Canada's approach to SARS-CoV-2 sero-surveillance: Lessons learned for routine surveillance and future pandemics.

SETTING: In Canada's federated healthcare system, 13 provincial and territorial jurisdictions have independent responsibility to collect data to inform health policies. During the COVID-19 pandemic (2020-2023), national and regional sero-surveys mostly drew upon existing infrastructure to quickly test specimens and collect data but required cross-jurisdiction coordination and communication. INTERVENTION: There were 4 national and 7 regional general population SARS-CoV-2 sero-surveys. Survey methodologies varied by participant selection approaches, assay choices, and reporting structures. We analyzed Canadian pandemic sero-surveillance initiatives to identify key learnings to inform future pandemic planning. OUTCOMES: Over a million samples were tested for SARS-CoV-2 antibodies from 2020 to 2023 but siloed in 11 distinct datasets. Most national sero-surveys had insufficient sample size to estimate regional prevalence; differences in methodology hampered cross-regional comparisons of regional sero-surveys. Only four sero-surveys included questionnaires. Sero-surveys were not directly comparable due to different assays, sampling methodologies, and time-frames. Linkage to health records occurred in three provinces only. Dried blood spots permitted sample collection in remote populations and during stay-at-home orders. IMPLICATIONS: To provide timely, high-quality information for public health decision-making, routine sero-surveillance systems must be adaptable, flexible, and scalable. National capability planning should include consortiums for assay design and validation, defined mechanisms to improve test capacity, base documents for data linkage and material transfer across jurisdictions, and mechanisms for real-time communication of data. Lessons learned will inform incorporation of a robust sero-survey program into routine surveillance with strategic sampling and capacity to adapt and scale rapidly as a part of a comprehensive national pandemic response plan.

RéSUMé: CONTEXTE: Au Canada, où le système de santé est fédéré, les 13 juridictions provinciales et territoriales ont la responsabilité individuelle de recueillir les données qui leur permettent d'élaborer leurs politiques de santé. Lors de la pandémie de COVID-19 (2020­2023), pour réaliser les enquêtes de séroprévalence à l'échelle régionale et nationale, les autorités ont principalement utilisé l'infrastructure existante pour pouvoir analyser les échantillons et recueillir des données rapidement, mais cela a également nécessité de la communication et de la coordination entre les différentes juridictions. INTERVENTION: Au Canada, il y a eu quatre enquêtes nationales et sept enquêtes régionales sur la séroprévalence du SARS-CoV-2 dans la population générale. Les méthodologies utilisées différaient selon la méthode de sélection des participants, le choix des tests d'analyses et les structures de rapports. Nous avons analysé la façon dont ces enquêtes avaient été réalisées afin d'en dégager des éléments essentiels qui permettront de planifier pour les futures pandémies. RéSULTATS: Entre 2020 et 2023, plus d'un million d'échantillons, répartis en 11 ensembles de données distincts, ont été analysés afin de rechercher la présence d'anticorps au SARS-CoV-2. Dans la plupart des enquêtes nationales, la taille de l'échantillon était insuffisante pour pouvoir estimer la prévalence à l'échelle régionale. La disparité des méthodologies utilisées a entravé la comparaison des enquêtes régionales. Seules quatre enquêtes fournissaient les données recueillies à partir des questionnaires. Il a été impossible de comparer les enquêtes entre elles en raison de la diversité des tests d'analyse utilisés, des méthodes d'échantillonnage et de la durée des enquêtes. Seules trois provinces avaient couplé leurs données avec les archives médicales. Pour réaliser les enquêtes dans les populations éloignées et lors des périodes de confinement, la méthode d'analyse sur gouttes de sang séché a été utilisée. CONCLUSION: Afin de pouvoir fournir, en temps et en heure, des données de haute qualité pour la prise de décisions en matière de santé publique, un système de sérosurveillance continuelle doit être adaptable, modulable et évolutif. En cas de pandémie, un plan national doit prévoir des consortiums pour la conception et la validation des tests d'analyse, des moyens d'amélioration de la capacité de dépistage, des documents de base pour le couplage des données, un mode de transfert du matériel entre les différentes juridictions et des moyens pour une communication en temps réel des données. Les leçons tirées de cette analyse permettront de mettre en place un solide programme d'enquêtes de séroprévalence au sein des systèmes de sérosurveillance continuelle, et que ce programme sera accompagné d'une stratégie d'échantillonnage et d'un plan d'intervention national, rapide et complet en cas de pandémie.

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.

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.

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.

Ionic current driven by a viscosity gradient.

Gradients of voltage, pressure, temperature, and salinity can transport objects in micro- and nanofluidic systems by well-known mechanisms. This paper explores the dynamics of particles in a viscosity gradient with numerical simulations. The different stochastic rules used to integrate the random motion of Brownian particles affect the steady-state distribution of particles in a diffusivity gradient. Importantly, the simulations illuminate the important role that the boundary conditions play, disallowing a steady-state flux when the boundary conditions mimic those of a closed container, but allowing flux when they mimic electrodes. These results provide an interpretation for measurements of a steady ionic current flowing between electrodes separated by a nanofluidic channel with a liquid viscosity gradient.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

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.

An Outbred Guinea Pig Disease Model for Lassa Fever Using a Host-Adapted Clade III Nigerian Lassa Virus.

Nigeria experiences annual outbreaks of Lassa fever (LF) with high case numbers. At least three clades of Lassa virus (LASV) have been documented in Nigeria, though recent outbreaks are most often associated with clade II or clade III viruses. Using a recently isolated clade III LASV from a case of LF in Nigeria in 2018, we developed and characterized a guinea pig adapted virus capable of causing lethal disease in commercially available Hartley guinea pigs. Uniform lethality was observed after four passages of the virus and was associated with only two dominant genomic changes. The adapted virus was highly virulent with a median lethal dose of 10 median tissue culture infectious doses. Disease was characterized by several hallmarks of LF in similar models including high fever, thrombocytopenia, coagulation disorders, and increased inflammatory immune mediators. High viral loads were noted in all solid organ specimens analyzed. Histological abnormalities were most striking in the lungs and livers of terminal animals and included interstitial inflammation, edema, and steatosis. Overall, this model represents a convenient small animal model for a clade III Nigeria LASV with which evaluation of specific prophylactic vaccines and medical countermeasures can be conducted.

Cross-Canada Variability in Blood Donor SARS-CoV-2 Seroprevalence by Social Determinants of Health.

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health. IMPORTANCE Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.

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.

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.

Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma.

Structural discovery of guanine nucleotide exchange factor (GEF) protein complexes is likely to become increasingly relevant with the development of new therapeutics targeting small GTPases and development of new classes of small molecules that inhibit protein-protein interactions. Syx (also known as PLEKHG5 in humans) is a RhoA GEF implicated in the pathology of glioblastoma (GBM). Here we investigated protein expression and purification of ten different human Syx constructs and performed biophysical characterizations and computational studies that provide insights into why expression of this protein was previously intractable. We show that human Syx can be expressed and isolated and Syx is folded as observed by circular dichroism (CD) spectroscopy and actively binds to RhoA as determined by co-elution during size exclusion chromatography (SEC). This characterization may provide critical insights into the expression and purification of other recalcitrant members of the large class of oncogenic-Diffuse B-cell lymphoma (Dbl) homology GEF proteins. In addition, we performed detailed homology modeling and molecular dynamics simulations on the surface of a physiologically realistic membrane. These simulations reveal novel insights into GEF activity and allosteric modulation by the plekstrin homology (PH) domain. These newly revealed interactions between the GEF PH domain and the membrane embedded region of RhoA support previously unexplained experimental findings regarding the allosteric effects of the PH domain from numerous activity studies of Dbl homology GEF proteins. This work establishes new hypotheses for structural interactivity and allosteric signal modulation in Dbl homology RhoGEFs.

Serologic testing for Bartonella in Manitoba, Canada, 2010-2020: a retrospective case series.

BACKGROUND: Bartonella are gram-negative bacilli not identified by routine bacterial culture. The objectives of this study were to review the results of all serologic testing for Bartonella ordered in Manitoba, Canada, and to review cases with positive test results among adults to assess species identification, risk factors, clinical manifestations and outcomes. METHODS: This retrospective study included all Bartonella serologic tests ordered in Manitoba and performed at the National Microbiology Laboratory, Winnipeg, from Jan. 1, 2010, until Dec. 31, 2020. We analyzed the aggregate data for all serologic tests for Bartonella for patients of all ages. We reviewed the charts of adult (age ≥ 18 yr) patients with serologic positivity for Bartonella who had a medical chart at 1 of Winnipeg's 2 largest hospitals (Health Sciences Centre and St. Boniface Hospital) to extract clinical and demographic data and create a case series. Descriptive statistics were performed. RESULTS: During the study period, 1014 Bartonella serologic tests were ordered in adult and pediatric patients, of which 24 (2.4%) gave a positive result. Sixteen adults (12 men and 4 women; mean age 48 yr) seen at a participating hospital had a positive result. Molecular species-level identification occurred on explanted cardiac valves in 5 (31%) of the 16 cases; B. quintana was identified in all 5. Six patients (38%) were diagnosed with probable B. quintana infection, for a total of 11 B. quintana cases (69%); 8 (73%) of the 11 had endocarditis. Four cases of B. quintana infection (36%) were associated with rural residence. Four cases (25%) of probable B. henselae were identified; 2 patients had fever and lymphadenopathy, and 2 had endocarditis. The remaining patient was deemed to have a false-positive result as his B. henselae titre was at the threshold for positivity, his B. quintana serologic test gave a negative result, and his clinical syndrome was not suggestive of Bartonella infection. Two patients died; both had multivalvular B. quintana endocarditis with ruptured intracranial mycotic aneurysms. INTERPRETATION: Bartonella quintana was a common cause of Bartonella serologic positivity among adults in Manitoba in 2010-2020 and was associated with endocarditis and systemic embolization. As B. quintana is transmitted by body lice, active case finding for people who lack suitable housing, both in urban and rural settings, should prioritize those with elevated Bartonella titres to receive echocardiography and detect endocarditis before systemic embolization occurs.

Multisystem Inflammatory Syndrome Following SARS-CoV-2 Vaccination in Two Children.

This report presents 2 pediatric cases of multisystem inflammatory syndrome in children and adults (MIS-C/A) post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination (MIS-V). Both children presented with MIS-V within 6 weeks of receiving their first and only dose of Pfizer-BioNTech's SARS-CoV-2 vaccine. The first patient had symptoms of MIS-C/A with peri-myocarditis and shock, and the second 1 had classic Kawasaki disease features. Both responded well to intravenous immunoglobulins and/or systemic corticosteroids. Both children were positive only for SARS-2-CoV antispike (S) (and not for antinucleocapsid [NC]) antibodies consistent with a postvaccine, and not a postinfection, event. Surveillance for rare adverse events following immunization should continue, especially now that SARS-CoV-2 vaccination is approved in the 5 to 11 year age group that has had the highest risk of developing MIS-C post SARS-CoV-2 infection. Our patients did not receive any further SARS-CoV-2 vaccines. Our report highlights the importance of measuring differentiating antibodies (anti-S and anti-NC) that can be used within a specific timeframe to help determine if a patient has MIS-V post vaccine (only anti-S present), or MIS-C/A post SARS-CoV-2 infection (both anti-S and anti-NC present).

A descriptive study of syphilis testing in Manitoba, Canada, 2015-2019.

Background: In 2018, Manitoba had the highest reported rate of infectious syphilis in Canada, at over three times the national average. Infectious syphilis in Manitoba is centred on young, marginalized heterosexual couples in Winnipeg's inner-city. Subsequently, a public health crisis involving congenital syphilis emerged in Manitoba, just prior to the coronavirus disease 2019 pandemic. Testing and screening (in the case of pregnancy) for syphilis is thought to be an effective measure to reduce the incidence of syphilis and its sequelae. The aim of this study is to describe syphilis testing practices in the general population and amongst pregnant women, during a period of shifting syphilis epidemiology. Methods: We used population-based syphilis testing data from Cadham Provincial Laboratory (Winnipeg, Manitoba) for 2015 to 2019. Directly age-standardized rates are reported, and Poisson regression used to model the determinants of testing rates. Rates of prenatal screening are also reported. Results: From 2015 to 2019, a total of 386,350 individuals were tested for syphilis. The rate increased annually, from 462 per 10,000 population in 2015 to 704 per 100,000 in 2019, while the female-to-male ratio decreased from 1.8 to 1.6. Prior to 2019, the majority of pregnant women (approximately 60%) were screened once, during the first trimester; however, 2019 saw more women having more than two tests during the course of their pregnancy. Conclusion: An overall increase in the number of individuals tested was observed, reflecting the increased rate of syphilis in Manitoba. Prenatal screening patterns shifted in 2019, likely in response to rising congenital syphilis numbers.