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During an infectious disease outbreak, public health policy makers are tasked with strategically implementing interventions whilst balancing competing objectives. To provide a quantitative framework that can be used to guide these decisions, it is helpful to devise a clear and specific objective function that can be evaluated to determine the optimal outbreak response. In this study, we have developed a mathematical modelling framework representing outbreaks of a novel emerging pathogen for which non-pharmaceutical interventions (NPIs) are imposed or removed based on thresholds for hospital occupancy. These thresholds are set at different levels to define four unique strategies for disease control. We illustrate that the optimal intervention strategy is contingent on the choice of objective function. Specifically, the optimal strategy depends on the extent to which policy makers prioritise reducing health costs due to infection over the costs associated with maintaining interventions. Motivated by the scenario early in the COVID-19 pandemic, we incorporate the development of a vaccine into our modelling framework and demonstrate that a policy maker's belief about when a vaccine will become available in future, and its eventual coverage (and/or effectiveness), affects the optimal strategy to adopt early in the outbreak. Furthermore, we show how uncertainty in these quantities can be accounted for when deciding which interventions to introduce. This research highlights the benefits of policy makers being explicit about the precise objectives of introducing interventions. Author summary: While often necessary to contain an infectious disease outbreak, extensive interventions result in education, economic and societal harms. For the optimal response to be determined, the trade-off between the costs and benefits of disease control requires policy makers to define and communicate their objectives for managing the outbreak. We use a mathematical model to simulate outbreaks where social distancing is implemented when disease prevalence within hospital settings is high. We consider four distinct strategies for managing the outbreak based on different hospital prevalence thresholds for switching between levels of social distancing. The optimal strategy to implement depends on how a policy maker balances the importance of reducing the number of hospitalisations and the costs of maintaining interventions. The optimal strategy to implement at the beginning of the outbreak is further impacted by beliefs regarding the future availability of a vaccine. We develop a quantitative decision making framework which explicitly considers the objectives of policy makers and allows robust strategies for future disease outbreaks to be designed. [ABSTRACT FROM AUTHOR]

Prophylactic interventions such as vaccine allocation are some of the most effective public health policy planning tools. The supply of vaccines, however, is limited and an important challenge is to optimally allocate the vaccines to minimize epidemic impact. This resource allocation question (which we refer to as VID) has multiple dimensions: when, where, to whom, etc. Most of the existing literature in this topic deals with the latter (to whom), proposing policies that prioritize individuals by age and disease risk. However, since seasonal influenza spread has a typical spatial trend, and due to the temporal constraints enforced by the availability schedule, the when and where problems become equally, if not more, relevant. In this paper, we study the VID problem in the context of seasonal influenza spread in the United States. We develop a national scale metapopulation model for influenza that integrates both short and long distance human mobility, along with realistic data on vaccine uptake. We also design GA, a greedy algorithm for allocating the vaccine supply at the state level under temporal constraints and show that such a strategy improves over the current baseline of pro-rata allocation, and the improvement is more pronounced for higher vaccine efficacy and moderate flu season intensity. Further, the resulting strategy resembles a ring vaccination applied spatiallyacross the US. [ABSTRACT FROM AUTHOR]

In May 2022, a cluster of mpox cases were detected in the UK that could not be traced to recent travel history from an endemic region. Over the coming months, the outbreak grew, with over 3000 total cases reported in the UK, and similar outbreaks occurring worldwide. These outbreaks appeared linked to sexual contact networks between gay, bisexual and other men who have sex with men. Following the COVID-19 pandemic, local health systems were strained, and therefore effective surveillance for mpox was essential for managing public health policy. However, the mpox outbreak in the UK was characterised by substantial delays in the reporting of the symptom onset date and specimen collection date for confirmed positive cases. These delays led to substantial backfilling in the epidemic curve, making it challenging to interpret the epidemic trajectory in real-time. Many nowcasting models exist to tackle this challenge in epidemiological data, but these lacked sufficient flexibility. We have developed a nowcasting model using generalised additive models that makes novel use of individual-level patient data to correct the mpox epidemic curve in England. The aim of this model is to correct for backfilling in the epidemic curve and provide real-time characteristics of the state of the epidemic, including the real-time growth rate. This model benefited from close collaboration with individuals involved in collecting and processing the data, enabling temporal changes in the reporting structure to be built into the model, which improved the robustness of the nowcasts generated. The resulting model accurately captured the true shape of the epidemic curve in real time. Author summary: During 2022, outbreaks of mpox, the disease caused by the monkeypox virus, occurred simultaneously in multiple non-endemic countries, including England. These outbreaks were distinct from historic outbreaks with a majority of cases in gay, bisexual and other men who have sex with men and in individuals without recent travel histories to endemic countries. To inform public health policy, understanding the number of new cases and growth rate of the outbreak in real-time is essential. However, the outbreak was characterised by long delays from individuals developing symptoms (or getting a test) and being reported as a positive case. This creates a biased picture of the outbreak, where observed real-time cases underestimates the true extent of the outbreak. We developed a mathematical model that accounts for these reporting delays to estimate the true shape of the epidemic curve in real-time. The modelled outputs are able to accurately capture the true shape of the epidemic, and provide improved real-time insight over the raw data. This model was used continuously throughout the outbreak response in the UK to provide insight to the incident management team at the UK Health Security Agency. [ABSTRACT FROM AUTHOR]

Heterogeneity in contact patterns, mortality rates, and transmissibility among and between different age classes can have significant effects on epidemic outcomes. Adaptive behavior in response to the spread of an infectious pathogen may give rise to complex epidemiological dynamics. Here we model an infectious disease in which adaptive behavior incentives, and mortality rates, can vary between two and three age classes. The model indicates that age-dependent variability in infection aversion can produce more complex epidemic dynamics at lower levels of pathogen transmissibility and that those at less risk of infection can still drive complexity in the dynamics of those at higher risk of infection. Policymakers should consider the interdependence of such heterogeneous groups when making decisions. Author summary: Behavior during epidemics is driven by incentives, which may vary among the different age classes. Here we include age-differentiated incentives in an adaptive behavioral epidemic model with two and three age classes. Our results indicate that this heterogeneity can drive the system into oscillations, chaos, and collapse. Those with less incentives to adopt protective behavior for themselves (i.e., the youth) can still drive epidemic dynamics and associated complexity in those who have more incentives to avoid contacts during epidemics (i.e., the elderly). This heterogeneity and interdependence should be taken into account when making public health policy that affects individual contact rates during an epidemic. [ABSTRACT FROM AUTHOR]

Population contact patterns fundamentally determine the spread of directly transmitted airborne pathogens such as SARS-CoV-2 and influenza. Reliable quantitative estimates of contact patterns are therefore critical to modeling and reducing the spread of directly transmitted infectious diseases and to assessing the effectiveness of interventions intended to limit risky contacts. While many countries have used surveys and contact diaries to collect national-level contact data, local-level estimates of age-specific contact patterns remain rare. Yet, these local-level data are critical since disease dynamics and public health policy typically vary by geography. To overcome this challenge, we introduce a flexible model that can estimate age-specific contact patterns at the subnational level by combining national-level interpersonal contact data with other locality-specific data sources using multilevel regression with poststratification (MRP). We estimate daily contact matrices for all 50 US states and Washington DC from April 2020 to May 2021 using national contact data from the US. Our results reveal important state-level heterogeneities in levels and trends of contacts across the US over the course of the COVID-19 pandemic, with implications for the spread of respiratory diseases. Author summary: Reliable quantitative estimates of contact patterns are in high demand because they are a critical input for modeling and reducing the spread of directly transmitted infectious diseases such as COVID-19 and influenza. But, while national-level contact data are available from surveys collected in many countries—including the United States—local-level estimates of age-specific contact patterns are almost never available. Yet these local-level contact patterns are crucial, since disease dynamics and public health policy vary by geography. Here, we introduce a new method for estimating levels and trends in local-level rates of disease-relevant contacts by combining information from national-level contact data and other locality-specific data sources. We illustrate our method by estimating novel state-level estimates of contact patterns in the US over the course of the COVID-19 pandemic. These estimates are an important resource for researchers and policymakers who wish to understand the state-level dynamics of the COVID-19 pandemic in the United States. The new methods we introduce are applicable to any directly transmitted infectious disease and can be applied in many different settings all over the world. [ABSTRACT FROM AUTHOR]

The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010–2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved satisfactory model performance (R2EpiEstim = 0.95, R2EpiFilter = 0.97), but disparities in performance were large at finer spatial scales when case counts are low (MASE EpiEstim = 1.23, MASEEpiFilter = 0.59). Impervious surfaces and vegetation with structure dominated by human management (without tree canopy) were positively associated with increased transmission intensity. Vegetation with structure dominated by human management (with tree canopy), on the other hand, was associated with lower dengue transmission intensity. We showed that dengue outbreaks were preceded by sustained periods of high transmissibility, demonstrating the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response. Author summary: The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010–2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved high accuracy, but disparities in performance were large at finer spatial scales when case counts are low. This study demonstrates the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response. [ABSTRACT FROM AUTHOR]

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy–either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures. Author summary: Calibration—that is, "fitting" the model to data—is a crucial part of using mathematical models to better forecast and control the population-level spread of infectious diseases. Evidence that the mathematical model is well-calibrated improves confidence that the model provides a realistic picture of the consequences of health policy decisions. To make informed decisions, Policymakers need information about uncertainty: i.e., what is the range of likely outcomes (rather than just a single prediction). Thus, modellers should also strive to provide accurate measurements of uncertainty, both for their model parameters and for their predictions. This systematic review provides an overview of the methods used to calibrate individual-based models (IBMs) of the spread of HIV, malaria, and tuberculosis. We found that less than half of the reviewed articles used reproducible, non-subjective calibration methods. For the remaining articles, the method could either not be identified or was described as an informal, non-reproducible method. Only one-third of the articles obtained estimates of parameter uncertainty. We conclude that the adoption of better-documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. [ABSTRACT FROM AUTHOR]