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.

System identifiability in a time-evolving agent-based model.

Mathematical models are a valuable tool for studying and predicting the spread of infectious agents. The accuracy of model simulations and predictions invariably depends on the specification of model parameters. Estimation of these parameters is therefore extremely important; however, while some parameters can be derived from observational studies, the values of others are difficult to measure. Instead, models can be coupled with inference algorithms (i.e., data assimilation methods, or statistical filters), which fit model simulations to existing observations and estimate unobserved model state variables and parameters. Ideally, these inference algorithms should find the best fitting solution for a given model and set of observations; however, as those estimated quantities are unobserved, it is typically uncertain whether the correct parameters have been identified. Further, it is unclear what 'correct' really means for abstract parameters defined based on specific model forms. In this work, we explored the problem of non-identifiability in a stochastic system which, when overlooked, can significantly impede model prediction. We used a network, agent-based model to simulate the transmission of Methicillin-resistant staphylococcus aureus (MRSA) within hospital settings and attempted to infer key model parameters using the Ensemble Adjustment Kalman Filter, an efficient Bayesian inference algorithm. We show that even though the inference method converged and that simulations using the estimated parameters produced an agreement with observations, the true parameters are not fully identifiable. While the model-inference system can exclude a substantial area of parameter space that is unlikely to contain the true parameters, the estimated parameter range still included multiple parameter combinations that can fit observations equally well. We show that analyzing synthetic trajectories can support or contradict claims of identifiability. While we perform this on a specific model system, this approach can be generalized for a variety of stochastic representations of partially observable systems. We also suggest data manipulations intended to improve identifiability that might be applicable in many systems of interest.

Estimating and forecasting the burden and spread of Colombia's SARS-CoV2 first wave.

Following the rapid dissemination of COVID-19 cases in Colombia in 2020, large-scale non-pharmaceutical interventions (NPIs) were implemented as national emergencies in most of the country's municipalities, starting with a lockdown on March 20th, 2020. Recently, approaches that combine movement data (measured as the number of commuters between units), metapopulation models to describe disease dynamics subdividing the population into Susceptible-Exposed-Asymptomatic-Infected-Recovered-Diseased and statistical inference algorithms have been pointed as a practical approach to both nowcast and forecast the number of cases and deaths. We used an iterated filtering (IF) framework to estimate the model transmission parameters using the reported data across 281 municipalities from March to late October in locations with more than 50 reported deaths and cases in Colombia. Since the model is high dimensional (6 state variables in every municipality), inference on those parameters is highly non-trivial, so we used an Ensemble-Adjustment-Kalman-Filter (EAKF) to estimate time variable system states and parameters. Our results show the model's ability to capture the characteristics of the outbreak in the country and provide estimates of the epidemiological parameters in time at the national level. Importantly, these estimates could become the base for planning future interventions as well as evaluating the impact of NPIs on the effective reproduction number ([Formula: see text]) and the critical epidemiological parameters, such as the contact rate or the reporting rate. However, our forecast presents some inconsistency as it overestimates the deaths for some locations as Medellín. Nevertheless, our approach demonstrates that real-time, publicly available ensemble forecasts can provide short-term predictions of reported COVID-19 deaths in Colombia. Therefore, this model can be used as a forecasting tool to evaluate disease dynamics and aid policymakers in infectious outbreak management and control.

How disease risk awareness modulates transmission: coupling infectious disease models with behavioural dynamics.

Epidemiological models often assume that individuals do not change their behaviour or that those aspects are implicitly incorporated in parameters in the models. Typically, these assumptions are included in the contact rate between infectious and susceptible individuals. However, adaptive behaviours are expected to emerge and play an important role in the transmission dynamics across populations. Here, we propose a theoretical framework to couple transmission dynamics with behavioural dynamics due to infection awareness. We modelled the dynamics of social behaviour using a game theory framework, which is then coupled with an epidemiological model that captures the disease dynamics by assuming that individuals are aware of the actual epidemiological state to reduce their contacts. Results from the mechanistic model show that as individuals increase their awareness, the steady-state value of the final fraction of infected individuals in a susceptible-infected-susceptible (SIS) model decreases. We also incorporate theoretical contact networks, having the awareness parameter dependent on global or local contacts. Results show that even when individuals increase their awareness of the disease, the spatial structure itself defines the steady state.

Contact tracing reveals community transmission of COVID-19 in New York City.

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that locations with higher vaccination coverage and lower numbers of visitors to points-of-interest had reduced within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.