Assessment of A20 infectious laryngotracheitis vaccine take in meat chickens using swab and dust samples following mass vaccination in drinking water.

Infectious laryngotracheitis, caused by the alphaherpesvirus infectious laryngotracheitis virus (ILTV), is an important disease of chickens. Partial control of this disease in meat chickens is commonly achieved by mass vaccination with live virus in drinking water. There is a need for a practical test to evaluate vaccination outcomes. For the Serva ILTV vaccine, quantitative real-time PCR (qPCR) enumeration of ILTV genome copies (GC) in flock level dust samples collected at 7-8 days post vaccination (dpv) can be used to differentiate flocks with poor and better vaccine take. This study aimed to validate this approach for A20, another widely used ILT vaccine in Australia. In four meat chicken flocks vaccinated with A20 in water using two different water stabilization times (20 or 40 min), swabs from the trachea and choanal cleft and dust samples were collected at 0, 7, 14 and 21 dpv. ILTV GC detection in swabs and dust was highest at 7 dpv and at this time ILTV GC load in dust was strongly and positively associated with vaccine take in individual birds assessed by swab samples. Choanal cleft swabs provided significantly fewer ILTV positive results than paired tracheal swab samples but the level of ILTV GC detected was similar. Water stabilization time had only minor effects on vaccination response in favour of the shorter time. Location of dust collection had no effect on viral load measured in dust samples. Dust samples collected at 0 and 7 dpv can be used to assess the vaccination status of flocks.

Development of a quantitative risk assessment of bovine viral diarrhea virus and bovine herpesvirus-1 introduction in dairy cattle herds to improve biosecurity.

A quantitative risk assessment model was developed to estimate the annual probability of introducing bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) at the farm level through animal movements. Data from 2017 official animal movements, biosecurity questionnaires, scientific literature, and expert opinion from field veterinarians were taken into consideration for model input parameters. Purchasing or introducing cattle, rearing replacement heifers offsite, showing cattle at competitions, sharing transport vehicles with other herds, and transporting cattle in vehicles that have not been cleaned and disinfected were considered in the model. The annual probability of introducing BVDV or BoHV-1 through infected animals was very heterogeneous between farms. The median likelihoods of BVDV and BoHV-1introduction were 12 and 9%, respectively. Farms that purchased cattle from within their region (i.e., local movements) and shared transport with other farms had a higher probability for BVDV and BoHV-1 introduction. This model can be a useful tool to support decision-making on biosecurity measures that should be prioritized to reduce the probability of introduction of these 2 diseases in dairy herds.

Epidemiological performance and subsequent costs of different surveillance strategies to control bovine herpesvirus type 1 in dairy farms.

This study aimed at comparing the surveillance program of bovine herpesvirus type 1 (BHV1) as laid down by EU Decision 2004/558/EC and 2007/584/EC ('conventional design') with an alternative design. The alternative design was based on monthly bulk-milk testing, clinical surveillance and a risk-based component that involves testing of animals that are purchased from non-free cattle herds. Scenario-tree analyses were carried out to determine sensitivities of the surveillance system (and its components) and the monthly confidence of freedom on herd-level. Also, the expected costs per surveillance design and components thereof were calculated. Results showed that the conventional (EU) and alternative surveillance designs to obtain a BHV1-free status performed equally well in terms of sensitivity. However, total costs per cattle herd to obtain a free status were highest in the conventional design. In an endemic situation and with a within-herd design prevalence of 10%, the conventional design led to a varying probability of freedom ranging from 99.6% to 100% per month. With the alternative design, in this situation, a constant probability of freedom of >99.9% per month was found. In a disease-free situation, both designs performed equally well (probability of freedom >99.9% per month). The yearly costs per farm for monitoring the disease-free status decreased by approximately 25% in the alternative design. The alternative strategy based on monthly bulk-milk monitoring therefore was deemed most cost-effective. This study showed that the surveillance regime to attain and maintain a BHV1-free status as described by EU-legislation can be improved to reduce the monitoring costs without reduction of the system's sensitivity, given a within-herd design prevalence of 10%. The assessment of various surveillance designs could be highly useful to support decision-making towards a more risk-based approach of animal health surveillance.

Implementing a probabilistic definition of freedom from infection to facilitate trade of livestock: putting theory into praxis for the example of bovine herpes virus-1.

International trade of livestock and livestock products poses a significant potential threat for spread of diseases, and importing countries therefore often require that imported animals and products are free from certain pathogens. However, absolute freedom from infection cannot be documented, since all test protocols are imperfect and can lead to false-negative results. It is possible instead to estimate the "probability of freedom from infection" and its opposite, the probability of infection despite having a negative test result. These probabilities can be estimated based on a pre-defined target prevalence, known surveillance efforts in the target population and known test characteristics of any pre-export test. Here, calculations are demonstrated using the example of bovine herpes virus-1 (BoHV-1). In a population that recently became free of BoHV-1 without using vaccination, the probability of being infected of an animal randomly selected for trade is 800 per 1 million and this probability is reduced to 64 (95% probability interval PI 6-161) per 1 million when this animal is tested negatively prior to export with a gB-ELISA. In a population that recently became free of BoHV-1 using vaccination, the probability of being infected of an animal randomly selected for trade is 200 per 1 million, and this probability can be reduced to 63 (95% PI 42-87) when this animal is tested negatively prior to export with a gE-ELISA. Similar estimations can be made on a herd level when assumptions are made about the herd size and the intensity of the surveillance efforts. Subsequently, the overall probability for an importing country of importing at least 1 infected animal can be assessed by taking into account the trade volume. Definition of the acceptable level of risk, including the probability of false-negative results to occur, is part of risk management. Internationally harmonized target prevalence levels for the declaration of freedom from infection from selected pathogens provide a significant contribution to the facilitation of international trade of livestock and livestock products by allowing exporting countries to design tailor-made output-based surveillance programs, while providing equivalent guarantees regarding the probability of freedom from infection of the population. Combining this with an approach to assess the overall probability of introducing at least 1 infected animal into an importing country during a defined time interval will help importing countries to achieve their desired level of acceptable risk and will help to assess the equivalence of animal health and food safety standards between trading partners.

Equine coital exanthema and its potential economic implications for the equine industry.

Equine coital exanthema (ECE) caused by equid herpesvirus 3 (EHV-3) is a contagious venereal disease characterised by the formation of painful papules, vesicles, pustules and ulcers on the external genitalia of both mares and stallions. EHV-3 is an alphaherpesvirus that is distinct from the other equine herpesviruses and endemic in most horse breeding populations worldwide. The negative impacts of ECE on equine breeding enterprises are the forced, temporary disruption of mating activities of mares and stallions, the additional care and supportive treatment that is required for affected horses, and the risk of virus spread by either fresh or frozen semen as well as by artificial insemination and embryo transfer. Because there are no effective surveillance systems to report ECE, its true prevalence and economic impact are difficult to assess and are probably underestimated. The purpose of this review is to describe the recent advances in understanding of EHV-3 infections and to consider the economic consequences of ECE within the current context of the equine industry.

Assessment of viremia associated with experimental primary feline herpesvirus infection or presumed herpetic recrudescence in cats.

OBJECTIVE: To detect feline herpesvirus type 1 (FHV-1) in blood of cats undergoing experimental primary herpetic disease or with spontaneous disease presumed to be caused by FHV-1 reactivation. ANIMALS: 6 young specific-pathogen-free (SPF) cats and 34 adult cats from a shelter. PROCEDURES: Conjunctiva and nares of SPF cats were inoculated with FHV-1, and cats were monitored for 21 days. Periodically, blood was collected for CBC, serum biochemical analyses, and detection of FHV-1 DNA via PCR assay. For shelter cats, a conjunctival swab specimen was collected for FHV-1 PCR assay, and blood mononuclear cells were tested via virus isolation (with or without hydrocortisone) and FHV-1 PCR assay. RESULTS: All SPF cats developed clinical and clinicopathologic evidence of upper respiratory tract and ocular disease only. Via PCR assay, FHV-1 DNA was detected in blood of all SPF cats at least once between 2 and 15 days after inoculation. Feline herpesvirus type 1 DNA was detected in conjunctival swabs of 27 shelter cats; 25 had clinical signs of herpetic infection. However, virus was not isolated from mononuclear cell samples of any shelter cat regardless of passage number or whether hydrocortisone was present in the culture medium; FHV-1 DNA was not detected in any mononuclear cell sample collected from shelter cats. CONCLUSIONS AND CLINICAL RELEVANCE: A brief period of viremia occurred in cats undergoing primary herpetic disease but not in cats undergoing presumed recrudescent herpetic disease. Viremia may be important in the pathogenesis of primary herpetic disease but seems unlikely to be associated with recrudescent disease.

Pro and contra IBR-eradication.

Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections such as infectious rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV, balanoposthitis (IBP), and abortion. Despite of a pronounced immune response, the virus is never eliminated from an infected host but establishes life-long latency and may be reactivated at intervals. Europe has a long history of fighting against BoHV-1 infections, yet, only a small number of countries has achieved IBR-eradication. Therefore, it seemed appropriate to review the reasoning pro and contra such a task. Clearly, the goal can indeed be achieved as has been demonstrated by a number of European countries. However, detection and stamping out of seemingly healthy virus carriers is inevitable in the process. Unfortunately, the use of vaccines is only of temporary and limited value. Therefore, there are numerous considerations to be put forward against such plans, including the high costs, the great risks, and the unsatisfactory quality of tools. If either control or eradication of IBR is nonetheless a goal, then better vaccines are needed as well as better companion tests. Moreover, better tools for the characterization of viral isolates are required. Collaborative actions to gather viral strains from as many countries as possible for inclusion into a newly created clustering library would be most advantageous.

Yield and future issues of nucleic acid testing.

Despite the much lower actual yield than that estimated for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) nucleic acid testing (NAT)-only positives in the USA and Germany, look-back procedures have revealed that no HCV transmission has occurred in Germany since the introduction of NAT. This indicates sufficient sensitivity of the pool-PCR approach. The slow ramp-up of hepatitis B virus (HBV) however, may require a different approach. It has been shown in Germany that the pooling of samples followed by virus enrichment results in a significant yield. Single donation testing for HBV would not increase the yield, because virus enrichment from mini-pool results in a similar sensitivity to that of single donation testing. Both strategies may be useful for extending future NAT to HBV screening. New candidate viruses for NAT are Parvo B19 and hepatitis A virus (HAV) because of their extreme resistance to inactivation procedures. Their low pathogenicity and epidemiologic characteristics, however, make them candidate viruses only for pooled source plasma. The main future issues of NAT will be related to the automation of pooling, extraction and amplification as a single homogeneous process. Depending on the throughput, automated single donation NAT as demonstrated by the 'Tigris' system may be an option, as far as all transfusion-relevant viruses will be included. In the near future high throughput systems will rely on pooled donor samples, most probably in conjunction with efficient enrichment procedures. For these systems, automation of the extraction and amplification process will be one of the first steps. These procedures will also limitthe costs of NAT and keep it available for use with future candidate viruses.

[Risk and economics of disease introduction to dairy farms]. / Risico en economie van insleep van ziekten op melkveebedrijven.

A more closed farming system will enhance the success of disease eradication programmes, because the introduction or re-introduction of infectious diseases is less likely. The objective of the study was to obtain input for the development of an on-farm decision support model to calculate the economic consequences of a more closed farming system. The input was based on bovine herpesvirus 1 (BHV1), since there were numerous data on this disease, but a more closed farming system will prevent introduction of other diseases as well (i.e. bovine virus diarrhoea virus (BVDV), L. hardjo, and S. dublin). Direct animal contacts, such as purchase of cattle, participation in cattle shows, and cattle that escape and mingle with other cattle, were found to be important risk factors for the introduction of BHV1. Furthermore, the use of protective farm clothing was found to be an important preventive factor. The effect of an IBR outbreak at an IBR-free farm on milk production caused limited losses of on average 0.9 kg per cow per day during 9 weeks, but the variability was high (95% CI 0-2 kg). Nine percent of Dutch IBR-free dairy farms that were also at risk for BVDV, L. hardjo or S. dublin had one introduction per year of one of these four diseases. All these results were incorporated in the economic model. Management measures to reduce the probability of introduction of BHV1, the costs of these measures, and the risk reduction after these measures were obtained from other sources. The calculations showed that the implementation of a more closed system will be profitable for most farms. The profitability will increase when a farm is at risk for more diseases, but will decrease when farms are limited in their facilities to rear replacement heifers or when a large proportion of pasture adjoins pasture of other cattle farms.

[Integrated disease control in dairy herds. A case study from the veterinarians' viewpoint]. / Integrale dierziektebestrijding op melkveebedrijven. Visie van rundveedierenartsen op een casus.

Integrated control of bovine virus diarrhoea virus, bovine herpesvirus-1, Leptospira interrogans serovar hardjo subtype hardjobovis, Mycobacterium avium subsp. paratuberculosis, and Salmonella dublin in dairy herds may provide economic benefits superior to those obtained by sequential disease control, because, among other things, it allows optimization of voluntary culling. However, in practice there are no adequate instruments to establish priorities in voluntary culling. Therefore, in this study the priorities in decision-making for voluntary culling of infected cattle, as indicated by more than 300 cattle veterinarians, were analysed. Based on our results and supplementary considerations, the priorities for voluntary culling in the Netherlands can be ranked as: 1st. cull S. dublin carriers, 2nd. cull persistently infected BVDV carriers, 3rd. cull paratuberculosis faecal culture positive cattle and their last offspring, 4th. cull, in paratuberculosis infected herds, paratuberculosis ELISA positive cattle and their last offspring and cull, in low prevalence herds, BHV1 gE-positive cattle, and 5th. cull leptospirosis seropositive cattle. Since this ranking was based on one case study only, other priorities may prevail in other herds.

[Outbreak of bovine virus diarrhea on Dutch dairy farms induced by a bovine herpesvirus 1 marker vaccine contaminated with bovine virus diarrhea virus type 2]. / Uitbraak van bovine virus diarree op Nederlandse rundveebedrijven na vaccinatie met een met BVDV type 2 gecontamineerd BHV1 markervaccin.

On 23 February 1999, the Dutch Animal Health Service advised all Dutch veterinary practices to postpone vaccination against bovine herpesvirus 1 (BHV1) immediately. The day before severe disease problems were diagnosed on four dairy farms after vaccination with the same batch of BHV1 marker vaccine. Using monoclonal antibodies, bovine virus diarrhoea virus (BVDV) type 2 was found in the vaccine batch. This paper describes an outbreak of BVDV type 2 infection caused by the use of a batch of modified live BHV1 marker vaccine contaminated with BDVD. Sources of information used were reports of farm visits, minutes of meetings, laboratory results, and oral communications from the people involved. The first symptoms of disease were observed on average six days after vaccination. Morbidity was high on 11 of the 12 farms. On five farms more than 70% of the animals became ill, while on one farm no symptoms could be detected. During the first week after vaccination, feed intake and milk production decreased. During the second week, some animals became clinically diseased having nasal discharge, fever, and diarrhoea. At the end of the second week and at the start of the third week, the number of diseased animals increased rapidly, the symptoms became more severe, and some animals died. Mortality varied among herds. Necropsy most often revealed erosions and ulcers of the mucosa of the digestive tract. In addition, degeneration of the liver, hyperaemia of the abomasum, and swollen mesenterial lymph nodes and swollen spleen were found. On 11 of the 12 farms all animals were culled between 32 and 68 days after vaccination after an agreement was reached with the manufacturer of the vaccine. This was the third outbreak of BVD in cattle after administration of a contaminated vaccine in the Netherlands. The possibilities to prevent contamination of a vaccine as a consequence of infection of fetal calf serum with BVDV are discussed. Improvement of controls to prevent contamination before and during vaccine production, and improvement of the monitoring of side-effects is necessary.

Evaluating control strategies for outbreaks in BHV1-free areas using stochastic and spatial simulation.

Several countries within the EU have successfully eradicated bovine herpesvirus type I (BHV1), while others are still making efforts to eradicate the virus. Reintroduction of the virus into BHV1-free areas can lead to major outbreaks - thereby causing severe economic losses. To give decision-makers more insight into the risk and economic consequences of BHV1 reintroduction and into the effectiveness of various control strategies, we developed the simulation model InterIBR. InterIBR is a dynamic model that takes into account risk and uncertainty and the geographic location of individual farms. Simulation of a BHV1-outbreak in the Netherlands starts with introduction of the virus on a predefined farm type, after which both within-farm and between-farm transmission are simulated. Monitoring and control measures are implemented to simulate detection of the infection and subsequent control. Economic consequences included in this study are related to losses due to infection and costs of control. In the simulated basic control strategy, dairy farms are monitored by monthly bulk-milk tests and miscellaneous farms are monitored by half-yearly serological tests. After detection, movement-control measures apply, animal contacts are traced and neighbour farms are put on surveillance. Given current assumptions on transmission dynamics, we conclude that a strategy with either rapid removal or vaccination of infected cattle does not reduce the number of infected farms compared to this basic strategy - but will cost more to control. Farm type with first introduction of BHV1 has a considerable impact on the expected number of secondarily infected farms and total costs. To limit the number of infected farms and total costs due to outbreaks, we suggest intensifying the monitoring program on farms with a high frequency of cattle trade, and monthly bulk-milk testing on dairy farms.

Assessment of the immune response to duck plague vaccinations.

An experiment was conducted to assess the immune responses of ducks to duck plague (DP) vaccinations employing one commercial and one laboratory-adapted (LA) DP vaccines. Virus neutralisation and leucocyte migration-inhibition tests were conducted at regular intervals before and after vaccinations. Similarly, ducks in vaccinated and control groups were subjected to challenge infection with virulent DP virus. The commercial vaccine yielded a poor immune response and partial protection on challenge whereas satisfactory responses were obtained in ducks receiving two doses of LA vaccine. The humoral as well as cellular factors were stimulated indicating possible involvement of both the immune responses in the protection from duck plague.

Assessment of antigenicity and genetic variation of glycoprotein B of murine cytomegalovirus.

An analysis of linear antibody-binding sites of the glycoprotein B (gB) molecule of murine cytomegalovirus (MCMV) and of genetic variation within these regions was performed. To achieve this, a series of overlapping fragments spanning the entire coding sequence of the gB gene of the K181 strain of MCMV was expressed in E. coli as fusion proteins with glutathione S-transferase (GST) using the pGEX expression system. Four antibody-binding regions were mapped to locations spanning amino acid residues 17-79 (BS), 155-278 (BE2), 809-926 (SS) and 347-508 (BB and EE), based on reactivity in Western blot analysis of GST-gB fusion proteins with murine polyclonal antiserum raised against MCMV. Only the antibody-binding region BE2 (155-278) elicited an antiserum that exhibited complement-dependent neutralizing activity, and immunization of mice with the fusion protein BE2 led to moderate but significant reductions in the level of MCMV replication in the spleen. Polyclonal antisera raised against the GST-gB fusion proteins detected purified virion proteins of 105 kDa (anti-BS and anti-BE2) and 52 kDa (anti-SS) and are therefore likely to recognize the N-terminal and C-terminal portions of the gB molecule, respectively. The antibody-binding region within amino acid residues 17-79 was found to be MCMV strain-specific, whereas antibody-binding regions within residues 155-278 and 809-926 were found to be conserved among MCMV field isolates. Comparative sequence analysis of the corresponding regions of MCMV gB revealed a level and extent of sequence of sequence heterogeneity consistent with these findings.

The significance of the blood-borne viruses: blood banking and transfusion medicine.

Most of the blood-borne infections that have held our attention during the last half of this century have been well characterized. Although HIV and the hepatitis viruses have enormous world-wide public health implications, there has been considerable success in their prevention of transmission by transfusion. The technology is available to treat and eliminate from virtually all non-cellular blood products the transmission of disease caused by those viruses for which we have had the greatest concern. However, for the cellular blood products the basic methods of prevention continue to be imperfect: donor selection and viral serological testing. The significance of the transmission of blood-borne agents by these products depends upon the frequency of the agent in the donor population and the serological screening performed. There is a marked degree of variation in frequency of these infections, dependent upon geography, living conditions, and life style. Data on the frequency of transfusion-transmitted disease are meagre and usually based upon indirect estimates. In the United States the frequency of the transmission of HIV by cellular blood products is estimated to be 1:125,000 products transfused. A similar estimate for the transmission of hepatitis is 1:200 products transfused. For the developing countries, some of which experience the highest rates of hepatitis and HIV infection in their populations, data on the frequency of transfusion transmission are not generally available. In recent years, new evidence has stimulated interest in a few transfusion-transmissible diseases that, although uncommon from the public health perspective, have both real and potential transfusion impacts for the use of plasma and plasma derivatives as well as cellular products.(ABSTRACT TRUNCATED AT 250 WORDS)

Whither immunization against viral infections?

Economic and social considerations with respect to the infectious diseases demand increased application of preventive measures. Vaccines provide high benefit at low cost and low risk. Past vaccines have emphasized use of live attenuated, or killed whole, or fractionated organisms. Future vaccines will involve recombinant and synthetic antigens, with emphasis on control of many different infections with single polyvalent vaccines directed against individual epitopes rather than complex antigens. Heightened interest in preventive medicine is evident among physicians, aided by the activities of the World Health Organization and governments, and individual academic and public health initiatives. An overview of the past, present, and future with respect to technological possibilities and other practical considerations for vaccines is presented.