scholarly journals Transmissible spongiform encephalopathy in goats: is PrP rapid test sensitivity affected by genotype?

2020 ◽  
Vol 32 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Marion M. Simmons ◽  
Leigh Thorne ◽  
Angel Ortiz-Pelaez ◽  
John Spiropoulos ◽  
Soteria Georgiadou ◽  
...  
Keyword(s):  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Rapid Test ◽  
Prnp Gene ◽  
Spongiform Encephalopathy ◽  
Sheep Population ◽  
Test Sensitivity ◽  
Goat Population ◽  
Clinical Stages ◽  
Rapid Tests

Transmissible spongiform encephalopathy (TSE) surveillance in goats relies on tests initially approved for cattle, subsequently assessed for sheep, and approval extrapolated for use in “small ruminants.” The current EU-approved immunodetection tests employ antibodies against various epitopes of the prion protein PrPSc, which is encoded by the host PRNP gene. The caprine PRNP gene is polymorphic, mostly at codons different from the ovine PRNP. The EU goat population is much more heterogeneous than the sheep population, with more PRNP-related polymorphisms, and with marked breed-related differences. The ability of the current tests to detect disease-specific PrPSc generated against these different genetic backgrounds is currently assumed, rather than proven. We examined whether common polymorphisms within the goat PRNP gene might have any adverse effect on the relative performance of EU-approved rapid tests. The sample panel comprised goats from the UK, Cyprus, France, and Italy, with either experimental or naturally acquired scrapie at both the preclinical and/or unknown and clinical stages of disease. Test sensitivity was significantly lower and more variable when compared using samples from animals that were preclinical or of unknown status. However, all of the rapid tests included in our study were able to correctly identify all samples from animals in the clinical stages of disease, apart from samples from animals polymorphic for serine or aspartic acid at codon 146, in which the performance of the Bio-Rad tests was profoundly affected. Our data show that some polymorphisms may adversely affect one test and not another, as well as underline the dangers of extrapolating from other species.

scholarly journals Investigations into Foot and Mouth Disease Outbreak among Small Ruminants in Karnataka State of India

2021 ◽  
Author(s):  
Raveendra Hegde ◽  
B.P. Shivashankar ◽  
N. Gautham ◽  
G.R. Praveenkumar ◽  
B. Rajasekar ◽  
...  
Keyword(s):  
Multiplex Pcr ◽  
Small Ruminants ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Perivascular Spaces ◽  
Grazing Land ◽  
Sheep Population ◽  
Goat Population ◽  
Karnataka State ◽  
Foot And Mouth

Background: Foot-and-Mouth Disease (FMD) remains a serious threat to the Indian livestock sector due to significant economic loss associated with it. Systematic vaccination of large ruminants over the years has lead to a gradual reduction in the number of disease outbreaks in India. However exposure to FMDV infection in small ruminants has been recorded during the past few years (Rout et al. 2013). Sheep and goat population have not been vaccinated so far against FMD under the FMD-Control program (FMD-CP). The present study highlighted the outbreak of FMD in small ruminants in Karnataka, India.Methods: During the period 2018-19, seven suspected FMD outbreaks among sheep population in Bellary and Tumakuru districts of Karnataka state were investigated. Tongue epithelium (oral swabs) and foot lesions (n=23) from clinically affected sheep and tissues such as heart, lung, liver, spleen, lymph nodes and kidneys from lambs during post mortem (n=67) were collected. All the samples were processed in the laboratory for the detection of FMD virus antigen by employing Serotype differentiating antigen detection ELISA and by multiplex PCR. Heart tissue samples were also collected in buffered formalin for histopathology study and processed by routine paraffin embedding technique and stained with Hematoxylin and Eosin (H and E). Serum samples from the recovered animals were collected and screened by NSP-ELISA and LPB-ELISA to check the antibody status in the affected herd. Result: A total of seven suspected outbreaks of FMD involving 688 small ruminants was investigated. The outbreak of FMD due to FMDV serotype O was confirmed by ELISA and multiplex PCR assays. Clinically, the affected adult sheep showed typical signs of FMD, while mortality in young lambs was observed without apparent signs of disease. Histologically, heart tissues from FMD affected lambs showed myocardial necrosis with marked aggregations of lymphocytes and neutrophils in the myocardium and perivascular spaces. History of FMD outbreaks in cattle and common grazing land for the livestock, as well as sheep within the reach of these villages, may be the major contributing factors for the outbreaks in sheep populations.

scholarly journals Characterization of an unusual transmissible spongiform encephalopathy in goat by transmission in knock-in transgenic mice

2013 ◽  
Vol 94 (8) ◽  
pp. 1922-1932 ◽  
Author(s):  
Rona Wilson ◽  
Declan King ◽  
Nora Hunter ◽  
Wilfred Goldmann ◽  
Rona M. Barron
Keyword(s):  
Unusual Case ◽  
Neurodegenerative Disorder ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Dairy Goat ◽  
Spongiform Encephalopathy ◽  
Variant Form ◽  
Sheep And Goats ◽  
The Uk ◽  
Mouse Lines

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle, and its transmission to humans through contaminated food is thought to be the cause of the variant form of Creutzfeldt–Jakob disease. BSE is believed to have spread from the recycling in cattle of ruminant tissue in meat and bone meal (MBM). However, during this time, sheep and goats were also exposed to BSE-contaminated MBM. Both sheep and goats are experimentally susceptible to BSE, and while there have been no reported natural BSE cases in sheep, two goat BSE field cases have been documented. While cases of BSE are rare in small ruminants, the existence of scrapie in both sheep and goats is well established. In the UK, during 2006–2007, a serious outbreak of clinical scrapie was detected in a large dairy goat herd. Subsequently, 200 goats were selected for post-mortem examination, one of which showed biochemical and immunohistochemical features of the disease-associated prion protein (PrPTSE) which differed from all other infected goats. In the present study, we investigated this unusual case by performing transmission bioassays into a panel of mouse lines. Following characterization, we found that strain properties such as the ability to transmit to different mouse lines, lesion profile pattern, degree of PrP deposition in the brain and biochemical features of this unusual goat case were neither consistent with goat BSE nor with a goat scrapie herdmate control. However, our results suggest that this unusual case has BSE-like properties and highlights the need for continued surveillance.

scholarly journals Molecular Profiling of Ovine Prion Diseases by Using Thermolysin-Resistant PrPSc and Endogenous C2 PrP Fragments

2007 ◽  
Vol 81 (19) ◽  
pp. 10532-10539 ◽  
Author(s):  
Jonathan P. Owen ◽  
Helen C. Rees ◽  
Ben C. Maddison ◽  
Linda A. Terry ◽  
Leigh Thorne ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Western Blots ◽  
Sheep Population ◽  
Natural Scrapie ◽  
Caudal Medulla ◽  
Scrapie Strains

ABSTRACT Disease-associated PrP fragments produced upon in vitro or in vivo proteolysis can provide significant insight into the causal strain of prion disease. Here we describe a novel molecular strain typing assay that used thermolysin digestion of caudal medulla samples to produce PrPres signatures on Western blots that readily distinguished experimental sheep bovine spongiform encephalopathy (BSE) from classical scrapie. Furthermore, the accumulation of such PrPres species within the cerebellum also appeared to be dependent upon the transmissible spongiform encephalopathy (TSE) strain, allowing discrimination between two experimental strains of scrapie and grouping of natural scrapie isolates into two profiles. The occurrence of endogenously produced PrP fragments, namely, glycosylated and unglycosylated C2, within different central nervous system (CNS) regions is also described; this is the first detailed description of such scrapie-associated fragments within a natural host. The advent of C2 fragments within defined CNS regions, compared between BSE and scrapie cases and also between two experimental scrapie strains, appeared to be largely dependent upon the TSE strain. The combined analyses of C2 fragments and thermolysin-resistant PrP species within caudal medulla, cerebellum, and spinal cord samples allowed natural scrapie isolates to be separated into four distinct molecular profiles: most isolates produced C2 and PrPres in all CNS regions, a second group lacked detectable cerebellar C2 fragments, one isolate lacked both cerebellar PrPres and C2, and a further isolate lacked detectable C2 within all three CNS regions and also lacked cerebellar PrPres. This CNS region-specific deposition of disease-associated PrP species may reflect the natural heterogeneity of scrapie strains in the sheep population in the United Kingdom.

scholarly journals Performance analysis of rapid diagnostic tests on atypical bovine spongiform encephalopathy

2012 ◽  
Vol 24 (5) ◽  
pp. 976-980 ◽  
Author(s):  
John G. Gray ◽  
Sandor Dudas ◽  
Catherine Graham ◽  
Stefanie Czub
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Test Performance ◽  
Rapid Test ◽  
Rapid Diagnostic Tests ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spongiform Encephalopathy ◽  
Analytical Sensitivity ◽  
Atypical Bovine Spongiform Encephalopathy ◽  
Surveillance Programs ◽  
Rapid Tests

The preferred method to determine the prevalence of bovine spongiform encephalopathy (BSE) in a country is to use immunology-based rapid-tests. Though these tests are validated to detect C-type BSE disease–associated prion (PrPsc), test-specific properties may influence their ability to detect H- and/or L-type BSE PrPsc, where both are atypical from C-type PrPsc. Molecular characterization shows atypical BSE PrPsc to have a different sensitivity to proteinase activity and different affinities for certain prion-specific antibodies. It is important to understand how atypical BSE PrPsc may affect the performance of rapid-tests, which are typically dependant on the use of specific proteases and antibodies. The current study used experimentally generated C-, H-, and L-type BSE PrPsc to evaluate 3 tests used in various national BSE surveillance programs: an immunochromatographic assay, a standard sandwich enzyme-linked immunosorbent assay (stndELISA), and a PrPsc-conformation–specific ELISA (confELISA). Although BSE PrPsc type had some effects on rapid-test performance, analytical sensitivity for atypical BSE PrPsc on all 3 platforms was not significantly compromised. When testing for atypical BSE PrPsc, the 3 tests were able to meet the same requirements that the European Food Safety Authority set when evaluating the tests for C-type BSE PrPsc.

scholarly journals Are fast test results preferable to high test sensitivity in contact-tracing strategies?

2021 ◽  
Author(s):  
Jonas L. Juul ◽  
Kaare Græsbøll
Keyword(s):  
Waiting Time ◽  
Waiting Times ◽  
Rapid Test ◽  
Contact Tracing ◽  
Test Results ◽  
False Negatives ◽  
Test Parameter ◽  
Test Sensitivity ◽  
Rapid Tests ◽  
Better Than

AbstractAcross the world, countries are fighting to reduce the spread of COVID-19. The backbone of the response is a test-trace-isolate strategy, where suspected infected get tested and isolated and possible secondary cases get traced, tested and isolated. Because more accurate tests often take longer to analyze, and the benefits of contact tracing are strengthened by rapid diagnosis, there exists a trade-off in test sensitivity and test waiting time in test-trace-isolate strategies. Here we ask: How many false negatives can be tolerated in a rapid test so that it reduces transmission better than a slower, more accurate test? How does this change with contact tracing efficiency and test waiting time? We find that a rapid, less sensitive test performs best for many test-parameter choices and that this is true even for modest contact tracing efficiency. For COVID-19-like viral parameters, a test with 40% false negatives and immediate result might reduce transmission as well as a test with no false negatives and a 3-day waiting time. Our analysis suggests employing rapid tests to reduce test waiting times as a viable strategy to reduce transmission when testing infrastructure is under stress.

scholarly journals Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue

2014 ◽  
Vol 95 (8) ◽  
pp. 1855-1859 ◽  
Author(s):  
Chris Plinston ◽  
Patricia Hart ◽  
Nora Hunter ◽  
Jean C. Manson ◽  
Rona M. Barron
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Brain Tissue ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Jakob Disease ◽  
Human Prion Protein ◽  
Sheep Brain ◽  
Increased Susceptibility

Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt–Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent.

Molecular typing of transmissible spongiform encephalopathy from Italian disease outbreaks in small ruminants

2006 ◽  
Vol 159 (22) ◽  
pp. 746-747 ◽  
Author(s):  
P. L. Acutis ◽  
F. Martucci ◽  
M. Mazza ◽  
S. Nodari ◽  
C. Maurella ◽  
...  
Keyword(s):  
Molecular Typing ◽  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Disease Outbreaks ◽  
Spongiform Encephalopathy

scholarly journals Classical and Atypical Scrapie in Sheep and Goats. Review on the Etiology, Genetic Factors, Pathogenesis, Diagnosis, and Control Measures of Both Diseases

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 691
Author(s):  
Cristina Acín ◽  
Rosa Bolea ◽  
Marta Monzón ◽  
Eva Monleón ◽  
Bernardino Moreno ◽  
...  
Keyword(s):  
Prion Protein ◽  
Genetic Factors ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Fatal Outcome ◽  
Small Ruminants ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrPC), originating with the pathogenic form (PrPSc). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. The aim of this review is to perform an overview of classical and atypical scrapie disease in sheep and goats, detailing those special issues of the disease, such as genetic factors, diagnostic procedures, and surveillance approaches carried out in the European Union with the objective of controlling the dissemination of scrapie disease.

scholarly journals Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme

2006 ◽  
Vol 87 (2) ◽  
pp. 471-477 ◽  
Author(s):  
S. J. Everest ◽  
L. Thorne ◽  
D. A. Barnicle ◽  
J. C. Edwards ◽  
H. Elliott ◽  
...  
Keyword(s):  
Prion Protein ◽  
Biochemical Analysis ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Relative Resistance ◽  
Sheep Population ◽  
Surveillance Programme ◽  
Naturally Occurring ◽  
Sheep Brain

Scrapie of sheep and goats is the most common prion disease (or transmissible spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase-resistant prion protein (PrPSc) are found in all naturally occurring prion diseases. During active surveillance of British sheep for TSEs, 29 201 sheep brain stem samples were collected from abattoirs and analysed for the presence of PrPSc. Of these samples, 54 were found to be positive by using an ELISA screening test, but 28 of these could not be confirmed initially by immunohistochemistry. These unconfirmed or atypical cases were generally found in PrP genotypes normally associated with relative resistance to clinical scrapie and further biochemical analysis revealed that they contained forms of PrPSc with a relatively protease-sensitive amyloid core, some resembling those of Nor98 scrapie. The presence of these atypical forms of protease-resistant PrP raises concerns that some TSE disorders of PrP metabolism previously may have escaped identification in the British sheep population.

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