Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed.

Infection, recovery and re-infection of farmed mink with SARS-CoV-2.

Mink, on a farm with about 15,000 animals, became infected with SARS-CoV-2. Over 75% of tested animals were positive for SARS-CoV-2 RNA in throat swabs and 100% of tested animals were seropositive. The virus responsible had a deletion of nucleotides encoding residues H69 and V70 within the spike protein gene as well as the A22920T mutation, resulting in the Y453F substitution within this protein, seen previously in mink. The infected mink recovered and after free-testing of 300 mink (a level giving 93% confidence of detecting a 1% prevalence), the animals remained seropositive. During further follow-up studies, after a period of more than 2 months without any virus detection, over 75% of tested animals again scored positive for SARS-CoV-2 RNA. Whole genome sequencing showed that the viruses circulating during this re-infection were most closely related to those identified in the first outbreak on this farm but additional sequence changes had occurred. Animals had much higher levels of anti-SARS-CoV-2 antibodies in serum samples after the second round of infection than at free-testing or during recovery from initial infection, consistent with a boosted immune response. Thus, it was concluded that following recovery from an initial infection, seropositive mink were readily re-infected by SARS-CoV-2.

Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020.

In June-November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25-30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.

Simulation of Foot-and-Mouth Disease Spread and Effects of Mitigation Strategies to Support Veterinary Contingency Planning in Denmark.

To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario 1), or in one specific livestock production system within each of the three species geographically distributed throughout Denmark (Scenario 2). When additional mitigation strategies were implemented on top of basic control strategies in the European foot-and-mouth disease spread model (EuFMDiS), no significant benefits were predicted in terms of the number of infected farms, the epidemic control duration, and the total economic cost. Further, the model results indicated that the choice of index herd, the resources for outbreak control, and the detection time of FMD significantly influenced the course of an epidemic. The present study results emphasise the importance of basic mitigation strategies, including an effective back-and-forward traceability system, adequate resources for outbreak response, and a high level of awareness among farmers and veterinarians concerning the detection and reporting of FMD at an early stage of an outbreak for FMD control in Denmark.

SARS-CoV-2 in Danish Mink Farms: Course of the Epidemic and a Descriptive Analysis of the Outbreaks in 2020.

SARS-CoV-2 infection is the cause of COVID-19 in humans. In April 2020, SARS-CoV-2 infection in farmed mink (Neovision vision) occurred in the Netherlands. The first outbreaks in Denmark were detected in June 2020 in three farms. A steep increase in the number of infected farms occurred from September and onwards. Here, we describe prevalence data collected from 215 infected mink farms to characterize spread and impact of disease in infected farms. In one third of the farms, no clinical signs were observed. In farms with clinical signs, decreased feed intake, increased mortality and respiratory symptoms were most frequently observed, during a limited time period (median of 11 days). In 65% and 69% of farms, virus and sero-conversion, respectively, were detected in 100% of sampled animals at the first sampling. SARS-CoV-2 was detected, at low levels, in air samples collected close to the mink, on mink fur, on flies, on the foot of a seagull, and in gutter water, but not in feed. Some dogs and cats from infected farms tested positive for the virus. Chickens, rabbits, and horses sampled on a few farms, and wildlife sampled in the vicinity of the infected farms did not test positive for SARS-CoV-2. Thus, mink are highly susceptible to infection by SARS-CoV-2, but routes of transmission between farms, other than by direct human contact, are unclear.

Simulation of transmission and persistence of African swine fever in wild boar in Denmark.

African swine fever (ASF) is caused by ASF virus (ASFV) and is currently circulating in the eastern part of Europe posing a serious risk regarding transmission to western European countries. Wild boar is a main driver of the transmission and persistence of ASFV in the endemic infected countries in Europe. Some European countries free from ASF, such as Denmark and the Netherlands, have limited population sizes of wild boar, but have large swine productions. In these countries, the patterns of transmission and persistence of ASFV in the existing wild boar population, in case of introduction of ASFV, are unknown. It is important to get a better understanding of ASFV in these wild boar populations, in order to better manage the existing wild boar population and thereby minimize the risk of virus introduction and transmission to domestic pigs, in case of an ASFV incursion. We created an agent-based spatio-temporal model and simulated the transmission of ASFV within Danish wild boar populations, using actual landscape data. The model was run with 50 and 100 wild boar groups used as initial population sizes, respectively, either distributed across the southern part of the mainland (Jutland) or across both the southern and middle parts of Jutland, where wild boar groups are believed to exist. At first, the model was run without ASFV for 25 years to assess wild boar population dynamics in both regions. Thereafter, ASFV was added to the model 1 year after initiation and run for up to another 4 years. The model predicted that wild boar populations may increase drastically over the next 25 years, if wild boar groups were distributed across both southern and middle Jutland and no mitigation actions were taken, while the population sizes will be restricted, if groups were distributed only across the southern part of Jutland. The density of the population is an important factor affecting the transmission and persistency of the disease. Model results indicated that ASF epidemics in the simulated populations would generally persist for few months. However, due to the high stochasticity of the process, in certain situations the epidemics may last for more than one year, posing a serious risk of ASFV introduction to domestic pigs.

Modeling the Effects of Duration and Size of the Control Zones on the Consequences of a Hypothetical African Swine Fever Epidemic in Denmark.

African swine fever (ASF) is a notifiable infectious disease. The disease is endemic in certain regions in Eastern Europe constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning, it is important to continuously explore strategies that can effectively control an epidemic of ASF. A previously published and well documented simulation model for ASF virus spread between herds was used to examine the epidemiologic and economic impacts of the duration and size of the control zones around affected herds. In the current study, scenarios were run, where the duration of the protection and surveillance zones were reduced from 50 and 45 days to 35 and 25 days or to 35 and 25 days, respectively. These scenarios were run with or without enlargement of the surveillance zone around detected herds from 10 to 15 km. The scenarios were also run with only clinical or clinical and serological surveillance of herds within the zones. Sensitivity analysis was conducted on influential input parameters in the model. The model predicts that reducing the duration of the protection and surveillance zones has no impact on the epidemiological consequences of the epidemics, while it may result in a substantial reduction in the total economic losses. In addition, the model predicts that increasing the size of the surveillance zone from 10 to 15 km may reduce both the epidemic duration and the total economic losses, in case of large epidemics. The ranking of the control strategies by the total costs of the epidemics was not influenced by changes of input parameters in the sensitivity analyses.

Relationship of trade patterns of the Danish swine industry animal movements network to potential disease spread.

The movements of animals were analysed under the conceptual framework of graph theory in mathematics. The swine production related premises of Denmark were considered to constitute the nodes of a network and the links were the animal movements. In this framework, each farm will have a network of other premises to which it will be linked. A premise was a farm (breeding, rearing or slaughter pig), an abattoir or a trade market. The overall network was divided in premise specific subnets that linked the other premises from and to which animals were moved. This approach allowed us to visualise and analyse the three levels of organization related to animal movements that existed in the Danish swine production registers: the movement of animals between two premises, the premise specific networks, and the industry network. The analyses of animal movements were done using these three levels of organisation. The movements of swine were studied for the period September 30, 2002 to May 22, 2003. For daily movements of swine between two slaughter pig premises, the median number of pigs moved was 130 pigs with a maximum of 3306. For movements between a slaughter pig premise and an abattoir, the median number of pigs was 24. The largest percentage of movements was from farm to abattoir (82.5%); the median number of pigs per movement was 24 and the maximum number was 2018. For the whole period the median and maximum Euclidean distances observed in farm-to-farm movements were 22 km and 289 km respectively, while in the farm-to-abattoir movements, they were 36.2 km and 285 km. The network related to one specific premise showed that the median number of premises was mainly away from slaughter pig farms (3) or breeder farms (26) and mainly to an abattoir (1535). The assumption that animal movements can be randomly generated on the basis of farm density of the surrounding area of any farm is not correct since the patterns of animal movements have the topology of a scale-free network with a large degree of heterogeneity. This supported the opinion that the disease spread software assuming homogeneity in farm-to-farm relationship should only be used for large-scale interpretation and for epidemic preparedness. The network approach, based on graph theory, can be used efficiently to express more precisely, on a local scale (premise), the heterogeneity of animal movements. This approach, by providing network knowledge to the local veterinarian in charge of controlling disease spread, should also be evaluated as a potential tool to manage epidemics during the crisis. Geographic information systems could also be linked in the approach to produce knowledge about local transmission of disease.

Resource Estimations in Contingency Planning for Foot-and-Mouth Disease.

Preparedness planning for a veterinary crisis is important to be fast and effective in the eradication of disease. For countries with a large export of animals and animal products, each extra day in an epidemic will cost millions of Euros due to the closure of export markets. This is important for the Danish husbandry industry, especially the swine industry, which had an export of €4.4 billion in 2012. The purposes of this project were to (1) develop an iterative tool with the aim of estimating the resources needed during an outbreak of foot-and-mouth disease (FMD) in Denmark, (2) identify areas, which can delay the control of the disease. The tool developed should easily be updated, when knowledge is gained from other veterinary crises or during an outbreak of FMD. The stochastic simulation model DTU-DADS was used to simulate spread of FMD in Denmark. For each task occurring during an epidemic of FMD, the time and personnel needed per herd was estimated by a working group with expertise in contingency and crisis management. By combining this information, an iterative model was created to calculate the needed personnel on a daily basis during the epidemic. The needed personnel was predicted to peak within the first week with a requirement of approximately 123 (65-175) veterinarians, 33 (23-64) technicians, and 36 (26-49) administrative staff on day 2, while the personnel needed in the Danish Emergency Management Agency (responsible for the hygiene barrier and initial cleaning and disinfection of the farm) was predicted to be 174 (58-464), mostly recruits. The time needed for surveillance visits was predicted to be the most influential factor in the calculations. Based on results from a stochastic simulation model, it was possible to create an iterative model to estimate the requirements for personnel during an FMD outbreak in Denmark. The model can easily be adjusted, when new information on resources appears from management of other crisis or from new model runs.

Simulating the epidemiological and economic effects of an African swine fever epidemic in industrialized swine populations.

African swine fever (ASF) is a notifiable infectious disease with a considerable impact on animal health and is currently one of the most important emerging diseases of domestic pigs. ASF was introduced into Georgia in 2007 and subsequently spread to the Russian Federation and several Eastern European countries. Consequently, there is a non-negligible risk of ASF spread towards Western Europe. Therefore it is important to develop tools to improve our understanding of the spread and control of ASF for contingency planning. A stochastic and dynamic spatial spread model (DTU-DADS) was adjusted to simulate the spread of ASF virus between domestic swine herds exemplified by the Danish swine population. ASF was simulated to spread via animal movement, low- or medium-risk contacts and local spread. Each epidemic was initiated in a randomly selected herd - either in a nucleus herd, a sow herd, a randomly selected herd or in multiple herds simultaneously. A sensitivity analysis was conducted on input parameters. Given the inputs and assumptions of the model, epidemics of ASF in Denmark are predicted to be small, affecting about 14 herds in the worst-case scenario. The duration of an epidemic is predicted to vary from 1 to 76days. Substantial economic damages are predicted, with median direct costs and export losses of €12 and €349 million, respectively, when epidemics were initiated in multiple herds. Each infectious herd resulted in 0 to 2 new infected herds varying from 0 to 5 new infected herds, depending on the index herd type.

Control of African swine fever epidemics in industrialized swine populations.

African swine fever (ASF) is a notifiable infectious disease with a high impact on swine health. The disease is endemic in certain regions in the Baltic countries and has spread to Poland constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning, it is important to explore strategies that can effectively control an epidemic of ASF. In this study, the epidemiological and economic effects of strategies to control the spread of ASF between domestic swine herds were examined using a published model (DTU-DADS-ASF). The control strategies were the basic EU and national strategy (Basic), the basic strategy plus pre-emptive depopulation of neighboring swine herds, and intensive surveillance of herds in the control zones, including testing live or dead animals. Virus spread via wild boar was not modelled. Under the basic control strategy, the median epidemic duration was predicted to be 21days (5th and 95th percentiles; 1-55days), the median number of infected herds was predicted to be 3 herds (1-8), and the total costs were predicted to be €326 million (€256-€442 million). Adding pre-emptive depopulation or intensive surveillance by testing live animals resulted in marginal improvements to the control of the epidemics. However, adding testing of dead animals in the protection and surveillance zones was predicted to be the optimal control scenario for an ASF epidemic in industrialized swine populations without contact to wild boar. This optimal scenario reduced the epidemic duration to 9days (1-38) and the total costs to €294 million (€257-€392 million). Export losses were the driving force of the total costs of the epidemics.

The costs of preventive activities for exotic contagious diseases-A Danish case study of foot and mouth disease and swine fever.

The present paper provides an overview of the costs of preventive activities, currently undertaken in Denmark, related to foot and mouth disease (FMD) and classical and African swine fever (SF). Only costs held between outbreaks were included. Costs were divided into public costs and costs paid by the pig and cattle industries, respectively. Data were retrieved from multiple sources such as databases, legal documents, official statistics, yearly reports and expert opinions. As no previous studies have assessed such costs, data collection and estimation procedures were discussed and decided upon in a group of experts from universities, industry, and public authorities. The costs of each preventive activity were related to the type of activity, the number of times the activity was carried out and the share of costs that could be associated with FMD or SF. Uncertainty about parameters was incorporated in the analysis by assuming that the FMD/SF shares of costs as well as total costs for each activity could take on a most likely as well as a minimum and maximum value. A high degree of transparency was prioritized in the cost analysis, which enables reproducibility and easy access to conducting sensitivity analyses. A total of 27 FMD/SF preventive activities were identified. The estimated median (minimum-maximum) of total costs amounted to €32 (18-50) million in 2013. The single most costly FMD/SF related activity, amounting to €8 (5-13) million or 26% of total costs, was a national legal requirement to clean lorries immediately after transportation of live animals. The distribution of costs between stakeholders was estimated to be as follows: pig industry 63%, cattle industry 27%, and the public authorities 10%. Most of the activities focused on reducing the probability of spreading FMD/SF, while only a few activities were directed mainly towards reducing the probability of introduction. Legally required FMD/SF activities (mainly based on EU legislation) accounted for 60% of the activities, while FMD/SF related measures agreed on at sector level and measures implemented due to individual initiatives, such as farmer's investment in specially built delivery facilities, each accounted for 20%.

Risk factors for infection of sow herds with porcine reproductive and respiratory syndrome (PRRS) virus.

In 1992, the porcine reproductive and respiratory syndrome virus (PRRSV) of European type (PRRSV-EU) was introduced in Denmark. By 1996, the virus had spread to approximately 25% of the Danish herds. In January 1996, a modified-live vaccine based on the American type of the virus (PRRSV-US) was used in replacement boars for Danish artificial insemination (AI) centres and from July 1996, the vaccine was used in PRRSV-EU infected herds for prevention of disease. Soon after vaccine introduction, PRRSV non-infected herds experienced outbreaks of disease due to infection with PRRSV-US. In this study, we investigated the risk factors (biosecurity level, animals, exposure from PRRSV-US-infected neighbour herds, semen, herd size, pig density and herd density) for infection with PRRSV-US in a cohort of 1071 sow herds; we used a nested case-control study. The retrospective observation period lasted from June 1996 (when they all were non-infected) to October 1997. Seventy-three non-vaccinated, closed sow herds became infected with the vaccine strain during this period. Each case herd was matched with two control herds from the cohort (controls had not been infected at the time of infection in the case herds). The data were analysed using a Cox-regression model. The hazard of infection increased significantly with exposure from PRRSV-US-infected neighbouring herds, purchase of animals from herds incubating PRRSV-US infection, increasing herd size and purchase of semen from boars at PRRSV-US-infected AI centres. The results are consistent with the modified-live vaccine strain spread to other herds by trade with animals and semen and by neighbour (area) transmission. We suggest that virus spread by aerosols was a frequent mode of transmission.

[The three types of influenza]. / De tre influenzasygdomme.

The unprecedented spread of the highly pathogenic avian influenza type A H5N1 is a threat to veterinary public health. However, the virus does not in its present form constitute a major threat to human public health. Only if the virus mutates to spread effectively from person to person will there be a risk of a new pandemic. It is not possible to predict if this will happen, when it may happen or how serious it may be. At present, seasonal influenza represents the greatest burden of illness among the three types of influenza A illness: seasonal, avian, and pandemic influenza.