Epidemiology and clinical manifestations of reported Lyme disease cases: Data from the Canadian Lyme disease enhanced surveillance system.

Lyme disease cases reported in seven Canadian provinces from 2009 to 2019 through the Lyme Disease Enhanced Surveillance System are described herein by demographic, geography, time and season. The proportion of males was greater than females. Bimodal peaks in incidence were observed in children and older adults (≥60 years of age) for all clinical signs except cardiac manifestations, which were more evenly distributed across age groups. Proportions of disease stages varied between provinces: Atlantic provinces reported mainly early Lyme disease, while Ontario reported equal proportions of early and late-stage Lyme disease. Early Lyme disease cases were mainly reported between May through November, whereas late Lyme disease were reported in December through April. Increased awareness over time may have contributed to a decrease in the proportion of cases reporting late disseminated Lyme disease. These analyses help better describe clinical features of reported Lyme disease cases in Canada.

Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting.

The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18-29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

2021-2022 AMMI Canada guidance on the use of antiviral drugs for influenza in the COVID-19 pandemic setting in Canada.

We provide an update to the Association of Medical Microbiology and Infectious Disease Canada seasonal influenza foundation guideline on the use of antiviral drugs for influenza for the upcoming 2021-2022 influenza season in Canada. Peramivir and baloxavir marboxil were licensed in Canada in 2017 and 2020, respectively, but neither is currently marketed. Thus, this guidance continues to focus on further optimizing the use of oseltamivir and zanamivir. Important issues for this year include the implications of co-circulation of severe acute respiratory syndrome coronavirus 2 and influenza viruses; the role of diagnostic testing in relation to impact on patient management; and dosing and administration recommendations for neuraminidase inhibitors for various at-risk age groups.

Une mise à jour des lignes directrices de base d'AMMI Canada sur l'utilisation de médicaments antiviraux contre l'influenza au cours de la saison grippale 2021-2022 au Canada est présentée. Le péramivir et le baloxavir marboxil ont été homologués au Canada en 2017 et en 2020, respectivement, mais ni l'un ni l'autre n'est encore commercialisé. Les lignes directrices continuent donc d'être axées sur l'optimisation de l'oseltamivir et du zanamivir. Les enjeux importants cette année incluent les effets de la cocirculation du coronavirus 2 du syndrome respiratoire aigu sévère et des virus de l'influenza, le rôle des tests diagnostiques sur la prise en charge des patients, de même que les recommandations en matière de posologie et d'administration des inhibiteurs de la neuraminidase dans divers groupes d'âge à risque.

SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively. OBJECTIVES: We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV. METHODS: We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay. RESULTS: SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO2. CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Estimating the population health burden of Lyme disease in Ontario, Canada: a microsimulation modelling approach.

BACKGROUND: If untreated, Lyme disease can lead to long-term sequelae and post-treatment Lyme disease syndrome (PTLDS), resulting in reduced health-related quality of life. The objective of this study was to develop a microsimulation model to estimate the population-level health burden of Lyme disease in Ontario, Canada. METHODS: We developed a Lyme disease history model using microsimulation, simulating 100 000 people (mean age 37.6 yr, 51% female) from 2017 in Ontario over a lifetime risk of infection and time horizon. We extracted the sensitivity and specificity of the 2-tier testing recommended by the Canadian Public Health Laboratory Network, probabilities and health state utility values from the published literature and health administrative data. Our reported outcomes from our stochastic analysis include diagnosed cases of Lyme disease (stratified by stage), undiagnosed infections, sequelae, individuals with PTLDS and quality-adjusted life-years (QALYs) lost. RESULTS: Our model estimated 333 (95% confidence interval [CI] 329-337) infections over the lifetime of 100 000 simulated people (mean age 37.6 yr, 51% female), with 92% (95% CI 91%-93%) of infections diagnosed. Of those 308 people with Lyme Disease diagnoses, 67 (95% CI 65-69) developed sequelae (e.g., arthritic, cardiac, neurologic sequelae), and 34 (95% CI 33-35) developed PTLDS. Lyme disease resulted in a loss of 84.5 QALYs (95% CI 82.9-86.2) over the lifetime of the simulated cohort. Sensitivity and scenario analysis showed that increasing incidence rates of Lyme disease, potential underreporting, duration of PTLDS and quality of life (health state utility) associated with PTLDS had the greatest impact on health burden. INTERPRETATION: Lyme disease contributes considerable health burden in terms of QALYs lost. Our analysis provides evidence to understand the disease burden and lays the foundation to assess the cost-effectiveness of pharmaceutical and nonpharmaceutical interventions.

Phylogenomics reveals viral sources, transmission, and potential superinfection in early-stage COVID-19 patients in Ontario, Canada.

The emergence and rapid global spread of SARS-CoV-2 demonstrates the importance of infectious disease surveillance, particularly during the early stages. Viral genomes can provide key insights into transmission chains and pathogenicity. Nasopharyngeal swabs were obtained from thirty-two of the first SARS-CoV-2 positive cases (March 18-30) in Kingston Ontario, Canada. Viral genomes were sequenced using Ion Torrent (n = 24) and MinION (n = 27) sequencing platforms. SARS-CoV-2 genomes carried forty-six polymorphic sites including two missense and three synonymous variants in the spike protein gene. The D614G point mutation was the predominate viral strain in our cohort (92.6%). A heterozygous variant (C9994A) was detected by both sequencing platforms but filtered by the ARTIC network bioinformatic pipeline suggesting that heterozygous variants may be underreported in the SARS-CoV-2 literature. Phylogenetic analysis with 87,738 genomes in the GISAID database identified global origins and transmission events including multiple, international introductions as well as community spread. Reported travel history validated viral introduction and transmission inferred by phylogenetic analysis. Molecular epidemiology and evolutionary phylogenetics may complement contact tracing and help reconstruct transmission chains of emerging diseases. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to limit future pandemics.

Long-Term Sequelae and Health-Related Quality of Life Associated With Lyme Disease: A Systematic Review.

Lyme disease (LD) is the most commonly reported vector-borne disease, but its clinical consequences remain uncertain. We conducted a systematic review of the long-term sequelae and health-related quality of life (HRQoL) associated with LD in North America and Europe. We performed searches in 6 electronic databases up to December 2018 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting long-term sequelae, HRQoL, and prognostic factors. We included 46 studies, published between 1994 and 2019. Based on 21 studies reporting attributable outcomes, higher proportions of sequelae reported from exposed patients were: neck pain, myalgia, arthralgia, paresthesia, sleep disorder, poor appetite, and concentration difficulties. Patients with PTLDS reported impaired HRQoL compared to the general US population. Included studies were highly heterogeneous in terms of study design, settings, patient characteristics, and quality. Patients with LD are more likely to report nonspecific long-term sequelae, especially those experiencing persistent symptoms posttreatment. Opportunities exist for prospective longitudinal studies to better understand LD outcomes.

2020-2021 AMMI Canada guidance on the use of antiviral drugs for influenza in the setting of co-circulation of seasonal influenza and SARS-CoV-2 viruses in Canada.

We provide an update to the Association of Medical Microbiology and Infectious Disease Canada foundation guidance for the upcoming 2020-2021 influenza season in Canada. Important issues for this year include the implications of co-circulation of SARS-CoV-2, the role of diagnostic testing, and a restatement of dosing and administration recommendations for neuraminidase inhibitors in various age groups and underlying health conditions. Although peramivir and baloxivir are now licensed in Canada, neither is currently marketed, so this guidance focuses on further optimizing the use of oseltamivir and zanamivir.

Nous actualisons l'information sur les directives de la Fondation de l'Association pour la microbiologie médicale et l'infectiologie Canada en vue de la saison grippale 2020­2021 au Canada. Cette année, les enjeux importants touchent les conséquences de la co-circulation de la maladie à coronavirus 2019, le rôle des tests diagnostiques et la réaffirmation des recommandations relatives aux maladies sous-jacentes ainsi qu'à la posologie et à l'administration des inhibiteurs de la neuraminidase dans divers groupes d'âge. Même si le péramivir et le baloxivir sont désormais homologués au Canada, ces médicaments n'y sont pas encore commercialisés, et c'est pourquoi les présentes directives visent à optimiser l'utilisation de l'oseltamivir et du zanamivir.

Estimating direct healthcare costs attributable to laboratory-confirmed Lyme disease in Ontario, Canada: A population-based matched cohort study using health administrative data.

The objective of this study was to determine healthcare costs attributable to laboratory-confirmed Lyme disease (LD) from the healthcare payer perspective in Ontario, Canada. A cost-of-illness study was conducted for incident LD subjects from 1 January 2006 through 31 December 2013 ascertained from provincial laboratory and reportable disease databases, linked to health administrative data. All LD subjects included were laboratory-confirmed, according to provincial case definitions. Incident LD subjects were propensity-score matched to uninfected subjects on age, sex, comorbidities and urban/rural status. We used phase-of-care methods to calculate attributable costs for two phases of illness: initial care (≤30 days following "index date") and continuing care (>30 days after index date to the end of the follow-up period). A total of 663 incident, confirmed LD subjects were identified from 2006 through 2013. Mean age was 44.2 ± 20.1 years; 339 (51.1%) were female; and 31 (4.7%) were hospitalized ≤30 days after index date. Six hundred fifty-eight (99.2%) LD subjects were matched to uninfected subjects; mean follow-up time was 3.3 years. Mean attributable costs per case during the initial care phase and continuing care were $277 (95% CI: $197, $357) and -$5 (-$27, $17), respectively. Attributable costs per LD subject aged 5-14 years were $440 ($132, $747), greater than the costs observed for other age strata. Expected 1-year attributable costs were $832, given continuing care costs were negligible. Limitations to our study include estimating costs using a cohort of only laboratory-confirmed LD cases, introducing selection bias for diagnosed and treated patients who may have a lower risk of developing sequelae. In conclusion, the initial care phase of LD is associated with increased healthcare costs, but without significant costs attributable to LD infection after 30 days. Estimates of costs attributable to LD are important for healthcare resource prioritization and the evaluation of novel interventions.

Use of antiviral drugs for seasonal influenza: Foundation document for practitioners-Update 2019.

This document updates the previous AMMI Canada Foundation Guidance (2013) on the use of antiviral therapy for influenza.

Le présent document est une mise à jour des précédentes directives d'AMMI Canada (2013) sur l'utilisation des antiviraux contre la grippe.

The evolving epidemiology of Clostridium difficile infection in Canadian hospitals during a postepidemic period (2009-2015).

BACKGROUND: The clinical and molecular epidemiology of health care-associated Clostridium difficile infection in nonepidemic settings across Canada has evolved since the first report of the virulent North American pulsed-field gel electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of this national, multicentre study was to describe the evolving epidemiology and molecular characteristics of health care-associated C. difficile infection in Canada during a post-NAP1-epidemic period, particularly patient outcomes associated with the NAP1 strain. METHODS: Adult inpatients with C. difficile infection were prospectively identified, using a standard definition, between 2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 64 acute care hospitals. Patient demographic characteristics, severity of infection and outcomes were reviewed. Molecular testing was performed on isolates, and strain types were analyzed against outcomes and epidemiologic trends. RESULTS: Over a 7-year period, 20 623 adult patients admitted to hospital with health care-associated C. difficile infection were reported to CNISP, and microbiological data were available for 2690 patients. From 2009 to 2015, the national rate of health care-associated C. difficile infection decreased from 5.9 to 4.3 per 10 000 patient-days. NAP1 remained the dominant strain type, but infection with this strain has significantly decreased over time, followed by an increasing trend of infection with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a higher rate of death attributable to C. difficile infection compared with non-NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.29-2.82). Isolates were universally susceptible to metronidazole; one was nonsusceptible to vancomycin. The proportion of NAP1 strains within individual centres predicted their rates of health care-associated C. difficile infection; for every 10% increase in the proportion of NAP1 strains, the rate of health care-associated C. difficile infection increased by 3.3% (95% CI 1.7%-4.9%). INTERPRETATION: Rates of health care-associated C. difficile infection have decreased across Canada. In nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1, although decreasing, continues to be the predominant circulating strain and remains significantly associated with higher attributable mortality.

Guidance for practitioners on the use of antiviral drugs to control influenza outbreaks in long-term care facilities in Canada, 2014-2015 season.

The AMMI Canada Guidelines document 'The use of antiviral drugs for influenza: A foundation document for practitioners', published in the Autumn 2013 issue of the Journal, outlines the recommendations for the use of antiviral drugs to treat influenza. This article, which represents the first of two updates to these guidelines published in the current issue of the Journal, aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season's vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in long-term care facilities for this season are provided.

Guidance on the use of antiviral drugs for influenza in acute care facilities in Canada, 2014-2015.

This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season's vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provided.