Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway
Introduction
A 7-valent conjugated pneumococcal vaccine (PCV-7) intended for use in children has been shown to be highly efficacious against invasive pneumococcal disease (IPD); a vaccine efficacy of 97.4% has been demonstrated when the vaccine is administered to infants in a four-dose regimen with three primary immunizations during the first year of life, and a booster in the second year of life [1]. PCV-7 was licensed in the United States in 2000, and a significant decline in IPD incidence rates among children under 2 years old was observed already in 2001 [2]. The decrease in IPD incidence rates extended beyond the target population to older children, adults and elderly persons [3], [4]. Conjugate vaccines reduce nasopharyngeal carriage of Streptococcus pneumoniae belonging to the vaccine serotypes, i.e. serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, leading to a reduced transmission and, subsequently, to herd immunity [5]. At least twice as many cases of IPD are prevented indirectly by herd immunity as by the direct effect of vaccination [4].
Ninety-one serotypes of pneumococci are currently known [6], [7]. PCV-7 covers the serotypes most commonly associated with IPD in children, although the serotype distribution, and thus the proportion of vaccine preventable IPD varies with time and geography [8], [9]. During the 1990s the incidence rate of IPD increased in Norway, as in other Scandinavian countries [10], [11]. In the period 1995–2001 the incidence rate of IPD was stable at approximately 19–20 cases/100,000 population, and vaccine serotype pneumococci were responsible for 73% of IPD in children <5 years [10]. However, the incidence rate of IPD caused by macrolide-resistant serotype 14 pneumococci in Norway started to increase in 2002, representing about 30% of cases in children aged less than 10 years by 2005 [12].
PCV-7 was licensed for use in a four-dose regimen, with three primary immunizations and a booster (3+1 schedule). However, the initial effects of vaccination in the United States were observed although complete immunization nationwide could not be performed due to vaccine shortages. The effectiveness of three- and four-dose schedules seems to be similar in a case-control study [13], and comparable serological responses have been observed in children receiving either three or four vaccine doses [14]. However, experiences with a three-dose (2+1) schedule vaccination programme are lacking.
Through the Norwegian Childhood Vaccination Programme, immunizations are offered free of charge to all children living in Norway. PCV-7 was introduced in the Norwegian Childhood Vaccination Programme in July 2006, with catch up for all children born in 2006 [15]. Immunization followed a 2+1 dose schedule, with two primary immunizations at 3 and 5 months of age, and a booster at 12 months of age. In the Childhood Vaccination Programme, PCV-7 is administered concomitantly to established vaccination against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae serotype b (DTP-IPV-Hib). This is the first report on the effectiveness of a 2+1 dose schedule of PCV-7 in a vaccination programme.
Section snippets
Study population
The total Norwegian population aged <5 years in 2002–2007 was included in this study. PCV-7 was licensed in Norway in 2001. All vaccine doses are distributed by the Norwegian Institute of Public Health (NIPH). Prior to 2006 approximately 800 vaccine doses were distributed from NIPH, and in 2006, approximately 12,000 doses were distributed outside the vaccination programme. PCV-7 was introduced as a programme vaccine on 1 July 2006, and immunization has been offered to all children born in 2006
Study population data
In the period from 2002 through 2007, the average population of Norway was 4,596,915. The average birth cohort was 56,953 children per year. During the study period, 523 cases of IPD among children aged <5 years were notified to MSIS.
PCV-7 vaccine coverage data
PCV-7 was offered to all children born after 1 January 2006, and by 1 January 2008, data on vaccine coverage showed that approximately 95% of children aged >3 months had received at least one immunization, approximately 90% of children aged >6 months had received
Discussion
The vaccine coverage for PCV-7 reached high levels soon after introduction in the Norwegian Childhood Vaccination Programme in July 2006. The incidence rate of IPD rapidly declined in the population targeted for vaccination; a significant decrease among children <1 year was observed already in 2006. This decrease continued in 2007, when a decrease among 1-year olds was also achieved. Thus, the initial decline in IPD incidence rates follows the 2006 birth cohort, the first cohort offered PCV-7.
Acknowledgements
We thank the personnel at the medical microbiological laboratories in Norway for their invaluable contributions to the surveillance of S. pneumoniae and invasive pneumococcal disease by forwarding pneumococcal isolates to the National Reference Laboratory at the Norwegian Institute of Public Health.
We are grateful for the notification and filling of the additional questionnaire by clinicians.
Anne R. Alme and Gunnhild Rødal are thanked for excellent technical assistance.
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