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Tetanus and diphtheria (Td) antibody titers can be measured to assess for seroprotection from immunization, though this is not routinely indicated. There are limited population level data on the utilization of these tests and their results. This is a population level retrospective study based on laboratory data collected from patients who underwent Td antibody testing. Td IgG titer requests from May 1, 2023, to December 31, 2024, were extracted from the provincial health information system of Alberta, Canada. Td anti-toxin test requests, geometric mean titers, and vaccination status of patients who underwent testing were analyzed. Individuals with multiple tests were assessed for changes in antibody levels, and the proportion of tested individuals who were vaccinated within the past 10 years was calculated. Geometric mean titers were interpreted in relation to established thresholds for long-term protective immunity. A total of 2,550 patients underwent testing for tetanus (n = 2,349) and diphtheria (n = 2,093) anti-toxin antibody levels. Geometric mean titers varied widely across physician specialties, with pediatrics and Immunology showing higher proportions of recent vaccinations and higher geometric mean titers, while general practice and nephrology had lower values. Nearly 40% of diphtheria test orders in patients immunized within the past 10 years were requested by general practice (n = 336). In contrast, less than 20% of tests were ordered by nephrology (n = 153), pediatrics (n = 95), and pharmacy (n = 12). Over half the tests were requested by general practice. Our study highlighted variability in vaccination patterns and immune responses across specialties. While antibody testing is useful for assessing protection, a considerable number of tests were performed in individuals likely to be protected by recent vaccination, pointing to inefficiencies and unnecessary healthcare spending. These findings underscore the importance of aligning test ordering practices with immunization history to optimize resource use, avoid redundant testing, support diagnostic stewardship, and inform more cost-effective public health strategies.

Background Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). Objectives We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. Methods We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. Results Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I 2  = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I 2  = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. Conclusions During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

The incidence of invasive group A Streptococcus (iGAS) disease in the general population in Alberta, Canada, has been steadily increasing. To determine whether rates for specific populations such as First Nations are also increasing, we investigated iGAS cases among First Nations persons in Alberta during 2003-2017. We identified cases by isolating GAS from a sterile site and performing emm typing. We collected demographic, social, behavioral, and clinical data for patients. During the study period, 669 cases of iGAS in First Nations persons were reported. Incidence increased from 10.0 cases/100,000 persons in 2003 to 52.2 cases/100,000 persons in 2017. The 2017 rate was 6 times higher for the First Nations population than for non-First Nations populations (8.7 cases/100,000 persons). The 5 most common emm types from First Nations patients were 59, 101, 82, 41, and 11. These data indicate that iGAS is severely affecting the First Nations population in Alberta, Canada.

The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29–4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33–1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.

After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being <65 years of age, experiencing homelessness, having a diagnosis of pneumonia or empyema, or using illicit drugs.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018–2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

Background Group A streptococci (Strep A) or Streptococcus pyogenes is a major human pathogen causing an estimated 500,000 deaths worldwide each year. Disease can range from mild pharyngitis to more severe infections, such as necrotizing fasciitis, septicemia, and toxic shock syndrome. Untreated, Strep A infection can lead to the serious post streptococcal pathologies of rheumatic fever/rheumatic heart disease and post-streptococcal glomerulonephritis. An effective vaccine against Strep A would have great benefits worldwide. Here, we test two products, J8 and p*17—both peptide derivatives of a highly conserved region in the M protein, in combination with the protein subunit K4S2 of SpyCEP, an IL-8 protease associated with neutrophil chemoattraction. Each peptide is individually conjugated to cross reacting material (CRM 197 ), and the conjugated peptide vaccines are abbreviated as J8-K4S2 or p*17-K4S2. Methods This single-site phase I, two-stage clinical trial in Edmonton, Alberta, Canada, aims to recruit a total of 30 healthy volunteers, aged 18–45 years, without any evidence of pre-existing valvular heart disease. The trial is divided into the initial unblinded safety test dose stage (stage 1) and the randomized, double-blinded, controlled trial stage (stage 2). Stage 1 will recruit 10 volunteers—5 each to receive either J8-K4S2 or p*17-K4S2 in an unblinded, staggered fashion, whereby volunteers are dosed with intentional spacing of at least 2 days in between doses to monitor for any immediate side effects before dosing the next. Once all 5 volunteers have received 3 doses of the first test vaccine, a similar process will follow for the second test vaccine. Once safety is established in stage 1, we will proceed to stage 2, which will recruit 20 volunteers to our 3-arm randomized controlled trial (RCT), receiving either of the trial vaccines, J8-K4S2 or p*17-K4S2, or comparator (rabies) vaccine. All product dosing will be at 0, 3, and 6 weeks. The primary outcome is vaccine safety; the secondary outcome is immunogenicity and comparative analyses of the different vaccine regimens. Discussion This Strep A vaccine clinical trial aims to investigate safety and immunogenicity of two novel conjugated peptide-based vaccines, J8-KS42 and p*17-K4S2. If one or both vaccine products demonstrate favorable primary and secondary outcomes, the product(s) will move into phase II and III studies. Trial registration ClinicalTrials.gov Identifier: NCT04882514. Registered on 2021–05-12, https://clinicaltrials.gov/study/NCT04882514 .

Background Group B streptococci (GBS) are important neonatal bacterial pathogens that can cause severe invasive disease in the newborn. It is thought that in many cases of invasive neonatal GBS disease, the bacteria ascend the vagina into the uterus and infect the amniotic fluid surrounding the fetus. Important constituents of this environment include the polyols or sugar alcohols of which erythritol, sorbitol and mannitol are examples. The aim of our study was to investigate the effect of polyols on GBS grown in media containing these sugar alcohols. Results GBS incubated in varying concentrations of polyols (erythritol, sorbitol or mannitol) did not display any significant enhancement or inhibition of bacterial growth. However, growth of GBS in the presence of erythritol significantly increased the surface expression of GBS-PGK (a plasminogen binding protein) 1.25 to 1.5-fold depending on the erythritol concentration and significantly enhanced the survival in human blood 3X to 18X depending on the concentration of polyol used. Interestingly, GBS grown in 1% erythritol significantly increased invasion by the bacteria of HeLa cells (epithelial cell line) (150% vs 100%) however, at higher concentrations (2% or 4% of polyol) the number of CFUs was significantly reduced (55-75% vs 100%) suggesting higher concentrations of polyols may inhibit invasion. Erythritol also increased GBS hemolytic activity as well as enhancing biofilm formation 1.4X to 3.3X depending on the concentration of polyol used. Conclusions GBS grown in the presence of polyols alters the bacteria’s phenotype resulting in changes associated with GBS virulence. This effect was greatest for the polyol erythritol.

Background.Routine infant vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) began in the Calgary Health Region (Alberta, Canada) in 2002. We measured the impact of this vaccine program on invasive pneumococcal disease (IPD). Methods.Prospective, population-based surveillance of all cases of IPD (with culture specimens obtained from sterile sites) was conducted from January 1998 through December 2007. Demographic and clinical data were collected. All viable isolates were saved and serotyped. Results.There were 1182 IPD cases over the 10-year period. Comparison of the vaccine period (2003–2007) with the prevaccine period (1998–2001) revealed that the incidence of IPD due to PCV7 serotypes decreased significantly by 86%, 59%, 38%, and 78% in the 6-23-month, 2-4-year, 16-64-year, and 65-84-year age groups, respectively. The total number of IPD cases decreased by 77%, 45%, and 34% in the 6-23-month, 2-4-year, and 65-84-year age groups, respectively. The incidence of IPD due to non-PCV7 serotypes increased by 183%, and the total incidence of IPD increased by 73% among adults aged 16-64 years; however, this increase was primarily attributed to a large outbreak of serotype 5 IPD among homeless adults during the period 2005–2007. There were 5 cases of IPD due to PCV7 serotypes among vaccinated children in the vaccine period. Conclusions.Since the introduction of PCV7 vaccine, there has been a profound decrease in the total number of cases of IPD among children and in cases due to PCV7 serotypes among subjects of all ages in Calgary, indicating a strong direct effect and herd effect of the vaccine. The serotypes that now cause IPD have changed significantly. The magnitude and impact of replacement IPD caused by non-PCV7 serotypes is not yet known.

Canada has one of the lowest rates of tuberculosis (TB) in the world, however, among certain sub-populations, disease incidence rates approach those observed in sub-Saharan Africa, and other high incidence regions. In this study, we applied mycobacterial interspersed repetitive unit (MIRU) variable number of tandem repeat (VNTR) and whole genome sequencing (WGS) to the analysis of Mycobacterium tuberculosis isolates obtained from Northern communities in the territory of Nunavut. WGS was carried out using the Illumina MiSeq, with identified variants used to infer phylogenetic relationships and annotated to infer functional implications. Additionally, the sequencing data from these isolates were augmented with publically available WGS to evaluate data from the Nunavut outbreak in the broader Canadian context. In this study, isolates could be classified into four major clusters by MIRU-VNTR analysis. These could be further resolved into sub-clusters using WGS. No evidence for antimicrobial resistance, either genetic or phenotypic, was observed in this cohort. Among most subjects with multiple samples, reactivation/incomplete treatment likely contributed to recurrence. However, isolates from two subjects appeared more likely to have occurred via reinfection, based on the large number of genomic single nucleotide variants detected. Finally, although quite distinct from previously reported Canadian MTB strains, isolates obtained from Nunavut clustered most closely with a cohort of samples originating in the Nunavik region of Northern Quebec. This study demonstrates the benefit of using WGS for discriminatory analysis of MTB in Canada, especially in high incidence regions. It further emphasizes the importance of focusing epidemiological intervention efforts on interrupting transmission chains of endemic TB throughout Northern communities, rather than relying on strategies applied in regions where the majority of TB cases result from importation of foreign strains.