Geneviève Deceuninck

Effectiveness of pneumococcal conjugate vaccine using a 2+1 infant schedule in Quebec, Canada.

Background: In the province of Quebec, Canada, pneumococcal conjugate vaccine (PCV) is offered to all children aged less than 5 years, and a 2+1 schedule (2, 4, and 12 months) is recommended for low-risk infants, with other schedules including a lower number of doses for older children. Objective: To estimate PCV effectiveness against invasive pneumococcal disease (IPD). Methods: IPD cases in children aged 2–59 months and reported during the years 2005–2007 were eligible and uninfected controls were randomly identified in the provincial health insurance registry. Parents were interviewed by telephone and immunization records were reviewed. The PCV effectiveness was computed using unconditional logistic regression models adjusting for potential confounders. Results: 180 IPD cases (60.4% of total reported) and 897 controls were included. Predictors of IPD risk were age, season, high-risk medical conditions, day-care attendance, and low family income. Overall PCV protection (≥1 dose) against IPD caused by any serotype was 60% (95% CI: 38%–75%), and was 92% (83%–96%) against IPD caused by vaccine serotypes. Among low-risk children who received the recommended 2+1 schedule, 6 cases of vaccine failure occurred after the first dose, 1 case after the second dose, and no cases after the booster dose. Conclusion: These results confirm the effectiveness of PCV after 2 and 3 doses.

Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec

CONTEXT In fall 2009 in Quebec, Canada, an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain, mostly using an AS03 adjuvant vaccine. By the end of the year, 57% of the 7.8 million residents had been vaccinated. OBJECTIVE To assess the risk of Guillain-Barré syndrome (GBS) following pandemic influenza vaccine administration. DESIGN Population-based cohort study with follow-up over the 6-month period October 2009 through March 2010. The investigation was ordered by the chief medical officer of health in accordance with the Quebec Public Health Act. SETTING All acute care hospitals and neurology clinics in Quebec. POPULATION Suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Medical records were reviewed and cases classified according to Brighton Collaboration definitions (categorized as level 1, 2, or 3, corresponding to criteria of decreasing certainty in diagnosis). Immunization status was verified and denominators were estimated from the provincial immunization registry (4.4 million vaccinated) and census data (total target population aged ≥6 months, 7.8 million), with a total of 3,623,046 person-years of observation. MAIN OUTCOME MEASURES Relative and attributable risks were calculated using a Poisson model and the self-controlled case-series method. RESULTS Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years. CONCLUSIONS In Quebec, the 2009 influenza A(H1N1) vaccine was associated with a small but significant risk of GBS. It is likely that the benefits of immunization outweigh the risks.

Reduced Physician Claims for Otitis Media After Implementation of Pneumococcal Conjugate Vaccine Program in the Province of Quebec, Canada

Background: In Canada, a 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in 2001, and free vaccination of children <5 years of age was offered in December 2004 in the province of Quebec. Objectives: To describe the frequency of physician claims for otitis media (OM) in relation to PCV-7 coverage during the period from 1996 to 2007. Methods: The monthly frequency of OM claims in the population aged <10 years was obtained from the provincial health insurance board. Time series in different age categories were analyzed using structural models with unobserved components, including seasonality, linear trends, level changes, and outliers. The candidate explanatory variable was PCV-7 uptake rate as measured in the population <5 years of age in the Quebec City area. Results: Free PCV-7 program implementation was followed by a marked increase in uptake and by the end of 2007, >90% of children had received ≥1 dose. In all models, seasonality was a major determinant of OM frequency rates and there were statistically significant downward trends, as well as downward level breaks and outliers. PCV-7 coverage (≥1 dose) was a significant predictor in children 6 months to 2 years of age. The effect was of lesser magnitude and not significant in the group of children aged 2 to 4 years, and absent in the group 5 to 9 years. Since PCV-7 licensure, an estimated 100,000 visits were averted in children <5 years of age, and OM claim frequency reduction attributable to PCV-7 was 13.2% by the end of the study period. Conclusion: PCV-7 implementation was associated with a significant reduction in the frequency of OM in the target population, and there was no indication of herd protection in older children.

International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

BACKGROUND The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. METHODS The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. RESULTS We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. CONCLUSIONS This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines.

Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec.

Context An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe. Objective To assess narcolepsy risk following administration of a similar vaccine in Quebec. Design Retrospective population-based study. Setting Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre. Population Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry. Main Outcome Measures Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method. Results A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009–2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50–11.12). RR was 2.07 (0.70–6.17) in the SCCS, and 1.48 (0.37–7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases. Conclusions Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

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.

Effectiveness of Serogroup C Meningococcal Conjugate Vaccine: A 7-Year Follow-up in Quebec, Canada

Background: A mass immunization campaign was implemented in 2001 to control a serogroup C meningococcal disease outbreak, and a newly licensed serogroup C meningococcal conjugate vaccine (C-MCV) was used. In 2002, 1 C-MCV dose was routinely offered to children 12 months of age. Objective: To assess the epidemiologic effect of the campaign and C-MCV effectiveness during a 7-year period according to age at vaccination and delay since vaccine administration. Methods: Cases of invasive meningococcal infection reported to public health authorities and the reference laboratory during the period 1990 to 2008 were obtained to calculate year- and age-specific incidence rates. Multiple sources were used to ascertain the immunization status of cases. Immunization registry data were used to estimate age-specific C-MCV uptake rates in different birth cohorts. Vaccine effectiveness was estimated by Mantel–Haenszel method and logistic regression models. Results: After mass immunization campaign, meningococcal C disease incidence decreased markedly not only in highly vaccinated but also in poorly vaccinated and nonvaccinated birth cohorts. Overall vaccine effectiveness was 87.4% (95% CI: 75.4%–94.2%) with lower protection in children vaccinated <2 years of age and waning of protection of higher magnitude in this age group. Conclusion: Results support the current Canadian recommendation to provide booster vaccination for adolescents.

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.

Effectiveness of Pandemic H1N1 Vaccine Against Influenza-Related Hospitalization in Children

OBJECTIVE: Young children are generally considered immunologically naive with respect to influenza exposure opportunities; thus, a 2-dose schedule is recommended when a child is first immunized with conventional influenza vaccine lacking adjuvant. We estimated the effectiveness of a single pediatric dose of AS03-adjuvanted vaccine against hospitalization for confirmed pandemic influenza A/H1N1 (pH1N1) infection in children aged 6 months to 9 years during the fall 2009 vaccination campaign. METHODS: In a matched case-control design, case subjects were children hospitalized for pH1N1 infection in the Fall of 2009, in Quebec, Canada. Controls were nonhospitalized children, matched by age and region of residence. Vaccination status in case subjects and controls was ascertained in relation to the case subjects date of illness onset. Vaccine effectiveness was estimated through conditional logistic regression. RESULTS: The overall effectiveness of a single pediatric dose of vaccine administered ≥14 days before illness onset was 85% (95% confidence interval [CI]: 61% to 94%), varying according to age category but with wide and overlapping CIs: 92% (95% CI: 51% to 99%) in 6–23 month-old children, 89% (95% CI: 34% to 98%) in 2–4 year-olds, and 79% (95% CI: −31% to 96%) in 5–9 year-olds. Overall vaccine effectiveness for immunization ≥10 days before illness onset was slightly lower at 80% (95% CI: 60% to 90%), with similar variation according to age. CONCLUSION: In children aged 6 months to 9 years, a single pediatric dose of the AS03-adjuvanted pH1N1 vaccine was highly protective against hospitalization beginning at 10 and 14 days after vaccination.

The Changing Epidemiology of Meningococcal Disease in Quebec, Canada, 1991–2011: Potential Implications of Emergence of New Strains

Background In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD) in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination. Methodology IMD cases reported to the provincial notifiable disease registry in 1991–2011 and isolates submitted for laboratory surveillance in 1997–2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST) by using multilocus sequence typing (MLST) were performed. Results Yearly overall IMD incidence rates ranged from 2.2–2.3/100,000 in 1991–1992 to 0.49/100,000 in 1999–2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997–2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups. Conclusion Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in guiding public policy decisions.