Causes of delayed outbreak responses and their impacts on epidemic spread

Livestock diseases have devastating consequences economically, socially and politically across the globe. In certain systems, pathogens remain viable after host death, which enables residual transmissions from infected carcasses. Rapid culling and carcass disposal are well-established strategies for stamping out an outbreak and limiting its impact; however, wait-times for these procedures, i.e. response delays, are typically farm-specific and time-varying due to logistical constraints. Failing to incorporate variable response delays in epidemiological models may understate outbreak projections and mislead management decisions. We revisited the 2001 foot-and-mouth epidemic in the United Kingdom and sought to understand how misrepresented response delays can influence model predictions. Survival analysis identified farm size and control demand as key factors that impeded timely culling and disposal activities on individual farms. Using these factors in the context of an existing policy to predict local variation in response times significantly affected predictions at the national scale. Models that assumed fixed, timely responses grossly underestimated epidemic severity and its long-term consequences. As a result, this study demonstrates how general inclusion of response dynamics and recognition of partial controllability of interventions can help inform management priorities during epidemics of livestock diseases

Vote-processing rules for combining control recommendations from multiple models

Mathematical modelling is used during disease outbreaks to compare control interventions. Using multiple models, the best method to combine model recommendations is unclear. Existing methods weight model projections, then rank control interventions using the combined projections, presuming model outputs are directly comparable. However, the way each model represents the epidemiological system will vary. We apply electoral vote-processing rules to combine model-generated rankings of interventions. Combining rankings of interventions, instead of combining model projections, avoids assuming that projections are comparable as all comparisons of projections are made within each model. We investigate four rules: First-past-the-post, Alternative Vote (AV), Coombs Method and Borda Count. We investigate rule sensitivity by including models that favour only one action or including those that rank interventions randomly. We investigate two case studies: the 2014 Ebola outbreak in West Africa (37 compartmental models) and a hypothetical foot-and-mouth disease outbreak in UK (four individual-based models). The Coombs Method was least susceptible to adding models that favoured a single action, Borda Count and AV were most susceptible to adding models that ranked interventions randomly. Each rule chose the same intervention as when ranking interventions by mean projections, suggesting that combining rankings provides similar recommendations with fewer assumptions about model comparability

Anticipating future learning affects current control decisions : a comparison between passive and active adaptive management in an epidemiological setting

Infectious disease epidemics present a difficult task for policymakers, requiring the implementation of control strategies under significant time constraints and uncertainty. Mathematical models can be used to predict the outcome of control interventions, providing useful information to policymakers in the event of such an epidemic. However, these models suffer in the early stages of an outbreak from a lack of accurate, relevant information regarding the dynamics and spread of the disease and the efficacy of control. As such, recommendations provided by these models are often incorporated in an ad hoc fashion, as and when more reliable information becomes available. In this work, we show that such trial-and-error-type approaches to management, which do not formally take into account the resolution of uncertainty and how control actions affect this, can lead to sub-optimal management outcomes. We compare three approaches to managing a theoretical epidemic: a non-adaptive management (AM) approach that does not use real-time outbreak information to adapt control, a passive AM approach that incorporates real-time information if and when it becomes available, and an active AM approach that explicitly incorporates the future resolution of uncertainty through gathering real-time information into its initial recommendations. The structured framework of active AM encourages the specification of quantifiable objectives, models of system behaviour and possible control and monitoring actions, followed by an iterative learning and control phase that is able to employ complex control optimisations and resolve system uncertainty. The result is a management framework that is able to provide dynamic, long-term projections to help policymakers meet the objectives of management. We investigate in detail the effect of different methods of incorporating up-to-date outbreak information. We find that, even in a highly simplified system, the method of incorporating new data can lead to different results that may influence initial policy decisions, with an active AM approach to management providing better information that can lead to more desirable outcomes from an epidemic

Synergistic interventions to control COVID-19 : mass testing and isolation mitigates reliance on distancing

Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies

Yersinia pestis Evolution on a Small Timescale: Comparison of Whole Genome Sequences from North America

Yersinia pestis, the etiologic agent of plague, was responsible for several devastating epidemics throughout history and is currently of global importance to current public heath and biodefense efforts. Y. pestis is widespread in the Western United States. Because Y. pestis was first introduced to this region just over 100 years ago, there has been little time for genetic diversity to accumulate. Recent studies based upon single nucleotide polymorphisms have begun to quantify the genetic diversity of Y. pestis in North America.To examine the evolution of Y. pestis in North America, a gapped genome sequence of CA88-4125 was generated. Sequence comparison with another North American Y. pestis strain, CO92, identified seven regions of difference (six inversions, one rearrangement), differing IS element copy numbers, and several SNPs.The relatively large number of inverted/rearranged segments suggests that North American Y. pestis strains may be undergoing inversion fixation at high rates over a short time span, contributing to higher-than-expected diversity in this region. These findings will hopefully encourage the scientific community to sequence additional Y. pestis strains from North America and abroad, leading to a greater understanding of the evolutionary history of this pathogen

Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models

The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-pharmaceutical interventions (e.g. lockdowns) to control the epidemic, making it difficult to estimate the relative transmissibility of variants. In this paper, we model the spatial spread of these variants in England using a meta-population agent-based model which correctly characterizes the regional variation in cases and distribution of variants. As a test of robustness, we additionally estimated the relative transmissibility of multiple variants using a statistical model based on the renewal equation, which simultaneously estimates the effective reproduction number R. Relative to earlier variants, the transmissibility of B.1.177 is estimated to have increased by 1.14 (1.12-1.16) and that of Alpha by 1.71 (1.65-1.77). The vaccination programme starting in December 2020 is also modelled. Counterfactual simulations demonstrate that the vaccination programme was essential for reopening in March 2021, and that if the January lockdown had started one month earlier, up to 30 k (24 k-38 k) deaths could have been prevented. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe