Effectiveness and Impact of the 4CMenB Vaccine against Group B Meningococcal Disease in Two Italian Regions Using Different Vaccination Schedules: A Five-Year Retrospective Observational Study (2014–2018)

Abstract

Background: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. Methods: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006–2018 for Tuscany and 2007–2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. Results: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL −0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. Conclusion: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.

Recent advances in meningococcal B disease prevention: real-world evidence from 4CMenB vaccination

“…Although the estimates of VE were similar in both regions, the post versus pre-4CMenB IRR showed a reduction in disease incidence of 68% (statistically significant) in Tuscany where the vaccination schedule commenced in early infancy (IRR 0.32 (95% CI 0.12, 0.91)) vs 31% (not significant) in Veneto (IRR 0.69 (95% CI 0.31, 1.56)) ( Table 2 ). By contrast, when taking into account the vaccination status, evaluation of disease incidence in the vaccinated cohorts showed significant reductions in both regions that were, as expected, similar to the VE estimates; 94% (95% CI 56, 99) in Tuscany and 90% (95% CI 57, 97) in Veneto 56 ( Fig. 2 ).…”

“…Mean coverage at age 24 months was 81.7% between 2017 and 2019. 56 Between 2014 and 2019 there were 4 cases of MenB IMD in Tuscany in children up to age 5 years; 1 case in a vaccinated child who had received 2 doses, and 3 cases in non-vaccinated children, giving a VE estimate of 93.6% (95% CI 55.4, 99.1) ( Table 3 ). Between 2014 and 2019 there were 7 cases of MenB IMD in children up to age 5 years in Veneto; 2 cases in vaccinated children and 5 in non-vaccinated children, giving a VE estimate of 91.0% (95% CI 59.9, 97.9) 56 ( Fig.…”

High coverage of diverse invasive meningococcal serogroup B strains by the 4-component vaccine 4CMenB in Australia, 2007–2011: Concordant predictions between MATS and genetic MATS

“…35 A reduction of 65% (within 5 years from introduction) and 35% (within 4 years from introduction) in MenB IMD cases was also observed in 2 regions in Italy in which routine 4CMenB vaccination was implemented according to different schedules. 36 Partial results of this study were used to support the licensure of 4CMenB in Australia, in individuals aged ≥2 months. Since October 2018, South Australia implemented a statefunded MenB immunization program with 4CMenB, for infants 6 weeks-12 months of age, and catch-up vaccinations for children >12 months-<4 years of age.…”

A Re-assessment of 4CMenB Vaccine Effectiveness Against Serogroup B Invasive Meningococcal Disease in England based on an Incidence Model

“…Our results are also aligned with 4CMenB effectiveness in infants and children reported by two recent observational studies in Italy (two regions, Tuscany and Veneto) and Portugal. 26,27 Still unclear is 4CMenB's potential impact on asymptomatic meningococcal carriage. A recent study in Australia failed to detect any effect on carriage, that could lead to indirect effects of vaccination, particularly in 10 adolescents.…”