| Updated: 05 August 2004
Contact:
Stephen M. Apatow
Founder, Director of Research & Development
Humanitarian Resource Institute
Humanitarian University Consortium Graduate Studies
Center for Medicine, Veterinary Medicine & Law
Phone: 203-668-0282
Email: s.m.apatow@humanitarian.net
Internet: www.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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