Gerdien van Schaik

Age at which dairy cattle become Mycobacterium avium subsp. paratuberculosis faecal culture positive.

Age at which cattle become faecal culture positive for Mycobacterium avium subsp. paratuberculosis (Map) can be used as a proxy parameter for age at onset of faecal shedding, which is an important parameter in the control of Map in cattle herds. To investigate the age at becoming faecal culture positive, survival analysis methods were applied. The analyses were carried out on asynchronous interval censored data of faecal culture results of samples collected from 18,979 female Holstein-Frisian cattle in 353 Dutch herds between 1996 and 2002. The data were analysed with a Weibull proportional hazards model. The results indicate that the distribution of age at onset of faecal shedding in Holstein-Frisian dairy cattle in infected herds is associated with the within-herd prevalence. In higher classes of apparent prevalence, cattle started to shed Map at younger age on average. In herds with an apparent prevalence <0.05, 0.05-0.1, 0.1-0.2 and ≥0.2, the proportion (95% CI) of cattle with onset of faecal shedding before 2 years of age was estimated at 1% (0.5%; 2%), 4% (3%; 5%), 8% (5%; 10%) and 20% (11%; 32%), respectively. This study indicates that a considerable proportion of young stock is shedding Map, especially in high prevalence herds. Therefore, infectious young stock should be a major concern in the control of paratuberculosis.

Inferences about the transmission of Schmallenberg virus within and between farms

In the summer of 2011 Schmallenberg virus (SBV), a Culicoides-borne orthobunyavirus, emerged in Germany and The Netherlands and subsequently spread across much of Europe. To draw inferences about the transmission of SBV we have developed two models to describe its spread within and between farms. The within-farm model was fitted to seroprevalence data for cattle and sheep farms in Belgium and The Netherlands, with parameters estimated using approximate Bayesian computation. Despite the short duration of viraemia in cattle and sheep (mean of 3–4 days) the within-farm seroprevalence can reach high levels (mean within-herd seroprevalence >80%), largely because the probability of transmission from host to vector is high (14%) and SBV is able to replicate quickly (0.03 per day-degree) and at relatively low temperatures (threshold for replication: 12.3 °C). Parameter estimates from the within-farm model were then used in a separate between-farm model to simulate the regional spread of SBV. This showed that the rapid spread of SBV at a regional level is primarily a consequence of the high probability of transmission from host to vector and the temperature requirements for virus replication. Our results, obtained for a region of the UK in a typical year with regard to animal movements, indicate that there is no need to invoke additional transmission mechanisms to explain the observed patterns of rapid spread of SBV in Europe. Moreover, the imposition of movement restrictions, even a total movement ban, has little effect on the spread of SBV at this scale.

Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study

Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.

Risk factors for malformations and impact on reproductive performance and mortality rates of Schmallenberg virus in sheep flocks in the Netherlands.

In Northwestern Europe, an epizootic outbreak of congenital malformations in newborn lambs due to infection with Schmallenberg virus (SBV) started at the end of 2011. The objectives of this study were to describe clinical symptoms of SBV infection, the effect of infection on mortality rates, and reproductive performance in sheep, as well as to identify and quantify flock level risk factors for SBV infections resulting in malformations in newborn lambs. A case-control study design was used, with 93 case flocks that had notified malformed lambs and 84 control flocks with no such lambs. Overall animal seroprevalence in case flocks was estimated at 82.0% (95% CI: 74.3–87.8), and was not significantly different from the prevalence in control flocks being 76.4% (95% CI: 67.2–83.6). The percentages of stillborn lambs or lambs that died before weaning, repeat breeders, and lambs with abnormal suckling behaviour were significantly higher in case flocks compared to control flocks. However, effect of SBV infection on mortality rates and reproductive performance seemed to be limited. Multivariable analysis showed that sheep flocks with an early start of the mating season, i.e. before August 2011 (OR = 33.1; 95% CI: 10.0–109.8) and in August 2011 (OR = 8.2; 95% CI: 2.7–24.6) had increased odds of malformations in newborn lambs caused by SBV compared to sheep flocks with a start of the mating season in October 2011. Other flock-level risk factors for malformations in newborn lambs were purchase of silage (OR 5.0; 95% CI: 1.7–15.0) and flocks with one or more dogs (OR = 3.3; 95% CI: 1.3–8.3). Delaying mating until October could be a potential preventive measure for naïve animals to reduce SBV induced losses. As duration of immunity after infection with SBV is expected to last for several years, future SBV induced congenital malformations are mainly expected in offspring of early mated seronegative animals.

Use of monthly collected milk yields for the detection of the emergence of the 2007 French BTV epizootic.

Two culicoides-borne diseases, Bluetongue (BTV) and Schmallenberg, have emerged in the European cattle population since 2006. Other diseases transmitted by these vectors could emerge. This justifies the development of syndromic surveillance programs whereby one or several indicators would be routinely monitored for the early detection of emerging diseases. The aim of this study was to evaluate milk yield from milk recording in dairy cattle as an indicator to be included in an emerging disease surveillance system. It was hypothesized that emergences would result in episodes of low milk production clustered in space and time. The 2007 BTV epizootic in France was used as a case study. Because it had already emerged in neighbouring countries, the disease emergence was expected and notification was mandatory. Herd-test-day milk productions were predicted for the entire country for 2006 and 2007 from herd historical data using linear mixed models. The differences between observed and predicted milk productions were averaged per week and per municipality and used as input for a space-time prospective scan statistic. Log likelihood ratios (LLR) associated with clusters were used to define alarms. The threshold chosen was a trade-off between detection timeliness and the number of false alarms per week. The first four BTV notifications occurred on the 12th (two notifications), 13th and 27th of July 2007. The 12th of July was considered to be the date of emergence. Alarms occurring before the 1st of March 2007 were considered to be false alarms. Using an LLR of 50, there were an average of 1.7 false alarms per week and the BTV emergence was detected seven weeks after emergence. Using an LLR of 100, there were an average of 0.8 false alarms per week and the BTV emergence was detected 9 weeks after emergence. Detection may have been delayed because of a discontinuation of milk recording between mid-July and mid-August. The first cluster with an LLR>100 located in the emergence area was further investigated. A difference between observed and predicted production of >1 kg/cow/day was observed around the time of emergence. However, a difference of equal magnitude was observed during the year preceding the outbreak. Milk production predicted from herd history alone did not allow the detection of the 2007 BTV emergence in France. Further research should be conducted on improving the prediction of test-day milk yield and on combining it with other indicators based on routinely collected data.

Evaluation of a Continuous Indicator for Syndromic Surveillance through Simulation. Application to Vector Borne Disease Emergence Detection in Cattle Using Milk Yield

Two vector borne diseases, caused by the Bluetongue and Schmallenberg viruses respectively, have emerged in the European ruminant populations since 2006. Several diseases are transmitted by the same vectors and could emerge in the future. Syndromic surveillance, which consists in the routine monitoring of indicators for the detection of adverse health events, may allow an early detection. Milk yield is routinely measured in a large proportion of dairy herds and could be incorporated as an indicator in a surveillance system. However, few studies have evaluated continuous indicators for syndromic surveillance. The aim of this study was to develop a framework for the quantification of both disease characteristics and model predictive abilities that are important for a continuous indicator to be sensitive, timely and specific for the detection of a vector-borne disease emergence. Emergences with a range of spread characteristics and effects on milk production were simulated. Milk yields collected monthly in 48 713 French dairy herds were used to simulate 576 disease emergence scenarios. First, the effect of disease characteristics on the sensitivity and timeliness of detection were assessed: Spatio-temporal clusters of low milk production were detected with a scan statistic using the difference between observed and simulated milk yields as input. In a second step, the system specificity was evaluated by running the scan statistic on the difference between observed and predicted milk yields, in the absence of simulated emergence. The timeliness of detection depended mostly on how easily the disease spread between and within herds. The time and location of the emergence or adding random noise to the simulated effects had a limited impact on the timeliness of detection. The main limitation of the system was the low specificity i.e. the high number of clusters detected from the difference between observed and predicted productions, in the absence of disease.

Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype

Bovine Neonatal Pancytopenia (BNP), a bleeding syndrome of neonatal calves, is caused by alloantibodies absorbed from the colostrum of particular cows. A commercial BVD vaccine is the likely source of alloantigens eliciting BNP associated alloantibodies. We hypothesized that the rare occurrence of BNP in calves born to vaccinated dams could be associated with genetic differences within dams and calves. We found that the development of BNP within calves was a heritable trait for dams, not for calves and had a high heritability of 19%. To elucidate which genes play a role in the development of BNP we sequenced candidate genes and characterized BNP alloantibodies. Alloantigens present in the vaccine have to be presented to the dam’s immune system via MHC class II, however sequencing of DRB3 showed no differences in MHC class II haplotype between BNP and non-BNP dams. MHC class I, a highly polymorphic alloantigen, is an important target of BNP alloantibodies. Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves. Alloantibodies were detected in both vaccinated BNP and non-BNP dams and we found no differences in alloantibody characteristics between these groups, but alloantibody levels were significantly higher in BNP dams. We concluded that the development of BNP in calves is a heritable trait of the dam rather than the calf and genetic differences between BNP and non-BNP dams are likely due to genes controlling the quantitative alloantibody response following vaccination.

Can routinely recorded reproductive events be used as indicators of disease emergence in dairy cattle? An evaluation of 5 indicators during the emergence of bluetongue virus in France in 2007 and 2008

In response to increasing risks of emerging infectious diseases, syndromic surveillance can be a suitable approach to detect outbreaks of such diseases across a large territory in an early phase. To implement a syndromic surveillance system, the primary challenge is to find appropriate health-related data. The objective of this study was to evaluate whether routinely collected dates of reproductive events in dairy cattle could be used to build indicators of health anomalies for syndromic surveillance. The evaluation was performed on data collected in France between 2003 and 2009. First, a set of 5 indicators was proposed to assess several types of reproductive disorders. For each indicator, the demographic coverage over the total number of cattle at risk was analyzed in time and space. Second, the ability to detect an emerging disease in an early phase was retrospectively evaluated during epidemics of bluetongue serotypes 1 and 8 (BTV-1, BTV-8) in France in 2007 and 2008. Reproductive indicators were analyzed weekly during these epidemics for each indicator in each infected French district (16 in 2007 and 50 in 2008 out of 94 districts). The indicators were able to detect the BTV epidemics despite their low demographic coverage on a weekly basis relatively to total number of cattle (median=1.21%; range=0-11.7%). Four indicators related to abortions, late embryonic death, and short gestations were abnormally elevated during both BTV epidemics. Median times to abnormal elevations in these indicators were 20 to 71 d after the first notification of clinical signs of BTV by veterinarians. These results demonstrate that reproduction data can be used as indicators of disease emergences, whereas in the specific case of these BTV epidemics, detection via these indicators was later than clinical detection by veterinarians. The emergence of bluetongue in 2007 in France was associated with gestations that were a few days shorter than expected. A short gestation indicator underwent high elevations relative to prior random fluctuations and was the earliest (out of the 4 indicators) to show abnormal elevations, making it possible to detect this emergence.

Application of syndromic surveillance on routinely collected cattle reproduction and milk production data for the early detection of outbreaks of Bluetongue and Schmallenberg viruses

This study aimed to evaluate the use of routinely collected reproductive and milk production data for the early detection of emerging vector-borne diseases in cattle in the Netherlands and the Flanders region of Belgium (i.e., the northern part of Belgium). Prospective space-time cluster analyses on residuals from a model on milk production were carried out to detect clusters of reduced milk yield. A CUSUM algorithm was used to detect temporal aberrations in model residuals of reproductive performance models on two indicators of gestation length. The Bluetongue serotype-8 (BTV-8) epidemics of 2006 and 2007 and the Schmallenberg virus (SBV) epidemic of 2011 were used as case studies to evaluate the sensitivity and timeliness of these methods. The methods investigated in this study did not result in a more timely detection of BTV-8 and SBV in the Netherlands and BTV-8 in Belgium given the surveillance systems in place when these viruses emerged. This could be due to (i) the large geographical units used in the analyses (country, region and province level), and (ii) the high level of sensitivity of the surveillance systems in place when these viruses emerged. Nevertheless, it might be worthwhile to use a syndromic surveillance system based on non-specific animal health data in real-time alongside regular surveillance, to increase the sense of urgency and to provide valuable quantitative information for decision makers in the initial phase of an emerging disease outbreak.

Estimation of the use of antibiotics in the small ruminant industry in The Netherlands in 2011 and 2012.

The aim of this study was to estimate the quantity of antibiotics and classes of antibiotics used in the small ruminant industry in the Netherlands in 2011 and 2012. Twelve large veterinary practices, located throughout the Netherlands were selected for this study. All small ruminant farms associated with these practices that had complete records on the quantity of antibiotics prescribed were included. The veterinary practices provided data on all antibiotics prescribed, and the estimated animal used daily dose of antibiotics per year (AUDD/Y) was calculated for each farm. The median AUDD/Y in small ruminant farms was zero in both years (mean 0.60 in 2011, and 0.62 in 2012). The largest quantity of antibiotic use was observed in the professional goat industry (herds of ≥32 goats) with a median AUDD/Y of 1.22 in 2011 and 0.73 in 2012. In the professional sheep industry (flocks of ≥32 sheep), the median AUDD/Y was 0 in 2011 and 0.10 in 2012. In the small scale industry (flocks or herds of <32 sheep or goats), the median AUDD/Y never exceeded 0. The most frequently prescribed antibiotics in the small scale industry and professional sheep farms belonged to the penicillin class. In professional goat farms, antibiotics of the aminoglycoside class were most frequently prescribed. This study provides the first assessment on the quantity of antibiotic use in the small ruminant industry. Given a comparable attitude towards antibiotic use, these results might be valid for small ruminant populations in other north-western European countries as well. The antibiotic use in the small ruminant industry appeared to be low, and is expected to play a minor role in the development of antibiotic resistance. Nevertheless, several major zoonotic bacterial pathogens are associated with the small ruminant industry, and it remains important that antibiotics are used in a prudent way.