Elsevier

Vaccine

Volume 33, Issue 23, 28 May 2015, Pages 2684-2689
Vaccine

Effectiveness of three pneumococcal conjugate vaccines to prevent invasive pneumococcal disease in Quebec, Canada

https://doi.org/10.1016/j.vaccine.2015.04.005Get rights and content

Abstract

Background

In Quebec, a pneumococcal conjugate vaccine (PCV) program was implemented in December 2004. The recommended schedule is 2 + 1 doses for low-risk infants. PCV-7 was first used (including catch-up for children <5 years of age), replaced by PCV10 in June 2009, and by PCV13 in January 2011 (no catch-up in both instances). From the beginning, >90% of children received the recommended number of doses.

Objective

To assess the effectiveness of the three PCVs sequentially used to prevent invasive infectious disease (IPD).

Methods

IPD cases in children 2–59 months during the years 2005–2013 were eligible. Controls were randomly identified in the provincial health insurance registry. Parents were interviewed and immunization records reviewed. Vaccine effectiveness (VE) was computed using multivariate logistic regression models.

Results

Out of 889 IPD cases reported, full participation was obtained for 516 cases (58%) and for 1767 controls. Against vaccine-type IPD, VE (≥1 dose) was 90% (82–95%) for PCV7, 97% (84–99%) for PCV10 and 86% (62–95%) for PCV13. Against 19A IPD, VE was, respectively, 42% (−9% to 69%), 71% (24–89%), and 74% (11–92%). VE (≥2 doses) against PCV13-type IPD was 85% for PCV10 (66–94%), 85% for PCV13 (55–94%), and 89% (58–97%) for a mixed PCV10 + PCV13 schedule.

Conclusions

All three PCV vaccines showed high level of protection against IPD caused by serotypes included in their formulation and there was a high level of cross-protection against 19A for PCV10. No substantial difference was seen between PCV10, PCV13, or a mixed PCV10 + PCV13 schedule.

Introduction

Invasive pneumococcal disease (IPD) constitutes a public health problem worldwide [1]. In Canada, the 7-valent CRM197 pneumococcal conjugate vaccine (PCV7) was licensed in May 2001. In the province of Quebec, high-risk children and those living in Nordic regions were offered a four (3 + 1) dose schedule of PCV7 starting in October 2002 [2]. Quebec was the first jurisdiction in the world to recommend a 3-dose (2 + 1) schedule for the routine immunization of infants, vaccines being offered respectively, at age 2, 4 and 12 months [3]. This publicly funded program was launched in December 2004, along with a catch-up program consisting of 2 doses for 12–23 month-old children and 1 dose for 2–5 year-old children. Vaccine uptake was low (<20%) up to the end of the year 2004 and increased very rapidly thereafter [4]. Since 2005, 97% of infants are receiving at least one PCV dose and 93% are receiving the recommended number of doses by age 24 months [5]. Starting in June 2009, the 10-valent protein-D pneumococcal conjugate vaccine (PCV10) replaced PCV7, and in January 2011, the 13-valent CRM197 vaccine (PCV13) replaced PCV10, with no catch-up in both instances [6], [7].

In Canada, marked changes in the epidemiology of IPD have been observed since the introduction of universal immunization of children with PCVs [8]. In Quebec, the incidence rate in children less than 5 years of age decreased from 63/100,000 in 2004, to 19/100,000 in 2012, with a progressive decline in the proportion of cases caused by the serotypes included in the three PCVs [9].

Since January 1st, 2005, IPD cases in children less than 5 years of age are prospectively enrolled in a province-wide case–control study. Results pertaining to the PCV program implementation period 2005–2007 have been published previously [10]. The objective of the present analysis was to assess the effectiveness of the three PCVs sequentially used in the context of a 2 + 1 doses recommendation during the period 2005–2013.

Section snippets

Methods

Details on the methodology have been described in a previous publication [10]. Laboratory-confirmed IPD cases in children aged 2–59 months notified to regional public health authorities during the years 2005–2013 were eligible for study. Serotyping was performed at the Quebec Public Health laboratory. A breakthrough case was defined as IPD occurrence 10 days or more after a PCV dose.

Parents were contacted by the regional public health services and invited to participate. Those who agreed were

Results

During the 8-year study period, 889 laboratory-confirmed eligible IPD cases were reported in children less than 5 years old. Initial consent to participate in the case–control study was obtained from 689 parents (78% of total). The others could not be contacted or declined the invitation. No telephone contact could be made for 9 cases initially recruited, 9 parents declined further participation and 3 cases were found to be not eligible. Telephone interviews were performed with 668 parents and

Discussion

This is the first study comparing the effectiveness of three pneumococcal conjugate vaccines used sequentially in the context of a 2 + 1 doses recommendation. PCV7 effectiveness to prevent IPD caused by homologous serotypes was high and the estimate (≥1 dose: 90%) similar to that observed in a case–control study in the US (≥1 dose: 94%) [12]. Although PCV7 does not generate high levels of functional opsonophagocytosic (OPA) antibodies against 19A Sp, VE estimates against 19A IPD and otitis media

Conclusions

All three PCV vaccines showed high level of protection against IPD caused by homologous serotypes. There was a high level of cross-protection against 19A for PCV10. No substantial difference in protection against PCV13 types was observed between a PCV10-only, a PCV13-only, or a mixed PCV10 + PCV13 schedule.

Acknowledgements

The study was supported by a grant from the Quebec Ministry of Health and Social Services (‘Ministère de la Santé et des Services sociaux du Québec’). The sponsor had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, and preparation, review, and approval of the manuscript.

The authors thank Josiane Rivard, Dany Laverdière, Diane Audet from the Quebec University Hospital Research Center and all those who helped in the recruitment of

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