra Community Health Centre.
Oscar Larios is Senior Medical Director, Infection Prevention and Control within Alberta Health Services, salaried by Alberta Health Services.
Joseph Vayalumkal—grants or contracts: Public Health Agency of Canada—Canadian Nosocomial Infections Surveillance Program—payments to the University of Calgary; Department of Pediatrics, University of Calgary—Innovation Award for Novel Interaction Design Hand Hygiene Project. Honoraria: Pediatric Infectious Diseases Conference Banff, Alberta 2023 (speaker honoraria); Canadian Pharmacists Association—Book Chapter, Acute Otitis Media (author honoraria).
No other authors have conflicts of interest to disclose related to the submitted work.
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