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Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD)., Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy., Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022., Exposures: Routine 4CMenB vaccination, per regional vaccination programs., Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact., Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose., Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.

Introduction: Invasive meningococcal disease (IMD) caused by non-serogroupable (NG) strains mainly affects immunocompromised individuals. Reduced susceptibility to penicillin in meningococci is increasing in Europe but ciprofloxacin resistance remains rare. In 2019, three travel-related meningococcal disease cases caused by a ciprofloxacin-resistant NG strain were identified in England, leading Germany to report four additional IMD cases (2016 to 2019). We describe these and newly identified cases and characterise the strain responsible., Methods: Cases were identified as part of national surveillance and by analysing available genomes using PubMLST tools., Results: Of the cases identified in England in 2019, two geographically distinct cases developed conjunctivitis after returning from Mecca (Kingdom of Saudi Arabia) and a third linked case presented with IMD. Of the four cases from Germany, three occurred in asylum seekers - two familial and a further geographically distinct case. Further IMD cases were identified in Italy (n = 2; 2017-2018), Sweden (n = 1; 2016) and England (n = 1; 2015). A single ST-175 clonal complex (cc175) strain with genosubtype P1.22-11,15-25 was responsible. Decreased susceptibility to penicillin was widespread with three ciprofloxacin resistant subclusters. Constituent isolates were potentially covered by subcapsular vaccines., Conclusion: This disease associated NG cc175 strain exhibits resistance to antibiotics commonly used to prevent IMD but is potentially covered by subcapsular (meningococcal B) vaccines., Competing Interests: Declaration of Competing Interest LW, JL, and RB perform contract research on behalf of Public Health England for GlaxoSmithKline, Pfizer, and Sanofi Pasteur. The Public Health England Immunisation and Countermeasures Division has provided vaccine manufactures with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. All other authors report no potential conflicts., (Copyright © 2020. Published by Elsevier Ltd.)