Elsevier

Vaccine

Volume 36, Issue 52, 18 December 2018, Pages 8039-8046
Vaccine

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

https://doi.org/10.1016/j.vaccine.2018.10.095Get rights and content

Highlights

  • An active surveillance found the 4CMenB vaccine to frequently cause fever and injection site reactions.

  • These adverse events resulted in absenteeism or medical consultations in 6.2% to 9.2% after dose 1 and 2.

  • Among children <10 years old, acetaminophen prophylaxis significantly reduced fever incidence.

Abstract

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 ≥40C. 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.

Introduction

Between 2007 and 2011, the incidence in Canada of invasive meningococcal disease due to serogroup B (IMD-B) was 0.33 per 100 000 person-years, nearly three times the rate reported in the United States [1], [2]. The province of Quebec had the highest incidence at 0.76 per 100 000 person-years and this was associated with the emergence of strains belonging to the ST-269 clonal complex [3]. The Saguenay– Lac-St-Jean was the most affected region of the province with an overall incidence of 3.4/100,000 between 2006 and 2013, nearly 5 times the provincial average, and an incidence of 11.5/100,000 person-years in individuals <20 years-old [3]. As the ST-269 cc expressed two (fHbp and NHBA) of the four antigens (PorA, NadA, fHbp and NHBA) included in the four-component serogroup B meningococcal vaccine (4CMenB) (Bexsero®, previously Novartis Vaccines now GSK), a vaccination campaign targeting ≈60,000 individuals 2 months-20 years-old was launched in May 2014 in this region shortly after Canadian licensure of this product [3].

At the time of the Quebec vaccination campaign, available vaccine safety data on 4CMenB were based on 7 published clinical trials conducted in ≈9,000 individuals including 7,200 infants ≤12 months, 113 children 40–44 months, and 1,755 adolescents and adults 11–50 years-old [4], [5], [6], [7], [8], [9], [10]. These previous data showed the 4CMenB to be quite reactogenic and associated with a higher incidence of fever occurring shortly after each dose and local reactions than other pediatric vaccines. Antipyretic prophylaxis reduces the risk of fever following administration of 4CMenB in infants [11]. Other safety signals of possible concern emerging from these studies included Kawasaki Disease (KD) [5], [6], febrile convulsions [5], [6], fever ≥40 °C [6], severe arthralgia and juvenile arthritis [4], [9], as well as relatively high rates of post-vaccination absenteeism [4]. Because of the limited clinical experience with this vaccine, the Quebec Ministry of Health mandated active surveillance for adverse events following immunization (AEFIs) with the 4CMenB vaccine in order to closely monitor its safety profile as the campaign progressed.

This article describes the findings of this active surveillance for the seven-day period following each dose with a focus on the reduction of fever associated with antipyretic prophylaxis and on absenteeism during this period related to injection site reactions or systemic AEFIs.

Section snippets

Methods

The vaccination campaign targeted all individuals born between May 6, 1993 and December 31, 2014 and residing or attending an educational institution in the region. Vaccination was voluntary and administered free of charge in schools for individuals 5–20 years-old and in public health clinics for others, starting on May 5, 2014. As recommended by the manufacturer, the schedule consisted of 4 doses for children 2 to 5 months of age (three infant doses with a two-month interval and a fourth dose

Vaccine coverage and participation in active surveillance

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 and 88% and 40% of eligible infants had received their third and fourth doses, respectively (Table 1). Overall, 70% of vaccinees provided an email address. Participation rates in the active surveillance component ranged by age from 31% to 39% among vaccinees with an email address (18% to 27% among all vaccinees). There were few differences between the

Discussion

This enhanced surveillance evaluation of a large-scale population use of the 4CMenB vaccine identified no unexpected AEFIs during the seven days post-immunization and showed a short-term safety profile consistent with previous findings under more limited clinical trial conditions. The vaccine was associated, as anticipated, with painful injection site reactions which, along with malaise and fever, resulted in absenteeism in 3%-5% of vaccinees for each dose. Co-administration with other

Contributors’ statements

Gaston De Serres, Marie-Noëlle Billard conceptualized and designed the study, supervised the data collection, carried out the initial analysis and drafted the initial manuscript.

Marie-Claude Gariépy, Isabelle Rouleau conceptualized and designed the study, made substantial contribution to the data collection and analysis, and revised critically the article for important intellectual content.

Eveline Toth, Monique Landry, Nicole Boulianne, Hélène Gagné, Vladimir Gilca, Geneviève Deceuninck, Manale

Acknowledgements

We would like to thank Chantale Bilodeau, France Bouchard, Sophie Auger, Rémi Gagné, Maryline Vivion, Joseline Zafack and the nurses who contacted individuals who reported serious adverse events.

Funding source

This study was funded by the Quebec Ministry of Health and Social Services (Ministère de la Santé et des Services sociaux du Québec) which had no role in the study design, the data collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the article for publication.

Conflict of Interest

Gaston De Serres has received grants for investigator-initiated studies from GSK and Pfizer and provided paid expert testimony for the Ontario Nurses Association, the Quebec Ministry of Justice and GSK. Other authors have no conflicts of interest to declare.

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