A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia
★ Editor's Choice
★ A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom
of Saudi Arabia
Michael B. Coulthart, Michael D. Geschwind, Shireen Qureshi, Nicolas
Phielipp, Alex Demarsh, Joseph Y. Abrams, Ermias Belay, Pierluigi Gambetti,
Gerard H. Jansen, Anthony E. Lang, Lawrence B. Schonberger
2609-2616 First published online: 26 September 2016 Michael B.
Coulthart
1 Canadian Creutzfeldt-Jakob Disease Surveillance System, Centre for
Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency
of Canada, Ottawa, ON K1A 0K9, Canada Michael D. Geschwind
2 Memory and Aging Center, Box 1207, University of California, San
Francisco (UCSF), San Francisco, CA 94143-1207, USA Shireen Qureshi
3 Consultant Neurologist, Dhahran Health Center, Dhahran, Saudi Arabia
Nicolas Phielipp
4 Department of Neurology, Parkinson’s and Movement Disorders Program,
University of California Irvine, Irvine, CA 92697, USA Alex Demarsh
5 Zoonoses Division, Centre for Foodborne, Environmental and Zoonotic
Infectious Diseases, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada
Joseph Y. Abrams
6 Division of High Consequence Pathogens and Pathology, National Center for
Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA 30333, USA Ermias Belay
6 Division of High Consequence Pathogens and Pathology, National Center for
Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA 30333, USA Pierluigi Gambetti
7 Department of Pathology, Case Western Reserve University, Cleveland, OH
44106, USA Gerard H. Jansen
8 Eastern Ontario Regional Laboratory Association, Ottawa Hospital, Ottawa,
ON K1Y 4E9, Canada Anthony E. Lang
7 Department of Pathology, Case Western Reserve University, Cleveland, OH
44106, USA Lawrence B. Schonberger
6 Division of High Consequence Pathogens and Pathology, National Center for
Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA 30333, USA
Summary As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease—the
human form of a prion disease of cattle, bovine spongiform encephalopathy—have
been reported from 12 countries. With few exceptions, the affected individuals
had histories of extended residence in the UK or other Western European
countries during the period (1980–96) of maximum global risk for human exposure
to bovine spongiform encephalopathy. However, the possibility remains that other
geographic foci of human infection exist, identification of which may help to
foreshadow the future of the epidemic. We report results of a quantitative
analysis of country-specific relative risks of infection for three individuals
diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were
born and raised in Saudi Arabia, but had histories of residence and travel in
other countries. To calculate country-specific relative probabilities of
infection, we aligned each patient’s life history with published estimates of
probability distributions of incubation period and age at infection parameters
from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The
distributions were then partitioned into probability density fractions according
to time intervals of the patient’s residence and travel history, and the density
fractions were combined by country. This calculation was performed for
incubation period alone, age at infection alone, and jointly for incubation and
age at infection. Country-specific fractions were normalized either to the total
density between the individual’s dates of birth and symptom onset (‘lifetime’),
or to that between 1980 and 1996, for a total of six combinations of parameter
and interval. The country-specific relative probability of infection for Saudi
Arabia clearly ranked highest under each of the six combinations of parameter ×
interval for Patients 1 and 2, with values ranging from 0.572 to 0.998,
respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint
incubation and age at infection × 1980–96). For Patient 3, relative
probabilities for Saudi Arabia were not as distinct from those for other
countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for
incubation period, age at infection and jointly for incubation and age at
infection. However, for this patient Saudi Arabia clearly ranked highest within
the 1980–96 period: 0.859, 0.871 and 0.865, respectively, for incubation period,
age at infection and jointly for incubation and age at infection. These findings
support the hypothesis that human infection with bovine spongiform
encephalopathy occurred in Saudi Arabia.
prion diseases variant Creutzfeldt-Jakob disease bovine spongiform
encephalopathy Saudi Arabia
snip...
Discussion
We have presented clinical and diagnostic findings for patients with vCJD,
including results of EEG, MRI, CSF protein marker assay, molecular genetic
analysis, PrP immunoblot, and histopathological examination of brain and/or
lymphoid tissue using PrP immunohistochemistry. All patients met established
criteria according to internationally accepted vCJD case definitions. The
diagnoses were supported by multiple forms of evidence, in two cases with
neuropathology (final diagnosis: definite vCJD) and one with tonsil pathology
(final diagnosis: probable vCJD). We also documented lifetime residence and
travel histories for each patient. These were used to estimate relative
probabilities of infectious exposure in the various countries in which each
patient had resided or travelled, using distributions of incubation period and
age at infection derived from probabilistic modelling of the best-studied cohort
from the UK vCJD epidemic (Garske and Ghani, 2010). Our conclusion in each case
was that the single most probable country in which infectious exposure took
place was Saudi Arabia.
There is compelling evidence that BSE is the zoonotic cause of vCJD (Will
et al., 1996; Bruce et al., 1997; Hill et al., 1997; Scott et al., 1999; Diack
et al., 2014). Exposure to BSE-contaminated UK beef products between 1980, when
epidemic transmission of BSE is estimated to have begun in the UK, and 1996 when
reinforced regulation of animal feed was implemented there, is considered the
major global risk factor for vCJD (Smith and Bradley, 2003). During this period
nearly 170 000 cases of BSE were confirmed in the UK, over 28 times the total
number of such cases reported in the rest of the world through 2014 [World
Organization for Animal Health (OIE), 2014]. It is estimated that 1–3 million UK
cattle were infected with BSE, of which most were undetected and processed for
human consumption (Anderson et al., 1996; Donnelly et al., 2002). This is
reflected in the fact that 178 of the 231 vCJD cases reported worldwide to date
have occurred in UK residents (NCJDRSU, UK). For countries reporting vCJD cases
not linked to UK residence, a significant correlation has been demonstrated
between the number of vCJD cases and the volume of UK beef imported between 1980
and 1996 (Sanchez-Juan et al., 2007). Even in France, with over 1000 BSE cases
and 27 vCJD cases reported as of 2015, imported UK beef was a major source of
exposure to BSE (Chadeau-Hyam and Alperovitch, 2005).
For the same reasons, it is not surprising that four of the nine patients
with vCJD who resided in countries outside the UK and Western Europe at time of
onset—including three of the seven who became ill and/or were diagnosed in
Canada and the USA—had resided in the UK for extended periods between 1980 and
1996 (Jansen et al., 2003; Holman et al., 2010; Yang et al., 2010). A fifth
case, the only one reported to date in a Japanese resident, was attributed to
exposure during a 24-day visit to the UK in early 1990, close to the peak of the
human BSE exposure risk there (Yamada and Variant CJD Working Group,
Creutzfeldt-Jakob Disease Surveillance Committee, Japan, 2006). The absence of
other vCJD cases in Japan supports this interpretation; however, this is the
only case to date in which infectious exposure has been attributed to such a
brief period outside the patient’s main country of residence (Yamada and Variant
CJD Working Group, Creutzfeldt-Jakob Disease Surveillance Committee, Japan,
2006).
In contrast with this general pattern, the three patients reported here
were all born and raised in Saudi Arabia, and resided there for at least 10
years during the period (1980–96) of maximal global exposure risk to
BSE-contaminated UK beef. None of the three had ever resided in the UK; two had
not visited there between 1980 and 1996; and the third had visited there for 2
weeks in late 1995. These features of the patients’ histories alone suggest that
their infectious exposures more likely occurred in Saudi Arabia than in the UK
or Europe. The results of our analysis of country-specific relative
probabilities of infectious exposure strongly support this conclusion. In all
cases—even for Patient 3, who spent the most time outside Saudi Arabia—the
single greatest weight of probability for country of infection was allocated to
Saudi Arabia.
Consistent with this interpretation are UK Customs and Excise data
indicating that over 19 000 tons of bovine carcass meat were exported to Saudi
Arabia in the period 1980–96 inclusively, with >2900 tons from 1988–90, and
>2580 tons during the period 1993–96. Only relatively small amounts (<8 1989="" 1990="" 1991="" 2="" a="" all="" and="" any="" applied="" arabia="" as="" be="" beef="" been="" bse="" by="" carcass="" case.="" communication="" could="" customs="" data="" demonstrate="" div="" during="" e.g.="" embargo="" epidemiological="" er="" even="" exposure="" for="" furthermore="" given="" has="" have="" human="" ig.="" importation="" in="" individual="" infected.="" inference="" it="" justify="" life-history="" likely="" majesty="" meat="" note="" occurred="" of="" or="" patients="" personal="" point="" products="" recorded="" reflecting="" revenue="" s="" saudi="" shipped="" short-term="" sufficient="" that="" the="" this="" three="" to="" tons="" uk="" we="" were="" would="">
Questions could be raised regarding the realism of the country-specific
probability weightings we have estimated. For example, despite our use of
incubation period and age at infection estimates from the largest, most recent
and best-studied cohort of UK vCJD cases, these estimates arguably may not be
directly applicable to non-UK populations (Garske and Ghani, 2010). A related
point has to do with the fact that earlier studies had yielded different values
(e.g. incubation periods in excess of 16 years)—presumably consistent with the
relatively late dates of onset of the three patients described here (2003, 2006
and 2010) (Valleron et al., 2001; Boelle et al., 2003).
To address these questions, we first point out that there is no specific
evidence to support such epidemiological differences and that, as noted above,
all three patients described here displayed clinical, paraclinical and
pathological features typical of vCJD cases reported from the UK and other
countries (Heath et al., 2010). As also noted above, the risk of exposure to
BSE-contaminated beef is considered to have applied globally, and not only in
the UK, suggesting that in a broad sense all cases of vCJD can be considered to
be part of the same epidemic. Lastly, to address the possibility that a longer
incubation period would have a significant effect on the results of our
analysis, we repeated the above computations using a mean incubation period of
16.7 years (Valleron et al., 2001). ***Although we found small differences in
some country-specific probabilities (for Patient 3 only), the key conclusions
were unchanged (results not shown).
The limited number of clinical cases of vCJD confirmed worldwide to date,
with only one vCJD case reported in 2013 (in the UK), one in 2014 (in the USA),
and two in 2016 (one each in the UK and Italy) supports an optimistic view that
few additional vCJD deaths are likely. Nevertheless, uncertainty remains
regarding size and duration of the rightward ‘tail’ of the epidemic curve
(Garske and Ghani, 2010). This uncertainty is accentuated by the results of a
laboratory-based survey of archived tonsil and appendix specimens, which
estimated a subclinical vCJD infection prevalence of 493 per million (95%
confidence interval: 282, 801) in the general UK population, much higher than
suggested by the number of clinical vCJD cases reported in that country to date
(Gill et al., 2013).
This tissue-based survey also demonstrated that even though almost all vCJD
patients examined to date, including the three reported here, have been
homozygous for the ATG (methionine) allele at codon 129 of the PRNP gene,
individuals with any of the three possible genotypes at this codon can be
infected by the BSE/vCJD agent. The potential epidemiologic significance of this
genetic risk factor has been further highlighted by a recent report from the UK
of an autopsy-confirmed case of vCJD in an individual who was heterozygous for
ATG (methionine) and GTG (valine) alleles at PRNP codon 129 (Will et al., 2016).
This finding is consistent with the hypothesis that future cases of vCJD may
occur in individuals with longer incubation periods who are heterozygous for
methionine and valine alleles at PRNP codon 129, or possibly homozygous for the
valine allele (Garske and Ghani, 2010).
We also note that Patient 3, who was heterozygous for GAG (glutamic acid)
and AAG (lysine) alleles at PRNP codon 219, is the third vCJD patient with this
genotype reported to date (Lukic et al., 2010). This genotype is relatively
common in Eastern and Southern Asia and the Pacific, where it reaches population
frequencies in the range of 1–10% and is deemed to be protective against
sporadic CJD, but very rare elsewhere (Shibuya et al., 1998; Jeong et al., 2005;
Soldevila et al., 2006). Heterozygosity at codon 219 has also been proposed to
increase susceptibility to vCJD, suggesting that the likelihood of future vCJD
cases occurring in residents of non-European countries may be influenced by this
genetic factor (Lukic et al., 2010). With the small number of such cases
reported to date, however, and noting that our Patient 3 was of South Asian
background, further investigation of this important hypothesis is
warranted.
Still other questions relate to atypical forms of BSE that appear to arise
spontaneously in cattle, as sporadic CJD is believed to originate in humans. It
is presently unknown whether atypical BSE can cause human disease, or whether
the original BSE outbreak emerged in this way (Comoy et al., 2008; Tranulis et
al., 2011). These uncertainties, as well as the prolonged incubation period of
vCJD and strong evidence of its transmissibility by blood transfusion, support
ongoing precaution. Current measures to monitor and control BSE and CJD
internationally remain key elements of a prudent long-term public health
strategy (Diack et al., 2014).
4th case of nvCJD in USA, 2nd nvCJD case in TEXAS, please remember;
***The specific overseas country where this patient’s infection occurred is
less clear largely because the investigation did not definitely link him to a
country where other known vCJD cases likely had been infected.
3rd case nvCJD ;
***Although we found small differences in some country-specific
probabilities (for Patient 3 only), the key conclusions were unchanged (results
not shown).
Sunday, November 23, 2014
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in
June 2014 confirmed as USA case NOT European
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas
Updated: October 7, 2014
CDC and the Texas Department of State Health Services (DSHS) have completed
the investigation of the recently reported fourth vCJD case in the United
States. It confirmed that the case was in a US citizen born outside the Americas
and indicated that the patient's exposure to the BSE/vCJD agent most likely
occurred before he moved to the United States; the patient had resided in
Kuwait, Russia and Lebanon. The completed investigation did not support the
patient's having had extended travel to European countries, including the United
Kingdom, or travel to Saudi Arabia. The specific overseas country where this
patient’s infection occurred is less clear largely because the investigation did
not definitely link him to a country where other known vCJD cases likely had
been infected.
>>>the patient had resided in Kuwait, Russia and Lebanon.
>>>The completed investigation did not support the patient's
having had extended travel to European countries, including the United Kingdom,
or travel to Saudi Arabia.
NOW we all know why the state of Texas or the CDC did not want to report
this case, because it was a home grown case of nvCJD right here in Texas?...tss
Monday, June 02, 2014
Confirmed Variant CJD Case in Texas
Variant Creutzfeldt-Jakob Disease Death, United States: 1st Case Report
The only variant Creutzfeldt-Jakob disease (vCJD) patient identified in the
United States died in 2004, and the diagnosis was confirmed by analysis of
autopsy tissue. The patient likely acquired the disease while growing up in
Great Britain before immigrating to the United States in 1992. Additional vCJD
patients continue to be identified outside the United Kingdom, including 2 more
patients in Ireland, and 1 patient each in Japan, Portugal, Saudi Arabia, Spain
and the Netherlands. The reports of bloodborne transmission of vCJD in 2
patients, 1 of whom was heterozygous for methionine and valine at polymorphic
codon 129, add to the uncertainty about the future of the vCJD outbreak.
snip...
see case history on 1st nvCJD case in USA here ;
A 22-year-old Florida resident became the first person in the USA to be
diagnosed with probable variant Creutzfeldt-Jakob disease (vCJD), according to
the US Centers for Disease Control and Prevention (CDC). Because the young woman
was raised in the UK when the BSE outbreak was at its peak, officials believe
that she contracted the disease there. The case report, which is published in
Morbidity and Mortality Weekly Report (2002; 51: 927—29;
Probable Variant Creutzfeldt-Jakob Disease in a US Resident—Florida,
2002
JAMA. 2002;288:2965-2967.
MMWR. 2002;51:927-929
On April 18, 2002, the Florida Department of Health and CDC announced the
occurrence of a likely case of variant Creutzfeldt-Jakob disease (vCJD) in a
Florida resident aged 22 years. This report documents the investigation of this
case and underscores the importance of physicians increasing their suspicion for
vCJD in patients presenting with clinical features described in this report who
have spent time in areas in which bovine spongiform encephalopathy (BSE) is
endemic.
In early November 2001, the patient sought medical care for depression and
memory loss that adversely affected the patient's work performance. The
primary-care physician referred the patient to a psychologist. In early December
2001, the patient received a traffic ticket for failing to yield the right of
way. In mid-December 2001, the patient had involuntary muscular movements, gait
changes, difficulty dressing, and incontinence. In January 2002, the patient was
evaluated in a local emergency department for these symptoms. A computerized
tomography scan of the head revealed no abnormalities; a panic attack was
diagnosed, and the patient was treated with an anti-anxiety medication.
In late January 2002, the patient's mother, a resident of the United
Kingdom, took the patient to England, where medical evaluations were conducted
during the next 3 months. During this period, the patient's memory loss and
other neurologic symptoms worsened. The patient experienced falls with minor
injuries, had difficulty taking a shower and dressing, and was unable to
remember a home telephone number or to make accurate mathematical calculations.
The patient subsequently became confused, hallucinated, and had speech
abnormalities with lack of content, bradykinesia, and spasticity. The patient
was referred to a neurologist, who suspected vCJD and subsequently referred the
patient to the National Prion Clinic in the United Kingdom.
Medical evaluations at the National Prion Clinic included an
electroencephalogram (EEG), which revealed a normal alpharhythm, and magnetic
resonance imaging (MRI) studies, which revealed signal abnormalities in the
pulvinar and metathalamus region that were suggestive of vCJD. The patient had a
tonsil biopsy, and a Western blot analysis of the biopsy tissue demonstrated the
presence of protease-resistant prion protein (PrP-res) with the characteristic
pattern of vCJD; an immunohistochemical test for PrP-res also supported a
diagnosis of vCJD. Analysis of the prion protein gene detected no mutation and
showed methionine homozygosity at codon 129, consistent with all 105 vCJD
patients tested in the United Kingdom (R. Will, Western General Hospital,
Edinburgh, Scotland, personal communication, 2002).
The patient received experimental treatment with quinacrine for 3 months.
As of late September 2002, the patient had become bedridden, experienced
considerable weight loss requiring surgical insertion of a feeding tube, and was
no longer communicating with family members. On the basis of a case definition
developed in the United Kingdom, the patient's illness met criteria for a
probable case of vCJD.1
The patient was born in the United Kingdom in 1979 and moved to Florida in
1992. The patient never had donated or received blood, plasma, or organs and
never had received human growth hormone. There was no family history of CJD. In
October 2001, before the onset of the illness, the patient's wisdom teeth were
extracted, but there was no history of major surgery.
Reported by:
S Wiersma, MD, State Epidemiologist, Florida Dept of Health. S Cooper,
MRCP, R Knight, FRCP, National Creutzfeldt-Jakob Disease Surveillance Unit,
Western General Hospital, Edinburgh, Scotland; AM Kennedy, MD, National Prion
Clinic, Dept of Neurology, St. Mary's Hospital, London; S Joiner, MSc, Medical
Research Council Prion Unit, Dept of Neurodegenerative Disease, Institute of
Neurology, London, United Kingdom. E Belay, MD, LB Schonberger, MD, Div of Viral
and Rickettsial Diseases, National Center for Infectious Diseases, CDC.
CDC Editorial Note:
snip...full text ;
Variant Creutzfeldt-Jakob Disease Death, United States: 2nd Case Report
vCJD (Variant Creutzfeldt-Jakob Disease)
Update: Variant Creutzfeldt-Jakob Disease in a U.K. Citizen Who Had
Temporarily Resided in Texas, 2001-2005
In November 2005, the U.K. National Creutzfeldt-Jakob Disease (CJD)
Surveillance Unit in Edinburgh, Scotland notified the Centers for Disease
Control and Prevention (CDC) about a probable variant CJD diagnosis in a
30-year-old man who resided in Texas during 2001-2005. The patient had onset of
symptoms in early 2005 while in Texas. He then returned to the United Kingdom,
where his illness progressed, and a diagnosis of variant CJD was made. This
diagnosis was confirmed neuropathologically after the patient's death.
The variant CJD diagnosis was initially based on typical clinical
manifestations of the disease and demonstration of the characteristic “pulvinar
sign” on magnetic resonance imaging of the brain. No biopsy tissues are
available for pathologic confirmation of the diagnosis. While living in the
United States, the patient had no history of hospitalization, of having invasive
medical procedures, or of donation or receipt of blood and blood products.
The patient almost certainly acquired the disease in the United Kingdom. He
was born in the United Kingdom and lived there throughout the defined period of
risk (1980-1996) for human exposure to the agent of bovine spongiform
encephalopathy (BSE, commonly known as “mad cow” disease). His stay in the
United States was too brief relative to what is known about the incubation
period for variant CJD. For additional information about the incubation period
for variant CJD, see Belay ED, Sejvar JJ, Shieh WJ, et al. “Variant
Creutzfeldt-Jakob Disease Death, United States,” Emerg Infect Dis 2005;
available at
By convention, variant CJD cases are ascribed to the country of initial
symptom onset, regardless of where the exposure occurred. Since variant CJD was
first reported in 1996, a total of 195 patients with this disease from 11
countries have been identified. As of August 11, 2006, variant CJD cases have
been reported from the following countries: 162 from the United Kingdom, 20 from
France, 4 from Ireland, 2 from the United States (including the current case),
and one each from Canada, Italy, Japan, Netherlands, Portugal, Saudi Arabia, and
Spain. Similar to the two U.S. cases, two of the four cases from Ireland and the
single cases from Canada and Japan were likely exposed to the BSE agent while
residing in the United Kingdom.One of the 20 French cases may also have been
infected in the United Kingdom. Strong scientific evidence indicates that
variant CJD results from the transmission to humans of the agent that causes BSE
in cattle. The BSE outbreak in cattle that was first detected in the 1980s in
the United Kingdom has spread to many other European countries, and cases in
cattle have been identified outside of Europe, in Canada, Israel, Japan, and the
United States.
Date: August 14, 2006 Content source: National Center for Infectious
Diseases
Variant Creutzfeldt-Jakob Disease Death, United States: 3rd Case Report
NO DETAILED case report I could find on this very unusual and assumed case
of nvCJD in the USA, but here is cdc short report ;
vCJD (Variant Creutzfeldt-Jakob Disease)
Confirmed Case of Variant Creutzfeldt Jakob Disease (vCJD) in the United
States in a Patient from the Middle East
The Virginia Department of Health and the Centers for Disease Control and
Prevention announce the recent confirmation of a vCJD case in a U.S. resident.
This is the third vCJD case identified in a U.S. resident. This latest U.S. case
occurred in a young adult who was born and raised in Saudi Arabia and has lived
in the United States since late 2005. The patient occasionally stayed in the
United States for up to 3 months at a time since 2001 and there was a shorter
visit in 1989. In late November 2006, the Clinical Prion Research Team at the
University of California San Francisco Memory and Aging Center confirmed the
vCJD clinical diagnosis by pathologic study of adenoid and brain biopsy tissues.
The two previously reported vCJD case-patients in U.S. residents were each born
and raised in the United Kingdom (U.K.), where they were believed to have been
infected by the agent responsible for their disease. There is strong scientific
evidence that the agent causing vCJD is the same agent that causes bovine
spongiform encephalopathy (BSE, commonly known as mad cow disease).
Variant CJD is a rare, degenerative, fatal brain disorder that emerged in
the United Kingdom in the mid-1990s. Although experience with this new disease
is limited, evidence to date indicates that there has never been a case
transmitted from person-to-person except through blood transfusion. Instead, the
disease is thought to result primarily from consumption of cattle products
contaminated with the BSE agent. Although no cases of BSE in cattle have been
reported in Saudi Arabia, potentially contaminated cattle products from the
United Kingdom may have been exported to Saudi Arabia for many years during the
large U.K. BSE outbreak.
The current case-patient has no history of receipt of blood, a past
neurosurgical procedure, or residing in or visiting countries of Europe. Based
on the patient's history, the occurrence of a previously reported Saudi case of
vCJD attributed to likely consumption of BSE-contaminated cattle products in
Saudi Arabia, and the expected greater than 7 year incubation period for
food-related vCJD, this U.S. case-patient was most likely infected from
contaminated cattle products consumed as a child when living in Saudi Arabia
(1). The current patient has no history of donating blood and the public health
investigation has identified no risk of transmission to U.S. residents from this
patient.
As of November 2006, 200 vCJD patients were reported world-wide, including
164 patients identified in the United Kingdom, 21 in France, 4 in the Republic
of Ireland, 3 in the United States (including the present case-patient), 2 in
the Netherlands and 1 each in Canada, Italy, Japan, Portugal, Saudi Arabia and
Spain. Of the 200 reported vCJD patients, all except 10 of them (including the
present case-patient) had resided either in the United Kingdom (170 cases) for
over 6 months during the 1980-1996 period of the large UK BSE outbreak or
alternatively in France (20 cases).
As reported in 2005 (1), the U.S. National Prion Disease Pathology
Surveillance Center at Case Western Reserve University confirmed the diagnosis
in the one previously identified case of vCJD in a Saudi resident. He was
hospitalized in Saudi Arabia and his brain biopsy specimen was shipped to the
United States for analysis. This earlier vCJD case-patient was believed to have
contracted his fatal disease in Saudi Arabia (1).
1) Belay ED, Sejvar JJ, Shieh W-J, Wiersma ST, Zou W-Q, Gambetti P, Hunter
S, Maddox RA, Crockett L, Zaki SR, Schonberger LB. Variant Creutzfeldt-Jakob
disease death, United States. Emerg Infect Dis 2005, 11 (9):1351-1354.
Date: November 29, 2006
The third US resident with vCJD was born and raised in Saudi Arabia and
beginning in 2001 he occasionally stayed in the United States for periods of up
to 3 months duration [30], [31]. The patient relocated to the United States in
2005 where onset of vCJD symptoms was experienced in the spring of 2006. The
diagnosis of vCJD was confirmed based on pathological study of adenoid and brain
biopsy tissues in November 2006. The patient died later in 2006. The patient had
no past history of neurosurgical procedures or visits to European countries. A
previous case of vCJD attributed to consumption of BSE-contaminated cattle
products had been reported in a Saudi Arabian resident [13].
The Virginia Department of Health and the Centers for Disease Control and
Prevention announce the recent confirmation of a case of variant
Creutzfeldt-Jakob disease (vCJD) in a Virginia resident. There is no evidence to
suggest that this case of vCJD was caused by anything the patient was exposed to
while residing in the U.S. or that this situation represents a public health
threat to any U.S. resident.
For more information on vCJD, visit CDC’s Web site at http://www.cdc.gov/ncidod/dvrd/vcjd/other/vCJD_112906.htm.
Virginia CJD Epidemiology CJD is currently a reportable condition in
Virginia only if the ill person is less than 55 years of age; therefore data on
this condition are very limited.
snip...
One limitation to our understanding of CJD in Virginia and the US is that
surveillance mainly uses death certificate data. However, it is very likely that
some cases do not get recorded. CJD is an uncommon disease and physicians who
are not familiar with the signs and symptoms may mistake it for other
conditions. Evidence of the under-reporting of cases comes from some European
countries, where enhanced surveillance has found higher than expected rates due
to increased awareness and better diagnosis. 11 In addition, one small study
reported that as many as 13% of patients diagnosed with Alzheimer’s disease were
found upon autopsy to have actually had CJD.12 Therefore, it seems likely that
the current data underestimate the true incidence of CJD in Virginia and in the
US.
Creutzfeldt-Jakob Disease (CJD) In 2006, a case of Creutzfeldt- Jakob
Disease (CJD) in an individual less than 55 years of age was reported. Sporadic
CJD occurs in Virginia; the age criteria is intended to screen for potential
cases of new variant CJD (nvCJD). On further investigation, this individual was
found to have new variant CJD. Epidemiologic investigation suggested that it was
extremely unlikely that this individual acquired the infection in the U.S.
However, this counted as only the third case of nvCJD ever diagnosed in the U.S.
A high index of suspicion and early testing is important for diagnosing CJD,
since arranging for brain biopsy or autopsy to confirm the diagnosis may be
important for families and healthcare professionals.
From: TSS Subject: Third case of vCJD reported in the United States Date:
December 7, 2006 at 11:08 am PST
##################### Bovine Spongiform Encephalopathy
#####################
Third case of vCJD reported in the United States Editorial Team
(eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office
A clinical diagnosis of variant Creutzfeldt Jakob Disease (vCJD) was
confirmed after brain biopsy investigations in a United States (US) resident and
reported in November [1]. The patient is a young man who grew up in Saudi Arabia
and lived in the US since late 2005. Before that he visited the US once in 1989
and several times after 2001. He has never visited any country in Europe or
received a blood transfusion nor has he undergone any neurosurgical procedure.
This vCJD case is the third in a US resident. The previous two patients both
grew up in the United Kingdom (UK), and this is where they were believed to have
been infected [2].
In Saudi Arabia, the first and only previous case of vCJD was reported in
2005. This was suspected to be related to consumption of meat contaminated with
the prion agent which causes bovine spongiform encephalitis in cattle (BSE). The
European Food Safety Authority (http://www.efsa.org) has not published a
geographical BSE risk assessment for Saudi Arabia [3] and there have been no
cases of BSE in cattle reported by Saudi Arabia to the World Organisation for
Animal Health (http://www.oie.int). Although
the UK is not the only potential beef exporter to have had a BSE epidemic, it
remains plausible, subject to Saudi Arabia's import policy, that contaminated
beef was inadvertently imported from the UK to Saudi Arabia in the period before
1996 (when the EU banned the export of UK beef and cattle).
Based on this patient's history, the occurrence of a previously reported
case of vCJD in Saudi Arabia, and the expected length of the incubation period
for food-related vCJD, the most likely source of infection is thought to be
contaminated meat products the patient consumed as a child when living in Saudi
Arabia. The patient has no known history of donating blood, and investigations
have identified no risk of onwards transmission within the US.
Variant Creutzfeldt-Jakob disease was first identified in the United
Kingdom in the mid-1990s. As of November 2006, worldwide there have been 200
vCJD cases: 164 patients in the United Kingdom, 21 in France, four in Ireland,
three in the US (including the present case), two in the Netherlands and one
each in Canada, Italy, Japan, Portugal, Saudi Arabia and Spain [4]. All
patients, except 10 (including the present case) had lived either in the United
Kingdom (170 cases) or in France (20 cases). Evidence so far indicates that the
most probable source of infection in most cases was consumption of meat products
contaminated with the prion agent causing BSE.
References: Centers for Disease Control and Prevention.
Confirmed Case of Variant Creutzfeldt Jakob Disease (vCJD) in the United
States in a Patient from the Middle East.
Belay ED, Sejvar JJ, Shieh W-J, Wiersma ST, Zou W-Q, Gambetti P, Hunter S,
Maddox RA, Crockett L, Zaki SR, Schonberger LB. Variant Creutzfeldt-Jakob
disease death, United States. Emerg Infect Dis 2005, 11 (9):1351-1354. European
Food Safety Authority . Geographical BSE Risk (GBR) assessments covering
2000-2006. List of countries and their GBR level of risk as assessed by the
Scientific Steering Committee and the (EFSA). 1 August 2006.
The most recent assessments (and reassessments) were published in June 2005
(Table I; 18), and included the categorisation of Canada, the USA, and Mexico as
GBR III. Although only Canada and the USA have reported cases, the historically
open system of trade in North America suggests that it is likely that BSE is
present also in Mexico.
Variant Creuzfeldt-Jakob disease. Current data – December 2006.
Wednesday, December 06, 2006
vCJD USA THIRD CASE DOCUMENTED
Wednesday, December 06, 2006
vCJD USA THIRD CASE DOCUMENTED
I propose that this third case of nvCJD documented in the USA has as much,
or even more of a chance of being an indigenous home grown nvCJD case in the
USA, as that of being exposed the short time this person was in Saudi Arabia, a
country that has never had a case of mad cow disease documented. THE USA import
of highly infectious materials from documented BSE countries, including the U.K.
was phenomenal, let alone it's own TME exposed MBM from right here in the USA.
Strange there is no case history of this supposedly Saudi Arabia source case and
history of time in the USA compared to time in Saudi Arabia, food habits, and
such? It would be nice to compare and try and figure up incubation time periods
with this third case, age, symptoms, beginning clinical signs to death, etc, a
good case study in other words, where is it ???
let's look at a few factors ;
>>>The patient is a young man who grew up in Saudi Arabia and
lived in the US since late 2005. Before that he visited the US once in 1989 and
several times after 2001. He has never visited any country in Europe or received
a blood transfusion nor has he undergone any neurosurgical
procedure.<<<
Heaven forbid anyone suggest that this unlucky Soul was contaminated in the
USA from vCJD. This would just be preposterous, wouldn't it $$$ i am reminded of
a few things deep throat told me years ago;
============================================================
The most frightening thing I have read all day is the report of Gambetti's
finding of a new strain of sporadic cjd in young people.........Dear God, what
in the name of all that is holy is that!!! If the US has different strains of
scrapie.....why???? than the UK...then would the same mechanisms that make
different strains of scrapie here make different strains of BSE...if the
patterns are different in sheep and mice for scrapie.....could not the BSE be
different in the cattle, in the mink, in the humans.......I really think the
slides or tissues and everything from these young people with the new strain of
sporadic cjd should be put up to be analyzed by many, many experts in
cjd........bse.....scrapie Scrape the damn slide and put it into
mice.....wait.....chop up the mouse brain and and spinal cord........put into
some more mice.....dammit amplify the thing and start the damned
research.....This is NOT rocket science...we need to use what we know and get
off our butts and move....the whining about how long everything takes.....well
it takes a whole lot longer if you whine for a year and then start the
research!!! Not sure where I read this but it was a recent press release or
something like that: I thought I would fall out of my chair when I read about
how there was no worry about infectivity from a histopath slide or tissues
because they are preserved in formic acid, or formalin or formaldehyde.....for
God's sake........ Ask any pathologist in the UK what the brain tissues in the
formalin looks like after a year.......it is a big fat sponge...the agent
continues to eat the brain ......you can't make slides anymore because the agent
has never stopped........and the old slides that are stained with Hemolysin and
Eosin......they get holier and holier and degenerate and continue...what you
looked at 6 months ago is not there........Gambetti better be photographing
every damned thing he is looking at.....
Okay, you need to know. You don't need to pass it on as nothing will come
of it and there is not a damned thing anyone can do about it. Don't even hint at
it as it will be denied and laughed at.......... USDA is gonna do as little as
possible until there is actually a human case in the USA of the nvcjd........if
you want to move this thing along and shake the earth....then we gotta get the
victims families to make sure whoever is doing the autopsy is credible,
trustworthy, and a saint with the courage of Joan of Arc........I am not
kidding!!!! so, unless we get a human death from EXACTLY the same form with
EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any
action........it is ALL gonna be sporadic!!!
And, if there is a case.......there is gonna be every effort to link it to
international travel, international food, etc. etc. etc. etc. etc. They will go
so far as to find out if a sex partner had ever traveled to the UK/europe, etc.
etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth.
They have all the cards, all the money, and are willing to threaten and carry
out those threats....and this may be their biggest downfall...
Thanks as always for your help.
(Recently had a very startling revelation from a rather senior person in
government here..........knocked me out of my chair........you must keep
pushing. If I was a power person....I would be demanding that there be a least a
million bovine tested as soon as possible and agressively seeking this disease.
The big players are coming out of the woodwork as there is money to be made!!!
In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the
burden to bare if there is any coverup!"
again it was said years ago and it should be taken seriously....BSE will
NEVER be found in the US! As for the BSE conference call...I think you did a
great service to freedom of information and making some people feign
integrity...I find it scary to see that most of the "experts" are employed by
the federal government or are supported on the "teat" of federal funds. A scary
picture! I hope there is a confidential panel organized by the new government to
really investigate this thing.
You need to watch your back........but keep picking at them.......like a
buzzard to the bone...you just may get to the truth!!! (You probably have more
support than you know. Too many people are afraid to show you or let anyone else
know. I have heard a few things myself... you ask the questions that everyone
else is too afraid to ask.)
================================================================
12/07/06
HOWEVER, if you ONLY consider an OUTSIDE source of mbm from the UK, you
will see that indeed the UK did dump a great deal of mad cow poison on the
middle east, compared to the amount they dumped on USA. comparing from my
records from the U.K., the USA imported about 44 tons of UK mbm or greaves,
Canada got 83 tons in 3 years, 1993, 1994, and 1995. compared to about 6,985
tons exported from the UK to Saudi Arabia over a period of about 20 years, with
Saudi importing mbm from UK as late as 1995. ISRAEL ALSO IMPORTED A GREAT DEAL
OF THIS POISON, 30,006 TONS of MBM FROM UK. A great deal was also imported to
Asian Countries as well. HOWEVER, we cannot state that this is indeed a case of
vCJD exported to the USA from Saudi with certainty. now we all know that the
USDA will paint this pig with lipstick and take it to the dance, to the prom and
anywhere else they can take it, but the fact still remains, they cannot state
this with scientific proof. IF you look at the USA and it's TSE problem, the
rendering industry, and the fact that the USA shipped the technology of
continous rendering to the UK, only to start using 5 years later, then look at
the 100s, if not thousands of tons of potentially and most likely TSE tainted
feed used in the USA for the last 2 decades, the likelyhood of this being a USA
source of vCJD, in my opinion, is possible as well. In 2006 alone, the amount of
ruminant protein still being fed to USA cattle is not only phenominal, but also
very very disturbing. ...TSS
see full text ;
*** Grant Agreement number: 222887 ***
*** Project acronym: PRIORITY ***
*** Project title: Protecting the food chain from prions: shaping European
priorities through basic and applied research Funding ***
Scheme: Large-scale integrating project Period covered: from Oct. 1, 2009
to Sept. 30, 2014
Name of the scientific representative of the project's co-ordinator1, Title
and Organisation: Jesús R. Requena, Ph.D., Associate Professor, Department of
medicine, University of Santiago de Compostela, Spàin. Tel: 34-881815464 Fax:
34-881815403 E-mail: jesus.requena@usc.es
Project website¡Error! Marcador no definido. address: www.prionpriority.eu
PRIORITY, PROJECT FINAL REPORT
*** 14) Concluding that atypical scrapie can transmit to Humans and that
its strain properties change as it transmits between species ***
snip...
Block D: Prion epidemiology
Studies on atypical scrapie were identified as a key element of this block,
given the potential risk associated to this agent. We studied the permeability
of Human, bovine and porcine species barriers to atypical scrapie agent
transmission. Experiments in transgenic mice expressing bovine, porcine or human
PrPC suggest that this TSE agent has the intrinsic ability to propagate across
these species barriers including the Human one. Upon species barrier passage the
biological properties and phenotype of atypical scrapie seem to be altered.
Further experiments are currently ongoing (in the framework of this project but
also in other projects) in order to: (i) characterize the properties of the
prion that emerged from the propagation of atypical scrapie in tg Hu; (ii) to
confirm that the phenomena we observed are also true for atypical scrapie
isolates other than the ones we have studied.
In parallel, studies in shep have concluded that:
*** Atypical scrapie can be transmitted by both oral and intracerebral
route in sheep with various PRP genotypes
*** Low but consistent amount of infectivity accumulates in peripheral
tissue (mammary gland, lymph nodes, placenta, skeletal muscles, nerves) of sheep
incubating atypical scrapie.
*** The combination of data from all our studies leads us to conclude that:
*** Atypical scrapie passage through species barriers can lead to the
emergence of various prions including classical BSE (following propagation in
porcine PRP transgenic mice).
*** Atypical scrapie can propagate, with a low efficacy, in human PrP
expressing mice. This suggests the existence of a zoonotic potential for this
TSE agent.
snip...
We advance our main conclusions and recommendations, in particular as they
might affect public policy, including a detailed elaboration of the evidence
that led to them. Our main recommendations are:
a. The issue of re-introducing ruminant protein into the food-chain The
opinion of the members of Priority is that sustaining an absolute feed ban for
ruminant protein to ruminants is the essential requirement, especially since the
impact of non-classical forms of scrapie in sheep and goats is not fully
understood and cannot be fully estimated. Therefore, the consortium strongly
recommends prohibiting re-introduction of processed ruminant protein into the
food-chain. Arguments in support of this opinion are:
• the large (and still uncharacterized) diversity of prion agents that
circulate in animal populations;
• the uncertainties related to prion epidemiology in animal
populations;
• the unknown efficacy of industrial processes applied to reduce
microbiological risk during processed animal protein (PAP) production on most
prion agents; • the intrinsic capacity of prions to cross interspecies
transmission barriers; • the lack of sensitive methodology for identifying cross
contamination in food.
• the evolution of natural food chains in nature (i.e. who eats whom or
what) has generated an efficient barrier preventing, to some extent, novel prion
epidemies and that this naturally evolved ecology should be respected.
The consortium is also hesitant to introduce processed ruminant proteins
into fish food considering the paucity of data on prion infections in fishes and
sea animals including those of mammalian origin, and the risk of establishing an
environmental contamination of the oceans that cannot be controlled.
b. Atypical prion agents and surveillance
Atypical prion agents (see below) will probably continue to represent the
dominant form of prion diseases in the near future, particularly in Europe.
*** Atypical L-type BSE has clear zoonotic potential, as demonstrated in
experimental models.
*** Similarly, there are now some data that seem to indicate that the
atypical scrapie agent can cross various species barriers.
*** Moreover, the current EU policy for eradicating scrapie (genetic
selection in affected flocks) is ineffective for preventing atypical scrapie.
*** The recent identification of cell-to-cell propagation and the
protein-encoded strain properties of human neurodegenerative diseases such as
Alzheimer's disease and Parkinson's disease, suggest that they bear the
potential to be transmissible even if not with the same efficiency as CJD. More
epidemiological data from large cohorts are necessary to reach any conclusion on
the impact of their transmissibility on public health. Re-evaluations of safety
precautions may become necessary depending on the outcome of these studies. In
that context it would appear valuable
• to develop knowledge related to the pathogenesis and inter-individual
transmission of atypical prion agents in ruminants (both intra- and
inter-species)
• to improve the sensitivity of detection assays that are applied in the
field towards this type of agent
• to maintain a robust surveillance of both animal and human populations
c. The need for extended research on prions
Intensified searching for a molecular determinants of the species barrier
is recommended, since this barrier is a key for many important policy areas -
risk assessment, proportional policies, the need for screening of human products
and food. In this respect, prion strain structural language also remains an
important issue for public health for the foreseeable future. Understanding the
structural basis for strains and the basis for adaptation of a strain to a new
host will require continued fundamental research. Prions maintain a complex
two-way relationship with the host cell and fundamental research is needed on
mechanisms for their transmission, replication and cause of nervous system
dysfunction and death.
Early detection of prion infection, ideally at preclinical stage, also
remains crucial for development of effective treatment strategies in humans
affected by the disease.
Position of the Priority consortium
Nearly 30 years ago, the appearance in the UK of Bovine Spongiform
Encephalopathy (BSE) quickly brought the previously obscure “prion diseases” to
the spotlight. The ensuing health and food crises that spread throughout Europe
had devastating consequences. In the UK alone, there were more than 36,000 farms
directly affected by BSE and the transmission of BSE prions to humans via the
food chain has caused over 200 people in Europe to die from variant
Creutzfeldt-Jakob disease (vCJD) (http://www.cjd.ed.ac.uk
Origins of prion epidemies
Classical BSE now appears to be under control, with 18 EU Member States
having achieved the World Organisation for Animal Health (Office International
Epizooties) „negligible risk‟ status (May 2014; http://www.oie.int/en/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/),
and the remaining MS assessed as „controlled‟ risk. Of note, research, including
EU-funded research, has played a key role in this success: while the origin of
the infection was never defined, the principle driver of the epidemic was
identified as prions in Meat and Bone Meal (MBM). Tests based on prion
protein-specific antibodies were developed, allowing detection of infected
animals, and a better understanding of disease pathogenesis and the distribution
of infectivity in edible tissues; experimental investigation of transmission
barriers between different species allowed a rational estimation of risks, etc.
All of this led to the implementation of rational and effective policies, such
as the MBM ban to protect the animal feed chain, and the Specified Risk Material
(SRM) regulations to protect the human food chain.
In spite of this progress, prions are still a threat. Epidemiological
re-assessment indicates that the ∼10 year incubation period separating the peaks
of the BSE and the vCJD epidemics is probably too short. In addition, results
from a large number of human tonsil and appendix analyses in the UK suggest that
there may be a high number of asymptomatic individuals who are positive for the
disease-associated conformer prion protein PrPSc. While vCJD is the only form of
human prion disease that has been consistently demonstrated to have
lymphoreticular involvement, there has been no systematic investigation of
lymphoid tissue in cases with other prion diseases.
The human prion problem
The clinical cases of vCJD identified to date have all shared a common PrP
genotype (M129M), although one pre-clinical case was confirmed as an M129V
heterozygote, and it has been mooted that perhaps only the M129M proportion of
the population is susceptible. However, in the UK appendix study, PrP
accumulation was described in samples representing every codon 129 genotype,
raising the possibility that genotype does not confer resistance but instead
modulates incubation period. Apart from the two UK studies, the lymphoid tissues
of non-CJD patients have not been examined for the presence of PrPSc, so, these
cases may not solely represent pre-clinical vCJD, but also other forms of prion
disease.
Recent experiments in highly susceptible mouse models indicate the presence
of infectivity in blood or blood components at late disease stages in sporadic
CJD. The significance of this experimental finding for humans has to be explored
in more detail and, at the present time, there is no evidence for the
transmission of prions via blood in sporadic CJD. However a likely scenario is
that all those with signs of infection or abnormal PrP accumulation in
peripheral tissue could have infective blood, posing the risk for transmission
via blood products, which has been clearly demonstrated in experimental models,
and confirmed in several cases of vCJD in man. Altogether, these data clearly
demonstrate the potential risk of a second wave of vCJD, particularly when the
number people identified with lymphoid accumulation of PrPSc (16/32,411) gives a
prevalence estimate in the UK of 493 per million, much higher than the number of
clinical cases seen to date.
The animal prion problem
An increasing number of reports on cases of “atypical” BSE in cattle
throughout the EU and beyond may lead to a new epidemic, particularly since we
still do not understand all factors determining the species barrier. Ovine
scrapie is another concern, because it could mask ovine BSE, presumably
transmissible to humans. Scrapie is endemic and not likely to be eradicated
soon, although current control measures are effective at greatly reducing
disease incidence. Atypical forms, which may be spontaneous, are not affected by
these control measures and these forms of disease will persist in the global
animal population. The low prevalence of these disease forms makes effective
surveillance very challenging. However, there is a clear risk attendant on
ignoring these cases without an understanding of their possible zoonotic
potential, particularly when most forms of human disease have no established
aetiology. In summary, atypical cases of BSE and scrapie presently clearly
outnumber classical cases in cattle and sheep in all member states.
We will highlight the state-of-the-art knowledge and point out scientific
challenges and the major questions for research. Strategic objectives and
priorities in Europe in the future for research that aims to control, eliminate
or eradicate the threat posed by prions to our food and health are also
indicated.
The Priority project has focused on 4 themes, namely the structure,
function, conversion and toxicity of prions; detection of prions; mechanisms of
prion transmission and spreading and epidemiology of prion diseases. This paper
summarizes the opinions/positions reached within these themes at the end of the
project.
WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
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.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
*** Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, 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. ***
O.08: H-type bovine spongiform encephalopathy associated with E211K prion
protein polymorphism: Clinical and pathologic features in wild-type and E211K
cattle following intracranial inoculation
S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy
Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA
USA
In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported
in an animal with an unusual polymorphism (E211K) in the prion protein gene.
Although the prevalence of this polymorphism is low, cattle carrying the K211
allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of
this study was to investigate the phenotype of this BSE strain in wild-type
(E211E) and E211K heterozygous cattle. One calf carrying the wild-type allele
and one E211K calf were inoculated intracranially with H-type BSE brain
homogenate from the US 2006 case that also carried one K211 allelle. In
addition, one wild-type calf and one E211K calf were inoculated intracranially
with brain homogenate from a US 2003 classical BSE case. All animals succumbed
to clinical disease. Survival times for E211K H-type BSE inoculated catttle (10
and 18 months) were shorter than the classical BSE inoculated cattle (both 26
months). Significant changes in retinal function were observed in H-type BSE
challenged cattle only. Animals challenged with the same inoculum showed similar
severity and neuroanatomical distribution of vacuolation and disease-associated
prion protein deposition in the brain, though differences in neuropathology were
observed between E211K H-type BSE and classical BSE inoculated animals. Western
blot results for brain tissue from challenged animals were consistent with the
inoculum strains.
This study demonstrates that the phenotype of E211K H-type BSE remains
stable when transmitted to cattle without the E211K polymorphism, and exhibits a
number of features that differ from classical BSE in both wild-type and E211K
cattle.
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, Val erie 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 longe 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.
P.73: Oral challenge of goats with atypical scrapie
Silvia Colussi1, Maria Mazza1, Francesca Martucci1, Simone Peletto1,
Cristiano Corona1, Marina Gallo1, Cristina Bona1, Romolo Nonno2, Michele Di
Bari2, Claudia D’Agostino2, Nicola Martinelli3, Guerino Lombardi3, and Pier
Luigi Acutis1 1Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e
Valle d’Aosta; Turin, Italy; 2Istituto Superiore di Sanit a; Rome, Italy;
3Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna;
Brescia, Italy
Atypical scrapie transmission has been demonstrated in sheep by
intracerebral and oral route (Simmons et al., Andreoletti et al., 2011) but data
about goats are not available yet. In 2006 we orally challenged four goats, five
months old, with genotype R/H and R/R at codon 154. Animals died starting from
24 to 77 months p.i. without clinical signs. They all resulted negative for
scrapie in CNS and peripheral tissues using Western blot and
immunohistochemistry. Nevertheless these goats could still represent carriers.
This hypothesis was investigated through bioassay in tg338 mice, a sensitive
animal model for atypical scrapie infectivity. By end-point dilution titration,
the starting inoculum contained 106.8 ID50/g. In contrast, all tissues from
challenged goats were negative by bioassay. These negative results could be
explained with the low infectivity of the starting inoculum, which could have
been unable to induce Prion 2015 Poster Abstracts S49 disease or infectivity
within our period of observation. However the challenge conditions could have
been a bias too: as the matter of the fact, while the oral challenge of
classical scrapie is still effective in sheep 6–10 months old (Andreoletti et
al., 2011), Simmons et al. (2011) demonstrated a very short efficacy period for
atypical scrapie (24 hours after birth), hypothesizing that natural transmission
could occur mainly via milk. Our work suggests that this could be true also for
goats and it should be taken into account in oral challenges. However a low
susceptibility of goats to atypical scrapie transmission via oral route cannot
be excluded.
>>> These results suggest that (i) at the level of protein-protein
interactions, CWD adapts to a new species more readily than does BSE and (ii)
the barrier preventing transmission of CWD to humans may be less robust than
estimated.
Accepted manuscript posted online 8 July 2015.
Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy
Species Barriers by Use of Real-Time Conversion
Kristen A. Davenport, Davin M. Henderson, Jifeng Bian, Glenn C. Telling,
Candace K. Mathiason and Edward A. Hoover Prion Research Center, Department of
Microbiology, Immunology and Pathology, College of Veterinary Medicine and
Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA K.
L. Beemon, Editor + Author Affiliations
Next Section ABSTRACT The propensity for transspecies prion transmission is
related to the structural characteristics of the enciphering and new host PrP,
although the exact mechanism remains incompletely understood. The effects of
variability in prion protein on cross-species prion transmission have been
studied with animal bioassays, but the influence of prion protein structure
versus that of host cofactors (e.g., cellular constituents, trafficking, and
innate immune interactions) remains difficult to dissect. To isolate the effects
of protein-protein interactions on transspecies conversion, we used recombinant
PrPC and real-time quaking-induced conversion (RT-QuIC) and compared chronic
wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE)
prions. To assess the impact of transmission to a new species, we studied feline
CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We
cross-seeded fCWD and FSE into each species' full-length, recombinant PrPC and
measured the time required for conversion to the amyloid (PrPRes) form, which we
describe here as the rate of amyloid conversion. These studies revealed the
following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD
was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii)
conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and
CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as
homologous sCJD prions. These results suggest that (i) at the level of
protein-protein interactions, CWD adapts to a new species more readily than does
BSE and (ii) the barrier preventing transmission of CWD to humans may be less
robust than estimated.
IMPORTANCE We demonstrate that bovine spongiform encephalopathy prions
maintain their transspecies conversion characteristics upon passage to cats but
that chronic wasting disease prions adapt to the cat and are distinguishable
from the original prion. Additionally, we showed that chronic wasting disease
prions are effective at seeding the conversion of normal human prion protein to
an amyloid conformation, perhaps the first step in crossing the species barrier.
snip...
Enciphering characteristics of cBSE and cBSE-derived prions are conserved
after transspecies transmission.cBSE and CWD are prion diseases that have been
naturally passaged in their respective species (cattle and deer), whereas feline
spongiform encephalopathy (FSE) and feline chronic wasting disease (fCWD) are
first-passage infections in a new host species (cat). To investigate the
biochemical properties of cBSE and CWD after transspecies transmission to
felines, we compared the amyloidogenicity of fCWD and FSE in the original host
and in feline substrate. We found fCWD to be a more efficient seed for its new
(feline) host, suggesting that adaptation to the new host had occurred (Fig.
4A). In contrast, FSE remained a more efficient seed for its enciphering
(bovine) host, despite its derivation from feline brain PrPC (Fig. 4B). Thereby,
these cross-species seeding experiments in RT-QuIC indicated that the
characteristics of cBSE were maintained upon passage to a new species whereas
CWD had adapted to its new host. These findings in felids suggest that cBSE may
retain its ability to cross species barriers even after transmission to a new
host species and that CWD may change substantially upon transspecies
transmission.
Human rPrPC can be converted by bovine, feline, and cervid prions.The
threat of zoonotic transmission of prion disease is evident and well documented,
yet such transmission is uncommonly observed and incompletely understood. We
thereby explored the propensity of heterologous prions to convert human rPrP. In
these human rPrPC experiments, we used sporadic CJD brain as a positive control
and normal bovine, white-tailed deer, and feline brain as negative controls.
sCJD, as expected, seeded human rPrPC most efficiently, so all other seeds were
normalized to the rate of conversion of sCJD. We found human rPrPC to be a
competent substrate in RT-QuIC for CWD, fCWD, cBSE, and FSE (Fig. 5A).
Interestingly, CWD and fCWD converted human rPrPC more efficiently than did cBSE
and FSE. These data suggest that at the level of PrPC-PrP seed interaction, CWD
has the ability to template the conversion of human rPrPC to ThT-positive
amyloid. In order to assess whether CWD was faster than cBSE due to an increased
concentration of prion seed, we performed Western blotting on the seed inocula.
Western blots indicated that the cBSE sample had a higher concentration of
PrPRes than the CWD sample, indicating that CWD was not a better seed than cBSE
due to PrPRes content (Fig. 5B). Finally, we assessed the behavior of 8 CWD
field isolates, brain samples from white-tailed deer infected naturally and
verified to be positive using full-length white-tailed deer RT-QuIC (Fig. 5C).
All 8 of these isolates converted human rPrPC, confirming that our observations
were not due to the use of experimentally CWD (Fig. 5D). In all, these
experiments suggest that the CWD prions naturally circulating in the western
United States have the capacity to convert human rPrPC in this assay of
protein-protein interactions.
snip...
In summary, real-time conversion demonstrates that CWD and BSE prions
differ in their enciphering rigidity and plasticity across species barriers. One
illustration is the conservation versus adaptation of enciphering prion
characteristics upon passage to cats. These experiments also demonstrate that
human rPrP can be converted to amyloid by both cBSE and CWD prions. These data
point to the importance of deciphering the mechanisms by which prions infect and
adapt to a new species and of prompt continued vigilance regarding indirect
pathways that may facilitate transspecies prion transmission.
Monday, September 19, 2016
Evidence of scrapie transmission to sheep via goat milk
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
2015 Annual Report
1a. Objectives (from AD-416): 1. Investigate the pathobiology of atypical
transmissible spongiform encephalopathies (TSEs) in natural hosts. A.
Investigate the pathobiology of atypical scrapie. B. Investigate the
pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate
the horizontal transmission of TSEs. A. Assess the horizontal transmission of
sheep scrapie in the absence of lambing. B. Determine routes of transmission in
chronic wasting disease (CWD) infected premises. C. Assess oral transmission of
CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine
CWD host range using natural routes of transmission. B. Investigate the
pathobiology of CWD.
1b. Approach (from AD-416): The studies will focus on three animal
transmissible spongiform encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic
wasting disease (CWD) of deer, elk, and moose. The research will address sites
of accumulation, routes of infection, environmental persistence, and ante mortem
diagnostics with an emphasis on controlled conditions and natural routes of
infection. Techniques used will include clinical exams, histopathology,
immunohistochemistry and biochemical analysis of proteins. The enhanced
knowledge gained from this work will help mitigate the potential for
unrecognized epidemic expansions of these diseases in populations of animals
that could either directly or indirectly affect food animals.
3. Progress Report: Research efforts directed toward meeting objective 1 of
our project plan include work in previous years starting with the inoculation of
animals for studies designed to address the pathobiology of atypical scrapie,
atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of
BSE. Post-mortem examination of the animals inoculated with atypical scrapie has
been initiated and laboratory analysis of the tissues is ongoing. Atypical BSE
animals have developed disease and evaluation of the samples is currently
underway. Animals inoculated with a genetic version of BSE have developed
disease with a manuscript reporting these results was published (2012), and
additional laboratory comparisons of genetic BSE to atypical and classical BSE
are ongoing. In addition, we have investigated the possibility that atypical
scrapie was present earlier than previously detected in the national flock by
analyzing archived field isolates using methods that were unavailable at the
time of original diagnosis. Sample quality was sufficiently degraded that modern
methods, beyond those applied to the tissues at the time the tissues were
archived, were not suitable for evaluation. In research pertaining to objective
2, "Investigate the horizontal transmission of TSEs", we have initiated a study
to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to
transmit scrapie to neonatal lambs. At this time, scrapie free ewes have lambed
in the presence of scrapie inoculated animals and the lambs are cohoused with
these inoculated animals.
4. Accomplishments 1. Changes in retinal function in cattle can be used to
identify different types of bovine spongiform encephalopathy (BSE). BSE belongs
to a group of fatal, transmissible protein misfolding diseases known as
transmissible spongiform encephalopathies (TSEs). Like other protein misfolding
diseases including Parkinson's disease and Alzheimer's disease, TSEs are
generally not diagnosed until the onset of disease after the appearance of
unequivocal clinical signs. As such, identification of the earliest clinical
signs of disease may facilitate diagnosis. The retina is the most accessible
part of the central nervous system. ARS scientist in Ames IA described
antemortem changes in retinal function and thickness that are detectable in BSE
inoculated animals up to 11 months prior to the appearance of any other signs of
clinical disease. Differences in the severity of these clinical signs reflect
the amount of PrPSc accumulation in the retina and the resulting inflammatory
response of the tissue. These results are the earliest reported clinical signs
associated with TSE infection and provide a basis for understanding the
pathology and evaluating therapeutic interventions. Further, this work shows
that High-type BSE and classical BSE can be differentiated by eye examination
alone, the first time BSE strains have been differentiable in a live animal.
2. Sheep genetics influences the susceptibility of sheep to scrapie. Sheep
scrapie is a transmissible spongiform encephalopathy that can be transmitted
between affected animals resulting in significant economic losses in affected
flocks. The prion protein gene (PRNP) profoundly influences the susceptibility
of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in
affected sheep. In this study, sheep of 3 different prion genetic types (denoted
VRQ/VRQ, VRQ/ARR and ARQ/ARR) were inoculated and subsequently euthanized upon
onset of disease. Disease aspects were uniform across genotypes and consistent
with manifestations of classical scrapie. Mean survival time differences were
associated with the genetic type such that VRQ/VRQ sheep survived 18 months,
whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively.
Microscopic evaluation revealed similar accumulations in central nervous system
tissues regardless of host genetic type. PrPSc in lymphoid tissue was
consistently abundant in VRQ/VRQ, present but confined to tonsil or
retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep.
The results of this study demonstrate the susceptibility of sheep with the
ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc
accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in
lymphoid tissue. These results are important for science based policy with
regard to testing of sheep for scrapie where some live animal testing is
conducted using lymphoid tissues which would not detect scrapie in some specific
genetic types which could limit the national scrapie eradication program.
Review Publications Greenlee J.J. 2014. The prion diseases of animals. In:
McManus, L.M., Mitchell, R.N., editors. Pathobiology of Human Disease. San
Diego: Elsevier. p. 1124-1133. Greenlee, J.J., Kunkle, R.A., Richt, J.A.,
Nicholson, E.M., Hamir, A.N. 2014. Lack of prion accumulation in lymphoid
tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of
scrapie. PLoS One. 9(9):e108029. Greenlee, J.J., West Greenlee, M.,H. 2015. The
transmissible spongiform encephalopathies of livestock. ILAR Journal.
56(1):7-25. Munoz-Gutierrez, J.F., Schneider, D.A., Baszler, T.V., Dinkel, K.D.,
Greenlee, J.J., Nicholson, E.M., Stanton, J.J. 2015. hTERT-immortalized ovine
microglia propagate natural scrapie isolates. Virus Research. 198:35-43.
Nicholson, E.M. 2015. Detection of the disease-associated form of the prion
protein in biological samples. Bioanalysis. 7(2):253-261. West Greenlee, M.H.,
Smith, J.D., Platt, E.M., Juarez, J.R., Timms, L.L, Greenlee, J.J. 2015. Changes
in retinal function and morphology are early clinical signs of disease in cattle
with bovine spongiform encephalopathy. PLoS ONE. 10(3):e0119431. Comoy, E.E.,
Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand,
V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J.,
Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie
prions to primate after an extended silent incubation period. Scientific
Reports. 5:11573.
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***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.
================
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***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.
===============
Saturday, May 30, 2015
PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
***P.170: Potential detection of oral transmission of H type atypical BSE
in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food
Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a
significant negative impact on the cattle industry worldwide. In response,
governments took actions to prevent transmission and additional threats to
animal health and food safety. While these measures seem to be effective for
controlling classical BSE, the more recently discovered atypical BSE has
presented a new challenge. To generate data for risk assessment and control
measures, we have challenged cattle orally with atypical BSE to determine
transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon
presentation of clinical symptoms, animals were euthanized and tested for
characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral
brain areas but the L-type challenged animal showed no evidence thereof. To our
surprise, neither of the animals euthanized, which were displaying clinical
signs indicative of BSE, showed conclusive mis-folded prion accumulation in the
brain or gut using standard molecular or immunohistochemical assays. To confirm
presence or absence of prion infectivity, we employed an optimized real-time
quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain
Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally
inoculated L type animal using the RT-QuIC. It is possible that these negative
results were related to the tissue sampling locations or that type specific
optimization is needed to detect PrPSc in this animal. We were however able to
consistently detect the presence of mis-folded prions in the brain of the H-type
inoculated animal. Considering the negative and inconclusive results with other
PrPSc detection methods, positive results using the optimized RT-QuIC suggests
the method is extremely sensitive for H-type BSE detection. This may be evidence
of the first successful oral transmission of H type atypical BSE in cattle and
additional investigation of samples from these animals are ongoing.
P.169: PrPSc distribution in brain areas of a natural German H-type BSE
case
Anne Balkema-Buschmann, Grit Priemer, Markus Keller, and Martin H Groschup
Friedrich Loeffler Institut, Institute for Novel and Emerging Infectious
Diseases; Greifswald, Insel Riems, Germany
Keywords: BSE H-type, brain, muscle
Ten years after the initial description of atypical BSE cases of the H-type
and L-type, the distribution of PrPSc in different brain areas and peripheral
tissues of natural cases of these BSE forms is still not fully understood.
Intracerebral challenge experiments have been performed with both atypical BSE
forms in cattle, and the distribution of the abnormal prion protein and
infectivity has been analysed in a variety of tissues, confirming the general
restriction to the central nervous system as it was already generally
acknowledged for classical BSE, but showing a slightly earlier and stronger
involvement of the peripheral nervous system and the skeletal muscle.
www.landesbioscience.com Prion 105
However, data from cattle orally challenged with atypical BSE, which might
mimic the natural situation, are not yet available. Unfortunately, for most
natural cases of atypical BSE, only the obex region is available for further
analysis. The PrPSc distribution in the brains of natural L-type BSE cases in
Italy has been described in some detail, but comparably few such data are yet
available for natural H-type cases. Here we describe the analysis of different
brain areas and muscle samples of a natural H-type BSE case diagnosed in Germany
in 2014, and compare these data with those obtained from the respective samples
collected from cattle challenged intracerebrally with H-type BSE.
*** P.159: Transgenic mice overexpressing rabbit prion protein are
susceptible to BSE, BASE and scrapie prion strains but resistant to CWD and
atypical scrapie
Natalia Fernández-Borges,1 Enric Vidal,2 Belén Pintado,4 Hasier Eraña,1
Montserrat Ordóñez,3 Mercedes Márquez,5 Francesca Chianini,6 Dolors Fondevila,5
Manuel A Sánchez-Martín,7 Olivier Andréoletti,8 Mark P Dagleish,6 Martí
Pumarola,5 and Joaquín Castilla1,3 1CIC bioGUNE; Parque tecnológico de Bizkaia;
Derio; Bizkaia, Spain; 2Centre de Recerca en Sanitat Animal (CReSA); UAB-IR TA,
Campus de la Universitat Autònoma de Barcelona; Bellaterra; Barcelona,
Catalonia, Spain; 3IKERBASQUE; Basque Foundation for Science; Bilbao, Bizkaia,
Spain; 4Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco;
Cantoblanco; Madrid, Spain; 5Department of Animal Medicine and Surgery;
Veterinary faculty; Universitat Autònoma de Barcelona (UAB); Bellaterra
(Cerdanyola del Vallès); Barcelona, Catalonia, Spain; 6Moredun Research
Institute; Bush Loan, Penicuik, Scotland, UK; 7Unidad de Generación de OMGs.
S.E.A. Department of Medicine; University of Salamanca; Salamanca, Spain; 8Ecole
Nationale du Veterinaire; Service de Pathologie du Bétail; Toulouse,
France
Interspecies transmission of prions is a well established phenomenon, both
experimentally and in field conditions. Upon passage through new hosts prion
strains have proven their capacity to change their properties. It is, in fact, a
source of strain diversity which needs to be considered when assessing the
potential risks associated with consumption of prion contaminated protein
sources.
Rabbits were considered for decades a prion resistant species until proven
recently otherwise. To determine the extent of rabbit susceptibility to prions
and to assess their effects on the passage of different prion strains through
this species, a transgenic mouse model overexpressing rabbit PrPC was developed
(TgRab). Intracerebral challenges with prion strains originating from a variety
of species including field isolates (SSBP1 scrapie, Nor98-like scrapie, BSE,
BASE and CWD), experimental murine strains (ME7 and RML), experimentally
obtained strains (sheepBSE) and strains obtained by in vitro crossing of the
species barrier using saPMCA (BSE-RabPrPres, SSBP1-RabPrPres and CWD-RabPrPres)
have been performed.
Interestingly, on first passage, TgRab were susceptible to the majority of
prions tested with the exception of SSBP1 scrapie, CWD and Nor98 scrapie.
Furthermore TgRab were capable of propagating strain-specific features such as
differences in incubation periods, brain lesion and PrPd deposition profiles and
PK resistant western blotting band patterns. Our results confirm previous
studies shattering the myth that rabbits are resistant to prion infection and
this should be taken into account when choosing protein sources to feed rabbits.
P.168: Evolution of the biological properties of L-BSE after passage in
sheep with susceptible and resistant PrP genotypes
Michele A Di Bari, Umberto Agrimi, Claudia D’Agostino, Geraldina Riccardi,
Stefano Marcon, Elena Esposito, Paolo Frassanito, Flavio Torriani, Shimon
Simson, and Romolo Nonno Istituto Superiore di Sanità (ISS) Department of
Veterinary Public Health and Food Safety; Rome, Italy
Background. Cattle L-BSE was efficiently transmitted to sheep with
susceptible (QQ171) and resistant (QR171) PrP genotypes. 1 Notably, the PrPSc
signature of L-BSE was preserved in QQ171 sheep but not in QR171 sheep.2
Notwithstanding, bioassay in transgenic mice expressing bovine or ovine (ARQ)
PrPC showed that L-BSE strain was preserved in both, QQ171 and QR171
sheep-passaged L-BSE.3
Here we studied the biological properties of sheep-passaged L-BSE by
bioassay in bank voles and transgenic mice expressing the ovine VRQ PrP (tg338),
both characterized by a comparatively low susceptibility to cattle L-BSE.
Material and Methods. Voles and tg338 mice were intracerebrally inoculated
with cattle L-BSE and sheep-passaged (QQ171 and QR171) L-BSE isolates. Survival
time, lesion profiles, Pet-blot and WB analysis were used for strain typing.
Results. Cattle L-BSE transmitted quite inefficiently to tg338 mice, with
survival time >400 days post-infection (d.p.i.), while sheep-passaged inocula
were much more efficient and all gave terminal disease by ~140 d.p.i. However,
after sub-passage all inocula converged to a survival time of ~145 d.p.i.. and
showed overlapping pathological phenotypes.
In voles, cattle L-BSE transmitted with very long survival times (~800
d.p.i.) and was accompanied by an upward shift of the PrPSc type. Again, all
sheep-passaged L-BSE isolates transmitted much more efficiently, with similar
survival times of ~360 d.p.i.. Upon second passage, three different strains were
isolated in vole, characterized by distinct pathological phenotypes. This
divergence is epitomized by the different survival times of vole-adapted L-BSE
strains, which were ~400 d.p.i. for cattle L-BSE, ~130 d.p.i. for QQ171-passaged
L-BSE and ~225 d.p.i. for QR171-passaged L-BSE.
Conclusions. These findings, along with previously published data,3 show
that the original L-BSE strain was recovered after passage in sheep when
bioassay was performed in animal models expressing bovine or ovine PrPC. In
contrast, strain changes were observed in both, QQ171- and QR171-passaged L-BSE
by bioassay in vole, a species with divergent PrP sequence compared to
ruminants. Importantly, QQ171- and QR171-passaged L-BSE were characterised by
different PrPSc types and, accordingly, showed different biological properties
when transmitted to voles, but not when transmitted to other animal models.
Overall, our work support the hypothesis that prion isolates are likely
composed of multiple prion components, emphasizes the role of host PrP
polymorphisms on strain selection and mutation, and highlights the risk for new
potentially zoonotic strains that could emerge from prion evolution in animal
reservoirs.
P.172: BSE exposure risk from bovine intestine and mesentery
Fulvio Barizzone,1 Herbert Budka,2 Christine Fast,3 John N Griffin,4
Giuseppe Ru,5 Pietro Stella1 and Olivier Andréoletti6 1European Food Safety
Authority; Parma, Italy; 2Institute of Neuropathology; University Hospital
Zurich; Zurich, Switzerland; 3Friedrich-Loeffler-Institut; Institute of Novel
and Emerging Infectious Diseases; Isle of Riems, Germany; 4Department of
Agriculture, Food and the Marine; Backweston, Celbridge, Co. Kildare, Ireland;
5Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e Valle d’Aosta;
Biostatistics Epidemiology and Analysis of Risk (BEAR) unit; Turin, Italy; 6UMR
Interactions Hôtes Agents Pathogènes; Ecole Nationale Vétérinaire INR A; ENVT;
Toulouse, France
Keywords: Bovine Spongiform Encephalopathy (BSE), cattle, intestine,
mesentery, specified risk material (SRM), quantitative risk assessment
(QRA)
Bovine intestines and mesenteries in the European Union (EU) are considered
among the tissues potentially containing the highest level of BSE infectivity
and have to be removed from the food and feed chain. A quantitative assessment
of the BSE infectious load potentially entering the food and feed chain yearly
in the European Union (EU) was developed. The evolution of the BSE infectious
titre and of the weight of the structures accumulating infectivity was
considered. The number of BSE infected cattle entering undetected in the food
and feed chain yearly was estimated. A model (TSEi) was developed to estimates
the evolution of the BSE infectious load in animals and the total yearly
infectious load that could enter the food and feed chain. In a BSE infected
bovine, the distribution of infectivity in intestines and mesentery varies with
the age. Up to 36 months of age the infectivity is mainly associated (on average
more than 90%) with the last 4 metres of small intestine and the caecum, over 36
and under 60 months of age, there is an inter-individual variability, from 60
months of age the infectivity is mainly associated (on average more than 90%)
with the mesenteric nerves and the celiac and mesenteric ganglion complex. The
total amount of infectivity peaks, about 15 BoID50, in animals younger than 18
months, it declines to 8-9 BoID50 (24–48 months of age) and it drops to 0.7
BoID50 in animals older than 60 months. The ileocaecal plate is the most
infectious part of the intestine and it can be used to estimate the potential
maximum level of exposure for an individual consumer.
In the EU, between 2007 and 2012, the yearly amount of BSE infectivity
associated with intestine and mesentery from animals entering the food and feed
chain was reduced by a factor of 10 (from about 23,000 to about 2,000 BoID50).
However, the maximum level of exposure to the BSE agent from intestine
remained stable (on average about 1.5-1.6 BoID50 per meter).
In case of re-emergence of BSE in the EU there would be an increase of the
potential maximum level of exposure to BSE from intestine. According to the TSEi
model the removal of the last four metres of the small intestine and of the
caecum from the food and feed chain would result in a major reduction of the BSE
exposure risk associated with intestine and mesentery in cattle.
P.131: Transmission of sheep-bovine spongiform encephalopathy in pigs
Carlos Hedman,1 Belén Marín,1 Fabian Corbière,3 Hicham Filali,1 Francisco
Vázquez, José Luis Pitarch,1 William Jirón,1 Rodrigo S Hernandez,1 Bernardino
Moreno,1 Martí Pumarola,2 Olivier Andréoletti,3 Juan José Badiola,1 and Rosa
Bolea1 1University of Zaragoza; Zaragoza, Spain; 2University of Barcelona;
Barcelona, Spain; 3Institut National de la Recherche (INR A); Toulouse,
France
Introduction. The transmissible spongiform encephalopathies (TSE) don´t
occur in swine in natural conditions. However, the bovine spongiform
encephalopathy (BSE) agent, inoculated by 3 simultaneous routes in pigs, is able
to reproduce a neurological disease in these animals. On the other hand, the BSE
agent after passage in sheep under experimental conditions (sheep- BSE) exhibits
altered pathobiologic properties. This new agent is able to cross the cattle-pig
transmission barrier more efficiently than BSE. The potential propagation of TSE
in animals from the human food chain, including pigs, needs to be assessed
regarding the risk for human infection by animals other than TSE-infected
ruminants. The aim of this work was to determine the susceptibility of pigs to
the Sheep-BSE agent and describe the pathological findings and PrPSc deposition
in different tissues.
Material and Methods. Seven minipigs were challenged intracerebrally with
sheep-BSE agent. Clinical observation and postmortem histopathology,
immunohistochemistry (antibody 2G11) and Western blotting were performed on
central nervous system (CNS), peripheral nervous system (PNS) and other
tissues.
Results. One pig was culled in an early incubation stage, and remaining six
were culled at the presence of clinical sings. Pigs developed a clinical disease
with locomotor disorders in an average time of 23 months post inoculation,
showing clinical findings in most of them earlier than those described in the
BSE in pigs experimental infection. TSE wasn´t confirmed in the preclinical pig.
In clinical pigs, the entire cerebral cortex showed severe neuropil vacuolation,
extensive and severe vacuolar changes affecting the thalamus, hippocampus and
cerebellum. PrPSc was found in CNS of all clinical pigs (6/6). Intracellular
(intraneuronal and intraglial) and neuropil-associated PrPSc deposition was
consistently observed in the brainstem, thalamus, and deeper layers of the
cerebral cortex. Also, PrPSc was observed in PNS, mainly in the myenteric plexus
and also in nerves belonging to the skeleton muscle. Moreover, the glycosylation
profile showed a 3 band pattern with a predominant monoglycosylated band in
positive pig samples.
This features concern on the potential risk of utilization of meat and
bound meal of small ruminants in feeding pigs.
P.177: Elements modulating the prion species barrier and its passage
consequences
Juan-Carlos Espinosa,1 Patricia Aguilar-Calvo,1 Ana Villa-Diaz,1 Olivier
Andréoletti,2 and Juan María Torres1 1Centro de Investigación en Sanidad Animal
(CISA-INI A); Valdeolmos, Madrid, Spain; 2UMR INR A-ENVT 1225; Interactions Hôte
Agent Pathogène; École Nationale Vétérinaire de Toulouse; Toulouse, France
The phenotypic features of Transmissible Spongiform Encephalopathy (TSE)
strains may be modified during passage across a species barrier. In this study
we investigated the biochemical and biological characteristics of Bovine
Spongiform Encephalopathy (BSE) infectious agent after transmission in both
natural host species (cattle, sheep, pigs, and mice) and in transgenic mice
overexpressing the corresponding cellular prion protein (PrPC) in comparison
with other non-BSE related prions from the same species. After these passages,
most characteristics of the BSE agent remained unchanged. BSE-derived agents
only showed slight modifications in the biochemical properties of the
accumulated PrPSc, which were demonstrated to be reversible upon re-inoculation
into transgenic mice expressing bovine-PrPC. Transmission experiments in
transgenic mice expressing bovine, porcine or human-PrP revealed that all
BSE-derived agents were transmitted with no or a weak transmission barrier. In
contrast, a high species barrier was observed for the non-BSE related prions
that harboured an identical PrP amino acid sequence such as sheep-scrapie, mouse
RML or human sCJD isolates, supporting the theory that the prion transmission
barrier is modulated by strain properties (presumably conformation-dependent)
rather than by PrP amino acid sequence differences between host and donor.
As identical results were observed with prions propagated either in natural
hosts or in transgenic mouse models, we postulate that the species barrier and
its passage consequences are uniquely governed by the host PrPC sequence and not
influenced by the PrPC expression level or genetic factors other than the PrPC
amino acid sequence. All these findings unequivocally demonstrate that the
species barrier and its passage consequences are uniquely driven by the PrPC
sequence, and not by other host genetic factors, demonstrating the validity of
transgenic PrP animals as models for studies of the species barrier.
The results presented herein reinforce the idea that the BSE agent is
highly promiscuous, infecting other species, maintaining its properties in the
new species, and even increasing its capabilities to jump to other species
including humans. These data are essential for the development of an accurate
risk assessment for BSE.
SNIP...SEE FULL TEXT ;
Monday, June 23, 2014
*** PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES
Sunday, June 29, 2014
*** Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
snip...see full report here ;
*** Calling Canadian beef unsafe is like calling your twin sister ugly,"
Dopp said.
Thursday, August 25, 2016
*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible
Specified Risk Materials Contamination the most high risk materials for BSE TSE
PRION AKA MAD COW TYPE DISEASE ***
Tuesday, August 9, 2016
*** Concurrence with OIE Risk Designations for Bovine Spongiform
Encephalopathy [Docket No. APHIS-2015-0055]
Saturday, July 23, 2016
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING,
AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY
2016
SPECIFIED RISK MATERIALS SRMs
USDA BSE TSE PRION SURVEILLANCE, FEED, TESTING, SRM FIREWALLS...LMAO!
THE USDA FDA TRIPLE MAD COW DISEASE FIREWALL, WERE NOTHING MORE THAN INK ON
PAPER !
infamous august 4, 1997 BSE TSE prion mad cow feed ban, part of usda fda et
al TRIPLE MAD COW FIREWALL, 10 YEARS AFTER ;
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST RECALLS AND FIELD CORRECTIONS:
VETERINARY MEDICINES -- CLASS II PRODUCT Bulk cattle feed made with recalled
Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed
delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing. REASON Blood meal used to make cattle
feed was recalled because it was cross- contaminated with prohibited bovine meat
and bone meal that had been manufactured on common equipment and labeling did
not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI
___________________________________
PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL
Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal,
TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY
Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST
POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY
Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC
MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR,
V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML
W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only
shipping documentation with commodity and weights identified. RECALLING
FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007.
Firm initiated recall is complete. REASON Products manufactured from bulk
feed containing blood meal that was cross contaminated with prohibited meat and
bone meal and the labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
16 years post mad cow feed ban August 1997
2013
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE
17 years post mad cow feed ban August 1997
Tuesday, December 23, 2014
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
*** Monday, October 26, 2015 ***
*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015 ***
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
SPECIFIED RISK MATERIAL SRM
DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH
RISK FOR MAD COW DISEASE ??? this recall was not for the welfare of the animals.
...tss
you can check and see here ; (link now dead, does not work...tss)
see listings of schools from state to state, county to county, was your
child exposed ;
try this link ;
*** Calling Canadian beef unsafe is like calling your twin sister ugly,"
Dopp said.
Thursday, August 25, 2016
*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible
Specified Risk Materials Contamination the most high risk materials for BSE TSE
PRION AKA MAD COW TYPE DISEASE ***
Saturday, July 16, 2016
*** Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Thursday, October 22, 2015
*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk
mad cow disease USDA and what really happened those mad cows in Texas ***
Monday, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program ***
Tuesday, September 06, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
***Moreover, sporadic disease has never been observed in breeding colonies
or primate research laboratories, most notably among hundreds of animals over
several decades of study at the National Institutes of Health25, and in nearly
twenty older animals continuously housed in our own facility.***
==============
***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.
==============
Monday, May 09, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease
(CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk
Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or
another, but we have found that H-BSE can infect humans. I hope we could publish
these data once the study is complete. Thanks for your interest.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
Monday, March 19, 2012
Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy PLoS One. 2012; 7(2): e31449.
Tuesday, August 9, 2016
*** Concurrence with OIE Risk Designations for Bovine Spongiform
Encephalopathy [Docket No. APHIS-2015-0055]
2016 PIGS TSE PRION UPDATE
WS-02
Scrapie in swine: A diagnostic challenge
Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2
1National Animal Disease Center, US Dept. of Agriculture, Agricultural
Research Service, United States; 2Iowa State University College of Veterinary
Medicine
A naturally occurring prion disease has not been recognized in swine, but
the agent of bovine spongiform encephalopathy does transmit to swine by
experimental routes. Swine are thought to have a robust species barrier when
exposed to the naturally occurring prion diseases of other species, but the
susceptibility of swine to the agent of sheep scrapie has not been thoroughly
tested.
Since swine can be fed rations containing ruminant derived components in
the United States and many other countries, we conducted this experiment to test
the susceptibility of swine to U.S. scrapie isolates by intracranial and oral
inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the
brains of clinically ill sheep from the 4th passage of a serial passage study of
the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous
ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were
inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24)
with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of
animals at approximately six months post inoculation (PI), at the time the pigs
were expected to reach market weight. Remaining pigs were maintained and
monitored for clinical signs of TSE until study termination at 80 months PI or
when removed due to intercurrent disease (primarily lameness). Brain samples
were examined by immunohistochemistry (IHC), western blot (WB), and
enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in
each inoculation group was used for bioassay in mice expressing porcine PRNP.
At six-months PI, no evidence of scrapie infection was noted by any
diagnostic method. However, at 51 months of incubation or greater, 5 animals
were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5).
Interestingly, positive bioassay results were obtained from all inoculated
groups (oral and intracranial; market weight and end of study).
Swine inoculated with the agent of scrapie by the intracranial and oral
routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by
IHC or WB by the time they reach typical market age and weight. However, strong
support for the fact that swine are potential hosts for the agent of scrapie
comes from positive bioassay from both intracranially and orally inoculated pigs
and multiple diagnostic methods demonstrating abnormal prion protein in
intracranially inoculated pigs with long incubation times.
Curriculum Vitae
Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion
Research Unit at the National Animal Disease Center, US Department of
Agriculture, Agricultural Research Service. He applies his specialty in
veterinary anatomic pathology to focused research on the intra- and interspecies
transmission of prion diseases in livestock and the development of antemortem
diagnostic assays for prion diseases. In addition, knockout and transgenic mouse
models are used to complement ongoing experiments in livestock species. Dr.
Greenlee has publications in a number of topic areas including prion agent
decontamination, effects of PRNP genotype on susceptibility to the agent of
sheep scrapie, characterization of US scrapie strains, transmission of chronic
wasting disease to cervids and cattle, features of H-BSE associated with the
E211 K polymorphism, and the development of retinal assessment for antemortem
screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM
degree and completed the PhD/residency program in Veterinary Pathology at Iowa
State University. He is a Diplomate of the American College of Veterinary
Pathologists.
Prion
Volume 9, Issue 4, 2015
Porcine prion protein amyloid
DOI:10.1080/19336896.2015.1065373Per Hammarströma & Sofie Nyströma*
pages 266-277
Received: 1 Jun 2015 Accepted: 17 Jun 2015 Accepted author version posted
online: 28 Jul 2015
© 2015 The Author(s). Published with license by Taylor & Francis Group,
LLC Additional license information
ABSTRACT
Mammalian prions are composed of misfolded aggregated prion protein (PrP)
with amyloid-like features. Prions are zoonotic disease agents that infect a
wide variety of mammalian species including humans. Mammals and by-products
thereof which are frequently encountered in daily life are most important for
human health. It is established that bovine prions (BSE) can infect humans while
there is no such evidence for any other prion susceptible species in the human
food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or
susceptible and resistant pets (cat and dogs, respectively). PrPs from these
species have been characterized using biochemistry, biophysics and neurobiology.
Recently we studied PrPs from several mammals in vitro and found evidence for
generic amyloidogenicity as well as cross-seeding fibril formation activity of
all PrPs on the human PrP sequence regardless if the original species was
resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was
among the studied. Experimentally inoculated pigs as well as transgenic mouse
lines overexpressing porcine PrP have, in the past, been used to investigate the
possibility of prion transmission in pigs. The pig is a species with
extraordinarily wide use within human daily life with over a billion pigs
harvested for human consumption each year. Here we discuss the possibility that
the largely prion disease resistant pig can be a clinically silent carrier of
replicating prions.
SNIP...
CONCLUDING REMARKS Should the topic of porcine PrP amyloid be more of a
worry than of mere academic interest? Well perhaps. Prions are particularly
insidious pathogens. A recent outbreak of peripheral neuropathy in human,
suggests that exposure to aerosolized porcine brain is deleterious for human
health.43,44 Aerosolization is a known vector for prions at least under
experimental conditions.45-47 where a mere single exposure was enough for
transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even
more so with PoPrP seed (Fig. 1), indicating that humans could be infected by
porcine APrP prions while neurotoxicity associated with spongiform
encephalopathy if such a disease existed is even less clear. Importantly
transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged
through domestic pigs implicating that efficient downstream neurotoxicity
pathways in the mouse, a susceptible host for prion disease neurotoxicity is
augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be
infectious to a third species. Data from Collinge and coworkers.21 propose that
species considered to be prion free may be carriers of replicating prions.
Especially this may be of concern for promiscuous prion strains such as
BSE.19,48 It is rather established that prions can exist in both replicating and
neurotoxic conformations.49,50 and this can alter the way in which new host
organisms can react upon cross-species transmission.51 The na€ıve host can
either be totally resistant to prion infection as well as remain non-infectious,
become a silent non-symptomatic but infectious carrier of disease or be
afflicted by disease with short or long incubation time. The host can harbor
and/or propagate the donor strain or convert the strain conformation to adapt it
to the na€ıve host species. The latter would facilitate infection and shorten
the incubation time in a consecutive event of intra-species transmission. It may
be advisable to avoid procedures and exposure without proper biosafety
precautions as the knowledge of silence carrier species is poor. One case of
iatrogenic CJD in recipient of porcine dura mater graft has been reported in the
literature.52 The significance of this finding is still unknown. The low public
awareness in this matter is exemplified by the practice of using proteolytic
peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic
drug. While Cerebrolysin may be beneficial for treatment of severe diseases such
as vascular dementia,53 a long term follow-up of such a product for recreational
use is recommended.
Friday, August 21, 2015
Porcine prion protein amyloid or mad pig disease PSE Porcine Spongiform
Encephalopathy ?
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a 10-year
incubation period. Neuropathologic examination revealed all of the features of a
prion disease: spongiform change, neuronal loss, and accumulation of PrPres
throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and protective
measures and the necessity for long-term experimental transmission studies to
assess the zoonotic potential of other animal prion strains.
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
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.
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1978 SCRAPIE IN CONFIDENCE SCJD
1979
SILENCE ON CJD AND SCRAPIE
1980
SILENCE ON CJD AND SCRAPIE
*** 1981 NOVEMBER
Thursday, August 04, 2016
*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL
SCJD
Tuesday, September 06, 2016
A comparison of classical and H-type bovine spongiform encephalopathy
associated with E211K prion protein polymorphism in wild type and EK211 cattle
following intracranial inoculation
Monday, September 05, 2016
*** Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission Major Findings for Norway ***
see more here ;
Monday, September 05, 2016
*** Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission Major Findings for Norway ***
Wednesday, September 7, 2016
*** An assessment of the long-term persistence of prion infectivity in
aquatic environments
Friday, September 02, 2016
*** Chronic Wasting Disease Drives Population Decline of White-Tailed
Deer
Monday, August 29, 2016
*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Thursday, August 18, 2016
*** PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the USAHA BSE,
CWD, SCRAPIE, PORCINE TSE PRION October 22 28, 2015 ***
Wednesday, September 28, 2016
Norway sides with OIE, decides to expose millions of consumers to the
ATYPICAL BSE SRM TSE Prion aka mad cow type disease
http://bse-atypical.blogspot.com/2016/09/norway-sides-with-oie-decides-to-expose.html
Friday, August 26, 2016
*** Journal Journal of Toxicology and Environmental Health, Part A Volume
79, 2016 - Issue 16-17 Prion Research in Perspective IV CANADA BSE CWD SCRAPIE
CJD TSE Prion Disease
*** Calling Canadian beef unsafe is like calling your twin sister ugly,"
Dopp said. ***
Thursday, August 25, 2016
*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible
Specified Risk Materials Contamination the most high risk materials for BSE TSE
PRION AKA MAD COW TYPE DISEASE ***
Saturday, July 16, 2016
Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Monday, September 19, 2016
Evidence of scrapie transmission to sheep via goat milk
Saturday, April 16, 2016
*** APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on
Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission
***
Wednesday, January 20, 2016
Exportation of Live Animals, Hatching Eggs, and Animal Germplasm From the
United States [Docket No. APHIS-2012-0049] RIN 0579-AE00 2016-00962
Thursday, January 14, 2016
EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address
Future Risks Report to the Chairman, Committee on Energy and Commerce, House of
Representatives December 2015 GAO-16-132
GAO
Saturday, September 24, 2016
Assessment of the PrPc amino-terminal domain in prion species barriers
Tuesday, July 12, 2016
*** Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy
BSE, TSE, Prion Zoonosis Science History see history of NIH may destroy human
brain collection
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
>>> We can prevent, effectively treat, and make an Alzheimer’s
cure possible by 2025.
PREVENT
this must be on the forefront of research i.e. ‘iatrogenic’ transmission.
Alzheimer’s disease, iatrogenic, and Transmissible Spongiform
Encephalopathy TSE Prion disease, that is the question ???
>>> The only tenable public line will be that "more research is
required’’ <<<
>>> possibility on a transmissible prion remains
open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is
"more research is required’’ enough time for evaluation ?
http://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf
SWISS MEDICAL WEEKLY
Alzheimer-type brain pathology may be transmitted by grafts of dura mater
26/01/2016 Singeltary comment ;
re-Evidence for human transmission of amyloid-β pathology and cerebral
amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26
April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated
online 11 September 2015 Erratum (October, 2015)
snip...see full Singeltary Nature comment here;
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Sunday, November 22, 2015
*** Effect of heating on the stability of amyloid A (AA) fibrils and the
intra- and cross-species transmission of AA amyloidosis Abstract
Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by
extracellular deposition of AA fibrils. AA fibrils are found in several tissues
from food animals with AA amyloidosis. For hygienic purposes, heating is widely
used to inactivate microbes in food, but it is uncertain whether heating is
sufficient to inactivate AA fibrils and prevent intra- or cross-species
transmission. We examined the effect of heating (at 60 °C or 100 °C) and
autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western
blot analysis, transmission electron microscopy (TEM), and mouse model
transmission experiments. TEM revealed that a mixture of AA fibrils and
amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at
135 °C produced large amorphous aggregates. AA fibrils retained antigen
specificity in Western blot analysis when heated at 100 °C or autoclaved at 121
°C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and
bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly
stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA
fibrils at 121 °C or 135 °C significantly decreased amyloid deposition.
Moreover, amyloid deposition in mice injected with murine AA fibrils was more
severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils
autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These
results suggest that AA fibrils are relatively heat stable and that similar to
prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA
fibrils. These findings may contribute to the prevention of AA fibril
transmission through food materials to different animals and especially to
humans.
Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD
54.00
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and
Greed by the Industry spread madcow type diseases from species to species and
around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
*** Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle ***
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” ...page 26.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
Human Prion Diseases in the United States Robert C. Holman ,
Ermias D. Belay, Krista Y. Christensen, Ryan A. Maddox, Arialdi M. Minino,
Arianne M. Folkema, Dana L. Haberling, Teresa A. Hammett, Kenneth D. Kochanek,
James J. Sejvar, Lawrence B. Schonberger
PLOS
Published: January 1, 2010 • http://dx.doi.org/10.1371/journal.pone.0008521
re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010
at 18:11 GMT I kindly disagree with your synopsis for the following reasons ;
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
*** ''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population'' ***
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Sent: Monday, January 08,2001 3:03 PM
TO: freas@CBS5055530.CBER.FDA.GOV
FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January
2001 Meeting Singeltary Submission
2001 FDA CJD TSE Prion Singeltary Submission
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
2001 FDA CJD TSE Prion Singeltary Submission TSEAC
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net
posted by Terry S. Singeltary Sr. | 12:04 PM
|
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