Modelling of strategies for genetic control of scrapie in sheep: The importance of population structure.

Scrapie is a transmissible spongiform encephalopathy in sheep and an example of a disease that may be controlled through breeding for disease resistance. Member states of the European Union have introduced strategies for breeding against scrapie based on the selection of genetically resistant breeding rams. An ambitious strategy adopted in The Netherlands consisted of selecting resistant rams for breeding throughout both breeding and production sectors.

Prion Type-Dependent Deposition of PRNP Allelic Products in Heterozygous Sheep.

Unlabelled: Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods.

Risk-based testing of imported animals: A case study for bovine tuberculosis in The Netherlands.

In intra-EU trade, the health status of animals is warranted by issuing a health certificate after clinical inspection in the exporting country. This certificate cannot provide guarantee of absence of infection, especially not for diseases with a long incubation period and no overt clinical signs such as bovine tuberculosis (bTB). The Netherlands are officially free from bTB since 1999.

Sheep prions with molecular properties intermediate between classical scrapie, BSE and CH1641-scrapie.

Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions that BSE, classical scrapie and CH1641-a rare scrapie variant-could occur as mixtures. In field samples including those from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant part of the disease‑associated form of prion protein (PrP(res)) represents a powerful tool for quick discrimination purposes.

TSE strain differentiation in mice by immunohistochemical PrP(Sc) profiles and triplex Western blot.

Unlabelled: TSE strains are routinely identified by their incubation period and vacuolation profile in the brain after intracerebral inoculation and serial passaging in inbred mouse lines. There are some major drawbacks to this method that are related to the variation in vacuolation that exists in the brains of mice infected with the same TSE strain and to variation between observers and laboratories in scoring vacuolation and determining the final incubation period.

Aim: We investigated the potential of PrP(Sc) immunohistochemistry and triplex Western blotting as possible alternative methods to differentiate between TSE strains.

Evaluation of two commercial, rapid, ELISA kits testing for scrapie in retro-pharyngeal lymph nodes in sheep.

Aims: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes.

Methods: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died.

Enhanced virulence of sheep-passaged bovine spongiform encephalopathy agent is revealed by decreased polymorphism barriers in prion protein conversion studies.

Unlabelled: Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication.

Clinical microbiology of Coxiella burnetii and relevant aspects for the diagnosis and control of the zoonotic disease Q fever.

Coxiella burnetii is the causative agent of the zoonotic disease Q fever. Since its first recognition as a disease in the 1930s, the knowledge about the agent and the disease itself has increased. This review summarizes the current knowledge on C.

Q fever in pregnant goats: humoral and cellular immune responses.

Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C.

Q fever in pregnant goats: pathogenesis and excretion of Coxiella burnetii.

Coxiella burnetii is an intracellular bacterial pathogen that causes Q fever. Infected pregnant goats are a major source of human infection. However, the tissue dissemination and excretion pathway of the pathogen in goats are still poorly understood.

Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein.

Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so-called ARR allele, in the sheep population have been demonstrated to be effective in reducing the occurrence of classical scrapie in the field.

Four independent molecular prion protein parameters for discriminating new cases of C, L, and h bovine spongiform encephalopathy in cattle.

In anticipation of the emergence of more variants of bovine spongiform encephalopathy (BSE), a semiquantitative display of the following four independent molecular diagnostic prion parameters was designed: N terminus, proteinase K (PK) resistance, glycoprofile, and mixed population. One H BSE case, three L BSE cases, six C BSE cases, and one unusual classical BSE (C BSE) case are reported.

[Active surveillance for scrapie in the Netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)?].

The susceptibility of sheep to scrapie is modulated by the prion protein (PrP) genotype of the animal. An ambitious voluntary scrapie control programme was started in the Netherlands in 1998, based on selection of rams with theARR/ARR genotype for breeding. This programme was followed by an obligatory programme in 2004; the programme has been voluntary since 2007.

Prion protein self-interactions: a gateway to novel therapeutic strategies?

Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders and include among others Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. The central event in disease development in TSEs is the refolding of the normal host-encoded cellular prion protein (PrP) into abnormal and disease associated prion protein. The agent is thought to consist mainly or exclusively of these pathologically folded PrP molecules.

The Q fever epidemic in The Netherlands: history, onset, response and reflection.

The 2007-2009 human Q fever epidemic in The Netherlands attracted attention due to its magnitude and duration. The current epidemic and the historical background of Q fever in The Netherlands are reviewed according to national and international publications. Seroprevalence studies suggest that Q fever was endemic in The Netherlands several decades before the disease was diagnosed in dairy goats and dairy sheep.

Scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance.

Background: Susceptibility of sheep to scrapie infection is known to be modulated by the PrP genotype of the animal. In the Netherlands an ambitious scrapie control programme was started in 1998, based on genetic selection of animals for breeding. From 2002 onwards EU regulations required intensive active scrapie surveillance as well as certain control measures in affected flocks.

Eradication of scrapie with selective breeding: are we nearly there?

Background: Following EU decision 2003/100/EC Member States have recently implemented sheep breeding programmes to reduce the prevalence of sheep with TSE susceptible prion genotypes. The present paper investigates the progress of the breeding programme in the Netherlands. The PrP genotype frequencies were monitored through time using two sets of random samples: one set covers the years 2005 to 2008 and is taken from national surveillance programme; the other is taken from 168 random sheep farms in 2007.

Prion protein self-peptides modulate prion interactions and conversion.

Background: Molecular mechanisms underlying prion agent replication, converting host-encoded cellular prion protein (PrP(C)) into the scrapie associated isoform (PrP(Sc)), are poorly understood. Selective self-interaction between PrP molecules forms a basis underlying the observed differences of the PrP(C) into PrP(Sc) conversion process (agent replication). The importance of previously peptide-scanning mapped ovine PrP self-interaction domains on this conversion was investigated by studying the ability of six of these ovine PrP based peptides to modulate two processes; PrP self-interaction and conversion.

[Two horses with neurological symptoms: could this be equine botulism?].

Symptoms, diagnosis and therapy of equine botulism are discussed by the presentation of two detailed reports of horses with neurological symptoms and the results of laboratory investigations over the period 2003-2008 in the Netherlands. In addition a brief summary of the available literature is presented. Prevailing symptoms of botulism in horses include paralysis of the tongue, salvation, dysphagia and paresis and paralysis of the skeletal muscles, as well as signs of colic.

Transmission and quantification of verocytotoxin-producing Escherichia coli O157 in dairy cattle and calves.

Data from a field study of 14 months duration in a naturally colonized dairy herd and data from an experiment with calves were used to quantify transmission of verocytotoxin-producing Escherichia coli (VTEC O157) in cattle. For the latter, two groups of 10 calves were randomly assigned and put out in one of two pastures. From each group, five animals were experimentally inoculated with 109 c.

TSE pathogenesis in cattle and sheep.

Many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (TSE). Only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (BSE) and scrapie in their natural hosts. In this review, we summarize the most recent insights into the pathogenesis of BSE and scrapie starting from the initial uptake of TSE agents and crossing of the gut epithelium.

Pathogenesis of bovine spongiform encephalopathy in sheep.

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen.

Identification of the characteristics and risk factors of the BSE epidemic in the Netherlands.

It is generally accepted that the bovine spongiform encephalopathy (BSE) epidemic is transmitted by feed contamination with meat and bone meal (MBM). Whether in some cases substances other than MBM have caused the spread of this disease cannot be excluded at present. Detailed knowledge about country-specific transmission routes and relevant risk factors is important to perform accurate risk analyses and to control BSE.