Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

Effectiveness of BNT162b2 Vaccine Against Omicron-SARS-CoV-2 Subvariants in Children 5-11 Years of Age in Quebec, Canada, January 2022 to January 2023.

BACKGROUND: In premarketing clinical trials conducted before Omicron emergence, BNT162b2 vaccine efficacy against COVID-19 was 90% in children. We conducted postmarketing evaluation of 1- and 2-dose vaccine effectiveness (VE) against Omicron BA.1, BA.2 and BA.4/5 subvariants in 5- to 11-year olds. METHODS: We estimated VE against SARS-CoV-2 infection using a test-negative design. Specimens collected between January 9, 2022, and January 7, 2023, from children 5-11 years old in Quebec, Canada, and tested by nucleic acid amplification test were eligible. We estimated VE by time since last vaccine dose, interval between doses and by period of Omicron subvariant predominance. RESULTS: A total of 48,826 NAATs were included in overall analysis. From 14-55 to 56-385 days postvaccination, 2-dose VE against symptomatic infection decreased from 68% (95% CI, 62-74) to 25% (95% CI, 11-36). Two-dose VE with restriction to specimens collected from acute care hospitals (emergency rooms or wards) did not decline but was stable at ~40%. VE against symptomatic infection remained comparable at any interval between doses but increased with longer interval among children tested in acute care settings, from 18% (95% CI, -17 to 44) with 21- to 55-day interval to 69% (95% CI, 43-86) with ≥84-day interval. Two-dose VE against symptomatic infection dropped from 70% (95% CI, 63-76) during BA.1, to 32% (95% CI, 13-47) with BA.2 and to nonprotective during BA.4/5 dominance. CONCLUSIONS: In children 5-11 years of age, VE against symptomatic infection was stable at any interval between doses but decreased with time since the last dose and against more divergent omicron subvariants.

Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada.

BACKGROUND: Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group. METHODS: This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3-14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants. FINDINGS: Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93-98) during the BA.1 period, 84% (81-87) during the BA.2 period, and 68% (63-72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6-8 months, and did not decline with age. INTERPRETATION: Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently. FUNDING: Ministère de la Santé et des Services Sociaux du Québec. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12-17 Years, by Dosing Interval and Duration.

BACKGROUND: Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. METHODS: Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. RESULTS: The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart. CONCLUSIONS: In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.

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.

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.

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.

Impact of the first vaccine dose on COVID-19 and its complications in long-term care facilities and private residences for seniors in Québec, Canada.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l'immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

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.

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.

Sexual behavior, clinical outcomes and attendance of cervical cancer screening by HPV vaccinated and unvaccinated sexually active women.

Concerns were raised about HPV vaccination possibly leading to riskier sexual behavior. We assessed sexual behaviors, risk of sexually transmitted infection, and attendance to cervical cancer screening by HPV vaccinated and unvaccinated young women. In this analysis, 1475 questionnaires completed by women aged 17-29 years were included. The majority of respondents (67.9%) were vaccinated against HPV. The proportion of those vaccinated decreased with age: from 93.2% in those aged 17-19 to 72.9% in those aged 20-22, and 21.8% in 23-29-year olds. A higher proportion of unvaccinated respondents had at least one sexual intercourse under the age of 15 when compared to those vaccinated (30% vs. 23%, p < .0001). The number of sexual partners during the last 12 months was similar between vaccinated and unvaccinated participants. Vaccinated participants reported more condom use (45% versus 38%; p = .0002), and less sexually transmitted infections (10% versus 28%; p < .0001), and less anogenital condylomas (2.2% vs. 11.6%; p < .0001). A screening test has been reported by 51% and 77% of vaccinated and unvaccinated participants, respectively (p < .0001). The association between vaccination status and cervical cancer screening disappeared when adjusting for participants' age. The study results consolidate the existing body of data regarding the absence of an impact of HPV vaccination on sexual behavior or use of contraceptives.

Role of high-risk antibiotic use in incidence of health-care-associated Clostridioides difficile infection in Quebec, Canada: a population-level ecological study.

BACKGROUND: The incidence of health-care-associated Clostridioides difficile infections has been declining in the Canadian province of Quebec since 2015. We examined whether changes in high-risk antibiotic use could account for this decrease, as reported in other jurisdictions. METHODS: We did a retrospective interrupted time-series analysis of 12 hospitals in the Canadian province of Quebec, representing a quarter of all health-care-associated C difficile infections in this region between April 1, 2012, and March 31, 2017. Data for high-risk antibiotic use (eg, amoxicillin-clavulanate, cephalosporins, fluoroquinolones, and clindamycin) in defined daily doses (DDDs) were extracted from local surveillance databases, and incidences of health-care-associated C difficile infections were extracted from provincial surveillance databases. We used hierarchical segmented Poisson regression to assess whether variations in rates of health-care-associated C difficile infections followed variations in antibiotic use. FINDINGS: Overall, 4455 health-care-associated C difficile infections and 6 281 960 patient-days were reported in the 12 participating hospitals, representing around a quarter of the provincial data. A 50% decrease in the annual incidence of health-care-associated C difficile infections was recorded between 2012-13 and 2016-17 (9·4 infections per 10 000 patient-days vs 4·7 infections per 10 000 patient-days), and a 67% decrease in the proportion of these infections due to the NAP1/027 strain of C difficile was seen (64% in 2013 vs 21% in 2017). In total, 1 266 960 DDDs of high-risk antibiotics were distributed during the study period. An increasing time trend was noted in high-risk antibiotic use, reaching a total of 223 DDDs per 1000 patient-days in 2016-17. An increase of one DDD per 1000 patient-days was associated with a 0·2% increase in the rate of health-care-associated C difficile infections in the following 4-week period. A significant change in incidence of health-care-associated C difficile infections persisted despite adjustment for high-risk antibiotic use, as shown by a significant residual step change (0·825, 95% CI 0·731-0·932) and change in trend (0·987, 0·980-0·994). INTERPRETATION: Changes in use of high-risk antibiotics do not entirely account for the sudden decrease in health-care-associated C difficile infections in the Canadian province of Quebec since 2015. Further studies are needed to understand factors implicated in the change in epidemiology of health-care-associated C difficile infections. FUNDING: Institut National de Santé Publique du Québec.

Participation in an action research project on vaccine services for children: relationship with vaccine delays.

Multicomponent interventions are effective in improving vaccine coverage. However, few studies have assessed their effect on timely vaccination. The aim of this study was to compare the proportion of children with vaccine delays at 2- and 12-month visits according to whether or not health centers have participated in an action research project on the organization of vaccination services for 0-5-year-olds. The action research project included a multicomponent intervention and was conducted between 2011 and 2015 in Quebec, Canada. An ecological before/after design was used for this analysis. A total of 264,579 DTaP-IPV-Hib (2-month visits) and 240,541 Men-C-C (12-month visits) vaccine doses were administered during 2011-2012 to 2014-2015 fiscal years, including 19% in 14 participating health centers and the remaining in 78 nonparticipating centers. Vaccine delays demonstrated a more pronounced decreasing trend in participating versus nonparticipating health centers (p < .0001 at 2 and 12 months). Between 2011-2012 and 2014-2015, participating centers managed to eliminate 35% of their vaccine delays at 2-month visits and 33% at 12-month visits, whereas nonparticipating centers eliminated 19% of delays at both visits. Our results are consistent with a positive impact of the multicomponent intervention, despite the fact that it had not specifically aimed at decreasing vaccine delays.

Vaccination during pregnancy: Canadian maternity care providers' opinions and practices.

A number of countries have implemented vaccination in pregnancy as a strategy to reduce the burden of influenza and pertussis. The aim of this study was to assess the involvement of Canadian maternity care providers in administration of vaccines to their pregnant patients. A cross-sectional web-based survey was sent to family physicians, obstetricians-gynecologists, midwives, pharmacists, and nurses. A multivariable logistic regression model was used to determine variables independently associated with offering vaccination services in pregnancy in providers' practice. A total of 1,135 participants participated. Overall, 64% (n = 724) of the participants reported offering vaccines in their practice and 56% (n = 632) reported offering vaccines to pregnant patients. The main reasons reported for not offering vaccination services in pregnancy were the belief that vaccination was outside of the scope of practice; logistical issues around access to vaccines; or lack of staff to administer vaccines. In multivariable analysis, the main factors associated with vaccination of pregnant patients in practices where vaccination services were offered were: providers' confidence in counseling pregnant patients about vaccines, seeing fewer than 11 pregnant patients on average each week, and being a nurse or a family physician. Although the majority of participants expressed strong support for vaccination during pregnancy, half were not offering vaccination services in their practice. Many were not equipped to offer vaccines in their practice or felt that it was not their role to do so. To enhance vaccine acceptance and uptake in pregnancy, it will be important to address the logistical barriers identified in this study.

Priming effect of bivalent and quadrivalent vaccine for HPV 31/33/45/52: an exploratory analysis from two clinical trials.

The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naïve (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naïve subjects. In study B, a dose of 9vHPV was administered 36-96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8-8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3-8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine.

Children vaccination coverage surveys: Impact of multiple sources of information and multiple contact attempts.

BACKGROUND: Monitoring vaccination coverage is an essential component of vaccination program evaluation. In Québec (Canada), children vaccination coverage surveys are conducted every two years since 2006. The objectives of this study were to evaluate the impact of supplementing data based on vaccination booklets with data from vaccine providers, on the final estimated vaccination coverage and to compare vaccination coverage between respondents to each survey contact attempt. METHODS: Data from six cross-sectional surveys were used, which included 3508 children aged 2 years. Parents were invited to transcribe the information available in their child's vaccination booklet on the questionnaire received by mail. The survey included a maximum of 4 contact attempts to obtain a response. Data were completed among vaccine providers identified by parents. The main outcome was a complete vaccination status by 24 months of age. RESULTS: The addition of data from vaccine providers to those present in vaccination booklets increased the proportion of children fully vaccinated from 5.5% to 23.7% depending on the survey year. The proportion of children fully vaccinated by 24 months of age estimated among respondents to contact 1 was only 2.1% higher than the estimates among all respondents. CONCLUSIONS: Without validation among vaccine providers for children with missing doses according to vaccination booklets, results underestimated vaccination coverage in the target population. Conducting multiple contact attempts increased the response rate but had limited impact on the validity of estimates. It would be useful in future surveys to present the coverage obtain from respondents to each contact attempt.

Promoting vaccination in maternity wards ─ motivational interview technique reduces hesitancy and enhances intention to vaccinate, results from a multicentre non-controlled pre- and post-intervention RCT-nested study, Quebec, March 2014 to February 2015.

BackgroundMany countries are grappling with growing numbers of parents who delay or refuse recommended vaccinations for their children. This has created a need for strategies to address vaccine hesitancy (VH) and better support parental decision-making regarding vaccination.AimTo assess vaccination intention (VI) and VH among parents who received an individual motivational-interview (MI) based intervention on infant immunisation during post-partum stay at a maternity ward between March 2014 and February 2015.MethodsThis non-controlled pre-/post-intervention study was conducted using the results from parents enrolled in the intervention arm of the PromoVaQ randomised control trial (RCT), which was conducted in four maternity wards across the Province of Quebec. Participants (n = 1,223) completed pre- and post-intervention questionnaires on VI and VH using Opel's score. Pre-/post-intervention measures were compared using McNemar's test for categorical variables and Wilcoxon signed-rank test for continuous variables.ResultsPre-intervention: overall VI was 78% and significantly differed across maternity wards (74%, 77%, 84%, 79%, p = 0.02). Post-intervention: VI rose significantly across maternity wards (89%, 85%, 95%, 93%) and the overall increase in VI was 12% (78% vs 90%, p < 0.0001). VH corroborated these observations, pre- vs post-intervention, for each maternity ward (28% vs 16%, 29% vs 21%, 27% vs 17%, 24% vs 13%). Overall, VH was curbed post-intervention by 40% (27% vs 16%; p < 0.0001).ConclusionsCompared with pre-intervention status, participants who received the MI-based intervention on immunisation displayed lower hesitancy and greater intention to vaccinate their infant at 2 months of age.

Long intervals between two doses of HPV vaccines and magnitude of the immune response: a post hoc analysis of two clinical trials.

The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6-month or a 3-8 -y interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9-10-y-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9-14 y received a dose of 9vHPV 3-8 y later (mean 5.4 y). In both studies, blood samples were collected before and 1 month post second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One month post second dose, the GMTs increased 40-91-fold for those with a 6-month interval between doses and 60-82-fold for those with a 3-8-y interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated.

Changes in vascular accesses and in incidence rates of dialysis-related bloodstream infections in Québec, Canada, 2011-2017.

OBJECTIVE: Surveillance of dialysis-related bloodstream infections (DRBSIs) has been mandatory in Québec since April 2011. The aim of this study was to describe the epidemiology of DRBSIs in Québec. METHODS: Cohort study of prevalent patients undergoing chronic dialysis in the 36 facilities that participated without interruption in the provincial surveillance, between April 2011 and March 2017. Two indicators were analyzed: proportion of patient months dialyzed using a fistula (a patient month is a 28-day cycle during which an individual patient received dialysis) and incidence rate of DRBSI. Binomial and Poisson regression with generalized estimating equations were used to describe the evolution of indicators over time and to quantify the association between facilities' proportion of fistulas and their incidence rate. RESULTS: Globally, 42.6% of all patient months were dialyzed using a fistula, but there was a statistically significant decrease over time (46.2% in 2011-2012 to 39.3% in 2016-2017). Despite this decline in the use of fistulas, rates of DRBSIs have also decreased, going from 0.38 DRBSIs per 100 patient months in 2011-2012 to 0.23 DRBSIs per 100 patient months in 2016-2017. No association was found between facility use of fistulas and the rate of DRBSI. At the individual level, however, the DRBSI rate was 4.12 times higher for patients using a catheter. CONCLUSIONS: In Québec, the rate of DRBSIs has decreased over a 6-year period despite an increasing proportion of patients dialyzed by catheter.