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During the 2022-2023 unprecedented mpox epidemic, near real-time short-term forecasts of the epidemic's trajectory were essential in intervention implementation and guiding policy. However, as case levels have significantly decreased, evaluating model performance is vital to advancing the field of epidemic forecasting. Using laboratory-confirmed mpox case data from the Centers for Disease Control and Prevention and Our World in Data teams, we generated retrospective sequential weekly forecasts for Brazil, Canada, France, Germany, Spain, the United Kingdom, the United States and at the global scale using an auto-regressive integrated moving average (ARIMA) model, generalized additive model, simple linear regression, Facebook's Prophet model, as well as the sub-epidemic wave and n-sub-epidemic modelling frameworks. We assessed forecast performance using average mean squared error, mean absolute error, weighted interval scores, 95% prediction interval coverage, skill scores and Winkler scores. Overall, the n-sub-epidemic modelling framework outcompeted other models across most locations and forecasting horizons, with the unweighted ensemble model performing best most frequently. The n-sub-epidemic and spatial-wave frameworks considerably improved in average forecasting performance relative to the ARIMA model (greater than 10%) for all performance metrics. Findings further support sub-epidemic frameworks for short-term forecasting epidemics of emerging and re-emerging infectious diseases.
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The 1918-20 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I) using information from Alaska death certificates dating between 1915 and 1921 (n=7,147). Goals include a reassessment of pandemic death numbers, analysis of P&I deaths beyond 1919, estimates of excess mortality patterns overall and by age using intercensal population estimates based on Alaska's demographic history, and comparisons between Alaska Native (AN) and non-AN residents. Results indicate that ANs experienced 83% of all P&I deaths and 87% of all-cause excess deaths during the pandemic. AN mortality was 8.1 times higher than non-AN mortality. Analyses also uncovered previously unknown mortality peaks in 1920. Both subpopulations showed characteristically high mortality of young adults, possibly due to imprinting with the 1889-90 pandemic virus, but their age-specific mortality patterns were different: non-AN mortality declined after age 25-29 and stayed relatively low for the elderly, while AN mortality increased after age 25-29, peaked at age 40-44, and remained high up to age 64. This suggests a relative lack of exposure to H1-type viruses pre-1889 among AN persons. In contrast, non-AN persons, often temporary residents, may have gained immunity before moving to Alaska.
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BACKGROUND: Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox, SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US. RESULTS: This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. CONCLUSIONS: We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA.
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COVID-19 , Predicción , Humanos , COVID-19/epidemiología , Predicción/métodos , SARS-CoV-2 , Epidemias/estadística & datos numéricos , Pandemias , Modelos Teóricos , Fiebre Hemorrágica Ebola/epidemiología , Modelos EstadísticosRESUMEN
BACKGROUND: While airport screening measures for COVID-19 infected passengers at international airports worldwide have been greatly relaxed, observational studies evaluating fever screening alone at airports remain scarce. The purpose of this study is to retrospectively assess the effectiveness of fever screening at airports in preventing the influx of COVID-19 infected persons. METHODS: We conducted a retrospective epidemiological analysis of fever screening implemented at 9 airports in Okinawa Prefecture from May 2020 to March 2022. The number of passengers covered during the same period was 9,003,616 arriving at 9 airports in Okinawa Prefecture and 5,712,983 departing passengers at Naha Airport. The capture rate was defined as the proportion of reported COVID-19 cases who would have passed through airport screening to the number of suspected cases through fever screening at the airport, and this calculation used passengers arriving at Naha Airport and surveillance data collected by Okinawa Prefecture between May 2020 and March 2021. RESULTS: From May 2020 to March 2021, 4.09 million people were reported to pass through airports in Okinawa. During the same period, at least 122 people with COVID-19 infection arrived at the airports in Okinawa, but only a 10 suspected cases were detected; therefore, the capture rate is estimated to be up to 8.2% (95% CI: 4.00-14.56%). Our result of a fever screening rate is 0.0002% (95%CI: 0.0003-0.0006%) (10 suspected cases /2,971,198 arriving passengers). The refusal rate of passengers detected by thermography who did not respond to temperature measurements was 0.70% (95% CI: 0.19-1.78%) (4 passengers/572 passengers). CONCLUSIONS: This study revealed that airport screening based on thermography alone missed over 90% of COVID-19 infected cases, indicating that thermography screening may be ineffective as a border control measure. The fact that only 10 febrile cases were detected after screening approximately 3 million passengers suggests the need to introduce measures targeting asymptomatic infections, especially with long incubation periods. Therefore, other countermeasures, e.g. preboarding RT-PCR testing, are highly recommended during an epidemic satisfying World Health Organization (WHO) Public Health Emergency of International Concern (PHEIC) criteria with pathogen characteristics similar or exceeding SARS-CoV-2, especially when traveling to rural cities with limited medical resources.
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Aeropuertos , COVID-19 , Fiebre , Tamizaje Masivo , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , Japón/epidemiología , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Estudios Retrospectivos , Tamizaje Masivo/métodos , SARS-CoV-2/aislamiento & purificación , Viaje , Masculino , Adulto , FemeninoRESUMEN
The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data.
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Evolución Biológica , Genoma Viral , Filogenia , Diagnóstico Precoz , Genoma Viral/genética , Genómica , SARS-CoV-2/genéticaRESUMEN
We estimated COVID-19 transmission potential and case burden by variant type in Alberta, British Columbia, and Ontario, Canada, during January 23, 2020-January 27, 2022; we also estimated the effectiveness of public health interventions to reduce transmission. We estimated time-varying reproduction number (Rt) over 7-day sliding windows and nonoverlapping time-windows determined by timing of policy changes. We calculated incidence rate ratios (IRRs) for each variant and compared rates to determine differences in burden among provinces. Rt corresponding with emergence of the Delta variant increased in all 3 provinces; British Columbia had the largest increase, 43.85% (95% credible interval [CrI] 40.71%-46.84%). Across the study period, IRR was highest for Omicron (8.74 [95% CrI 8.71-8.77]) and burden highest in Alberta (IRR 1.80 [95% CrI 1.79-1.81]). Initiating public health interventions was associated with lower Rt and relaxing restrictions and emergence of new variants associated with increases in Rt.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/transmisión , Ontario/epidemiología , Colombia Británica/epidemiología , Alberta/epidemiología , Incidencia , Número Básico de Reproducción , Salud PúblicaRESUMEN
Seroprevalence studies assessing community exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana concluded that population-level immunity remained low as of February 2021. Thus, it is important to demonstrate how increasing vaccine coverage reduces the economic and public health impacts associated with SARS-CoV-2 transmission. To that end, this study used a Susceptible-Exposed-Presymptomatic-Symptomatic-Asymptomatic-Recovered-Dead-Vaccinated compartmental model to simulate coronavirus disease 2019 (COVID-19) transmission and the role of public health interventions in Ghana. The impact of increasing vaccination rates and decline in transmission rates due to nonpharmaceutical interventions (NPIs) on cumulative infections and deaths averted was explored under different scenarios. Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) was used to investigate the uncertainty and sensitivity of the outcomes to the parameters. Simulation results suggest that increasing the vaccination rate to achieve 50% coverage was associated with almost 60,000 deaths and 25 million infections averted. In comparison, a 50% decrease in the transmission coefficient was associated with the prevention of about 150,000 deaths and 50 million infections. The LHS-PRCC results indicated that in the context of vaccination rate, cumulative infections and deaths averted were most sensitive to vaccination rate, waning immunity rates from vaccination, and waning immunity from natural infection. This study's findings illustrate the impact of increasing vaccination coverage and/or reducing the transmission rate by NPI adherence in the prevention of COVID-19 infections and deaths in Ghana.
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Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Cobertura de Vacunación , Humanos , Ghana/epidemiología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Cobertura de Vacunación/estadística & datos numéricos , Adulto , Persona de Mediana EdadRESUMEN
An ensemble n-sub-epidemic modeling framework that integrates sub-epidemics to capture complex temporal dynamics has demonstrated powerful forecasting capability in previous works. This modeling framework can characterize complex epidemic patterns, including plateaus, epidemic resurgences, and epidemic waves characterized by multiple peaks of different sizes. In this tutorial paper, we introduce and illustrate SubEpiPredict, a user-friendly MATLAB toolbox for fitting and forecasting time series data using an ensemble n-sub-epidemic modeling framework. The toolbox can be used for model fitting, forecasting, and evaluation of model performance of the calibration and forecasting periods using metrics such as the weighted interval score (WIS). We also provide a detailed description of these methods including the concept of the n-sub-epidemic model, constructing ensemble forecasts from the top-ranking models, etc. For the illustration of the toolbox, we utilize publicly available daily COVID-19 death data at the national level for the United States. The MATLAB toolbox introduced in this paper can be very useful for a wider group of audiences, including policymakers, and can be easily utilized by those without extensive coding and modeling backgrounds.
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Mathematical models based on systems of ordinary differential equations (ODEs) are frequently applied in various scientific fields to assess hypotheses, estimate key model parameters, and generate predictions about the system's state. To support their application, we present a comprehensive, easy-to-use, and flexible MATLAB toolbox, QuantDiffForecast, and associated tutorial to estimate parameters and generate short-term forecasts with quantified uncertainty from dynamical models based on systems of ODEs. We provide software ( https://github.com/gchowell/paramEstimation_forecasting_ODEmodels/) and detailed guidance on estimating parameters and forecasting time-series trajectories that are characterized using ODEs with quantified uncertainty through a parametric bootstrapping approach. It includes functions that allow the user to infer model parameters and assess forecasting performance for different ODE models specified by the user, using different estimation methods and error structures in the data. The tutorial is intended for a diverse audience, including students training in dynamic systems, and will be broadly applicable to estimate parameters and generate forecasts from models based on ODEs. The functions included in the toolbox are illustrated using epidemic models with varying levels of complexity applied to data from the 1918 influenza pandemic in San Francisco. A tutorial video that demonstrates the functionality of the toolbox is included.
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Modelos Biológicos , Programas Informáticos , Humanos , IncertidumbreRESUMEN
Simple dynamic modeling tools can help generate real-time short-term forecasts with quantified uncertainty of the trajectory of diverse growth processes unfolding in nature and society, including disease outbreaks. An easy-to-use and flexible toolbox for this purpose is lacking. This tutorial-based primer introduces and illustrates GrowthPredict, a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using phenomenological dynamic growth models based on ordinary differential equations. This toolbox is accessible to a broad audience, including students training in mathematical biology, applied statistics, and infectious disease modeling, as well as researchers and policymakers who need to conduct short-term forecasts in real-time. The models included in the toolbox capture exponential and sub-exponential growth patterns that typically follow a rising pattern followed by a decline phase, a common feature of contagion processes. Models include the 1-parameter exponential growth model and the 2-parameter generalized-growth model, which have proven useful in characterizing and forecasting the ascending phase of epidemic outbreaks. It also includes the 2-parameter Gompertz model, the 3-parameter generalized logistic-growth model, and the 3-parameter Richards model, which have demonstrated competitive performance in forecasting single peak outbreaks. We provide detailed guidance on forecasting time-series trajectories and available software ( https://github.com/gchowell/forecasting_growthmodels ), including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance across different models, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. This tutorial and toolbox can be broadly applied to characterizing and forecasting time-series data using simple phenomenological growth models. As a contagion process takes off, the tools presented in this tutorial can help create forecasts to guide policy regarding implementing control strategies and assess the impact of interventions. The toolbox functionality is demonstrated through various examples, including a tutorial video, and the examples use publicly available data on the monkeypox (mpox) epidemic in the USA.
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To study the SARS-CoV-2 transmission potential in Rhode Island (RI) and its association with policy changes and mobility changes, the time-varying reproduction number, Rt, was estimated. The daily incident case counts (16 March 2020, through 30 November 2021) were bootstrapped within a 15-day sliding window and multiplied by Poisson-distributed multipliers (λ = 4, sensitivity analysis: 11) to generate 1000 estimated infection counts, to which EpiEstim was applied to generate Rt time series. The median Rt percentage change when policies changed was estimated. The time lag correlations were assessed between the 7-day moving average of the relative changes in Google mobility data in the first 90 days, and Rt and estimated infection count, respectively. There were three major pandemic waves in RI in 2020-2021: spring 2020, winter 2020-2021 and fall-winter 2021. The median Rt fluctuated within the range of 0.5-2 from April 2020 to November 2021. Mask mandate (18 April 2020) was associated with a decrease in Rt (-25.99%, 95% CrI: -37.42%, -14.30%). Termination of mask mandates on 6 July 2021 was associated with an increase in Rt (36.74%, 95% CrI: 27.20%, 49.13%). Positive correlations were found between changes in grocery and pharmacy, Rt retail and recreation, transit, and workplace visits, for both Rt and estimated infection count, respectively. Negative correlations were found between changes in residential area visits for both Rt and estimated infection count, respectively. Public health policies enacted in RI were associated with changes in the pandemic trajectory. This ecological study provides further evidence of how non-pharmaceutical interventions and vaccination slowed COVID-19 transmission in RI.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Rhode Island/epidemiología , Pandemias , Política de SaludRESUMEN
Mobility restrictions were widely practiced to reduce contact with others and prevent the spatial spread of COVID-19 infection. Using inter-prefectural mobility and epidemiological data, a statistical model was devised to predict the number of imported cases in each Japanese prefecture. The number of imported cases crossing prefectural borders in 2020 was predicted using inter-prefectural mobility rates based on mobile phone data and prevalence estimates in the origin prefectures. The simplistic model was quantified using surveillance data of cases with an inter-prefectural travel history. Subsequently, simulations were carried out to understand how imported cases vary with the mobility rate and prevalence at the origin. Overall, the predicted number of imported cases qualitatively captured the observed number of imported cases over time. Although Hokkaido and Okinawa are the northernmost and the southernmost prefectures, respectively, they were sensitive to differing prevalence rate in Tokyo and Osaka and the mobility rate. Additionally, other prefectures were sensitive to mobility change, assuming that an increment in the mobility rate was seen in all prefectures. Our findings indicate the need to account for the weight of an inter-prefectural mobility network when implementing countermeasures to restrict human movement. If the mobility rates were maintained lower than the observed rates, then the number of imported cases could have been maintained at substantially lower levels than the observed, thus potentially preventing the unnecessary spatial spread of COVID-19 in late 2020.
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COVID-19 , Humanos , COVID-19/epidemiología , Japón/epidemiología , Modelos Estadísticos , Viaje , PrevalenciaRESUMEN
The successful application of epidemic models hinges on our ability to estimate model parameters from limited observations reliably. An often-overlooked step before estimating model parameters consists of ensuring that the model parameters are structurally identifiable from the observed states of the system. In this tutorial-based primer, intended for a diverse audience, including students training in dynamic systems, we review and provide detailed guidance for conducting structural identifiability analysis of differential equation epidemic models based on a differential algebra approach using differential algebra for identifiability of systems (DAISY) and Mathematica (Wolfram Research). This approach aims to uncover any existing parameter correlations that preclude their estimation from the observed variables. We demonstrate this approach through examples, including tutorial videos of compartmental epidemic models previously employed to study transmission dynamics and control. We show that the lack of structural identifiability may be remedied by incorporating additional observations from different model states, assuming that the system's initial conditions are known, using prior information to fix some parameters involved in parameter correlations, or modifying the model based on existing parameter correlations. We also underscore how the results of structural identifiability analysis can help enrich compartmental diagrams of differential-equation models by indicating the observed state variables and the results of the structural identifiability analysis.
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Algoritmos , Modelos Biológicos , HumanosRESUMEN
Sharka is a disease affecting stone fruit trees. It is caused by the Plum pox virus (PPV), with Myzus persicae being one of the most efficient aphid species in transmitting it within and among Prunus orchards. Other agricultural management strategies are also responsible for the spread of disease among trees, such as grafting and pruning. We present a mathematical model of impulsive differential equations to represent the dynamics of Sharka disease in the tree and vector population. We consider three transmission routes: grafting, pruning, and through aphid vectors. Grafting, pruning, and vector control occur as pulses at specific instants. Within the model, human risk perception towards disease influences these agricultural management strategies. Model results show that grafting with infected biological material has a significant impact on the spread of the disease. In addition, detecting infectious symptomatic and asymptomatic trees in the short term is critical to reduce disease spread. Furthermore, vector control to prevent aphid movement between trees is crucial for disease mitigation, as well as implementing awareness campaigns for Sharka disease in agricultural communities that provide a long-term impact on responsible pruning, grafting, and vector control.
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In May 2022, public health officials noted an unprecedented surge in mpox cases in non-endemic countries worldwide. As the epidemic accelerated, multi-model forecasts of the epidemic's trajectory were critical in guiding the implementation of public health interventions and determining policy. As the case levels have significantly decreased as of early September 2022, evaluating model performance is essential to advance the growing field of epidemic forecasting. Using laboratory-confirmed mpox case data from the Centers for Disease Control and Prevention (CDC) and Our World in Data (OWID) teams through the week of January 26th, 2023, we generated retrospective sequential weekly forecasts (e.g., 1-4-weeks) for Brazil, Canada, France, Germany, Spain, the United Kingdom, the USA, and at the global scale using models that require minimal input data including the auto-regressive integrated moving average (ARIMA), general additive model (GAM), simple linear regression (SLR), Facebook's Prophet model, as well as the sub-epidemic wave (spatial-wave) and n-sub-epidemic modeling frameworks. We assess forecast performance using average mean squared error (MSE), mean absolute error (MAE), weighted interval score (WIS), 95% prediction interval coverage (95% PI coverage), and skill scores. Average Winkler scores were used to calculate skill scores for 95% PI coverage. Overall, the n-sub-epidemic modeling framework outcompeted other models across most locations and forecasting horizons, with the unweighted ensemble model performing best across all forecasting horizons for most locations regarding average MSE, MAE, WIS, and 95% PI coverage. However, many locations had multiple models performing equally well for the average 95% PI coverage. The n-sub-epidemic and spatial-wave frameworks improved considerably in average MSE, MAE, and WIS, and Winkler scores (95% PI coverage) relative to the ARIMA model. Findings lend further support to sub-epidemic frameworks for short-term forecasting epidemics of emerging and re-emerging infectious diseases.
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A computational approach is adapted to analyze the parameter identifiability of a compartmental model. The model is intended to describe the progression of the COVID-19 pandemic in Chile during the initial phase in early 2020 when government declared quarantine measures. The computational approach to analyze the structural and practical identifiability is applied in two parts, one for synthetic data and another for some Chilean regional data. The first part defines the identifiable parameter sets when these recover the true parameters used to create the synthetic data. The second part compares the results derived from synthetic data, estimating the identifiable parameter sets from regional Chilean epidemic data. Experiments provide evidence of the loss of identifiability if some initial conditions are estimated, the period of time used to fit is before the peak, and if a significant proportion of the population is involved in quarantine periods.
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COVID-19 , Humanos , COVID-19/epidemiología , Chile/epidemiología , Pandemias/prevención & control , Modelos Biológicos , CuarentenaRESUMEN
BACKGROUND: COVID-19 brought enormous challenges to public health surveillance and underscored the importance of developing and maintaining robust systems for accurate surveillance. As public health data collection efforts expand, there is a critical need for infectious disease modeling researchers to continue to develop prospective surveillance metrics and statistical models to accommodate the modeling of large disease counts and variability. This paper evaluated different likelihoods for the disease count model and various spatiotemporal mean models for prospective surveillance. METHODS: We evaluated Bayesian spatiotemporal models, which are the foundation for model-based infectious disease surveillance metrics. Bayesian spatiotemporal mean models based on the Poisson and the negative binomial likelihoods were evaluated with the different lengths of past data usage. We compared their goodness of fit and short-term prediction performance with both simulated epidemic data and real data from the COVID-19 pandemic. RESULTS: The simulation results show that the negative binomial likelihood-based models show better goodness of fit results than Poisson likelihood-based models as deemed by smaller deviance information criteria (DIC) values. However, Poisson models yield smaller mean square error (MSE) and mean absolute one-step prediction error (MAOSPE) results when we use a shorter length of the past data such as 7 and 3 time periods. Real COVID-19 data analysis of New Jersey and South Carolina shows similar results for the goodness of fit and short-term prediction results. Negative binomial-based mean models showed better performance when we used the past data of 52 time periods. Poisson-based mean models showed comparable goodness of fit performance and smaller MSE and MAOSPE results when we used the past data of 7 and 3 time periods. CONCLUSION: We evaluate these models and provide future infectious disease outbreak modeling guidelines for Bayesian spatiotemporal analysis. Our choice of the likelihood and spatiotemporal mean models was influenced by both historical data length and variability. With a longer length of past data usage and more over-dispersed data, the negative binomial likelihood shows a better model fit than the Poisson likelihood. However, as we use a shorter length of the past data for our surveillance analysis, the difference between the Poisson and the negative binomial models becomes smaller. In this case, the Poisson likelihood shows robust posterior mean estimate and short-term prediction results.