Abstract

BackgroundEstimating the effectiveness of meningococcal vaccines with high accuracy and precision can be challenging due to the low incidence of the invasive disease, which ranges between 0.5 and 1 cases per 100,000 in Europe and North America. Vaccine effectiveness (VE) is usually estimated with a screening method that combines in one formula the proportion of meningococcal disease cases that have been vaccinated and the proportion of vaccinated in the overall population. Due to the small number of cases, initial point estimates are affected by large uncertainties and several years may be required to estimate VE with a small confidence interval.MethodsWe used a Monte Carlo maximum likelihood (MCML) approach to estimate the effectiveness of meningococcal vaccines, based on stochastic simulations of a dynamic model for meningococcal transmission and vaccination. We calibrated the model to describe two immunization campaigns: the campaign against MenC in England and the Bexsero campaign that started in the UK in September 2015. First, the MCML method provided estimates for both the direct and indirect effects of the MenC vaccine that were validated against results published in the literature. Then, we assessed the performance of the MCML method in terms of time gain with respect to the screening method under different assumptions of VE for Bexsero.ResultsMCML estimates of VE for the MenC immunization campaign are in good agreement with results based on the screening method and carriage studies, yet characterized by smaller confidence intervals and obtained using only incidence data collected within 2 years of scheduled vaccination. Also, we show that the MCML method could provide a fast and accurate estimate of the effectiveness of Bexsero, with a time gain, with respect to the screening method, that could range from 2 to 15 years, depending on the value of VE measured from field data.ConclusionsResults indicate that inference methods based on dynamic computational models can be successfully used to quantify in near real time the effectiveness of immunization campaigns against Neisseria meningitidis. Such an approach could represent an important tool to complement and support traditional observational studies, in the initial phase of a campaign.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0642-2) contains supplementary material, which is available to authorized users.

Highlights

  • Estimating the effectiveness of meningococcal vaccines with high accuracy and precision can be challenging due to the low incidence of the invasive disease, which ranges between 0.5 and 1 cases per 100,000 in Europe and North America

  • Results indicate that inference methods based on dynamic computational models can be successfully used to quantify in near real time the effectiveness of immunization campaigns against Neisseria meningitidis

  • Simulation of serogroup B meningococcal (MenB) vaccine campaign in England and Monte Carlo maximum likelihood (MCML) settings In the second part of our work, we simulated the mass immunization campaign against MenB disease that started in England in September 2015

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Summary

Introduction

Estimating the effectiveness of meningococcal vaccines with high accuracy and precision can be challenging due to the low incidence of the invasive disease, which ranges between 0.5 and 1 cases per 100,000 in Europe and North America. Neisseria meningitidis is an aerobic Gram-negative diplococcus that causes annually 1.2 million cases of meningitis and 135,000 deaths globally [1]. This human-restricted opportunistic pathogen is part of the commensal flora that colonizes the upper respiratory tract of healthy. Carriage in infants is low, and grows slowly up to approximately 10 % in pre-adolescents. A sharp increase of carriage prevalence is observed after 15 years of age, reaching 25 % or more at the age of 20, and it decreases slowly to approximately 10 % in the elderly [19]

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