A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

Invasive group A streptococcal disease surveillance in Canada, 2021-2022.

Background: Invasive group A streptococcal (iGAS, Streptococcus pyogenes) disease has been a nationally notifiable disease in Canada since 2000. This report summarizes the demographics, emm types, and antimicrobial resistance of iGAS isolates collected in Canada in 2021 and 2022. Methods: The Public Health Agency of Canada's National Microbiology Laboratory collaborates with provincial and territorial public health laboratories to conduct national surveillance of invasive S. pyogenes. Emm typing was performed using the Centers for Disease Control and Prevention emm sequencing protocol or extracted from whole-genome sequencing data. Antimicrobial susceptibilities were determined using Kirby-Bauer disk diffusion according to Clinical and Laboratory Standards Institute guidelines or predicted from whole-genome sequencing data based on the presence of resistance determinants. Results: Overall, the incidence of iGAS disease in Canada was 5.56 cases per 100,000 population in 2021, decreasing from the peak of 8.6 cases per 100,000 population in 2018. A total of 2,630 iGAS isolates were collected during 2022, representing an increase from 2021 (n=2,179). In particular, there was a large increase in isolates collected from October to December 2022. The most predominant emm type overall in 2021 and 2022 was emm49, at 21.5% (n=468) and 16.9% (n=444), respectively, representing a significant increase in prevalence since 2018 (p<0.0001). The former most prevalent type, emm1, increased from 0.5% (n=10) in 2021 to 4.8% (n=125) in 2022; similarly, emm12 increased from 1.0% (n=22) in 2021 to 5.8% (n=151) in 2022. These two types together accounted for almost 25% of isolates collected in late 2022 (October to December). Antimicrobial resistance rates in 2021 and 2022 included: 14.9%/14.1% erythromycin resistance, 4.8%/3.0% clindamycin resistance, and <1% chloramphenicol resistance. Conclusion: The increase of iGAS isolates collected in Canada is an important public health concern. Continued surveillance of iGAS is critical to monitor expanding emm types and antimicrobial resistance patterns.

Socioeconomic, health-related, and primary care physician characteristics associated with adherence to seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage cohort study.

OBJECTIVE: There is a lack of published evidence on factors associated with adherence (maintenance of cumulative vaccination) to seasonal influenza vaccination (SIV) in Manitoba, Canada. We sought to assess the associations. METHODS: A cohort study utilizing Manitoba administrative health databases. Participants received SIV in 2010/11 influenza season, remained registered Manitoba residents and received at least one SIV during the 2011/12‒2019/20 seasons. We dichotomized adherence into "more adherent" (6‒9 SIVs) and "less adherent" (1‒5 SIVs) and used multivariable adjusted generalized estimating equation logistic regression models to assess association between adherence and socioeconomic, health-related, and primary care physician (PCP) characteristics, stratified by age group (< 5, 5‒17, 18‒44, 45‒64, ≥ 65) and sex. Results are adjusted odds ratios with 95% confidence intervals. RESULTS: There were 152,493 participants. Males had lower odds of being more adherent except among ≥ 65-year-olds (1.03, 95% CI 1.01‒1.05). Compared with the lowest income quintile, those in higher income quintiles had higher odds of being more adherent. The odds mostly increased with increase in income quintile. Those with more contact with their PCP/hospitalization one year prior had higher odds of being more adherent. The odds increased with increased contact among those 18‒44, 45‒64 and ≥ 65 years old. Those who had PCP with more years of practice had higher odds of being more adherent. The odds increased as years of practice increased. These observations were mostly consistent irrespective of sex. CONCLUSION: Female gender, having higher income, having more contact with the health system, and having an experienced PCP may determine increased adherence to SIV in Manitoba. These findings require attention.

RéSUMé: OBJECTIF: Il y a un manque de données publiées sur les facteurs associés à l'adhésion vaccinale (le maintien de la vaccination cumulée) pour le vaccin contre la grippe saisonnière (VGS) au Manitoba (Canada). Nous avons cherché à évaluer ces associations. MéTHODE: Étude de cohorte utilisant les bases de données administratives sur la santé du Manitoba. Les participantes et les participants ont reçu le VGS durant la saison grippale 2010‒2011, ont continué d'être des résidents inscrits du Manitoba et ont reçu au moins un VGS au cours des saisons 2011‒2012 à 2019‒2020. Nous avons dichotomisé l'adhésion en « adhésion importante ¼ (6 à 9 VGS) et en « faible adhésion ¼ (1 à 5 VGS) et utilisé des modèles de régression logistique ajustés multivariés avec des équations d'estimation généralisées pour déterminer l'association entre l'adhésion et les caractéristiques liées au statut socioéconomique, à l'état de santé et au médecin de premier recours (MPR), stratifiées par groupe d'âge (< 5 ans, 5‒17 ans, 18‒44 ans, 45‒64 ans et ≥ 65 ans) et par sexe. Les résultats sont des rapports de cotes ajustés avec des intervalles de confiance de 95%. RéSULTATS: Il y a eu 152 493 personnes participantes. La probabilité d'une adhésion importante était inférieure chez les hommes, sauf chez les ≥ 65 ans (1,03, IC 95% 1,01‒1,05). La probabilité d'une adhésion importante était aussi plus élevée dans les quintiles de revenu supérieurs que dans le quintile de revenu inférieur. Cette probabilité augmentait principalement avec l'augmentation du quintile de revenu. Les personnes ayant eu plus de contacts avec leur MPR ou ayant été hospitalisées au cours de l'année antérieure étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec l'augmentation des contacts dans les groupes d'âge de 18‒44 ans, de 45‒64 ans et de ≥ 65 ans. Les personnes dont le MPR exerçait depuis un grand nombre d'années étaient plus susceptibles d'afficher une adhésion importante. Cette probabilité augmentait avec le nombre d'années d'exercice. Ces observations étaient pour la plupart cohérentes quel que soit le sexe. CONCLUSION: Le sexe féminin, le revenu élevé, le fait d'avoir plus de contacts avec le système de santé et le fait d'avoir un MPR d'expérience peuvent déterminer l'adhésion accrue à la vaccination contre la grippe saisonnière au Manitoba. Ces constats méritent d'être pris en considération.

Characteristics and determinants of seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage study.

Background: Seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba. Methods: We conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01-2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals. Results: SIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5-17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18-44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45-64-year-olds receiving the SIV in 2000-2004, 2005-2009, 2010-2014 and 2015-2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex. Conclusion: SIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions.

A population-based, province-wide, record-linkage interrupted time series analysis of impact of the universal seasonal influenza vaccination policy on seasonal influenza vaccine uptake among 5-64-year-olds in the province of Manitoba, Canada.

INTRODUCTION: Universal seasonal influenza vaccination policy (USIVP) was introduced in Manitoba, Canada in 2010. Its impact on seasonal influenza vaccine (SIV) uptake remains underexplored. METHODS: We used population-wide data from Manitoba to assess the impact of the USIVP on SIV uptake. The study covered twenty influenza seasons (2000/01-2019/20). We summarized SIV uptake for influenza seasons before and after the USIVP. Utilizing a single-group interrupted time series analysis and appropriately accounting for autocorrelation, we estimated absolute change and annual trend in SIV uptake percentages among 5-17-, 18-44-, and 45-64-year-olds across strata of certain population socioeconomic and health-related characteristics following the USIVP. RESULTS: Average SIV uptake percentage in all age groups was significantly higher after compared with before the USIVP. Following the USIVP, there was no significant absolute change in SIV uptake percentage among 18-44- and 45-64-year-olds overall; however, a significant decrease was observed among 18-44-year-old males in the higher income quintiles, across healthcare utilization, and in some regions of residence. A significant increase was observed among 5-17-year-olds in the lowest income quintiles, in Northern Manitoba, and among those with less healthcare utilization, and no chronic disease. Overall, there was mostly no significant annual trend in SIV uptake percentage among 18-44-year-olds, and while a significant upward and downward trend was observed among 5-17-year-olds and 45-64-year-olds, respectively, a significant downward trend was observed across all strata of population characteristics within all age groups in Northern Manitoba. CONCLUSIONS: The USIVP in Manitoba was followed by an absolute increase in SIV uptake percentage only in some socioeconomically disadvantaged subpopulations among 5-17-year-olds. While there was mostly an upward annual trend in SIV uptake percentage among 5-17-year-olds, a downward trend was observed among 45-64-year-olds and across all age groups and subpopulations in socioeconomically disadvantaged Northern Manitoba. These findings are novel for Manitoba and require investigation and public health attention.

Variability in Newborn Screening Across Canada: Spinal Muscular Atrophy and Beyond.

BACKGROUND: Newborn screening (NBS) identifies infants with severe, early-onset diseases, enabling early diagnosis and treatment. In Canada, decisions regarding disease inclusion in NBS programs occur at the provincial level, which leads to variability in patient care. We aimed to determine whether important differences exist in NBS programs across provinces and territories. Given that spinal muscular atrophy (SMA) is the most recent disease added to NBS programs, we hypothesized that its inclusion would show interprovincial variability and be more likely in provinces already screening for a greater number of diseases. METHODS: We conducted a cross-sectional survey of all NBS labs in Canada to understand: 1) what conditions were included in their program; 2) what genetic-based testing was performed and; 3) if SMA was included. RESULTS: All NBS programs (N = 8) responded to this survey by June 2022. There was a 2.5-fold difference in the number of conditions screened (N = 14 vs N = 36) and a 9-fold difference in the number of conditions screened by gene-based testing. Only nine conditions were common to all provincial NBS programs. NBS for SMA was performed in four provinces at the time of our survey, with BC recently becoming the fifth province to add SMA to their NBS on October 1, 2022. Currently, 72% of Canadian newborns are screened for SMA at birth. CONCLUSION: Although healthcare in Canada is universal, its decentralization gives rise to regional differences in NBS programs which creates inequity in the treatment, care, and potential outcomes of affected children across provincial jurisdictions.

A global systematic evidence review with meta-analysis of the epidemiological characteristics of the 2022 Mpox outbreaks.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarized published full-text epidemiological data from the outbreaks. METHODS: A global evidence review (protocol: osf.io/j3kb7) with systematic literature search up to February 09, 2023. We focused on experimental/observational studies of laboratory confirmed Mpox, excluding case reports and case series of < 5 cases. Epidemiological data were pooled using an inverse variance, random-effects model, and pooled estimates presented with associated 95% confidence intervals. RESULTS: We included 66 studies. Mean incubation period was 7.8 days (6.6-9.0 days, 8 studies: 560 cases), reproductive number 1.8 (1.7-1.9, 6 studies), mean duration from symptom onset to diagnosis 5.8 days (4.8-6.8 days, 4 studies: 982 cases), mean symptom duration 17.5 days (14.7-20.2 days, 3 studies: 292 cases), mean serial interval 8.5 days (7.3-9.9 days, 1 study), hospitalisation 6% (4-9%, 26 studies: 5339 cases), and vaccine effectiveness 78% (65-91%, 3 studies: 953 cases). Highly relevant clinical manifestations were pleomorphic skin lesions 82% (68-94%, 26 studies: 4093 cases), anogenital lesions 64% (51-77%, 9 studies: 10,398 cases), fever 54% (50-57%, 52 studies: 25,992 cases), and lymphadenopathy 51% (46-57%, 42 studies: 17,803 cases), with cases mostly men who have sex with men (MSM). Possibly relevant manifestations were perianal lesions, fatigue, asthenia, myalgia, and headache. CONCLUSIONS: The 2022 Mpox outbreaks presented with sex-related clinical manifestations and were mostly reported among MSM.

Riding high: seroprevalence of SARS-CoV-2 after 4 pandemic waves in Manitoba, Canada, April 2020-February 2022.

BACKGROUND: Canada is emerging from the largest SARS-CoV-2 Omicron wave to date, with over 3.3 million confirmed cases. Unfortunately, PCR confirmed cases illuminate only a small portion of infections in the community and underestimate true disease burden. Population based seroprevalence studies, which measure antibody levels against a virus can more accurately estimate infection rates in the community and identify geographical and epidemiological trends to inform public health responses. METHODS: The Manitoba COVID-19 Seroprevalence (MCS) study is a population-based cross-sectional study to assess the prevalence of SARS-CoV-2 antibodies across the province. Residual convenience specimens (n = 14,901) were tested for anti-SARS-CoV-2 nucleocapsid and spike IgG antibodies from April 1, 2020 to February 31, 2022. We estimated the monthly and cumulative prevalence using an exponential decay model, accounting for population demographics, sensitivity/specificity, and antibody waning. This approach generated estimates of natural infection as well as total antibody including vaccine-induced immunity within the community. FINDINGS: After four waves of the pandemic, 60.1% (95%CI-56.6-63.7) of Manitobans have generated SARS-CoV-2 antibodies due to natural exposure independent of vaccination. Geographical analysis indicates a large portion of provincial prevalence stems from increased transmission in the Northern (92.3%) and Southern (71.8%) regional health authorities. Despite the high mortality rates reported by Manitoba, infection fatality ratios (IFR) peaked at 0.67% and declined to 0.20% following the Omicron wave, indicating parity with other national and international jurisdictions. Manitoba has achieved 93.4% (95%CI- 91.5-95.1) total antibody when including vaccination. INTERPRETATION: Our data shows that more than 3 in 5 Manitobans have been infected by SARS-CoV-2 after four waves of the pandemic. This study also identifies key geographical and age specific prevalence rates that have contributed greatly to the overall severity of the pandemic in Manitoba and will inform jurisdictions considering reduction of public health measures.

Impact of the universal seasonal influenza vaccination policy in the province of Manitoba, Canada: A population-based, province-wide record-linkage study.

INTRODUCTION: In 2010, the government of the province of Manitoba, Canada introduced universal seasonal influenza vaccination policy (USIVP), providing free-of-charge vaccination to all registered residents of the province at least six months of age. Impact of the policy on seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba remains unclear, as there is a lack of published evaluations. METHODS: We conducted an ecological study, utilizing population-wide data from several linked de-identified Manitoba Health and Seniors Care administrative health databases. The study period was from 2000/01-2019/20 influenza seasons. The primary exposure was USIVP (five influenza seasons pre-policy [2005/06-2009/10] compared with post-policy [2010/11-2014/15]). The outcome was SIV uptake. We conducted pre/post logistic regression analysis stratified by age group (<5-, 5-17-, 18-44-, 45-64-, ≥65-year-olds) and certain population socioeconomic and health-related characteristics. Results are adjusted odds ratios with associated 95 % confidence intervals. RESULTS: We observed significantly increased adjusted odds of SIV uptake post-policy relative to pre-policy in all age groups except ≥65-year-olds already covered from inception of the vaccination programme. The adjusted odds ratios ranged from 0.76 (0.75-0.76) among ≥65-year-olds to 2.15 (2.13-2.18) among 5-17-year-olds, and were largely homogeneous within age groups across sex, income quintiles, regions of residence, and categories of number of visits to primary care physician/hospitalization one year prior to an influenza season except among <5- and 5-17-year-olds. These findings were mostly consistent irrespective of sex and region of residence although there was variability across income quintiles in Northern Manitoba region. CONCLUSIONS: Introduction of the USIVP in Manitoba was followed by a significant increase in SIV uptake in the five years post policy among <65-year-olds, with similar increased relative odds of vaccination observed within age groups across subpopulations. The observed variations in the relative odds of vaccination across income quintiles in Northern Manitoba region requires administrative attention.

The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020-2023.

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Genomic investigation of the most common Streptococcus pneumoniae serotypes causing invasive infections in Canada: the SAVE study, 2011-2020.

OBJECTIVES: To investigate the lineages and genomic antimicrobial resistance (AMR) determinants of the 10 most common pneumococcal serotypes identified in Canada during the five most recent years of the SAVE study, in the context of the 10-year post-PCV13 period in Canada. METHODS: The 10 most common invasive Streptococcus pneumoniae serotypes collected by the SAVE study from 2016 to 2020 were 3, 22F, 9N, 8, 4, 12F, 19A, 33F, 23A and 15A. A random sample comprising ∼5% of each of these serotypes collected during each year of the full SAVE study (2011-2020) were selected for whole-genome sequencing (WGS) using the Illumina NextSeq platform. Phylogenomic analysis was performed using the SNVPhyl pipeline. WGS data were used to identify virulence genes of interest, sequence types, global pneumococcal sequence clusters (GPSC) and AMR determinants. RESULTS: Of the 10 serotypes analysed in this study, six increased significantly in prevalence from 2011 to 2020: 3, 4, 8, 9N, 23A and 33F (P ≤ 0.0201). Serotypes 12F and 15A remained stable in prevalence over time, while serotype 19A decreased in prevalence (P < 0.0001). The investigated serotypes represented four of the most prevalent international lineages causing non-vaccine serotype pneumococcal disease in the PCV13 era: GPSC3 (serotypes 8/33F), GPSC19 (22F), GPSC5 (23A) and GPSC26 (12F). Of these lineages, GPSC5 isolates were found to consistently possess the most AMR determinants. Commonly collected vaccine serotypes 3 and 4 were associated with GPSC12 and GPSC27, respectively. However, a more recently collected lineage of serotype 4 (GPSC192) was highly clonal and possessed AMR determinants. CONCLUSIONS: Continued genomic surveillance of S. pneumoniae in Canada is essential to monitor for the appearance of new and evolving lineages, including antimicrobial-resistant GPSC5 and GPSC162.

Comparative evaluation of the clinical presentation and epidemiology of the 2022 and previous Mpox outbreaks: a rapid review and meta-analysis.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarised and compared the findings from published observational studies on the clinical presentation and epidemiology of the 2022 and previous outbreaks of Mpox. METHODS: We registered a review protocol with the Open Science Framework (osf.io/j3kb7). We searched MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases, and relevant websites up to August 30, 2022. Retrieved literature citations were screened for eligibility, and summary clinical presentation and epidemiological data from the included studies were pooled, when possible, using an inverse variance, random-effects model. RESULTS: Seventy-nine studies met the eligibility. Irrespective of outbreak, fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat were potentially highly relevant Mpox manifestations, while conjunctivitis, cough, and possibly reactivation of varicella zoster virus may be part of the clinical presentation. The mean incubation period for the 2022 outbreaks was 7.4 d (6.4-8.4 d, I2 64.2%; 4 studies: 270 cases) and for previous outbreaks, 12.9 d (10.4-15.5 d; one study: 31 cases), p < .001. None of the male cases from previous outbreaks was reported to have sex with men (MSM) whereas almost all reported male cases from the 2022 outbreak were MSM. Concomitant sexually transmitted infections and perianal lesions were reported only among male cases from the 2022 outbreak, with the cases mostly presenting with genital lesions. CONCLUSIONS: The 2022 Mpox outbreaks appear to be mostly among MSM and have a lower incubation period compared with previous outbreaks.Key messages79 studies met the review's inclusion criteria.The 2022 Mpox outbreaks appear to have shorter incubation period compared with previous outbreaks.Established clinical presentation of Mpox includes fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat.Almost all reported cases from the 2022 Mpox outbreaks were men who had sex with men (MSM).Concomitant sexually transmitted infections and perianal lesions were only reported among cases from the 2022 Mpox outbreaks.A significantly higher proportion of Mpox cases from the 2022 outbreaks had genital lesions compared with cases from previous outbreaks.The 2022 Mpox outbreaks appear to be mostly among MSM.

Dorfman pooling enhances SARS-CoV-2 large-scale community testing efficiency.

PCR-based analysis is the gold standard for detection of SARS-CoV-2 and was used broadly throughout the pandemic. However, heightened demand for testing put strain on diagnostic resources and the adequate amount of PCR-based testing required exceeded existing testing capacity. Pooled testing strategies presented an effective method to increase testing capacity by decreasing the number of tests and resources required for laboratory PCR analysis of SARS-CoV-2. We sought to conduct an analysis of SARS-CoV-2 pooling schemes to determine the sensitivity of various sized Dorfman pooling strategies and evaluate the utility of using such pooling strategies in diagnostic laboratory settings. Overall, a trend of decreasing sensitivity with larger pool sizes was observed, with modest sensitivity losses in the largest pools tested, and high sensitivity in all other pools. Efficiency data was then calculated to determine the optimal Dorfman pool sizes based on test positivity rate. This was correlated with current presumptive test positivity to maximize the number of tests saved, thereby increasing testing capacity and resource efficiency in the community setting. Dorfman pooling methods were evaluated and found to offer a high-throughput solution to SARS-CoV-2 clinical testing that improve resource efficiency in low-resource environments.

Expanded prenatal syphilis screening in Manitoba, Canada: a direct short-term cost-avoidance analysis in an outbreak context.

OBJECTIVE: The objective of this study is to provide a direct short-term cost-avoidance analysis of expanded three-time prenatal syphilis screening in the context of Manitoba's ongoing outbreak. METHODS: A conservative modelling approach increased all financial costs of prenatal screening and minimized the direct costs of congenital syphilis treatment. The cost of syphilis screening was calculated using instrument, reagent and consumable costs as well as laboratory overhead and labour costs as documented by Cadham Provincial Laboratory. The short-term direct costs of treating congenital syphilis were calculated using hospital costs and doctor's billing fees. All costs were calculated in 2021 Canadian dollars. These numbers were applied to Manitoba's 2021 congenital syphilis statistics to provide a pragmatic cost-avoidance analysis. RESULTS: The cost of applying three-time prenatal syphilis screening to all 16,800 yearly pregnancies in Manitoba equalled CAD $139,608.00 per year. The direct short-term cost of treating one uncomplicated case of congenital syphilis was $18,151.40. As 81 cases of congenital syphilis were treated in Manitoba in 2021, the short-term direct cost of treating congenital syphilis in Manitoba in 2021 was $1,470,263.40. Applying screening costs to the 125 adequately prevented cases of congenital syphilis in 2021, the screening program is associated with a cost-avoidance ratio of 16.25. If no prenatal syphilis program existed in Manitoba, an expanded screening program would be associated with a cost-avoidance ratio of 26.8. CONCLUSION: Expanding prenatal syphilis screening is highly cost-avoidant in Manitoba. The 81 cases of congenital syphilis treated in Manitoba in 2021 highlight the need for novel community-based approaches to increase accessibility and engagement with prenatal care.

RéSUMé: OBJECTIF: Dans le contexte de l'éclosion de syphilis qui sévit actuellement au Manitoba, notre étude vise à présenter une analyse des coûts directs à court terme qui pourraient être évités en étendant le dépistage de la syphilis au cours des trois trimestres de la grossesse. MéTHODE: En adoptant une approche de modélisation prudente, nous avons accru tous les coûts financiers du dépistage anténatal et réduit les coûts de traitement directs de la syphilis congénitale. Les coûts de dépistage de la syphilis ont été calculés en utilisant les coûts des instruments, des réactifs et des consommables, ainsi que les frais généraux et les coûts de main-d'œuvre des laboratoires selon le Laboratoire provincial Cadham. Les coûts directs à court terme du traitement de la syphilis congénitale ont été calculés en utilisant les frais hospitaliers et les frais facturés par les médecins. Tous les coûts ont été calculés en dollars canadiens de 2021. Ces chiffres ont été appliqués aux statistiques de 2021 du Manitoba sur la syphilis congénitale pour produire une analyse pragmatique de prévention des coûts. RéSULTATS: Le coût d'étendre le dépistage de la syphilis au cours des trois trimestres de la grossesse aux 16 800 grossesses annuelles au Manitoba représentait 139 608 $ CAN par année. Le coût direct à court terme du traitement d'un cas de syphilis congénitale sans complications était de 18 151,40 $. Étant donné que 81 cas de syphilis congénitale ont été traités au Manitoba en 2021, le coût direct à court terme du traitement de syphilis congénitale dans la province en 2021 s'est élevé à 1 470 263,40 $. En appliquant les coûts de dépistage aux 125 cas de syphilis congénitale que l'on a réussi à prévenir en 2021, le programme de dépistage est associé à un rapport de prévention des coûts de 16,25. S'il n'existait aucun programme de dépistage anténatal de la syphilis au Manitoba, un programme de dépistage élargi serait associé à un rapport de prévention des coûts de 26,8. CONCLUSION: L'expansion du dépistage anténatal de la syphilis serait une mesure de prévention des coûts très efficace au Manitoba. Les 81 cas de syphilis congénitale traités dans la province en 2021 montrent qu'il faut adopter de nouvelles approches de proximité pour améliorer l'accès et la participation aux soins anténatals.

The descriptive epidemiology of pre-omicron SARS-CoV-2 breakthrough infections and severe outcomes in Manitoba, Canada.

Introduction: Vaccination plays a key role in curbing severe outcomes resulting from COVID-19 disease. With the Omicron variant and the relaxing of public health protections breakthrough infections are increasingly common, and certain groups remain at higher risk for severe outcomes from breakthrough infections. We analysed population-based public health data from Manitoba, Canada to understand characteristics of those experiencing breakthrough infections and severe outcomes from breakthrough infections. Data from previous pandemic stages can provide valuable information regarding severe outcomes associated with breakthrough infection in the Omicron and future phases. Methods: Positive SARS-CoV-2 PCR tests from Cadham Provincial Laboratory were linked to case information from the population-based Public Health Information Management System. A retrospective design was used with time-to-event analyses to examine severe outcomes among those experiencing breakthrough infection. Results: Breakthrough cases were more likely to have 2 + chronic conditions, compared to age-, sex-, and time-period matched unvaccinated cases (24% vs. 17%), with hypertension (30%), diabetes (17%), and asthma (14%) being the most prevalent chronic conditions amongst breakthrough cases. Severe outcomes resulting from breakthrough infection was associated with age and chronic conditions, with those with 2 + chronic conditions at higher risk of severe outcomes (adjusted hazard ratio: 3.6, 95% confidence intervals: 2.0-6.4). Risk of severe outcomes varied by age group, with those 70 + years at over 13 times the risk of severe outcomes (95% CI: 4.5-39.8), compared to those 18-29 years of age. Discussion: Our results demonstrate the impact of chronic conditions on the likelihood of, and severity of outcomes from breakthrough infections. These findings underscore the importance of vaccination programs prioritizing vulnerable populations.

Characteristics of polymerase chain reaction-positive syphilis cases in Manitoba, Canada, 2017 to 2020: Demographic analysis, specimen types, and Treponema pallidum gene targets.

BACKGROUND: A resurgence of syphilis infections has been described in a number of countries including Canada in the last decade. METHODS: This study identified polymerase chain reaction (PCR) positive syphilis cases based on detection of Treponema pallidum genes (polA, tpp47, and bmp) in 3,350 clinical specimens obtained from patients in the province of Manitoba, Canada between 2017 and 2020. Patient demographics were obtained from specimen requisition forms. RESULTS: PCR identified 740 syphilis cases: 718 were adolescents and adults, while 22 were congenital syphilis cases. For non-congenital syphilis investigation, the clinical specimens with the highest yield of positive PCR results were genital (632), oral (73), and anal (55), while for congenital syphilis, they were nasal or nasopharyngeal secretions (20), followed by blood (5) and umbilical cord (4). Female syphilis cases appeared younger (61.7% between 14 and 29 years), while male syphilis cases appeared older (58.4% between 30 and 65 years). Although, overall more syphilis cases (62.7%) occurred in the urban cities; the proportion of urban cases showed a significant decline from 87.0% in 2017 to 55.6% in 2020, while in rural regions it increased from 13.0% in 2017 to 44.4% in 2020. Most (98.8%) PCR- positive specimens were found to contain all three T. pallidum genes and 99.8% also displayed the macrolide resistance genotype. CONCLUSIONS: This study identified the clinical specimen types and T. pallidum genes most suitable for PCR diagnosis of syphilis. Changing demographics of cases were noted over time.

HISTORIQUE: Depuis dix ans, les infections par la syphilis sont en recrudescence dans plusieurs pays, y compris le Canada. MÉTHODOLOGIE: La présente étude relève les cas positifs à l'amplification en chaîne par polymérase (PCR) d'après la détection des gènes du Treponema pallidum (polA, tpp47 et bmp) dans 3 350 échantillons cliniques prélevés auprès de patients de la province du Manitoba, au Canada, entre 2017 et 2020. Les caractéristiques démographiques des patients sont tirées des formulaires de réquisition des prélèvements. RÉSULTATS: Le test PCR a permis de détecter 740 cas de syphilis, soit 718 chez des adolescents et des adultes et 22 cas de syphilis congénitale. Pour ce qui est des examens de la syphilis non congénitale, les échantillons cliniques donnant le plus fort taux de résultats positifs au test PCR ont été prélevés dans la région génitale (632), orale (73) et anale (55), tandis qu'à l'égard des cas de syphilis congénitale, ils provenaient des sécrétions nasales ou nasopharyngées (20), suivis du sang (5) et du cordon ombilical (4). La syphilis se manifestait chez des femmes plus jeunes (61,7 % entre 14 et 29 ans) et plus tard chez les hommes (58,4 % entre 30 et 65 ans). Même si, dans l'ensemble, plus de cas de syphilis (62,7 %) se déclaraient en région urbaine, cette proportion a connu un recul important, passant de 87,0 % en 2017 à 55,6 % en 2020, tandis que la proportion des cas en région rurale a progressé de 13,0 % en 2017 à 44,4 % en 2020. La plupart des échantillons ayant obtenu un résultat positif au test PCR (98,8 %) contenaient les trois gènes du T. pallidum, et 99,8 % possédaient également le génotype de résistance aux macrolides. CONCLUSIONS: La présente étude a relevé les types d'échantillons cliniques et les gènes de T. pallidum les plus appropriés pour le diagnostic de syphilis par test PCR. On constate une évolution de la démographie des cas au fil du temps.

Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decrease post-vaccination. Similar increases in nasal CD8+CD69+CD103- T cells are observed, particularly following the second dose. CD4+ cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8+ T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

Evaluation of the Hologic Aptima Combo 2 Assay for Detection of Neisseria gonorrhoeae from Joint Fluid Specimens.

Gonorrhea is a sexually transmitted bacterial infection caused by Neisseria gonorrhoeae. Nucleic acid amplification testing is the preferred method for routine diagnosis of gonorrhea from urogenital specimens, but culture is commonly used for diagnosis of disseminated infections, including gonococcal arthritis. The Hologic Aptima Combo 2 (AC2), a transcription-mediated amplification assay, is FDA and Health Canada licensed for detection of N. gonorrhoeae and Chlamydia trachomatis from urogenital, rectal, and pharyngeal specimens, but not joint fluid. In the current study, we compared the performance of microscopy, culture, and the AC2 for detection of N. gonorrhoeae from 170 joint fluid specimens. A total of five specimens were culture-positive, whereas 14 were AC2-positive. Gram-negative diplococci, characteristic of Neisseria, were observed in only two joint fluid specimens. Complementary testing confirmed the presence of N. gonorrhoeae in seven discordant (i.e., culture-negative/AC2-positive) specimens. These results indicate that the AC2 is more sensitive than culture for the diagnosis of gonococcal arthritis.