Meningococcal C conjugate age-dependant long-term loss of effectiveness

Abstract

Introduction

Although different epidemiological studies have assessed meningococcal C conjugate vaccine effectiveness within 1 and >1 year since vaccination, none of them evaluated long-term effectiveness. In order to assess if epidemiological data correlates with the findings described in seroprevalence studies we evaluated long-term vaccine effectiveness over time, up to 10 years since vaccination.

Methods

Cases targeted by vaccination programs and notified to the Spanish Surveillance System between 2001 and 2013 were included in the study. Vaccine effectiveness was estimated using the screening method. Relationship between vaccine effectiveness and time since vaccination was explored using point estimates, simple logistic regression or restricted cubic splines logistic regression model for all and for those vaccinated at <1, 1–11 and at 12–19 years of age.

Results

From 345 confirmed cases reported in the period and targeted by vaccination programs, 125 (36.23%) were vaccine failures. Proportion of vaccine failures decreased with age of vaccination: 63.97% at <1 year; 36.84% at 1–11 years; and 3.88% at 12–19 years. Using the best model for each group, vaccine effectiveness decreased from 99.12% to 90.85% (%change = −8.3%) for all; from 99.04% to 48.60% (%change = −50.9%) for those vaccinated at <1 years and from 99.45% to 90.18% (%change = −9.3%) for those vaccinated at 1–11 years after 10 years since vaccination. For those vaccinated at 12–19 years no changes were observed in vaccine effectiveness after 10 years (p = 0.968).

Conclusions

After 10 years, vaccine effectiveness decreased by 50% in those vaccinated at <1 year, while those vaccinated with one dose at 12–19 years showed no changes. Vaccine failures occurred early after vaccination and more frequently in those vaccinated at younger ages. Vaccination at ≥12 years seems to be related to a low number of vaccine failures and a higher and endurable protection over time.

Introduction

Meningococcal serogroup C conjugate vaccine (MCC) was authorized in 1999/2000 and introduced progressively with different vaccination schedules within European countries [1]. Regardless of the vaccination schedule that has been followed, all countries that implemented MCC experienced substantial declines in incidence of the disease [2], [3], [4] and a reduction in acquisition of meningococcal serogroup C (MenC) carriage [5].

MCC was included in the Spanish vaccination schedule in December of 2000 at 2, 4 and 6 months of age. Based on the evidence available at that moment [5], [6], [7], [8], [9], [10], in 2006 the routine was changed to two doses at 2 and 4–6 months and a booster dose during the second year of age to improve long-term effectiveness [6], [8], [10], [11]. Additionally, since year 2000, catch-up campaigns were undertaken in most Spanish regions targeted for children less than 6 years of age and additional successive catch-up campaigns were launched to extend vaccination up to adolescence (<20 years) [6], [12].

More than ten years since the beginning of vaccination with the conjugated vaccine for MenC, Spain shows an epidemiological situation of low rates of the disease. Incidence decreased 84% (CI95%: 86–82.5%) in the period 2006/2007–2012/2013 compared with 1997/1998–1999/2000 seasons reaching the lowest incidence rate described in the country in 2012/2013 season (0.07 cases per 100,000 inhabitants) [12]. That decrease was higher among those targeted by the vaccine. Thus, since 2006/2007 season 60.3% of the cases were over 34 years old and therefore not targeted by any of the vaccination programmes launched in the country [12]. This fact increased the awareness about long-term effectiveness and how to protect older groups in the future, in which additionally case fatalities rates were higher [12].

Seroprevalence studies developed in different countries showed a decline in effectiveness in infants parallel to a decline in serum bactericidal antibody titres (SBA), while in adolescents, effectiveness and SBA titres remained more stable in time [9], [13], [14], [15], [16], [17], [18]. Moreover, SBA titres increased gradually with age between 6 and 18 years of age, in which a single dose of vaccine resulted in persistently high and bactericidal antibody levels up to at least five years after vaccination [16], [17], [18]. In 2014, a new change in the Spanish routine vaccination schedule was proposed to increase long-term protection against the disease. The change was based on both antibodies persistence studies in infants and adolescents [9], [13], [14], [15], [16], [17], [18], [19] and the epidemiological situation of the disease. Focus on ensuring long-term protection, the new schedule started on January 1st 2014 with 3 doses at 2–4 months, 12 months and 12 years.

Although many studies have assessed seroprevalence of SBA titres, these studies are difficult to implement for many years of follow-up. Long-term loss of vaccine effectiveness (VE) using epidemiological data has proved, as well, difficult to assess. Previous studies [11], [20], [21], [22], [23], including those developed by our country [6], [12], have assessed VE within 1 year and more than 1 year since vaccination. In all those studies, overall VE increased with age. Additionally, differences between VE ≤ 1 and VE > 1 year since vaccination decreased with age of administration, suggesting that loss of VE was lower with age [6], [11], [12], [20], [21], [22], [23] and correlated with seroprevalence studies evidence [9], [13], [14], [15], [17], [18].

The aim of this study was to continue investigating data published in our previous article [12] for evaluating vaccine failures distribution and long-term loss of VE over time, overall and by age-groups.