VARIANT CJD (vCJD) or nvCJD: Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case

Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case

Abigail B. Diack, Aileen Boyle, Diane Ritchie, Chris Plinston, Dorothy Kisielewski, Jesús de Pedro-Cuesta, Alberto Rábano, Robert G. Will,1 Jean C. Manson1

We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.

I n 2008 in Spain, 2 cases of variant Creutzfeldt-Jakob disease (vCJD) in first-degree relatives were identified. After the death of a 41-year-old man (patient 1) from vCJD, his 64-year-old mother (patient 2) began showing symptoms of anxiety and depression and, 2 months later, a gait disorder and progressive dementia. Although the clinical duration was relatively short and the early symptoms uncommon in comparison to vCJD cases in the United Kingdom, the overall clinical phenotype and posterior thalamic hyperintensities as seen in an MRI brain scan led to a diagnosis of suspected vCJD. Neuropathological examination confirmed the diagnosis of vCJD. Both patients were 129MM homozygous, had never received a blood transfusion or tissue graft, and had lived in the same town within the Castilla-León region of Spain (Table 1) (1). The region is a farming area at high risk for bovine spongiform encephalopathy (BSE); 3 of the 5 cases of vCJD reported in Spain came from this region (1). The patients had similar eating habits, which included ingestion of bovine brain. We conducted a study to determine whether these 2 vCJD cases were caused by the BSE agent, whether the agent strain was similar to previously characterized human vCJD cases, and whether the age of the patients would influence the strain characteristics.

Conclusions

This transmission study of central nervous system tissue from 2 first-degree relatives with vCJD confirms that the same infectious transmissible spongiform encephalopathy (TSE) agent was responsible for both cases. Comparisons of incubation period, TSE neuropathology, and PrPres biochemistry indicate that this strain is consistent with that of a UK case of vCJD and with historical vCJD transmission data (6). The epidemiologic investigation of the 2 related patients indicated that they had shared a common residence and dietary habits, including cattle brain consumption, for >30 years. This finding suggests a common source of infection linked to the consumption of highrisk material in a known BSE area, and these transmission studies support the hypothesis that consumption of BSE-contaminated food products is a major risk factor for vCJD (7).

A feature of the UK vCJD epidemic was the relatively young age of the patients at onset. During 1995–2014, only 6 of 177 cases of vCJD identified in the United Kingdom were in persons >55 years of age at the onset of symptoms. Clinical phenotypes in these 6 patients were less consistent than those observed in younger patients (8). The evidence suggests that age is not a barrier to either infection or developing the disease; diagnosis of vCJD may become more important as exposed populations become older. Our study demonstrates that older persons harbor the vCJD agent in the central nervous system in a similar manner to younger persons. Small differences in incubation periods and the intensity of TSE vacuolation are apparent, which may be indicative of variation in the titer of the isolates. It is unknown when the 2 patients from Spain were infected, but if they were exposed at the same time, the 23-year difference in age at time of exposure may have influenced pathogenesis and the ability of the agent to replicate. A delay in neuroinvasion or slower rates of replication in the brain could explain why clinical symptoms are more variable in older patients.

Although our study demonstrates that clinical presentation and infective titer may differ between patients, the overall strain characteristics remain similar. Thus, the vCJD strain can be identified using our strain typing panel regardless of these variable factors.

This study highlights the need for awareness of vCJD in older age groups, particularly in patients with clinical manifestations of atypical dementias. These findings add additional supporting evidence to the hypothesis that a single strain of TSE agent is responsible for vCJD cases, regardless of geographic origin or age at infection, and indirectly support the hypothesis of a dietary origin for primary cases of vCJD.

https://wwwnc.cdc.gov/eid/article/23/9/pdfs/17-0159.pdf

the UKBSEnvCJD of adolescents only theory falls further into the abyss, along with the notion that it was nvCJD only that was zoonosis zoonotic disease there from, imo...tss

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

***is the third potentially zoonotic PD (with BSE and L-type BSE),

***thus questioning the origin of human sporadic cases.

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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***thus questioning the origin of human sporadic cases***

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***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efﬁciency comparable to that of cattle BSE. While the efﬁciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Saturday, April 23, 2016

Scrapie ZOONOSIS PRION CONFERENCE TOKYO 2016

*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 ***

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

SUNDAY, AUGUST 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html

TUESDAY, AUGUST 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html