SEARCH VEGSOURCE:

 

 

Follow Ups | Post Followup | Back to Discussion Board | VegSource
See spam or
inappropriate posts?
Please let us know.
  




From: TSS (216-119-144-20.ipset24.wt.net)
Subject: Risk of oral infection with bovine spongiform encephalopathy agent in primates FULL TEXT
Date: February 1, 2005 at 1:35 pm PST

-------- Original Message --------
Subject: Risk of oral infection with bovine spongiform encephalopathy agent in primates FULL TEXT
Date: Tue, 1 Feb 2005 10:19:40 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

For personal use. Only reproduce with permission from Elsevier Ltd
Research Letters

Published online
January 27, 2005

Risk of oral infection with bovine spongiform
encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia,
Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown,
Jean-Philippe Deslys


The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)which can lead to variant
Creutzfeldt-Jakob disease (vCJD)is compounded by incomplete knowledge
about the efficiency of oral infection
and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral
transmission of BSE to non-human primates. We gave two macaques a 5 g
oral dose of brain homogenate from a
BSE-infected cow. One macaque developed vCJD-like neurological disease
60 months after exposure, whereas the
other remained free of disease at 76 months. On the basis of these
findings and data from other studies, we made a
preliminary estimate of the food exposure risk for man, which provides
additional assurance that existing public
health measures can prevent transmission of BSE to man.

Up to 400 000 cows with undiagnosed bovine spongiform
encephalopathy (BSE) infection are estimated to
have been slaughtered for food before brain and spinal
cord were banned from human consumption in 1989.
More restricted exposure to BSE could have continued
through 1995 from consumption of processed meat
products containing mechanically recovered meat
contaminated with central nervous system (CNS) tissue
and spinal ganglia.1 The discovery of BSE in Canada and
the USA, where consumption of brain and other viscera
was allowed until 2003, and of secondary cases of variant
Creutzfeldt-Jakob disease (vCJD) in the UK, possibly
attributable to contaminated blood donated by people
with pre-clinical primary infection, reinforces the need
for an experimental assessment of the risk of oral
exposure to BSE. We therefore investigated oral
transmission of BSE to non-human primates.

We chose cynomolgus macaques for the study because
these old-world monkeys have a digestive physiology
similar to that of human beings, are methionine
homozygous at codon 129 of the PRNP gene, and have a
BSE neuropathology similar to that of vCJD.2,3 We gave
two 4-year-old adult macaques a 5 g oral dose of brain
homogenate from a BSE-affected cow. We tested for
proteinase-resistant prion protein (PrPres) in this
homogenate with a commercial BSE-testing ELISA kit
(Bio-Rad, Marnes-la-Coquette, France). A sample of the
100% homogenate brain paste inoculum that was fed to
the primates was rehomogenised at 20% weight-pervolume
in the kit buffer. Serial dilutions were made with
a pool of 20% weight-per-volume BSE-negative brain
homogenate in the same buffer. Testing was done
according to the manufacturers instructions and results
were confirmed by a western blot test (Bio-Rad) with a
similar process of PrPres dilution. With both methods,
dilutions of up to 1 in 300 provided a positive signal
(figure A).

One macaque developed neurological disease
60 months after exposure and was killed at 63 months
because of recumbency. Histopathological examination
of the brain of this animal showed the typical pathology
of vCJD (figure B) and an accumulation of PrPres
associated with the follicular dendritic cells in tonsils
(figure C), spleen, and intestine. A western blot showed
similar patterns of PrPres in a brain sample from the
macaque and the BSE-infected bovine inoculum
(figure D). The other macaque remained free of clinical
signs 76 months after exposure, and a tonsil biopsy done
at 72 months was negative (figure E).

In a previous study, two macaques orally dosed with
5 g of brain from a macaque with terminal clinical BSE
became ill after 44 and 47 months.4 The results of the
present study suggest that the incubation period for
interspecies transmission of BSE can be considerably
longer than that of intraspecies transmission (60 months
vs 44 and 47 months, representing 36% and 28%
increases, respectively). The interval between the period of
peak exposure to infectious BSE tissue and the hitherto
peak incidence of vCJD is about 1015 years, but
incubation periods of up to 40 years have followed oral
infection with kuru between human beings.5 Therefore,
maximum incubation periods might exceed 50 years in
cases of oral transmission of BSE from cattle to man.

The present data do not provide a definitive minimum
infective dose for transmission of cattle BSE to primates,
but they do give enough information for a preliminary
assessment of the adequacy of existing measures to
protect the human food chain. Results of ongoing
experiments provide a rough estimation of the intraspecies
transmission rates in cattle. The BSE brain
inoculum to which the cattle were exposed had an
infectivity titre of 103·5 mouse infectious (intracerebral
and intraperitoneal) units ID50 per g (ID50 is the dose at
which 50% of animals become infected). Interim results
at 6 years after exposure suggest that the oral ID50 in
cattle may be between 100 mg and 1 g (table 1; S A C
Hawkins, T Konold, G A H Wells, unpublished data).

Since the brain of a cow weighs 500 g and a spinal cord
200 g, CNS tissues from a cow with clinical signs of BSE
could contain enough infective agent to transmit disease
orally to 4901400 cows (70% of 700 g if 1g is needed, or
20% of 700 g if 100 mg is sufficient), or to 70 primates
(50% of 700 g if 5 g represents the oral ID50).

The accuracy of estimates of the oral ID50 for man will
not be improved until completion, several years from
now, of a large dose-response European study (QLK1-
2002-01096) in macaques, in which the minimum dose
is 50 mg. However, because similar inocula were used in
both the cattle and macaque studies,6 a tentative comparison
can be made between the efficiency of oral infection
in cattle and that in primates. On this basis, a factor of
720 could be considered as the range of magnitude of a
bovine-to-primate species barrier for oral BSE infection
(70 primates infected compared with 490 or 1400 cows,
with a similar dose).

Elimination from the human food chain of CNS
tissues from cows with clinical BSE is estimated to have
reduced the risk of human exposure to the disease by
about 90%.7 Risk was further reduced in continental
Europe by systematic screening for the diagnostic
presence of PrPres in the brainstem of all cattle older than
30 months, and in the UK by the total interdiction of
cows older than 30 months. In an oral exposure study to
assess the pathogenesis of BSE in cattle, in which the
same European Union-evaluated test as we used in the
present study was applied to CNS tissues, some
preclinical cases of the disease were diagnosed.8

Using the same test, pooled brainstem from cows with
clinical BSE has yielded a endpoint titre of PrPres
corresponding to a 1-in-300 to 1-in-1000 dilution of
positive brainstem.6,9 If people were to eat CNS tissues
from a cow with preclinical BSE with a concentration of
PrPres just below the test detection limit of 1 in 300, they
would need to ingest at least 1·5 kg to reach the degree
of exposure equivalent to that in the 5 g of brain used for
oral transmission to the macaque in the present study. If
the oral ID50 for man was one log below this dose (ie,
similar to that in cattle, and not accounting for any
species barrier between cattle and man; see table), 150 g
of CNS tissue that tested falsely negative could represent
an infective dose. Because use of cattle brain and spinal
cord for human consumption is prohibited, and in view
of the existing mechanically recovered meat regulations,
a person would be very unlikely to ingest this amount of
cattle CNS tissue.

The minimum sensitivity of screening tests to detect
100% of BSE-infected animals has yet to be ascertained.
However, our results provide reassurance that BSE
screening procedures combined with CNS removal are
effective measures to protect the human food chain.


Published online
January 27, 2005
http://image.thelancet.com/
extras/05let1056web.pdf
Commissariat à lEnergie
Atomique/Direction des
Sciences du Vivant/Départment
de Recherche Médicale,
18 Route du Panorama, 92265
Fontenay-aux-Roses, France
(C I Lasmézas DrMedVet,
E Comoy DrMedVet,
C Herzog DipBiol,
F Mouthon DipBiol, F Auvré,
E Correia,
N Lescoutra-Etchegaray DipBiol,
Prof N Salès PhD, J-P Deslys MD);
Veterinary Laboratories
Agency, New Haw, Addlestone,
UK (S Hawkins MIBiol,
T Konold DrMedVet,
G Wells BVetMed); and 7815
Exeter Road, Bethesda, MD
20814, USA (P Brown PhD)
Correspondence to:
Dr Jean-Philippe Deslys
e-mail: jpdeslys@cea.fr
www.thelancet.com Published online January 27, 2005
http://image.thelancet.com/extras/05let1056web.pdf 1

Risk of oral infection with bovine spongiform
encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia,
Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown,
Jean-Philippe Deslys

B
C
E
A
Dilution
D
3·215
1·989
0·984
0·302
0·131
0·065
0·052
1/10
1/30
1/100
1/300
1/1000
1/3000
Neg
36 kDa
36 kDa
22 kDa
22 kDa
16 kDa
1 2 3 4
ELISA detection of PrPres (absorbance units)
Figure: PrPres content of brain homogenate and histopathological
assessment of macaque tissues
(A) Results of in-vitro testing for PrPres in BSE-infected inoculum by
ELISA and western blot. Neg=normal bovine
brain material. (B) Typical florid plaque in the occipital cortex of the
macaque that developed disease.
PrPres detected by proteinase K treatment with SAF32 anti PrP monoclonal
antibody (kindly provided by Jacques
Grassi, CEA Saclay). The dense core of PrPres is surrounded by several
vacuoles in a fibrillar proteinaceous corona;
bar=10 m. (C) Positive PrPres staining in tonsil (80% of follicules
stained positive) of the macaque that developed
disease; bar=50 m. (E) Negative PrPres staining in tonsil of the
macaque that did not develop disease; bar=50 m.
(D) Western blot showing similar PrPres patterns in samples from a
patient with vCJD (lane 1), the macaque that
developed disease (lane 3), and the bovine BSE inoculum (lane 4). By
contrast, a macaque inoculated intracerebrally
with material from a patient with sporadic CJD showed a different PrPres
pattern (lane 2).
For personal use. Only reproduce with permission from Elsevier Ltd
Research Letters

Contributors
J-P Deslys, C Lasmézas, and E Comoy were responsible for design and
management of this study. G Wells, S Hawkins, and T Konold were
responsible for the pathogenesis study in ruminants. C Lasmézas,
C Herzog, and N Lescoutra-Etchegaray were in charge of the primate
experiments. F Auvré undertook the biochemical analyses. N Salès was
responsible for the immunohistochemical analyses, which were done
by E Correia. C Lasmézas, E Comoy, F Mouthon, G Wells, P Brown, and
J-P Deslys drafted the manuscript.
Conflict of interest statement
Commissariat à lEnergie Atomique owns a patent covering the BSE
diagnostic test commercialised by Bio-Rad. All authors had full access to
all data and had responsibility to submit for publication. The funding
sources had no role in the collection, analysis, and interpretation of
data, writing of the report, or decision to submit the paper for
publication.
2 www.thelancet.com Published online January 27, 2005
http://image.thelancet.com/extras/05let1056web.pdf
BSE bovine brain inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15
(7%) 1/15 (7%)
RIII mice (icip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection    
The comparison is made on the basis of calibration of the bovine
inoculum used in our study with primates against a bovine brain inoculum
with a similar PrPres concentration that was
inoculated into mice and cattle.8 *Data are number of animals
positive/number of animals surviving at the time of clinical onset of
disease in the first positive animal (%). The accuracy of
bioassays is generally judged to be about plus or minus 1 log.
icip=intracerebral and intraperitoneal.
Table 1: Comparison of transmission rates in primates and cattle
infected orally with similar BSE brain inocula
For personal use. Only reproduce with permission from Elsevier Ltd
Research Letters
Acknowledgments
We gratefully acknowledge the expert care of the primate animals
provided by René Rioux, Sébastien Jacquin, and Anthony Fort, and the
technical expertise of Dominique Marcé, Capucine Dehen,
Sophie Freire, and Aurore Jolit Charbonnier. This work has received
financial support from the French Ministry of Research (GIS Prion). It is
now continued within the framework of the EU consortium QLK1-2002-
01096 and the European network of Excellence NeuroPrion. Ongoing
studies by the Veterinary Laboratories Agency in cattle are funded by the
UK Department for Environment, Food, and Rural Affairs.
References
1Anderson RM, Donnelly CA, Ferguson NM, et al. Transmission
dynamics and epidemiology of BSE in British cattle. Nature 1996;
382: 77988.
2 Lasmézas CI, Deslys JP, Demaimay R, et al. BSE transmission to
macaques. Nature 1996; 381: 74344.
3 Lasmézas CI, Fournier JG, Nouvel V, et al. Adaptation of the bovine
spongiform encephalopathy agent to primates and comparison with
Creutzfeldt-Jakob disease: implications for human health. Proc Natl
Acad Sci USA 2001; 98: 414247.
4 Herzog C, Salès N, Etchegaray N, et al. Tissue distribution of bovine
spongiform encephalopathy agent in primates after intravenous or
oral infection. Lancet 2004; 363: 42228.
5 Klitzman RL, Alpers MP, Gajdusek DC. The natural incubation
period of kuru and the episodes of transmission in three clusters of
patients. Neuroepidemiol 1984; 3: 320.
6 Deslys JP, Comoy E, Hawkins S, et al. Screening slaughtered cattle
for BSE. Nature 2001; 409: 47678.
7 European Commission. Opinion of the Scientific Steering
Committee on the Human Exposure Risk via food with respect to
BSE. Adopted on 10 December 1999. http://europa.eu.int./comm/
food/fs/sc/ssc/out67_en.pdf (accessed Jan 17, 2004).
8 Grassi J, Comoy E, Simon S, et al. Rapid test for the preclinical
postmortem diagnosis of BSE in central nervous system tissue.
Vet Rec 2001; 149: 57782.
9 Moynagh J, Schimmel H. Tests for BSE evaluated. Bovine
spongiform encephalopathy. Nature 1999; 400: 105.
www.thelancet.com Published online January 27, 2005
http://image.thelancet.com/extras/05let1056web.pdf 3TSS


GREETINGS,

> However, our results provide reassurance that BSE
> screening procedures combined with CNS removal are
> effective measures to protect the human food chain.


I guess they think were all just idots or something?

FOR whatever it's worth, I totally disagree with there guess work.
THE screening procedures combined with CNS removal may
be effective, but you must guarantee enforcement first.
THIS has yet to happen in all of North America.
IN FACT IT HAS BEEN PUT OFF UNTIL February 1, 2006!
WE are still feeding ruminants to ruminants, including CNS materials.
THEY have absolutely no idea what the oral ID load for humans are,
but yet they make stupid claims they cannot back up such as ;

>> However, our results provide reassurance that BSE
>> screening procedures combined with CNS removal are
>> effective measures to protect the human food chain.
>

it's a shame people cannot learn from past mistakes.

http://www.maddeer.org/gummer.html

http://www.maddeer.org/canadianprimeminister.JPG

I am pondering low dose orally compared to a low dose from dura
diagnostic procedure.
WHAT is threshold for clinical disease, via different routes and
sources, depending on
infectivity in each tissue consumed from each animal? is that constant?
i think not...


DISCUSSION

We describe a 47 year old patient who developed pathology proven CJD 38
years after hGH injections. The patient was never treated with hGH but
received a small dose as part of a diagnostic procedure. The onset of
CJD was signalled by prodromal symptoms of paraesthesia followed by a
rapidly progressive ataxia. The disease presentation and course with
predominantly cerebellar and eye movement disorders are compatible with
iatrogenic CJD caused by hGH treatment.6,
8


snip...

When he was 9 years old, a nitrogen retention test with 6 IU hGH over
five days was performed to exclude growth hormone deficiency. Since the
result was not decisive, a quantitative amino acid test was performed,
which measures 30 amino acids during fasting and one, two, and three
hours after growth hormone injection. No abnormal amino acid
concentrations were found making the diagnosis of primordial dwarfism
most likely. Therefore, no treatment with hGH was given.

snip...

http://jnnp.bmjjournals.com/cgi/content/full/72/6/792

I understand orally would be different from low dose diagnostic for hGH,
but do they understand that
never say never with human/animal TSEs until it is proven is a must.
MORE false assurances from PB et al
is more than some of us can handle...


TSS

######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########


J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

TSS



Follow Ups:



Post a Followup

Name:
E-mail: (optional)
Subject:

Comments:

Optional Link URL:
Link Title:
Optional Image URL: