Changes in meningococcal C epidemiology and vaccine effectiveness after vaccine introduction and schedule modification
Introduction
Meningococcal C conjugate vaccine was included in the Spanish vaccination schedule in December of 2000 at 2, 4 and 6 months of age. At the same time a catch-up campaign was undertaken in most Spanish regions targeted for children less than 6 years of age. Since 2000, additional successive catch-up campaigns were launched to extend vaccination up to adolescence (< 20 years) with differences in starting date, duration, targeted age-groups and coverage between regions.
In 2005, recommended routine vaccination schedule was modified based on the conclusions of the VE studies developed in Spain [1] and UK [2] that showed loss of VE after the elapse of more than 1 year since vaccination. The new schedule started in 2006 and it is currently in use with two priming doses of vaccine at 2 and 4–6 months and a booster during the second year of age. Vaccine coverage has been high since the introduction of the vaccine in the childhood vaccination calendar remaining over 95% since 2002, while booster coverage, slightly lower than priming coverage, remained over 94% since 2008. On the other hand, coverage in catch-up campaigns showed high heterogeneity among regions and targeted age-groups varying from an average coverage of 95% (range: 86.1%–98.9%) for two doses scheduled for infants between 6–12 months; of 85% (range: 80%–97.5%) for one dose scheduled for children between >12 months to <6 years of age; and of 77% (range: 45.8%–96.1%) for one dose scheduled for children/adolescents ≥6 years.
Even though booster doses after the first year of age have proved to sustain population immunity against meningococcal serogroup C (MenC) disease and are recommended to achieve the control of the disease [3], [4], [5], vaccine failure related to loss of vaccine protection after 1 year of vaccination continued to be one of the main unresolved issues even after booster administration [6], [7], [8]. Seroprevalence studies in infants and adolescents showed a decline in effectiveness in infants parallel to a decline in serum bactericidal antibody (SBA) titres while adolescent effectiveness and SBA titres remained more stable in time [9], [10], [11], [12], [13]. Therefore, different studies support the idea that multiple doses in early infancy provide little if any additional benefit compared to a reduced primary vaccination schedule [14], [15]. Furthermore, a recent study has concluded that a single priming dose of NeisVac-C® at 4 or 6 months of age followed by a booster dose at 12–13 months of age showed high seroprotection rates and SBA titres and can be an adequate alternative to the two-dose priming vaccination schedule [16]. However, it is known that MenC conjugated to tetanus toxoid produce higher levels of SBA [6], [17] and those results could not be extrapolated to all MenC vaccine types. Additionally, some countries [9], [18], [19] are extending the recommendation of routine vaccination inclusion in adolescents to enhance long-term protection.
The aim of this study was both to assess the VE of the two different routine vaccination schedules applied in Spain and include the successive catch-up campaigns in children/adolescents up to 19 years of age to obtain a global estimation of the VE in the country. Loss of protection after 1 year of vaccination and VE related to age of administration of vaccine, as well as risk of MenC during the first year of life were assessed. This information may be useful in the current discussion about the need of a new vaccination schedule in Spain, and can be used, as well, to compare future vaccination scenarios.
Section snippets
Methods
Data on cases of meningococcal disease reported in Spain were obtained from the National Notifiable Disease Surveillance System. Reporting of the weekly number of invasive meningococcal disease (IMD) has been mandatory since 1964, but in 1996 notification was enhanced to obtain further information including case-based epidemiological and microbiological data.
Epidemiological seasons for IMD were defined as yearly periods between week 41 of one year and week 40 of the following year. Cases of
Trends in MenC disease incidence
From 1996/97 till the end of 2012/13 season a total number of 3,331 cases of laboratory confirmed MenC disease were reported. Trends of incidence by epidemiological season are shown in Fig. 1 for all, < 25 years cases and ≥ 25 years. In 1996/97 season MenC in Spain showed still higher incidence due to hyper-virulent strain of serogroup C (2.27 cases per 100,000 pop.) similar to other European countries during the mid-1990s [24], [25]. Between 1997/98 and 1999/00 seasons the MenC incidence rates
Discussion
After the inclusion of conjugate vaccine against MenC in the Spanish childhood vaccination schedule, meningococcal C disease incidence and mortality rates have been reduced significantly among those targeted by routine or catch-up first [1] and in non-vaccine targeted age-groups after. Higher reduction was shown in < 4 years age-group, directly protected by routine vaccination. It achieved in the last period a decrease in incidence of 97% (p < 0.001) with no deaths notified compared with the
Conclusions
Incidence of MenC disease fell by 84% since the introduction of the vaccine. Low incidence of MenC disease in our country and, especially, dramatic reduction in infants <1 year of age incidence in Spain have allowed to move one of the priming doses to older ages (at 11-12 years) where it can generate higher and endurable seroprotection and herd immunity. Additional consideration should be done regarding more than 60% of cases in non-targeted groups and the possibility of extending vaccination
Conflict of interest statement
The authors declare that they have no competing interests.
Acknowledgements
The authors would like to thank all the epidemiologists and vaccine health officers who have participated in meningococcal disease surveillance and vaccine programmes in the Spanish Autonomous Regions for unstintingly collecting and relaying the data needed to conduct this study, particularly, to Aurora Limia for providing us detailed information about the different catch-up campaigns and their coverages.
References (26)
- et al.
Impact and effectiveness of meningococcal C conjugate vaccine following its introduction in Spain
Vaccine
(2005) - et al.
Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction
Lancet
(2004) - et al.
Investigation of serum bactericidal activity in childhood and adolescence 3-6 years after vaccination with a single dose of serogroup C meningococcal conjugate vaccine
Vaccine
(2009) - et al.
Single priming dose of meningococcal group C conjugate vaccine (NeisVac-C(R)) in infants
Vaccine
(2013) - et al.
Meningococcal C conjugate vaccine: the experience in England and Wales
Vaccine
(2009) - et al.
Recent emergence of serogroup C meningococcal disease in Greece
FEMS Immunol Med Microbiol
(1999) - et al.
Kinetics of antibody persistence following administration of a combination meningococcal serogroup C and haemophilus influenzae type b conjugate vaccine in healthy infants in the United Kingdom primed with a monovalent meningococcal serogroup C vaccine
Clin Vaccine Immunol
(2010) - et al.
Immunity against Neisseria meningitidis serogroup C in the Dutch population before and after introduction of the meningococcal c conjugate vaccine
PLoS One
(2010) - et al.
Antibody persistence after serogroup C meningococcal conjugate immunization of United Kingdom primary-school children in 1999-2000 and response to a booster: a phase 4 clinical trial
Clin Infect Dis
(2010) - et al.
Antibody persistence 12 months after a booster dose of meningococcal-C conjugated vaccine in the second year of life
Pediatr Infect Dis J
(2010)