#Prion shedding is reduced by chronic wasting disease {#CWD} #vaccination

 

Abstract

Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30–90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014166

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Case Report: #CJD and #diagnosis #challenges: case report and evidence synthesis

 

Abstract

Introduction

Prion diseases are mortal neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD). Due to its heterogenous clinical presentation diagnosis uncertainties are common. In this paper we explore CJD diagnostic challenges focusing on differential diagnosis and diagnostic delays.

Methods

We report a case of a patient who was misclassified and evaluated by several medical specialties before the CJD suspicion. A systematic review of the literature of the CJD case reports focused on the timely and differential diagnosis was carried out in Medline and Embase until May 2023.

Results

Patient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In systematic review, fifteen articles were selected, who reported 31 cases of CJD with problems in the timely diagnosis and incorrect initial diagnosis, the main initial differential diagnoses were psychiatry exacerbation, myelopathy, epilepsy, stroke, parkinsonism, cerebellar ataxia and autoimmune encephalitis. The most common clinical onset was psychobehavioral disturbances (apathy, confusion and sleep disturbance), extrapyramidal signs and cognitive impairment. The diagnosis delay was from one to eighteen months.

Conclusion

A discussion of the case report and the diagnostic challenges reported in the literature was made. Patients can present a wide range of symptoms. It is recommended to consider CJD for the differential diagnosis in patients with behavioral symptoms, and cognitive impairment.

Source: 

Link: https://f1000research.com/articles/14-425

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#Transmission and Characterization of #CJD and #CWD in the North #American Deer #Mouse

Abstract

Prion transmission into rodents is essential for understanding prion strains. However, it is often limited by a “species barrier” that makes transmission challenging and complicates the study of animal and human prion diseases. Here, we report that North American deer mice (Peromyscus maniculatus) are susceptible to infection with both human sporadic Creutzfeldt–Jakob disease (sCJD) and chronic wasting disease (CWD). Experimental transmission of both sCJD and CWD in deer mice resulted in 100% attack rates, albeit with differing incubation times, with CWD-inoculated mice taking nearly three times longer than sCJD-inoculated mice to succumb. We observed distinct patterns of spongiform vacuolation and prion-protein deposition in the brain, as well as distinct protein-glycosylation profiles and seeding kinetics in RT-QuIC for each strain. Adaptation on the second passage led to reduced incubation periods and marked strain-specific pathology, as seen predominantly in the cortex in sCJD and the thalamus in CWD. Notably, primary transmission of CWD resulted in infrequent vacuoles and widespread punctate deposits of prion protein in the brain, while diffuse staining and remarkable vacuolation of the thalamus were seen on passage. Prion seeding kinetics for sCJD and CWD were indistinguishable in the second passage; however, the distinct glycosylation patterns seen on immunoblot of the prion protein were maintained. Adaptation also resulted in extraneural dissemination of prion seeding activity distinct to CWD infection. Overall, the ability to transmit both CWD and sCJD to this model, resulting in clear differences in incubation period, biochemical properties, clinical signs, pathology and seeding kinetics, indicates that the model has the potential for use as a tool to investigate atypical cases of sCJD that may indicate CWD spillover to humans.

Source: Viruses, https://www.mdpi.com/1999-4915/17/4/576

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Isolation of a novel #human #prion #strain from a PRNP codon 129 heterozygous #vCJD #patient

Abstract

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), caused variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. Codon 129 polymorphism of the human prion protein gene (PRNP), encoding either methionine (M) or valine (V), dictates the propagation of distinct human prion strains and up to now all but one neuropathologically confirmed vCJD patients have had a 129MM genotype. Concordant with this genetic association, transgenic modelling has established that human PrP 129V is incompatible with the vCJD prion strain and that depending on codon 129 genotype, primary human infection with BSE prions may, in addition to vCJD, result in sporadic CJD-like or novel phenotypes. In 2016 we saw the first neuropathologically confirmed case of vCJD in a patient with a codon 129MV genotype. This patient’s neuropathology and molecular strain type were pathognomonic of vCJD but their clinical presentation and neuroradiological features were more typical of sporadic CJD, suggestive of possible co-propagation of another prion strain. Here we report the transmission properties of prions from the brain and lymphoreticular tissues of the 129MV vCJD patient. Primary transmissions into transgenic mice expressing human PrP with different codon 129 genotypes mainly produced neuropathological and molecular phenotypes congruent to those observed in the same lines of mice challenged with prions from 129MM vCJD patient brain, indicative that the vCJD prion strain was the dominant propagating prion strain in the patient’s brain. Remarkably however, some transgenic mice challenged with 129MV vCJD patient brain propagated a novel prion strain type which at secondary passage was uniformly lethal in mice of all three PRNP codon 129 genotypes after similar short mean incubation periods. These findings establish that cattle BSE prions can trigger the co-propagation of distinct prion strains in humans.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012904

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Detection of #Prions in Wild #Pigs (Sus scrofa) from Areas with Reported #CWD Cases, #USA

Abstract

Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.

Source: Emerging Infectious Diseases Journal, https://wwwnc.cdc.gov/eid/article/31/1/24-0401_article

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