Since 2020, large-scale outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in Great Britain have resulted in substantial poultry mortality and economic losses. Alongside the costs, the risk of circulation leading to a viral reassortment that causes zoonotic spillover raises additional concerns. However, the precise mechanisms driving transmission between poultry premises and the impact of potential control measures in Great Britain, such as vaccination, are not fully understood. We have developed a spatial transmission model for the spread of HPAI in poultry premises calibrated to infected premises data for the 2022-23 season using Markov chain Monte Carlo. Our results indicate that reducing the susceptibility of the premises surrounding an identified infected premises (for example, through enhanced biosecurity measures and/or vaccination) can substantially reduce the overall number of infected premises. Our findings highlight that enhanced control measures could limit the future impact of HPAI on the poultry industry and reduce the risk of broader health threats.

In Fig 5, the stacked bar heights normalization is incorrect.The height of each stacked bar should be 1.0 instead of 0.8.Additionally, there is an error in the legend.The shade red should be associated with "Recovered Severe Infected Case (R S )" and yellow with "Recovered Mild Infected Case (R M )".Please see the correct Fig 5 and captions here.In S1 Text, there are errors in the legend of the Figures D, L, P, and T. The shade red should correspond to "Recovered severe infected case (R S )" and yellow to "Recovered mild infected case (R M )".Please view the correct S1 Text below.

Reducing reliance on pesticides is an important global challenge. With increasing constraints on their use, in recent years there has been a declining trend in pesticide use for arable crops in the UK. But with increasing disease pressures and global demand for food, there is a greater need for effective measures of pest and disease control. These circumstances highlight the need for widespread adoption of sustainable alternative control measures. Integrated Pest Management (IPM) is one such solution, comprising a set of management strategies which focus on the long-term prevention, detection and control of pests, weeds and diseases. While many of these methods are acknowledged to offer effective control, their implementation has thus far been limited in practice. As a case study we considered Septoria tritici blotch (STB) (Zymoseptoria tritici), an economically important disease of wheat. We used epidemiological modelling techniques to investigate the potential of different IPM control strategies (crop residue burial, delayed sowing, variety mixtures and biocontrols). Combining existing data with a deterministic, compartmental infectious disease model of STB transmission, we simulated the implementation of an IPM regime into the STB disease system. We investigated the outcomes on disease prevalence and crop yield when comparing conventional and IPM control regimes. In a single field, for the individual implementation of IPM measures we found the starkest difference in potential yield outcomes between delayed sowing and biocontrols (greatest yields), and crop residue burial and variety mixtures (lowest yields). We also found that the collective use of IPM measures has the potential to offer individual growers comparable control to a standard fungicide regime. For a multi-field setting, representing a community of crop growers, a high proportion of growers using IPM can reduce the level of external infection incurred by the growers who maintain a fungicide regime.

BACKGROUND: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. METHODS AND FINDINGS: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens-seasonal influenza, pandemic influenza and SARS-CoV-2-we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. CONCLUSIONS: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.

The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Now, despite substantial infection- and vaccine-induced immunity in host populations worldwide, waning immunity and the emergence of novel variants continue to cause significant waves of infection and disease. Policy makers must determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is therefore whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. This remains true for a range of assumptions about booster vaccine supply and timing, and for different assumed policy objectives of booster vaccination.

[This corrects the article DOI: 10.1371/journal.pcbi.1007096.].

The spread of infection amongst livestock depends not only on the traits of the pathogen and the livestock themselves, but also on the veterinary health behaviours of farmers and how this impacts their implementation of disease control measures. Controls that are costly may make it beneficial for individuals to rely on the protection offered by others, though that may be sub-optimal for the population. Failing to account for socio-behavioural properties may produce a substantial layer of bias in infectious disease models. We investigated the role of heterogeneity in vaccine response across a population of farmers on epidemic outbreaks amongst livestock, caused by pathogens with differential speed of spread over spatial landscapes of farms for two counties in England (Cumbria and Devon). Under different compositions of three vaccine behaviour groups (precautionary, reactionary, non-vaccination), we evaluated from population- and individual-level perspectives the optimum threshold distance to premises with notified infection that would trigger responsive vaccination by the reactionary vaccination group. We demonstrate a divergence between population and individual perspectives in the optimal scale of reactive voluntary vaccination response. In general, minimising the population-level perspective cost requires a broader reactive uptake of the intervention, whilst optimising the outcome for the average individual increased the likelihood of larger scale disease outbreaks. When the relative cost of vaccination was low and the majority of premises had undergone precautionary vaccination, then adopting a perspective that optimised the outcome for an individual gave a broader spatial extent of reactive response compared to a perspective wanting to optimise outcomes for everyone in the population. Under our assumed epidemiological context, the findings identify livestock disease intervention receptiveness and cost combinations where one would expect strong disagreement between the intervention stringency that is best from the perspective of a stakeholder responsible for supporting the livestock industry compared to a sole livestock owner. Were such discord anticipated and achieving a consensus view across perspectives desired, the findings may also inform those managing veterinary health policy the requisite reduction in intervention cost and/or the required extent of nurturing beneficial community attitudes towards interventions.

Rapid testing strategies that replace the isolation of close contacts through the use of lateral flow device tests (LFTs) have been suggested as a way of controlling SARS-CoV-2 transmission within schools that maintain low levels of pupil absences. We developed an individual-based model of a secondary school formed of exclusive year group bubbles (five year groups, with 200 pupils per year) to assess the likely impact of strategies using LFTs in secondary schools over the course of a seven-week half-term on transmission, absences, and testing volume, compared to a policy of isolating year group bubbles upon a pupil returning a positive polymerase chain reaction (PCR) test. We also considered the sensitivity of results to levels of participation in rapid testing and underlying model assumptions. While repeated testing of year group bubbles following case detection is less effective at reducing infections than a policy of isolating year group bubbles, strategies involving twice weekly mass testing can reduce infections to lower levels than would occur under year group isolation. By combining regular testing with serial contact testing or isolation, infection levels can be reduced further still. At high levels of pupil participation in lateral flow testing, strategies replacing the isolation of year group bubbles with testing substantially reduce absences, but require a high volume of testing. Our results highlight the conflict between the goals of minimising within-school transmission, minimising absences and minimising testing burden. While rapid testing strategies can reduce school transmission and absences, they may lead to a large number of daily tests.

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create 'COVID-secure' workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.

Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. We present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. The model captures a range of age-dependent heterogeneities, reduced transmission from asymptomatic infections and produces a good fit to the key epidemic features over time. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020 on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. We find that significant relaxation of social distancing measures from 7th May onwards can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. Our work confirms the effectiveness of stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. It also provides strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.

The COVID-19 outbreak has highlighted our vulnerability to novel infections. Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission-successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.

For infectious disease prevention, policy-makers are typically required to base policy decisions in light of operational and monetary restrictions, prohibiting implementation of all candidate interventions. To inform the evidence-base underpinning policy decision making, mathematical and health economic modelling can be a valuable constituent. Applied to England, this study aims to identify the optimal target age groups when extending a seasonal influenza vaccination programme of at-risk individuals to those individuals at low risk of developing complications following infection. To perform this analysis, we utilise an age- and strain-structured transmission model that includes immunity propagation mechanisms which link prior season epidemiological outcomes to immunity at the beginning of the following season. Making use of surveillance data from the past decade in conjunction with our dynamic model, we simulate transmission dynamics of seasonal influenza in England from 2012 to 2018. We infer that modified susceptibility due to natural infection in the previous influenza season is the only immunity propagation mechanism to deliver a non-negligible impact on the transmission dynamics. Further, we discerned case ascertainment to be higher for young infants compared to adults under 65 years old, and uncovered a decrease in case ascertainment as age increased from 65 to 85 years of age. Our health economic appraisal sweeps vaccination age space to determine threshold vaccine dose prices achieving cost-effectiveness under differing paired strategies. In particular, we model offering vaccination to all those low-risk individuals younger than a given age (but no younger than two years old) and all low-risk individuals older than a given age, while maintaining vaccination of at-risk individuals of any age. All posited strategies were deemed cost-effective. In general, the addition of low-risk vaccination programmes whose coverage encompassed children and young adults (aged 20 and below) were highly cost-effective. The inclusion of elder age-groups to the low-risk programme typically lessened the cost-effectiveness. Notably, elderly-centric programmes vaccinating from 65-75 years and above had the least permitted expense per vaccine.

Seasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological outcomes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.

In Bangladesh, the poultry industry is an economically and socially important sector, but it is persistently threatened by the effects of H5N1 highly pathogenic avian influenza. Thus, identifying the optimal control policy in response to an emerging disease outbreak is a key challenge for policy-makers. To inform this aim, a common approach is to carry out simulation studies comparing plausible strategies, while accounting for known capacity restrictions. In this study we perform simulations of a previously developed H5N1 influenza transmission model framework, fitted to two separate historical outbreaks, to assess specific control objectives related to the burden or duration of H5N1 outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular, we explore the optimal implementation of ring culling, ring vaccination and active surveillance measures when presuming disease transmission predominately occurs from premises-to-premises, versus a setting requiring the inclusion of external factors. Additionally, we determine the sensitivity of the management actions under consideration to differing levels of capacity constraints and outbreaks with disparate transmission dynamics. While we find that reactive culling and vaccination policies should pay close attention to these factors to ensure intervention targeting is optimised, across multiple settings the top performing control action amongst those under consideration were targeted proactive surveillance schemes. Our findings may advise the type of control measure, plus its intensity, that could potentially be applied in the event of a developing outbreak of H5N1 amongst originally H5N1 virus-free commercially-reared poultry in the Dhaka division of Bangladesh.