Inference of transmission dynamics and retrospective forecast of invasive meningococcal disease

The pathogenic bacteria Neisseria meningitidis, which causes invasive meningococcal disease (IMD), predominantly colonizes humans asymptomatically; however, invasive disease occurs in a small proportion of the population. Here, we explore the seasonality of IMD and develop and validate a suite of models for simulating and forecasting disease outcomes in the United States. We combine the models into multi-model ensembles (MME) based on the past performance of the individual models, as well as a naive equally weighted aggregation, and compare the retrospective forecast performance over a six-month forecast horizon. Deployment of the complete vaccination regimen, introduced in 2011, coincided with a change in the periodicity of IMD, suggesting altered transmission dynamics. We found that a model forced with the period obtained by local power wavelet decomposition best fit and forecast observations. In addition, the MME performed the best across the entire study period. Finally, our study included US-level data until 2022, allowing study of a possible IMD rebound after relaxation of non-pharmaceutical interventions imposed in response to the COVID-19 pandemic; however, no evidence of a rebound was found. Our findings demonstrate the ability of process-based models to retrospectively forecast IMD and provide a first analysis of the seasonality of IMD before and after the complete vaccination regimen.Author summary: This paper presents a time series analysis of Invasive Meningococcal Disease caused by the pathogenic bacteria Neisseria meningitidis as well as the development and validation of a suite of models for simulating and forecasting disease outcomes in the United States. We present the models and their performance and construct a multi-model ensemble (MME) forecast that combines individual models based on past forecast performance, as well as an equally weighted aggregation. Deployment of a complete vaccination regimen, introduced for adolescents in 2011, coincided with a change in the periodicity of IMD, suggesting altered transmission dynamics. We found that a model forced with the period obtained by local power wavelet decomposition best fits and forecasts observations. In addition, the MME forecasts performed the best across the entire study period. Finally, our study included US-level data until 2022, allowing study of a possible IMD rebound after the relaxation of non-pharmaceutical interventions imposed in response to the COVID-19 pandemic; however, no evidence of a rebound was found. Our findings demonstrate the ability of process-based models to retrospectively forecast IMD and provide a first analysis of the seasonality of IMD before and after the complete vaccination regimen.