| Updated: 05 August 2004
Contact:
Stephen M. Apatow
Director
of Research
& Development
Humanitarian
Resource
Institute Legal Resource Center
Biodefense
Reference
Library
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USA: (203) 668-0282
Western USA: (775) 884-4680
Internet:
http://www.humanitarian.net/law/biodefense
Email:
s.m.apatow@humanitarian.net
Transmissible
Spongiform
Encephalopathies in North America
Information
Sites
In
The News
Related
Information
US
Geographical BSE Risk
Analysis
European
Commission: Scientific
Steering Committee
Conclusion
of the Resulting
Risks: During the period covered by the European Commission Assessment
of the Geographic BSE Risk of the USA (1980-1999) the US -system was
not
able to prevent propagation of BSE should it have entered, even if this
ability was significantly improved with the MBM-ban of 1997.
Report
on the Assessment
of the Geographical BSE - Risk of the U.S.A. (July 2000)(220kb)
http://www.humanitarian.net/biodefense/fazdc/ref/us_gbr2000.pdf
Harvard
BSE Risk Assessment
Analysis
finds that the U.S.
is highly resistant to any introduction of BSE or a similar disease.
BSE
is extremely unlikely to become established in the U.S.
http://www.aphis.usda.gov/lpa/issues/bse/bse-riskassmt.html
CJD:
Increases more than
50 fold since 1979, going from 857 deaths to more than 50,000 in 2000
"Mad
Cow: Linked to thousands
of CJD cases?," 29, December 2003
(http://www.nlm.nih.gov/medlineplus/news/fullstory_15312.html):
--
The U.S. government's
monitoring system for cases of Creutzfeldt-Jakob disease, a fatal human
brain illness, could be missing tens of thousands of victims,
scientists
and consumer advocates have told United Press International.
--
Clusters of CJD have
been reported in various areas of the United States -- Pennsylvania in
1993, Florida in 1994, Oregon in 1996, New York in 1999-2000 and Texas
in 1996.
--
People who develop CJD
from eating mad-cow-contaminated beef have been thought to develop a
specific
form of the disorder called variant CJD. But new research, released
last
December, indicates the mad cow pathogen can cause both sporadic CJD
and
the variant form.
-- "Now
people are beginning
to realize that because something looks like sporadic CJD they can't
necessarily
conclude that it's not linked to (mad cow disease)," said Laura
Manuelidis,
section chief of surgery in the neuropathology department at Yale
University,
who conducted a 1989 study that found 13 percent of Alzheimer's
patients
actually had CJD.
-- Several
studies, including the one by Manuelidis, have found autopsies reveal
3-percent-to-13-percent
of patients diagnosed with Alzheimer's or dementia actually suffered
from
CJD. Those numbers might sound low, but there are 4-million Alzheimer's
cases and hundreds of thousands of dementia cases in the United States.
A small percentage of those cases could add up to 120,000 or more CJD
victims
going undetected and not included in official statistics.
-- At
the same time autopsies have been declining, the number of deaths
attributed
to Alzheimer's has increased more than 50-fold since 1979, going from
857
deaths then to nearly 50,000 in 2000. Though it is unlikely the
dramatic increase in Alzheimer's is due entirely to misdiagnosed CJD
cases,
it "could explain some of the increase we've seen," Manuelidis said.
Young
Onset Dementia
Young
Onset Dementia: Epidemiology,
clinical symptoms, family burden, support and outcome, Dr Richard J
Harvey
MD MRCPsych (http://web.kamogawa.ne.jp/~miyake/yod.pdf):
Dementia
affecting the under
65 years age group is increasingly recognised as an important medical
and
social problem. This report is based upon research carried out over a
2½
year period in two London boroughs. A comprehensive methodology was
used
to attempt to identify every case of dementia which began before the
affected
person was age 65 years and to establish a specific cause. The study
identified
185 cases of young onset dementia, giving a prevalence of 67.2 cases
per
100,000
at risk
in the 30-64 years
age group. Extrapolating these figures suggests that there may be
16,737
(95% CI: 13,975-19,879) people affected in the wider UK population. The
prevalence rates for specific dementias included Alzheimer’s disease
(21.7/100,000
(15.6-29.3), Vascular Dementia (10.9/100,000 (6.7-16.5)) and
Frontotemporal
dementia (9.3/100,000 (5.5-14.7). It was notable that Alzheimer’s
disease
accounted for less than half of the cases of dementia.
Presenile
dementia syndromes:
an update on taxonomy and diagnosis, M D Greicius, M D Geschwind and B
L Miller, Journal of Neurology Neurosurgery and Psychiatry
2002;72:691-700
(http://jnnp.bmjjournals.com/cgi/content/full/72/6/691):
The
four major degenerative
dementias that often begin in presenescence: are reviewed. These are
Alzheimer's
disease, frontotemporal dementia, dementia with Lewy bodies, and
Creutzfeldt–Jakob
disease. Their epidemiological, genetic, and clinical features are
reviewed,
and controversies in taxonomy arising from recent discoveries
described.
Particular attention is given to the pathological role of protein
aggregation,
which appears to be a factor in each disease.
Related
Publications
Transmissible
Spongiform
Encephalopathies
The
article "Brain
trust: Local scientist, world-renowned expert reflects on half century
of work with TSEs" outlines important research associated with
Transmissible
Mink Encephalopathy (TME) in the U.S. in 1963, Chronic Wasting Disease
(CWD) in 1979. CWD, proved to be transmissible experimentally to
mule deer, mink, domestic ferrets, squirrel monkeys and goats, is a
significant
finding since environmental contamination is attributed to the spread
of
the contagion.
According
to "Transmissible
Mink Encephalopathy Veterinary Services February 2002" (http://www.priondata.org/data/A_tme.html):
--
The first documented TME
outbreak in the United States occurred in 1947 on one ranch in
Wisconsin
and then on a ranch in Minnesota that had received mink from the
Wisconsin
ranch.
-- In
1961, TME outbreaks
occurred on five ranches in Wisconsin.
-- In
1963, outbreaks occurred
in Idaho, Minnesota, and Wisconsin. Epidemiologic data from the
Minnesota
and Wisconsin outbreaks trace the cases in those States to one common
purchased
food source.
-- The
most recent TME outbreak
occurred on one mink ranch in Stetsonville, WI, in 1985. In the herd of
7,300 adult mink, 60 percent of the animals died.
------------------------------------------------
J
Comp Pathol. 1995 Oct;113(3):241-51.
Experimental
infection of
cattle with the agents of transmissible mink encephalopathy and scrapie.
Robinson
MM, Hadlow WJ,
Knowles DP, Huff TP, Lacy PA, Marsh RF, Gorham JR.
USDA-ARS
Animal Disease Research
Unit, Washington State University, Pullman 99164-7030, USA.
Cattle
are susceptible to
experimental infection with the Stetsonville isolate of the
transmissible
mink encephalopathy (TME) agent. To determine if they are susceptible
to
other TME isolates, two groups of calves were inoculated
intracerebrally
with homogenate of mink brain containing the Hayward isolate or the
Blackfoot
isolate. For comparison, a third group was inoculated with a brain
homogenate
from a steer infected with the Stetsonville isolate in its primary
cattle
passage and a fourth group was inoculated with a pool of brain
homogenate
from three cattle experimentally infected with a sheep and goat scrapie
agent in its primary cattle passage. Clinical signs of neurological
disease
appeared in each steer of every group between 15 and 25 months after
inoculation.
An encephalopathy characterized by severe spongiform change and
pronounced
astrocytosis occurred in the three groups inoculated with the TME
agent.
In contrast, the neurohistological changes in the steers inoculated
with
the cattle-passaged scrapie agent were slight and subtle. Analysis of
the
octapeptide repeat region of the bovine protease-resistant protein
(PrP)
gene showed that variations in incubation period, clinical signs, and
neurohistological
changes were unrelated to the homozygous or heterozygous condition of
six
or six/five octapeptide repeats.
PMID:
8592050 [PubMed - indexed
for MEDLINE]
------------------------------------------------
The
following research by
USDA points to subclincal infection (positive for prion protein by
immunohistochemistry)
without obvious histologic changes indicative of spongiform
encephalopathy
(SE)
Cross-Species
Transmission
of Chronic Wasting Disease (Cwd-Mule Deer) to Domestic Livestock at the
National Animal Disease Center (http://www.ars.usda.gov/research/publications/Publications.htm?seq_no_115=149095):
Submitted
to: American Association
Of Veterinary Laboratory Diagnosticians
Publication
Acceptance Date:
October 9, 2003
Publication
Date: October
9, 2003
Technical
Abstract: To determine
the transmissibility of chronic wasting disease (CWD) to cattle and
sheep,
13 calves and 8 lambs were inoculated intracerebrally with brain
suspension
from mule deer (CWD-mule deer) naturally affected with CWD. Both
investigations
are currently in progress. The cattle experiment was started in 1997.
Five
and half years post inoculation (PI), 10/13 cattle have either died or
were euthanized. Five of these were positive for prion protein (by
immunohistochemistry).
However, only the initial 2 cattle, euthanized at 23 and 24 months PI,
had clinical signs (weight loss), and none revealed obvious histologic
changes indicative of spongiform encephalopathy (SE). Three cattle
remain
alive and apparently healthy. The ovine experiment is 4 years PI and so
far 2 sheep (both QQ at codon 171) have been euthanized. Only 1 had
clinical
signs and histopathologic lesions of SE that were indistinguishable
from
sheep scrapie, and the brain was positive for prion protein. Six
remaining
sheep (2 QQ and 4 QR at 171) are apparently healthy. These preliminary
findings demonstrate that although the CWD-mule deer agent can be
transmitted
to cattle and sheep by intracerebral inoculation, an obvious neurologic
manifestation of the disease is only seen in the latter species. These
results also indicate that the diagnostic techniques currently used for
bovine spongiform encephalopathy (BSE) surveillance would also detect
the
CWD agent in cattle and sheep should it occur naturally. Since
intracerebral
inoculation is an unnatural route for TSE infection, it has little
bearing
on the potential for cattle to become infected under natural conditions
of exposure and these data may not reflect the situation seen after a
natural
infection.
------------------------------------------------
Veterinarians
question
Transmissible Spongiform Encephalopathies (TSE) and infected feed as a
link to CDS (Cognitive Disorder, Alzheimer's), the most common
degenerative
neurological disease in dogs and cats in the U.S.
Deer
and Dog Spongiform Encephalopathy
survey
http://www.priondata.org/data/A_deerdog.html
Putative
TSE in hounds -
work started 1990 -(see para 41)
Robert
Higgins, a Veterinary
Investigation Officer at Thirsk, had been working on a hound survey in
1990. Gerald Wells and I myself received histological sections from
this
survey along with the accompanying letter (YB90/11.28/1.1) dated
November
1990. This letter details spongiform changes found in brains from hunt
hounds failing to keep up with the rest of the pack, along with the
results
of SAF extractions from fresh brain material from these same animals.
SAFs
were not found in brains unless spongiform changes were also present.
The
spongiform changes were
not pathognomonic (ie. conclusive proof) for prion disease, as they
were
atypical,being largely present in white matter rather than grey matter
in the brain and spinal cord. However, Tony Scott, then head of
electron
microscopy work on TSEs, had no doubt that these SAFs were genuine and
that these hounds therefore must have had a scrapie-like disease. I
reviewed
all the sections myself (original notes appended) and although the
pathology
was not typical, I could not exclude the possibility that this was a
scrapie-like
disorder, as white matter vacuolation is seen in TSEs and Wallerian
degeneration
was also present in the white matter of the hounds, another feature of
scrapie.
Terry
Singletary reviewed
the literature on hound neuropathology, and discovered that micrographs
and descriptive neuropathology from papers on 'hound ataxia' mirrored
those
in material from Robert Higgins' hound survey. Dr Tony Palmer
(Cambridge)
had done much of this work, and I obtained original sections from hound
ataxia cases from him. This enabled me provisionally to conclude that
Robert
Higgins had in all probability detected hound ataxia, but also that
hound
ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind'
examination
of single restricted microscopic fields that there was no distinction
between
the white matter vacuolation present in BSE and scrapie cases, and that
occurring in hound ataxia and the hound survey cases.
Hound
ataxia had reportedly
been occurring since the 1930's, and a known risk factor for its
development
was the feeding to hounds of downer cows, and particularly bovine
offal.
Circumstantial evidence suggests that bovine offal may also be causal
in
FSE, and TME in mink. Despite the inconclusive nature of the
neuropathology,
it was clearly evident that this putative canine
spongiform
encephalopathy
merited further investigation.
The
inconclusive results
in hounds were never confirmed, nor was the link with hound ataxia
pursued.
I telephoned Robert Higgins six years after he first sent the slides to
CVL. I was informed that despite his submitting a yearly report to the
CVO including the suggestion that the hound work be continued, no
further
work had been done since 1991. This was surprising, to say the very
least.
The
hound work could have
provided valuable evidence that a scrapie-like agent may have been
present
in cattle offal long before the BSE epidemic was recognized. The MAFF
hound
survey remains unpublished.
Transmissible
Spongiform Encephalopathies
UK -
European Commission
CJD/BSE:
TSE Guidance
Note the
Appendix includes:
Statement
on ACDP/SEAC
Part
1 - Introduction
(44kb)
Part 2 -
Health and Safety
management of TSEs (35kb)
Part 3 -
Laboratory containment
and control measures (156kb)
Part 4 -
Infection control
of CJD and related disorders in the healthcare setting (62kb)
Annex
A.1 - Distribution
of TSE Infectivity in Human Tissues and Body Fluids (14kb)
Annex
A.2 Distribution
of TSE infectivity in Animal Tissues and Body Fluids - see 1998
guidance,
annex A
Annex B
- Diagnostic criteria
(19kb)
Annex C
- Decontamination
and waste disposal (179kb)
Annex D
- Transport of TSE-infected
material (98kb)
Annex E
- Quarantining of
surgical instruments (9kb)
Annex F
- Decontamination
of endoscopes (23kb)
Annex G
- Decontamination
of other specialised equipment (see 1998 guidance, annex B)
Annex H
- After death (25kb)
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