Monique Landry

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.

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.

The clinical spectrum of the oculo-respiratory syndrome after influenza vaccination.

Oculo-respiratory syndrome (ORS), a new influenza vaccine associated adverse event, was identified in 2000. The 2000 case definition (ORS-2000) required the presence of bilateral red eyes or respiratory symptoms or facial edema occurring between 2 and 24h following immunization and lasting <or=48 h. We compared clinical manifestations of cases outside these timelines. Cases were classified as ORS-early (onset <2 h after immunization), ORS-late (onset >24 h), ORS-persistors (duration >48 h).Overall, the distribution of symptoms was similar between ORS-2000 and other case categories. ORS-early and ORS-late had less ocular involvement, ORS-late and ORS-persistors had more cough and sore throat, ORS-early had more facial edema and ORS-late had less. In comparison to ORS-2000, ORS-early were younger whereas ORS-persistors and ORS-late were significantly older suggesting that clinical manifestations of ORS vary with age with a more rapid induction of symptoms in younger individuals and longer duration for older ones.

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.

Oculo-respiratory syndrome following influenza vaccination: evidence for occurrence with more than one influenza vaccine

We assessed the occurrence of oculo-respiratory syndrome (ORS) following two influenza vaccines: Fluviral (Shire Biologics) or Vaxigrip (Aventis Pasteur). ORS was identified amongst 5.3 and 4.6% of recipients, respectively (P=0.54). With both vaccines, the risk of ORS was much greater in individuals who had ORS the previous year (2000) than in those without such history. In multivariate analysis, the odds ratio for ORS for patients with a prior history of ORS varied between 9.4 and 9.6 (P<0.001) whereas that comparing Fluviral and Vaxigrip varied between 1.5 and 1.9 (P=0.02-0.05). ORS is an adverse event that is present with more than one vaccine and may be present with any influenza vaccines to a greater or lesser degree.

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.

Solicited Adverse Events After Influenza Immunization Among Infants, Toddlers, and Their Household Contacts

OBJECTIVES. We assessed adverse events, including oculorespiratory syndrome, following influenza immunization during the first year of a publicly-funded program for infants, toddlers and their household members in Canada. METHODS. Parents bringing infants and toddlers for influenza immunization to clinics in Quebec or British Columbia consented to structured telephone interview 5 to 10 days later. One adult provided information for all household members. Symptom experience commencing before and after immunization was assessed. Non-immunized persons also served as a comparison group for immunized household members. RESULTS. Sample included 690 immunized infants and toddlers and 1801 household members, 1374 immunized. Only fussiness, fever, decreased appetite, drowsiness, and nasal congestion/coryza were reported for >5% of infants/ toddlers within 72 hours of immunization, but only arm discomfort was reported among >5% of immunized household contacts. In multivariate analysis, muscle ache was the only systemic symptom reported more often by immunized household members compared to non-immunized persons. Oculorespiratory symptoms were infrequent and there was no difference between immunized and non-immunized household members in their report. Less than 1% of adults required time off work because of adverse events following influenza immunization in the household. Less than 2% of subjects experiencing an adverse event following influenza immunization were considered unlikely to be vaccinated again. CONCLUSION. Influenza vaccine is well-tolerated by infants, toddlers and their household members. Post-marketing observational designs are an expedient way to assess adverse events following influenza immunization. These methods should be established and rehearsed annually in preparation for a pandemic.

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.

Parents’ and Adolescents’ Willingness to be Vaccinated Against Serogroup B Meningococcal Disease during a Mass Vaccination in Saguenay–Lac-St-Jean (Quebec)

Since the implementation of the meningococcal C conjugate vaccine as a component of the routine vaccination schedule of children in Quebec, the incidence of meningitis caused by serogroup C Neisseria meningitidis has declined significantly. Currently, serogroup B causes the majority of cases of invasive meningococcal disease in Quebec. A vaccine against serogroup B became available in 2013; accordingly, a mass vaccination campaign was launched in Saguenay–Lac-St-Jean, Quebec, in 2014. At the beginning of the campaign, a telephone survey was conducted to assess opinions on the vaccine, and willingness to be vaccinated among adolescents (16 to 18 years of age) and parents of children <16 years of age.