Transmission of BSE by blood transfusion in sheep

doi:10.1016/S0140-6736(00)02719-7

The Lancet

Volume 356, Issue 9234, 16 September 2000, Pages 999-1000

https://doi.org/10.1016/S0140-6736(00)02719-7 Get rights and content

Summary

We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom.free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted—a possible protective measure against any risk from blood transmission—this report suggests that blood donated by symptom—free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK.

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Citation Excerpt :
As mentioned earlier, vCJD can also be transmitted by blood transfusion (Unit TNCRS, 2020; Urwin et al., 2016; Seed et al., 2018). Transmission of BSE prions to sheep parallels that to humans with regard to the subsequent tissue distribution of infectivity (Houston et al., 2000). Transfusion studies using blood components of sheep orally infected with BSE prions have shown that prion infectivity in sheep is associated with plasma, platelets, red blood cells, and white blood cells (Salamat et al., 2021).
In several neurodegenerative disorders, proteins that typically exhibit an α-helical structure misfold into an amyloid conformation rich in β-sheet content. Through a self-templating mechanism, these amyloids are able to induce additional protein misfolding, facilitating their propagation throughout the central nervous system. This disease mechanism was originally identified for the prion protein (PrP), which misfolds into PrP^Sc in a number of disorders, including variant Creutzfeldt–Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE). More recently, the prion mechanism of disease was expanded to include other proteins that rely on this self-templating mechanism to cause progressive degeneration, including α-synuclein misfolding in Parkinson’s disease (PD). Several studies now suggest that PD patients can be subcategorized based on where in the body misfolded α-synuclein originates, either the brain or the gut, similar to patients developing sporadic CJD or vCJD. In this review, we discuss the human and animal model data indicating that α-synuclein and PrP^Sc misfolding originates in the gut in body-first PD and vCJD, and summarize the data identifying the role of the autonomic nervous system in the gut-brain axis of both diseases.
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Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<10⁶ WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrP^Sc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.
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Fast track — Research LettersTransmission of BSE by blood transfusion in sheep

Summary

Lancet

Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent

Nature

Fast track — Research Letters
Transmission of BSE by blood transfusion in sheep