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SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics-Virus Spread model (PeDViS), an individual-based model that combines pedestrian behaviour models with virus spread models incorporating direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place and compared this to benchmark 'at risk' interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to the buildup of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent. This uncertainty should be considered when assessing transmission risks upon different types of human interactions in indoor spaces. We illustrated the multi-dimensionality of indoor SARS-CoV-2 transmission that emerges from the interplay of human behaviour and the spread of respiratory viruses. A modelling strategy that incorporates this in risk assessments can help inform policy makers and citizens on the safe use of indoor spaces with varying inter-human interactions.

Abstract Although most infections are transmitted through the environment, the processes underlying the environmental stage of transmission are still poorly understood for most systems. Improved understanding of the environmental transmission dynamics is important for effective non-pharmaceutical intervention strategies. To study the mechanisms underlying environmental transmission we formulated a parsimonious modelling framework including hypothesised mechanisms of pathogen dispersion and decay. To calibrate and validate the model, we conducted a series of experiments studying distance-dependent transmission of Campylobacter jejuni in broilers. We obtained informative simultaneous estimates for all three model parameters: the parameter of C. jejuni inactivation, the diffusion coefficient describing pathogen dispersion, and the transmission rate parameter. The time and distance dependence of transmission in the fitted model is quantitatively consistent with marked spatiotemporal patterns in the experimental observations. These results, for C. jejuni in broilers, show that the application of our modelling framework to suitable transmission data can provide mechanistic insight in environmental pathogen transmission.

Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level and individual-level interactions between vector, host and pathogen. Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito, and assessed if and how RVFV infection subsequently developed in the exposed animal. Aedes aegypti mosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. Aedes aegypti colony mosquitoes were used as they are easy to maintain and readily feed in captivity. Other mosquito spp. could be examined with similar methodology. Lambs were exposed to either 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peak-levels of viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a single bite of an infectious mosquito can result in disease. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for life traits of Aedes aegypti or related mosquitoes into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naïve populations (i.e., R0 >1). The model revealed that relatively high vector-to-host ratios as well as mosquitoes feeding preferably on competent hosts are required for R0 to exceed 1. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is one of the most challenging and persistent health issues in many countries worldwide. In several countries, bTB control is complicated due to the presence of wildlife reservoirs of infection, i.e. European badger (Meles meles) in Ireland and the UK, which can transmit infection to cattle. However, a quantitative understanding of the role of cattle and badgers in bTB transmission is elusive, especially where there is spatial variation in relative density between badgers and cattle. Moreover, as these two species have infrequent direct contact, environmental transmission is likely to play a role, but the quantitative importance of the environment has not been assessed. Therefore, the objective of this study is to better understand bTB transmission between cattle and badgers via the environment in a spatially explicit context and to identify high-risk areas. We developed an environmental transmission model that incorporates both within-herd/territory transmission and between-species transmission, with the latter facilitated by badger territories overlapping with herd areas. Model parameters such as transmission rate parameters and the decay rate parameter of M. bovis were estimated by maximum likelihood estimation using infection data from badgers and cattle collected during a 4-year badger vaccination trial. Our estimation showed that the environment can play an important role in the transmission of bTB, with a half-life of M. bovis in the environment of around 177 days. Based on the estimated transmission rate parameters, we calculate the basic reproduction ratio (R) within a herd, which reveals how relative badger density dictates transmission. In addition, we simulated transmission in each small local area to generate a first between-herd R map that identifies high-risk areas.

IntroductionSARS-CoV-2 is known to jump across species. The occurrence of transmission in households between humans and companion animals has been shown, but the contribution of companion animals to the overall transmission within a household is unknown. The basic reproduction number (R0) is an important indicator to quantify transmission. For a pathogen with multiple host species, such as SARS-CoV-2, the basic reproduction number needs to be calculated from the partial reproduction numbers for each combination of host species.MethodIn this study, the basic and partial reproduction numbers for SARS-CoV-2 were estimated by reanalyzing a survey of Dutch households with dogs and cats and minimally one SARS-CoV-2-infected human.ResultsFor households with cats, a clear correlation between the number of cats and the basic reproduction number (Spearman's correlation: p 0.40, p-value: 1.4 × 10−5) was identified, while for dogs, the correlation was smaller and not significant (Spearman's correlation: p 0.12, p-value: 0.21). Partial reproduction numbers from cats or dogs to humans were 0.3 (0.0–2.0) and 0.3 (0.0–3.5) and from humans to cats or dogs were 0.6 (0.4–0.8) and 0.6 (0.4–0.9).DiscussionThus, the estimations of within-household transmission indicated the likelihood of transmission from these companion animals to humans and vice versa, but the observational nature of this study limited the ability to establish conclusive evidence. This study's findings support the advice provided during the pandemic to COVID-19 patients to maintain distance from companion animals as a precautionary measure and given the possibility of transmission, although there is an overall relatively limited impact on the pandemic when compared to human-to-human transmission.

Abstract Background Recent research shows that genetic selection has high potential to reduce the prevalence of infectious diseases in livestock. However, like all interventions that target infectious diseases, genetic selection of livestock can exert selection pressure on pathogen populations. Such selection on the pathogen may lead to escape strategies and reduce the effect of selection of livestock for disease resistance. Thus, to successfully breed livestock for lower disease prevalence, it is essential to develop strategies that prevent the invasion of pathogen mutants that escape host resistance. Here we investigate the conditions under which such “escape mutants” can replace wild-type pathogens in a closed livestock population using a mathematical model of disease transmission. Results Assuming a single gene that confers sufficient resistance, results show that genetic selection for resistance in livestock typically leads to an “invasion window” within which an escape mutant of the pathogen can invade. The bounds of the invasion window are determined by the frequency of resistant hosts in the population. The lower bound occurs when the escape mutant has an advantage over the wild-type pathogen in the population. The upper bound occurs when local eradication of the pathogen is expected. The invasion window is smallest when host resistance is strong and when infection with the wild-type pathogen provides cross immunity to infection with the escape mutant. Conclusions To minimise opportunities for pathogens to adapt, under the assumptions of our model, the aim of disease control through genetic selection should be to achieve herd-level eradication of the infection faster than the rate of emergence of escape mutants of the pathogen. Especially for microparasitic infections, this could be achieved by placing animals into herds according to their genetic resistance, such that these herds stay completely out of the invasion window. In contrast to classical breeding theory, our model suggests that multi-trait selection with gradual improvement of each trait of the breeding goal might not be the best strategy when resistance to infectious disease is part of the breeding goal. Temporally, combining genetic selection with other interventions helps to make the invasion window smaller, and thereby reduces the risk of invasion of escape mutants.

ABSTRACT The susceptibility of domestic cats to infection with SARS-CoV-2 has been demonstrated by several experimental studies and field observations. We performed an extensive study to further characterize the transmission of SARS-CoV-2 between cats, through both direct and indirect contact. To that end, we estimated the transmission rate parameter and the decay parameter for infectivity in the environment. Using four groups of pair-transmission experiment, all donor (inoculated) cats became infected, shed virus, and seroconverted, while three out of four direct contact cats got infected, shed virus, and two of those seroconverted. One out of eight cats exposed to a SARS-CoV-2-contaminated environment became infected but did not seroconvert. Statistical analysis of the transmission data gives a reproduction number R0 of 2.18 (95% CI = 0.92 to 4.08), a transmission rate parameter β of 0.23 day−1 (95% CI = 0.06 to 0.54), and a virus decay rate parameter μ of 2.73 day−1 (95% CI = 0.77 to 15.82). These data indicate that transmission between cats is efficient and can be sustained (R0 > 1), however, the infectiousness of a contaminated environment decays rapidly (mean duration of infectiousness 1/2.73 days). Despite this, infections of cats via exposure to a SARS-CoV-2-contaminated environment cannot be discounted if cats are exposed shortly after contamination. IMPORTANCE This article provides additional insight into the risk of infection that could arise from cats infected with SARS-CoV-2 by using epidemiological models to determine transmission parameters. Considering that transmission parameters are not always provided in the literature describing transmission experiments in animals, we demonstrate that mathematical analysis of experimental data is crucial to estimate the likelihood of transmission. This article is also relevant to animal health professionals and authorities involved in risk assessments for zoonotic spill-overs of SARS-CoV-2. Last but not least, the mathematical models to calculate transmission parameters are applicable to analyze the experimental transmission of other pathogens between animals.

Abstract The H9N2 subtype avian influenza virus (AIV) inactivated vaccine has been used extensively in poultry farms, but it often fails to stimulate a sufficiently high immune response in poultry in the field, although it works well in laboratory experiments; hence, the virus still causes economic damage every year and poses a potential threat to public health. Based on surveillance data collected in the field, we found that broilers with high levels of maternal-derived antibodies (MDAs) against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine. In contrast, specific pathogen-free (SPF) chickens without MDAs responded efficiently to that vaccination. When MDAs were mimicked by administering passively transferred antibodies (PTAs) into SPF chickens in the laboratory, similar results were observed: H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine, suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used. After challenge with homologous H9N2 virus, the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs, indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field. When different titers of PTAs were used to mimic MDAs in SPF chickens, high (HI = 12 log2) and medium (HI = log 9 log2) titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination, but a booster dose would induce a high and faster humoral immune response even of PTA interference. This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field.

Large epidemics provide the opportunity to understand the epidemiology of diseases under the specific conditions of the affected population. Whilst foot-and-mouth disease (FMD) epidemics have been extensively studied in developed countries, epidemics in developing countries have been sparsely studied. Here we address this limitation by systematically studying the 2001 epidemic in Uruguay where a total of 2,057 farms were affected. The objective of this study was to identify the risk factors (RF) associated with infection and spread of the virus within the country. The epidemic was divided into four periods: (1) the high-risk period (HRP) which was the period between the FMD virus introduction and detection of the index case; (2) the local control measures period (LCM) which encompassed the first control measures implemented before mass vaccination was adopted; (3) the first mass vaccination, and (4) the second mass vaccination round. A stochastic model was developed to estimate the time of initial infection for each of the affected farms. Our analyses indicated that during the HRP around 242 farms were probably already infected. In this period, a higher probability of infection was associated with: (1) animal movements [OR: 1.57 (95% CI: 1.19–2.06)]; (2) farms that combined livestock with crop production [OR: 1.93 (95% CI: 1.43–2.60)]; (3) large and medium farms compared to small farms (this difference was dependent on regional herd density); (4) the geographical location. Keeping cattle only (vs farms that kept also sheep) was a significant RF during the subsequent epidemic period (LCM), and remained as RF, together with large farms, for the entire epidemic. We further explored the RF associated with FMDV infection in farms that raised cattle by fitting another model to a data subset. We found that dairy farms had a higher probability of FMDV infection than beef farms during the HRP [OR: 1.81 (95% CI: 1.12–2.83)], and remained as RF until the end of the first round of vaccination. The delay in the detection of the index case associated with unrestricted animal movements during the HRP may have contributed to this large epidemic. This study contributes to the knowledge of FMD epidemiology in extensive production systems.

Although vaccines have been widely used for many years, they have failed to control H9N2 avian influenza virus (AIV) in the field in China. The high level of maternal-derived antibodies (MDAs) against H9N2 virus contributes to the H9N2 influenza vaccine failure in poultry. The study aimed to generate a new vaccine to overcome MDAs interference in H9N2 vaccination in chickens. We used turkey herpesvirus (HVT) as a vaccine vector to express H9 hemagglutinin (HA) proteins. The recombinant HVT expressing H9 HA proteins (rHVT-H9) was successfully generated and characterized in primary chicken embryonic fibroblasts (CEFs). Western blot and indirect immunofluorescence assay (IFA) showed that the rHVT-H9 consistently expressed HA proteins. In addition, the rHVT-H9 had similar growth kinetics to the parent HVT. Preliminary animal experiments showed that compared to the conventional inactivated whole virus (IWV) vaccine, the rHVT-H9 stimulated robust humoral immunity in chickens with passively transferred antibodies (PTAs) that were used to mimic MDAs. Transmission experiments showed that the rHVT-H9 induced both humoral and cellular immunity in chickens with PTAs. Furthermore, we used mathematical models to quantify the vaccine’s efficacy in preventing the transmission of H9N2 AIV. The results showed that the rHVT-H9 reduced the virus shedding period and decreased the reproduction ratio (R) value in chickens with PTAs after homologous challenge. However, the vaccination in this trial did not yet bring R

Denmark is a major pig exporter and applies a high level of biosecurity, with washing and disinfecting stations for returning livestock vehicles. The introduction of African Swine Fever (ASF) would have significant economic consequences related to loss of export of live pigs and products thereof. In this study, we focused on the role of empty livestock vehicles returning after exports of pigs for the introduction of ASF. Initially, the current components and measures related to export of livestock were described. Next, analyses of strengths, weaknesses, opportunities, and threats (SWOT) were conducted, covering the components and measures identified. Then, export of pigs was described either through assembly centers or directly from farms. Washing and disinfection, as required and undertaken at the designated stations, constitutes the most important among all risk-reducing measures identified. Recommendations are to: (1) ensure the quality of washing and disinfection through staff training; (2) find new, safe, and more efficient disinfectants; (3) ensure the required temperature, and therefore effect, of the disinfectant and water. It was impossible to assess, the influence of export through assembly centers compared to direct transport. However, through SWOT analyses we identified the strengths and weaknesses of the two pathways. Moreover, components/measures with risks of unknown sizes are also discussed, such as vehicles undertaking cabotage and the current vehicle quarantine periods.

Abstract Background Reassortment between human and avian influenza viruses (AIV) may result in novel viruses with new characteristics that may threaten human health when causing the next flu pandemic. A particular risk may be posed by avian influenza viruses of subtype H9N2 that are currently massively circulating in domestic poultry in Asia and have been shown to infect humans. In this study, we investigate the characteristics and compatibility of a human H1N1 virus with avian H9N2 derived genes. Methods The polymerase activity of the viral ribonucleoprotein (RNP) complex as combinations of polymerase-related gene segments derived from different reassortment events was tested in luciferase reporter assays. Reassortant viruses were generated by reverse genetics. Gene segments of the human WSN-H1N1 virus (A/WSN/1933) were replaced by gene segments of the avian A2093-H9N2 virus (A/chicken/Jiangsu/A2093/2011), which were both the Hemagglutinin (HA) and Neuraminidase (NA) gene segments in combination with one of the genes involved in the RNP complex (either PB2, PB1, PA or NP). The growth kinetics and virulence of reassortant viruses were tested on cell lines and mice. The reassortant viruses were then passaged for five generations in MDCK cells and mice lungs. The HA gene of progeny viruses from different passaging paths was analyzed using Next-Generation Sequencing (NGS). Results We discovered that the avian PB1 gene of H9N2 increased the polymerase activity of the RNP complex in backbone of H1N1. Reassortant viruses were able to replicate in MDCK and DF1 cells and mice. Analysis of the NGS data showed a higher substitution rate for the PB1-reassortant virus. In particular, for the PB1-reassortant virus, increased virulence for mice was measured by increased body weight loss after infection in mice. Conclusions The higher polymerase activity and increased mutation frequency measured for the PB1-reassortant virus suggests that the avian PB1 gene of H9N2 may drive the evolution and adaptation of reassortant viruses to the human host. This study provides novel insights in the characteristics of viruses that may arise by reassortment of human and avian influenza viruses. Surveillance for infections with H9N2 viruses and the emergence of the reassortant viruses in humans is important for pandemic preparedness.

Habitat availability determines the distribution of migratory waterfowl along their flyway, which further influences the transmission and spatial spread of avian influenza viruses (AIVs). The extensive habitat loss in the East Asian-Australasian Flyway (EAAF) may have potentially altered the virus spread and transmission, but those consequences are rarely studied. We constructed 6 fall migration networks that differed in their level of habitat loss, wherein an increase in habitat loss resulted in smaller networks with fewer sites and links. We integrated an agent-based model and a susceptible-infected-recovered model to simulate waterfowl migration and AIV transmission. We found that extensive habitat loss in the EAAF can 1) relocate the outbreaks northwards, responding to the distribution changes of wintering waterfowl geese, 2) increase the outbreak risk in remaining sites due to larger goose congregations, and 3) facilitate AIV transmission in the migratory population. In addition, our modeling output was in line with the predictions from the concept of "migratory escape", i.e., the migration allows the geese to "escape" from the location where infection risk is high, affecting the pattern of infection prevalence in the waterfowl population. Our modeling shed light on the potential consequences of habitat loss in spreading and transmitting AIV at the flyway scale and suggested the driving mechanisms behind these effects, indicating the importance of conservation in changing spatial and temporal patterns of AIV outbreaks.

ABSTRACT The H9N2 subtype avian influenza virus (AIV) has become endemic in poultry globally; however due to its low pathogenicity, it is not under primary surveillance and control in many countries. Recent reports of human infection caused by H9N2 AIV has increased public concern. This study investigated the genetic and antigenic characteristics of H9N2 AIV isolated from local markets in nine provinces in Southern China from 2013 to 2018. We detected an increasing annual isolation rate of H9N2 AIV. Phylogenetic analyses of hemagglutinin (HA) genes suggests that isolated strains were rooted in BJ94 lineage but have evolved into new subgroups (II and III), which derived from subgroup I. The estimated substitution rate of the subgroup III strains was 6.23 × 10−3 substitutions/site/year, which was 1.5-fold faster than that of the average H9N2 HA rate (3.95 × 10−3 substitutions/site/year). Based on the antigenic distances, subgroup II and III strains resulted in two clear antigenic clusters 2 and 3, separated from the vaccine strain F98, cluster 1. New antigenic properties of subgroup III viruses were associated with 11 amino acid changes in the HA protein, suggesting antigenic drift in H9N2 viruses. Our phylogenetic and antigenic analyses of the H9N2 strains circulating in local markets in Southern China provide new insights on the antigenic diversification of H9N2 viruses. IMPORTANCE The H9N2 low pathogenicity avian influenza (LPAI) virus has become endemic in poultry globally. In several Asian countries, vaccination against H9N2 avian influenza virus (AIV) was approved to reduce economic losses in the poultry industry. However, surveillance programs initiated after the introduction of vaccination identified the persistence of H9N2 AIV in poultry (especially in chicken in South Korea and China). Recent reports of human infection caused by H9N2 AIV has increased public concern. Surveillance of H9N2 circulating in poultry in the fields or markets was essential to update the vaccination strategies. This study investigated the genetic and antigenic characteristics of H9N2 AIVs isolated from local markets in nine provinces in Southern China from 2013 to 2018. The discovery of mutations in the hemagglutinin (HA) gene that result in antigenic changes provides a baseline reference for evolutionary studies of H9N2 viruses and vaccination strategies in poultry.

Abstract Background For infectious diseases, the probability that an animal gets infected depends on its own susceptibility, and on the number of infectious herd mates and their infectivity. Together with the duration of the infectious period, susceptibility and infectivity determine the basic reproduction ratio of the disease ($$ R_{0} $$ R0 ). $$ R_{0} $$ R0 is the average number of secondary cases caused by a typical infectious individual in an otherwise uninfected population. An infectious disease dies out when $$ R_{0} $$ R0 is lower than 1. Thus, breeding strategies that aim at reducing disease prevalence should focus on reducing $$ R_{0} $$ R0 , preferably to a value lower than 1. In animal breeding, however, $$ R_{0} $$ R0 has received little attention. Here, we estimate the additive genetic variance in host susceptibility, host infectivity, and $$ R_{0} $$ R0 for the endemic claw disease digital dermatitis (DD) in Holstein Friesian dairy cattle, and estimate genomic breeding values (GEBV) for these traits. We recorded DD disease status of both hind claws of 1513 cows from 12 Dutch dairy farms, every 2 weeks, 11 times. The genotype data consisted of 75,904 single nucleotide polymorphisms (SNPs) for 1401 of the cows. We modelled the probability that a cow got infected between recordings, and compared four generalized linear mixed models. All models included a genetic effect for susceptibility; Models 2 and 4 also included a genetic effect for infectivity, while Models 1 and 2 included a farm*period interaction. We corrected for variation in exposure to infectious herd mates via an offset. Results GEBV for $$ R_{0} $$ R0 from the model that included genetic effects for susceptibility only had an accuracy of ~ 0.39 based on cross-validation between farms, which is very high given the limited amount of data and the complexity of the trait. Models with a genetic effect for infectivity showed a larger bias, but also a slightly higher accuracy of GEBV. Additive genetic standard deviation for $$ R_{0} $$ R0 was large, i.e. ~ 1.17, while the mean $$ R_{0} $$ R0 was 2.36. Conclusions GEBV for $$ R_{0} $$ R0 showed substantial variation. The mean $$ R_{0} $$ R0 was only about one genetic standard deviation greater than 1. These results suggest that lowering DD prevalence by selective breeding is promising.

Abstract Johne’s disease (JD) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), with control primarily aimed at preventing new infections among calves. The aim of the current study was to quantify calf-to-calf transmission of MAP among penmates in an experimental trial. Newborn Holstein bull calves (n = 32) were allocated into pens of 4, with 2 inoculated (IN) calves and 2 calves that were contact exposed (CE). Calves were group-housed for 3 months, with frequent collection of fecal and blood samples and tissue collection after euthanasia. The basic reproduction ratio (R0) was estimated using a final size (FS) model with a susceptible-infected model, based on INF-γ ELISA and tissue culture followed by qPCR. In addition, the transmission rate parameter (β) for new shedding events was estimated using a general linearized method (GLM) model with a susceptible-infected-susceptible model based on culture, followed by qPCR, of fecal samples collected during group housing. The R0 was derived for IN and CE calves separately, due to a difference in susceptibility, as well as differences in duration of shedding events. Based on the FS model, interferon-γ results from blood samples resulted in a R0IG of 0.90 (0.24, 2.59) and tissue culture resulted in a R0T of 1.36 (0.45, 3.94). Based on the GLM model, the R0 for CE calves to begin shedding (R0CE) was 3.24 (1.14, 7.41). We concluded that transmission of MAP infection between penmates occurred and that transmission among calves may be an important cause of persistent MAP infection on dairy farms that is currently uncontrolled for in current JD control programs.

Abstract Background Macroparasites, such as ticks, lice, and helminths, are a concern in livestock and aquaculture production, and can be controlled by genetic improvement of the host population. Genetic improvement should aim at reducing the rate at which parasites spread across the farmed population. This rate is determined by the basic reproduction ratio, i.e. $${\text{R}}_{0}$$ R0 , which is the appropriate breeding goal trait. This study aims at providing a method to derive the economic value of $${\text{R}}_{0}$$ R0 . Methods Costs of a disease are the sum of production losses and expenditures on disease control. Genetic improvement of $${\text{R}}_{0}$$ R0 lowers the loss-expenditure frontier. Its economic effect depends on whether the management strategy is optimized or not. The economic value may be derived either from the reduction in losses with constant expenditures or from the reduction in expenditures with constant losses. Results When $${\text{R}}_{0}$$ R0 ≤ 1, the economic value of a further reduction is zero because there is no risk of a major epidemic. When $${\text{R}}_{0}$$ R0 > 1 and management is optimized, the economic value increases with decreasing values of $${\text{R}}_{0}$$ R0 , because both the mean number of parasites per host and frequency of treatments decrease at an increasing rate when $${\text{R}}_{0}$$ R0 decreases. When $${\text{R}}_{0}$$ R0 > 1 and management is not optimized, the economic value depends on whether genetic improvement is used for reducing expenditures or losses. For sea lice in salmon, the economic value depends on a reduction in expenditures with constant losses, and is estimated to be 0.065€/unit $${\text{R}}_{0}$$ R0 /kg production. Discussion Response to selection for measures of disease prevalence cannot be predicted from quantitative genetic theory alone. Moreover, many studies fail to address the issue of whether genetic improvement results in reduced losses or expenditures. Using $${\text{R}}_{0}$$ R0 as the breeding goal trait, weighed by its appropriate economic value, avoids these issues. Conclusion When management is optimized, the economic value increases with decreasing values of $${\text{R}}_{0}$$ R0 (until the threshold of $${\text{R}}_{0} = 1$$ R0=1 , where it drops to zero). When management is not optimized, the economic value depends on whether genetic improvement is used for reduced expenditures or production losses. For sea lice in salmon, the economic value is estimated to be 0.065 €/unit $${\text{R}}_{0}$$ R0 /kg production.

Quantitative understanding of transmission with and without control measures is important for the control of infectious diseases because it helps to determine which of these measures (or combinations thereof) will be effective to reduce transmission. In this paper, the statistical methods used to estimate transmission parameters are explained. To show how these methods can be used we reviewed literature for papers describing foot-and-mouth disease virus (FMDV) transmission in pigs and we used the data to estimate transmission parameters. The analysis showed that FMDV transmits very well when pigs have direct contact. Transmission, however, is reduced when a physical barrier separates infected and susceptible non-vaccinated pigs. Vaccination of pigs can prevent infection when virus is administered by a single intradermal virus injection in the bulb of the heel, but it cannot prevent infection when pigs are directly exposed to either non-vaccinated or vaccinated FMDV infected pigs. Physical separation combined with vaccination is observed to block transmission. Vaccination and separation can make a significant difference in the estimated number of new infections per day. Experimental transmission studies show that the combined effect of vaccination and physical separation can significantly reduce transmission (R < 1), which is a very relevant result for the control of between-farm transmission.

Domestic cats are susceptible to SARS-CoV-2 virus infection and given that they are in close contact with people, assessing the potential risk cats represent for the transmission and maintenance of SARS-CoV-2 is important. Assessing this risk implies quantifying transmission from humans-to-cats, from cats-to-cats and from cats-to-humans. Here we quantified the risk of cat-to-cat transmission by reviewing published literature describing transmission either experimentally or under natural conditions in infected households. Data from these studies were collated to quantify the SARS-CoV-2 reproduction number R0 among cats. The estimated R0 was significantly higher than one, hence cats could play a role in the transmission and maintenance of SARS-CoV-2. Questions that remain to be addressed are the risk of transmission from humans-to-cats and cats-to-humans. Further data on household transmission and data on virus levels in both the environment around infected cats and their exhaled air could be a step towards assessing these risks

Abstract Background Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual’s disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. Results We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each animal, the optimal recording interval was 25 to 50% of the average infectious period. Conclusions Our model was able to estimate genetic effects on susceptibility and infectivity. In future genome-wide association studies, it may serve as a starting point to identify genes that affect disease transmission and disease prevalence.

Since 1986, use of a Bovine International Standard (BIS) for bovine tuberculin has been required to ensure national and international uniformity regarding the potency designation of bovine tuberculin Purified Protein Derivative (PPDb) preparations produced by multiple manufacturers. The BIS is the unique golden standard in the guinea pig potency assay, representing 100% potency, where potencies of production batches are calculated as relative potencies in comparison with the potency of the BIS which was set at 32,500 international Unit (IU) per mg. The stock supply and lifetime of the BIS is limited.The aim of this study was to develop a model to determine the potency of a newly produced in-house Reference Standard (RS) for PPDb with great accuracy in the target species (cattle) and to prove its precision and accuracy in the guinea pig potency test. First simulations were done to estimate the required number of cattle needed. Then, 30 naturally bTB infected cattle were subjected to a tuberculin skin test using multiple injections of both the RS and the BIS. Both were applied randomly in the same volume and concentration (1 dose). The potency of the RS against the BIS was directly derived from the least square means (LSMEANS) and was estimated as 1.067 (95% CI: 1.025–1.109), equal to a potency of 34,700 ± 1,400 IU/mg. In six guinea pig potency assays the RS was used to assign potencies to production batches of PPDb. Here, precision and accuracy of the RS was determined according to the parallel-line assay. Relative potencies were estimated by exponentiation of the common slope. The corresponding 95% confidence intervals were obtained according to Fieller's theorem. In sensitized guinea pigs, the relative potency of the RS against the BIS was 1.115 (95% CI: 0.871–1.432), corresponding to an absolute potency of 36,238 IU/mg (95% CI: 28,308–46,540).In conclusion: the method used to determine the potency of the RS against the BIS in naturally bTB infected cattle, resulted in a highly accurate potency estimate of the RS. The RS can be used in the guinea pig test to assign potencies to PPDb production batches with high precision and accuracy.

The mechanism of nanoscopic domain switching in ferroelectric hafnium oxide and its implications for antiferroelectric-like behavior as well as for the wake-up effect is still widely discussed. Understanding this mechanism is of vital importance for a multitude of applications like piezoelectric actuators, pyroelectric sensors, and nonvolatile memory devices. In this article, electrical and physical analysis methods are used to characterize ferroelectric hafnium oxide on the nanoscopic as well as the macroscopic length scale. Evidence for nanoscopic domains is found using transmission Kikuchi diffraction. In combination with macroscopic Preisach density measurements, strong evidence is found that antiferroelectric-like behavior and wake-up are governed by ferroelastic switching, i.e., a 90° domain wall motion. Based on these insights, the material stack can be optimized to further improve microelectronic applications based on HfO2. [ABSTRACT FROM AUTHOR]