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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The dynamics of vaccination against SARS-CoV-2 are complicated by age-dependent factors, changing levels of infection, and the relaxation of non-pharmaceutical interventions (NPIs) as the perceived ...risk declines, necessitating the use of mathematical models. Our aims were to use epidemiological data from the UK together with estimates of vaccine efficacy to predict the possible long-term dynamics of SARS-CoV-2 under the planned vaccine rollout.
In this study, we used a mathematical model structured by age and UK region, fitted to a range of epidemiological data in the UK, which incorporated the planned rollout of a two-dose vaccination programme (doses 12 weeks apart, protection onset 14 days after vaccination). We assumed default vaccine uptake of 95% in those aged 80 years and older, 85% in those aged 50–79 years, and 75% in those aged 18–49 years, and then varied uptake optimistically and pessimistically. Vaccine efficacy against symptomatic disease was assumed to be 88% on the basis of Pfizer-BioNTech and Oxford-AstraZeneca vaccines being administered in the UK, and protection against infection was varied from 0% to 85%. We considered the combined interaction of the UK vaccination programme with multiple potential future relaxations (or removals) of NPIs, to predict the reproduction number (R) and pattern of daily deaths and hospital admissions due to COVID-19 from January, 2021, to January, 2024.
We estimate that vaccination alone is insufficient to contain the outbreak. In the absence of NPIs, even with our most optimistic assumption that the vaccine will prevent 85% of infections, we estimate R to be 1·58 (95% credible intervals CI 1·36–1·84) once all eligible adults have been offered both doses of the vaccine. Under the default uptake scenario, removal of all NPIs once the vaccination programme is complete is predicted to lead to 21 400 deaths (95% CI 1400–55 100) due to COVID-19 for a vaccine that prevents 85% of infections, although this number increases to 96 700 deaths (51 800–173 200) if the vaccine only prevents 60% of infections. Although vaccination substantially reduces total deaths, it only provides partial protection for the individual; we estimate that, for the default uptake scenario and 60% protection against infection, 48·3% (95% CI 48·1–48·5) and 16·0% (15·7–16·3) of deaths will be in individuals who have received one or two doses of the vaccine, respectively.
For all vaccination scenarios we investigated, our predictions highlight the risks associated with early or rapid relaxation of NPIs. Although novel vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake, both of which need to be carefully monitored.
National Institute for Health Research, Medical Research Council, and UK Research and Innovation.
Quarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable ...and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Early warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation ...offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Countries around the world have implemented a series of interventions to contain the pandemic of coronavirus disease (COVID-19), and significant lessons can be drawn from the study of the full ...transmission dynamics of the disease caused by-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-in the Eastern, Madinah, Makkah, and Riyadh regions of Saudi Arabia, where robust non-pharmaceutical interventions effectively suppressed the local outbreak of this disease. On the basis of 333732 laboratory-confirmed cases, we used mathematical modelling to reconstruct the complete spectrum dynamics of COVID-19 in Saudi Arabia between 2 March and 25 September 2020 over 5 periods characterised by events and interventions. Our model account for asymptomatic and presymptomatic infectiousness, time-varying ascertainable infection rate, and transmission rates. Our results indicate that non-pharmaceutical interventions were effective in containing the epidemic, with reproduction numbers decreasing on average to 0.29 (0.19-0.66) in the Eastern, Madinah, Makkah, and Riyadh region. The chance of resurgence after the lifting of all interventions after 30 consecutive days with no symptomatic cases is also examined and emphasizes the danger presented by largely hidden infections while switching control strategies. These findings have major significance for evaluating methods for maintaining monitoring and interventions to eventually reduce outbreaks of COVID-19 in Saudi Arabia in the future.
Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making ...approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45-£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or ...vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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