The impact of influenza on the ability to work, volunteer and provide care: results from an online survey of Canadian adults 50 years and older.

BACKGROUND: Influenza is associated with a decline in functional abilities among Canadian older adults, although specific impacts on daily life have not been fully explored. METHODS: In August 2019 and May 2020, we conducted surveys of Canadian adults 50-64 years and 65 years and older through an online market research platform. The survey included questions about the impact of diagnosed influenza or self-reported influenza-like-illness (ILI) on working, volunteering and caregiving. RESULTS: We surveyed 1006 adults in the 50-64 year age group about the 2018/19 season and 1001 about the 2019/20 season. In the 65 years and older age group, we surveyed 3548 and 3500 individuals about the 2018/19 and 2019/20 influenza seasons, respectively. In each season, nearly two-thirds of individuals 50-64 years with influenza/ILI were employed; 51.7% reported absenteeism in 2018/19 and 53.6% in 2019/20. Of the 20% of individuals 65 years and older who were employed, 47.0% of those with influenza/ILI were absent while ill in 2018/19 (39.8% in 2019/20). In 2018/2019, 29.6% of respondents 50-64 years old with influenza/ILI identified as volunteers (29.3% in 2019/2020). In both seasons, nearly half were unable to do so while ill. Of the 164 (32.7%) individuals 65 years and older who volunteered during the 2018/19 season, 80 (48.8%) did not while ill; 224 (37.3%) respondents volunteered in the 2019/20 season, and half were absent while ill. Of those 50-64 years with influenza/ILI, 97 (42.2%) and 57 (22.2%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19 and 2019/20, 40 (41.2%) and 28 (49.1%) caregivers were unable to provide care when ill, respectively. Of those with influenza/ILI in the 65 years and older age group, 123 (24.6%) and 162 (27.0%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19, 18 (14.6%) caregivers with influenza/ILI did not provide care while ill (42 [25.9%] in 2019/20). DISCUSSION: In Canadian older adults, influenza and ILI had notable impacts on ability to volunteer and provide care across two recent seasons. Optimization of influenza prevention in this population may yield important societal benefits.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

Effectiveness and cost-effectiveness of vaccination against herpes zoster in Canada: a modelling study.

BACKGROUND: Two vaccines against herpes zoster are currently authorized for use in Canada: the recombinant subunit zoster vaccine and live attenuated zoster vaccine. We compared the effectiveness and cost-effectiveness of these 2 vaccines. METHODS: We used a decision analytic static cohort model parametrized with Canadian epidemiologic and economic data. We performed the economic analysis from the health care system perspective, using a lifetime horizon and a 3% discount rate for costs and benefits. The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained, relative to no vaccination. We ran 30 000 simulations varying all model parameters, including vaccine costs, efficacy and waning. RESULTS: The number needed to vaccinate (NNV) was higher for the live attenuated zoster vaccine than for the recombinant subunit zoster vaccine for all herpes zoster-related events at all ages. For example, in persons exactly 65 years old, for herpes zoster, median NNV was 21 (90% uncertainty interval [UI] 13-31) versus 8 (90% UI 6-18), and for postherpetic neuralgia, NNV was 64 (90% UI 33-93) versus 31 (90% UI 23-73). For the recombinant vaccine, the median cost-effectiveness ratios varied between cost-saving and $25 881 per QALY gained for adults aged 50 years or older. For the live vaccine, the cost-effectiveness ratios varied between cost-saving and $130 587 per QALY gained and were less than $45 000 per QALY gained only for those 65 to 75 years old. Given its higher efficacy, we estimated that the cost for the complete series of the recombinant vaccine could be $150 to $200 more than the cost of the live vaccine and still be considered cost-effective. INTERPRETATION: Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older, and is likely more cost-effective than live attenuated zoster vaccine. These results have informed updated national and provincial recommendations on herpes zoster vaccination.

EXamining the knowledge, Attitudes and experiences of Canadian seniors Towards influenza (the EXACT survey).

BACKGROUND: Older adults are at high risk for influenza-related complications including worsening frailty and function. We surveyed older Canadians to explore the impact of influenza and determine how influenza knowledge influences vaccination decision-making. METHODS: We disseminated an online survey through a national polling panel. The survey included questions about the respondents' influenza vaccination practices and knowledge about influenza. Using validated measures, they reported their frailty and functional status prior to the 2016/17 influenza season, during illness (if applicable), and following the season. Regression analyses were used to examine predictors of poor functional outcomes. RESULTS: Five thousand and fourteen adults aged 65 and older completed the survey; mean age was 71.3 ± 5.17 years, 42.6% had one or more chronic conditions, 7.8% were vulnerable and 1.8% were frail. 67.9% reported receiving last season's influenza vaccine. Those who rarely/never receive the influenza vaccine were significantly less likely to correctly answer questions about influenza's impact than those who receive the vaccine more consistently. Of the 1035 (21.5%) who reported experiencing influenza or influenza-like illness last season, 40% indicated a recovery longer than 2 weeks, and one-fifth had health and function declines during this time. Additionally, 3.1% of those afflicted "never fully recovered". Older age, significant trouble with memory and having influenza/ILI were among the independent predictors of persistent declines in health and function. CONCLUSIONS: Given that frailty and function are important considerations for older adults' well-being and independence, healthcare decision-makers must understand the potential for significant temporary and long-term impacts of influenza to make informed vaccine-related policies and recommendations.

Factors associated with human papillomavirus (HPV) test acceptability in primary screening for cervical cancer: A mixed methods research synthesis.

Primary screening for cervical cancer is transitioning from the longstanding Pap smear towards implementation of an HPV-DNA test, which is more sensitive than Pap cytology in detecting high-risk lesions and offers greater protection against invasive cervical carcinomas. Based on these results, many countries are recommending and implementing HPV testing-based screening programs. Understanding what factors (e.g., knowledge, attitudes) will impact on HPV test acceptability by women is crucial for ensuring adequate public health practices to optimize cervical screening uptake. We used mixed methods research synthesis to provide a categorization of the relevant factors related to HPV primary screening for cervical cancer and describe their influence on women's acceptability of HPV testing. We searched Medline, Embase, PsycINFO, CINAHL, Global Health and Web of Science for journal articles between January 1, 1980 and October 31, 2017 and retained 22 empirical articles. Our results show that while most factors associated with HPV test acceptability are included in the Health Belief Model and/or Theory of Planned Behavior (e.g., attitudes, knowledge), other important factors are not encompassed by these theoretical frameworks (e.g., health behaviors, negative emotional reactions related to HPV testing). The direction of influence of psychosocial factors on HPV test acceptability was synthesized based on 14 quantitative studies as: facilitators (e.g., high perceived HPV test benefits), barriers (e.g., negative attitudes towards increased screening intervals), contradictory evidence (e.g., sexual history) and no impact (e.g., high perceived severity of HPV infection). Further population-based studies are needed to confirm the impact of these factors on HPV-based screening acceptability.

Herpes Zoster Burden in Canadian Provinces: A Narrative Review and Comparison with Quebec Provincial Data.

BACKGROUND: The main aim of this review was to assess incidence rates and trends of medically attended and death cases of herpes zoster in Canada. METHODS: The search was conducted in five databases (PubMed, Cochrane, Embase, PsycNET, and Web of Science). Data on herpes zoster-related consultations and hospitalisations and deaths were also extracted from three Quebec provincial administrative databases (RAMQ, MED-ECHO, and ISQ). RESULTS: The electronic search yielded 587 publications. Seventeen publications satisfied inclusion criteria. These publications reported data from eleven studies. Ten studies used provincial databases, and one study used the Canadian Primary Care Sentinel Surveillance Network electronic database. Seven studies evaluated overall rates of medically attended cases (consultations and hospitalisations). Four of these studies reported an increase in rates of medically attended cases during the study period; one study reported stable rates, and two studies reported only an average rate. The rates varied from 316 to 450/100,000 p.y. The Quebec analysis shows similar rates with a slight decreasing trend (from 369 to 350/100,000 p.y.). Incidence rates of consultations were reported separately in three studies. Two studies reported an increase in rates (from 258 to 348/100,000 p.y. and from 324 to 366/100,000 p.y.), and the third study reported a decrease (from 525 to 479/100,000 p.y.). Hospitalization rates were reported separately in two studies, both reporting a decrease (from 12 to 8 cases/100,000 p.y. and from 9 to 4 cases/100,000 p.y.). Quebec data also showed a decrease, from 9 to 6 cases/100,000 p.y. One study reported herpes zoster-related deaths. In this study, the reported death rate was 0.7/1,000,000 p.y. in the overall population and 5.5/1,000,000 p.y. in those aged ≥65 years. Quebec analysis showed a death rate of 1.2/1,000,000 p.y. in the overall population and 8.6/1,000,000 p.y. in those aged ≥65 years. CONCLUSIONS: The results of the reviewed studies and our analysis of Quebec provincial data indicate important variations in the reported overall incidence rates of medically attended herpes zoster cases in Canada. The trends in time are heterogeneous in studies in which hospitalisations and medical consultations were pooled together. We observed a decrease in hospitalization rates and a slight increase in consultation rates in studies reporting hospitalisations and consultations separately. These results consolidate the understanding of the herpes zoster burden in Canada and might be used as a tool in decision-making regarding future preventive interventions.

Impact of an Immunization Campaign to Control an Increased Incidence of Serogroup B Meningococcal Disease in One Region of Quebec, Canada.

Background: Invasive meningococcal disease (IMD) incidence increased in Quebec, starting in 2003, and was caused by a serogroup B sequence type 269 clone. The Saguenay-Lac-Saint-Jean (SLSJ) region was particularly affected with a rate of 3.4 per 100000 person-years in 2006-2013. In May 2014, an immunization campaign was launched in SLSJ, using the 4-component protein-based meningococcal vaccine (MenB-4C). We aimed to evaluate the impact of the campaign 2 years after its initiation. Methods: Immunization registry data and serogroup B invasive meningococcal disease (B-IMD) cases notified to public health authorities and confirmed by culture or polymerase chain reaction from July 1996 to December 2016 were analyzed, including a multivariate Poisson regression model of incidence rates. Results: By the end of the campaign, 82% of the 59000 targeted SLSJ residents between 2 months and 20 years of age had been immunized. Following the initiation of the campaign, no B-IMD case occurred among vaccinees, whereas 2 cases were reported among unvaccinated adult SLSJ residents, and a third case in an unvaccinated child who had stayed in the region during the week prior to disease onset, in 2015. B-IMD incidence decreased in all other regions in the years 2015-2016 but sporadic cases continued to occur. A multivariate analysis showed a significant effect of the campaign in the SLSJ region (relative B-IMD risk: 0.22; P = .04). Conclusions: Results suggest a high level of protection provided by MenB-4C following mass vaccination at regional level. This, along with reassuring safety data, supports the current recommendations for MenB-4C use for controlling outbreaks caused by clones covered by the vaccine.

Psychosocial determinants of parental human papillomavirus (HPV) vaccine decision-making for sons: Methodological challenges and initial results of a pan-Canadian longitudinal study.

BACKGROUND: HPV vaccination decision-making is a complex process that is influenced by multiple psychosocial determinants. Given the change in policy recommendation to include males in routine HPV vaccination, our goals were to assess the HPV vaccination uptake in Canada, to understand where Canadian parents were situated in the HPV vaccine decision-making process for their son, how they changed over time and which psychosocial determinants were relevant for this process. METHODS: We used an online survey methodology and collected data from a nationally representative sample of Canadian parents of boys aged 9-16 at baseline (T1, February 2014) and at 9 months' follow-up (T2). Our analyses were guided by the Precaution Adoption Process Model (PAPM), a theoretical health behavior model that classifies parents in one of six stages: unaware, unengaged, undecided, decided not to vaccinate, decided to vaccinate and those who had already vaccinated their sons. Rigorous methods were used to filter out careless responders: response variance, bogus items, psychometric antonyms and psychometric synonyms. RESULTS: At T1 and T2, we received 3,784 and 1,608 respectively completed questionnaires; after data cleaning 3,117 (T1) and 1,427 (T2) were retained. Less than 3% of boys were vaccinated at both time points. At both T1 and T2, most parents (over 70%) belonged to the earlier vaccination adoption stages: 57% were unaware (T1) and 15.3% (T2); 20.9% were unengaged (T1) and 32.4% (T2); and 9.1% were undecided (T1) and 25.2% (T2). At follow-up, 37.7% of participants did not move from their initial PAPM decision-making stage. Most parents (55%) preferred to receive information from their healthcare provider (HCP) but only 6% (T1) and 12% (T2) had actually spoken with a HCP about the HPV vaccine for their son. CONCLUSIONS: HPV vaccination uptake in Canadian boys was very low in the absence of a publicly funded HPV vaccination programs for boys. Optimal HPV information preferences were identified and can be used in interventions to increase HPV knowledge and increase HPV vaccine uptake. Intentions to vaccinate or planning to speak to one's HCP did not translate into action for most parents over the 9-month follow up; this finding is critical to consider to inform implementation strategies. Methodological challenges are described and suggestions for future research are offered.

Dramatic reduction in hepatitis B through school-based immunization without a routine infant program in a low endemicity region.

BACKGROUND: Hepatitis B (HB) prevention in the low-endemicity province of Quebec Canada, (population: ~8.2 million; birth cohort ~85,000/year), includes two decades of pre-adolescent school-based immunization, as well as catch-up immunization for those born since 1983 and pre-natal maternal HBsAg screening. To estimate the potential added benefit of routine infant HB immunization, notifiable disease reports were analyzed (1990-2013). Clinical and demographic information about cases was retrieved from standard questionnaires used by local public health units to investigate HB cases. METHODS: The Quebec provincial registry of notifiable diseases was used to identify confirmed HB cases reported between 1990 and 2013. Clinical and demographic information on cases was retrieved from the standard questionnaires used by local public health units to investigate reported HB cases. RESULTS: Between 1990-2013, acute-HB incidence per 100,000 population decreased by 97 % from 6.5 to 0.2. Compared to 1990, incidence fell from 0.6 to zero since 2010 among children ≤9 years of age (yoa), from 3.2 to zero since 2007 in those 10-19 yoa, and from 15 to zero in 2013 among adults 20-29 yoa, previously the age group of highest incidence (all p < 0.0001). During the same period, the newly-reported chronic HB rate per 100,000 decreased by 66 % from 17.7 to 6.1 (p < 0.0001), with a reduction of 92 % (2.4 to 0.2;p < 0.001) in children ≤9 yoa and 83 % (7.2 to 1.2;p = 0.003) in those 10-19 yoa. The incidence of unspecified HB cases did not decrease significantly overall (5.9 vs. 5.4; p = 0.24), in children ≤ 9 yoa (0.3 vs. 0.2;p = 0.70) or 10-19 yoa (1.6 vs. 1.5;p = 0.45). Overall, 91 % of cases ≤19 yoa were immigrants likely infected before arrival in Canada. Among those ≤9 yoa, there were 9 acute-HB case reports between 2005 and 2013, of whom 8 were not preventable by infant immunization. CONCLUSIONS: Two decades of school-based immunization coupled with prenatal screening achieved striking reduction in disease burden in the low-endemicity province of Quebec, Canada. The oldest cohorts targeted by catch-up campaigns are now beyond the average age at childbirth so that neo-natal transmission and the potential incremental benefit of infant immunization will likely further diminish.

Global travel patterns and risk of measles in Ontario and Quebec, Canada: 2007-2011.

BACKGROUND: In 2011 the largest measles outbreak in North America in a decade occurred in Quebec, Canada with over 700 cases. In contrast, measles activity in neighbouring province Ontario remained low (8 cases). Our objective was to determine the extent to which the difference could be explained by differing travel patterns. METHODS: We explored the relationship between measles cases over 2007-2011, by importation classification, in Quebec and Ontario in relation to global travel patterns to each province using an ecological approach. Global measles exposure was estimated by multiplying the monthly traveler volume for each country of origin into Quebec or Ontario by the yearly measles incidence rate for the corresponding country. Visual inspection of temporal figures and calculation of Pearson correlation coefficients were performed. RESULTS: Global measles exposure was similar in Ontario and Quebec. In Quebec, there was a nearly perfectly linear relationship between annual measles cases and its global measles exposure index over 2007-2011 (r = 0.99, p = 0.001). In contrast, there was a non-significant association in Ontario. The 2011 rise in Quebec's index was largely driven by a dramatic increase in measles activity in France the same year. CONCLUSIONS: Global measles activity was associated with measles epidemiology in Quebec. Global measles exposure risk is higher in Ontario than Quebec. Differences in measles epidemiology between Ontario and Quebec from 2007-2011 are not explained by greater exposure in Quebec. A combination of alternative factors may be responsible, including differences in population susceptibility.

Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v).

BACKGROUND: Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. METHODS: Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged ≥65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). RESULTS: The overall prevalence of HI titers of ≥40 against A(H3N2)v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. CONCLUSIONS: A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread. CLINICAL TRIALS REGISTRATION: NCT01140009 and NCT01368796.

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.

Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA-Vaccinated and Nonvaccinated Individuals in Quebec, Canada.

Importance: The Omicron variant is phylogenetically and antigenically distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron reinfection, with and without vaccination, requires quantification. Objective: To estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine. Design, Setting, and Participants: This test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada. Exposures: Prior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination. Main Outcomes and Measures: The main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 - the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results: This study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning. Conclusions and Relevance: The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

Continuing Medical Education Improves Physician Communication Skills and Increases Likelihood of Pediatric Vaccination: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-II.

This study evaluated the impact of a continuing medical education (CME) program that emphasized actionable information, motivation to act, and skills to strengthen physician recommendations for seasonal influenza vaccination in children 6 through 23 months of age for whom influenza immunization rates are suboptimal. Physicians were randomly assigned to an accredited CME program or to no CME. Participants completed pre- and post-study questionnaires. Influenza immunization rates were compared between groups. A total of 33 physicians in the CME group and 35 in the control group documented 292 and 322 healthy baby visits, respectively. Significantly more parents immunized their children against influenza after interacting with CME-trained physicians than those with no CME training (52.9% vs. 40.7%; p = 0.007). The odds ratio for vaccination after visits with CME-trained physicians was 1.52 (95% confidence interval 1.09 to 2.12; p = 0.014), which was unaffected by the socioeconomic status of parents. Parents who discussed influenza vaccination with CME-trained physicians were 20% more likely to choose an approved but publicly unfunded adjuvanted pediatric influenza vaccine. The percentages of physicians reporting the highest levels of knowledge, ability, and confidence doubled or tripled after the CME intervention. Significantly more parents immunized very young children after interacting with physicians who had undergone CME training.

Clinicians Are Not Able to Infer Parental Intentions to Vaccinate Infants with a Seasonal Influenza Vaccine, and Perhaps They Should Not Try: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-IV.

This prospective cohort survey evaluated the concordance of clinicians' perceptions of parental intentions and parents' actual intentions to vaccinate their infants against influenza. During a routine healthy baby visit, clinicians provided parents with information about influenza, children's vulnerability to influenza, and nonadjuvanted and adjuvanted trivalent influenza vaccines (TIV and aTIV, respectively). Before and after the clinician−parent interaction, parents were surveyed about their attitudes, their perceptions of support from significant others, and the intention to vaccinate their infant with aTIV. Clinicians were asked about their perception of parents' intentions to choose aTIV for their children. These assessments included 24 clinicians at 15 community practices and nine public health clinics, and 207 parents. The correlation coefficients of the clinicians' assessment of parents' intention to vaccinate were 0.483 (p < 0.001) if the vaccine was presented as free of cost, 0.266 (p < 0.001) if the cost was $25, and 0.146 (p = 0.036) if the cost was $50, accounting for 23%, 7%, and 2% of the variance in parental intentions, respectively. The clinicians were poor at predicting parental intentions to immunize, particularly when cost was involved. Information on vaccine options and influenza infection should be provided for every eligible patient to allow parents to determine if the vaccine is appropriate for their child.

Parental Attitudes and Perceptions of Support after Brief Clinician Intervention Predict Intentions to Accept the Adjuvanted Seasonal Influenza Vaccination: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-I.

Adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against seasonal influenza in children compared with nonadjuvanted trivalent influenza vaccine (TIV). This prospective cohort study assessed parental attitudes, beliefs, and intentions to vaccinate their infants aged 6-23 months with aTIV. Parents were surveyed before and after routine healthy baby visits, and post clinician interaction results were analyzed using multivariable logistic regression. Physicians at 15 community practice clinics and nurses at 3 public health clinics participated; 207 parents were surveyed. After clinician consultation, most parents considered immunization with aTIV to be safe (72.9%), effective (69.6%), and important (69.0%); most perceived support for vaccination from significant others (62.8%) and clinicians (81.6%); and 66.6% intended to vaccinate their infant with aTIV. Parental attitudes toward vaccinating their infant with aTIV were strongly correlated with perceptions of vaccine safety, efficacy, and importance, and these represented the strongest influence on intentions to vaccinate (odds ratio (OR) 79.25; 95% confidence interval (CI) 6.05-1037.50). Parental intentions were further influenced by perceived strength of clinician recommendation (OR 4.55, 95% CI 1.38-15.06) and social support for vaccination (OR 3.46, 95% CI 0.50-24.13). These findings may inform clinician approaches to parental education to ensure optimal seasonal pediatric influenza vaccination.

Understanding the Impact of Approved but Unfunded Vaccine Status on Parental Acceptance of an Adjuvanted Seasonal Influenza Vaccine for Infants: Results from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-III.

The adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against influenza for infants but is not publicly funded (NPF). The objective of this prospective cohort study of parents with children 6 through 23 months of age was to understand how NPF status influences parental perceptions of approved but unfunded vaccines and their intentions to vaccinate. At healthy baby visits, clinicians provided parents with information about influenza and vaccination. Before and after these interactions, a research nurse assessed parents' intentions to vaccinate their children and their beliefs about the safety, efficacy, and necessity of vaccinating their children with aTIV in both publicly funded (PF) and NPF settings. Overall, 15 community practice clinics (n = 15 physicians) and nine public health clinics (n = 9 nurses) recruited 207 parents. The percentage of parents intending to immunize their children with aTIV decreased from 72% (vaccine PF, free of charge), to 42% (NPF, $25 per dose), to 27% (NPF, $50 per dose). Funding status strongly influenced whether parents perceived immunization with aTIV to be necessary, safe, and effective. Information on influenza and influenza vaccines should be provided to parents routinely to allow for well-informed decisions on the suitability of specific influenza vaccines for their child.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

Canadian oncogenic human papillomavirus cervical infection prevalence: systematic review and meta-analysis.

BACKGROUND: Oncogenic human papillomavirus (HPV) infection prevalence is required to determine optimal vaccination strategies. We systematically reviewed the prevalence of oncogenic cervical HPV infection among Canadian females prior to immunization. METHODS: We included studies reporting DNA-confirmed oncogenic HPV prevalence estimates among Canadian females identified through searching electronic databases (e.g., MEDLINE) and public health websites. Two independent reviewers screened literature results, abstracted data and appraised study quality. Prevalence estimates were meta-analyzed among routine screening populations, HPV-positive, and by cytology/histology results. RESULTS: Thirty studies plus 21 companion reports were included after screening 837 citations and 120 full-text articles. Many of the studies did not address non-response bias (74%) or use a representative sampling strategy (53%). Age-specific prevalence was highest among females aged < 20 years and slowly declined with increasing age. Across all populations, the highest prevalence estimates from the meta-analyses were observed for HPV types 16 (routine screening populations, 8 studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5% [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18 (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9 studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4-27.9%]. CONCLUSION: Our results support vaccinating females < 20 years of age, along with targeted vaccination of some groups (e.g., under-screened populations). The highest prevalence occurred among HPV types 16 and 18, contributing a combined cervical cancer prevalence of 65.9%. Further cancer protection is expected from cross-protection of non-vaccine HPV types. Poor study quality and heterogeneity suggests that high-quality studies are needed.