Effectiveness of the ten- and thirteen-valent pneumococcal conjugate vaccines to prevent serotype 19A invasive pneumococcal disease in Quebec, Canada. A Canadian immunization research network (CIRN) study.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7, PCV10, PCV13 and a mixed PCV10/PCV13 schedule were sequentially used without catch-up. The effectiveness of vaccination schedules to prevent serotype 19A invasive pneumococcal disease (IPD) in <5-year-old children was estimated by the indirect cohort method during 2009-2023. A total of 248 19A IPD cases and 457 IPD controls were included in the analysis. Adjusted vaccine effectiveness (VEa) for ≥1 dose was 57 % [95 %CI: -1 %,82 %] for PCV10 and 62 % [16 %,83 %] for PCV13. VEa for 3 doses was 69 % [17 %,88 %] for PCV10, 76 % [39 %,90 %] for PCV13 and 86 % [64 %,95 %] for the 2PCV10 + 1PCV13 schedule. Protection provided by the PCV10-only schedule tended to be of lower magnitude compared to the two other schedules. The mixed PCV10 + PCV13 schedule showed a protection against 19A IPD at least comparable to that of 3 PCV-13 doses.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Factors associated with intention for revaccination among patients with adverse events following immunization.

OBJECTIVES: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. METHODS: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. RESULTS: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). CONCLUSION: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children, Canada.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysis.

Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated. Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics. Interpretation: These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered. Funding: The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministère de la Santé et des Services sociaux du Québec'). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance « Tous Unis contre le Virus ¼ (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

Infected popliteal pseudoaneurysm in a youth basketball player: A case report and brief review of the literature.

INTRODUCTION: An infected popliteal pseudoaneurysm has never been described in the pediatric population. Physicians need to be aware of its presentation and management, in order to diagnose and treat this medical condition adequately. METHODS: We describe the case of a 14-year-old boy who developed myositis and cellulitis centered at the popliteal fossa after playing basketball. A treatment of intravenous cefazolin was started. 5 days later, he experienced a knee pain flare-up, which turned out to be a popliteal pyomyositis with a pseudoaneurysm of the popliteal artery. A saphenous vein graft bypass of the popliteal artery and an excision of the popliteal pseudoaneurysm were performed. Intravenous cefazolin was continued for 6 weeks and prophylactic acetylsalicylic acid for 6 months. RESULTS AND CONCLUSION: This case highlighted the importance of repeating radiologic investigations if a patient suffering from soft tissue infection has persistent pain after several days of appropriate antibiotics. A popliteal pseudoaneurysm can be diagnosed with ultrasound imaging and treated with a popliteal-popliteal bypass. Our patient needed a catheter-guided dilation of the anastomosis at the vein graft 6 months post-surgery, and then evolved favorably and went back to playing basketball 6 months post-dilation.

Revaccination and Adverse Event Recurrence in Patients with Adverse Events following Immunization.

OBJECTIVES: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence. STUDY DESIGN: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis. RESULTS: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%). CONCLUSIONS: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination.

Do intentions lead to action? Results of a longitudinal study assessing determinants of Tdap vaccine uptake during pregnancy in Quebec, Canada.

BACKGROUND: In Canada, vaccination against pertussis (Tdap) during pregnancy has been recommended since 2018, with suboptimal uptake. We aimed to assess the determinants of intention and uptake of Tdap vaccine among pregnant women in Quebec. METHODS: Participants (< 21 weeks of pregnancy) were recruited in four Quebec regions. Two online surveys were administered during pregnancy (< 21 weeks and > 35 weeks). One measured vaccination intention and the other assessed the actual decision. Questionnaires were informed by the Theory of Planned Behaviour (TPB). We used logistic multivariate analysis to identify determinants of Tdap vaccination uptake during pregnancy using responses to both questionnaires. RESULTS: A total of 741 women answered the first survey and 568 (76.7%), the second survey. In the first survey most participants intended to receive the Tdap vaccine during their pregnancy (76.3%) and in the second survey, 82.4% reported having been vaccinated against Tdap during their pregnancy. In multivariate analysis, the main determinants of vaccine uptake were: a recommendation from a healthcare provider (OR = 7.6), vaccine intention (OR = 6.12), social norms (or thinking that most pregnant women will be vaccinated (OR = 3.81), recruitment site (OR = 3.61 for General Family Medicine unit) perceived behavioral control (or low perceived barriers to access vaccination services, (OR = 2.32) and anticipated feeling of guilt if not vaccinated (OR = 2.13). Safety concerns were the main reason for not intending or not receiving the vaccine during pregnancy. CONCLUSION: We observed high vaccine acceptance and uptake of pertussis vaccine in pregnancy. The core components of the TPB (intention, social norms and perceived behavioral control) were all predictors of vaccine uptake, but our multivariate analysis also showed that other determinants were influential: being sufficiently informed about Tdap vaccination, not having vaccine safety concerns, and anticipated regret if unvaccinated. To ensure high vaccine acceptance and uptake in pregnancy, strong recommendations by trusted healthcare providers and ease of access to vaccination services remain instrumental.