Data analysis supports monitoring and surveillance of goat health and welfare in the Netherlands.

Monitoring and surveillance systems have an increasingly important role in contemporary society ensuring high levels of animal health and welfare, securing export positions, and protecting public health by ensuring animal health and product safety. In the Netherlands, a voluntary monitoring and surveillance system is in place since 2003 to provide a broad overview of livestock trends in addition to disease-specific surveillance systems, including insight into the occurrence and prevalence of new and emerging non-notifiable diseases and disorders. Being a major surveillance component of this monitoring and surveillance system for small ruminant health in the Netherlands, an annual data analysis on routine census data is performed to retrospectively monitor trends and developments regarding goat health and welfare. This paper aims to describe the process of the data analysis on goat farms in the Netherlands in 2020 and subsequent results are discussed. The data analysis provides key monitoring indicators such as animal and farm density, mortality, animal movements, and numbers and origin of imported small ruminants. Trends were analysed over a five-year, period and associations between herd characteristics and herd health are evaluated. Results showed that in 2020 the Dutch goat population consisted of 670,842 goats, distributed over 14,730 unique herds and increased by 2.3 % compared to 2019. Between 2016 and 2020, although probably underestimated, recorded mortality rates showed a decline on both small-scale and professional farms, with a strongest decrease on farms with herd sizes over more than 200 animals. Seventy-five percent of all professional farms registered animal introductions, in addition to 63 % of small-scale farms, including 2439 imported goats. Performing risks analyses requires demographic knowledge of the goat industry. During and after several disease outbreaks, such as bluetongue and Schmallenberg virus disease, the data analysis proved to function as a valuable tool, however, appeared just as important for recording outbreak-free data. Since its start in 2006, the concept of the data-analysis has continuously been improved, and will in the future be further developed, especially if more complete data sets become available. Subsequently, data analysis will increasingly support monitoring and surveillance of goat health and welfare.

Balancing treatment efficacy, toxicity and complication risk in elderly patients with metastatic renal cell carcinoma.

The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly.

Schmallenberg disease in sheep or goats: Past, present and future.

Schmallenberg disease has emerged in North-Western Europe in 2011 and has since spread widely, even across the European borders. It has the potency to infect many, mainly ruminant, species, but seems to lack zoonotic potential. Horizontal transmission occurs through various Culicoides biting midges and subsequent trans-placental transmission causes teratogenic effects. In some small ruminants, clinical signs, including fever, decreased milk production and diarrhea occur during the viraemic phase, but infection is mostly asymptomatic. However, fetal Schmallenberg virus infection in naïve ewes and goats can result in stillborn offspring, showing a congenital arthrogryposis-hydranencephaly syndrome. The economic impact of infection depends on the number of malformed lambs, but is generally limited. There is debate on whether Schmallenberg virus has newly emerged or is re-emerging, since it is likely one of the ancestors of Shamonda virus, both Orthobunyaviruses belonging to the species Sathuperi virus within the Simbu serogroup viruses. Depending on the vector-borne transmission and the serologic status, future outbreaks of Schmallenberg disease induced congenital disease are expected.

Coxiella burnetii infections in sheep or goats: an opinionated review.

Q fever is an almost ubiquitous zoonosis caused by Coxiella burnetii, which is able to infect several animal species, as well as humans. Cattle, sheep and goats are the primary animal reservoirs. In small ruminants, infections are mostly without clinical symptoms, however, abortions and stillbirths can occur, mainly during late pregnancy. Shedding of C. burnetii occurs in feces, milk and, mostly, in placental membranes and birth fluids. During parturition of infected small ruminants, bacteria from birth products become aerosolized. Transmission to humans mainly happens through inhalation of contaminated aerosols. In the last decade, there have been several, sometimes large, human Q fever outbreaks related to sheep and goats. In this review, we describe C. burnetii infections in sheep and goats, including both advantages and disadvantages of available laboratory techniques, as pathology, different serological tests, PCR and culture to detect C. burnetii. Moreover, worldwide prevalences of C. burnetii in small ruminants are described, as well as possibilities for treatment and prevention. Prevention of shedding and subsequent environmental contamination by vaccination of sheep and goats with a phase I vaccine are possible. In addition, compulsory surveillance of C. burnetii in small ruminant farms raises awareness and hygiene measures in farms help to decrease exposure of people to the organism. Finally, this review challenges how to contain an infection of C. burnetii in small ruminants, bearing in mind possible consequences for the human population and probable interference of veterinary strategies, human risk perception and political considerations.

Bulk tank milk surveillance as a measure to detect Coxiella burnetii shedding dairy goat herds in the Netherlands between 2009 and 2014.

In the period from 2005 to 2009, Coxiella burnetii was a cause of abortion waves at 28 dairy goat farms and 2 dairy sheep farms in the Netherlands. Two years after the first abortion waves, a large human Q fever outbreak started mainly in the same region, and aborting small ruminants were regarded as most probable source. To distinguish between infected and noninfected herds, a surveillance program started in October 2009, based on PCR testing of bulk tank milk (BTM) samples, which had never been described before. The aim of this study was to analyze the effectiveness of this surveillance program and to evaluate both the effect of culling of pregnant dairy goats on positive farms and of vaccination on BTM results. Bulk tank milk samples were tested for C. burnetii DNA using a real-time PCR, and results were analyzed in relation to vaccination, culling, and notifiable (officially reported to government) C. burnetii abortion records. In spring and autumn, BTM samples were also tested for antibodies using an ELISA, and results were evaluated in relation to the compulsory vaccination campaign. Between October 2009 and April 2014, 1,660 (5.6%) out of 29,875 BTM samples from 401 dairy goat farms tested positive for C. burnetii DNA. The percentage of positive samples dropped from 20.5% in 2009 to 0.3% in 2014. In a multivariable model, significantly higher odds of being PCR positive in the BTM surveillance program were found in farms of which all pregnant dairy goats were culled. Additionally, the risk for C. burnetii BTM PCR positivity significantly decreased after multiple vaccinations. Bulk tank milk ELISA results were significantly higher after vaccination than before. The ELISA results were higher after multiple vaccinations compared with a single vaccination, and ELISA results on officially declared infected farms were significantly higher compared with noninfected farms. In conclusion, BTM surveillance is an effective and useful tool to detect C. burnetii shedding dairy goat herds and to monitor a Q fever outbreak, and thus the effect of implemented measures.

Haemonchus contortus resistance to monepantel in sheep.

In a sheep farm in the Netherlands with a suspected Haemonchus contortus resistance to monepantel (Zolvix®, Novartis Animal Health), a fecal egg count reduction test was carried out in two groups of lambs, according to the method of the World Association for the Advancement of Veterinary Parasitology. Group 1 was the untreated control group, and group 2 was treated with monepantel at the manufacturer's recommended dose rate. Efficacy of treatment with monepantel was 0%. Larval identification of pre- and post-treatment coprocultures revealed 100% H. contortus larvae. On this farm, after a perceived reduction in efficacy of ivermectin and doramectin, the sheep farmer started using monepantel in July 2012, and since then, monepantel was used as the sole anthelmintic. Breeding sheep were treated twice each year in 2013 and 2014, and lambs two times in 2012, four times in 2013, and three times in 2014, before monepantel resistance was suspected, and confirmed three weeks later. Although the frequency of monepantel treatments on this farm was relatively high with treatments on thirteen separate occasions in two years time, possibly establishing favorable conditions for a competitive advantage for resistant H. contortus, it is remarkable that resistance to monepantel was established in such a very short period. This study confirms, to the best of our knowledge, the first case of H. contortus resistance to monepantel occurring in the field.

Demography of Q fever seroprevalence in sheep and goats in The Netherlands in 2008.

At the end of 2007, the first year of what later turned out to be one of the largest Q fever outbreaks in the world with ultimately almost 3500 human patients notified in three years time, dairy goats were suspected to be the possible cause. However, current information on the Q fever prevalence in small ruminants in The Netherlands was lacking. A serological survey, using an indirect ELISA, was carried out in 15,186 sheep and goats in The Netherlands in 2008. In total, 2.4% (95% CI: 2.2-2.7) of the sheep and 7.8% (95% CI: 6.9-8.8) of the goats was seropositive for antibodies against Coxiella burnetii. In 14.5% (95% CI: 12.5-16.5) of the sheep flocks and 17.9% (95% CI: 14.2-21.5) of the goat herds at least one seropositive animal was found. In sheep flocks with at least one seropositive sheep, the within herd seroprevalence was 14.8% (95% CI: 12.6-17.0). In goat herds with at least one seropositive goat, the within herd seroprevalence was 29.0% (95% CI: 24.6-33.3). The seropositive sheep were equally distributed across the country. The seroprevalence in goats in the south-eastern part of The Netherlands, the area where most of the human Q fever cases were notified, was significantly higher than the seroprevalence in goats in the rest of The Netherlands. Dairy sheep and dairy goats had a significantly higher chance of being seropositive than non-dairy sheep and goats. During pregnancy and in the periparturient period, small ruminants tested significantly more often seropositive than in the early- or non-pregnant period. The seroprevalence as well as the true prevalence among small ruminants in The Netherlands were lower than prevalences reported elsewhere. The seroprevalence among sheep was also lower than reported in an earlier Dutch study in 1987. The Q fever seroprevalence was highest in pregnant and periparturient dairy goats in the south-eastern part of The Netherlands, which coincides with the region with the highest human incidence of Q fever.

Abortion in small ruminants in the Netherlands between 2006 and 2011.

During five successive lambing seasons between 2006 and 2011, 453 submissions of abortion material, 282 of ovine and 171 of caprine origin, were examined at the Animal Health Service in the Netherlands. Infectious agents as the most plausible cause of the abortion were found in 48 percent of the ovine submissions and in 34 percent of the caprine submissions. Submission of both aborted fetus and placental membranes increased the diagnostic yield of laboratory investigations (17 percent and 21 percent for ovine and caprine submissions, respectively). The main infectious causes of abortion in sheep were Chlamydia abortus, Campylobacter spp., Toxoplasma gondii, Listeria spp., and Yersinia pseudotuberculosis. The main infectious causes of abortion in goats were Coxiella burnetii, Chlamydia abortus, Listeria spp., Toxoplasma gondii, and Campylobacter spp. In 42 percent of the ovine and in 56 percent of the caprine submissions a causal agent was not identified. Furthermore, in 12 percent of the ovine and 10 percent of the caprine submissions evidence of placentitis, indicative of an infectious cause of the abortion, was found, but no infectious agent was identified. Most infectious causes of ovine and caprine abortion have zoonotic potential. Humans, especially pregnant women, who are in close contact with lambing sheep or goats should be aware of the importance of precautionary hygiene measures.

Epizootic of ovine congenital malformations associated with Schmallenberg virus infection.

Epizootic outbreaks of congenital malformations in sheep are rare and have, to the best of our knowledge, never been reported before in Europe. This paper describes relevant preliminary findings from the first epizootic outbreak of ovine congenital malformations in the Netherlands. Between 25 November and 20 December 2011, congenital malformations in newborn lambs on sheep farms throughout the country were reported to the Animal Health Service in Deventer. Subsequently, small ruminant veterinary specialists visited these farms and collected relevant information from farmers by means of questionnaires. The deformities varied from mild to severe, and ewes were reported to have given birth to both normal and deformed lambs; both male and female lambs were affected. Most of the affected lambs were delivered at term. Besides malformed and normal lambs, dummy lambs, unable to suckle, were born also on these farms. None of the ewes had shown clinical signs during gestation or at parturition. Dystocia was common, because of the lambs' deformities. Lambs were submitted for post-mortem examination, and samples of brain tissue were collected for virus detection. The main macroscopic findings included arthrogryposis, torticollis, scoliosis and kyphosis, brachygnathia inferior, and mild-to-marked hypoplasia of the cerebrum, cerebellum and spinal cord. Preliminary data from the first ten affected farms suggest that nutritional deficiencies, intoxication, and genetic factors are not likely to have caused the malformations. Preliminary diagnostic analyses of precolostral serum samples excluded border disease virus, bovine viral diarrhoea virus, and bluetongue virus. In December 2011, samples of brain tissue from 54 lambs were sent to the Central Veterinary Institute of Wageningen University Research, Lelystad. Real-time PCR detected the presence of a virus, provisionally named the Schmallenberg virus, in brain tissue from 22 of the 54 lambs, which originated from seven of eight farms that had submitted lambs for post-mortem examination. This Schmallenberg virus was first reported in Germany and seems to be related to the Shamonda, Aino, and Akabane viruses, all of which belong to the Simbu serogroup of the genus Orthobunyavirus of the family Bunyaviridae. These preliminary findings suggest that the Schmallenberg virus is the most likely cause of this epizootic of ovine congenital malformations, which is the first such outbreak reported in Europe.

Coxiella burnetii in bulk tank milk samples from dairy goat and dairy sheep farms in The Netherlands in 2008.

In 2007, a human Q fever epidemic started, mainly in the south eastern part of The Netherlands with a suspected indirect relation to dairy goats, and, to a lesser degree, to dairy sheep. This article describes the Q fever prevalences in Dutch dairy goat and dairy sheep bulk tank milk (BTM) samples, using a real-time (RT) PCR and ELISA. Results of BTM PCR and ELISA were compared with the serological status of individual animals, and correlations with a history of Q fever abortion were determined. When compared with ELISA results, the optimal cut-off value for the RT-PCR was 100 bacteria/ml. In 2008, there were 392 farms with more than 200 dairy goats, of which 292 submitted a BTM sample. Of these samples, 96 (32.9 per cent) were PCR positive and 87 (29.8 per cent) were ELISA positive. All farms with a history of Q fever abortion (n=17) were ELISA positive, 16 out of 17 were also PCR positive. BTM PCR or ELISA positive farms had significantly higher within-herd seroprevalences than BTM negative farms. In the south eastern provinces, the area where the human Q fever outbreak started in 2007, a significantly larger proportion of the BTM samples was PCR and ELISA positive compared to the rest of The Netherlands. None of the BTM samples from dairy sheep farms (n=16) were PCR positive but three of these farms were ELISA positive. The higher percentage of BTM positive farms in the area where the human Q fever outbreak started, supports the suspected relation between human cases and infected dairy goat farms.

Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors.

Gamma-hydroxybutyrate (GHB) is a neuromodulator with high affinity binding sites in the mammalian brain. However, the receptor for GHB has not yet been identified. There are indications that GHB and gamma-aminobutyric acid (GABA) mediate their effects via the same receptor. We tested this hypothesis using GABA(B)R1/R2 receptors co-expressed with Kir3 channels in Xenopus oocytes. GHB activated these receptors with an EC50 of approximately 5 mM and a maximal stimulation of 69% when compared to the GABA(B) receptor agonist L-baclofen. GHB and L-baclofen did not amplify each others effect nor did they stimulate the GABA(B) receptor in a linearly additive manner. CGP54626A, 2-OH saclofen and CGP35348, three competitive GABA(B) receptor antagonists, inhibited the GHB induced response completely. A concentration of 30 mM GHB displaced [125I]CGP64213 binding at GABA(B)R1 expressed in COS cells by 21%. These results indicate that GHB is a weak partial agonist at the GABA binding site of GABA(B)R1/R2.

A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol.

BACKGROUND: Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question--are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol? METHODS: Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable. RESULTS: In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%). CONCLUSION: Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.

Differentiation of peripheral and central effects of analgesic drugs.

The nonsteroidal antiphlogistic and antinociceptive agents acetylsalicylic acid, diclofenac-Na and paracetamol, and the centrally acting analgesic morphine, were tested in the isolated perfused rabbit ear. This model allows for the distinction between centrally and peripherally acting analgesic drugs. It was found that local acetylsalicylic acid, diclofenac-Na and paracetamol inhibited the pain reflexes (blood pressure change, "head-flick" response) induced by bradykinin, whereas local morphine proved to be inactive. In contrast, after systemic administration, only morphine, but not acetylsalicylic acid, diclofenac-Na and paracetamol, was active in a therapeutic dose range. Thus, the isolated rabbit ear model is useful for differentiating peripheral from central sites of action of an analgesic agent.

Leukotrienes reduce nociceptive responses to bradykinin.

The biotransformation of arachidonic acid leads to two important groups of inflammatory mediators, the leukotrienes and the prostaglandins. Hyperalgesic effects have been demonstrated for prostaglandins in a variety of animal models but the effects of leukotrienes on inflammatory pain are less well documented. Using the isolated rabbit ear model of algesia we have shown that perfusion of the ear with the leukotrienes B4, C4 and D4 (10(-8)-10(-7) M) causes a reversible, dose- and time-dependent reduction of the reflex fall in systemic blood pressure and the "head flick" response induced by injection of bradykinin (400 ng), without affecting similar responses induced by the neurotransmitter acetylcholine. The antagonistic effect of leukotrienes on the algesic action of bradykinin could be reversed by the leukotriene antagonist FPL55712 (2 micrograms/ml). This result implies that the leukotrienes may have a desensitizing effect on the nociceptor during an inflammatory response in contrast to the pain threshold-lowering action of the E- and I-type prostaglandins.