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.

Nephrotic syndrome following four-component meningococcal B vaccination: Epidemiologic investigation of a surveillance signal.

BACKGROUND: In May 2014, a mass vaccination campaign with four-component meningococcal serogroup B (4CMenB) vaccine was launched in a localized region of Quebec, Canada experiencing high invasive meningococcal B disease endemicity. Active post-marketing surveillance identified several cases of nephrotic syndrome (NS) among ∼49,000 vaccinated individuals aged 2 months to 20 years. We report the epidemiologic investigation of this potential vaccine safety signal. METHODS: Active vaccine safety surveillance was conducted electronically, with participants completing an online questionnaire prompted at 7 days after each dose and 6 months following the last dose. Additional NS cases were sought from provincial hospitalization and emergency room databases. RESULTS: In the year following the first dose of 4CMenB vaccination, four confirmed NS cases (three hospitalized) were identified among vaccinated children 2-5-years-old with onset several months post-vaccination. None had renal biopsy but given their age, and positive response to steroids, idiopathic NS was presumptively diagnosed. Among vaccinated children 1-9-years-old, the NS incidence in the year post-vaccination was 17.7 per 100,000 (1 per 5650 vaccinees) with an NS hospitalization rate (i.e. excluding the outpatient case) that was 3.6-fold higher (95%CI = 0.7-11.8; p = 0.12) than the rest of the province for the same period, and 8.3-fold greater (95%CI = 1.1-62.0; p = 0.039) than during the eight years preceding the immunization campaign in the affected region. CONCLUSION: Active safety surveillance identified an unexpected increase in NS incidence following 4CMenB vaccination. Further epidemiological investigation identified four vaccinated cases in total over a 12 month period of follow up. The greater risk in vaccinees had wide confidence intervals with he lower limit including or just above the nul value, an observation with no or marginal statistical significance. The temporal association with vaccination may be explained by other causes and/or chance clustering of a rare event unrelated to vaccination. To confirm or refute a potential link to vaccination, surveillance in other jurisdictions administering 4CMenB to children 1-9-years-old is needed.

Rate of Recurrence of Adverse Events Following Immunization: Results of 19 Years of Surveillance In Quebec, Canada.

BACKGROUND: While adverse events following immunization (AEFI) are frequent, there are limited data on the safety of reimmunizing patients who had a prior AEFI. Our objective was to estimate the rate and severity of AEFI recurrences. METHODS: We analyzed data from the AEFI passive surveillance system in Quebec, Canada, that collects information on reimmunization of patients who had a prior AEFI. Patients with an initial AEFI reported to the surveillance system between 1998 and 2016 were included. Rate of AEFI recurrence was calculated as number of patients with recurrence/total number of patients reimmunized. RESULTS: Overall, 1350 patients were reimmunized, of which 59% were 2 years of age or younger. The AEFI recurred in 16% (215/1350) of patients, of whom 18% (42/215) rated the recurrence as more severe than the initial AEFI. Large local reactions extending beyond the nearest joint and lasting 4 days or more had the highest recurrence rate (67%, 6/9). Patients with hypotonic hyporesponsive episodes had the lowest rate of recurrence (2%, 1/50). Allergic-like events recurred in 12% (76/659) of patients, but none developed anaphylaxis. Of 33 patients with seizures following measles mumps rubella with/without varicella vaccine, none had a recurrence. Compared with patients with nonserious AEFIs, those with serious AEFIs were less often reimmunized (60% versus 80%; rate ratio: 0.8; 95% confidence interval: 0.66-0.86). CONCLUSIONS: Most patients with a history of mild or moderate AEFI can be safely reimmunized. Additional studies are needed in patients with serious AEFIs who are less likely to be reimmunized.

Impact of vaccine delays at the 2, 4, 6 and 12 month visits on incomplete vaccination status by 24 months of age in Quebec, Canada.

BACKGROUND: Timeliness in the administration of recommended vaccines is often evaluated using vaccine delays and provides more information regarding the susceptibility of children to vaccine-preventable diseases compared with vaccine coverage at a given age. The importance of on-time administration of vaccines scheduled at the first visit is well documented, but data are scarce about the impact of vaccine delays at other visits on vaccination status by 24 months of age. Using vaccine delays for the first three doses of DTaP-containing vaccines and for the first dose of measles-containing vaccines as markers of timeliness at the 2, 4, 6 and 12 month visits, we estimated the proportion of incomplete vaccination status by 24 months of age attributable to a vaccine delay at each of these visits. METHODS: We used the data from six cross-sectional coverage surveys conducted in the Province of Quebec from 2006 to 2016 which included 7183 children randomly selected from the universal health insurance database. A vaccine dose was considered delayed if received 30 days or more after the recommended age. The impact of new vaccine delays at each visit on incomplete vaccination status by 24 months of age was estimated with the attributable risk in the population. RESULTS: The proportion of children with vaccine delay was 5.4% at 2 months, 13.3% at 4 months, 23.1% at 6 months and 23.6% at 12 months. Overall, 72.5% of all 2-year-old children with an incomplete status by 24 months were attributable with a vaccine delay, of which 16.1% were attributable with a first vaccine delay at 2 months, 10.6% at 4 months, 14.0% at 6 months and 31.8% at 12 months. CONCLUSIONS: While great emphasis has been put on vaccine delays at the first vaccination visit, the prevalence of vaccine delays was greater with later visits and most children with an incomplete vaccination status by 24 months had a vaccine delay occurring during these later visits. Interventions to improve timeliness should address vaccine delays at each visit and not only focus on the first visit.

Short-term safety of 4CMenB vaccine during a mass meningococcal B vaccination campaign in Quebec, Canada.

BACKGROUND: To address a high incidence of serogroup B invasive meningococcal disease (IMD-B) in the Saguenay-Lac-Saint-Jean region, Quebec, Canada, a mass vaccination campaign targeting nearly 60,000 individuals ≤20 years old was launched in May 2014. Because of the limited clinical experience with the four-component meningococcal B vaccine (4CMenB), active surveillance for adverse events following immunization (AEFI) was conducted. This paper reports 4CMenB AEFI surveillance findings. METHODS: Active surveillance assessed AEFIs with acute onset within 7-days post-immunization, AEFI-associated absenteeism and medical consultations, impact of antipyretic prophylaxis and coadministration of other vaccines. RESULTS: By July 17, 2015, 83% and 77% of the 59,098 individuals targeted by the campaign had received a first and a second dose of 4CMenB. The incidence of fever on days1-2 was highest in children <2 years old but only 0.6% reported a temperature ≥40◦C. Among children <10 years old, ≥2doses of acetaminophen prophylaxis significantly reduced fever incidence on days1-2 after dose1&2. Absenteeism or a medical consultation during the 7 days following vaccination was reported by 6.2% of vaccinees post-dose1 and 9.2% post-dose2 and was most often reported in association with fever/malaise (4.2%) or injection site reactions (3.6%). CONCLUSION: Large-scale population-based surveillance identified a 7-day reactogenicity profile consistent with earlier clinical trials with the 4CMenB vaccine but indicating frequent AEFI-associated absenteeism and medical consultations affecting the societal cost of this vaccine. We conclude acceptable vaccine safety and risk-benefit profile overall on the short term, particularly as an intervention to address a high regional incidence of IMD-B.

Investigation of an increase in large local reactions following vaccine schedule change to include DTaP-HB-IPV-Hib (Infanrix-hexa®) and MMRV (ProQuad®) at 18 months of age.

CONTEXT: In 2015 in Quebec, Canada, the passive vaccine adverse event reporting system detected an increase in large local reactions associated with vaccines recommended at the 18-month visit. This followed changes to the pediatric vaccine schedule to include hexavalent diphtheria-tetanus-acellular-pertusis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine (DTaP-IPV-Hib-HB, Infanrix-hexa®, GSK) and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV, ProQuad®, Merck) as 18-month booster doses. OBJECTIVES: To determine if the excess of large local reactions was caused by a specific vaccine or their co-administration in the same limb or during the same visit. METHODS: A case-control study was conducted among cases born between January 2012 and April 2015 with a large local reaction following MMR ±â€¯V or DTaP-IPV-Hib ±â€¯HB vaccines administered between 16 and 23 months of age. Controls were randomly selected from the provincial medicare database among children born during the same period. RESULTS: Our analysis included 96 cases and 494 controls vaccinated with MMRV or DTaP-IPV-Hib ±â€¯HB vaccines. Among the 96 cases, 46% had a cellulitis and 54% had an injection site reaction extending beyond the nearest joint and/or lasting ≥ 4 days. Among the 39 cases who were immunized in different limbs, 77% of the large local reactions were located at the Infanrix-hexa® site, 5% at the DTaP-IPV-Hib site and 18% at the ProQuad® site. Large local reactions were significantly more frequent with Infanrix-hexa® than with DTaP-IPV-Hib vaccine (OR 5.9 95% CI: 1.4-25.7). Administration of ProQuad® and Infanrix-hexa® in the same limb did not increase the risk of large local reactions. CONCLUSION: This investigation suggested that most large local reactions were causally associated with the Infanrix-hexa® vaccine and that the risk was not greater when ProQuad® and Infanrix-hexa® were administered in the same limb. Given the improved vaccine coverage for hepatitis B, benefit-risk analysis likely still favours ongoing use of Infanrix-hexa® with informed parental consent.

Impact of the addition of new vaccines in the early childhood schedule on vaccine coverage by 24 months of age from 2006 to 2016 in Quebec, Canada.

CONTEXT: Between 2004 and 2016, in the province of Quebec (Canada), 4 new antigens were added in the early childhood vaccine schedule from birth to 18 months, increasing the number of injections or doses needed from 7 to 12. These additions may have decreased the proportion of children who had received all recommended vaccines. OBJECTIVES: To assess the impact of the introduction of new vaccines to the childhood schedule on the 24-month vaccine coverage from 2006 to 2016 and identify factors associated with incomplete vaccination status by 24 months of age. METHODS: We used the data from six cross-sectional vaccine coverage surveys conducted every two years which included a total of 3515 children aged 2 years old and randomly selected from the Quebec public health insurance database. Factors associated with an incomplete vaccine status by 24 months were identified with multivariable logistic regression. RESULTS: Despite the addition of 4 new vaccine antigens since 2004, the vaccine coverage remained high from 2006 (82.4%) through 2016 (88.3%) for vaccines present in the schedule since 2006. In 2016, vaccine coverage was 78.2% for all vaccines included in the schedule. The vaccine coverage of new vaccines increases rapidly within 2 years of their introduction. For both new and older vaccines, incomplete vaccine status by 24 months of age is associated with a delay of 30 days or more in receiving the vaccines scheduled at 2 and 12 months of age. CONCLUSIONS: Increasing to 12 the number of doses in the recommended schedule has slightly reduced the vaccine coverage by 24 months of age and the vaccine coverage of vaccines already in the schedule remained stable over the years. Future additions to the vaccine schedule may not be similarly accepted by the population and this will require continuing the monitoring of vaccine coverage.

Early use of the HPV 2-dose vaccination schedule: Leveraging evidence to support policy for accelerated impact.

Although human papillomavirus (HPV) vaccines were initially licensed based on efficacy after three-dose regimens in women aged 15-26 years, it was recognized early in clinical development that comparable immunogenicity could be obtained after just two doses when administered to younger girls. In both Canada and Mexico, public health authorities made the decision to administer two doses 6 months apart with a planned additional dose at 60 months, while simultaneously doing further study to determine if the third dose would confer meaningful additional benefit. This delayed third dose approach permitted a more cost-effective program with opportunities for improved compliance while minimizing injections and leaving open the opportunity to provide a full three-dose vaccination series. It required close cooperation across many governmental and civil society leadership bodies and real-time access to emerging data on HPV vaccine effectiveness. Although still limited, there is increasing evidence that even one-dose vaccination is sufficient to provide prolonged protection against HPV infection and associated diseases. Ongoing clinical trials and ecological studies are expected to consolidate existing data regarding one dose schedule use. However, to accelerate the preventive effect of HPV vaccination some jurisdictions, in particular those with limited resources may already consider the initiation of a one dose vaccination with the possibility of giving the second dose later in life if judged necessary. Such an approach would facilitate vaccination implementation and might permit larger catch-up vaccination programs in older girls (or as appropriate, girls and boys), thereby accelerating the impact on cervical cancer and other HPV-associated diseases.

Prevalence of risk factors for acquiring measles during the 2011 outbreak in Quebec and impact of the province-wide school-based vaccination campaign on population immunity.

BACKGROUND: A large measles outbreak occurred in Quebec, Canada, in 2011. Although nearly two-thirds of the cases occurred in only two health districts, a mass vaccination campaign targeting all Quebec elementary and high school students without valid two-dose history was undertaken to prevent future outbreaks. We compared rates of non-vaccination and age at first measles vaccine dose among students in the two most-affected districts and the rest of the province and estimated the improvement in overall student measles immunity due to the mass school-based vaccination campaign. METHODS: Data were extracted from the provincial vaccination registry for students in kindergarten to grade 11 during the 2011/2012 school year. A telephone survey was conducted in three sub-groups: students whose first measles vaccine dose recorded in the vaccination registry was received during the 2011 school vaccination campaign; students with no dose recorded in the registry whose parents refused receipt during the school campaign; and students with no dose recorded in the registry and no information about parental consent/refusal during the school campaign. RESULTS: Neither the prevalence of being non-vaccinated nor a younger age at first pediatric dose were higher in the two most-affected districts versus the rest of the province. The school campaign vaccinated nearly 8% of all students including 7% who previously received at least one dose. Before the outbreak, 3% of students were not vaccinated and one-third of these (1%/3%) were vaccinated during the campaign. The campaign likely increased the absolute school population immunity by just 1.7%. CONCLUSION: The concentration of measles cases in the two most-affected health districts during the large Quebec outbreak is not explained by more students who were unvaccinated or who had received their first vaccine dose at a younger age. The vaccination campaign reached one-third of unvaccinated students and only marginally improved population immunity.

Parents' and adolescents' willingness to be vaccinated against serogroup B meningococcal disease during a mass vaccination in Saguenay-Lac-St-Jean (Quebec).

A mass vaccination campaign with the 4CMenB vaccine (Bexsero®; Novartis Pharmaceutical Canada Inc) was launched in a serogroup B endemic area in Quebec. A telephone survey was conducted to assess parental and adolescent opinions about the acceptability of the vaccine. Intent to receive the vaccine or vaccine receipt was reported by the majority of parents (93%) and adolescents (75%). Meningitis was perceived as being a dangerous disease by the majority of parents and adolescents. The majority of respondents also considered the 4CMenB vaccine to be safe and effective. The main reason for positive vaccination intention or behaviour was self-protection, while a negative attitude toward vaccination in general was the main reason mentioned by parents who did not intend to have their child vaccinated. Adolescents mainly reported lack of interest, time or information, and low perceived susceptibility and disease severity as the main reasons for not intending to be vaccinated or not being vaccinated.

Une campagne de vaccination de masse avec le vaccin 4CMenB (Bexsero®; Novartis Pharma Canada Inc.) a été lancée dans une région du Québec endémique au sérogroupe B. Un sondage téléphonique afin d'évaluer l'acceptabilité du vaccin par les parents et les adolescents a été réalisé. La majorité des parents (93 %) et des adolescents (75 %) ont déclaré avoir l'intention de se faire vacciner / de faire vacciner leur enfant ou l'avoir déjà fait. La majorité des parents et des adolescents percevaient la méningite comme dangereuse et considéraient le vaccin 4CMenB comme sécuritaire et efficace. La protection de l'enfant était la principale raison d'accepter le vaccin chez les parents, tandis qu'une attitude négative envers la vaccination en général était la principale raison que donnaient les parents qui n'avaient pas l'intention de faire vacciner leur enfant. Les adolescents déclaraient surtout un manque d'intérêt, de temps ou d'information, la perception d'être peu susceptibles à la maladie et la perception que la maladie n'était pas très grave comme principales raisons de ne pas s'être fait vacciner ou de ne pas avoir l'intention de le faire.

Paresthesia and sensory disturbances associated with 2009 pandemic vaccine receipt: Clinical features and risk factors.

BACKGROUND: Paresthesia was the third-most-common adverse event following immunization (AEFI) with 2009 monovalent AS03-adjuvanted A(H1N1)pdm09 vaccine in Quebec, Canada and was also frequently reported in Europe. This study assessed clinical features and risk factors associated with this unexpected AEFI. METHODS: Reports to the passive surveillance system were summarized. A case-control study was conducted to assess risk factors and additional investigations were undertaken among cases with symptoms persisting ≥12 months. RESULTS: There were 328 reports of paresthesia affecting the vaccinated arm (58%), but also face (45%), lower limbs (40%) and back/thorax (23%) with numbness but also muscle weakness (61%), motor impairment (61%), generalized myalgia (37%), visual (14%) and/or speech effects (15%). Reporting rate was highest in women of reproductive age, peaking at 30-39 years-old (28/100,000 doses administered) and exceeding that of men of the same age (7/100,000 doses) by 4-fold. Median time to onset was 2h. Symptoms subsided within one week in 37% but lasted ≥6 months in 26%. No consistent or objective neurological findings were identified. Risk was increased with allergy history, respiratory illness the day of vaccination, depressive symptoms and family history of pulmonary disease, but decreased with physical activity the day of vaccination, and regular weekly alcohol consumption. CONCLUSION: Paresthesia following 2009 pandemic vaccine receipt lasted several weeks and included other motor-sensory disturbances in an important subset of patients. Although it does not correspond with known neurological disease, and causality remains uncertain, further investigation is warranted to understand the nature and frequency of paresthesia as a possible AEFI with influenza vaccines.

Acceptability of live attenuated influenza vaccine by vaccine providers in Quebec, Canada.

A live attenuated influenza vaccine (LAIV) was offered during the 2012-13 influenza season in Quebec, Canada, to children aged between 2 and 17 years with chronic medical conditions. Despite the offer, uptake of the vaccine was low. We assessed the perceptions and opinions about seasonal influenza vaccination and LAIV use among vaccine providers who participated in the 2012-13 campaign. More than 70% of them thought that LAIV was safe and effective and more than 90% considered that the vaccine was well-received by parents and healthcare professionals. According to respondents, the most frequent concerns of parents about LAIV were linked to vaccine efficacy. LAIV is well-accepted by vaccine providers involved in influenza vaccination clinics, but more information about the vaccine and the recommendations for its use are needed to increase vaccine uptake.

Influenza immunization of chronically ill children in pediatric tertiary care hospitals.

Despite a publicly funded immunization program and continuous promotional efforts, vaccine uptake for seasonal influenza in Quebec (Canada) remains under its goal of 80%. Missed opportunities can explain the low influenza vaccine rates among chronically ill children. To address that, demonstration projects using the live attenuated influenza vaccine (LAIV) were implemented in 3 pediatric tertiary care hospitals to evaluate the feasibility and acceptability of implementing influenza immunization of chronically ill children in hospitals' outpatient clinics. A diary was used to document barriers and enabling factors regarding the implementation, and a questionnaire was distributed to healthcare professionals involved in the project in each hospital. Parent's knowledge, attitudes and behaviors (KAB) about influenza immunization and acceptability of immunization in outpatient clinics were also measured with a questionnaire. As part of the project, 2,478 children were immunized. Enabling factors included the financial support received from Quebec ministry of Health, the nasal mode of administration of the LAIV and the presence of a leader specifically dedicated to influenza immunization. Barriers to influenza immunization in outpatient clinics included difficulties of hiring extra staff to work in immunization clinics and additional tasks added to regular activities of the clinics. Results from both questionnaires illustrated a high level of acceptability of seasonal influenza immunization in hospitals' outpatient clinics by parents and healthcare professionals. Influenza immunization in pediatric tertiary care hospital is an effective way to reach chronically ill children and does not involve major feasibility or acceptability issues.

Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec, Canada.

INTRODUCTION: In Quebec, Canada, receipt of the 2009 AS03-adjuvanted pandemic H1N1 vaccine was associated with increased risk of anaphylaxis and other allergic-like events (ALE), especially among women of childbearing age. In response to this safety signal, a case-control study was conducted to identify potential risk factors. METHODS: A total of 435 ALE (50 anaphylaxis) occurring <24h following pandemic vaccination were compared to 849 age-gender matched controls randomly selected from the provincial Pandemic Influenza Vaccination Registry. More than 60 potential risk factors were evaluated through phone interviews and included demographic information, medical history, medication use or acute respiratory illnesses (ARI) concurrent with vaccination and other risk factors associated with general allergy. Odds ratios (ORs) with 95% confidence intervals were estimated with unconditional logistic regression. RESULTS: Factors associated with increased risk of anaphylaxis included concurrent ARI (18% cases vs. 4% controls, ORadj 7.67, 95%CI: 3.04-13.37), food allergy (26% cases vs. 4% controls, ORadj 3.84, 95%CI: 1.51-9.74) and vaccination during the first four weeks of the campaign (66% cases vs. 50% controls, ORadj 2.16, 95%CI: 1.10-4.25) whereas alcohol exposure (≥1 drink/week) was associated with reduced risk (29% cases vs. 42% controls, ORadj 0.26, 95%CI: 0.13-0.57). These factors were also significantly associated with any ALE but the strength of association was weaker. Allergy to components found in the vaccine (e.g., egg, thimerosal) was infrequent and did not significantly differ between cases and controls. CONCLUSION: Increased anaphylaxis and other allergic-like events observed in association with AS03-adjuvanted pandemic H1N1 vaccine remain mostly unexplained despite extensive risk factor review. However, prior to mass vaccination with similar formulations this safety signal warrants further consideration and better understanding. In particular, the predominance among women of childbearing age may be a clue to underlying biological or hormonal influences on adverse immunological responses to vaccine.

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.

Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine.

BACKGROUND: Anaphylaxis after trivalent influenza vaccination is typically reported at a rate of <1 per million doses. In Quebec, Canada, anaphylaxis following administration of the monovalent AS03-adjuvanted H1N1pdm09 vaccine was reported through passive surveillance at a rate of 8 per million doses administered. This was 20 times higher than the reporting rate for non-adjuvanted trivalent vaccines administered during the six previous seasons. However, adequate estimation of the incidence of anaphylaxis is hindered by wide variations in definitions and diagnosis. METHODS: Using the Brighton collaboration case definition of anaphylaxis, all cases with allergic symptoms (AS) reported to public health were reviewed to estimate the incidence of anaphylaxis following AS03-adjuvanted H1N1pdm09 vaccine. RESULTS: Among 752 reports of allergic symptoms, 33 were initially reported as anaphylaxis of which 20/33 (60%) met the Brighton definition (19/20 with certainty levels 1 or 2). A total of 38 additional cases with onset within 1h of vaccination also met the Brighton definition of anaphylaxis (27 (71%) with certainty levels 1 or 2). The 58 cases meeting Brighton Level 1 or 2 criteria for anaphylaxis represent a 75% increase over the 33 passively reported and an incidence of 13 per million doses administered. CONCLUSION: A substantial number of patients with early-onset allergic symptoms met the most specific levels of the Brighton case definition but were not reported as anaphylaxis. Based on this specific case definition, the incidence of anaphylaxis after AS03-adjuvanted H1N1pdm09 vaccine substantially exceeded that reported with seasonal influenza vaccines, a signal that warrants better understanding.

Largest measles epidemic in North America in a decade--Quebec, Canada, 2011: contribution of susceptibility, serendipity, and superspreading events.

BACKGROUND: The largest measles epidemic in North America in the last decade, occurred in 2011 in Quebec, Canada, where rates of 1- and 2-dose vaccine coverage among children 3 years of age were 95%-97% and 90%, respectively, with 3%-5% unvaccinated. METHODS: Case patients identified through passive surveillance and outbreak investigation were contacted to determine clinical course, vaccination status, and possible source of infection. RESULTS: There were 21 measles importations and 725 cases. A superspreading event triggered by 1 importation resulted in sustained transmission and 678 cases. The overall incidence was 9.1 per 100,000; the highest incidence was in adolescents 12-17 years old (75.6 per 100,000), who comprised 56% of case patients. Among adolescents, 22% had received 2 vaccine doses. Outbreak investigation showed this proportion to have been an underestimate; active case finding identified 130% more cases among 2-dose recipients. Two-dose recipients had milder illness and a significantly lower risk of hospitalization than those who were unvaccinated or single-dose recipients. CONCLUSIONS: A chance superspreading event revealed an overall level of immunity barely above the elimination threshold when unexpected vulnerability in 2-dose recipients was taken into account. Unvaccinated individuals remain the immunization priority, but a better understanding of susceptibility in 2-dose recipients is needed to define effective interventions if elimination is to be achieved.

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.