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International audience; The purpose of this study was to investigate the origin of the genetic variation in the prevalence of bovine digital dermatitis (DD) by comparing a genetic analysis of infection events to a genetic analysis of disease status. DD is an important endemic infectious disease affecting the claws of cattle. For disease status, we analysed binary data on individual disease status (0,1; indicating being free versus infected), whereas for infections, we analysed binary data on disease transmission events (1,0; indicating becoming infected or not). The analyses of the two traits were compared using cross-validation. The analysis of disease status captures a combination of genetic variation in disease susceptibility and the ability of individuals to recover, whereas the analysis of infections captures genetic variation in susceptibility only. Estimated genetic variances for both traits indicated substantial genetic variation. The GEBV for disease status and infections correlated with only 0.60, indicating that both models indeed capture distinct information. Together, these results suggest the presence of genetic variation not only in disease susceptibility, but also in the ability of individuals to recover from DD. We argue that the presence of genetic variation in recovery implies that breeders should distinguish between infected individuals versus infectious individuals. This is because epidemiological theory shows that selection for recovery is effective only when it targets recovery from being infectious.

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 R 0 IG of 0.90 (0.24, 2.59) and tissue culture resulted in a R 0 T of 1.36 (0.45, 3.94). Based on the GLM model, the R0 for CE calves to begin shedding (R 0 CE ) 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.

Infectious diseases have profound effects on life, both in nature and agriculture. However, a quantitative genetic theory of the host population for the endemic prevalence of infectious diseases is almost entirely lacking. While several studies have demonstrated the relevance of transmission of infections for heritable variation and response to selection, current quantitative genetics ignores transmission. Thus, we lack concepts of breeding value and heritable variation for endemic prevalence, and poorly understand response of endemic prevalence to selection. Here, we integrate quantitative genetics and epidemiology, and propose a quantitative genetic theory for the basic reproduction number R0 and for the endemic prevalence of an infection. We first identify the genetic factors that determine the prevalence. Subsequently, we investigate the population-level consequences of individual genetic variation, for both R0 and the endemic prevalence. Next, we present expressions for the breeding value and heritable variation, for endemic prevalence and individual binary disease status, and show that these depend strongly on the prevalence. Results show that heritable variation for endemic prevalence is substantially greater than currently believed, and increases strongly when prevalence decreases, while heritability of disease status approaches zero. As a consequence, response of the endemic prevalence to selection for lower disease status accelerates considerably when prevalence decreases, in contrast to classical predictions. Finally, we show that most heritable variation for the endemic prevalence is hidden in indirect genetic effects, suggesting a key role for kin-group selection in the evolutionary history of current populations and for genetic improvement in animals and plants., Bijma, Hulst, and De Jong develop a quantitative genetic theory of the host population for both R0 and the prevalence of infectious diseases, showing that most of the heritable variation for endemic prevalence is hidden due to Indirect Genetic Effects resulting from transmission dynamics of the infection. Consequently, genetic variation in the host population and response to selection for the prevalence are large and increase strongly when prevalence decreases. In contrast to classical theory, genetic selection can eradicate infectious diseases.

H9N2 subtype avian influenza has spread dramatically in China ever since first reported in the 1990s. A national vaccination program for poultry was initiated in 1998. Field isolation data show that the widely used inactivated H9N2 vaccine does not provide effective control of the transmission of this low pathogenic avian influenza (LPAI) virus in poultry. Current research has focused on two reasons: (i) insufficient immune response triggered by the vaccination with the inactivated virus, (ii) the occurrence of escape mutants selected by vaccine-induced immune pressure. However, the lack of effectivity of the inactivated virus vaccine to sufficiently reduce transmission has been noticed. We mimicked the natural infection and transmission process of the H9N2 virus in vaccinated and non-vaccinated chickens. A statistical model was used to estimate the transmission rate parameters among vaccinated chickens, varying in serum hemagglutinin inhibition titers (HIT) and non-vaccinated chickens. We demonstrate, for the first time, that the transmission is not sufficiently reduced by the H9N2 vaccine, even when vaccinated chickens have an IgG serum titer (HIT>23), which is considered protective for vaccination against homologous highly pathogenic avian influenza (HPAI) virus. Our study does, on the other hand, cast new light on virus transmission and immune escape of LPAI H9N2 virus in vaccinated chickens populations, and shows that new mitigation strategies against LPAI viruses in poultry are needed.

Understanding the dynamics of the selection of influenza A immune escape variants by serum antibody is critical for designing effective vaccination programs for animals, especially poultry where large populations have a short generation time and may be vaccinated with high frequency. In this report, immune-escape mutants of A/turkey/New York/4450/1994 H7N2 low pathogenic avian influenza virus, were selected by serially passaging the virus in the presence of continuously increasing concentrations of homologous chicken polyclonal sera. Amino acid mutations were identified by sequencing the parental hemagglutinin (HA) gene and every 10 passages by both Sanger and deep sequencing, and the antigenic distance of the mutants to the parent strain was determined. Progressively, a total of five amino acid mutations were observed over the course of 30 passages. Based on their absence from the parental virus with deep sequencing, the mutations appear to have developed de novo. The antigenic distance between the selected mutants and the parent strain increased as the number of amino acid mutations accumulated and the concentration of antibodies had to be periodically increased to maintain the same reduction in virus titer during selection. This selection system demonstrates how H7 avian influenza viruses behave under selection with homologous sera, and provides a glimpse of their evolutionary dynamics, which can be applied to developing vaccination programs that maximize the effectiveness of a vaccine over time.

Lumpy skin disease (LSD) is an acute or inapparent viral disease of cattle which is endemic in many African and Middle East countries. LSD is one of the major transboundary livestock diseases in Ethiopia. A cross-sectional study using multistage cluster sampling was undertaken in central and north-western parts of Ethiopia with the objectives to estimate seroprevalence and to identify and quantify risk factors contributing to the occurrence of the disease. A total of 2386 cattle sera were sampled from 605 herds and 30 clusters (kebeles) located in 10 districts and tested for presence of LSD virus antibodies using virus neutralization test. All the serum samples were collected from cattle having no history of LSD vaccination. The overall animal level and herd level apparent seroprevalences were 25.4% (95% CI: 23.7–27.2) and 48.9% (95% CI: 44.9-52.9), respectively and varied significantly between districts. The true animal level and herd level prevalences were estimated as 26.5% (95% CI: 24.7–28.3) and 52.6% (95% CI: 48.3–56.9), respectively. At animal level, adult age (OR = 2.44 (95% CI: 1.67–3.55) compared to calf), contact with other animals (OR = 0.41 (95% CI: 0.23-0.74), compared to no contact) and presence of water bodies (OR = 1.61 (95% CI: 1.03–2.52), compared to no such bodies) were identified as the most important risk factors in relation to testing LSD positive. The putative risk factors altitude, breed, sex, and presence of animal trade route showed no significant association with LSD sero-status. Generally, cattle population with many adult animals and that live in wet areas are at highest risk, whereas cattle in frequent contact with other animals and animal species have lower risk, potentially due to a dilution effect of vectors.

Migration can influence dynamics of pathogen-host interactions. However, it is not clearly known how migration pattern, in terms of the configuration of the migration network and the synchrony of migration, affects infection prevalence. We therefore applied a discrete-time SIR model, integrating environmental transmission and migration, to various migration networks, including networks with serial, parallel, or both serial and parallel stopover sites, and with various levels of migration synchrony. We applied the model to the infection of avian influenza virus in a migratory geese population. In a network with only serial stopover sites, increasing the number of stopover sites reduced infection prevalence, because with every new stopover site, the amount of virus in the environment was lower than that in the previous stopover site, thereby reducing the exposure of the migratory population. In a network with parallel stopover sites, both increasing the number and earlier appearance of the stopover sites led to an earlier peak of infection prevalence in the migratory population, because the migratory population is exposed to larger total amount of virus in the environment, speeding-up the infection accumulation. Furthermore, higher migration synchrony reduced the average number of cumulative infection, because the majority of the population can fly to a new stopover site where the amount of virus is still relatively low and has not been increased due to virus shedding of infected birds. Our simulations indicate that a migration pattern with multiple serial stopover sites and with highly synchronized migration reduces the infection prevalence.

Digital Dermatitis (DD) is a claw disease mainly affecting the hind feet of dairy cattle. Digital Dermatitis is an infectious disease, transmitted via the environment, where the infectious “agent” is a combination of bacteria. The standardized classification for DD lesions developed by Döpfer et al. (1997) and extended by Berry et al. (2012) has six distinct classes: healthy (M0), an active granulomatous area of 0–2 cm (M1), an ulcerative lesion of >2 cm (M2), an ulcerative lesion covered by a scab (M3), alteration of the skin (M4), and a combination of M4 and M1 (M4.1).We hypothesize that classes M1, M2, M3, M4, and M4.1 are the potentially infectious classes that can contribute to the basic reproduction ratio (R0), the average number of new infections caused by a typical infected individual. Here, we determine differences in infectivity between the classes, the sojourn time in each of the classes, and the contribution of each class to R0.The analysis is based on data from twelve farms in the Netherlands that were visited every two weeks, eleven times.We found that 93.89% of the transitions from M0 was observed as a transition to class M4, and feet with another class-at-infection rapidly transitioned to class M4. As a consequence, about 70% of the infectious time was spent in class M4. Transmission rate parameters of class-at-infection M1, M2, M3, and M4 were not significantly different from each other, but differed from class-at-infection M4.1. However, due to the relative large amount of time spend in class M4, regardless of the class-at-infection, R0 was almost completely determined by this class. The R0 was 2.36, to which class-at-infection M4 alone contributed 88.5%.Thus, M4 lesions should be prevented to lower R0 to a value below one, while painful M2 lesions should be prevented for animal welfare reasons. Keywords: Mortellaro, Hairy heel wrat, Infectivity, Cow, Infection, Basic reproduction ratio

Lumpy skin disease (LSD), an infectious viral disease of cattle, causes considerable financial losses in livestock industry of affected countries. A questionnaire survey with the objectives of determining direct economic losses of LSD (mortality loss, milk loss, draft loss) and treatment costs (medication and labour cost) per affected herd, and assessing the cost effectiveness of vaccination as a means for LSD control was carried out in the central and north-western parts of Ethiopia. From a total of 4430 cattle (in 243 herds) surveyed, 941 animals (in 200 herds) were reported to be infected. The overall morbidity and mortality at animal level were 21.2% and 4.5%, and at herd level these were 82.3% and 24.3%. There was a significant difference in animal level morbidity and mortality between categories of animals. Over 94% of the herd owners ranked LSD as a big or very big problem for cattle production. A large proportion (92.2%) of the herd owners indicated that LSD affects cattle marketing. A median loss of USD 375 (USD 325 in local Zebu and USD 1250 in Holstein-Friesian local Zebu cross cattle) was estimated per dead animal. Median losses per affected lactating cow were USD 141 (USD 63 in local Zebu cows and USD 216 in Holstein-Friesian local Zebu cross cows) and, USD 36 per affected ox. Diagnosis and medication cost per affected animal were estimated at USD 5. The median total economic loss of an LSD outbreak at herd level was USD 1176 (USD 489 in subsistence farm and USD 2735 in commercial farm). At herd level, the largest component of the economic loss was due to mortality (USD 1000) followed by milk loss (USD 120). LSD control costs were the least contributor to herd level losses. The total herd level economic losses in the commercial farm type were significantly higher than in the subsistence farm type. The financial analysis showed a positive net profit of USD 136 (USD 56 for subsistence farm herds and USD 283 for commercial herds) per herd due to LSD vaccine investment. It should be noted that only the noticeable direct costs and treatment costs associated with the disease were considered in the study. Generally, vaccination is economically effective and should be encouraged.

Understanding virus shedding patterns of avian influenza virus (AIV) in poultry is important for understanding host-pathogen interactions and developing effective control strategies. Many AIV strains were studied in challenge experiments in poultry, but no study has combined data from those studies to identify general AIV shedding patterns. These systematic review and meta-analysis were performed to summarize qualitative and quantitative information on virus shedding levels and duration for different AIV strains in experimentally infected poultry species. Methods were designed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases were used to collect literature. A total of 1155 abstract were screened, with 117 studies selected for the qualitative analysis and 71 studies for the meta-analysis. A large heterogeneity in experimental methods was observed and the quantitative analysis showed that experimental variables such as species, virus origin, age, inoculation route and dose, affect virus shedding (mean, peak and duration) for highly pathogenic AIV (HPAIV), low pathogenic AIV (LPAIV) or both. In conclusion, this study highlights the need to standardize experimental procedures, it provides a comprehensive summary of the shedding patterns of AIV strains by infected poultry and identifies the variables that influence the level and duration of AIV shedding.

Background Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. Methods In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. Results We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Discussion Our results suggest that – for the antigenic distances we investigated – vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.

Vaccination of cattle against bovine Tuberculosis (bTB) has been a long-term policy objective for countries where disease continues to persist despite costly test-and-slaughter programs. The potential use of vaccination within the European Union has been linked to a need for field evaluation of any prospective vaccine and the impact of vaccination on the rate of transmission of bTB. We calculate that estimation of the direct protection of BCG could be achieved with 100 herds, but over 500 herds would be necessary to demonstrate an economic benefit for farmers whose costs are dominated by testing and associated herd restrictions. However, the low and variable attack rate in GB herds means field trials are unlikely to be able to discern any impact of vaccination on transmission. In contrast, experimental natural transmission studies could provide robust evaluation of both the efficacy and mode of action of vaccination using as few as 200 animals., eLife digest Bovine tuberculosis is an infectious disease of livestock and wildlife in many parts of the world. It also can spread to humans. In the United Kingdom (UK), infected cattle and badgers contribute to its spread. To control bovine tuberculosis, cattle are tested and infected animals are slaughtered. Badgers in areas near cattle are killed to keep their populations small and reduce the likelihood of them infecting cattle. These control strategies are very controversial. Testing and slaughtering cattle is expensive and many people object to badger culling. Developing a vaccine that would protect cattle against bovine tuberculosis is a potential alternative approach being investigated by the UK government. But such a vaccination is currently illegal in Europe because vaccinated animals may test positive for infection, creating confusion. Tests for bovine tuberculosis exist, but these DIVA (short for “Differentiates Infected from Vaccinated Animals”) tests are not yet licensed for use in the UK. The European Union (EU) said it would consider relaxing its laws against bovine tuberculosis vaccination if the UK government is able to prove a vaccine is effective on farms. Now, Conlan et al. show that the specific field trials recommended by the EU would have to be extremely large to show a benefit of vaccination. Mathematical models were used to calculate how many cattle herds a bovine tuberculosis vaccine study would need to show that it protects cattle from infection, reduces transmission of the disease, and saves farmers money. Conlan et al. show that a study including 100 herds would be large enough to prove the vaccine protected individual animals. But a trial would have to include 500 herds to show that vaccination saves farmers money. Because transmission of bovine tuberculosis is slow in the UK, trials on working farms are unlikely to be able to measure whether vaccination reduces the spread of the disease. Instead, Conlan et al. show that smaller, less expensive experiments in controlled settings would be able to estimate the effects of bovine tuberculosis vaccination on transmission. These results informed the UK government decision to delay farm-based studies of a bovine tuberculosis vaccine until a DIVA test is available. If vaccination and the use of a DIVA test can be proven to be effective enough to replace test and slaughter policies it could be a huge economic boon to farmers, particularly those in lower income countries.

The current study was carried out in central and North-western parts of Ethiopia to assess the efficacy of Kenyan sheep pox virus strain vaccine (KS1 O-180) against natural lumpy skin disease (LSD) infection under field conditions by estimating its effect on the transmission and severity of the disease. For this study, an LSD outbreak was defined as the occurrence of at least one LSD case in a specified geographical area. An observational study was conducted on a total of 2053 (1304 vaccinated and 749 unvaccinated) cattle in 339 infected herds located in 10 sub-kebeles and a questionnaire survey was administered to 224 herd owners. Over 60% of the herd owners reported that the vaccine has a low to very low effect in protecting animals against clinical LSD; almost all of them indicated that the vaccine did not induce any adverse reactions. In the unvaccinated group of animals 31.1% were diagnosed with LSD while this was 22.5% in the vaccinated group (P < 0.001). Severity of the disease was significantly reduced in vaccinated compared to unvaccinated animals (OR = 0.68, 95% CI: 0.49; 0.96). Unvaccinated infected animals were more likely (predicted fraction = 0.89) to develop moderate and severe disease than vaccinated infected animals (predicted fraction = 0.84). LSD vaccine efficacy for susceptibility was estimated to be 0.46 (i.e. a susceptibility effect of 0.54) while the infectiousness effect of the vaccine was 1.83. In other words, the vaccine reduces the susceptibility by a factor of two and increases infectiousness by approximately the same amount. LSD transmission occurred in both vaccinated and unvaccinated animals, the estimated reproduction ratio (R) was 1.21 in unvaccinated animals compared to 1.19 in vaccinated ones, and not significantly different. In conclusion, KS1 O-180 vaccination, as applied currently in Ethiopia, has poor efficacy in protecting cattle populations against LSD, neither by direct clinical protection nor by reducing transmission, and this signifies the urgent need to either improve the quality of the vaccine or to develop potent alternative vaccines that will confer good protection against LSD.

SummaryA fierce debate is going on about the risks of animal husbandry for human health and the quality of control measures to reduce such risks. Risks include the occurrence of infectious diseases, in particular zoonoses, and the high antibiotic use in livestock production contributing to emergence of antibiotic resistance and its spread from animals to humans. On the other hand, many infectious diseases of animals and humans have been eliminated, including brucellosis, tuberculosis, leptospirosis, and BSE, resulting in an animal husbandry that perhaps has never been as safe as nowadays. So while many health risks have been brought under control, the public opinion appears to reflect a feeling of anxiety and mistrust in authorities and producers to deal with the potential and remaining public health risks associated with animal husbandry. These risks, often associated with the intensification of animal production, are nonetheless indeed real. An animal husbandry that is “completely” safe and healthy for humans and animals requires a central role for disease prevention in the design and management of animal husbandry systems. It also requires that rapid and adequate responses are taken by veterinary and medical authorities on both perceived and real risks. Communication on health risks must be complete and open. Because actions to protect the health of animals often also benefit human health, there is usually no conflict of interests between humans and animals regarding their health needs. We emphasize the need to use the precautionary principle in matters of human and animal health. This implies that there must not be a “clash of cultures” between medical and veterinary professionals and policy makers.

Fish-borne Zoonotic Trematodes (FZTs) are a risk to human health and need to be controlled. A mathematical model was developed to give insight into how and to what extent control strategies change the dynamics of FZTs on integrated agriculture–aquaculture farms. The reproduction ratio R evaluates the effects of control strategies. R > 1 implies that the infection may persist, whereas R 54% of reservoir hosts. Snail control could result in R 25 g as compared to 0.5 g that is usual in aquaculture practice, or at > 14 g in combination with treating all humans, led to R

Extended-spectrum and AmpC β-lactamase-producing Escherichia coli (ESBL/AmpC-EC) are found throughout the broiler production pyramid. Transmission of resistance between broilers and humans could occur at any point, representing a potential public health issue. Insight in farm transmission dynamics could provide a basis for control, leading to fewer contaminated broilers. The aim was quantifying transmission rates and routes of ESBL/AmpC-EC, and specific phylogenetic groups, in an organic broiler flock without antibiotic use. In each of two consecutive production rounds, 80 randomly chosen broilers were followed individually. Cloacal swabs from these, 20 other randomly chosen broilers, and 11 environmental samples were taken at several moments from arrival till slaughter. ESBL/AmpC-EC were isolated by selective pre-enrichment, and ESBL/AmpC-genes and E. coli phylogenetic groups were determined. Transmission parameters (β) were estimated using a Generalised Linear Model with a susceptible-infectious-susceptible model. Effect of direct broiler contact as compared to contact through the environment and previous carriage c.q. infectious status and their interaction were included as explanatory variables. Multiplying β by the length of the infectious period gives the reproduction ratio (R). On day 1, prevalence was 28.8% (95%CI 19.2–40.0%) and 0.0% (95%CI 0.0–4.5%) among individually followed broilers, in round 1 and 2 respectively. In round 2, the environment was positive before arrival of day-old chicks. After 3 days, almost 100% of broilers and environmental samples were positive in both rounds. Most samples were positive for CTX-M-1 group genes, and A1 and B1 were predominant phylogenetic groups. From day 3 there was a shift towards more phylogenetic groups. R was 1.70 (95%CI 0.55–5.25) for total ESBL/AmpC-EC. Risk for broilers to become infectious was lower if previously infectious (βpreviously infectious = 0.02 vs. βnot previously infectious = 3.41; P

Live vaccines for coccidiosis control are infrequently used in broilers, mainly due to variability in efficacy and relatively high costs. More insight in transmission of vaccine and wild-type strains can facilitate optimization of vaccination strategies and might increase its use as an alternative for anticoccidial drugs. The aim of this study was to quantify transmission of a live Eimeria acervulina vaccine strain and to determine the degree of protection against a subsequent infection with a wild-type E. acervulina strain. An experiment was carried out with 4 groups of 22 SPF broilers. At 2 days of age, 11 birds of groups 2 to 4 were vaccinated directly by oral application of E. acervulina oocysts of the Paracox (TM) vaccine and 11 birds were placed in contact with these birds (contact-vaccinated). Birds in group 1 remained unvaccinated (controls) and were not exposed to vaccinated birds. At day 28 of age, 6 groups of 10 birds were formed, with 2 groups (duplo) for each treatment group, i.e. vaccinated, contact-vaccinated or unvaccinated control birds. Five birds of each group were orally inoculated with wild-type E. acervulina oocysts and five were contact-exposed. Single droppings were examined daily from days 5 to 49 of age for oocyst output and to determine the time of infection. The transmission rate of the vaccine strain was estimated to be 1.6 per day and of the wild-type strain 2.3, 8.7 and 20.8 per day for vaccinated, contact-vaccinated and unvaccinated birds, respectively. Although transmission of wild-type coccidia was not significantly reduced in vaccinated or contact-vaccinated groups, both groups were equally protected against high oocyst output after infection compared to unvaccinated groups. These results suggest that factors influencing transmission of live vaccine strains in flocks may be important targets for improvement of vaccine efficacy and warrant further research.

The prevalence of methicillin resistant Staphylococcus aureus (MRSA) in pigs at abattoirs is higher than in pigs sampled on farms. This study investigated whether MRSA negative pigs can become MRSA positive during transportation from the farm to the abattoir after exposure to other pigs and environmental sources of MRSA. Nasal swabs were collected from four batches of pigs during loading at the farm, on arrival at the abattoir and after stunning. Environmental wipes were taken from lorries after transporting pigs and from lairages after holding pigs. All pigs (n = 117) tested MRSA negative before transportation. On arrival at the abattoir, 12/117 (10.3%) pigs in two batches tested MRSA positive. In lorries that tested positive after transportation, the prevalence of MRSA positive pigs was 21.1%, whereas no MRSA was detected in pigs that had been transported in lorries that tested negative after transportation. At stunning, all batches and 70/117 (59.8%) pigs tested MRSA positive. Pigs can become MRSA positive in the short period of time during transportation from the farm to stunning at the abattoir.

Sources for human hepatitis E virus (HEV) infections of genotype 3 are largely unknown. Pigs are potential animal reservoirs for HEV. Intervention at pig farms may be desired when pigs are confirmed as a source for human infections, requiring knowledge about transmission routes. These routes are currently understudied. The current study aims to quantify the likelihood of pig feces in causing new HEV infections in pigs due to oral ingestion. We estimated the daily infection risk for pigs by modeling the fate of HEV in the fecal-oral (F-O) pathway. Using parameter values deemed most plausible by the authors based on current knowledge the daily risk of infection was 0.85 (95% interval: 0.03-1). The associated expected number of new infections per day was ∼4 (2.5% limit 0.1, the 97% limit tending to infinity) compared to 0.7 observed in a transmission experiment with pigs, and the likelihood of feces causing the transmission approached 1. In alternative scenarios, F-O transmission of HEV was also very likely to cause new infections. By reducing the total value of all explanatory variables by 2 orders of magnitude, the expected numbers of newly infected pigs approached the observed number. The likelihood of F-O transmission decreased by decreasing parameter values, allowing for at most 94% of infections being caused by additional transmission routes. Nevertheless, in all scenarios F-O transmission was estimated to contribute to HEV transmission. Thus, despite the difficulty in infecting pigs with HEV via oral inoculation, the F-O route is likely to cause HEV transmission among pigs.

In the past decades, mathematical models have become more and more accepted as a tool to develop surveillance programs and to evaluate the efficacy of intervention measures for the control of infectious diseases such as highly pathogenic avian influenza. Predictive models are used to simulate the effect of various control measures on the course of an epidemic; analytical models are used to analyze data from outbreaks or from experiments. A key parameter in both types of models is the reproductive ratio, which indicates whether virus can be transmitted in the population, resulting in an epidemic, or not. Parameters obtained from real data using the analytical models can subsequently be used in predictive models to evaluate control strategies or surveillance programs. Examples of the use of these models are described here.

To optimize control of an avian influenza outbreak knowledge of within-flock transmission is needed. This study used field data to estimate the transmission rate parameter (beta) and the influence of risk factors on within-flock transmission of highly pathogenic avian influenza (HPAI) H7N7 virus in the 2003 epidemic in The Netherlands. The estimation is based on back-calculation of daily mortality data to fit a susceptible-infectious-dead format, and these data were analysed with a generalized linear model. This back-calculation method took into account the uncertainty of the length of the latent period, the survival of an infection by some birds and the influence of farm characteristics. After analysing the fit of the different databases created by back-calculation, it could be concluded that an absence of the latency period provided the best fit. The transmission rate parameter (beta) from these field data was estimated at 4.50 per infectious chicken per day (95% CI: 2.68-7.57), which was lower than what was reported from experimental data. In contrast to general belief, none of the studied risk factors (housing system, flock size, species, age of the birds in weeks and date of depopulation) had significant influence on the estimated beta.

The herd sensitivity (HSe) and herd specificity (Hsp) of clinical diagnosis of an infection with classical swine fever (CSF) virus during veterinary inspection of breeding sows in a herd was evaluated. Data gathered from visits to herds during the CSF outbreak in 1997¿1998 in The Netherlands were used for the analysis. Herds were visited one or more times by the same or by different veterinarians. On the basis of the veterinarians¿ reports, each visit was coded as 0 (negative clinical diagnosis) or 1 (positive clinical diagnosis). The HSe for clinical diagnosis of CSF was modelled as a function of days elapsed since introduction of the virus. The moment of introduction of the CSF virus in the CSF-positive herds was unknown, so for each herd, a probability distribution for the unknown number of days since introduction was derived from serum samples collected at depopulation. The information from the reports of the veterinarians and from the test results of the serum samples at depopulation was combined in a Bayesian analysis. Data from CSF-negative herds were analysed to estimate HSp of clinical diagnosis of CSF. The HSe of clinical diagnosis was 0.5 at 37 days after virus introduction (95% CI: 31, 45) and reached 0.9 at 47 days after virus introduction (95% CI: 41, 54). The estimated herd specificity was 0.72 (95% CI: 0.64, 0.79). Dependence of HSe and HSp on characteristics of the veterinarians and the herds also was studied. Specialisation of the veterinarian significantly, although not markedly, affected the HSe.

Objective: To determine the within-host population dynamics of Campylobacter jejuni and Escherichia coli in chickens during and after treatment with fluoroquinolones. Materials and methods: Total and resistant faecal counts were determined from cloacal swabs during and after treatment with enrofloxacin. Chickens were housed individually to avoid confounding as a result of interaction between animals, and to be able to focus solely on the within-host dynamics. To determine the molecular basis of resistance, a number of isolates were checked for mutations in gyrA. Results: Treatment with enrofloxacin at doses routinely prescribed (50 ppm) rapidly reduced the faecal counts of E. coli below the detection limit and did not induce resistance. In C. jejuni, on the other hand, treatment with enrofloxacin quickly selected for high frequencies of fluoroquinolone-resistant strains. In all phenotypically resistant isolates, resistance was traced to mutations in the gyrA gene. Conclusions: (1) A licensed dosage (50 ppm) of enrofloxacin in drinking water of chickens is effective (i.e. markedly reduced faecal counts) and is safe on a short time scale in E. coli (i.e. did not rapidly select for resistance), but is neither safe nor effective in C. jejuni. (2) The rapid emergence of resistance to quinolones in C. jejuni does not necessarily result from horizontal transmission of resistant strains among chickens, but could solely be the result of de novo selection of resistance in individual chickens.

[b]Introduction[/b]. The airborne transmission of infectious diseases in livestock production is increasingly receiving research attention. Reliable techniques of air sampling are crucial to underpin the findings of such studies. This study evaluated the physical and biological efficiencies and detection limits of four samplers (Andersen 6-stage impactor, all-glass impinger “AGI-30”, OMNI-3000 and MD8 with gelatin filter) for collecting aerosols of infectious bursal disease virus (IBDV). [b]Materials and Method[/b]. IBDV aerosols mixed with a physical tracer (uranine) were generated in an isolator, and then collected by the bioaerosol samplers. Samplers’ physical and biological efficiencies were derived based on the tracer concentration and the virus/tracer ratio, respectively. Detection limits for the samplers were estimated with the obtained efficiency data. [b]Results.[/b] Physical efficiencies of the AGI-30 (96%) and the MD8 (100%) were significantly higher than that of the OMNI-3000 (60%). Biological efficiency of the OMNI-3000 (23%) was significantly lower than 100% (P < 0.01), indicating inactivation of airborne virus during sampling. The AGI-30, the Andersen impactor and the MD8 did not significantly inactivate virus during sampling. The 2-min detection limits of the samplers on airborne IBDV were 4.1 log[sub]10[/sub] 50% egg infective dose (EID[sub]50[/sub]) m [sup]-3[/sup] for the Andersen impactor, 3.3 log[sub]10[/sub] EID50 m [sup]-3[/sup] for the AGI-30, 2.5 log[sub]10[/sub] EID50 m [sup]-3[/sup] for the OMNI-3000, and 2.9 log[sub]10[/sub] EID[sub]50[/sub] m [sup]-3[/sup] for the MD8. The mean half-life of IBDV aerosolized at 20 °C and 70% was 11.9 min. Conclusion. Efficiencies of different samplers vary. Despite its relatively low sampling efficiency, the OMNI-3000 is suitable for use in environments with low viral concentrations because its high flow rate gives a low detection limit. With the 4 samplers investigated, negative air samples cannot guarantee virus-free aerial environments, which means that transmission of infectious agents between farms may still occur even when no virus has been detected.

A long-term research programme has been underway in Ireland to evaluate the usefulness of badger vaccination as part of the national bTB (bovine tuberculosis) control strategy. This culminated in a field trial which commenced in county Kilkenny in 2009 to determine the effects of badger vaccination on Mycobacterium bovis transmission in badgers under field conditions. In the present study, we sought to optimise the characteristics of a multiplex chemiluminescent assay for detection of M. bovis infection in live badgers. Our goal was to maximise specificity, and therefore statistical power, during evaluation of the badger vaccine trial data. In addition, we also aimed to explore the effects of vaccination on test characteristics. For the test optimisation, we ran a stepwise logistic regression with analytical weights on the converted Relative Light Units (RLU) obtained from testing blood samples from 215 badgers captured as part of culling operations by the national Department of Agriculture, Food and the Marine (DAFM). The optimised test was applied to two other datasets obtained from two captive badger studies (Study 1 and Study 2), and the sensitivity and specificity of the test was attained separately for vaccinated and non-vaccinated badgers. During optimisation, test sensitivity was maximised (30.77%), while retaining specificity at 99.99%. When the optimised test was then applied to the captive badger studies data, we observed that test characteristics did not vary greatly between vaccinated and non-vaccinated badgers. However, a different time lag between infection and a positive test result was observed in vaccinated and non-vaccinated badgers. We propose that the optimized multiplex immunoassay be used to analyse the vaccine trial data. In relation to the difference in the time lag observed for vaccinated and non-vaccinated badgers, we also present a strategy to enable the test to be used during trial evaluation.

Receiver operating characteristic (ROC) curves assess the quality of tests over the entire range of test signals. We compared the ability of an ELISA to detect antibodies to Aujeszky's disease (pseudorabies) virus gE in colostrum (test A) and in a single droplet of whole blood (test B) with the results obtained in serum (gold standard) in the target population by constructing and analyzing such curves. The area under the ROC curve, which is a quantitative measure of test performance, proved to be significantly (p < 0.01) smaller in test A than in test B or the gold standard. No significant differences in the area under the ROC curve were observed between test B and the gold standard.

Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds.

Estimates of the per-contact probability of transmission between farms of Highly Pathogenic Avian Influenza virus of H7N7 subtype during the 2003 epidemic in the Netherlands are important for the design of better control and biosecurity strategies. We used standardized data collected during the epidemic and a model to extract data for untraced contacts based on the daily number of infectious farms within a given distance of a susceptible farm. With these data, we used a maximum likelihood estimation approach to estimate the transmission probabilities by the individual contact types, both traced and untraced. The estimated conditional probabilities, conditional on the contact originating from an infectious farm, of virus transmission were: 0.000057 per infectious farm within 1 km per day, 0.000413 per infectious farm between 1 and 3 km per day, 0.0000895 per infectious farm between 3 and 10 km per day, 0.0011 per crisis organisation contact, 0.0414 per feed delivery contact, 0.308 per egg transport contact, 0.133 per other-professional contact and, 0.246 per rendering contact. We validate these outcomes against literature data on virus genetic sequences for outbreak farms. These estimates can be used to inform further studies on the role that improved biosecurity between contacts and/or contact frequency reduction can play in eliminating between-farm spread of the virus during future epidemics. The findings also highlight the need to; 1) understand the routes underlying the infections without traced contacts and, 2) to review whether the contact-tracing protocol is exhaustive in relation to all the farm’s day-to-day activities and practices.

Survival of airborne virus influences the extent of disease transmission via air. How environmental factors affect viral survival is not fully understood. We investigated the survival of a vaccine strain of Gumboro virus which was aerosolized at three temperatures (10°C, 20°C, and 30°C) and two relative humidities (RHs) (40% and 70%). The response of viral survival to four metrics (temperature, RH, absolute humidity [AH], and evaporation potential [EP]) was examined. The results show a biphasic viral survival at 10°C and 20°C, i.e., a rapid initial inactivation in a short period (2.3 min) during and after aerosolization, followed by a slow secondary inactivation during a 20-min period after aerosolization. The initial decays of aerosolized virus at 10°C (1.68 to 3.03 ln % min −1 ) and 20°C (3.05 to 3.62 ln % min −1 ) were significantly lower than those at 30°C (5.67 to 5.96 ln % min −1 ). The secondary decays at 10°C (0.03 to 0.09 ln % min −1 ) tended to be higher than those at 20°C (−0.01 to 0.01 ln % min −1 ). The initial viral survival responded to temperature and RH and potentially to EP; the secondary viral survival responded to temperature and potentially to RH. In both phases, survival of the virus was not significantly affected by AH. These findings suggest that long-distance transmission of airborne virus is more likely to occur at 20°C than at 10°C or 30°C and that current Gumboro vaccination by wet aerosolization in poultry industry is not very effective due to the fast initial decay.

A quantitative understanding of the spread of contaminated farm dust between locations is a prerequisite for obtaining much-needed insight into one of the possible mechanisms of disease spread between farms. Here, we develop a model to calculate the quantity of contaminated farm-dust particles deposited at various locations downwind of a source farm and apply the model to assess the possible contribution of the wind-borne route to the transmission of Highly Pathogenic Avian Influenza virus (HPAI) during the 2003 epidemic in the Netherlands. The model is obtained from a Gaussian Plume Model by incorporating the dust deposition process, pathogen decay, and a model for the infection process on exposed farms. Using poultry- and avian influenza-specific parameter values we calculate the distance-dependent probability of between-farm transmission by this route. A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.

The infection dynamics of Eimeria species determine the clinical manifestation of the disease coccidiosis in poultry flocks, and a better understanding of the dynamics may contribute to improvement of control measures. Our aim was to study the course of infection and the transmission of Eimeria acervulina in groups of broilers by quantifying the transmission rate parameter and oocyst output. Three transmission experiments were carried out with groups of 20 male SPF broilers. At 2 days of age, one bird in each trial was orally inoculated with five sporulated E. acervulina oocysts (DO post-inoculation, pi). One day after inoculation (D1 pi), the inoculated bird was housed with 19 non-inoculated contact birds. Individual faecal droppings were examined daily from D3-D32 pi to quantify the number of oocysts per gram faeces. The inoculated bird started shedding oocysts at D5 pi and contact birds between D10 and D17 pi. Contact birds that became infected due to oocyst excretion by the inoculated bird were characterized as first generation contact birds (C1). Contact birds excreting from D15 pi onwards (C2) became infected after the first Cl birds had started shedding and were considered to belong to a successive generation of the flock infection. Oocyst output was significantly lower for C1 compared to C2 birds, but the transmission rate parameter remained constant for both infection generations. These results suggest that although oocyst load increases, the transmission rate of E. acervulina remains constant between successive generations of infection in a flock.

Background Infectious diseases in plants, animals and humans are often transmitted indirectly between hosts (or between groups of hosts), i.e. via some route through the environment instead of via direct contacts between these hosts. Here we study indirect transmission experimentally, using transmission of Campylobacter jejuni (C. jejuni) between spatially separated broilers as a model system. We distinguish three stages in the process of indirect transmission; (1) an infectious “sender” excretes the agent, after which (2) the agent is transported via some route to a susceptible “receiver”, and subsequently (3) the receiver becomes colonised by the agent. The role of the sender and receiver side (stage 1 and stage 3) was studied here by using acidification of the drinking water as a modulation mechanism. Results In the experiment one control group and three treatment groups were monitored for the presence of C. jejuni by taking daily cloacal swabs. The three treatments consisted of acidification of the drinking water of the inoculated animals (the senders), acidification of the drinking water of the susceptible animals (the receivers) or acidification of the drinking water of both inoculated and susceptible animals. In the control group 12 animals got colonised out of a possible 40, in each treatment groups 3 animals out of a possible 40 were found colonised with C. jejuni. Conclusions The results of the experiments show a significant decrease in transmission rate (β) between the control groups and treatment groups (p < 0.01 for all groups) but not between different treatments; there is a significant negative interaction effect when both the sender and the receiver group receive acidified drinking water (p = 0.01). This negative interaction effect could be due to selection of bacteria already at the sender side thereby diminishing the effect of acidification at the receiver side.

Although reduction in transmission of an agent in the host population is an important goal of many vaccinations, suitable experimental methods to measure transmission have been lacking. Therefore, we designed and tested an animal experiment to quantify transmission among vaccinated and unvaccinated animals. We used Aujeszky's disease virus (ADV) in pigs, because a serological test was available to detect infection in vaccinated pigs and because vaccination against ADV will be used in an attempt to eliminate ADV from the Netherlands. Our experiments showed that vaccinating twice with vaccine 783 significantly reduces ADV transmission. In unvaccinated groups, the estimated maximum number of secondary cases per infectious individual, i.e. the basic reproduction ratio R0, was 10.0. In contrast, the reproduction ratio for the vaccinated groups R, i.e. the average number of secondary cases per infectious individual in a totally vaccinated population, was 0.5. These results show that it is possible to measure transmission experimentally. Therefore, such measurements should be obtained for all vaccines that are intended to eliminate agents causing animal diseases, either on a single farm or in a whole country.

The principal wildlife reservoir of Mycobacterium bovis in Ireland is the European badger. Studies in the Republic of Ireland (RoI) have shown that badgers culled in association with cattle herd tuberculosis breakdowns (focal culling) have a higher prevalence of infection than the badger population at large. This observation is one rationale for the medium term national strategy of focal badger culling. A vaccination strategy for the control of bovine tuberculosis (bTB) in badgers is a preferred long-term option. The Bacillus Calmette-Guérin (BCG) vaccine has been shown to decrease disease severity in captive badgers under controlled conditions. As the vaccine has been tested in a controlled environment with precise information on infection pressure, it cannot be assumed a priori that the effects of vaccination are similar in the wild, where other environmental and/or ecological factors prevail. For this reason we have designed a vaccine field trial to assess the impact of vaccination on the incidence of TB infection in a wild badger population. The selected study area for the vaccine trial (approximately 755 square kilometers) is divided into three zones each of which has similar characteristics in terms of size, number of main badger setts, cattle herds, cattle and land classification type. Three vaccination levels (100%, 50% and 0%) will be allocated to the three zones in a way that a gradient of vaccination coverage North to South is achieved. The middle zone (zone B) will be vaccinated at a 50% coverage but zone A and C will be randomly allocated with 100% or 0% vaccination coverage. Vaccination within zone B will be done randomly at individual badger level. The objective of this paper is to describe the design of a field tuberculosis vaccination trial for badgers, the epidemiological methods that were used to design the trial and the subsequent data analysis. The analysis will enable us to quantify the magnitude of the observed vaccination effect on M. bovis transmission in badgers under field conditions and to improve our knowledge of the biological effects of vaccination on susceptibility and infectiousness.

Fish-borne trematodes are reported to affect the health of more than 40 million people worldwide. Few experimental studies are available on fish size dependent gain (attack rates of cercariae) or loss (mortality of metacercariae) of fish-borne trematodes. Aim was to quantify the relation between fish size and attack rates of fish-borne trematodes in common carps (Cyprinus carpio). Effect of fish size and cercariae dose were tested in a 3 × 4 factorial design with 5 fish per combination of treatments (n = 60). Individually kept small (1 g), medium (25 g) and large (45 g) carps were exposed to 0, 10, 50 or 250 parapleurolophocercous-cercariae (Heterophyidae) for 48 h. Fish were digested 21 days post exposure to count metacercariae. Percentages of fish containing metacercariae, and attack rates of cercariae to fish were higher (63%, 0.08 fish infected per cercariae) for small common carps than for medium (20%, 0.004 fish infected per cercariae) and large common carps (5%, 0.0007 fish infected per cercariae), but never zero. It was concluded that exposure of small fish is an important risk factor for transmission of fish-borne trematodes. The results suggest that control measurements aimed at reducing transmission to small fish may considerably reduce the absolute amount of fish-borne trematodes.

In 2001 the epidemics of foot-and-mouth disease virus (FMDV) in Great Britain, The Netherlands and France have shown how fast FMDV may spread between farms. The massive socio-economic impact of these epidemics and the intervention measures taken demonstrate the need for quantitative assessments of the efficacy of candidate intervention strategies. Here we use a mathematical model to describe the spatial transmission of FMDV in The Netherlands and use the Dutch 2001 outbreak data to estimate model parameters. We assess the effect of ring culling strategies using a novel and fast approach producing risk maps, and discuss its consequences for ring vaccination. These risk maps identify both the geographical areas of low risk, where a given intervention strategy is likely to achieve epidemic control within only two or three farm-to-farm infection generations, and high-risk areas, where control is likely to take (much) longer. Our results indicate that certain densely populated livestock areas in the Netherlands remain high-risk areas even for strategies that extend EU minimum measures with culling or vaccination within a ring radius of several kilometres. Depending on an economic assessment, area-wide vaccination might be judged appropriate once an FMDV outbreak would have been confirmed in or close to such a high-density area. The modeling approach developed here could be readily applied to outbreak data for other diseases and in other countries.

Background Worldwide, hepatitis E virus (HEV) genotype 3 is observed in pigs and transmission to humans is implied. To be able to estimate public health risks from e.g. contact with pigs or consumption of pork products, the transmission routes and dynamics of infection should be identified. Hence, the course of HEV-infection in naturally infected pigs should be studied. Results To resemble natural transmission, 24 HEV-susceptible pigs were infected either by one-to-one exposure to intravenously inoculated pigs (C1-pigs; n = 10), by one-to-one exposure to contact-infected pigs (C2-pigs: n = 7; C3-pigs: n = 5) or due to an unknown non-intravenous infection route (one C2-pig and one C3-pig). The course of HEV-infection for contact-infected pigs was characterized by: faecal HEV RNA excretion that started at day 7 (95% confidence interval: 5–10) postexposure and lasted 23 (19–28) days; viremia that started after 13 (8–17) days of faecal HEV RNA excretion and lasted 11 (8–13) days; antibody development that was detected after 13 (10–16) days of faecal HEV RNA excretion. The time until onset of faecal HEV RNA excretion and onset of viremia was significantly shorter for iv-pigs compared to contact-infected pigs, whereas the duration of faecal HEV RNA excretion was significantly longer. At 28 days postinfection HEV RNA was detected less frequently in organs of contact-infected pigs compared to iv-pigs. For contact-infected pigs, HEV RNA was detected in 20 of 39 muscle samples that were proxies for pork at retail and in 4 of 7 urine samples. Conclusion The course of infection differed between infection routes, suggesting that contact-infection could be a better model for natural transmission than iv inoculation. Urine and meat were identified as possible HEV-sources for pig-to-pig and pig-to-human HEV transmission.

In a recent update of the Dutch contingency plan for controlling outbreaks of classical swine fever (CSF), emergency vaccination is preferred to large-scale pre-emptive culling. This policy change raised two questions: can emergency vaccination be as effective as pre-emptive culling, and what are the implications for showing freedom of infection? Here, we integrate quantitative information available on CSF virus transmission and vaccination effects into a stochastic mathematical model that describes the transmission dynamics at the level of animals, farms and livestock areas. This multilevel approach connects individual-level interventions to large-scale effects. Using this model, we compare the performance of five different control strategies applied to hypothetical CSF epidemics in The Netherlands and, for each of these strategies, we study the properties of three different screening scenarios to show freedom of infection. We find that vaccination in a ring of 2 km radius around a detected infection source is as effective as ring culling in a 1 km radius. Feasible screening scenarios, adapted to the use of emergency vaccination, can reduce the enhanced risks of (initially) undetected farm outbreaks by targeting vaccinated farms. Altogether, our results suggest that emergency vaccination against CSF can be equally effective and safe as pre-emptive culling.

International audience; Locally acquired hepatitis E in humans from industrialized countries has been repeatedly suggested to originate from pigs. Pigs may serve as a reservoir of hepatitis E virus (HEV) for humans when a typical infected pig causes on average more than one newly infected pig, a property that is expressed by the basic reproduction ratio $R_0$. In this study, $R_0$ for HEV transmission among pigs was estimated from chains of one-to-one transmission experiments in two blocks of five chains each. Per chain, susceptible first-generation contact pigs were contact-exposed to intravenously inoculated pigs, subsequently susceptible second-generation contact pigs were contact-exposed to infected first-generation contact pigs, and lastly, susceptible third-generation contact pigs were contact-exposed to infected second-generation contact pigs. Thus, in the second and third link of the chain, HEV-transmission due to contact with a contact-infected pig was observed. Transmission of HEV was monitored by reverse transcriptase polymerase chain reaction (RT-PCR) on individual faecal samples taken every two/three days. For susceptible pigs, the average period between exposure to an infectious pig and HEV excretion was six days (standard deviation: 4). The length of HEV-excretion (i.e. infectious period) was estimated at 49 days (95% confidence interval (CI): 17-141) for block 1 and 13 days (95% CI: 11-17) for block 2. The R0 for contact-exposure was estimated to be 8.8 (95% CI: 4-19), showing the potential of HEV to cause epidemics in populations of pigs.

This study describes the results of a transmission experiment with highly pathogenic avian influenza (HPAI) H7N7 virus in 12-week-old turkeys. Cloacal and tracheal swabs as well as serum samples were taken to monitor the infection both in inoculated and in susceptible contact turkeys, which were all either unvaccinated, vaccinated once or vaccinated twice with H7N1. Swabs were tested by real-time RT-PCR and serum samples with hemagglutination inhibition test (HI). Unvaccinated contact birds had a mean infectious period of 6.2 days, and an estimated transmission rate parameter of 1.26 per infectious bird per day. However, no virus shedding was found in inoculated vaccinated turkeys and thus we concluded that vaccination with H7N1 protected against challenge with HPAI H7N7 virus.

Highly pathogenic avian influenza viruses can affect many bird species, with disease symptoms ranging from severe morbidity and high mortality to mild transient illness. Much is known about infections in chickens, but for other captive birds the relations between disease symptoms, excretion patterns, and transmission, as well as the effect of vaccination on these relations are not clear. We report results from experimental transmission studies with a highly pathogenic H7N7 virus and two commonly kept bird species (ringed teals and golden pheasants). The results show that depending on the host species the virus can spread in unvaccinated birds with or without disease symptoms. Vaccination reduces disease symptoms markedly, but need not always reduce virus transmission. We discuss the implications for the control of highly pathogenic avian influenza. (C) 2007 Elsevier Ltd. All rights reserved.

We investigated the influence of the spatial pattern of farms on the geographical spread of infectious livestock diseases, such as classical swine fever, foot-and-mouth disease and avian influenza in a combined analytical-numerical approach. Our purpose of this paper is to develop a method to identify the areas in which an infection has the potential to spread in an outbreak. In our model, each infected farm can infect neighbouring farms and the probability of transmission is a function of the inter-farm distance (spatial kernel). Therefore, the density of farms in an area is a good indicator for the probability of a major outbreak. In the epidemiological nomenclature, such density corresponds to a local reproduction ratio and we studied the critical behaviour of both the local density and the local reproduction ratio. We found that a threshold can be defined above which major outbreaks can occur, and the threshold value depends on the spatial kernel. Our expression for the threshold value is derived based on scaling arguments and contains two parameters in the exponents of the equation. We estimated these parameters from numerical results for the spatial spread using one particular mathematical function for the form of the spatial kernel. Subsequently, we show that our expression for the threshold using these estimated parameters agrees very well with numerical results for a number of different other functional forms of the spatial kernel (thus suggesting that we are dealing with universal parameters). As an illustration of the practical relevance of the presented method, we calculated the threshold value for avian influenza in the Netherlands and use it to produce a risk map for this disease. © 2007 Elsevier B.V. All rights reserved.

This article presents a model to evaluate the accuracy of diagnostic tests. Data from three tests for the detection of EF-positive Streptococcus suis serotype 2 strains in sows were analyzed. The data were collected in a field study in the absence of a gold standard, that is, the true disease status (noninfected or infected) of the tested animals was unknown. Two tests were based on a polymerase chain reaction (PCR); one test was applied to a tonsil swab (taken from the live animal), and the other test was applied to the whole tonsil (collected at slaughter). The third test was based on a bacterial examination (BE) of the whole tonsil. To reduce experimental cost BE was performed only for a subset of the animals in the sample. The model allows for dependence between tests, conditional upon the unknown true disease status of the animals. Accuracy was expressed in terms of sensitivity and specificity of the tests. A Bayesian analysis was performed that incorporated prior information about the accuracy of the tests. The model parameters have a simple interpretation and specification of priors is straightforward. Posterior inference was carried out with Markov chain Monte Carlo (MCMC) methods, employing the Gibbs sampler, as implemented in the WinBUGS program. Different parameterizations to allow for selection and missing values, use of different priors, practical problems in the analysis, and some interesting issues in a joint analysis of the binary (positive or negative) results of PCR and BE and two additional continuous enzyme-linked immunosorbent assays (ELISA) are discussed.

An epidemic of high-pathogenicity avian influenza (HPAI) A virus subtype H7N7 occurred in The Netherlands in 2003 that affected 255 flocks and led to the culling of 30 million birds. To evaluate the effectiveness of the control measures, we quantified between-flock transmission characteristics of the virus in 2 affected areas, using the reproduction ratio Rh. The control measures markedly reduced the transmission of HPAI virus: Rh before detection of the outbreak in the first infected flock was 6.5 (95% confidence interval [CI], 3.1-9.9) in one area and 3.1 in another area, and it decreased to 1.2 (95% CI, 0.6-1.9) after detection of the first outbreak in both areas. The observation that Rh remained >1 suggests that the containment of the epidemic was probably due to the reduction in the number of susceptible flocks by complete depopulation of the infected areas rather than to the reduction of the transmission by the other control measures

The foot-and-mouth disease outbreak in The Netherlands in 2001 most likely started on a mixed veal-calf/dairy-goat farm. The outbreak among the 74 calves on this farm appeared to be limited to four animals, and no clinical signs of FMD were reported. Also on a second veal-calf farm minor clinical signs and limited virus transmission were observed. Since FMD is known to be a very contagious disease, and can cause severe lesions, these observations were disputed. Therefore, we carried out two experiments to determine whether the Dutch FMD virus isolate from 2001 does spread among individually housed calves with limited contacts, either indirect (experiment 1) or direct (experiment 2). In experiment 1, four pairs of calves were housed in an individual box at 1m distance from each other. In experiment 2, two groups of three calves were housed in individual boxes, directly bordering each other. We infected one animal per pair in experiment 1, and the calf in the middle in experiment 2. We recorded clinical signs, virus shedding in saliva and the development of antibodies. In addition, we determined whether the virus was transmitted from the inoculated calves to the neighbour(s). All inoculated calves showed mild signs of FMD--fever, and some vesicles on hooves and/or in the mouth--but only one calf showed signs that were visible without physical examination. All inoculated calves shed virus in the saliva and developed neutralising antibodies. None of the contact animals seroconverted, indicating that virus transmission did not occur. These experiments showed that no virus transmission among individual housed calves can occur. This finding supports the hypothesis of the route of virus introduction to The Netherlands in 2001 and show that the observations on the two veal-calf farms were not impossible.

The safety of using meat and bone meal (MBM) in mammal feed was studied in view of BSE, by quantifying the risk of BSE transmission through different infection routes. This risk is embodied in the basic reproduction ratio R(0) of the infection, i.e. the average number of new infections induced by one initial infection. Only when R(0) is below 1, will the disease die out with certainty and the population will become free from BSE. Unfortunately this is a slow process due to the slow progression of the disease. We calculate R(0) explicitly from basic ingredients taking several different transmission routes into account. Several of the basic ingredients are functions of age or of infection-age. We also calculate the exponential growth rate r in terms of the same basic ingredients. Next we quantify the ingredients from available data and compute the effects on R(0) of various scenario's for controlling BSE, with examples for the UK and the Netherlands.

Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

Foot-and-mouth disease virus (FMDV) infected animals can contaminate the environment with their secretions and excretions. To quantify the contribution of a contaminated environment to the transmission of FMDV, this study used calves that were not vaccinated and calves that were vaccinated 1 week prior to inoculation with the virus in direct and indirect contact experiments. In direct contact experiments, contact calves were exposed to inoculated calves in the same room. In indirect contact experiments, contact calves were housed in rooms that previously had held inoculated calves for three days (either from 0 to 3 or from 3 to 6 days post inoculation). Secretions and excretions from all calves were tested for the presence of FMDV by virus isolation; the results were used to quantify FMDV transmission. This was done using a generalized linear model based on a 2 route (2R, i.e. direct contact and environment) SIR model that included information on FMDV survival in the environment. The study shows that roughly 44% of transmission occurs via the environment, as indicated by the reproduction ratio \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {{\widehat{R}}_0}^{2R} environment $$\end{document}R^02Renvironment that equalled 2.0, whereas the sum of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {{\widehat{R}}_0}^{2R} contact $$\end{document}R^02Rcontact and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {{\widehat{R}}_0}^{2R} environment $$\end{document}R^02Renvironment equalled 4.6. Because vaccination 1 week prior to inoculation of the calves conferred protective immunity against FMDV infection, no transmission rate parameters could be estimated from the experiments with vaccinated calves. We conclude that a contaminated environment contributes considerably to the transmission of FMDV therefore that hygiene measures can play a crucial role in FMD control. Electronic supplementary material The online version of this article (doi:10.1186/s13567-015-0156-5) contains supplementary material, which is available to authorized users.