Evidence in Sheep for Pre-Natal Transmission of Scrapie to Lambs from
Infected Mothers
James D. Foster, Wilfred Goldmann, Nora Hunter*
The Roslin Institute and Royal (Dick) School of Veterinary Studies, The
University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom
Abstract
Natural scrapie transmission from infected ewes to their lambs is thought
to occur by the oral route around the time of birth. However the hypothesis that
scrapie transmission can also occur before birth (in utero) is not currently
favoured by most researchers. As scrapie is an opportunistic infection with
multiple infection routes likely to be functional in sheep, definitive evidence
for or against transmission from ewe to her developing fetus has been difficult
to achieve. In addition the very early literature on maternal transmission of
scrapie in sheep was compromised by lack of knowledge of the role of the PRNP
(prion protein) gene in control of susceptibility to scrapie. In this study we
experimentally infected pregnant ewes of known PRNP genotype with a distinctive
scrapie strain (SSBP/1) and looked for evidence of transmission of SSBP/1 to the
offspring. The sheep were from the NPU Cheviot flock, which has endemic natural
scrapie from which SSBP/1 can be differentiated on the basis of histology,
genetics of disease incidence and strain typing bioassay in mice. We used embryo
transfer techniques to allow sheep fetuses of scrapie-susceptible PRNP genotypes
to develop in a range of scrapie-resistant and susceptible recipient mothers and
challenged the recipients with SSBP/1. Scrapie clinical disease, caused by both
natural scrapie and SSBP/1, occurred in the progeny but evidence (including
mouse strain typing) of SSBP/1 infection was found only in lambs born to fully
susceptible recipient mothers. Progeny were not protected from transmission of
natural scrapie or SSBP/1 by washing of embryos to International Embryo Transfer
Society standards or by caesarean derivation and complete separation from their
birth mothers. Our results strongly suggest that pre-natal (in utero)
transmission of scrapie may have occurred in these sheep.
SNIP...
In conclusion therefore, our study has presented evidence that suggests
that transmission of scrapie can occur from the infected mother sheep to her
lamb before birth, although it is almost certain not to be the only route by
which a lamb can become infected. Further studies are clearly necessary in order
to understand the underlying mechanisms and to be able to assess whether the
very different placental structures in humans will protect babies from infection
if born to CJD infected mothers. Other studies are near completion in our
laboratory aimed at clarifying the rate of maternal transmission using
scrapie-free sheep of New Zealand origin and therefore without the potential
interference from natural scrapie. The ultimate aim of control and eradiation of
scrapie infection in sheep clearly depends on understanding all the potential
routes of transmission as the use of genetically resistant sheep is not always
possible, especially for some rare breeds.
Citation: Foster JD, Goldmann W, Hunter N (2013) Evidence in Sheep for
Pre-Natal Transmission of Scrapie to Lambs from Infected Mothers. PLoS ONE
8(11): e79433. doi:10.1371/journal.pone.0079433
Editor: Ilia V. Baskakov, University of Maryland School of Medicine, United
States of America
Received September 11, 2013; Accepted September 19, 2013; Published
November 18, 2013
Copyright: 2013 Foster et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Funding: The project was funded by Defra (UK Department for the
Environment, Food and Rural Affairs) Grant number SE1823 (www.gov.co.uk/defra)
with core support funding to the Institute for Animal Health from BBSRC (UK
Biotechnology and Biological Sciences Research Council). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests
exist.
* E-mail: nora.hunter@roslin.ed.ac.uk
>>>Further studies are clearly necessary in order to understand
the underlying mechanisms and to be able to assess whether the very different
placental structures in humans will protect babies from infection if born to CJD
infected mothers.<<<
Evidence of in utero transmission of classical scrapie in sheep
John Spiropoulos⇑, Stephen A.C. Hawkins, Marion M. Simmons and Susan J.
Bellworthy
+ Author Affiliations Animal Health and Veterinary Laboratories Agency
(AHVLA) Weybridge, Addlestone, Surrey KT15 3NB, UK
ABSTRACT
Classical scrapie is one of the Transmissible Spongiform Encephalopathies
(TSE), a group of fatal infectious diseases that affect the central nervous
system (CNS). Classical scrapie can transmit laterally from ewe to lamb
perinatally, or between adult animals. Here we report detection of infectivity
in tissues of an unborn foetus, providing evidence that in utero transmission of
classical scrapie is also possible.
FOOTNOTES Corresponding Author: John Spiropoulos: Department of Pathology,
Animal Health and Veterinary Laboratories Agency, Woodham Lane, New Haw,
Addlestone, Surrey, KT15 3NB, Email: john.spiropoulos@ahvla.gsi.gov.uk, Tel: +44
(0) 1932 357795, Fax: +44 (0) 1932 357805 Copyright © 2014, American Society for
Microbiology. All Rights Reserved.
Tuesday, September 17, 2013
Mother to Offspring Transmission of Transmissible Spongiform Encephalopathy
TSE prion disease snip... Maternal CWD infection also appears to result in lower
percentage of live birth offspring. In addition, evolving evidence from protein
misfolding cyclic amplification (PMCA) assays on fetal tissues suggest that
covert prion infection occurs in utero. Overall, our findings demonstrate that
transmission of prions from mother to offspring can occur, and may be
underestimated for all prion diseases.
snip...
Here, in an experimental model of CWD, we have demonstrated the
transmission of infectious prions from clinical and subclinical mothers to
full-term viable, nonviable and in utero harvested offspring, revealing that the
transmission of TSEs from mother to offspring can occur and may be
underestimated for all prion diseases. snip... please see full text ; Tuesday,
September 17, 2013
*** Mother to Offspring Transmission of Transmissible Spongiform
Encephalopathy TSE prion disease ***
Friday, May 10, 2013
Evidence of effective scrapie transmission via colostrum and milk in
sheep
Tuesday, April 30, 2013
Transmission of classical scrapie via goat milk
Veterinary Record2013;172:455 doi:10.1136/vr.f2613
Envt.18: Mother to Offspring Transmission of Chronic Wasting Disease
Candace K. Mathiason,† Amy Nalls, Kelly Anderson, Jeanette Hayes-Klug,
Jenny G. Powers, Nicholas J. Haley and Edward A. Hoover
Colorado State University; Fort Collins, CO USA†Presenting author; Email:
ckm@lamar.colostate.edu
We have developed a new cervid model in small Asian muntjac deer (Muntiacus
reevesi) to study potential modes of vertical transmission of chronic wasting
disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally
infected with CWD tested PrPCWD lymphoid positive by four months post infection.
Ten fawns were born to these CWD-infected doe— four of the fawns were viable,
five were non-viable and one was a first trimester fetus harvested from a
CWD-infected doe euthanized at end-stage disease. The viable fawns have been
monitored for CWD infection by immunohistochemistry and sPMCA performed on
serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in
one fawn by IHC as early as 40 days of age. Moreover, sPMCA performed on rectal
lymphoid tissue has yielded positive results on another fawn at ten days of age.
In addition, sPMCA assays have demonstrated amplifiable prions in fetal
placental or spleen tissue of three non-viable fawns and mammary tissue of the
dams.
Additional pregnancy related fluids and tissues from the doe as well as
tissue from the nonviable fawns are currently being probed for the presence of
CWD. In summary, we have employed the muntjac deer model, to demonstrate for the
first time the transmission of CWD from mother to offspring. These studies
provide the foundation to investigate the mechanisms and pathways of maternal
prion transfer.
===========================
PPo3tss-18: A Possible Case of Maternal Transmission of the BSE Agent
within Captive Cheetah Affected with Feline Spongiform Encephalopathy
Anna Bencsik, Sabine Debeer, Thierry Petit and Thierry Baron
Afssa; Unité ATNC; Lyon, France; Zoo de la Palmyre; Les Mathes, France
Key words: BSE, FSE, vertical transmission
Introduction. Feline spongiform encephalopathy (FSE) is considered to be
related to bovine spongiform encephalopathy (BSE). It has been reported in
domestic cats as well as in captive wild cats including cheetahs, first in the
United Kingdom (UK) and then in other European countries. In France, several
cases were described in cheetahs either imported from UK or born in France. Here
we report details of two other FSE cases in captive cheetah. These cases are of
particular interest since the 2nd case of FSE in a cheetah born in France,
appears most likely due to maternal transmission.1
Results. Complete PrPd study showed the close likeness between the two
cheetah cases. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah
FSE revealed similar vacuolar lesion profiles, PrPd brain mapping with
occurrence of typical florid plaques.
Materials and Methods. Using immunohistochemistry (IHC), pathological form
of PrP(PrPd) was analyzed in the brains and peripheral organs of these two
cheetahs. Transmission studies to the TgOvPrP4 mouse line were also performed,
for comparison with the transmission of cattle BSE. Lesion profiles of the
infected transgenic mice were analyzed as well as type and brain distribution of
PrPd.
Conclusion. Collectively, these data indicate that both FSE cases harbor
the same strain of agent as the cattle BSE agent. Because this is most probably
a case of maternal transmission of the disease, this new observation may have
some impact on our knowledge of vertical transmission of BSE agent-linked TSEs
such as in human variant Creutzfeldt Jakob disease.
References
1. Bencsik et al. PLoS One 2009; 4:6929.
=========================
PPo3tss-40: Mother to Offspring Transmission of Chronic Wasting Disease
Candace K. Mathiason, Amy V. Nalls, Kelly Anderson, Jeanette Hayes-Klug,
Nicholas Haley and Edward A. Hoover
Colorado State University, Department of Microbiology, Immunology and
Pathology, Fort Collins, CO USA
Key words: Chronic wasting disease, vertical transmission, muntjac deer
We have developed a new cervid model in small Asian muntjac deer (Muntiacus
reevesi) to study potential modes of vertical transmission of chronic wasting
disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally
infected with CWD tested PrPCWD lymphoid positive by 4 months post infection.
Six fawns were born to these CWD-infected doe. Six fawns were born to 6
CWD-infected doe; 4 of the fawns were non-viable. The viable fawns have been
monitored for CWD infection by immunohistochemistry and sPMCA performed on
serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in
one fawn as early as 40 days of age. Moreover, sPMCA performed on rectal
lymphoid tissue has yield positive results on another fawn at 10 days of age. In
addition, sPMCA assays have also demonstrated amplifiable prions in maternal
placental (caruncule) and mammary tissue of the dam.
Additional pregnancy related fluids and tissues from the doe as well as
tissue from the nonviable fawns are currently being probed for the presence of
CWD. In summary, we have employed the muntjac deer model, to demonstrate for the
first time the transmission of CWD from mother to offspring. These studies
provide the foundation to investigate the mechanisms and pathways of maternal
prion transfer.
PRION 2011
landesbioscience.com
International Prion Congress: From agent to diseaseSeptember 8–11,
2010Salzburg, Austria
Friday, December 23, 2011
Detection of PrPres in Genetically Susceptible Fetuses from Sheep with
Natural Scrapie
http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/detection-of-prpres-in-genetically.html
Monday, November 22, 2010
Monday, November 22, 2010
SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK
Saturday, April 12, 2008
Evidence of scrapie transmission via milk
[6] Date: Fri 4 Feb 2005
From: Terry S. Singeltary Sr. flounder@wt.net
Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position
Paper, January 2005 [edited]
Position Statement: Maternal Transmission of variant Creutzfeldt-Jakob
disease Issue:
1. The Chief Medical Officer for England asked SEAC to consider current
evidence and comment on the potential transmission of variant Creutzfeldt-Jakob
disease (vCJD) from mother to child via human breast milk. In utero transmission
was also considered. The committee also commented on the scientific basis of a
risk reduction measure for possible transmission of vCJD via banked breast milk.
Background:
2. No diagnostic test is currently available for the detection of abnormal
PrP in milk. Research is under way to develop tests to screen for the possible
presence of abnormal prion protein (PrP) in milk samples from cattle
experimentally infected with BSE [A joint FSA/SEAC milk working group is
monitoring and providing advice on this research carried out at the Veterinary
Laboratories Agency.] These modified tests may also be applicable to human milk.
However, it is not yet clear when/if a reliable test will be available.
3. A small number of breast milk banks in the UK supply highly vulnerable
premature babies for whom no milk may be available from the mother. A model
developed by the Department of Health to assess the effect of pooling breast
milk from multiple donors on the possible risks of transmission of vCJD via
breast milk banks was considered.
4. There is some, albeit limited, published epidemiological and
experimental research on maternal transmission of prion diseases. There are also
unpublished surveillance data of children born to vCJD cases from the National
CJD Surveillance Unit and UK surveillance of neurological illness in children
which might inform on potential risks of maternal transmission. Breast milk
banks:
5. There is no evidence that vCJD infectivity has ever been transmitted
through breast milk. However, a theoretical risk exists. Modelling studies
clearly show that the practice of pooling breast milk increases the number of
donors to which a recipient is exposed and thereby increases the potential risk
of an infant receiving milk contaminated with vCJD infectivity. The theoretical
risk of infection can be minimised by not pooling the milk, by the use of
individual hand operated breast milk pumps for single donors, and by the use of
single-use sterilised bottles for collection. In addition, available evidence
suggests that infection/inflammation of the breast results in increased
lymphocytes in milk and therefore increased risk of infectivity. This risk would
be minimised if milk from donors showing signs of infection were not used.
6. The committee suggested that, if practicable, milk could be stored for
an appropriate period of time to allow the health status of donors to be
monitored, before it is released. However, information was not available to the
committee on whether long-term storage of human milk is detrimental to its
nutritional quality. Maternal transmission
7. There is evidence from animal studies for low-level maternal
transmission of prions in cattle and sheep. This transmission may occur in
utero, via milk and/or perinatally. However, the possibility that this putative
maternal transmission might have been due to another mode of transmission, for
example through a contaminated environment or feed, cannot be ruled out.
8. In contrast, in humans there is no evidence for maternal transmission in
cases of familial prion disease, other than the transfer of a mutant form of the
PrP gene, and there is no evidence of maternal transmission of Kuru [a chronic,
progressive, uniformly fatal nervous system disorder caused by prions,
associated with cannibalism among the Fore tribe and neighboring peoples in New
Guinea. - CopyEd.PG]. However, compared with other human prion diseases vCJD may
pose a greater risk because of the greater involvement of the lymphoreticular
system in vCJD pathogenesis. Although, breast tissue (and placenta) from a
single vCJD case tested negative for PrPvCJD, transfer of infectivity to breast
milk may depend on the physiological status of the mammary gland. Similar tests
or infectivity bioassays have not been conducted on breast tissue from lactating
patients with vCJD.
9. A published study suggesting transmission of sCJD in colostrum (ref. 1)
was considered unreliable because tissues not normally associated with high
levels of infectivity (blood and placenta) showed equivalent infectivity to that
of the brain in this study.
10. Analysis of prospective surveillance data of UK children born to
mothers with, or that had subsequently developed clinical vCJD, provide no
evidence for maternal transmission of vCJD. However, the number of cases is very
small and the incubation period of vCJD, if transmitted from mother to child, is
unknown and so the children may yet be too young to have developed symptoms.
11. The phenotype of BSE infection in humans expressing PrP genotypes other
than M/M at codon 129 is not known. Given recently published studies in mice
expressing the human PrP gene (ref. 2), which suggest that the human PrP
genotype may affect disease phenotype, the committee considered it very
important that undiagnosed neurological diseases be carefully monitored. In this
respect, amongst others, it is recommended that the careful monitoring of
neurological illnesses through the PIND surveillance of children (ref. 3)
continue. Conclusions
12. In summary, there is currently no epidemiological evidence for maternal
transmission of vCJD, including transmission via breast milk. However, there is
a hypothetical risk. Although available evidence is limited and mostly indirect
rather than direct, this risk, if any, appears to be low. As a risk cannot be
excluded, a watching brief should be maintained.
References: (1) Tamai Y et al. Demonstration of the transmissible agent in
tissue from a pregnant woman with CJD. New Eng J Med 1992 327, 649. (2)
Wadsworth et al. Human prion protein with valine 129 prevents expression of
variant CJD phenotype. Science. 2004 306, 1793-1796. (3) Devereux G et al.
Variations in neurodegenerative disease across the UK: findings from the
national study of Progressive Intellectual and Neurological Deterioration
(PIND). Arch DisChild. 2004 89, 8-12. -- Terry S. Singeltary Sr. flounder@wt.net
******
P.4.31
Prion infectivity in milk from ARQ/ARQ sheep experimentally infected with
Scrapie and MAEDI-VISNA virus
Ciriaco Ligios1, Maria Giovanna Cancedda1, Antonello Carta2, Cinzia
Santucciu1 Caterina Maestrale1, Francesca Demontis1, Sonia Attene1, Maria
Giovanna Tilocca1, Cristiana Patta1, Massimo Basagni5, Paola Melis1, James C.
De- Martini3, Christina Sigurdson4 1Istituto Zooprofilattico Sperimentale della
Sardegna, Italy; 2Research Unit: Genetics and Biotechnology, DIRPA, AGRIS
Sardinia, Italy; 3Department of Microbiology, Immunology, and Pathology,
Colorado State University, Fort Collins, CO, USA; 4Department of Pathology,
School of Medicine, University of California San Diego, USA; 5Prion Diagnostica
Rho, Italy
Background:
Scrapie in sheep is characterized by the deposition of misfolded and
aggregated prion protein (PrPSc) in the central nervous system (CNS) and within
the lymphoreticular system (LRS). PrPSc was shown to accumulate in organs beyond
the CNS and the LRS when lymphofollicular or granulomatous inflammation was also
present.
Objectives:
Our aim was to determine whether ectopic PrPSc accumulation in the inflamed
mammary gland of sheep with scrapie results in infectious prion secretion into
the milk.
Methods:
We fed approximately 1.1 - 2.1 L of milk from sheep with lymphofollicular
mastitis and clinical scrapie to each of 8 ARQ/ARQ lambs derived from
scrapie-free flocks. The milk donor sheep had been previously inoculated with
Maedi-Visna virus (MVV) intratracheally and intravenously and scrapie brain
homogenate orally. In addition, 3 ARQ/ARQ lambs were fed approximately 1.4 – 1.7
L of milk from ARQ/ARQ sheep that had been experimentally infected with only
scrapie. Additional control ARQ/ARQ lambs were inoculated with scrapie brain
homogenate only, or with milk from uninfected sheep.
Results:
Two lambs which had received milk from sheep with mastitis and scrapie
developed clinical signs of scrapie at 677 and 745 days post-inoculation. One
additional clinically healthy lamb from this group, which was sacrificed for a
cause unrelated to scrapie, was found to have PrPSc in brain and tonsil. The
control lambs and those which received milk from sheep affected only with
scrapie are, to date, clinically healthy.
Discussion:
This is the first evidence of clinical scrapie in sheep fed milk from
scrapie sick sheep. The experiment is ongoing, however these preliminary results
indicate that milk and/or colostrum from ARQ/ARQ sheep with clinical scrapie and
lymphofollicular mastitis could contribute to scrapie transmission.
Monday, August 03, 2009
Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed
Sheep
Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16
0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American
Society for Microbiology. All Rights Reserved.
TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY
a non-profit Swiss Foundation (January, 2009) TAFS1 STATEMENT ON TRANSMISSION OF
SCRAPIE VIA MILK
Prions in Milk from Ewes Incubating Natural Scrapie
ProMED-mail
Archive Number 20050211.0467 Published
Date 11-FEB-2005 Subject PRO/AH/EDR> CJD (new var.) update 2005
(02)
snip...
******
[3] Date: Thu 20 Jan 2005 From: Terry S. Singeltary Sr.
Chronic Lymphocytic Inflammation Specifies the Organ Tropism of
Prions
Chronic Lymphocytic Inflammation Specifies the Organ Tropism of
Prions
----------------------------------------------------------------------
[The following is the summary of a paper by Mathias Heikenwalder and 8
others, published in Science online, 10.1126/science.1106460, Thu 20 Jan 2005
.
This paper describes work that illustrates that chronic inflammatory
conditions may affect and expand the natural and iatrogenic transmission of
prions - Mod.CP]
Prions typically accumulate in nervous and lymphoid tissues. Because
proinflammatory cytokines and immune cells are required for lymphoid prion
replication, we tested whether inflammatory conditions affect prion
pathogenesis. We administered prions to mice with 5 inflammatory diseases of
kidney, pancreas or liver. In all cases, chronic lymphocytic inflammation
enabled prion accumulation in otherwise prion-free organs. Inflammatory foci
consistently correlated with lymphotoxin upregulation and ectopic induction of
PrPC-expressing FDC-M1+ cells, whereas inflamed organs of mice lacking
lymphotoxin-alpha or its receptor accumulate neither PrPSc nor infectivity upon
prion inoculation. By expanding the tissue distribution of prions, chronic
inflammatory conditions may act as modifiers of natural and iatrogenic prion
transmission.
****** [4] Date: Thu 20 Jan 2005 From: Terry S. Singeltary Sr. Source:
Reuters News Agency, Thu 20 Jan 2005 [edited]
Study Finds that Illness May Promote Spread of Mad Cow Prion
------------------------------------------------------------
The agent that transmits mad cow disease and related diseases may spread
further in the body of an animal suffering from certain illnesses, scientists
said on Thu 20 Jan 2005. Their finding raises the question of whether measures
aimed at curbing the spread of mad cow disease, or bovine spongiform
encephalopathy (BSE), are adequate, the researchers said.
Tests on mice showed that prions, the protein-like fragments that transmit
BSE and related diseases [e.g. variant Creutzfeldt-Jakob disease in humans], can
show up in organs they are not supposed to if the mouse has an inflammatory
condition. Scientists have believed that BSE-causing prions are limited to the
brain, spleen, spinal cord and lymph tissue, although some tests have suggested
blood and muscle tissue may also harbor the prions. The latest study, published
in the journal Science, suggests prions may also sometimes be found in the
kidney, pancreas and liver. "We administered prions to mice with 5 inflammatory
diseases of kidney, pancreas or liver," wrote the researchers, led by top prion
expert Dr. Adriano Aguzzi of the University Hospital of Zurich in
Switzerland.
Aguzzi and colleagues in Britain and the United States inoculated specially
bred mice with prions and checked to see if the prions spread in their bodies
when the mice had an inflammatory condition. This is because other studies had
suggested that prions might be attracted to immune system inflammatory cells.
"In all cases, chronic lymphocytic inflammation enabled prion accumulation in
otherwise prion-free organs," the researchers wrote.
BSE peaked in British cattle herds in the mid-1990s, and a few cases have
been reported in other countries. Canada reported its 3rd case this month.
People who eat BSE-infected beef products can develop a related human brain
disease called variant Creutzfeldt-Jakob disease or vCJD. There is no treatment
or cure. [As of 4 Feb 2005, so far in the UK for the year 2005 there have 8
referrals of suspected CJD; and there have been 8 deaths from sporadic CJC, one
from GSS and none from familial, iatrogenic or variant CJD. - Mod.CP]. It has
killed 148 Britons, and 5 [now 6] Britons are alive with the disease, according
to the British Department of Health's monthly report on the disease. The World
Health Organization says it has reports of 6 cases in France, one in Ireland,
one in Italy, one in Canada and one in the United States [and one in Japan: see;
ProMED-mail post "CJD (new var.) - Japan: death 20050204.0381" - Mod.CP]
Experts believed BSE first appeared when cattle were fed improperly
rendered remains of sheep infected with scrapie, a related disease. In 1997, the
United States and Canada imposed animal feed bans, and have mandated the removal
of materials believed to carry infectious prions. These include the skull,
brain, nerves attached to the brain, eyes, tonsils, spinal cord and attached
nerves, plus a portion of the small intestine. The study suggests that even
symptom-free animals may also have prions in their liver, kidney, and
pancreas.
-- Terry S. Singeltary Sr.
****** [5] Date: Fri 21 Jan 2005 From: ProMED-mail Souce: New York Times,
Fri 21 Jan 2005 [edited]
Study Finds Broader Reach for Mad Cow Proteins
----------------------------------------------
Mad cow disease has long been thought to occur in just the brains and
nervous systems of infected animals. But scientists are reporting today that the
proteins thought to cause the disease can travel to other organs as well. The
research is based on experiments with mice, but if it is borne out in other
species, it may suggest that no part of an infected animal is safe to eat. The
disease leads to a fatal brain disease in humans [variant Creutzfeldt-Jakob
disease].
In the mouse experiments, reported in the journal Science [see [3] above],
researchers in Switzerland found that prions, proteins that are the infectious
agent in mad cow disease, follow immune cells, called lymphocytes, in the body.
When mice were given chronic infectious diseases of the liver, kidney and
pancreas and then inoculated with prions, the prions made their way to the
infected organs. Dr. Adriano Aguzzi, a neuropathologist at the University
Hospital in Zurich, who led the experiments, said this meant that cows and sheep
infected with prions could harbor the disease in any inflamed organ.
But Dr. David R. Smith, a veterinarian at the University of Nebraska, said
the research did not raise alarms about American beef. For one thing, he said,
livestock with obvious signs of systemic infection, like a fever, are not
allowed into the food supply. And most American cattle are slaughtered while
they are young and at reduced risk of infection.
Many countries, including the United States, require the removal of skulls,
brains, eyes, spinal cords and other nervous tissues from slaughtered animals
because prions are known to accumulate in those tissues. Even in countries with
mad cow disease, mainly in Europe, meat is considered safe if those tissues are
removed, Dr. Aguzzi said. But the disease could spread more readily if
infections are not obvious or if inspections are sloppily done, he said.
[Byline: Sandra Blakeslee]
-- ProMED-mail
****** [6] Date: Fri 4 Feb 2005 From: Terry S. Singeltary Sr.
Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position
Paper, January 2005 [edited]
Position Statement: Maternal Transmission of variant Creutzfeldt-Jakob
disease
-----------------------------------------------
Issue:
1. The Chief Medical Officer for England asked SEAC to consider current
evidence and comment on the potential transmission of variant Creutzfeldt-Jakob
disease (vCJD) from mother to child via human breast milk. In utero transmission
was also considered. The committee also commented on the scientific basis of a
risk reduction measure for possible transmission of vCJD via banked breast
milk.
Background:
2. No diagnostic test is currently available for the detection of abnormal
PrP in milk. Research is under way to develop tests to screen for the possible
presence of abnormal prion protein (PrP) in milk samples from cattle
experimentally infected with BSE [A joint FSA/SEAC milk working group is
monitoring and providing advice on this research carried out at the Veterinary
Laboratories Agency.] These modified tests may also be applicable to human milk.
However, it is not yet clear when/if a reliable test will be available.
3. A small number of breast milk banks in the UK supply highly vulnerable
premature babies for whom no milk may be available from the mother. A model
developed by the Department of Health to assess the effect of pooling breast
milk from multiple donors on the possible risks of transmission of vCJD via
breast milk banks was considered.
4. There is some, albeit limited, published epidemiological and
experimental research on maternal transmission of prion diseases. There are also
unpublished surveillance data of children born to vCJD cases from the National
CJD Surveillance Unit and UK surveillance of neurological illness in children
which might inform on potential risks of maternal transmission.
Breast milk banks:
5. There is no evidence that vCJD infectivity has ever been transmitted
through breast milk. However, a theoretical risk exists. Modelling studies
clearly show that the practice of pooling breast milk increases the number of
donors to which a recipient is exposed and thereby increases the potential risk
of an infant receiving milk contaminated with vCJD infectivity. The theoretical
risk of infection can be minimised by not pooling the milk, by the use of
individual hand operated breast milk pumps for single donors, and by the use of
single-use sterilised bottles for collection. In addition, available evidence
suggests that infection/inflammation of the breast results in increased
lymphocytes in milk and therefore increased risk of infectivity. This risk would
be minimised if milk from donors showing signs of infection were not used.
6. The committee suggested that, if practicable, milk could be stored for
an appropriate period of time to allow the health status of donors to be
monitored, before it is released. However, information was not available to the
committee on whether long-term storage of human milk is detrimental to its
nutritional quality. Maternal transmission
7. There is evidence from animal studies for low-level maternal
transmission of prions in cattle and sheep. This transmission may occur in
utero, via milk and/or perinatally. However, the possibility that this putative
maternal transmission might have been due to another mode of transmission, for
example through a contaminated environment or feed, cannot be ruled out.
8. In contrast, in humans there is no evidence for maternal transmission in
cases of familial prion disease, other than the transfer of a mutant form of the
PrP gene, and there is no evidence of maternal transmission of Kuru [a chronic,
progressive, uniformly fatal nervous system disorder caused by prions,
associated with cannibalism among the Fore tribe and neighboring peoples in New
Guinea. - CopyEd.PG]. However, compared with other human prion diseases vCJD may
pose a greater risk because of the greater involvement of the lymphoreticular
system in vCJD pathogenesis. Although, breast tissue (and placenta) from a
single vCJD case tested negative for PrPvCJD, transfer of infectivity to breast
milk may depend on the physiological status of the mammary gland. Similar tests
or infectivity bioassays have not been conducted on breast tissue from lactating
patients with vCJD.
9. A published study suggesting transmission of sCJD in colostrum (ref. 1)
was considered unreliable because tissues not normally associated with high
levels of infectivity (blood and placenta) showed equivalent infectivity to that
of the brain in this study.
10. Analysis of prospective surveillance data of UK children born to
mothers with, or that had subsequently developed clinical vCJD, provide no
evidence for maternal transmission of vCJD. However, the number of cases is very
small and the incubation period of vCJD, if transmitted from mother to child, is
unknown and so the children may yet be too young to have developed
symptoms.
11. The phenotype of BSE infection in humans expressing PrP genotypes other
than M/M at codon 129 is not known. Given recently published studies in mice
expressing the human PrP gene (ref. 2), which suggest that the human PrP
genotype may affect disease phenotype, the committee considered it very
important that undiagnosed neurological diseases be carefully monitored. In this
respect, amongst others, it is recommended that the careful monitoring of
neurological illnesses through the PIND surveillance of children (ref. 3)
continue.
Conclusions
12. In summary, there is currently no epidemiological evidence for maternal
transmission of vCJD, including transmission via breast milk. However, there is
a hypothetical risk. Although available evidence is limited and mostly indirect
rather than direct, this risk, if any, appears to be low. As a risk cannot be
excluded, a watching brief should be maintained.
References:
(1) Tamai Y et al. Demonstration of the transmissible agent in tissue from
a pregnant woman with CJD. New Eng J Med 1992 327, 649.
(2) Wadsworth et al. Human prion protein with valine 129 prevents
expression of variant CJD phenotype. Science. 2004 306, 1793-1796.
(3) Devereux G et al. Variations in neurodegenerative disease across the
UK: findings from the national study of Progressive Intellectual and
Neurological Deterioration (PIND). Arch DisChild. 2004 89, 8-12.
-- Terry S. Singeltary Sr.
******
snip...
ProMED-mail promed@promedmail.org
******[6]Date: Fri 4 Feb 2005
From: Terry S. Singeltary Sr.
Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position
Paper, January 2005 [edited]
snip...
******[6]Date: Fri 4 Feb 2005
From: Terry S. Singeltary Sr.
Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position
Paper, January 2005 [edited]
SNIP...SEE FULL TEXT ; p.s. ProMed archives are pay-per-view now. ...tss
SNIP...SEE FULL TEXT ;
cjd mother to child transmission ???
Mother passes on CJD to unborn baby Sun, 17 Sep 2000 Telegraph By Rajeev
Syal, Jenny Booth and Chris Hastings
Dr Will offers me a tour of the laboratories. As we are getting up to go, I
broach something that has been bothering me. Does he think the victims will get
any younger?
'Well, we now have a 12-year-old.'
A 12-year-old?
'That's what I said.' He looks almost ashamed.
Girl or boy?
'I can't say.'
But if the incubation period is at least 10 years, then the child was
barely eating solid food when it contracted the infection. 'I'm not saying
anything,' the neurologist says wearily. 'You've got small children of your own,
Allison. You do the maths.'
The child has been ill since she was born but tests to pinpoint the cause
of the problem have so far proved inconclusive INCONCLUSIVE. What does not put
an end to a thing. Inconclusive presumptions are those which may be overcome by
opposing proof; for example, the law presumes that he who possesses personal
property is the owner of it, but evidence is allowed to contradict this
presumption, and show who is . At birth the baby, who cannot be named for legal
reasons, could not swallow and was unable to gain weight.
Wednesday, December 30, 2009
Is there evidence of vertical transmission of variant CJD ?
J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.172148
Is there evidence of vertical transmission of variant CJD?
Katy Murray (kmurray12@doctors.org.uk) + Author Affiliations
NationalCJD Surveillance Unit, United Kingdom James Peters
(jimmypeters1980@yahoo.co.uk) + Author Affiliations
NationalCJD Surveillance Unit, United Kingdom Lesley Stellitano
(lesley.stellitano@addenbrookes.nhs.uk) + Author Affiliations
Addenbrooke's Hospital, United Kingdom Annemarie Winstone
(annemarie.winstone@addenbrookes.nhs.uk) + Author Affiliations
Addenbrooke's Hospital, United Kingdom Christopher Verity
(christopher.verity@addenbrookes.nhs.uk) + Author Affiliations
Addenbrooke's Hospital, United Kingdom Robert Will (r.g.will@ed.ac.uk) +
Author Affiliations
NationalCJD Surveillance Unit, United Kingdom Published Online First 27
April 2009 Abstract Objectives: The possibility of vertical transmission of
variant CJD (vCJD) has been raised, because of the widespread distribution of
infectivity in vCJD and the demonstration that this condition can be transmitted
through blood transfusion. The aim is to search for evidence of this type of
transmission of vCJD.
Methods: A national surveillance system for CJD has been established in the
UK since 1990. Through this register details were extracted of all children born
to vCJD cases up to March 2009. This list was checked against the CJD register
and cases identified through the UK study of progressive intellectual and
neurological deterioration in children (PIND) to determine whether any of the
children of vCJD cases had themselves developed a progressive neurological
disorder or vCJD.
Results: 125 children have been born to parents with a diagnosis of vCJD.
Nine of these children were born to females with vCJD who were symptomatic at
conception, birth or within a year of clinical onset. Only one woman was known
to have breast fed her child. None of the children of vCJD cases have been
referred to the NCJDSU as suspected vCJD and none have been classified as
suffering from a progressive neurodegenerative disorder through the PIND study.
One of the children has been investigated by the National Prion Unit (see
accompanying case report).
Interpretation: To date there is no evidence of vertical transmission of
vCJD. However, the incubation period through this mechanism might be prolonged
and it will be many years before observational data can exclude this
possibility.
snip...see more here ;
Wednesday, December 30, 2009
Is there evidence of vertical transmission of variant CJD ?
http://creutzfeldt-jakob-disease.blogspot.com/2009/12/is-there-evidence-of-vertical.html
Thursday, January 23, 2014
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except
for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
2013 Tuesday, September 17, 2013
*** Mother to Offspring Transmission of Transmissible Spongiform
Encephalopathy TSE prion disease ***
To date, 125 children have been born to women who later developed CJD [11].
This is concerning because PrPCJD has been detected in the fetal and pregnancy
related tissues of a woman infected with CJD [12]. Although decades may pass
before the onset of clinical effects associated with such transmission due to a
long subclinical carrier state, the probability that these individuals harbor
infectious prions remains high.
Sunday, August 25, 2013
Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats,
blood, and mother to offspring transmission
snip...
Oral.08: Mother to offspring transmission of chronic wasting disease in
Reeve's Muntjac deer Amy Nalls,1 Erin McNulty,1 Jenny Powers,2 Davis Seelig,1
Clare Hoover,1 Nicholas Haley,1 Jeanette Hayes-Klug,1 Kelly Anderson,1 Paula
Stewart,3 Wilfred Goldmann,3 Edward A. Hoover1 and Candace K. Mathiason1
1Colorado State University; Fort Collins, CO USA; 2National Park Service; Fort
Collins, CO USA; 3The Roslin Institute and Royal School of Veterinary Studies;
Edinburgh, UK To investigate the role mother to offspring transmission plays in
chronic wasting disease (CWD), we have developed a cervid model employing the
Reeve's muntjac deer (Muntiacus reevesi). Eight muntjac doe were orally
inoculated with CWD and tested PrPCWD lymphoid positive by 4 mo post infection.
Fourteen fawns were born to these eight CWD-infected doe-3 were born viable, 6
were born non-viable and 5 were harvested as fetuses from early or end-stage
CWD-infected doe. All three viable fawns have demonstrated CWD IHC lymphoid
biopsy positivity between 43 d post birth and 11 mo post birth. Two of these
three CWD positive viable offspring have developed clinical signs consistent
with TSE disease (28-33 mo post birth). Moreover, CWD prions have been detected
by sPMCA in 11 of 16 tissues harvested from 6 full-term non-viable fawns and in
7 of 11 fetal tissues harvested in utero from the second and third trimester
fetuses. Additional tissues and pregnancy related fluids from doe and offspring
are being analyzed for CWD prions. In summary, using the muntjac deer model we
have demonstrated CWD clinical disease in offspring born to CWD-infected doe,
and in utero transmission of CWD from mother to offspring. These studies provide
basis to further investigate the mechanisms of maternal transfer of prions.
snip...
Sunday, August 25, 2013
Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats,
blood, and mother to offspring transmission
>>> Here, in an experimental model of CWD, we have demonstrated
the transmission of infectious prions from clinical and subclinical mothers to
full-term viable, nonviable and in utero harvested offspring, revealing that the
transmission of TSEs from mother to offspring can occur and may be
underestimated for all prion diseases. <<<
2014
Sunday, January 19, 2014
National Prion Disease Pathology Surveillance Center Cases Examined1 as of
January 8, 2014
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except
for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
Monday, January 27, 2014
Evidence of in utero transmission of classical scrapie in sheep
Terry S. Singeltary Sr.
