Probability of and risk factors for introduction of infectious diseases into Dutch SPF dairy farms: a cohort study

A 2-year cohort study was conducted to investigate the probability of disease introduction into Dutch dairy farms. The farms were tested regularly for diseases and were visited biannually to collect management data. Ninety-five specific pathogen-free (SPF) dairy farms were selected from a database of bovine herpesvirus type 1 (BHV1)-free farms to study the probability of, and risk factors for, introduction of BHV1, bovine viral diarrhoea virus (BVDV), Salmonella enterica subsp. enterica serotype Dublin (S. dublin), and Leptospira interrogans serovar hardjo (L. hardjo).Although most of the 95 SPF farms had a low risk on introduction of infectious diseases, one disease was introduced into 12 farms and two diseases were introduced into one farm. Three farms experienced an outbreak of BHV1, one farm an outbreak of L. hardjo, two farms BVDV, six farms S. dublin, and one farm both BHV1 and S. dublin. The total incidence rate was 0.09 (0.06-0.12) per herd-year at risk. The results suggest that the "non-outbreak" farms were significantly more closed than the "outbreak" farms. Direct animal contacts with other cattle should be avoided and professional visitors should be instructed to wear protective clothing before handling cattle.     

Risk factors for introduction of BHV1 into BHV1-free Dutch dairy farms: a case-control study

In May 1998, a compulsory eradication programme for BHV1 started in the Netherlands. In December 1999 approximately 24% of Dutch dairy farms were certified BHV1-free (Animal Health Service (AHS)). Ninety-three certified BHV1-free dairy farms participated in a cohort study that investigated the probability of introduction of infectious diseases. The probability of introduction of BHV1 was determined from March 1997 until April 1999. Ninety of these farms remained BHV1-free and could be used as control farms. From January 1997 until March 1998, BHV1 was introduced into 41 BHV1-free dairy farms in the Netherlands (case farms). Management data were collected for both cases and controls and were complete for 37 case farms and 82 control farms. For small data sets and for data in which both low and high frequencies were expected in the contingency tables, the asymptotic methods were unreliable. Our data set clearly resembled such a data set; the risk factors were rare events because the BHV1-free farms were closed farms on which few direct animal contacts occurred. Therefore, an exact stratified modelling approach was most suitable for the data. The study showed that dairy farms should prevent cattle from escaping or mingling with other cattle and that professional visitors should always wear protective farm clothing.     

Comparison of performance of dairy herds that were or were not vaccinated with a bovine herpes virus 1 marker vaccine in 1998

This study analysed the effects of the use of bovine herpesvirus 1 (BHV1) marker vaccine on the performance of dairy cattle. In Spring of 1999, vaccination of 12 herds with the BHV1 marker vaccine resulted in severe animal health problems and mortality. The vaccines used on these farms were all from a batch that appeared to be contaminated with bovine virus diarrhoea virus type 2. This led to a general call to farmers and veterinary practitioners to report side-effects of this vaccine. As a result, more than 7000 farmers reported symptoms. The information was obtained by means of a questionnaire; there was no control group. To determine the effects of the use of the marker vaccine, it was necessary to perform a study based on objectively acquired information. The information collected by the Royal Dutch Cattle Syndicate and the office of Identification and Registration was complied into herd indices on production, udder health, reproduction, and culling. Two groups of dairy farms that had used the BHV1 marker vaccine (attenuated and inactivated vaccine) were compared with farms that were certified BHV1-free. The analyses were performed based on intra-herd comparisons, meaning that per herd each index calculated over a certain period of time after the use of the marker vaccine was compared to a similar period of time prior to the use of the marker vaccine. A total of 144 comparisons were made. Seven comparisons were statistically significant. In two comparisons, the results were in favour of the BHV1-free farms and in five comparisons, the result were in favour of the vaccinated farms. Thus use of the BHV1 marker vaccine could not be proven to affect herd performance. The sensitivity of the tests was very high, so with a high level of probability even very small differences in indices between groups would have been detected.     

Eradication of infectious bovine rhinotracheitis in Switzerland: review and prospects

Ten years after the first outbreak of infectious bovine rhinotracheitis (IBR) in Swiss dairy cows, the national cattle herd is almost free from infection with IBR virus (bovine herpesvirus 1, BHV 1). The national programme for the eradication of IBR was divided into four phases: (1) Prevention of transmission of the infection by restrictions on trade of bovines and assessment of the prevalence of cattle with antibodies to BHV 1. (2) Slaughtering animals with antibodies to BHV 1 in order to eradicate BHV 1 from breeding herds. (3) Detection and eradication of further BHV 1 reservoirs (e.g. fattening cattle). (4) Monitoring programme and legal actions in order to maintain the favourable situation. Approximately 50,000 animals were slaughtered in the course of the eradication of IBR. The total costs amounted to approximately SFr. 110,000,000 over 10 years. The costs for maintaining the situation are estimated at approximately SFr. 5,000,000 per annum.     

Characteristics of foot and mouth disease virus in Taiwan

Since March 1997 two strains of foot and mouth disease (FMD) virus have found their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals by natural route. The epidemic spread over the whole region of Taiwan within two months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only species infected and those infected cattle did not develop pathological lesions. Seroconversions of serum neutralization antibody and on non-structural protein (NSP) antibodies were the best indicators for infection in non-vaccinated herds. The infected animals, however, excreted infectious levels of virus to infect new hosts. Based on the detection of the specific antibody to FMD virus, and virus isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese yellow cattle located in Kinmen and Taiwan were declared to have been infected. During the period of January to March 2000, however, five outbreaks caused by FMD virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan. The infected species included goats, Chinese yellow cattle and dairy cattle. Those outbreaks have caused high mortality in goat kids under two weeks old and also developed typical clinical signs of infection in dairy cattle.     

Evaluation of surveillance strategies for bovine brucellosis in Japan using a simulation model

Bovine brucellosis is caused by Brucella abortus and induces abortions in female cattle, with other cattle at risk of infection from the aborted fetus or contaminated placenta. In Japan, the number of cases has dramatically reduced due to national surveillance and eradication strategies. Bovine brucellosis is now believed to be eradicated in Japan. Here, we examine the surveillance strategies currently in place for early detection of infected cattle in the event of a future reintroduction of the disease. We compared current serological surveillance for the dairy population with bulk-milk surveillance and abortion surveillance, and used time to detection as the main criterion of surveillance efficacy. A stochastic individual-based model (IBM) was developed to simulate disease transmission within and between farms. Using outputs from the transmission model, a comparison of surveillance strategies was simulated. For evaluation of the robustness of the parameter values used in the transmission model, a sensitivity analysis was conducted. For the purpose of evaluating the direct costs of each surveillance strategy, the annual number of samples to be tested and the annual number of farms to be visited were estimated. Our results indicated that current serological surveillance with 60-month test intervals is not effective enough for rapid detection of a brucellosis outbreak. Bulk-milk surveillance appeared the most effective method based on the early detection of infected cows and a reduced number of samples required. The time to detection for abortion surveillance was greater than that of bulk-milk surveillance but varied widely depending on the reported ratio of abortions. Results from the surveillance model were consistent when alternative scenarios were applied to the transmission model. Although our model cannot exactly replicate an actual brucellosis outbreak, or the results of surveillance, our results may help decision-makers to choose the most effective surveillance strategy.     

Epidemiologically non-feasible singleton reactors at the final stage of BoHV1 eradication: Serological evidence of BoHV2 cross-reactivity

A voluntary marker-independent Bovine Herpesvirus 1 (BoHV1) eradication program started in 1986; in 1998 it changed to a compulsory one. Certification of free regions in European member states is based on Article 10 of directive 64/432/EEC. According to this rule Bavaria is listed as free of BoHV1 since October 2011. Surveillance of BoHV1-free dairy cattle farms is currently performed with quarterly bulk-milk testing. Non-negative bulk-milk results must be confirmed by blood tests in cattle older than nine months. An increased regional rate of non-negative bulk-milk samples and the subsequent detection of epidemiologically non-feasible singleton BoHV1-reactors by analysis of blood were observed at the final stage of eradication in southwest Bavaria. Nineteen case farms (734 animals) defined by singleton reactors born at least two years after certification of the farms as BoHV1-free, 23 negative control (NC) farms (NC I: 321 animals) from the same region, 11 NC-farms (NC II: 423 animals) from an already-certified Article 10 region in northeast Bavaria and two BoHV1-infected farms (264 animals) were analysed using BoHV1-, BoHV2- and Feline Herpesvirus 1 (FeHV1)-neutralisation tests (NTs), and three commercially available ELISAs supplied by Idexx Laboratories, B.V., The Netherlands: the CHEKIT? Trachitest 2nd Gen. test for milk or serum (Trachitest), Herdchek? gB- (gB-ELISA) and Herdchek? gE-ELISA (gE-ELISA). Significantly increased levels of BoHV2 antibodies were observed on case farms compared to NC I or II farms. Additionally, reactivity by gB-ELISA and the Trachitest was significantly increased for animals with BoHV2 neutralising antibodies. Singleton BoHV1-reactors tested negative by gE-ELISA even if an elevated cut-off of 0.95±0.05 was applied. At this cut-off, the gE-ELISA was as sensitive and specific as the gB-ELISA. Comparative titration of milk samples from seropositive animals from a BoHV1-infected dairy cattle farm and from singleton BoHV1-reactors performed in CHEKIT? Trachitest 2nd Gen. Milk revealed that the slopes of both groups were distinct; therefore, optimised cut-offs for bulk-milk testing to exclude singleton BoHV1-reactors are proposed.     

Adaptive conjoint analysis to determine perceived risk factors of farmers, veterinarians and AI technicians for introduction of BHV1 to dairy farms

A study was carried out to determine the possibility of a more-closed farming system for (Dutch) dairy farms. The objective of the study was to provide effective and economically profitable management advice for improving the animal-health status of farms. Management measures will only be successfully applied if supported by farmers and their advisors (such as veterinarians). Therefore, the perception of farmers and advisors of the importance of various risk factors for the introduction of diseases to a farm was determined by using bovine herpes virus type 1 (BHV1) as an example.

As part of the study, an evening-long workshop was organized and run thrice. In total, 49 farmers, veterinarians and AI technicians participated in these workshops. The computerized questionnaire technique was based on adaptive conjoint analysis (ACA). ACA has the advantage that participants can work with a large number of risk factors in a relatively short period of time. Another advantage of ACA (compared with standard questionnaires) is that the answers from each participant can be checked with regard to consistency with respect to the importance assigned to them. Data from participants with inconsistent responses can be excluded from further analyses. The results of the ACA interview were compared with the risk factors reported in the literature as being associated with BHV1 status (e.g. purchase of cattle, participation in cattle shows) and with farmers' actual management to prevent the introduction of diseases.

The workshop participants were all operating in the dairy sector and they seemed well aware of the risk of direct animal contacts for the introduction of BHV1. Farmers thought visitors to be more risky than did AI technicians and (especially) veterinarians. Farmers who purchased cattle or participated in cattle shows were of the opinion that the risks of direct animal contacts were more important than did farmers who were not involved in those practices. Farmers whose farms were BHV1-positive (and participated in cattle shows more often) thought the risk of participation smaller than did farmers with BHV1-negative farms.     

BHV-1 eradication program in Bavaria: a marker-independent strategy

In Bavaria a BHV-1 eradication program was initiated in 1986 and was changed to a compulsory program in 1998. The eradication success increased progressively from < 50% in 1986 to 87% of the farms in 2002. BHV 1-free farms are controlled by bulk milk serology twice a year along with blood serology in animals that are negative but from herds where positive field virus infected animals are present. All serological tests are performed with an indirect ELISA test, all positive results are confirmed by a gB ELISA. Currently about 100.000 virus infected cattle are in Bavarian herds, approximately 80% of these animals are in heavily infected herds (> 10 infected animals). These herds comprise about 5% of all Bavarian herds. The eradication of the virus in these heavily infected herds is the most diifficult, whereas the prevention of new infections appears controllable. In this review current problems in BHV1 eradication are named and possible improvements are discussed.     

Bovine herpesvirus 1 (BHV1) seroprevalence in the breeding cattle population of the Veneto region: prospects for the implementation of a control programme

The results of a serological survey for bovine herpes virus (BHV1) antibodies in the breeding cattle population of the Veneto region are presented. The data do not support the hypothesis of an high prevalence of BHV1; on farms where vaccination was not carried out most animals were seronegative, and seropositive animals were generally older. Therefore, when drawing up the guidelines for a control programme, systematic immunization (with glycoprotein E-deleted vaccines) should be restricted only to farms with a high prevalence of BHV1 antibodies and/or with a high risk of BHV1 occurrence; in most unvaccinated farms a 'test and removal' policy appears to be more appropriate in order to rapidly eradicate BHV1 from the entire stock.     

Salmonella Dublin infection in Queensland dairy cattle

Objective: To investigate the presence of Salmonella Dublin in Queensland cattle.
Design: An epidemiological study using diagnostic laboratory information and farm records.
Procedure: Outbreaks of gastroenteritis or pneumonia in calves, and abortions and enteritis in cows were routinely investigated for the presence of salmonellae. Where S Dublin was isolated, attempts were made to gather further epidemiological information.
Results: Prior to 1983 only two outbreaks of S Dublin have been recorded in Queensland dairy cattle. In 1983 S Dublin abortions were diagnosed in dairy heifers introduced from southern Australia to south-east Queensland. Sampling indicated that at least 10% of the 500 introduced heifers were faecal excretors of S Dublin. On 3 of the 7 farms from which S Dublin was recorded, infection spread to other cattle that were in contact. From February 1985 to February 1996, 29 outbreaks of S Dublin in cattle occurred on 29 farms (28 in south east Queensland and 1 in north Queensland). Calves were primarily affected. Continuing outbreaks were confirmed on only 4 of these 29 farms. On 15 farms S Dublin infections were associated with the purchase of infected calves or cows, while another farm adjoined 2 previously infected farms. No source of S Dublin was evident for the other 13 farms, where histories were often inadequate.
Conclusion: There has been a marked increase in S Dublin outbreaks in Queensland dairy cattle since 1983. Introduction of S Dublin carrier and aborting dairy heifers from southern Australia, where S Dublin is not uncommon, was associated with the initial outbreaks.     

Quantification of the transmission of bovine herpesvirus 1 among red deer (Cervus elaphus) under experimental conditions

Bovine herpesvirus 1 (BHV1) is endemically present in a cattle population that lives in a nature reserve in the Netherlands. Red deer (Cervus elaphus), living in the same nature reserve, can come into contact with the BHV1-infected cattle and could then become infected with BHV1. For the eradication of BHV1 in cattle, it is, therefore, important to know whether red deer alone can play a role in the transmission of BHV1. For that reason, we quantified the transmission of BHV1 among farmed red deer under experimental conditions. Two groups of ten animals were formed. In each group, five of these animals were inoculated with BHV1 and the other five served as contact animals. Three inoculated animals in each transmission experiment became infected and none of the contact animals became infected. The one-sided 95% confidence interval for R [0.0-0.94] showed that limited transmission might occur among red deer. Based on these results, we would expect only minor outbreaks of BHV1 to occur in red deer populations. We concluded that BHV1 will probably not survive longer than a few decades (several times the mean deer lifetime) in red deer populations. Consequently, it is not necessary for the eradication of BHV1 in cattle to eradicate BHV1 in red deer populations as well.     

Risk factors for the introduction of high pathogenicity Avian Influenza virus into poultry farms during the epidemic in the Netherlands in 2003

An epidemic of high pathogenicity Avian Influenza (HPAI) occurred in the Netherlands in 2003. A census survey of 173 infected and 401 uninfected commercial poultry farms was carried out to identify factors associated with the introduction of the HPAI virus into poultry farms. Data on farm size, production characteristics, type of housing, presence of cattle and pigs were gathered by the National Inspection Service for Livestock and Meat from all farms included in this study. For each risk factor (RF) available for analysis, the Mantel-Haenszel odds ratio was calculated (stratified on farm size and housing type). We found an increased risk of HPAI virus introduction in layer finisher type poultry: OR = 2.05 (95% confidence interval, CI = 1.29-3.27). An explanation for this increased risk is the high number of contacts between these farms, especially via cardboard egg trays used for removal of eggs during the epidemic. Our analysis did not indicate significant differences between the infected and uninfected farms with regard to housing type, presence of cattle or pigs. Since layer finisher type farms are assumed to be at higher risk for HPAI virus introduction, more specific control measures might be applied in future outbreaks.     

Integrated disease control in dairy herds. A case study from the veterinarians' viewpoint

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.     

Experiences with the eradication of the bovine herpes virus 1 in Lower Saxony

In this paper first the general cascade of animal disease eradication from the voluntary control programme up to culling of infected animals is described. Afterwards the development of the eradication of Bovine Herpes Virus in Lower Saxony is illustrated. Obvious the number of farms which are not eradicating decreases since the testing on BHV1 is obligate in Germany. In 2004 60% of the cattle holdings were free from BHV1. At least the measures which will be taken in Lower Saxony to increase the success of eradication are explained.     

A rapid and sensitive PCR-based diagnostic assay to detect bovine herpesvirus 1 in routine diagnostic submissions

We describe a rapid, sensitive and specific polymerase chain reaction (PCR) assay for the detection of BHV1 DNA in a range of routine diagnostic submissions without the need for prior virus isolation. The assay, which is based on the selected amplification of a portion of the viral tk gene, detected both BHV1.1 and BHV1.2 subtypes in a panel of 15 characterised field isolates, and its sensitivity was estimated to be <0.125 TCID(50). BHV2, alcephaline herpesvirus, BHV4, equine herpesvirus 1 (EHV1), EHV4 and pseudorabies virus were not detected confirming the specificity of the assay. One hundred and five diagnostic submissions, including tissues, nasal secretions and nasal swabs were taken from cattle with respiratory disease and tested using the routine methods of virus isolation (VI) and the fluorescent antibody test (FAT), and the results were compared with those obtained by PCR. The PCR assay detected BHV1 DNA in all samples that were positive by VI. BHV1 DNA was also detectable by PCR in raw and extended semen samples at a sensitivity of 1 TCID(50) per 50microl. The assay also detected BHV5, permitting differentiation between it and BHV1 by virtue of the size of the amplified PCR product. The PCR assay is more sensitive and independent of sample quality than either virus isolation or FAT, and it is faster than virus isolation. The sample preparation method is simple with few steps involved. There are no extra post-amplification blotting/hybridisation steps and the assay is not based on a nested PCR strategy that might otherwise exacerbate the problem of oversensitivity/contamination in the routine use of such a test in a diagnostic laboratory. This assay would permit discrimination between those animals naturally infected with wild type BHV1 and those vaccinated with tk-BHV1 strains.     

Epidemiological and financial considerations for the control of Neospora caninum on Swiss dairy farms

Neospora caninum is widely recognized as one of the most important abortifacients in cattle and causes substantial financial losses to bovine livestock production. This study aimed to calculate the losses caused by N. caninum on Swiss dairy farms and to evaluate the efficacy and profitability of the control strategies culling, not breeding replacements and chemotherapy of calves on farm level. Three different farm sizes with high, medium and low herd prevalences were defined. Epidemiological and financial models were used to simulate the effect of control strategies on the prevalence over time and to perform a cost-benefit analysis. The median annual losses on farm level ranged between CHF 3094.- (= Euro 1875; 60 dairy cattle, high prevalence) and CHF 134.- (= Euro 81; 15 dairy cattle, low prevalence). Culling of animals that had any abortion or a N. caninum abortion, or not breeding replacements from such animals, respectively, were neither effective nor profitable. Only the strategy "not breeding replacements from N. caninum seropositive cows" on farms with a high prevalence was financially attractive. The strategy "chemotherapy of calves" should be re-evaluated as soon as new data regarding the efficacy of treatment and a corresponding protocol have been scientifically validated.     

Identification of an introduced bovine herpesvirus type 1 strain in a closed dairy herd by experimental virus reactivation followed by DNA restriction enzyme analysis

In a closed dairy herd in the province of Utrecht in 1995, nine replacement heifers were erroneously intramuscularly vaccinated with Tracherine, a live virus IBR vaccine. More than 18 months later, serology of the herd revealed that a large part of the herd had developed an antibody response towards BHV1 (62 of 87 animals). To investigate whether Tracherine had recirculated on the farm, four BHV1 antibody positive animals, of which two had been vaccinated with Tracherine, were treated with corticosteroids to reactivate latent BHV1. Two virus isolates were obtained and subsequently analysed by resctriction enzyme analysis. Both isolates were identified as BHV1.1 subtypes. One of the isolates was clearly distinct from Tracherine and was most likely a BHV1 field virus. A BHV1 field virus was most likely introduced into the farm even though the herd was closed, the animals had not been in contact with other cattle, and preventive hygienic measures had been implemented. There was no indication that Tracherine had recirculated.     

The detection of bovine herpesvirus type 1 (BHV 1) using an intradermal test. I. Field studies

An intradermal test (delayed hypersensitivity test) for the diagnosis of BHV1 infection was evaluated in 791 cattle of 16 dairy farms. The skin reactions were compared with the results of serological examinations using a commercial BHV1 ELISA kit (Trachitest). As antigen concentrated, purified and inactivated BHV1 was used. The skin reaction (increase of the skin fold thickness) was used for the interpretation of test results. The best results were obtained with the control of the skin reaction on the third day after injection of the antigen. From 393 serologically BHV1 negative cattle with an age of more than 6 months 391 (99.5%) had a skin reaction up to 1.0 mm and 2 animals (0.5%) had a reaction of 1.3 and 1.9 mm, respectively. The mean increase of skin fold thickness was 0.2 mm. Out of 291 serologically BHV1 positive cattle with an age of more than 6 months 270 had antibodies from natural infection and, partially, from additional vaccination with inactivated BHV1 vaccine. 266 (98.5%) of these animals showed a skin reaction of more than 2.0 mm, in 3 animals (1.1%) a skin reaction up to 1.0 mm was observed and 1 animal (0.4%) had a reaction of 2.0 mm. The mean increase of the skin fold thickness was 6.3 mm. 21 animals had BHV1 antibodies only because of vaccination with inactivated BHV1 vaccine. Only 4 animals had a skin reaction of more than 2.0 mm. Among 107 animals with an age up to 6 months 30 were serologically BHV1 positive and 77 were BHV1 negative. In all animals the skin reaction was less than 1.0 mm, the mean was 0.2 mm.     

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

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.