Single-Dose Messenger RNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Workers Extending 16 Weeks Postvaccination: A Test-Negative Design From Québec, Canada.

BACKGROUND: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination. METHODS: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly matched (10:1), randomly sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. RESULTS: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%-73%) against SARS-CoV-2 infection; 73% (95% CI, 71%-75%) against illness; and 97% (95% CI, 92%-99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%-90%) and 93% (95% CI, 89%-95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact. CONCLUSIONS: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Changing Patterns of Disease Severity in Blastomyces dermatitidis Infection, Quebec, Canada.

This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988-2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00-1.07), immunosuppression (aOR 4.2, 95% CI 1.5-11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9-14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec, Canada: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity. METHODS: Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence. RESULTS: Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63-6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03-1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12-1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13-1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30-0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39-0.98). INTERPRETATION: Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

Mortality associated with Blastomyces dermatitidis infection: A systematic review of the literature and meta-analysis.

Published case fatality in blastomycosis patients ranges between 4% and 78%. This study aimed to assess mortality associated with blastomycosis and identify its associated risk factors. We conducted a systematic review of publications related to Blastomyces dermatitidis available in PubMed and Scopus databases. Studies that reported data on blastomycosis mortality and that were published from inception through February 2018 were assessed and included in the analysis. Using the R meta package, a random-effect model meta-analysis was used to calculate pooled and stratified estimates of case-fatality proportions and risk ratios. Of 1553 publications, we included 20 studies reporting on a total of 2820 cases of blastomycosis between 1970 and 2014 and three case series reports with 10, 21, and 36 patients. The mean or median ages ranged from 28 to 59 years. Mortality was defined as attributable mortality caused by blastomycosis in 13 studies. Among 14 studies with a standard error ≤0.05, the overall pooled mortality was 6.6% (95% confidence interval [CI], 4.9-8.2) with 57% heterogeneity. The mortality rate was 37% (95% CI, 23-51) in immunocompromised patients and 75% (95% CI, 53-96) in patients who developed an acute respiratory distress syndrome (ARDS) (n = 3 studies each). ARDS was the only identified risk factor in general patients (risk ratio = 10.2). The overall mortality was significantly higher in studies involving immunocompromised patients and ARDS patients. Our analysis showed considerable heterogeneity among studies. Inconsistent mortality definitions may have contributed to the observed heterogeneity. Further research is needed to assess potential risk factors for mortality.

Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case-control study.

BACKGROUND: Anosmia and dysgeusia have been reported as potential symptoms of coronavirus disease 2019. This study aimed to confirm whether anosmia and dysgeusia are specific symptoms among those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted an age-matched case-control study in the Eastern Townships region of Quebec between Mar. 10 and Mar. 23, 2020. We included adults (age ≥ 18 yr) who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction. Cases were matched (1:1) according to 5-year age groups with control patents selected randomly from among all patients who tested negative for SARS-CoV-2 during the same period. Demographic and laboratory information was collected from medical records. Clinical symptoms and comorbidities associated with anosmia and dysgeusia were obtained by telephone interview with a standardized questionnaire. RESULTS: Among 2883 people tested for SARS-CoV-2, we identified 134 positive cases (70 women [52.2%] and 64 men [47.8%]; median age 57.1 [interquartile range 41.2-64.5] yr). The symptoms independently associated with SARS-CoV-2 positivity in conditional logistic regression were anosmia or dysgeusia or both (adjusted odds ratio [OR] 62.9, 95% confidence interval [CI] 11.0-359.7), presence of myalgia (adjusted OR 7.6, 95% CI 1.9-29.9), blurred vision (adjusted OR 0.1, 95% CI 0.0-0.8) and chest pain (adjusted OR 0.1, 95% CI 0.0-0.6). INTERPRETATION: We found a strong association between olfactory and gustatory symptoms and SARS-CoV-2 positivity. These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative.

Case Series: Report of the First Two Human Indigenous Cases of Cryptococcus gattii Infection in Eastern Canada.

We report the two first cases of human C. gattii meningoencephalitis acquired on the Canadian east coast, from the province of Quebec. Unlike C. neoformans, C. gattii is not known to have an established ecological niche on the North American east coast. C. gattii has recently been responsible for major outbreaks in British Columbia, Canada, and in the American pacific northwest. However, no human cases acquired in other Canadian provinces have been reported to our knowledge. The source of acquisition remains unclear for both patients but since neither had traveled outside of the province of Quebec, we discuss the possibilities of environmental and animal-associated acquisition, as well as the possible established endemicity in new areas. These cases add to the growing reported human and animal cases in areas previously not thought to be endemic for C. gattii.

CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling.

BACKGROUND: Ovarian cancer (OC) ascites consist in a proinflammatory tumor environment that is characterized by the presence of various cytokines, chemokines and growth factors. The presence of these inflammatory-related factors in ascites is associated with a more aggressive tumor phenotype. CCL18 is a member of CCL chemokines and its expression has been associated with poor prognosis in some cancers. However, its role in OC progression has not been established. Therefore, the aim of the current study was to elucidate the role of ascites CCL18 in OC progression. METHODS: ELISA and tissue microarrays were used to assess CCL18 in ascites and phospho-Pyk2 expression in cancer tissues respectively. Cell migration was assessed using Boyden chambers. CCL18 and ascites signaling was examined in ovarian cancer cells utilizing siRNA and exogenous gene expression. RESULTS: Here, we show that CCL18 levels are markedly increased in advanced serous OC ascites relative to peritoneal effusions from women with benign conditions. Ascites and CCL18 dose-dependently enhanced the migration of OC cell lines CaOV3 and OVCAR3. CCL18 levels in ascites positively correlated with the ability of ascites to promote cell migration. CCL18 blocking antibodies significantly attenuated ascites-induced cell migration. Ascites and CCL18 stimulated the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) in CaOV3 and OVCAR3 cells. Most importantly, the expression of phosphorylated Pyk2 in serous OC tumors was associated with shorter progression-free survival. Furthermore, enforced expression of Pyk2 promoted tumor cell migration while siRNA-mediated downregulation of Pyk2 attenuated cell migration. Downregulation of Pyk2 markedly inhibited ascites and CCL18-induced cell migration. CONCLUSIONS: Taken together, our findings establish an important role for CCL18, as a component of ascites, in the migration of tumor cells and identify Pyk2 as prognostic factor and a critical downstream signaling pathway for ascites-induced OC cell migration.

Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections.

OBJECTIVES: Patients with Clostridium difficile infection (CDI) who are re-exposed to antibiotics have a high likelihood of recurrence. We aimed to determine whether oral vancomycin as secondary prophylaxis reduces the risk of recurrence in patients recently diagnosed with CDI who undergo subsequent antibiotic exposure (CDI-AE). METHODS: We conducted a retrospective cohort study of patients diagnosed with CDI (initial episode or recurrence) between 2003 and 2011 in two tertiary care centers in Quebec, Canada and who received antibiotics not targeted against CDI within 90 days after their CDI diagnosis. Risk factors for subsequent recurrence after this exposure to antibiotics were assessed through Cox regression analyses. RESULTS: We included 551 episodes of CDI-AE (379 initial episodes, 172 recurrences). Recurrence occurred after exposure to antibiotics in 181 episodes (32.9%). Recurrence was more likely in older patients (for each additional year of age: adjusted hazard ratio (AHR), 1.01; 95% confidence interval (CI), 1.00-1.03; P=0.02) and among cases where the CDI-AE episode was itself a first (AHR, 3.59; 95% CI, 2.52-5.13; P<0.0001) or a second recurrence (AHR, 4.88; 95% CI, 3.38-7.06; P<0.0001). Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose CDI-AE itself was a recurrence (AHR, 0.47; 95% CI, 0.32-0.69; P<0.0001) but not in those whose CDI-AE was an initial episode (AHR, 0.91; 95% CI, 0.57-1.45; P=0.68). CONCLUSIONS: Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers.

BACKGROUND: Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. METHODS: A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival<6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients. RESULTS: Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P≤0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating potential was with CA125 and leptin (AUC=0.936, 95% CI: 0.894-0.978). CONCLUSION: IL-6 was found to be strongly associated with advanced serous EOC and could be used in combination with serum CA125 to discriminate benign and EOC. Furthermore, the combination of serum CA125 and ascites leptin was a strong predictor of clinical resistance to first-line therapy.

Anosmie et dysgueusie associées à l'infection au SRAS-CoV-2: étude cas­témoins appariée selon l'âge.

CONTEXTE: On a signalé l'anosmie et la dysgueusie comme symptômes potentiels de la maladie à coronavirus 2019. Cette étude visait à confirmer si ces symptômes sont caractéristiques chez les personnes ayant eu un résultat positif au dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2). MÉTHODES: Nous avons réalisé une étude cas­témoins appariée selon l'âge dans la région des Cantons-de-l'Est, au Québec, entre le 10 et le 23 mars 2020. Nous avons inclus les adultes (18 ans et plus) ayant obtenu un résultat positif au dépistage du SRAS-CoV-2 par test d'amplification en chaîne par polymérase couplée à une transcription inverse. Les cas ont été appariés (1:1) par tranche d'âge de 5 ans avec des témoins sélectionnés aléatoirement parmi tous les patients ayant eu un résultat négatif au dépistage pendant la même période. Les données démographiques et de laboratoire ont été récupérées dans les dossiers médicaux. Les symptômes cliniques et les comorbidités associés à l'anosmie et à la dysgueusie ont été notés lors d'entrevues téléphoniques faites au moyen d'un questionnaire standardisé. RÉSULTATS: Parmi les 2883 personnes soumises au dépistage du SRAS-CoV-2, nous avons recensé 134 cas positifs (70 femmes [52,2 %] et 64 hommes [47,8 %]; âge médian 57,1 ans [intervalle interquartile 41,2­64,5 ans]). Les symptômes indépendamment associés à l'infection confirmée au SRAS-CoV-2 dans une analyse de régression logistique conditionnelle étaient les suivants : anosmie et/ou dysgueusie (rapport de cotes [RC] ajusté 62,9; intervalle de confiance [IC] de 95 % 11,0­359,7), myalgie (RC ajusté 7,6; IC de 95 % 1,9­29,9), vision trouble (RC ajusté 0,1; IC de 95 % 0,0­0,8) et douleur thoracique (RC ajusté 0,1; IC de 95 % 0,0­0,6). INTERPRÉTATION: Nous avons observé un lien étroit entre les symptômes olfactifs et gustatifs et la positivité au SRAS-CoV-2. Ces symptômes devraient être considérés comme une caractéristique fréquente et distinctive de l'infection au SRAS-CoV-2 et devraient servir d'indication de dépistage, et même de répétition du dépistage chez les personnes dont le résultat initial est négatif.

The safety of seasonal influenza vaccination among adults prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. METHODS: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. RESULTS: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results. CONCLUSION: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

Fatal Mycobacterium colombiense/cytomegalovirus coinfection associated with acquired immunodeficiency due to autoantibodies against interferon gamma: a case report.

BACKGROUND: Reports of acquired immunodeficiency due to autoantibodies against interferon gamma in the adult population are increasing. The interleukin-12-dependent interferon-gamma axis is a major regulatory pathway of cell-mediated immunity and is critical for protection against a few intracellular organisms, including non-tuberculous mycobacteria and Salmonella spp. We report the first case of a fatal disseminated Mycobacterium colombiense/cytomegalovirus coinfection in an adult woman associated with the acquisition of autoantibodies against interferon-gamma. CASE PRESENTATION: A 49-year-old woman, born to nonconsanguineous parents in Laos, but who had lived in Canada for the past 30 years, presented with a 1-month history of weight loss, fatigue, cough, and intermittent low-grade fever. A thoracic computed tomography scan revealed an 8 × 7 cm irregular mass impacting the right superior lobar bronchus along with multiple mediastinal and hilar adenopathies. On the fourth day of admission, the patient developed fever with purulent expectorations. Treatment for a post-obstructive bacterial pneumonia was initiated while other investigations were being pursued. Almost every culture performed during the patient's hospitalization was positive for M. colombiense. Given the late presentation of symptoms - at the age of 49 years - and the absence of significant family or personal medical history, we suspected an acquired immunodeficiency due to the presence of anti-interferon-gamma autoantibodies. This was confirmed by their detection at high levels in the plasma and a STAT1 phosphorylation assay on human monocytes. The final diagnosis was immunodeficiency secondary to the production of autoantibodies against interferon-gamma, which resulted in a post-obstructive pneumonia and disseminated infection of M. colombiense. The clinical course was complicated by the presence of a multiresistant Pseudomonas aeruginosa post-endobronchial ultrasound mediastinitis, cytomegalovirus pneumonitis with dissemination, and finally, susceptible P. aeruginosa ventilator-associated pneumonia with septic shock and multiple organ failure, leading to death despite appropriate antibacterial and anti-mycobacterial treatment. CONCLUSIONS: Although rare, acquired immunodeficiency syndromes should be considered in the differential diagnosis of patients with severe, persistent, or recurrent infections. Specifically, severe non-tuberculous mycobacteria or Salmonella infections in adults without any other known risk factors may warrant examination of autoantibodies against interferon-gamma because of their increasing recognition in the literature.

Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study.

BACKGROUND: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination. METHODS: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection. FINDINGS: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47-63), two (69%, 64-73), or three (70%, 66-74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65-78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95-96), but was not improved with a third dose (96%, 95-97). INTERPRETATION: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant. FUNDING: Ministère de la Santé et des Services Sociaux du Québec.

Current and future burden from Lyme disease in Québec as a result of climate change.

Context: Environmental changes will foster the spread of Ixodes scapularis ticks and increase the incidence of Lyme disease in Québec in the coming years. The objective of this study is to estimate the epidemiological and clinical burden and part of the current economic burden of Lyme disease in Québec and to estimate the number of cases expected by 2050. Methods: Cases of Lyme disease reported in Québec from 2015 to 2019 were used to describe their demographic, geographical and clinical characteristics and the cost of their initial care. Three incidence rate scenarios were then developed to estimate the number of cases expected by 2050, based on demographic and climate projections. Results: From 2016 to 2019, 1,473 cases of Lyme disease were reported in Québec. Over 90% of those cases were acquired in two regions of southern Québec (Estrie and Montérégie), while the individuals infected were residents from all over Québec. The average age of cases is 44 years and 66% of infections were at the localized stage, the first stage of Lyme disease. The cost of initial care is estimated at an average of $182 CAN per patient ($47 CAN at the localized stage and $443 CAN at the disseminated stage). According to projections, over 95% of the Québec population will live in a climate zone conducive to the establishment of ticks by 2050, with a number of cases acquired in Québec being 1.3 to 14.5 times higher than in 2019, depending on the incidence rate scenario used. Conclusion: The epidemiological burden is concentrated primarily in southern Québec, but the clinical and economic burden is already distributed throughout the province. The projections for 2050 should help the regions of Québec adapt and optimize public health protection measures.

Identification of an unusual cluster of human granulocytic anaplasmosis in the Estrie region, Québec, Canada in 2021.

Background: Human granulocytic anaplasmosis (HGA) is a potentially severe tick-borne infection caused by the bacterium Anaplasma phagocytophilum (A. phagocytophilum) of the genus Rickettsia. Here, we describe the epidemiological and clinical characteristics of an unusual cluster of HGA cases detected in the Estrie region in Québec, Canada, during the 2021 transmission season. Methods: Confirmed cases of HGA were defined as individuals with typical clinical manifestations and a positive polymerase chain reaction assay. The cases were interviewed using a structured questionnaire and clinical data was obtained from medical records. Results: A total of 25 confirmed cases were identified during the 2021 transmission season, thus constituting the largest known cluster of HGA in Canada. The most common symptoms reported were fever, fatigue and headaches. Laboratory investigations found that 20 (80%) of the patients had thrombocytopenia and 18 (72%) had leukopenia at presentation. Almost half of the patients required hospitalization (n=11, 44%), with a median duration of four days (interquartile range [IQR] 2.5-5 days), including one patient who required intensive care. No deaths were recorded during the study. Epidemiological investigation found that all cases were domestically acquired, and yard maintenance was the most prevalent at-risk activity identified. Only seven (28%) cases had been aware of a tick bite in the previous two weeks. Conclusion: Detection of this unusual cluster of HGA cases provides further evidence that A. phagocytophilum may now be established along the southern border of Québec. Clinicians should consider HGA when assessing patients with typical symptoms and recent exposure to high-risk environments for tick bite.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its first variants in fourplex real-time quantitative reverse transcription-PCR assays.

The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of SARS-CoV-2. In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give the virus a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes. Furthermore, a newly developed primer-probe set targeted human ß2-microglobulin (B2M) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected ≤ 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of nine logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Fourplex assays were evaluated using 160 clinical samples positive for SARS-CoV-2. Results showed that SARS-CoV-2 viral RNA was detected in all samples, including viral strains harboring mutations in the Spike coding sequence that became dominant in the pandemic. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to allow quicker detection of circulating relevant variants in a single reaction.

Impact and benefit-cost ratio of a program for the management of latent tuberculosis infection among refugees in a region of Canada.

INTRODUCTION: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants from high-incidence regions who move to low-incidence countries is generally considered an ineffective strategy because only ≈14% of them comply with the multiple steps of the 'cascade of care' and complete treatment. In the Estrie region of Canada, a refugee clinic was opened in 2009. One of its goals is LTBI management. METHODS: Key components of this intervention included: close collaboration with community organizations, integration within a comprehensive package of medical care for the whole family, timely delivery following arrival, shorter treatment through preferential use of rifampin, and risk-based selection of patients to be treated. Between 2009-2020, 5131 refugees were evaluated. To determine the efficacy and benefit-cost ratio of this intervention, records of refugees seen in 2010-14 (n = 1906) and 2018-19 (n = 1638) were reviewed. Cases of tuberculosis (TB) among our foreign-born population occurring before (1997-2008) and after (2009-2020) setting up the clinic were identified. All costs associated with TB or LTBI were measured. RESULTS: Out of 441 patients offered LTBI treatment, 374 (85%) were compliant. Adding other losses, overall compliance was 69%. To prevent one case of TB, 95.1 individuals had to be screened and 11.9 treated, at a cost of $16,056. After discounting, each case of TB averted represented $32,631, for a benefit-cost ratio of 2.03. Among nationals of the 20 countries where refugees came from, incidence of TB decreased from 68.2 (1997-2008) to 26.3 per 100,000 person-years (2009-2020). Incidence among foreign-born persons from all other countries not targeted by the intervention did not change. CONCLUSIONS: Among refugees settling in our region, 69% completed the LTBI cascade of care, leading to a 61% reduction in TB incidence. This intervention was cost-beneficial. Current defeatism towards LTBI management among immigrants and refugees is misguided. Compliance can be enhanced through simple measures.

Management and clinical outcomes of Lyme disease in acute care facilities in 2 endemic regions of Quebec, Canada: a multicentre retrospective cohort study.

BACKGROUND: Despite increases in cases of Lyme disease, little is known about the management and clinical course of the disease in Canada. We aimed to describe the management and clinical course of Lyme disease in patients treated in acute care facilities in Quebec and to assess adherence to the 2006 Infectious Diseases Society of America (IDSA) guideline. METHODS: This retrospective multicentre cohort study included pediatric and adult patients with serologically confirmed Lyme disease treated in acute care facilities (12 community hospitals and 2 tertiary care centres) of 2 endemic regions of Quebec (Estrie and Montérégie), from 2004 to 2017. We considered drug choice, prescribed dose and treatment duration in assessing adherence of prescriptions to the 2006 IDSA guideline. The main outcome was complete resolution of symptoms at 3 months after the initiation of treatment. RESULTS: We included 272 patients from 14 institutions (age range 3-87 yr). Early disseminated Lyme disease (140 patients [51%]) was predominant. Adherence to the IDSA guideline was observed in 235 (90%) of the 261 cases with complete information, and adherence was stable over time (2004-2013: 57/64 [89%]; 2014-2015: 64/71 [90%]; 2016-2017: 114/126 [90%]; p = 0.8). Non-adherence to the guideline (n = 26) was predominantly due to longer-than-recommended treatment duration (16/26 [62%]). Resolution of objective signs at 3 months after treatment initiation occurred in 265 (99%) of 267 patients, whereas post-treatment Lyme disease syndrome was observed in 27 patients (10%) with increasing incidence over time (2004-2013: 3/65 [5%]; 2014-2015: 4/73 [5%]; 2016-2017: 20/129 [16%]; p = 0.02). INTERPRETATION: We observed clinical resolution of Lyme disease in 99% of the patients, and most treatments (90%) complied with the 2006 IDSA guideline. The incidence of post-treatment Lyme disease syndrome increased over the study period, warranting further prospective studies.