Invasive pneumococcal diseases in birth cohorts vaccinated with PCV-7 and/or PHiD-CV in the province of Quebec, Canada
Highlights
► The 10-valent pneumococcal conjugate vaccine was introduced in 2009 in Quebec. ► We present the first data on the effectiveness of this vaccine. ► Invasive pneumococcal disease rates were lower in cohorts exposed to PHiD-CV as compared to PCV-7. ► There was no vaccine-type case following ≥2 PHiD-CV primary doses or one booster dose. ► Results are compatible with high level of protection against IPD caused by homologous serotypes.
Introduction
In the province of Quebec, Canada, a pneumococcal conjugate vaccine program was implemented in December 2004 [1]. The recommended schedule is 2+1 doses for low-risk infants (2, 4, and 12 months) and 3+1 doses for high-risk infants (2, 4, 6 and 12 months). The seven-valent CRM197 vaccine (PCV-7; Prevnar™, Pfizer) was first used (including the initial catch-up for children up to age 5 years), and then replaced by the 10-valent Hi-Protein-D vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline) in the summer of 2009, and by the 13-valent CRM197 vaccine (PCV-13; Prevnar13™, Pfizer) in January 2011 (no catch-up in both instances). Transition to the new vaccines were recommended regardless of the number of PCV7 or PHiD-CV-10 doses already administered (see e-Table for details). PCV-7 covers seven Streptococcus pneumoniae (Sp) serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) and cross-protection against 6A has been demonstrated [2]. PHiD-CV includes 3 additional serotypes (1, 5 and 7F) and PCV-13 adds another three ones (3, 6A and 19A). From the beginning, vaccine uptake has been high and stable in Quebec and transitions did not affect vaccine coverage [3], [4], [5]. Results from the 2010 provincial immunization survey showed that 90% of the children had received ≥3 pneumoccocal vaccine doses by 12 months of age, 93% by age 15 months, and 94% by age 24 months [5]. Implementation of the PCV-7 program was rapidly followed by a decrease in the frequency of invasive pneumococcal diseases (IPD) caused by the 7 vaccine-serotypes in all age groups [1], [6], [7]. Concurrently, an increase in the incidence of serotypes not included in PCV-7 was observed, more in adults than in children [1], [6], [7].
PHiD-CV was licensed in Canada on the basis of immunogenicity data showing a non-inferior immune response as compared to PCV-7 in a 3+1 schedule for the common serotypes, and the induction of functional antibodies and an immune memory for the additional serotypes [8]. Currently, there is no published study on the effectiveness of PHiD-CV in preventing IPD in children and on the impact of PHiD-CV use at the population level.
The objective of the present study was to analyze IPD rates in children born in Quebec in 2007–2010 and followed up to December 31, 2010. The first cohorts were exposed to PCV-7 only. The following cohorts received PCV-7 for the primary series and PHiD-CV for the booster dose. Thereafter, PHiD-CV was used for both the primary series and the booster dose. PCV-13 was only administered to a small number of children born in 2010.
Section snippets
Methods
This is a population-based ecological study of children born in 2007–2010 in the province of Quebec, Canada, and followed up to December 31, 2010. Denominator figures on the monthly number of births were provided by the Quebec Statistical Institute. We assumed that in each cohort, the number of persons at risk remained constant from birth up to the 4th anniversary.
IPD is in the list of notifiable diseases in Quebec and all microbiology laboratories are invited to transmit isolates from children
Results
A total of 265 laboratory-confirmed IPD cases were reported in the study population including 349,218 children, representing 690,274 person-years (p-y) of observation. The most prevalent serotype was 19A (n = 122; 46% of total cases), followed by 7F (n = 28; 11% of total cases). Serotypes included in PCV-7 were not frequent (n = 10; 4% of total cases). Details on the distribution of IPD cases in the 48 monthly cohorts of births is shown in e-Figure, according to the serotype and the main vaccine or
Discussion
In Quebec, the introduction of PHiD-CV was associated with a decreasing incidence of IPD in exposed children. No breakthrough PHiD-CV-type IPD case was observed among those who had received ≥2 PHiD-CV doses for the primary immunization series or a single PHiD-CV dose as a booster. There was also a decrease of the incidence of all other serotypes in PHiD-CV cohorts and this was not seen in older age groups.
Results of ecological studies should be interpreted with care as it is always difficult to
Acknowledgements
The study was supported by a research grant from the ‘Ministère de la santé et des Services sociaux du Québec’. The funder had no role in the design and conduct of the study; collection, management, analysis and interpretation of data; and preparation of the manuscript.
References (21)
- et al.
Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case–control study
Lancet
(2006) - et al.
Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumonia and non-typable Haemophilus influenza: a randomised double-blind efficacy study
Lancet
(2006) - et al.
Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete
Epidemics
(2010) - et al.
Impact of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) on bacterial nasopharyngeal carriage
Vaccine
(2011) - et al.
How to compare the efficacy of conjugate vaccines to prevent acute otitis media?
Vaccine
(2009) - et al.
Impact du programme d’immunisation par le vaccin pneumococcique conjugué heptavalent (VPC-7) au Québec
(2011) - et al.
Enquête sur la couverture vaccinale des enfants québécois en 2006
(2007) - et al.
Enquête sur la couverture vaccinale des enfants de 1 an et 2 ans au Québec en 2008
(2009) - et al.
Enquête sur la couverture vaccinale des enfants de 1 an et 2 ans au Québec en 2010
(2011) - et al.
Programme de surveillance du pneumocoque: Rapport 2010
(2012)
Cited by (45)
Constrained Optimization for Pneumococcal Vaccination in Brazil
2021, Value in Health Regional IssuesCost-Effectiveness Comparison of Pneumococcal Conjugate Vaccines in Turkish Children
2019, Value in Health Regional IssuesCharacteristics of children with refractory acute otitis media treated at the pediatric emergency department
2019, International Journal of Pediatric Otorhinolaryngology