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Older adults are at high risk of influenza-related complications or hospitalization. The purpose of this systematic review is to assess the relative cost-effectiveness of all influenza vaccine options for older adults.This systematic review identified economic evaluation studies assessing the cost-effectiveness of influenza vaccines in adults ≥65 years of age from 5 literature databases. Two reviewers independently selected, extracted, and appraised relevant studies using the JBI Critical Appraisal Checklist for Economic Evaluations and Heyland's generalizability checklist. Costs were converted to 2019 Canadian dollars and adjusted for inflation and purchasing power parity.A total of 27 studies were included. There were 18 comparisons of quadrivalent inactivated vaccine (QIV) versus trivalent inactivated vaccine (TIV): 5 showed QIV dominated TIV (ie, lower costs and higher health benefit), and 13 showed the results depended on willingness to pay (WTP). There were 9 comparisons of high-dose TIV (TIV-HD) versus TIV: 5 showed TIV-HD dominated TIV, and 4 showed the results depended on WTP. There were 8 comparisons of adjuvanted TIV (TIV-ADJ) versus TIV: 4 showed TIV-ADJ dominated TIV, and 4 showed the results depended on WTP. There were few pairwise comparisons among QIV, TIV-HD, and TIV-ADJ.The evidence suggests QIV, TIV-HD, and TIV-ADJ are cost-effective against TIV for a WTP threshold of $50 000 per quality-adjusted life-year. Future studies should include new and existing vaccine options for broad age ranges and use more robust methodologies-such as real-world evaluations or modeling studies accounting for methodological, structural, and parameter uncertainty.

Background: Reliable reports on hand hygiene performance throughout the COVID-19 pandemic are lacking as most hospitals continue to rely on direct observation to measure this quality indicator. Using group electronic hand hygiene monitoring, we sought to assess the impact of COVID-19 on adherence to hand hygiene. Methods: Across 12 Ontario hospitals (5 university and 7 community teaching hospitals), a group electronic hand hygiene monitoring system was installed before the pandemic to provide continuous measurement of hand hygiene adherence across 978 ward and 367 critical care beds. We performed an interrupted time-series study of institutional hand hygiene adherence in association with a COVID-19 inpatient census and the Ontario daily count of COVID-19 cases during a baseline period (Nov. 1, 2019, to Feb. 29, 2020), the pre-peak period of the first wave of the pandemic (Mar. 1 to Apr. 24, 2020), and the post-peak period of the first wave (Apr. 25 to July 5, 2020). We used a Poisson regression model to assess the association between the hospital COVID-19 census and institutional hand hygiene adherence while adjusting for the correlation within inpatient units. Results: At baseline, the rate of hand hygiene adherence was 46.0% (6 325 401 of 13 750 968 opportunities) and this improved beginning in March 2020 to a daily peak of 79.3% (66 640 of 84 026 opportunities) on Mar. 30, 2020. Each patient admitted with COVID-19 was associated with improved hand hygiene adherence (incidence rate ratio [IRR] 1.0621, 95% confidence interval [CI] 1.0619–1.0623). Increasing Ontario daily case count was similarly associated with improved hand hygiene (IRR 1.0026, 95% CI 1.0021–1.0032). After peak COVID-19 community and inpatient numbers, hand hygiene adherence declined and returned to baseline. Interpretation: The first wave of the COVID-19 pandemic was associated with significant improvement in hand hygiene adherence, measured using a group electronic monitoring system. Future research should seek to determine whether strategies that focus on health care worker perception of personal risk can achieve sustainable improvements in hand hygiene performance.

ObjectivesThe COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment.DesignRapid scoping reviewData sourcesMedline, Embase and biorxiv/medrxiv from inception to 15 May 2021.SettingHospital and community care.ParticipantsCOVID-19 patients of all ages.InterventionsCOVID-19 treatment.ResultsThe literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively.Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%).The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%).The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively.ConclusionsThis rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

Adults previously infected with SARS-CoV-2 develop short-term immunity and may have increased reactogenicity to COVID-19 vaccines. This prospective, multi-center active surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2.Canadian adults vaccinated between December 22, 2020 and November 27, 2021 were sent an electronic questionnaire 7 days post dose 1, dose 2 and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism or required a medical consultation, including hospitalization.Among 684,998 vaccinated individuals, 2.6% (18,127/684,998) reported a prior history of SARS-CoV-2 infection a median of 4 months (interquartile range 2-6 months) previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA1273 or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation; adjusted odds ratio (AOR) 3.96 (95% CI 3.67-4.28) for BNT162b2, 5.01 (4.57-5.50) for mRNA1273 and 1.84 (1.54-2.20) for ChAdox1-S compared to no infection. Following dose 2 and 3, the greater risk associated with previous infection was also present but attenuated compared to dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection.Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine doses.

Background: Outbreaks cause significant morbidity and mortality in healthcare settings. Current testing methods can identify specific viral respiratory pathogens, yet the approach to outbreak management remains general. Objectives: Our aim was to examine pathogen-specific trends in respiratory outbreaks, including how attack rates, case fatality rates and outbreak duration differ by pathogen between hospitals and long-term care (LTC) and retirement homes (RH) in Ontario. Methods: Confirmed respiratory outbreaks in Ontario hospitals and LTC/RH reported between September 1, 2007, and August 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Median attack rates and outbreak duration and overall case fatality rates of pathogen-specific outbreaks were compared in both settings. Results: Over the 10-year surveillance period, 9,870 confirmed respiratory outbreaks were reported in Ontario hospitals and LTC/RH. Influenza was responsible for most outbreaks (32% in LTC/RH, 51% in hospitals), but these outbreaks were shorter and had lower attack rates than most non-influenza outbreaks in either setting. Human metapneumovirus, while uncommon (

Contexte : Les éclosions provoquent une morbidité et une mortalité importantes dans les établissements de soins de santé. Les méthodes de dépistage actuelles permettent de cerner des agents pathogènes respiratoires viraux spécifiques, mais l’approche de la gestion des éclosions reste générale. Objectifs : Notre objectif était d’examiner les tendances spécifiques aux agents pathogènes dans les éclosions respiratoires, y compris la façon dont le taux d’attaque, le taux de létalité et la durée de l’éclosion diffèrent par agent pathogène entre les hôpitaux, et les établissements de soins de longue durée et les maisons de retraite en Ontario. Méthodes : Les éclosions d’infections respiratoires confirmées dans les hôpitaux et les établissements de soins de longue durée ou les maisons de retraite de l’Ontario signalées entre le 1er septembre 2007 et le 31 août 2017 ont été extraites du Système intégré d’information sur la santé publique (SIISP). Les taux d’attaque médians, la durée des éclosions et les taux généraux de létalité des éclosions spécifiques à un pathogène ont été comparés dans les deux types d’établissements. Résultats : Au cours de la période de surveillance de 10 ans, 9 870 éclosions respiratoires confirmées ont été signalées dans les hôpitaux et les établissements de soins de longue durée ou les maisons de retraite de l’Ontario. La grippe était à l’origine de la plupart des éclosions (32 % dans les établissements de soins de longue durée et les maisons de retraite, 51 % dans les hôpitaux), mais ces éclosions étaient plus courtes et présentaient des taux d’attaque inférieurs à ceux de la plupart des éclosions non grippales dans les deux types d’établissements. Le métapneumovirus humain, bien que peu fréquent (moins de 4 % des éclosions), présentait des taux de létalité élevés dans les deux types d’établissements. Conclusion : Les taux d’attaque et les taux de létalité variaient selon l’agent pathogène, tout comme la durée de l’éclosion. L’élaboration de conseils propres à la gestion des éclosions, qui tiennent compte de l’agent pathogène et de l’établissement de soins de santé, pourrait être utile pour limiter la charge des éclosions respiratoires.

BackgroundPost-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case.MethodsThis is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power atα = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates ofp0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment.DiscussionHarnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection.Trial registrationThis trial was registered atwww.ClinicalTrials.gov(NCT04321174) on March 25, 2020.

Objective:To determine whether combinations of diagnosis and procedures codes can improve the detection of prosthetic hip and knee joint infections from administrative databases.Design:We performed a validation study of all readmissions from January 1, 2010, until December 31, 2016, following primary arthroplasty comparing the diagnosis and procedure codes obtained from an administrative database based upon the International Classification of Disease, Tenth Revision (ICD-10) to the reference standard of chart review.Setting:Four tertiary-care hospitals in Toronto, Canada, from 2010 to 2016.Participants:Individuals who had a primary arthroplasty were identified using procedure codes.Intervention:Chart review of readmissions identified the presence of a prosthetic joint infection and, if present, the surgical procedure performed.Results:Overall, 27,802 primary arthroplasties were performed. Among 8,844 readmissions over a median follow-up of 669 days (interquartile range, 256–1,249 days), a PJI was responsible for or present in 586 of 8,844 (6.6%). Diagnosis codes alone exhibited a sensitivity of 0.88 (95% CI, 0.85–0.92) and positive predictive value (PPV) of 0.78 (95% CI, 0.74–0.82) for detecting a PJI. Combining a PJI diagnosis code with procedure codes for an arthroplasty and the insertion of a peripherally inserted central catheter improved detection: sensitivity was 0.92 (95% CI, 0.88–0.94) and PPV was 0.78 (95% CI, 0.74–0.82). However, procedure codes were unable to identify the specific surgical approach to PJI treatment.Conclusions:Compared to PJI diagnosis codes, combinations of diagnosis and procedure codes improve the detection of a PJI in administrative databases.

Background Hand hygiene (HH) is an important patient safety measure linked to the prevention of health care-associated infection, yet how outbreaks affect HH performance has not been formally evaluated. Methods A controlled, interrupted time series was performed across 5 acute-care academic hospitals using group electronic monitoring. This system captures 100% of all hand sanitizer and soap dispenser activations via a wireless signal to a wireless hub; the number of activations is divided by a previously validated estimate of the number of daily HH opportunities per patient bed, multiplied by the hourly census of patients on the unit. Daily HH adherence 60 days prior and 90 days following outbreaks on inpatient units was compared to control units not in outbreaks over the same period, using a Poisson regression model adjusting for correlations within hospitals and units. Predictors of HH improvement were assessed in this multivariate model. Results In the 60 days prior to outbreaks, units destined for outbreaks had significantly lower HH adherence compared to control units (incidence rate ratio [IRR], 0.91; 95% confidence interval [CI], .90–.93; P Conclusions Hospital outbreaks tend to occur in units with lower HH adherence and are associated with rapid improvements in HH performance. Group electronic monitoring of HH could be used to develop novel, prospective feedback interventions designed to avert hospital outbreaks.

Background The objective of this review was to examine the current guidelines for infection prevention and control (IPAC) of coronavirus disease-19 (COVID-19) or other coronaviruses in adults 60 years or older living in long-term care facilities (LTCF). Methods EMBASE, MEDLINE, Cochrane library, pre-print servers, clinical trial registries, and relevant grey literature sources were searched until July 31, 2020, using database searching and an automated method called Continuous Active Learning® (CAL®). All search results were processed using CAL® to identify the most likely relevant citations that were then screened by a single human reviewer. Full-text screening, data abstraction, and quality appraisal were completed by a single reviewer and verified by a second. Results Nine clinical practice guidelines (CPGs) were included. The most common recommendation in the CPGs was establishing surveillance and monitoring systems followed by mandating the use of PPE; physically distancing or cohorting residents; environmental cleaning and disinfection; promoting hand and respiratory hygiene among residents, staff, and visitors; and providing sick leave compensation for staff. Conclusions Current evidence suggests robust surveillance and monitoring along with support for IPAC initiatives are key to preventing the spread of COVID-19 in LTCF. However, there are significant gaps in the current recommendations especially with regard to the movement of staff between LTCF and their role as possible transmission vectors. Systematic review registration PROSPERO CRD42020181993

BACKGROUND: In pandemics, local hospitals need to anticipate a surge in health care needs. We examined the modelled surge because of the coronavirus disease 2019 (COVID-19) pandemic that was used to inform the early hospital-level response against cases as they transpired. METHODS: To estimate hospital-level surge in March and April 2020, we simulated a range of scenarios of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in the Greater Toronto Area (GTA), Canada, using the best available data at the time. We applied outputs to hospital-specific data to estimate surge over 6 weeks at 2 hospitals (St. Michael’s Hospital and St. Joseph’s Health Centre). We examined multiple scenarios, wherein the default (R(0) = 2.4) resembled the early trajectory (to Mar. 25, 2020), and compared the default model projections with observed COVID-19 admissions in each hospital from Mar. 25 to May 6, 2020. RESULTS: For the hospitals to remain below non-ICU bed capacity, the default pessimistic scenario required a reduction in non-COVID-19 inpatient care by 38% and 28%, respectively, with St. Michael’s Hospital requiring 40 new ICU beds and St. Joseph’s Health Centre reducing its ICU beds for non-COVID-19 care by 6%. The absolute difference between default-projected and observed census of inpatients with COVID-19 at each hospital was less than 20 from Mar. 25 to Apr. 11; projected and observed cases diverged widely thereafter. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. INTERPRETATION: Scenario-based analyses were reliable in estimating short-term cases, but would require frequent re-analyses. Distribution of the city’s surge was expected to vary across hospitals, and community-level strategies were key to mitigating each hospital’s surge.

Background The current approach to measuring hand hygiene (HH) relies on human auditors who capture Methods A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. Results After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47–1.99]; P Conclusions The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.

Pregnant individuals have been receiving COVID-19 vaccines following pre-authorisation clinical trials in non-pregnant people. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals.We did an observational cohort study, set in seven Canadian provinces and territories including Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Yukon, and Prince Edward Island. Eligibility criteria for vaccinated individuals were a first dose of a COVID-19 vaccine within the previous 7 days; an active email address and telephone number; ability to communicate in English or French; and residence in the aforementioned provinces or territories. Study participants were pregnant and non-pregnant females aged 15-49 years. Individuals were able to participate as controls if they were unvaccinated and fulfilled the other criteria. Data were collected primarily by self-reported survey after both vaccine doses, with telephone follow-up for those reporting any medically attended event. Participants reported significant health events (new or worsening of a health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) occurring within 7 days of vaccination or within the past 7 days for unvaccinated individuals. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines, adjusting for age group, previous SARS-CoV-2 infection, and trimester, as appropriate.As of Nov 4, 2021, 191 360 women aged 15-49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4-8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55-0·72]) and dose two (aOR 0·62 [0·54-0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention.COVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy.Canadian Institutes of Health Research, Public Health Agency of Canada.

IntroductionCOVID-19 vaccines require enhanced safety monitoring after emergency approval. The Canadian National Vaccine Safety Network monitors the safety of COVID-19 vaccines and provides enhanced monitoring for healthy, auto-immune, immunocompromised, pregnant and breastfeeding populations and allows for the detection of safety signals.Methods and analysisOnline participant reporting of health events in vaccinated and unvaccinated individuals 12 years of age and older is captured in three surveys: 1 week after dose 1, 1 week after dose 2 and 7 months after dose 1. Medically attended events are followed up by telephone. The number, percentage, rate per 10 000 and incident rate ratios with 95% CIs are calculated by health event, vaccine type, sex and in 10-year age groups.Ethics and disseminationEach study site has Research Ethics Board approvals for the project (UBC Children’s & Women’s, CIUSSS de l'Estrie—CHUS, Health PEI, Conjoint Health Research Ethics Board, University of Calgary and Alberta Health Services, IWK Health, Unity Health Toronto and CHU de Québec-Université Laval Research Ethics Boards). Individuals are invited to participate in this active surveillance and electronic consent is given before proceeding to each survey. Weekly reports are shared with public health and posted on the study website. At least one peer-reviewed manuscript is produced.

The IR Biotyper and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) using ClinProTools software (MALDI-TOF MS–ClinProTools) are two novel typing methods that rely on the analysis of carbohydrate and peptide residues in intact bacterial cells. These two methods have shown promising results in the rapid and accurate typing of bacteria. In this study, we evaluated these novel typing methods in comparison with genotypic typing for cluster analysis of Burkholderia cenocepacia epidemic strain ET12, isolated from adult cystic fibrosis patients. Sixty-six isolates of B. cenocepacia were used in this study, 35 of which were identified as the ET12 strain and 31 as non-ET12 strains by repetitive-element PCR (rep-PCR). Twelve isolates were used for the creation of typing models using IR Biotyper and MALDI-TOF MS–ClinProTools, and 54 isolates were used for external validation of the typing models. The IR Biotyper linear discriminant analysis (LDA) model had a diagnostic sensitivity of 84.6% for typing the epidemic strain, ET12. At a cutoff of 70%, MALDI-TOF MS–ClinProTools had 87.5% diagnostic sensitivity in detecting the ET12 strain (P = 1.00). Both methods had a diagnostic specificity of ≥80% for detecting the ET12 strain. In conclusion, IR Biotyper and MALDI-TOF MS–ClinProTools offer rapid typing using proteomics and analysis of small cellular molecules with a low running cost. Our pilot study showed suboptimal accuracy of both methods for typing outbreak strains of B. cenocepacia. Extending the spectral region analyzed by the IR Biotyper can improve the accuracy and has the potential of improving the generalizability of this technique for typing other organisms. IMPORTANCE Respiratory infections due to Burkholderia cenocepacia, particularly the ET12 epidemic strain, are considered sentinel events for persons with cystic fibrosis, as they are often associated with person-to-person transmission and accelerated decline in lung function and early mortality. Current typing methods are generally only available at reference centers, with long turn-around-times, which can affect the identification of outbreaks and critical patient triage. This pilot study aims to add to the growing literature illustrating the potential utility of Fourier transform infrared spectroscopy (FTIR), a novel rapid method, for the successful typing of clinically significant bacteria. In this study, we evaluated its utility to discriminate between the ET12 clone and non-ET12 isolates of B. cenocepacia and compared it to proteomics cluster analysis using MALDI-TOF MS and ClinProTools software. Both methods had encouraging but suboptimal accuracy (≥85% sensitivity and ≥83% specificity), which will likely be improved by extending the spectral region analyzed by the IR Biotyper with updated software.

Objectives:An accurate estimate of the average number of hand hygiene opportunities per patient hour (HHO rate) is required to implement group electronic hand hygiene monitoring systems (GEHHMSs). We sought to identify predictors of HHOs to validate and implement a GEHHMS across a network of critical care units.Design:Multicenter, observational study (10 hospitals) followed by quality improvement intervention involving 24 critical care units across 12 hospitals in Ontario, Canada.Methods:Critical care patient beds were randomized to receive 1 hour of continuous direct observation to determine the HHO rate. A Poisson regression model determined unit-level predictors of HHOs. Estimates of average HHO rates across different types of critical care units were derived and used to implement and evaluate use of GEHHMS.Results:During 2,812 hours of observation, we identified 25,417 HHOs. There was significant variability in HHO rate across critical care units. Time of day, day of the week, unit acuity, patient acuity, patient population and use of transmission-based precautions were significantly associated with HHO rate. Using unit-specific estimates of average HHO rate, aggregate HH adherence was 30.0% (1,084,329 of 3,614,908) at baseline with GEHHMS and improved to 38.5% (740,660 of 1,921,656) within 2 months of continuous feedback to units (P < .0001).Conclusions:Unit-specific estimates based on known predictors of HHO rate enabled broad implementation of GEHHMS. Further longitudinal quality improvement efforts using this system are required to assess the impact of GEHHMS on both HH adherence and clinical outcomes within critically ill patient populations.

Background: Adults are at risk of being exposed to influenza from many sources. Healthcare personnel (HCP) have the additional risk of being exposed to ill patients.Objective:To determine whether HCP were at higher risk than adults working in nonhealthcare roles (non-HCP).Design:Prospective cohort study.Setting:Acute-care hospitals and other businesses in Toronto, Ontario, Canada.Methods:Adults aged 18–69 years were enrolled for 1 or more of the 2010/2011, 2011/2012, and 2012/2013 influenza seasons. Swabs collected during acute respiratory illnesses were tested for influenza and pre- and postseason blood samples were tested for influenza-specific immune response.Results:The adjusted odds of influenza were similar for HCP and non-HCP (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.63–2.63). Older adults and those vaccinated against influenza had lower odds, and those who shared their workspace and who used corrective eyewear had higher odds of influenza.Conclusions:HCP and other working adults are at similar risk of influenza infection.

Objective:To determine infection prevention and control (IPAC) practices for carbapenemase-producing Enterobacteriaceae (CPE), an emerging threat, at acute-care hospitals in Ontario, Canada.Design:A descriptive cross-sectional survey.Methods:We surveyed IPAC directors and managers at all acute-care hospitals in Ontario, Canada, to gather information on IPAC practices related to CPE, including admission screening, other patient screening, environmental testing, use of precautions to prevent transmission, and outbreak management.Results:Of 116 acute-care hospitals, 105 (91%) responded. Admission screening included patients previously colonized or infected with CPE (n = 64, 61%), patients recently hospitalized outside of Canada (Indian subcontinent, n = 62, 59%; other countries, n = 56, 53%), and patients recently hospitalized in Canada (n = 22, 21%). Fifty-one hospitals (49%) screened patients for colonization during an outbreak. Almost all hospitals (n = 101, 96%) used precautions to prevent transmission from patients with CPE colonization or infection; most hospitals (n = 54, 53%) continued precautions indefinitely. Few hospitals (n = 19, 18%) performed environmental cultures. Eight hospitals (8%) reported at least 1 outbreak, and 6 hospitals (6%) reported transmission from sink or shower drains to patients.Conclusions:Variability in practices may result from lack of evidence and challenges in updating guidelines as evidence emerges. A coordinated approach to slow the emergence of CPE should be considered in our population.

Background:Healthcare workers (HCWs) are at risk of acquiring and transmitting respiratory viruses while working in healthcare settings.Objectives:To investigate the incidence of and factors associated with HCWs working during an acute respiratory illness (ARI).Methods:HCWs from 9 Canadian hospitals were prospectively enrolled in active surveillance for ARI during the 2010–2011 to 2013–2014 influenza seasons. Daily illness diaries during ARI episodes collected information on symptoms and work attendance.Results:At least 1 ARI episode was reported by 50.4% of participants each study season. Overall, 94.6% of ill individuals reported working at least 1 day while symptomatic, resulting in an estimated 1.9 days of working while symptomatic and 0.5 days of absence during an ARI per participant season. In multivariable analysis, the adjusted relative risk of working while symptomatic was higher for physicians and lower for nurses relative to other HCWs. Participants were more likely to work if symptoms were less severe and on the illness onset date compared to subsequent days. The most cited reason for working while symptomatic was that symptoms were mild and the HCW felt well enough to work (67%). Participants were more likely to state that they could not afford to stay home if they did not have paid sick leave and were younger.Conclusions:HCWs worked during most episodes of ARI, most often because their symptoms were mild. Further data are needed to understand how best to balance the costs and risks of absenteeism versus those associated with working while ill.

Background: People receiving in-center hemodialysis face a high risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and experience poor outcomes. During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Ontario (between March and June 2020), it was unclear whether asymptomatic or presymptomatic cases were common and whether widespread testing of all dialysis patients and staff would identify cases earlier and prevent transmission. Ontario has a population of about 14.5 million. Approximately 8900 people receive dialysis across 102 in-center dialysis units. Objective: The objective of this study was to determine participation rates for patients and staff in point prevalence testing in dialysis units across the province and to determine the prevalence of asymptomatic or presymptomatic infection. Design: Cross-sectional study design. Setting: In-center hemodialysis units at 27 renal programs across Ontario. Participants: Patients and staff in in-center dialysis units in Ontario. Measurements: Participation rates, demographic data, SARS-CoV-2 positivity rates, and COVID-19-related symptom data. Methods: From June 8 to 30, 2020, all in-center dialysis patients and staff in the Province of Ontario were requested to undergo a symptom screening assessment and nasopharyngeal swab. Testing was done using polymerase chain reaction to detect SARS-CoV-2. A standardized questionnaire of atypical and typical COVID-19-related symptoms was administered to patients, to assess for new or worsening COVID-19-related symptoms. Results: Patient participation was 83% (7155 of 8612) of which 15 tests were positive: less than 5 (Limitations: As point prevalence testing was voluntary, not all patients and staff participated. Lower participation rate may be due to decreasing new cases in Ontario, and testing or pandemic fatigue, among other factors. This study did not use serology to identify prior infections because it was not widely available in Ontario. With respect to the standardized symptom questionnaire, it was only available in English and French and could not be tested due to the urgency of the initiative. Conclusions: Participation among patients in point prevalence testing was good, but participation among staff was relatively low. Asymptomatic positivity in the dialysis patient and staff population was rare during the first wave of the COVID-19 pandemic in Ontario.

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-β-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental blaVIM-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010–2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); blaVIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with blaVIM-1-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two blaVIM-1-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of blaVIM-1-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.

Background Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. Methods We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. Results Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case’s spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05–36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92–25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52–27.40). Conclusions Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.

BackgroundA hospital-level pandemic response involves anticipating local surge in healthcare needs.MethodsWe developed a mechanistic transmission model to simulate a range of scenarios of COVID-19 spread in the Greater Toronto Area. We estimated healthcare needs against 2019 daily admissions using healthcare administrative data, and applied outputs to hospital-specific data on catchment, capacity, and baseline non-COVID admissions to estimate potential surge by day 90 at two hospitals (St. Michael’s Hospital [SMH] and St. Joseph’s Health Centre [SJHC]). We examined fast/large, default, and slow/small epidemics, wherein the default scenario (R0 2.4) resembled the early trajectory in the GTA.ResultsWithout further interventions, even a slow/small epidemic exceeded the city’s daily ICU capacity for patients without COVID-19. In a pessimistic default scenario, for SMH and SJHC to remain below their non-ICU bed capacity, they would need to reduce non-COVID inpatient care by 70% and 58% respectively. SMH would need to create 86 new ICU beds, while SJHC would need to reduce its ICU beds for non-COVID care by 72%. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. If physical distancing reduces contacts by 20%, maximizing the diagnostic capacity or syndromic diagnoses at the community-level could avoid a surge at each hospital.InterpretationAs distribution of the city’s surge varies across hospitals over time, efforts are needed to plan and redistribute ICU care to where demand is expected. Hospital-level surge is based on community-level transmission, with community-level strategies key to mitigating each hospital’s surge.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007-2015 in south-central Ontario, Canada. We reviewed patients' medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007–2015 in south-central Ontario, Canada. We reviewed patients’ medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Background Antimicrobial stewardship programs (ASPs) using audit and feedback in the intensive care unit (ICU) setting can reduce harms related to inappropriate antibiotic use. However, inappropriate discontinuation or narrowing of antibiotic treatment could increase infection-related mortality in this population. Individual ASP studies are underpowered to detect differences in mortality. Methods We conducted a systematic review and meta-analysis of audit and feedback in the ICU setting, using mortality as our outcome. Results Of 2447 citations, 11 studies met our inclusion criteria. Although a variety of study designs were used to assess reductions in antibiotic use, mortality was analyzed using an uncontrolled before-after study design in all studies. Five studies directed audit and feedback to all or most ICU patients receiving antibiotics and measured overall ICU mortality. In the meta-analysis of these studies, the pooled relative risk of ICU mortality was 1.03 (95% confidence interval, .93-1.14). A second meta-analysis of 3 smaller studies that evaluated mortality only in patients directly assessed by the ASP found a pooled relative risk of ICU mortality of 1.06 (95% confidence interval, .80 to 1.4). Three studies were not appropriate for meta-analysis, but their results were consistent with our overall findings. Conclusions Our systematic review did not identify a change in mortality associated with antimicrobial stewardship using audit and feedback in the ICU setting. These results increase our confidence that audit and feedback can be safely implemented in this setting. Future studies should report standardized estimates of mortality and use more robust study designs to assess mortality, when feasible.

Background Influenza vaccine coverage rates among healthcare workers (HCWs) in acute care facilities in Canada remain below national targets. Objective To determine factors associated with influenza vaccine uptake among HCWs. Methods This secondary analysis of a prospective cohort study included HCWs aged 18-69 years, working ≥20 h/wk in a Canadian acute care hospital. Questionnaires were administered to participants in the fall of the season of participation (2011/12-2013/14) which captured demographic/household characteristics, medical histories, occupational, behavioural and risk factors for influenza. Generalized estimating equation logistic regression was used to determine factors associated with vaccine uptake in the season of participation. Results The adjusted odds ratio for influenza vaccination in the current season was highest for those vaccinated in 3 of 3 previous seasons (OR 156; 95% CI 98, 248) followed by those vaccinated in 2 of 3 and 1 of 3 previous seasons when compared with those not vaccinated. Compared with nurses, physicians (OR 4.2; 95% CI 1.4, 13.2) and support services staff (OR 1.8; 95% CI 1.3, 2.4) had higher odds ratios for vaccine uptake. Conversely, HCWs identifying as Black had lower odds of uptake compared with those with European ancestry (OR 0.44, 95% CI 0.26-0.75) when adjusted for other factors in the model. Conclusion Healthcare workers differ in their annual uptake of influenza vaccine based on their past vaccination history, occupation and ethnicity. These findings indicate a need to determine whether there are other vaccine-hesitant groups within healthcare settings and learn which approaches are successful in increasing their uptake of influenza vaccines.

This report describes transmission of a Burkholderia cenocepacia ET12 strain (ET12-Bc) at the Toronto Adult Cystic Fibrosis (CF) Centre occurring from 2008 to 2017. Epidemiological and genomic data from 11 patients with CF were evaluated. Isolates were analysed using whole genome sequencing (WGS). Epidemiological investigation and WGS analysis suggested nosocomial transmission, despite enhanced infection control precautions. This was associated with subsequent deaths in 10 patients. ET12-Bc positive patients are no longer cared for on the same unit as ET12-Bc negative patients.

Objectives To determine whether a smartphone app, containing local bacterial resistance patterns (antibiogram) and treatment guidelines, improved knowledge of prescribing antimicrobials among medical trainees. Methods We conducted a prospective, controlled, pre-post study of medical trainees with access to a smartphone app (app group) containing our hospital's antibiogram and treatment guidelines compared to those without access (control group). Participants completed a survey which included a knowledge assessment test (score range, 0 [lowest possible score] to 12 [highest possible score]) at the start of the study and four weeks later. The primary outcome was change in mean knowledge assessment test scores between week 0 and week 4. Change in knowledge assessment test scores in the app group were compared to the difference in scores in the control group using multivariable linear regression. Results Sixty-two residents and senior medical students participated in the study. In a multivariable analysis controlling for sex and prior knowledge, app use was associated with a 1.1 point (95% CI: 0.10, 2.1) [β = 1.08, t(1) = 2.08, p = 0.04] higher change in knowledge score compared to the change in knowledge scores in the control group. Among those in the app group, 88% found it easy to navigate, 85% found it useful, and about one- quarter used it daily. Conclusions An antibiogram and treatment algorithm app increased knowledge of prescribing antimicrobials in the context of local antibiotic resistance patterns. These findings reinforce the notion that smartphone apps can be a useful and innovative means of delivering medical education.

Background The hospital water environment is a CPE reservoir, and transmission of CPE from drains to patients is a risk. Methods We cultured sink and shower drains in patient rooms and communal shower rooms that were exposed to inpatients with CPE colonization/infection from October 2007 to December 2017 at 10 hospitals. We compared patient room drain CPE to prior room occupant CPE using Illumina and MinION whole-genome sequencing. Results Three-hundred and ten inpatients exposed 1,209 drains, of which 53 (4%) yielded 62 CPE isolates at 7 (70%) hospitals. Compared to room occupant CPE isolates, drain CPE isolates were more likely Enterobacter spp. (6, 10% vs. 25, 51%, p< 0.0001) or KPC-producers (9, 15% vs. 23, 47%, p=0.0002). Of the 49 CPE isolates in patient room drains, 4 (8%) were linked to a prior room occupant (Table), 24 (49%) had the same carbapenemase as a prior room occupant but isolates/carbapenemase gene-containing plasmids that were unrelated, and 21 (43%) did not share a carbapenemase with a prior room occupant. The 4 drains linked to prior room occupants were likely contaminated by these room occupants, who were CPE-colonized prior to drain exposure. Despite few links between drain and room occupant CPE, there were 10 isolates harbouring related blaNDM-1-containing IncHI2A/HI2-type plasmids in 8 rooms on two units at one hospital. Nine of these were Enterobacter hormaechei ST66 isolates that were 0 to 6 SNVs apart and one was a Klebsiella oxytoca STnovel isolate. Table. Four patient room drain CPE isolates (D1b, D4, D5, D12) and isolates from prior room occupants that they were related to by whole-genome sequencing. Conclusion It was uncommon for drain CPE to be linked to prior patient exposure. This suggests contamination of most drains by undetected colonized patients and a need for more aggressive patient screening in our hospitals. This may also suggest retrograde (drain-to-drain) transmission, especially considering the 10 isolate drain cluster at one hospital. Reasons for the preponderance of Enterobacter spp. in drains requires further study. Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

Background: The current approach to measuring hand hygiene (HH) relies on human auditors who capture Methods: A stepped-wedge cluster randomized quality improvement study was undertaken across 5 acute-care hospitals in Ontario, Canada. Overall, 746 inpatient beds were electronically monitored across 26 inpatient medical and surgical units. Daily HH performance as measured by group electronic monitoring was reported to inpatient units who discussed results to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (%) between baseline and intervention. Secondary outcomes included transmission of antibiotic resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. Results: After adjusting for the correlation within inpatient units, there was a significant overall improvement in HH adherence associated with the intervention (IRR, 1.73; 95% CI, 1.47–1.99; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1,395,450 of 4,544,144) to 37% (598,035 of 1,536,643) within 1 month, followed by consecutive incremental increases up to 53% (804,108 of 1,515,537) by 10 months (P < .0001). We identified a trend toward reduced healthcare-associated transmission of MRSA (0.74; 95% CI, 0.53–1.04; P = .08). Conclusions: The introduction of a system for group electronic monitoring led to rapid, significant, and sustained improvements in HH performance within a 2-year period.Funding: NoneDisclosures: None

Background Prosthetic hip and knee joint infections (PJIs) are challenging to eradicate despite prosthesis removal and antibiotic therapy. There is a need to understand risk factors for PJI treatment failure in the setting of prosthesis removal. Methods A retrospective cohort of individuals who underwent prosthesis removal for a PJI at 5 hospitals in Toronto, Canada, from 2010 to 2014 was created. Treatment failure was defined as recurrent PJI, amputation, death, or chronic antibiotic suppression. Potential risk factors for treatment failure were abstracted by chart review and assessed using a Cox proportional hazards model. Results A total of 533 individuals with prosthesis removal were followed for a median (interquartile range) of 814 (235–1530) days. A 1-stage exchange was performed in 19% (103/533), whereas a 2-stage procedure was completed in 88% (377/430). Treatment failure occurred in 24.8% (132/533) at 2 years; 53% (56/105) of recurrent PJIs were caused by a different bacterial species. At 4 years, treatment failure occurred in 36% of 1-stage and 32% of 2-stage procedures (P = .06). Characteristics associated with treatment failure included liver disease (adjusted hazard ratio [aHR], 3.12; 95% confidence interval [CI], 2.09–4.66), the presence of a sinus tract (aHR, 1.53; 95% CI, 1.12–2.10), preceding debridement with prosthesis retention (aHR, 1.68; 95% CI, 1.13–2.51), a 1-stage procedure (aHR, 1.72; 95% CI, 1.28–2.32), and infection due to Gram-negative bacilli (aHR, 1.35; 95% CI, 1.04–1.76). Conclusions Failure of PJI therapy is common, and risk factors are not easily modified. Improvements in treatment paradigms are needed, along with efforts to reduce orthopedic surgical site infections., Prosthetic joint infections are challenging to eradicate and in this retrospective cohort the characteristics associated with treatment failure included liver disease, presence of a sinus tract, prior debridement with prosthesis retention, a one-stage procedure, and infection with a Gram-negative bacilli.

Background Timely strain typing of group A Streptococci (GAS) is necessary to guide outbreak recognition and investigation. We evaluated the use of (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) combined with cluster analysis software to rapidly distinguish between related and unrelated GAS isolates in real-time. Methods We developed and validated a typing model using 177 GAS isolates with known emm types. The typing model was created using 43 isolates, which included 8 different emm types, and then validated using 134 GAS isolates of known emm types that were not included in model generation. Results Twelve spectra were generated from each isolate during validation. The overall accuracy of the model was 74% at a cutoff value of 80%. The model performed well with emm types 4, 59, and 74 but showed poor accuracy for emm types 1, 3, 12, 28, and 101. To evaluate the ability of this tool to perform typing in an outbreak situation, we evaluated a virtual outbreak model using a “virtual outbreak strain; emm74” compared with a non-outbreak group or an “outgroup “ of other emm types. External validation of this model showed an accuracy of 91.4%. Conclusions This approach has the potential to provide meaningful information that can be used in real time to identify and manage GAS outbreaks. Choosing isolates characterized by whole genome sequencing rather than emm typing for model generation should improve the accuracy of this approach in rapidly identifying related and unrelated GAS strains.