Neighborhood-level vaccine impact on COVID-19 infection and hospital admission in Quebec, Canada, during the Delta and early Omicron periods.

OBJECTIVE: To assess the impact of COVID-19 vaccination on COVID-19 infection and hospitalisation at the population-level, and to assess the indirect effects of vaccination in the province of Quebec, Canada. METHODS: We performed a time-stratified, neighborhood-level ecologic study. The exposure was neighborhood-level vaccination (primary series) coverage; outcomes were COVID-19 infection and hospitalisation rates. We used robust Poisson regression to estimate weekly relative rates of infection and hospitalisation versus vaccination. RESULTS: Higher vaccination coverage was associated with lower COVID-19 infection rates from July 18-December 4 for the year 2021 (Delta period) (RR≈0.46 [0.39; 0.54] - 0.94 [0.83; 1.05], 85-100% vs. 60-74% coverage). From December 5-December 25, this association reversed (RR≈1.28 [1.16; 1.41] - 1.41 [1.31; 1.52]), possibly due to the Omicron variant, social behaviors and accumulation of susceptibles in more vaccinated neighborhoods. Vaccine impact against hospitalisation was maintained throughout (RR≈0.43 [0.29; 0.65] - 0.88 [0.64; 1.22]). Vaccination provided substantial indirect protection (RR≈0.43 [0.34; 0.54] - 0.81 [0.65; 1.03]). CONCLUSIONS: This study confirmed the protective impact of vaccination against severe disease regardless of variant, at the population level. Ecological analyses are a valuable strategy to evaluate vaccination programs. Population-level effects can have substantial effects and should be accounted for in public health and vaccination program planning.

Correlates of Neisseria gonorrhoeae antimicrobial resistance: cross-sectional results from an open cohort sentinel surveillance network in Québec, Canada, 2016-2019.

OBJECTIVES: To examine correlates of Neisseria gonorrhoeae antimicrobial resistance (AMR) to first-line antimicrobials (azithromycin, cefixime and ceftriaxone). DESIGN AND SETTING: The sentinel surveillance network is an open cohort of gonococcal infection cases from Québec, Canada. Cross-sectional results are reported herein. PARTICIPANTS: Between 1 January 2016 and 31 December 2019, data from 886 individuals accounting for 941 gonorrhoea cases were included. METHODS: Epidemiological and clinical data were collected using an auto-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. Generalised estimating equations were used for regression. RESULTS: The prevalence of azithromycin resistance with a minimal inhibitory concentration (MIC) of ≥2 mg/L was 21.3%. In 2016, men who have sex with men were more likely to be infected with an azithromycin-resistant N. gonorrhoeae isolate (adjusted prevalence ratio (aPR)=4.73, 95% CI 1.48 to 15.19) or with an isolate with increased third-generation cephalosporin (3GC) MIC (aPR=5.32, 95% CI 1.17 to 24.11 for cefixime (MIC≥0.06 mg/L) and aPR=4.38, 95% CI 1.53 to 12.54 for ceftriaxone (MIC≥0.03 mg/L)). However, these associations were not maintained between 2017 and 2019, with increased MIC observed in men who have sex exclusively with women and women. Overall, azithromycin resistance was significantly more likely in cases who self-reported HIV infection (aPR=1.65, 95% CI 1.00 to 2.71). Cefixime increased MIC were more likely in individuals 25-34 years old (aPR=2.23, 95% CI 1.18 to 4.21). Cefixime and ceftriaxone increased MIC were both more likely in cases who reported ≥5 sexual partners (cefixime: aPR=2.10, 95% CI 1.34 to 3.27 and ceftriaxone: aPR=1.62, 95% CI 1.14 to 2.30). CONCLUSION: Significant correlates of N. gonorrhoeae AMR to first-line antimicrobials were observed. Antimicrobial stewardship may be particularly important for 3GC. Active monitoring and interventions are critical for 3GC non-susceptible strains, especially considering the very low prevalence in Québec.

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.

Frequency and Determinants of a Short-Interval Follow-up Recommendation After an Abnormal Screening Mammogram.

PURPOSE: After imaging assessment of an abnormal screening mammogram, a follow-up examination 6 months later is recommended to some women. Our aim was to identify which characteristics of lesions, women, and physicians are associated to such short-interval follow-up recommendation in the Quebec Breast Cancer Screening Program. METHODS: Between 1998 and 2008, 1,839,396 screening mammograms were performed and a total of 114,781 abnormal screens were assessed by imaging only. Multivariate analysis was done with multilevel Poisson regression models with robust variance and generalized linear mixed models. RESULTS: A short-interval follow-up was recommended in 26.7% of assessments with imaging only, representing 2.3% of all screens. Case-mix adjusted proportion of short-interval follow-up recommendations varied substantially across physicians (range: 4%-64%). Radiologists with high recall rates (≥15%) had a high proportion of short-interval follow-up recommendation (risk ratio: 1.82; 95% confidence interval: 1.35-2.45) compared to radiologists with low recall rates (<5%). The adjusted proportion of short-interval follow-up was high (22.8%) even when a previous mammogram was usually available. CONCLUSIONS: Short-interval follow-up recommendation at assessment is frequent in this Canadian screening program, even when a previous mammogram is available. Characteristics related to radiologists appear to be key determinants of short-interval follow-up recommendation, rather than characteristics of lesions or patient mix. Given that it can cause anxiety to women and adds pressure on the health system, it appears important to record and report short-interval follow-up and to identify ways to reduce its frequency. Short-interval follow-up recommendations should be considered when assessing the burden of mammography screening.

Seasonal influenza vaccination uptake in Quebec, Canada, 2 years after the influenza A(H1N1) pandemic.

BACKGROUND: A decrease in seasonal influenza vaccine uptake was observed after the influenza A(H1N1) pandemic in 2009. The goal of our study was to assess seasonal influenza vaccine uptake in 2011-2012, 2 years after the influenza A(H1N1) pandemic mass immunization campaign and to identify the main reasons for having or not having received the vaccine. METHODS: A telephone survey using random-digit dialing methodology was conducted. Case-weights were assigned to adjust for disproportionate sampling and for nonresponse bias. Descriptive statistics were generated for all variables. RESULTS: Seasonal influenza vaccine uptake was 57% among adults aged ≥60 years, 35% among adults with chronic medical conditions, and 44% among health care workers. The main reasons given for having been vaccinated were to be protected from influenza and a high perceived susceptibility to influenza, whereas low perceived susceptibility to influenza and low perceived severity of influenza were the main reasons for not having been vaccinated. CONCLUSIONS: An increase in seasonal influenza vaccine uptake was observed 2 years after the influenza A(H1N1) pandemic. However, vaccine coverage is still below the target level of 80%. More efforts are needed to develop effective strategies to increase seasonal influenza vaccine uptake.

Impact of 2+1 pneumococcal conjugate vaccine program in the province of Quebec, Canada.

BACKGROUND: Quebec was the first jurisdiction in the world to recommend a 3-dose (2+1) pneumococcal conjugate vaccine (PCV) schedule. The program was implemented in December 2004 with a catch-up for children <5 years. PCV-7 was first used and replaced, respectively, by PCV-10 in 2009 and by PCV-13 in 2011. METHODS: Cases of invasive pneumococcal disease (IPD) notified to public health authorities and isolates submitted to the provincial reference laboratory during the period 2000-2011 were analyzed. RESULTS: IPD incidence in children <5 years was 67/100,000 in 2001-2004, and decreased to 32/100,000 in 2007-2009 following PCV-7 implementation (p<0.01). A further decrease to 24/100,000 was observed in 2010-2011 following PCV-10 introduction (p<0.01). PCV-7 serotypes represented 82% of the total IPD cases in 2000-2004 and elimination was achieved in 2011. Main emerging serotypes were 19A and 7F. Children exposed to the PCV-10 experienced lower IPD rates and all serotypes contributed to the decline, mainly 7F and 19A. In adults, a decrease of low magnitude was observed in 2005-2006 but rates in 2007-2009 were higher than in the prevaccination period. CONCLUSIONS: A 3-dose PCV schedule with high uptake is highly effective and should be recommended worldwide. Serotype replacement eroded benefits especially in adults. PCV-10 introduction had an effect and the impact of PCV-13 use remains to be evaluated.

Measles in children vaccinated with 2 doses of MMR.

OBJECTIVE: A previous measles outbreak investigation in a high school in Quebec, Canada identified 2-dose vaccine effectiveness of 94%. The risk of measles in 2-dose recipients was significantly higher (2-4 times) when measles vaccine was first administered at 12 versus ≥ 15 months of age, with no significant effect of the age at second dose. Generalizability of this association was also assessed in the expanded provincial data set of notified cases. METHODS: This matched case-control study included only 2-dose recipients. All confirmed (laboratory or epidemiologically linked) cases in patients aged 5 to 17 years were included. Each case was matched to 5 controls. RESULTS: A total of 102 cases and 510 controls were included; 89% of cases were in patients 13 to 17 years old. When the first dose was administered at 12 to 13 months compared with ≥ 15 months of age, the risk of measles in participants outside the outbreak school was 6 times higher (95% confidence interval, 1.33-29.3) and was 5.2 times higher (95% confidence interval, 1.91-14.3) in the pooled estimate (participants from the outbreak school + outside that school). CONCLUSIONS: A significantly greater risk of measles among 2-dose recipients whose first dose was given at 12 to 13 months rather than ≥ 15 months of age is confirmed in the larger Quebec data set. The mechanism remains unknown, but vaccine failures in 2-dose recipients could have substantial implications for measles elimination efforts through 2-dose vaccination. The optimal age at first dose may warrant additional evaluation.

Invasive pneumococcal diseases in birth cohorts vaccinated with PCV-7 and/or PHiD-CV in the province of Quebec, Canada.

BACKGROUND: The 10-valent protein D pneumococcal conjugate vaccine (PHiD-CV) was licensed on the basis of immunogenicity studies and there are no published data on its effectiveness to prevent invasive pneumococcal disease (IPD). In the province of Quebec, Canada, PHiD-CV was introduced in the summer of 2009, replacing the 7-valent CRM197 vaccine (PCV-7). Transition to the new vaccine was recommended regardless of the number of PCV7 doses already administered. METHODS: IPD rates in children born in 2007-2010 and observed up to the end of 2010 were computed from laboratory surveillance data. The main vaccine used for the infant primary immunization series (mainly 2 doses at 2-4 months) and the toddler (12 months) booster dose was inferred from the Quebec City Immunization Registry data. RESULTS: IPD rates were significantly lower in the cohorts exposed to PHiD-CV (35/100,000 person-years) as compared with those exposed to PCV-7 (64/100,000 person-years; p=0.03). There was no breakthrough vaccine-type IPD case among children who had received ≥2 PHiD-CV doses for the primary series or a single PHiD-CV dose as a booster. There was also a statistically non-significant lower frequency of 19A and other non-vaccine types IPD cases in children exposed to 2+1 PHiD-CV doses as compared with those exposed to PCV-7. INTERPRETATION: Results are compatible with a high level of protection induced by PHiD-CV against IPD caused by homologous serotypes.

Higher risk of measles when the first dose of a 2-dose schedule of measles vaccine is given at 12-14 months versus 15 months of age.

BACKGROUND: In 2011, >750 cases of measles were reported in Quebec, Canada, where a routine 2-dose measles immunization schedule, in which measles vaccine is given at 12 and 18 months of age, had been in effect since 1996. Effectiveness of this schedule was assessed during a high school outbreak. METHODS: Cases were identified by passive followed by active surveillance. Classical cases met the national surveillance definition; attenuated cases showed clinical signs and high measles-specific immunoglobulin G but did not fulfill all classical criteria. Immunization status was ascertained from written records, and vaccine effectiveness (VE) was calculated as 1 - [(risk of measles in vaccinated individuals)/(risk in unvaccinated individuals)] × 100%. RESULTS: Among 1306 students, 110 measles cases were identified; 98 were classical cases, and 12 were attenuated cases. The attack rates among unvaccinated and fully vaccinated students were 82% and 4.8%, respectively. The VE among 2-dose recipients was 95.5% against classical and 94.2% against all (classical + attenuated) measles. Among 2-dose recipients, attack rates with first immunization at 12 and ≥15 months of age were 5.8% and 2.0%, respectively, with corresponding VE values of 93.0% and 97.5%. The risk of measles in 2-dose recipients was significantly (3-4-fold) higher when vaccine was first administered at 12 months of age, compared with ≥15 months of age (P = .04). CONCLUSIONS: Despite compliance with the recommended 2-dose measles immunization schedule, 6% of high school students were susceptible during this outbreak. Residual susceptibility was 2-4-fold higher among 2-dose recipients who had received the first dose of vaccine prior to 15 months of age. If confirmed in other settings, these results suggest that administration of the first dose of measles vaccine before 15 months of age may not be optimal for measles elimination efforts.

Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss: a case-control study.

OBJECTIVE: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) remains unknown, but vascular involvement is one of the main hypotheses. The main objective of this study was to investigate the association between ISSHL and cardiovascular and thromboembolic risk factors. STUDY DESIGN: Multicentric case-control study. METHODS: Ninety-six Caucasian patients with ISSHL and 179 sex- and age-matched controls were included. Patients were evaluated on the day of the inclusion and 1 week, 3 weeks and 3 months later. Clinical information concerning personal and familial cardiovascular and thromboembolic risk factors and concerning the ISSHL was collected. Blood samples were collected for genetic analysis of factor V Leiden and G20210A polymorphism in the factor II gene. The severity of the hearing loss was classified as mild (21-40 dB), moderate (41-70 dB), severe (71-90 dB) and profound or total (>90 dB). Hearing improvement was calculated as a relative improvement of hearing thresholds using the contralateral ear as baseline. RESULTS: Systolic blood pressure was higher in patients (130 ± 1.7 mm Hg) than in controls (124 ± 1.1 mm Hg, p = 0.003). The personal/familial history of cardiovascular events was also more prevalent in patients (p = 0.023 and p = 0.014, respectively), whereas no difference was found in the prevalence of personal cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking habits). There was no correlation between the audiogram type, the hearing outcome and the presence of cardiovascular risk factors. No significant difference was observed in the personal/familial history or in the presence of thromboembolic risk factors. The prothrombin and factor V mutations were uncommon in both patients and controls. The final hearing threshold was only correlated with the severity of the initial hearing loss (p < 0.001), but not influenced by the presence of vertigo, audiogram type, time elapsed from onset of ISSHL to hospitalization or failure of a previous oral therapy. Hearing stabilization was obtained at 21 days in 92% of patients. CONCLUSION: These results support the theory of vascular involvement as the etiology of some cases of ISSHL. The sole predictive factor of poor final hearing is the severity of the initial hearing loss.

Search for an association between V249I and T280M CX3CR1 genetic polymorphisms, endothelial injury and preeclampsia: the ECLAXIR study.

BACKGROUND: Preeclampsia and coronary-artery disease share risk factors, suggesting common pathophysiological mechanisms. CX3CR1/CX3CL1 mediates leukocyte migration and adhesion and has been implicated in the pathophysiology of several inflammatory diseases. M280/I249 variants of CX3CR1 are associated with an atheroprotective effect and reduced endothelial dysfunction. The aim of this study was to search for an association between V249I and T280M polymorphisms of CX3CR1, preeclampsia and endothelial dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: We explored these polymorphisms with real-time polymerase chain reaction in a case-control study (184 white women with preeclampsia and 184 matched normotensive pregnant women). Endothelial dysfunction biomarkers including von Willebrand factor, VCAM-1 and thrombomodulin, as well as the soluble form of CX3CL1 were measured by enzyme-linked immunosorbent assays (ELISA). The I249 and M280 alleles were associated neither with preeclampsia, nor with its more severe form or with endothelial injury. In contrast, we found a trend toward increased CX3CL1 levels in preeclampsia patients, especially in early-onset- preeclampsia as compared to its level in later-onset- preeclampsia. CONCLUSIONS/SIGNIFICANCE: This is the first study to characterize the CX3CR1 gene polymorphisms in patients with preeclampsia. We found no differences in genotype or haplotype frequencies between patients with PE and normal pregnancies, suggesting that maternal CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to preeclampsia. Further studies should be performed to directly evaluate the pathophysiological role of CX3CL1, a molecule abundantly expressed in endometrium, which has been shown to stimulate human trophoblast migration.