Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and decontamination possibilities for the TSE prion
Subject: Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and
decontamination possibilities for the TSE prion
please note, all Iatrogenic Creutzfeldt Jakob Disease iCJD is, is sporadic
Creutzfeldt Jakob Disease sCJD, until route and source of iatrogenic event took
place, and documented. until then, it’s all sporadic CJD.
I have put together a few cases from the past, of folks and hospitals that
were exposed to the TSE prion disease...also, some science on the extent of
decontamination of the TSE prion disease. ...
kind regards, terry
>>>Prions, the causative agents of the transmissible spongiform
encephalopathies, are notoriously difficult to inactivate. Current
decontamination recommendations by the World Health Organization include
prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium
hypochlorite, or autoclaving. For decontamination of large stainless steel
surfaces and equipment as in abattoirs, for example, these methods are harsh or
unsuitable. The current study was designed to evaluate the effectiveness of a
commercial product containing sodium percarbonate to inactivate prions. Samples
of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML)
were exposed to a sodium percarbonate-based product (SPC-P). Treated samples
were evaluated for abnormal prion protein (PrPSc)- immunoreactivity by western
blot analysis, and residual infectivity by mouse bioassay.<<<
>>This study demonstrates that exposure of the RML scrapie agent to
an SPC-containing product alone or in combination with SDS does not eliminate
prion infectivity, but does render PrPSc sensitive to proteinase K. Because of
this, it is interesting to consider the potential viability of a combination of
SPC and SDS, even at relatively low concentrations and mild temperatures,
concomitant with or followed by a protease for prion decontamination. Also,
because the SPC product we used contains additional proprietary ingredients, we
cannot rule-out contributions to increased PK-sensitivity or increased survival
by other components of the product. Studies in our laboratory are currently
underway examining exposure of prions to chemical grade SPC with or without SDS
followed by exposure to a protease. <<<
SNIP...another study below ;
>>>Conventional sterilization and disinfection methods are
inadequate in reducing prion infectivity of contaminated instruments, and World
Health Organization recommendations for disinfection using bleach or sodium
hydroxide are often impractical for routine decontamination.<<<
======================
Iatrogenic Creutzfeldt-Jakob disease via surgical instruments
Jonathan G. Thomas Affiliations Department of Neurosurgery, Baylor College
of Medicine, Houston, TX, USA , Carol E. Chenoweth Affiliations Department of
Infection Control and Epidemiology, and Department of Internal
Medicine-Infectious Diseases, University of Michigan, Ann Arbor, MI, USA ,
Stephen E. Sullivan Affiliations Department of Neurosurgery, University of
Michigan, 1500 E. Medical Center Drive, Room 3552 Taubman Center, Ann Arbor, MI
48109-5338, USA Corresponding Author InformationCorresponding author. Tel.: +1
734 936 9579; fax: +1 734 936 9294. email address Received 1 August 2012;
accepted 24 January 2013.
Abstract
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative prion disease that
can spread via contaminated neurosurgical instruments previously used on an
infected patient. We examine current guidelines on how to recognize, handle, and
prevent instrument-related iatrogenic CJD. Despite only four reported patients
worldwide implicating contaminated neurosurgical instruments, and none in the
past 30 years, the public health consequences of potential instrument-related
iatrogenic CJD can be far-reaching. Conventional sterilization and disinfection
methods are inadequate in reducing prion infectivity of contaminated
instruments, and World Health Organization recommendations for disinfection
using bleach or sodium hydroxide are often impractical for routine
decontamination. Recently, possible CJD exposure via infected surgical
instruments was suspected at a large teaching hospital. Although CJD was later
disproven, the intervening investigation exposed the difficulty in tracking
infected surgical instruments and in protecting subsequent surgical patients
from prion infection. To identify patients at risk for iatrogenic CJD,
infectivity of instruments after this index patient is estimated using simple
scenario modeling, assuming a certain log reduction of infectivity for each
cleansing cycle. Scenario modeling predicts that after six cycles of instrument
use with conventional cleansing following an index patient, other patients are
highly unlikely to be at risk for iatrogenic CJD. Despite its rarity, the threat
of iatrogenic CJD transmission via contaminated instruments poses tremendous
challenges to neurosurgeons. Basic prevention strategies should be employed for
patients with suspected CJD, including use of disposable instruments where
possible and quarantining non-disposable instruments until the diagnosis is
ascertained, or using special instrument reprocessing methods if CJD is
suspected.
Keywords: Creutzfeld-Jakob disease, Iatrogenic, Sterilization, Transmission
Appendix 2: Scrapie Disinfection Guidelines
*** The following suggested procedures do not guarantee total and complete
disinfection and inactivation of the infectious agent.
Nonetheless, current information regarding the efficiency of following
these disinfection procedures under laboratory conditions suggests these
procedures will reduce infectivity in the environment. Until more specific
information is available, good sanitary practices are recommended following each
lambing. The following methods below should be applied to lambing areas where
infected or exposed animals have lambed. Pastures
1. If practical, till soil under or do not use the area to graze
susceptible animals.
2. If this is impractical, do not use the pasture until the animal waste
has decomposed and the weather has had an opportunity to dilute any infectivity.
Drylots
1. Remove the manure and bedding and, when practical, the top 1 to 2 inches
of soil to reduce contamination.
2. Bury or till under the removed material; or, compost the removed
material in areas not accessed by domestic or wild ruminants until it can be
buried or tilled under. Earth Surfaces Inside Structures or Used for Confined
Lambing Pens
1. Remove the organic material and, when practical, the top 1 to 2 inches
of soil to reduce contamination.
2. Bury or till under the removed material; or, compost the removed
material in areas not accessed by domestic or wild ruminants until it can be
buried or tilled under. Non-earth Surfaces (These include cement, wood, metal,
tools, equipment, instruments, feed, hay, bedding, and other materials.)
1. Remove all organic material. Bury, incinerate, or compost the removed
material in areas not accessed by domestic or wild ruminants and then till
under, bury or incinerate.
2. When practical for other items bury or incinerate by high-temperature
incineration methods.
3. Clean and wash surfaces and remaining items using hot water and
detergent. Allow all surfaces, tools, and equipment to dry completely before
disinfecting and sanitizing using the following suggested methods.
a. Autoclave instruments, small tools, and other items at 277 °F for 1
hour. This method is more effective when preceded by the treatment described in
b or c below.
For General Distribution 67
Scrapie Program Standards Volume 2 June 2013
b. To clean dry surfaces, apply a 2 percent available chlorine solution1
(equivalent to about 20,000 p/m available chlorine: 50 ounces [6-1/4 cups]
bleach to 78 ounces [9 ¾ cups] water to give 1 gallon of solution) at room
temperature (at least 65 °F) for at least 1 hour. Note: Bleach is caustic and
can be hazardous if swallowed, gets in the eyes, is breathed in, or is left on
the skin. Further, care must be taken to prevent contamination of water from run
off and to comply with any environmental regulations for use of this product.
Read the material safety data sheet prior to use and use appropriate personal
protective equipment or hire trained personnel to do the work.
*** c. To clean dry surfaces, apply 1-molar solution of sodium hydroxide1
(approximately 4-percent solution [5 ounces sodium hydroxide dissolved in l
gallon water]) at room temperature (at least 65 °F) for at least 1 hour.
Synonyms for sodium hydroxide are caustic soda, soda lye, and sodium hydrate.
Note: Sodium hydroxide is caustic and can be hazardous if swallowed, gets in the
eyes, is breathed in, or is left on the skin. Further, care must be taken to
prevent contamination of water from run off and to comply with any environmental
regulations for use of this product. Read the material safety data sheet prior
to use and use appropriate personal protective equipment or hire trained
personnel to do the work.
1 40 CFR § 152 declares prions a pest under the Federal Insecticide,
Fungicide and Rodenticide Act (FIFRA). Accordingly, only products registered
with the Environmental Protection Agency (EPA) specifically for the reduction of
prion infectivity can be used at these sites. Currently there are no EPA
registered products available; EPA has therefore granted APHIS an exemption for
the use of chlorine and sodium hydroxide for use in its prion control and
eradication programs. The instructions above conform to those on the exemption
labels.
For General Distribution 68
Scrapie Program Standards Volume 2 June 2013
Exposure of RML scrapie agent to a sodium percarbonate-based product and
sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate
infectivity
BMC Veterinary Research 2013, 9:8 doi:10.1186/1746-6148-9-8 Jodi D Smith
(jodi.smith@ars.usda.gov) Eric M Nicholson (eric.nicholson@ars.usda.gov) Gregory
H Foster (ghfoster@mac.com) Justin J Greenlee (justin.greenlee@ars.usda.gov)
ISSN 1746-6148
Article type Research article Submission date 18 September 2012 Acceptance
date 8 January 2013 Publication date 11 January 2013 Article URL http://www.biomedcentral.com/1746-6148/9/8
BMC Veterinary Research
© 2013 Smith et al.
Exposure of RML scrapie agent to a sodium percarbonate-based product and
sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate
infectivity
Jodi D Smith1 Email: jodi.smith@ars.usda.gov Eric M Nicholson1 Email:
eric.nicholson@ars.usda.gov Gregory H Foster1 Email: ghfoster@mac.com Justin J
Greenlee1* * Corresponding author Email: justin.greenlee@ars.usda.gov
1 Virus and Prion Research Unit, National Animal Disease Center, USDA,
Agricultural Research Service, 1920 Dayton Ave, Ames, IA 50010, USA
Abstract
Background
Prions, the causative agents of the transmissible spongiform
encephalopathies, are notoriously difficult to inactivate. Current
decontamination recommendations by the World Health Organization include
prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium
hypochlorite, or autoclaving. For decontamination of large stainless steel
surfaces and equipment as in abattoirs, for example, these methods are harsh or
unsuitable. The current study was designed to evaluate the effectiveness of a
commercial product containing sodium percarbonate to inactivate prions. Samples
of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML)
were exposed to a sodium percarbonate-based product (SPC-P). Treated samples
were evaluated for abnormal prion protein (PrPSc)- immunoreactivity by western
blot analysis, and residual infectivity by mouse bioassay.
Results
Exposure to a 21% solution of SPC-P or a solution containing either 2.1% or
21% SPC-P in combination with sodium dodecyl sulfate (SDS) resulted in increased
proteinase K sensitivity of PrPSc. Limited reductions in infectivity were
observed depending on treatment condition. A marginal effect on infectivity was
observed with SPC-P alone, but an approximate 2–3 log10 reduction was observed
with the addition of SDS, though exposure to SDS alone resulted in an
approximate 2 log10 reduction.
Conclusions
This study demonstrates that exposure of a mouse-adapted scrapie strain to
SPC-P does not eliminate infectivity, but does render PrPSc protease sensitive.
Keywords Inactivation, Prion, Scrapie, Sodium dodecyl sulfate, Sodium
percarbonate
SNIP...
A major finding of this study was the increased sensitivity of PrPSc to PK
by the SPC-based product without (SPC-PH only) or with SDS at room temperature,
as judged by immunoblotting after exposure of the samples to limited
proteolysis. Based on the loss of detectable PrPSc immunoreactivity after
incubation at pH 11, it appears this effect may be largely pH-dependent. It is
well established that prion infectivity is reduced under extremely basic
conditions, such as exposure to NaOH (pH 12–14) [19-21]. While the pH generated
by SPC-P is lower at 11, it appears to be a favorable characteristic of the
compound with regard to PrPSc protease sensitivity. However, a solely
pH-dependent effect does not explain why SPC-PL treatment alone (pH 11) did not
yield similar WB results. One possible explanation is that a lower concentration
of the product may have contained diminished buffering capacity resulting in a
drop in pH as treatment proceeded, but serial pH evaluation of treated brain
homogenate at 30, 90, and 180 min revealed that the pH remained above 10.7.
Although treatment with the SPC product did render PrPSc sensitive to digestion
by proteinase K, it did not eliminate infectivity. Recent studies examining
prion infectivity in infected tissue and cell cultures have also demonstrated
loss of detectable PrPSc on western blot, but residual infectivity [22,23]. Our
results support the inference that biochemical analysis alone is insufficient
for determination of prion infectivity. The observed PrPSc/infectivity mismatch
in this study and in others warrants a number of considerations including WB
sensitivity, epitope disruption by inactivation treatments, and alternative
infectious agents to PrPSc, such as PK-sensitive forms of PrP or viruses. It is
possible the amount of residual PrPSc in our treated samples was below the
detection limit of our WB (0.025 mg equivalents of brain tissue for this
particular inoculum [24]), or it may be that a true dissociation of PrPSc and
TSE infectivity exists supporting the actuality of alternative infectious agents
to PrPSc [25]. A recent study has demonstrated poor correlation between
infectivity and WB results for sheep scrapie and sheep BSE [26] in line with
observations that PK-sensitive PrP particles are associated with disease
[27,28].
The bioassay results we present indicate that exposure to the selected
SPC-based product alone or in combination with 2.5% SDS is not a viable option
for the inactivation of prions. No decrease in infectivity was observed using
the SPC-PL solution alone, and a modest 1 log10 reduction was achieved with the
SPC-PH solution. However, recent investigations have demonstrated differential
susceptibility of distinct prion strains to the same inactivation procedure
[29]; therefore, we are currently investigating the efficacy of these treatment
conditions in an ovine scrapie model. It should also be acknowledged that
chemical treatment of the scrapie agent has been shown to delay the
dose–response relationship [30,31] resulting in prolonged incubation times
without a change in calculable titer. It is possible our results could be
reflecting this phenomenon, but without bioassay data from serial dilutions of
treated brain homogenate this cannot be definitively determined. Some caution
may therefore be warranted when interpreting these results. The addition of 2.5%
SDS to the SPC-P solutions resulted in a 2–3 log10 reduction in infectivity, but
exposure to SDS alone resulted in an approximate 2 log10 reduction. This
suggests much of the observed combinatorial effect was due to SDS. Prior studies
using SDS have demonstrated minimal effects on CJD infectivity [16], but up to a
3 log10 reduction on scrapie infectivity [17]. Exposure of hamster-adapted Sc237
scrapie to room temperature SDS at pH values of ≤4.5 or ≥10 resulted in
increased PK sensitivity of PrPSc, and exposure to acidic SDS resulted in
decreased infectivity [11]. Since SDS at room temperature is an effective
denaturant at a pH ≥10, this could have contributed to the loss of detectable
PrPScimmunoreactivity we observed after proteolysis in samples treated with
SPC-P and SDS. There was also enhanced reduction in infectivity with the
combination of SPC-PL and SDS. This may be indicative of an enhanced effect of
SDS under basic conditions or a two-step mechanism whereby denaturation of PrPSc
by the relatively high pH of the solution and/or SDS is followed by exposure of
sites sensitive to oxidative damage. Alternatively, the two treatment components
could be acting on different PrPSc fractions in the inoculum resulting in an
additive effect since the combination of SPC-PL and SDS was roughly equivalent
to slightly greater than the sum of the effects of each individual component.
The combination of SPC-PH and SDS did not provide an equivalent or better
increase in survival time than the combination of SPC-PL and SDS. While we are
confident in this result, we cannot definitively explain this observation.
Perhaps disease in this group was exacerbated by oxidative damage induced by the
introduction of treated brain samples containing a greater concentration of
sodium percarbonate. Oxidative stress, whether a cause or consequence of disease
progression, is considered an important contributor to prion neuropathology
[32-34]. It is also possible that the SPC-P solution at higher concentration may
somehow be interfering with the denaturing action of SDS. SDS action may be
enhanced when combined with lower concentrations of SPC-P for longer exposure
times, but restricted by higher concentrations, perhaps via chemical
modification of SDS binding sites on the protein.
Oxidizing agents have been used with variable success in prion inactivation
studies. Exposure of prions to halogens such as sodium hypochlorite at ≥ 20,000
ppm is an accepted means of decontamination [8], but chlorine dioxide is much
less effective at inactivating hamster-adapted 263 K scrapie [35]. Peroxygens
such as liquid hydrogen peroxide [13,35,36] and peracetic acid [37] also promote
limited inactivation. However, recent studies using vaporized hydrogen peroxide
to decontaminate stainless steel surfaces have demonstrated significant
reductions in infectivity for hamster-adapted 263 K scrapie and mouse-adapted
BSE [13,15]. A protective effect from oxidation by peracetic acid has been
demonstrated with the ME7 scrapie agent and attributed to prion aggregation
[37]. Peracetic acid at 2% was effective at inactivating the ME7 scrapie agent
in intact brain tissue, but not homogenized tissue. Samples in the current study
were homogenized, which may have imparted a degree of protection from oxidation
and contributed to the ineffectiveness of SPC-P alone at decreasing infectivity.
We propose that the addition of SDS would have decreased aggregation of cell
membranes to which infectivity is bound, thus enhancing the activity of SPC-P
and perhaps contributing to the increased survival observed with the
combination.
Conclusions
This study demonstrates that exposure of the RML scrapie agent to an
SPC-containing product alone or in combination with SDS does not eliminate prion
infectivity, but does render PrPSc sensitive to proteinase K. Because of this,
it is interesting to consider the potential viability of a combination of SPC
and SDS, even at relatively low concentrations and mild temperatures,
concomitant with or followed by a protease for prion decontamination. Also,
because the SPC product we used contains additional proprietary ingredients, we
cannot rule-out contributions to increased PK-sensitivity or increased survival
by other components of the product. Studies in our laboratory are currently
underway examining exposure of prions to chemical grade SPC with or without SDS
followed by exposure to a protease.
Saturday, January 12, 2013
Exposure of RML scrapie agent to a sodium percarbonate-based product and
sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate
infectivity
Research Article Resistance of Bovine Spongiform Encephalopathy (BSE)
Prions to Inactivation Kurt Giles, Affiliations: Institute for Neurodegenerative
Diseases, University of California San Francisco, San Francisco, California,
United States of America, Department of Neurology, University of California San
Francisco, San Francisco, California, United States of America
X David V. Glidden, Affiliation: Department of Epidemiology and
Biostatistics, University of California San Francisco, San Francisco,
California, United States of America
X Robyn Beckwith, Affiliation: Institute for Neurodegenerative Diseases,
University of California San Francisco, San Francisco, California, United States
of America
X Rose Seoanes, Affiliation: Institute for Neurodegenerative Diseases,
University of California San Francisco, San Francisco, California, United States
of America
X David Peretz, Affiliations: Institute for Neurodegenerative Diseases,
University of California San Francisco, San Francisco, California, United States
of America, Department of Neurology, University of California San Francisco, San
Francisco, California, United States of America
Current address: Novartis Vaccines and Diagnostics, Emeryville, California,
United States of America
X Stephen J. DeArmond, Affiliations: Institute for Neurodegenerative
Diseases, University of California San Francisco, San Francisco, California,
United States of America, Department of Pathology, University of California San
Francisco, San Francisco, California, United States of America
X Stanley B. Prusiner mail * E-mail: stanley@ind.ucsf.edu
Affiliations: Institute for Neurodegenerative Diseases, University of
California San Francisco, San Francisco, California, United States of America,
Department of Neurology, University of California San Francisco, San Francisco,
California, United States of America, Department of Biochemistry and Biophysics,
University of California San Francisco, San Francisco, California, United States
of America
X
Abstract Distinct prion strains often exhibit different incubation periods
and patterns of neuropathological lesions. Strain characteristics are generally
retained upon intraspecies transmission, but may change on transmission to
another species. We investigated the inactivation of two related prions strains:
BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation
was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH,
and different temperatures. Infectivity was measured using transgenic mouse
lines that are highly susceptible to either BSE or 301V prions. Bioassays
demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation
than 301V prions while Western immunoblotting showed that short acidic SDS
treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at
similar rates. Our findings argue that despite being derived from BSE prions,
mouse 301V prions are not necessarily a reliable model for cattle BSE prions.
Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and
hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more
resistant to inactivation, respectively. Our studies contend that any prion
inactivation procedures must be validated by bioassay against the prion strain
for which they are intended to be used.
Author Summary “Mad cow” disease, formally known as bovine spongiform
encephalopathy (BSE), belongs to a family of diseases affecting humans and a
number of commercially important animal species. These diseases are not spread
by bacteria or viruses, but by infectious proteins, termed “prions.” Prions are
known to be very difficult to inactivate, but little is known about the relative
difficulty of inactivation for prions from different species. Here, we studied
the inactivation of BSE prions and compared it to the inactivation of prions
from humans, mice, and hamsters. We used highly sensitive, genetically
engineered mouse models to detect low levels of infectivity. We then quantified
the levels of inactivation for a range of treatments and calculated differences
between prions from different species. We found that naturally occurring BSE
prions can be up to 1 million times more difficult to inactivate than the most
commonly used hamster prions. BSE prions were also 1,000 times more difficult to
inactivate than a mouse prion that was thought to be a surrogate for BSE prions.
This study demonstrates that prion inactivation procedures need to be validated
directly against the prion strains for which they are intended to be used.
Citation: Giles K, Glidden DV, Beckwith R, Seoanes R, Peretz D, et al.
(2008) Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to
Inactivation. PLoS Pathog 4(11): e1000206.
doi:10.1371/journal.ppat.1000206
Editor: David Westaway, University of Alberta, Canada
Received: March 7, 2008; Accepted: October 15, 2008; Published: November
14, 2008
Copyright: © 2008 Giles 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: This work was supported by grants from the National Institutes of
Health (R01AI064709, AG02132, AG10770, and AG021601) as well as by a gift from
the G. Harold and Leila Y. Mathers Charitable Foundation.
Competing interests: The authors have declared that no competing interests
exist.
snip...
Discussion The application of survival analysis techniques to prion
incubation periods provides a more accurate representation of the data. The
distribution of animals succumbing to disease is rarely symmetrical, and not all
animals become sick at low levels of infectivity. These factors are reflected by
reporting median incubation periods and asymmetric 95% ci, which are by
definition wider than standard deviation or standard error of the mean. These
techniques also allow us to quantify inactivation using different Tg model
systems, in an unbiased way.
We previously demonstrated that human CJD prions were significantly more
resistant to inactivation than hamster Sc237 prions [23]. This differential
inactivation of prion strains has also been observed by others. The phenolic
detergent Environ LpH was shown to inactivate all detectable infectivity of
hamster Sc237 prions [44],[45], but only modestly reduced infectivity of mouse
RML prions [46].
Rodent-passaged prion strains are widely used in prion research. While
these have been invaluable for understanding prion biology, great care must be
taken in extrapolating any characteristics of these prions back to the original
species and strain from which they were derived. Recommendations for the
inactivation of human CJD prions were partly based on experiments on adapted
strains of CJD passaged in mice [47], hamsters [48], and guinea pigs [49].
However, since the sequence of PrPSc is encoded by the host in which the prions
were last passaged, these “CJD” strains are actually mouse, hamster and guinea
pig prions, respectively, which may exhibit different resistances to
inactivation compared to the human CJD prions from which they were originally
derived.
Gel electrophoresis can be used to identify the PK-resistant core of PrPSc,
which can differ between strains. This technique was used to classify human
prion strains based on the size of the unglycosylated, protease-resistant PrPSc
fragments: type 1 results from cleavage at residue 82 and has a fragment size of
21 kDa and type 2 results from cleavage at residue 97 and has a fragment size of
19 kDa [50]. Despite the assumption that 301V is representative of the BSE
strain from which it was derived, we observed a difference in the sizes of the
unglycosylated bands between the two strains (Figure 1), which is consistent
with previously published results. A mixture of N-terminal sequences was
obtained from the 301V strain, starting with residue 81 [51]. In contrast, BSE
was not recognized by an antibody directed against residues 89–104, suggesting
the major cleavage point is within this region [52]. Furthermore, cattle BSE and
mouse 301V PrPSc have different susceptibilities to acidic SDS (Figure 1B,
Tables 1 and 2), suggesting that they are different strains.
We observed differences in the relative effectiveness of treatments on the
two strains, as measured by Western blots and infectivity bioassay. In all
cases, increasing the time and temperature of acidic SDS treatments led to
reduced PrPSc levels and increased inactivation. For acidic SDS treatments of
<8 18="" 1="" 1b="" 1c="" 301v="" 4="" 65="" 8="" a="" acidic="" acoh="" alone="" and="" approaching="" as="" at="" background="" bioassay.="" blots="" both="" bse="" by="" cattle="" compared="" contrast="" demonstrated="" detected="" div="" exposure="" fold="" for="" h="" igure="" immunoblots="" implies="" in="" inactivation="" incubation="" infectivity="" levels="" logs="" longer="" min="" more="" mouse="" of="" or="" prions.="" prions="" prpsc="" reduced="" reduction="" relatively="" residual="" resistant="" sds="" showed="" signal="" significantly="" similar="" that="" the="" to="" treated="" treatments="" unchanged="" up="" water="" were="" western="" which="" with="">
Western blotting is a rapid and convenient way of determining the level of
PrPSc, but it is limited by a dynamic range of ~100-fold. It has long been known
that the PrPSc level correlates with infectivity [53], but the precise
relationship between the two remains to be determined. While PrPSc was
originally defined as resistance to PK, we have since shown that there are both
protease-resistant (r) and protease-sensitive (s) forms of PrPSc [54]. Western
blotting only detects rPrPSc, while the conformation-dependent immunoassay [8]
and the amyloid seeding assay [55] are able to detect both rPrPSc and
sPrPSc.
The apparent discrepancies we observed between PrPSc level and infectivity
for 301V and BSE prions may be due to several factors. First, the sPrPSc
fraction, and its associated infectivity, may be variable between 301V and BSE.
If 301V and BSE have differing amounts of rPrPSc and sPrPSc, and at least some
infectivity is associated with sPrPSc, then Western blot results would not
necessarily correlate with infectivity. Second, structural differences between
the strains may result in different levels of inactivation. Presumably, the
quaternary structure would be broken down first when inactivating prions,
whereas the tertiary structure would have to be unfolded to diminish higher
levels of infectivity. In such a case, mouse 301V prions may have an equally
stable quaternary structure but less stable tertiary structure compared to
cattle BSE prions.
Cattle or human prions passaged in rodents give rise to rodent prions.
Mouse 301V prions are very resistant to inactivation [56]. Additionally, a human
prion strain causing Gerstmann-Sträussler-Scheinker disease was passaged in
mice; the resulting strain, termed M1000, was reported to be highly resistant to
inactivation [57]. However, for both 301V and M1000, the relative
susceptibilities to inactivation were not directly compared to their respective
parent strains. We demonstrate here that mouse 301V and its parent strain, BSE,
have different resistances to inactivation. Therefore, any extrapolation from a
rodent-passaged prion strain to the original parent strain must be interpreted
cautiously. A more suitable model for BSE prions may be BSE passaged in
Tg(BoPrP) mice, which produce PrPSc with the BoPrP sequence as well as with the
same electrophoretic mobility and glycosylation pattern as cattle BSE prions
[58]. Infected brains from this line were recently shown to be suitable for
evaluation of BSE tests [59]. However, these bovine prions are in the milieu of
mouse brain homogenate rather than cattle brain homogenate, and it remains to be
determined whether this has an effect on the inactivation characteristics.
As with the results reported previously for hamster Sc237 and human sCJD
prions [23], the inactivation of cattle BSE and mouse 301V prions from
stainless-steel surfaces is more difficult than inactivating similar levels of
infectivity in brain homogenates. Stainless-steel wire as a model for surface
contamination [60] provides a useful tool to study prion inactivation from
surgical instruments or machinery used in slaughterhouses. After 4-mm wires were
incubated in 10% brain homogenate, then washed extensively, we were able to
elute PrP equivalent to ~250 ng of brain tissue from each wire. Other
investigators were able to elute substantially higher PrP levels from wires
soaked in brain homogenate [61], but their wires were not exhaustively washed,
as ours were. Previous studies, using very similar washing strategies, reported
the inability to detect eluted PrP or other proteins from stainless-steel wires
[62]. However, 2 M NaOH used in those studies may have hydrolyzed many of the
proteins, including PrP.
In conclusion, we have quantified the relative resistance to inactivation
of four prion strains from different species. Cattle BSE prions appear to be the
most resistant strain studied. In comparison, human sCJD prions are
approximately 10-fold less resistant to inactivation by SDS at neutral or acidic
pH, or by heat alone. Mouse 301V prions are 100- to 1,000-fold less resistant,
and hamster Sc237 prions are up to 1,000,000-fold less resistant to
inactivation. As shown by our findings, prion inactivation based on
rodent-passaged prion strains may not be effective against the naturally
occurring strains for which they were developed.
HOSPITAL EPIDEMIOLOGY AND INFECTION CONTROL
POLICIES AND PROCEDURES FOR PATIENTS WITH SUSPECTED OR CONFIRMED HUMAN
PRION DISEASE (E.G., CREUTZFELDT-JAKOB DISEASE [CJD])*
POLICY 4.2
Issued: 4/89
Last Reviewed: 05/12
Bovine Spongiform Encephalopathy Mad Cow Disease, BSE
Last Updated: May 2012
Even the harshest combination of chemical and physical disinfection is not
guaranteed to destroy all prions. In experiments, a stainless-steel wire
remained infectious after cleaning with sodium hydroxide and autoclaving.
Surgical instruments that have undergone repeated cycles of cleaning and
disinfection have transmitted the sporadic (genetic) form of CJD iatrogenically.
For this reason, disposable equipment and instruments may be recommended instead
of disinfection during some medical procedures.
The emergence of vCJD in humans has been causally linked to ingestion of
BSE (Bruce et al., 1997). Recommended safety precautions for handling the agent
are based on the assumption that BSE is zoonotic. Biocontainment for necropsies
and tissue handling should be risk-based and compliant with relevant national
regulations; any procedure creating aerosols must be conducted under containment
level 3 (see Chapter 1.1.2 Biosafety and biosecurity in the veterinary
microbiology laboratory and animal facilities), and the laboratory must comply
with national biocontainment and biosafety regulations to protect staff from
exposure to the pathogen. Recommended decontamination procedures may not be
completely effective when dealing with high-titre material or when the agent is
protected within dried organic matter. Recommended physical inactivation is by
porous load autoclaving at 134°C–138°C for 18 minutes at 30 lb/in2 (208 kPa or
2.2 bar). However, temperatures at the higher end of the range may be less
effective than those at the lower end and total inactivation may not be achieved
under certain conditions, such as when the test material is in the form of a
macerate. Recommended decontamination procedures may not be completely effective
under some circumstances. Disinfection of potential fomites is carried out using
sodium hypochlorite containing 2% available chlorine, or 2 N sodium hydroxide,
applied for more than 1 hour at 20°C for surfaces, or overnight for equipment.
The safest and most unambiguous method for ensuring that there is no risk
of residual infectivity on contaminated instruments and other materials is to
discard and destroy them by incineration.6 Current recommendations for
inactivation of prions on instruments and other materials are based on the use
of sodium hypochlorite, NaOH, Environ LpH and the moist heat of autoclaving with
combinations of heat and chemical being most effective (Table 9).5,6 Surgical
Procedures Precautions for surgical procedures on patients diagnosed with prion
disease are outlined in an infection control guideline for transmissible
spongiform encephalopathies developed by a consultation convened by the WHO in
1999.6 Sterilization of reusable surgical instruments and decontamination of
surfaces should be performed in accordance with recommendations described by the
CDC (www.cdc.gov) and the WHO infection control guidelines.6 Table 9 summarizes
the key recommendations for decontamination of reusable instruments and
surfaces. Contaminated disposable instruments or materials should be incinerated
at 1000° C or greater.7
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform
Encephalopathies Updated 2010
Dissociation between Transmissible Spongiform Encephalopathy (TSE)
Infectivity and Proteinase K-Resistant PrPSc Levels in Peripheral Tissue from a
Murine Transgenic Model of TSE Disease Karen Dobie and Rona Barron + Author
Affiliations
Neurobiology Division, The Roslin Institute & R(D)SVS, Easter Bush,
Midlothian, United Kingdom ABSTRACT Most current diagnostic tests for
transmissible spongiform encephalopathies (TSE) rely on the presence of
proteinase K (PK)-resistant PrPSc (PrP-res) in postmortem tissues as an
indication of TSE disease. However, a number of studies have highlighted a
discrepancy between TSE infectivity and PrP-res levels in both natural and
experimental cases of TSE disease. Previously, we have shown high TSE
infectivity levels in the brain tissue of mice that have a clinical TSE disease
with associated vacuolar pathology but little or no detectable PrP-res. Here,
the levels of TSE infectivity and PrP-res within a peripheral tissue of this
mouse model were investigated. Biochemical analysis showed that low levels of
PrP-res were present in the spleen tissue in comparison to the levels observed
in the spleen of mice infected with ME7 or 79A. However, upon subpassage of
brain and spleen tissue from clinically ill mice with little or no PrP-res
detectable, similar short incubation periods to disease were observed,
indicating that infectivity levels were similarly high in both tissues. Thus,
the discrepancy between PrP-res and TSE infectivity was also present in the
peripheral tissues of this disease model. This result indicates that peripheral
tissues can contain higher levels of infectivity given the correct combination
of host species, PrP genotype, and TSE agent. Therefore, the assumption that the
levels of peripheral infectivity are lower than those in the central nervous
system is not always correct, and this could have implications for current food
safety regulations.
FOOTNOTES Received 19 December 2012. Accepted 7 March 2013. Address
correspondence to Rona Barron, rona.barron@roslin.ed.ac.uk. Published ahead of
print 13 March 2013
Copyright © 2013, American Society for Microbiology. All Rights Reserved.
2012
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
The present study demonstrated successful intraspecies transmission of
H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc
in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be
minimally defined by oral transmission of different TSE agents (C-type, L-type,
and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected
cattle have been initiated and are underway to provide information regarding the
extent of similarity in the immunohistochemical and molecular features before
and after transmission.
In addition, the present data will support risk assessments in some
peripheral tissues derived from cattle affected with H-type BSE.
Sunday, August 26, 2012
Detection of PrPSc in peripheral tissues of clinically affected cattle
after oral challenge with BSE
Monday, September 3, 2012
Sale of misbranded and/or non-inspected meat and meat products to Omaha
Public Schools indicted
Thursday, September 05, 2013
Possible Patient Exposure to Creutzfeldt-Jakob Disease Announced New
Hampshire DHHS
Press Release
Friday, July 19, 2013
Beaumont Hospital in Dublin assessing patients for CJD
Monday, April 15, 2013
Dr. Stephen B. Thacker Director Centers for Disease Control and
Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS)
dies from Creutzfeldt Jakob Disease CJD
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob
Disease CJD Greenville Memorial Hospital
Thursday, August 02, 2012
CJD case in Saint John prompts letter to patients Canada CJD case in Saint
John prompts letter to patients
Wednesday, November 30, 2011
First iCJD Death Confirmed in Korea
Thursday, December 08, 2011
A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had
received a German-manufactured human dura mater graft 23 years ago
Thursday, December 8, 2011
S. Korea confirms second case of iatrogenic Creutzfeldt-Jakob disease
48-year-old man
2011/12/08 11:08 KST
Monday, December 12, 2011
Second iatrogenic CJD case confirmed Korea
Saturday, February 12, 2011
Another Pathologists dies from CJD, another potential occupational death ?
another happenstance of bad luck, a spontaneous event from nothing, or
friendly fire ???
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS
AND SURGICAL PROCEDURES AROUND THE GLOBE
Mad cow disease warning to 38 patients in Wales
Section Health | Published on 29 Mar 2011
Public Health Wales has contacted 38 patients who may have been put at
risk of contracting Creutzfeldt-Jakob Disease (CJD) during surgery.
CJD, an incurable brain disease, is commonly known as a human form of mad
cow disease because bovine spongiform encephalopathy is the cause of variant
Creutzfeldt-Jakob disease in humans.
Letters were sent to those at risk after it became apparent that a patient
who underwent surgery in a hospital in the Abertawe Bro Morgannwg Health Board
area in 2007 was at high risk of the disease.
All surgical instruments used on the patient were removed from use when
the patient’s history became known, and all patients operated on with the same
instruments in the interim have now been informed.
Public Health Wales says that the risk of transmission of CJD from one
patient to another via surgical instruments is extremely low. There have only
ever been six cases worldwide of any form of CJD being transmitted in this
way.
Dr Jörg Hoffmann, Consultant in Communicable Disease Control for Public
Health Wales, said: “In this incident, we do not have a single confirmed case of
CJD. However, we do have one patient who was at high risk and 38 people at
extremely low risk.
“We know that all the surgical instruments used on this group of patients
were cleaned, disinfected and sterilised normally. However, it is possible that
the proteins that cause CJD, known as prions, survived these routine
sterilisation procedures so an extremely small risk of transmission
remains.
“We have identified and written to all patients concerned to make them
aware of the extremely low risk. They have been offered information and support
and a helpline has been set up for anyone who has received a letter and has
further questions.
“All patients at risk have been contacted and there is no risk to anybody
else. People who have had any type of surgery in the Abertawe Bo Morgannwg
Health Board area since 2007 but who have not been contacted by us have no
reason at all to worry.”
CJD is a rare disease that affects the structures of the brain and causes
incurable neurological symptoms. There is currently no treatment or cure for
CJD.
Anyone who is aware they are at increased risk of CJD should not donate
blood or organs and should always inform their surgeon or other health care
professional before undergoing any health procedure.
More information on CJD is available from the Public Health Wales website
at: http://www.wales.nhs.uk/sitesplus/888/page/43948
cjd and surgical instruments
Tulane Medical Center alerts patients after medical gear improperly
sterilized
Published: Thursday, March 10, 2011, 9:30 PM
Tulane Medical Center has notified 360 patients that it failed to properly
sanitize gastrointestinal scoping equipment used during seven weeks last fall,
potentially exposing the group to various infectious diseases.
Dr. Robert Lynch, the hospital’s CEO, acknowledged the error in a Jan. 3
letter that invited affected patients to obtain free screening for hepatitis B,
hepatitis C and HIV. The letter, however, characterized the chances of infection
as “minimal to non-existent.”
Lynch cited a mistake in one of five steps in its sanitizing protocol and
framed the tests as a way “to reassure patients whose procedures were
impacted.”
State epidemiologist Dr. Raoult Ratard, who has conferred with Tulane
officials about the case, said the chances of the equipment transmitting an
infection “would be extremely, extremely small. I think Tulane just wants to be
careful.”
That has not satisfied at least one patient, identified as “John Doe” in
the lawsuit he filed Feb. 22 in Orleans Parish Civil District Court. The suit,
which seeks class-action status, accuses the hospital of negligence and alleges
a long list of harmful effects ranging from “mental anguish” to “loss of
enjoyment of life.”
According to Lynch’s letter and a follow-up written statement released
Thursday, a routine maintenance inspection confirmed that part of the
disinfecting procedure for endoscopes and bronchoscopes did not occur at a
sufficient temperature. The error persisted from Oct. 7 to Dec. 1 on equipment
used for colonoscopies, sigmoidoscopies and upper-endoscopies of the stomach.
“Once this was discovered, it was remediated immediately,” Lynch wrote,
explaining that the hospital immediately contacted infection control experts,
including the Ratard’s unit at the Louisiana Department of Health and
Hospitals.
According to the Centers for Disease Control and Prevention, infection
associated with the use of endoscopes occurs in about 1 in 1.8 million
procedures, low odds but enough to make endoscopes the most likely medical
device to yield outbreaks associated with health-care institutions.
Neither the letter nor Tulane’s statement detailed its sanitizing
procedure.
According to Ratard, the scopes in question cannot be sanitized using steam
because of the likelihood of heat damage. Instead, the key step of the cleaning
process calls for application of a chemical disinfectant or sterilant for a
specified period of time at an elevated temperature. Ratard said the settings on
the sanitizer were elevated, but still too low, though he could not recall
specifics. He attributed the mistake to human error.
Ratard characterized Tulane’s mistake as “fairly common” in American
health care and said the hospital “has handled this by the book” by notifying
patients and offering them several rounds of testing, along with follow-up
counseling.
Harvey attorney Ron Austin, lead counsel on John Doe’s class-action
petition, said the hospital’s admission of error does not mitigate the risk
involved for the affected patients.
“This is extremely serious, and it’s unfortunate,” he said. “They are
petrified. They are extremely angry. How do you have that conversation with your
partner that you may have HIV, and what of the social fallout for anyone who
discovers that?”
The suit also names John Doe’s wife, Jane Doe, as a plaintiff, because of
her potential exposure through the couple’s sexual relations.
Austin said both Does have been tested for infectious diseases and both
have been negative, though follow-up testing will be ordered because of the
incubation periods of some viruses.
The case has been assigned to Judge Paulette Irons, who will decide
whether to certify the matter as a class action.
Tulane Medical Center is jointly owned by the for-profit Health Care
Corporation of America and Tulane University.
A decade ago, the hospital suffered a black eye and a subsequent legal
tussle when it announced that eight surgery patients had been exposed to a rare,
incurable brain disorder because they all underwent operations using some of the
same instruments used on a patient with Creutzfeldt-Jakob disease.
Those incidents were not a clear-cut matter of errant sanitizing, however.
With a similar pathology to mad-cow disease, Creutzfeldt-Jakob disease is spread
through protein agents that, at least at the time, were resistant to standard
sterilizing procedures. The condition was diagnosed with certainty in an initial
Tulane surgery patient only after death.
The hospital settled a negligence claim by one of the subsequently exposed
patients. The financial terms were never disclosed. None of the eight is known
to have developed the disease.
Bill Barrow can be reached at bbarrow@timespicayune.com or
504.826.3452.
Related topics: tulane medical center, tulane university
Saturday, September 11, 2010
Brisbane hospital workers feared mad cow
snip...see full text ;
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS
AND SURGICAL PROCEDURES AROUND THE GLOBE
Pathologist dies of suspected Creutzfeldt-Jakob (Mad cow) disease
29 March, 2009 03:33:00
Creutzfeldt-Jakob disease (mad cow) research pathologist Antonio Ruiz
Villaescusa died Sat., March 28, from the disease. Colleagues suspect he may
have contracted the disease from exposure to infected human tissue, according to
the Barcelona Reporter newspaper.
Ruiz headed the department of pathology at the University Hospital in
Madrid and was studying whether the disease is passed on to people who have been
exposed to infected tissue.
The head of the pathology department at the Fundación Alcorcón, Dr. Radish,
will perform an autopsy to clarify the cause of death and the final results will
be announced in about a month, according to the Spanish news site.
Ruiz was recognized internationally for his study in the fields of
neuropathology and anatomopatología, and devoted much of his professional life
to the study of human transmissible spongiform encephalopathy.
Creutzfeldt-Jakob disease is a rare and invariably fatal brain disorder,
according to the National Institute of Neurological Disorders and Stroke. There
is currently no single diagnostic test for the disease. The only way to confirm
a Creutzfeldt-Jakob disease diagnosis is by brain biopsy or autopsy.
e-mail: fpinedo@fhalcorcon.es e-mail: mpdominguez@fhalcorcon.es
Dr. Alberto Rábano Gutiérrez. Fundación Hospital Alcorcón. Madrid
Thursday, April 12, 2012
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to
2010
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to
2010
E Alcalde-Cabero1, J Almazán-Isla1, J P Brandel2, M Breithaupt3, J
Catarino4, S Collins5, J Haybäck6, R Höftberger7, E Kahana8, G G Kovacs7,9, A
Ladogana10, E Mitrova11, A Molesworth12, Y Nakamura13, M Pocchiari10, M
Popovic14, M Ruiz-Tovar1, A L Taratuto15, C van Duijn16, M Yamada17, R G Will12,
I Zerr3, J de Pedro Cuesta ()1 1.National Centre of Epidemiology - Consortium
for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación
Biomédica en Red sobre Enfermedades Neurodegenerativas – CIBERNED), Carlos III
Institute of Health, Madrid, Spain 2.Institut National de la Santé et de la
Recherche Médicale (INSERM) UMRS 975, National CJD Surveillance Network,
Assistance publique - Hôpitaux de Paris (APHP), National Reference Centre for
CJD, Pitié-Salpêtrière Hospital Group, Paris, France 3.Department of Neurology,
National Reference Centre for TSE, Georg-August University, Göttingen, Germany
4.Alameda Epidemiology and Health Statistics Department, Lisbon, Portugal
5.Department of Pathology, University of Melbourne, Melbourne, Australia
6.Institute of Neuropathology, Zurich University Hospital, Zurich, Switzerland
7.Institute of Neurology, Vienna Medical University, Vienna, Austria
8.Department of Neurology, Barzilai Medical Centre, Ashkelon, Israel 9.National
Reference Centre for Human Prion Diseases, Semmelweis University, Budapest,
Hungary 10.Department of Cell Biology and Neurosciences, Health Institute, Rome,
Italy 11.Department of Prion Diseases, Slovak Medical University Research Base,
Bratislava, Slovakia 12.National CJD Research and Surveillance Unit, Western
General Hospital, Edinburgh, United Kingdom 13.Department of Public Health,
Jichi Medical University, Shimotsuke, Japan 14.Institute of Pathology, Medical
Faculty, University of Ljubljana, Ljubljana, Slovenia 15.Department of
Neuropathology/FLENI, Referral Centre for CJD and other TSEs, Institute for
Neurological Research, Buenos Aires, Argentina 16.National Surveillance of CJD,
Erasmus MC, Rotterdam, The Netherlands 17.Neurology Department, Kanazawa
University Hospital, Kanazawa, Japan
--------------------------------------------------------------------------------
Citation style for this article: Alcalde-Cabero E, Almazán-Isla J, Brandel
JP, Breithaupt M, Catarino J, Collins S, Haybäck J, Höftberger R, Kahana E,
Kovacs GG, Ladogana A, Mitrova E, Molesworth A, Nakamura Y, Pocchiari M, Popovic
M, Ruiz-Tovar M, Taratuto AL, van Duijn C, Yamada M, Will RG, Zerr I, de Pedro
Cuesta J. Health professions and risk of sporadic Creutzfeldt–Jakob disease,
1965 to 2010 . Euro Surveill. 2012;17(15):pii=20144. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20144
Date of submission: 04 November 2011
--------------------------------------------------------------------------------
In 2009, a pathologist with sporadic Creutzfeldt–Jakob Disease (sCJD) was
reported to the Spanish registry. This case prompted a request for information
on health-related occupation in sCJD cases from countries participating in the
European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses
from registries in 21 countries revealed that of 8,321 registered cases, 65
physicians or dentists, two of whom were pathologists, and another 137
healthcare workers had been identified with sCJD. Five countries reported 15
physicians and 68 other health professionals among 2,968 controls or non-cases,
suggesting no relative excess of sCJD among healthcare professionals. A
literature review revealed: (i) 12 case or small case-series reports of 66
health professionals with sCJD, and (ii) five analytical studies on
health-related occupation and sCJD, where statistically significant findings
were solely observed for persons working at physicians' offices (odds ratio: 4.6
(95 CI: 1.2–17.6)). We conclude that a wide spectrum of medical specialities and
health professions are represented in sCJD cases and that the data analysed do
not support any overall increased occupational risk for health professionals.
Nevertheless, there may be a specific risk in some professions associated with
direct contact with high human-infectivity tissue.
snip...
Discussion
Despite a number of case reports of sCJD in physicians and technicians, the
findings of this EuroCJD survey do not suggest an increased risk of sCJD in
health professionals, nor do analytical studies show a clear excess risk for
health-related professions. Methodological limitations of analytical studies in
which occupational data were frequently provided by informants who were probably
aware of the sCJD diagnosis [3-7,26] argue in favour of a cautious
interpretation of the positive association reported for persons working at
physicians’ offices [19]. Consequently, the main finding of this literature
review and complementary EuroCJD observation is that health professionals,
including medical staff, are not at greater risk of developing sCJD. However,
this cannot exclude the possibility that there may be an occupational risk in
specific circumstances, for example, for people in contact with high-risk
central nervous system tissue, and appropriate precautions, as recommended by
national authorities, should therefore be followed, particularly regarding
laboratory work.
Although in some studies occupation was specifically analysed [19,25] and
occupation may be the subject of specific inquiry in some surveillance systems,
a limitation of some registries and scientific studies is that occupation may
not have been systematically recorded. When occupation was recorded, it is
unlikely that a framework for consistent occupational data collection was used,
so that neither registries nor case–control studies have incorporated the
classic epidemiological double approach. Recording of occupation may not
identify specific chemical or biological exposures, which would require data for
professions (job titles, medical specialisations) being cross-referenced with
branches of activity (laboratory, administrative or clinical patient-contact
work). The lack of registered surveillance data that combine profession with
activity (e.g. contact with human tissue), when compared with the descriptions
from previous case reports and the incident in Spain, illustrates the limits of
the validity of available data for analytical purposes and precludes formal use
of statistical testing. Although our study does not provide evidence of an
excess risk of sCJD in health professionals, the fact that the data collected
were mainly linked to medical speciality rather than actual activity might have
concealed an excess risk of sCJD for some specific health professionals.
A case–control study seeking to examine the putative occupational risk
posed by surgical injuries should have a biologically clear working hypothesis
and a custom-tailored methodology. Matrices designed by linking medical
speciality and surgical/forensic-anatomical/pathological activity, in which the
health professional can come into direct contact with high human-infectivity
tissue by accident might not provide a sufficient background for analysis,
without appropriate control being made for the influence of PRNP genotype,
surgical or laboratory work history and long latency. Assuming that among
non-cases or controls the proportion of medical specialities with potential
exposure (surgeons, forensic surgeons and other surgical specialists,
pathologists) may be low, i.e. approximately 1 per 1,000 (based on the figures
of 3/2,968 in Table 2), the study size that would afford the necessary
statistical power for a proper examination of the specific practices of health
professions is higher than that provided by existing CJD registries in any one
country. Since complementary analyses would be needed for professional and
activity categories defined in terms of temporal references that have not been
explored to date, such as ‘ever employed’ or ‘currently employed’, as well as
duration of employment, requirements for study size and collaboration would be
even higher.
In conclusion, a wide spectrum of medical specialities and health
professions are represented in sCJD registries. Although selection due to higher
ascertainment may lie behind the case reports of certain professions involved in
clinical management or care of patients with sCJD, the biological significance
of these observations remains uncertain and available data do not indicate an
increased risk of sCJD in health professionals. However, the methodological
issues mentioned above indicate the need for caution in drawing conclusions from
the data and large-scale studies with specific causal hypotheses are needed in
order for further research to be undertaken into the potential link between
health professions and sCJD.
Wednesday, December 28, 2011
FDA Targets Risks From Reused Devices
From: TSS
Subject: Investigation of a Possible Iatrogenic Case of Creutzfeldt-Jakob
Disease After a Neurosurgical Procedure
Date: December 10, 2006 at 12:10 pm PST
Investigation of a Possible Iatrogenic Case of Creutzfeldt-Jakob Disease
After a Neurosurgical Procedure
Natalie Keeler, DVM, Lawrence B. Schonberger, MD, Ermias D. Belay, MD,
Lynne Sehulster, PhD, George Turabelidze, MD, and James J. Sejvar, MD
Volume 27(2006), pages 1352 - 1357 DOI: 10.1086/509844
Abstract Objective. To investigate a case of Creutzfeldt-Jakob disease
(CJD) possibly acquired from contaminated neurosurgical instruments.
Design. Retrospective review of medical records, hospital databases,
service log books, and state vital statistics.
Setting. A tertiary care hospital (hospital A) in Missouri.
Patients. The case patient was a 38-year-old African American woman with a
9-month history of progressive memory loss, visual disturbances, and dementia.
She underwent neurosurgery in November 1996. CJD was confirmed in April 2004 by
immunodiagnostic testing of brain biopsy samples. All patients who underwent
neurosurgery at the same hospital within 6 months before or after the case
patient's procedure were identified and investigated for preoperative or
postoperative evidence of CJD.
Results. We reviewed data on 268 neurosurgical procedures, 84 pathology log
entries, and 60 death certificates for neurosurgical patients at hospital A and
identified 2 suspected cases of CJD. Clinical features and definitive prion
testing of stored brain biopsy samples excluded a diagnosis of CJD. Standard
operating room procedures were in place, but specific protocols for handling
instruments potentially contaminated with prions were not used.
Conclusions. Neurosurgical instruments were not implicated as the source
exposure for CJD in the case patient. The 2 patients with suspected CJD were
identified from different data sources, suggesting good internal consistency in
data collection. The key elements of this investigation are suggested for use in
future investigations into potential cases of iatrogenic CJD.
Diseases and Conditions Reportable In Missouri (19 CSR 20-20.020)
Numbers in parenthesis represent ICD-9 and ICD-10 Codes
Report Diseases and Conditions to your local health agency or to:
Missouri Department of Health and Senior Services during business hours
573-751-9071, after hours
and on weekends 800-392-0272 or by fax 573-751-6417
2. Category II diseases or findings and their
reporting requirements are –
(A) Category IIA diseases or finding shall be
reported to the local health authority or the
Department of Health and Senior Services within
three (3) days of first knowledge or suspicion.
Category IIA diseases or findings are—
snip...
* Creutzfeldt-Jakob disease (046.1, A81.0)
snip...end...TSS
-------- Original Message --------
Subject: Re: A NEW BRUNSWICKER REPORTED DEAD OF CJD AFTER BRAIN SURGERY (7
CJD cases possible in N.B., officials say)
Date: Fri, 26 Sep 2003 17:11:39 –0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
References: <3f71d32b .5000506="" wt.net=""> <3f72fb5f .5030205="" wt.net="">
<3f743ce8 .8070804="" wt.net="">
European Journal of Epidemiology 16 (4) p.353-355 April 2000 Kluwer
Creutzfeldt–Jakob Disease in health professionals in Slovakia Mitrová Eva1
and Belay Girma1
1.Institute of Preventive and Clinical Medicine, Limbová 14, 833 01
Bratislava, Slovakia
Creutzfeldt–Jakob disease (CJD) is the most important human transmissible
spongiform encephalopathy (prion disease), recognised in sporadic, genetic but
also iatrogenic forms. The identification of 8 health care workers in a group of
114 definitive CJD patients in Slovakia suggested the possibility of
professionaly acquired CJD and induced the investigation of potential endo- and
exogenous risk factors. In CJD-affected health professionals special attention
was paid to a detailed occupational history, including a possible professional
contact with CJD patient and to the findings characteristic for iatrogenic CJD:
early cerebellar symptomatology, long duration of the disease, absence of
typical EEG finding and homozygosity of PRNP gene at codon 129. Analysis of
epidemiological, clinical and molecular biological data in investigated group of
CJD-affected health professionals gave no evidence of an occupational risk for
CJD.
????? Creutzfeldt–Jakob disease, Health professionals, Iatrogenic
PDF(63K)
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EndNode
Copyright© 2000 Kluwer Academic Publishers All rights reserved
comments from Tom about these cases;
Comment (webmaster): 7% of sporadic CJD in health professionals is way too
high to occur by chance, despite the tone of the abstract. Now the first thing
Dr. Mitrova would have done is rule out familial CJD of the form E200K, which
has a very extensive cluster in Slovakia, though the abstract does not really
say what was sequenced besides codon 129 of the prion gene. Little credence can
be given to the idea that a characteristic pattern exists for iatrogenic CJD,
which is a total hodge-podge after the dominant forms, growth hormone and dura
mater, are subtracted.
One very real possibility in Slovakia is that the high numbers of E200K
cases, prior to diagnosis, has led to a secondary epidemic in health care
workers. This source would be missed by epidemiology because only exposure to
clinical E200K (hospice workers) would be considered.
One clear-cut case of a health worker at occupational risk is the
orthopedic surgeon who removed dura mater from sheep brain for the company in
Germany selling dura mater for human transplants.
Until Germany conducts a Prionics-type survey of its sheep, we will have no
real idea of the prevalence of scrapie there. The whole dura mater tragedy
unfolding in Japan may have resulted from sheep dura mater being used instead of
human cadaver. If so, this unfortunate 'experiment' would prove transmissibility
of scrapie to humans (though who would doubt this in a scrapie dura mater brain
transplant?).
Spinal dura contains elastin and collagen gene products, which would allow
the species origin of the transplant to be determined even decades later (if it
is not resorbed). Thus it is still possible to determine is causing the Japanese
dura mater outbreak.
The other related case of a possibly affected caregiver is a
husband-and-wife pair who contracted sporadic CJD within a few years of each
other:
i'd say this doctor has seemingly misrepresented medical information that
was readily available to him from official Health Canada web sites and prominent
previous alerts that he and his hospital would have previously received.
Tutogen Medical, Inc. was formerly known as Pfrimmer-Viggo GmbH+Co,
Erlangen, Germany). Their Canadian distributor is listed as Centerpulse Dental
Canada (hmmm) where in the US it is Tutogen Medical Inc.[Product lines: Dental,
Spine, Membrans, Sports Medicine, Bone (more hmmm) ]
what would you call this Health Canada statement ...
"The April 2001, edition of "Neurology" published details of the first case
of classical Creutzfeldt-Jakob Disease (CJD) associated with the use of
Tutoplast Dura. Following the publication of this news, Health Canada took
action to obtain further information on the current surgical need for the use of
Tutoplast Dura in Canada. It wrote to orthopaedic, neurosurgical and
otolaryngological professional associations seeking advice on the importance to
their members of the continued availability of Tutoplast dura mater. The
Canadian Neurosurgical Society (CNSS) responded by conducting a survey of their
members. Of those who replied, 61% supported discontinuing the use of donor dura
mater.
On April 10, 2002, Health Canada suspended the medical device licence for
Tutoplast Dura. The suspension means that the importation and sale of this
medical device is no longer permitted in Canada. Tutoplast Dura manufactured
before 1992 was processed with a less concentrated disinfectant solution than
material manufactured after October 1992. The disinfectant used initially, which
was in accordance with what was known regarding prion diseases at the time, was
a ten times weaker solution of sodium hydroxide than was used starting in 1992.
Tutoplast Dura (manufactured by Tutogen Medical GmbH of Germany) was first sold
in Canada in January, 1982."
On the company's website in Germany, it seems they have now gone over to
Tutomesh ... from bovine pericardium " that is prepared using the TUTOPLAST®
procedure thus eliminating antigenic properties"
Some previous experiences in Japan:
"The most recent recipient of a dura mater graft among the 43
graft-associated CJD patients was a woman aged 65 years at the time of onset of
CJD. She had two neurosurgical procedures in 1991 to repair a cerebral arterial
aneurysm (one in September and one in October); dura mater grafts were used
during both operations. In February 1994, 28 months after the second operation,
she developed progressive dysphagia, dysarthria, and unsteady gait, followed
within a few weeks by dementia. In April 1995, she developed generalized
myoclonic jerks and akinetic mutism. An electroencephalograph showed a 6- to
10-Hz background rhythm with the periodic synchronized slow activity complexes
typical of CJD. Examination of the cerebrospinal fluid revealed a normal protein
level and cell count. A magnetic resonance imaging scan showed marked cerebral
and cerebellar atrophy. The patient died in October 1995, and no autopsy was
performed.
Neither the brand nor year of processing of the dura mater grafts used in
this patient in 1991 could be determined. However, the hospital in which both
neurosurgical procedures were performed opened in 1989 and reported using only
two brands of dura mater grafts in 1991, LYODURA{Registered} and Tutoplast
(Pfrimmer-Viggo GmbH+Co, Erlangen, Germany). The investigation suggested that in
this pa tient, the use of LYODURA{Registered} processed before May 1987 was
unlikely but could not be ruled out.
... Even stringent donor screening and processing of each dura separately
to avoid possible cross-contamination may not completely eliminate the potential
for an infectious graft. In addition, the treatment of dura with NaOH may not
inactivate all of the infectious agent that may be present (6). Therefore,
surgeons should be aware of the possibly inherent risk for CJD transmission by
dura mater grafts and may want to consider the alternative use of autologous
fascia lata, fascia temporalis, or synthetic substitutes (4). "
September 2003
Information
Tutoplast Dura mater
Health Canada is the national authority that regulates the safety, efficacy
and quality of therapeutic products (such as medical devices) used in Canada. It
derives its statutory authority over therapeutic products from the Food and
Drugs Act and Regulations.
Tutoplast Dura mater is a medical device that was available in Canada
between January 1982 and April 2002 for use in various surgical treatments,
including neurosurgery.
The term "medical device" covers a wide range of products used in the
treatment, mitigation, diagnosis or prevention of a disease or abnormal physical
condition. Some examples include pacemakers, artificial heart valves, hip
implants, synthetic skin, medical laboratory diagnostic instruments, test kits
for diagnosis and contraceptive devices.
The Medical Devices Bureau of the Therapeutic Products Directorate (TPD) at
Health Canada is the national authority that monitors and evaluates the safety,
effectiveness and quality of diagnostic and therapeutic medical devices in
Canada. The Medical Devices Bureau enforces the Medical Devices Regulations,
which aim to ensure to the extent possible, the safety, effectiveness and
quality of medical devices in Canada. This is done through a combination of
pre-market review, post-approval surveillance and quality systems in the
manufacturing process.
In Canada, certain medical devices must have a Medical Device Licence
before they can be sold. To determine which ones need a Licence, all medical
devices have been categorized based on the risk associated with their use. This
approach means that all medical devices are grouped into four classes with Class
I devices presenting the lowest potential risk (e.g. a thermometer) and Class IV
devices presenting the greatest potential risk (e.g. pacemakers).
Prior to selling a medical device in Canada, manufacturers of Class II, III
and IV devices must obtain a Medical Device Licence. Although Class I devices do
not require a Licence, they are monitored through Establishment Licences.
What is Tutoplast dura mater?
Dura mater is a tissue that covers and protects the brain and spinal cord.
Commercially processed dura mater, obtained from human donors, has been used in
the surgical treatment of many conditions in Canada since the 1970s.
Tutoplast Dura manufactured before 1992 was processed with a less
concentrated disinfectant solution than material manufactured after October
1992. The disinfectant used initially, which was in accordance with what was
known regarding prion diseases at the time, was a ten times weaker solution of
sodium hydroxide than was used starting in 1992.
Processed dura mater is regulated as a class IV medical device. Tutoplast
Dura (manufactured by Tutogen Medical GmbH of Germany) was first sold in Canada
in January, 1982.
The April 2001, edition of "Neurology" published details of the first case
of classical Creutzfeldt-Jakob Disease (CJD) associated with the use of
Tutoplast Dura.
Following the publication of this news, Health Canada took action to obtain
further information on the current surgical need for the use of Tutoplast Dura
in Canada. It wrote to orthopaedic, neurosurgical and otolaryngological
professional associations seeking advice on the importance to their members of
the continued availability of Tutoplast dura mater. The Canadian Neurosurgical
Society (CNSS) responded by conducting a survey of their members. Of those who
replied, 61% supported discontinuing the use of donor dura mater.
On April 10, 2002, Health Canada suspended the medical device licence for
Tutoplast Dura. The suspension means that the importation and sale of this
medical device is no longer permitted in Canada.
Physicians were advised at the time to place any existing Tutoplast product
in a secure location and immediately inform the manufacturer or
distributor.
This action was based on the following considerations:
Advice received through Health Canada's consultation with the Canadian
Neurosurgical Society The recommendations of a leading Canadian expert on prion
illness (Dr. Neil Cashman). The availability of adequate alternative materials
that can be used instead of commercially-processed dura mater obtained from
human donors.
The Canadian distributor of Tutoplast Dura conducted the recall of the
product as per Health Canada's request.
The day following the suspension of the licence (April 11, 2002), Health
Canada initiated an Import Alert with Canadian Customs.
Health Canada informed international partners of the suspension and recall
action through the National Competent Authority Report system. Health Canada
forwarded copies of the medical device suspension letter and of the Safety
Advisory to the German authorities for information pertaining to the
manufacturer Tutogen Medical GmbH in their jurisdiction.
Health Canada sent a letter to health care professionals on April 11, 2002,
advising them:
Not to use Tutoplast Dura manufactured by Tutogen Medical GmbH in any
surgical procedure, as it is no longer licensed for sale in Canada. To place any
remaining stocks of Tutoplast Dura in a secure location so that it can no longer
be used and immediately inform the manufacturer or distributor who sold the
product.
Individuals who want more information on the recall may leave a message on
the Medical Devices Hotline at 1-800-267-9675. A Health Canada official will
return the call.
Last Updated: 2003-09-24
TSS
Terry S. Singeltary Sr. wrote:
> I was amazed at the comment the doctor made about this in an
> article yesterday. i had to send a note to him.....tss
>
> snip...
>
> Dr. Dow said he doubted that the woman had died of an infected
brain
> patch. And while there is a theoretical risk that the disease could
be
> spread through instruments contaminated with prion proteins from
a
> patient with CJD, he added to my knowledge there has been no
proven
> case of a neurosurgical instrument contaminated with protein from
a
> patient with CJD causing infection in another patient.
>
> snip...
>
> end
>
>
>
> what do you call this;
>
> 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
>
>
> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by
> electrodes contaminated during neurosurgery.
>
> Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek
DC.
>
> Laboratory of Central Nervous System Studies, National Institute
of
> Neurological Disorders and Stroke, National Institutes of
Health,
> Bethesda, MD 20892.
>
> Stereotactic multicontact electrodes used to probe the cerebral
> cortex of a middle aged woman with progressive dementia were
> previously implicated in the accidental transmission of
> Creutzfeldt-Jakob disease (CJD) to two younger patients. The
> diagnoses of CJD have been confirmed for all three cases. More
than
> two years after their last use in humans, after three cleanings
and
> repeated sterilisation in ethanol and formaldehyde vapour, the
> electrodes were implanted in the cortex of a chimpanzee.
Eighteen
> months later the animal became ill with CJD. This finding serves
to
> re-emphasise the potential danger posed by reuse of instruments
> contaminated with the agents of spongiform encephalopathies,
even
> after scrupulous attempts to clean them.
>
> PMID: 8006664 [PubMed - indexed for MEDLINE]
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
>
>
>
> 7 CJD cases possible in N.B., officials say
> Brain-wasting ailment confirmed in woman who died in July, after she
had
> neurosurgery
>
> RICHARD FOOT
> CanWest News Service
>
>
> Thursday, September 25, 2003
> ADVERTISEMENT
>
> Click here to find out more!
>
>
>
>
>
>
> New Brunswick health officials have warned seven former hospital
> patients they may have contracted Creutzfeldt-Jakob disease
during
> neurosurgery in Moncton, N.B., following the death of a woman
this
> summer from the rare but fatal brain-wasting illness.
>
> The woman died on July 31, about six weeks after undergoing
neurosurgery
> at Moncton Hospital, where doctors noticed she was showing symptoms
of
> the disease.
>
> On Monday, autopsy results of her brain tissue confirmed she died
of
> classical Creutzfeldt-Jakob disease, or CJD.
>
> Only about 30 Canadians are diagnosed each year with classical
CJD,
> which is a related but separate illness from the human form of mad
cow
> disease, called variant-CJD.
>
> "I want to make it very clear that this is not a case of mad cow
> disease,'' Gordon Dow, the hospital's chief of infectious diseases,
said
> yesterday in Moncton.
>
> How the woman contracted classical CJD remains a mystery. It's
also
> unclear what specific type of infection she had.
>
> If she died of sporadic CJD, her death poses no risk to the seven
other
> patients. However, officials cannot rule out the chance she died of
a
> less common form called iatrogenic CJD.
>
> This is contracted when the disease is mistakenly passed from one
person
> to another, through shared surgical instruments or through brain
tissue
> transplants. The woman may have been infected during a brain
tissue
> transplant on her spinal cord in 1992, when doctors implanted a
tissue
> graft taken from the brains of human cadavers.
>
> The type of implant used in 1992, known as Tutoplast dura mater,
was
> banned by Health Canada last year because of concerns that it
could
> transmit CJD.
>
> The woman returned to hospital for a second operation in June this
year,
> and died shortly afterwards. The instruments used in her operation
have
> since been incinerated, but of the seven patients warned in the wake
of
> the woman's death, two may have been exposed to those instruments
before
> they were destroyed. Five others received similar brain tissue
> transplants in the early 1990s.
>
> © Copyright 2003 Montreal Gazette
>
>
>
> Terry S. Singeltary Sr. wrote:
>
>>
>>
>> Brain-wasting disease confirmed in N.B. woman
>>
>>
>> By LUMA MUHTADIE
>> Globe and Mail Update
>>
>>
>>
>>
>>
>>
>> A New Brunswick woman died in hospital from Creutzfeldt-Jakob
disease,
>> health officials in Moncton announced on Wednesday.
>>
>> Officials stressed that the case of so-called “classical” CJD
cannot
>> spread from person to person, and is not connected to the variant
of the
>> disease, which has been linked to mad cow or bovine
spongiform
>> encephalopathy.
>>
>> “This is not a case of mad cow disease,” Gordon Dow, chief of
infectious
>> diseases at Moncton Hospital, told the press conference.
>>
>> However, health officials said that tests were inconclusive as
to
>> whether the disease developed spontaneously in the 55-year-old
woman (as
>> it does in about 30 Canadians a year) or whether it was
iatrogenic,
>> meaning it resulted from an infection acquired during a
medical
>> procedure.
>>
>> In 1992, doctors in Moncton grafted a patch made from tissue taken
from
>> a human corpse onto the woman's brain. She returned to the
Moncton
>> Hospital in June for a secondary neurosurgical operation, and in
a
>> follow-up consultation on June 18, possible CJD was diagnosed. She
died
>> on July 31 and the diagnosis of CJD was confirmed through an
autopsy on
>> Monday.
>>
>> Health Canada banned the use of brain-tissue patches taken from
human
>> corpses last year due to CJD fears.
>>
>> Dr. Dow said he doubted that the woman had died of an infected
brain
>> patch. And while there is a theoretical risk that the disease
could be
>> spread through instruments contaminated with prion proteins from
a
>> patient with CJD, he added “to my knowledge there has been no
proven
>> case of a neurosurgical instrument contaminated with protein from
a
>> patient with CJD causing infection in another patient.”
>>
>> He said it would be very useful to know if the patient represented
a
>> sporadic form of CJD, in which case there would be “absolutely no
risk
>> to anybody else” or if she acquired the disease from the graft
she
>> received in 1992, “whereby potentially, other patients could have
been
>> exposed to the same graft.”
>>
>> As a safety measure, the Moncton Hospital quarantined all
neurosurgical
>> and spinal instruments in the region, later narrowing the
quarantine to
>> only those instruments used in the woman's more recent
operation.
>>
>> The hospital also searched the charts of all patients who received
graft
>> surgery within one year on either side of the woman's original
surgery
>> -– or from 1991 to 1993 -– to identity all potential recipients of
the
>> same graft. Seven individuals were found and informed that they
were at
>> a small risk of infection.
>>
>> CJD is a degenerative disease of the central nervous system
that
>> initially alters the personality or makes social interaction
difficult,
>> but quickly progresses into problems with speech, memory and
vision. It
>> eventually leads to motor problems such as stiffness, paralysis
and
>> twitching.
>>
>> “During this rapid deterioration, patients quickly become confined
to
>> bed in a mute, paralyzed state -- probably in a semi-comatose
state --
>> with very little insight or understanding ... or sensation of
their
>> illness and subsequently die,” Dr. Dow said.
>>
>> It generally takes six months from the onset of symptoms until
death.
>> There is currently no treatment available for CJD.
>>
>>
>>
>>
>> spontaneous my @ss..... how can these people continue to believe
that
>> 85%+ of all CJDs happen from nothing (a spontaneous happening
without
>> route and source). this is total BSeee and they cannot prove this.
it is
>> only
>> wishful thinking by scientist and there politicians that advocate
this
>> myth $$$
>>
>> TSS
>>
>> Terry S. Singeltary Sr. wrote:
>>
>>> ######## Bovine Spongiform Encephalopathy
>>> #########
>>>
>>> New Brunswicker reported dead of Creutzfeldt-Jakob
>>> Last Updated Wed, 24 Sep 2003 12:25:17
>>>
>>> MONCTON - A New Brunswick resident has died of
Creutzfeldt-Jakob
>>> disease
>>> after brain surgery, CBC has learned.
>>>
>>> Sources tell CBC News that this case was not the CJD variant
caused by
>>> eating tainted beef and is not related to bovine
spongiform
>>> encephalopathy, or mad cow disease.
>>>
>>> Diagnosis of the disease cannot be confirmed until after
death.
>>>
>>> Public health authorities are expected to hold a news
conference later
>>> Wednesday to release more details.
>>>
>>> * FROM APRIL 13, 2002: Health Canada bans 'brain patch' linked
to
>>> brain disease
>>>
>>>
<%20%0Ahttp://www.cbc.ca/storyview/CBC/2002/04/12/Consumers/brainpatch_020412>
>>>
>>>
>>>
>>> * FROM MAY 9, 2001: Possible Creutzfeldt-Jakob case reported
in
>>> Windsor
>>>
>>> Classical CJD, which occurs naturally in a small number of
people, can
>>> be transmitted by transplants of human tissue.
>>>
>>> The disease affects the central nervous system.
>>>
>>> It occurs in the world population at a rate of about one case
per
>>> million people per year – about 30 cases are diagnosed each
year in
>>> Canada. Most cases die within months.
>>>
>>> Written by CBC News Online staff
>>>
>>>
>>> it would be most interesting how this hospital has handled
the
>>> quarantining
>>> of the surgical instruments and the operating/surgical arena
after this
>>> surgery
>>> and the finding of CJD in the patient. were the instruments
used on
>>> this
>>> victim used on any other persons and can they trace all tools
???
>>>
>>> TSS
>>>
>>> ########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
>>> ############
>>>
>>
>>
>
>
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Thursday, July 08, 2010
Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from
a risk-based assessment of surgical interventions Public release date:
8-Jul-2010
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Wednesday, June 02, 2010
CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated:
May 2010
Tuesday, May 11, 2010
Current risk of iatrogenic Creutzfeld–Jakob disease in the UK: efficacy of
available cleaning chemistries and reusability of neurosurgical instruments
Tuesday, May 04, 2010
Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010
Tuesday, March 16, 2010
Transmissible Spongiform Encephalopathy Agents: Safe Working and the
Prevention of Infection: Part 4 REVISED FEB. 2010
Monday, August 17, 2009
Transmissible Spongiform Encephalopathy Agents: Safe Working and the
Prevention of Infection: Annex J,K, AND D Published: 2009
Monday, July 20, 2009
Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD)
risk in neurosurgery and eye surgery units
Friday, July 17, 2009
Revision to pre-surgical assessment of risk for vCJD in neurosurgery and
eye surgery units Volume 3 No 28; 17 July 2009
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June
12, 2009 (Singeltary submission)
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan,
1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number
2-February 2009 Research
Wednesday, August 20, 2008
Tonometer disinfection practice in the United Kingdom: A national survey
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition
2007 (occupational exposure to prion diseases)
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in
Endodontic Practice in Absence of Adequate Prion Inactivation
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
CJD: update for dental staff.
Tuesday, December 18, 2012
Bioassay Studies Support the Potential for Iatrogenic Transmission of
Variant Creutzfeldt Jakob Disease through Dental Procedures
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Sunday, June 9, 2013
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory
Committee Meeting Webcast
Friday, August 16, 2013
*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and
Contaminated blood products induce a highly atypical prion disease devoid of
PrPres in primates
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010
From: Terry S. Singeltary Sr.
Sent: Saturday, September 07, 2013 12:33 PM
To: jon.burns@house.ga.gov
Cc: stephen.allison@house.ga.gov ; jimmy.pruett@house.ga.gov ;
sharon.beasley-teague@house.ga.gov ; rbruce5347@aol.com ;
pam.dickerson@house.ga.gov ; emory.dunahoo@house.ga.gov ; earl@ehrhart.4emm.com
; david.knight@house.ga.gov ; tommccall@bellsouth.net ;
john.meadows@house.ga.gov ; jay.roberts@house.ga.gov ; jason.shaw@house.ga.gov ;
jason.spencer@house.ga.gov ; al.williams@house.ga.gov
Subject: Georgia House Bill 1043 and Chronic Wasting Disease CWD
Greetings Honorable Representatives of the House, Game, Fish, & Parks,
I wish to submit some recent science about chronic wasting disease cwd from
the Prion2013 congressional abstracts.
I lost my mother to hvCJD ‘confirmed’, and have been following the mad cow
follies for almost 16 years daily. sadly, cwd is just another part of those
follies.
I have studied and kept up with these follies daily for almost 16 years, as
a layperson.
I believe that when officials are making decisions, they need all the
scientific information available to make sound decisions. many times this does
not happen due to the industries involved and politics and greed there from.
So, I send this science on the cwd tse prion disease in good faith.
TO date, with the limited CWD testing in Georgia, CWD has not been
detected. does not mean it is not already there. BUT, if you approve Bill 1043,
the chances of CWD being introduced into your state goes up greatly.
Inactivation of the TSE Prion disease
Chronic Wasting Disease CWD, and other TSE prion disease, these TSE prions
know no borders.
these TSE prions know no age restrictions.
The TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit.
you cannot cook the TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a
mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the TSE Prion agent will survive in the
environment for years, if not decades.
you can bury it and it will not go away.
The TSE agent is capable of infected your water table i.e. Detection of
protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done with.
that’s what’s so worrisome about Iatrogenic mode of transmission, a simple
autoclave will not kill this TSE prion agent.
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
The infectious agents responsible for transmissible spongiform
encephalopathy (TSE) are notoriously resistant to most physical and chemical
methods used for inactivating pathogens, including heat. It has long been
recognized, for example, that boiling is ineffective and that higher
temperatures are most efficient when combined with steam under pressure (i.e.,
autoclaving). As a means of decontamination, dry heat is used only at the
extremely high temperatures achieved during incineration, usually in excess of
600°C. It has been assumed, without proof, that incineration totally inactivates
the agents of TSE, whether of human or animal origin.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Histochemical analysis of hamster brains inoculated with the solid residue
showed typical spongiform degeneration and vacuolation. Re-inoculation of these
brains into a new cohort of hamsters led to onset of clinical scrapie symptoms
within 75 days, suggesting that the specific infectivity of the prion protein
was not changed during the biodiesel process. The biodiesel reaction cannot be
considered a viable prion decontamination method for MBM, although we observed
increased survival time of hamsters and reduced infectivity greater than 6 log
orders in the solid MBM residue. Furthermore, results from our study compare for
the first time prion detection by Western Blot versus an infectivity bioassay
for analysis of biodiesel reaction products. We could show that biochemical
analysis alone is insufficient for detection of prion infectivity after a
biodiesel process.
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
The data presented here demonstrate that sPMCA can detect low levels of
PrPCWD in the environment, corroborate previous biological and experimental data
suggesting long term persistence of prions in the environment2,3 and imply that
PrPCWD accumulation over time may contribute to transmission of CWD in areas
where it has been endemic for decades. This work demonstrates the utility of
sPMCA to evaluate other environmental water sources for PrPCWD, including
smaller bodies of water such as vernal pools and wallows, where large numbers of
cervids congregate and into which prions from infected animals may be shed and
concentrated to infectious levels.
A Quantitative Assessment of the Amount of Prion Diverted to Category 1
Materials and Wastewater During Processing
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
In this article the development and parameterization of a quantitative
assessment is described that estimates the amount of TSE infectivity that is
present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for
cattle and classical/atypical scrapie for sheep and lambs) and the amounts that
subsequently fall to the floor during processing at facilities that handle
specified risk material (SRM). BSE in cattle was found to contain the most oral
doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to
a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep
infected with classical and atypical scrapie, respectively. Lambs contained the
least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie
and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity
falling to the floor and entering the drains from slaughtering a whole carcass
at SRM facilities were found to be from cattle infected with BSE at rendering
and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate
plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and
collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains
are from lambs infected with classical and atypical scrapie at intermediate
plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO
ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key
inputs for the model in the companion paper published here.
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute
and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
Scrapie and chronic wasting disease probably spread via environmental
routes, and there are also concerns about BSE infection remaining in the
environment after carcass burial or waste 3disposal. In two demonstration
experiments we are determining survival and migration of TSE infectivity when
buried for up to five years, as an uncontained point source or within bovine
heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters
containing either sandy or clay soil. Migration from the boluses is being
assessed from soil cores taken over time. With the exception of a very small
amount of infectivity found 25 cm from the bolus in sandy soil after 12 months,
no other infectivity has been detected up to three years. Secondly, ten bovine
heads were spiked with TSE infected mouse brain and buried in the two soil
types. Pairs of heads have been exhumed annually and assessed for infectivity
within and around them. After one year and after two years, infectivity was
detected in most intracranial samples and in some of the soil samples taken from
immediately surrounding the heads. The infectivity assays for the samples in and
around the heads exhumed at years three and four are underway. These data show
that TSE infectivity can survive burial for long periods but migrates slowly.
Risk assessments should take into account the likely long survival rate when
infected material has been buried.
The authors gratefully acknowledge funding from DEFRA.
PPo3-22:
Detection of Environmentally Associated PrPSc on a Farm with Endemic
Scrapie
Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh
Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of
Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories
Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University
of Nottingham; Sutton Bonington, Loughborough UK
Key words: scrapie, evironmental persistence, sPMCA
Ovine scrapie shows considerable horizontal transmission, yet the routes of
transmission and specifically the role of fomites in transmission remain poorly
defined. Here we present biochemical data demonstrating that on a
scrapie-affected sheep farm, scrapie prion contamination is widespread. It was
anticipated at the outset that if prions contaminate the environment that they
would be there at extremely low levels, as such the most sensitive method
available for the detection of PrPSc, serial Protein Misfolding Cyclic
Amplification (sPMCA), was used in this study. We investigated the distribution
of environmental scrapie prions by applying ovine sPMCA to samples taken from a
range of surfaces that were accessible to animals and could be collected by use
of a wetted foam swab. Prion was amplified by sPMCA from a number of these
environmental swab samples including those taken from metal, plastic and wooden
surfaces, both in the indoor and outdoor environment. At the time of sampling
there had been no sheep contact with these areas for at least 20 days prior to
sampling indicating that prions persist for at least this duration in the
environment. These data implicate inanimate objects as environmental reservoirs
of prion infectivity which are likely to contribute to disease transmission.
Wednesday, July 10, 2013
Rapid assessment of bovine spongiform encephalopathy prion inactivation by
heat treatment in yellow grease produced in the industrial manufacturing process
of meat and bone meals
BMC Veterinary Research 2013, 9:134 doi:10.1186/1746-6148-9-134
snip...
Subject: Georgia House Bill 1043 and Chronic Wasting Disease CWD
Greetings Honorable Representatives of the House, Game, Fish, & Parks,
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing
an extreme increase of 48% between 2008 and 2010 (Prion2013)
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing
an extreme increase of 48% between 2008 and 2010
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Friday, June 29, 2012
Highly Efficient Prion Transmission by Blood Transfusion
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion
risk factors there from
Article in Press
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to
Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
Monday, May 6, 2013
Warning of mad cow disease threat to blood transfusions
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
Tuesday, May 21, 2013
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the
International Society of Blood Transfusion, Amsterdam, The Netherlands, June
2-5, 2013
4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD
By Terry S Singeltary
Bacliff, Texas USA Jan 24, 07
4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD
FC5.1.1
Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,
and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;
Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama,
USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General
Hospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible Spongiform
Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical
and clinical phases of disease. Results in a (presumably more appropriate)
non-human primate model have not been reported.
Objective: To determine if blood components (red cells, white cells,
platelets, and plasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and
intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic
Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob
disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma
samples from chimpanzees infected with either sCJD or
Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a
period of 5 years, and all dying or sacrificed animals had post-mortem
neuropathological examinations and Western blots to determine the presence or
absence of the misfolded prion protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated with
blood components from patients with sporadic or variant CJD. All donor
chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their
pre-clinical phase plasmapheresis, several months earlier than the expected
onset of illness. One monkey inoculated with purified leukocytes from a
pre-clinical GSS chimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood components
from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a
single transmission from a chimpanzee-passaged strain of GSS shows that
infectivity may be present in leukocytes, and the shock of general anaesthesia
and plasmspheresis appears to have triggered the onset of illness in
pre-clinical donor chimpanzees.
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...
Prion2013
Oral.05: Contaminated blood products induce a highly atypical prion disease
devoid of PrPres in primates
Emmanuel Corney,1 Nina Jaffre,1 Jacqueline Mikol,1 Valerie Durand,1
Christelle Jas-Duval,1,2 Sophie Luccantoni-Freire,1 Evelyne Correia,1 Nathalie
Lescoutra-Etcheqaray,3 Nathalie Streichenberqer,4 Stephane Haik,5 Chryslain
Sumian,3 Paul Brown1 and Jean-Philippe Deslys1
1Commissariat a l'Energie Atomique; Institute of Emerging Diseases and
Innovative Therapies (iMETI); Division of Prions and Related Diseases (SEPIA);
Fontenay-aux- Roses, France; 2EFS·Nord de France; Lille, France; 3MacoPharm;
Tourcoing, France; 4Hospices Civils de Lyon; Prion Unit; Neurobiology
Department; Bron, France; 5Inserm; U 975·CNRS; UMR 7225 - Universite Pierre et
Marie Curie; Paris, France
Background, Concerns about the blood-borne risk of prion infection have
been confirmed by the occurrence in the UK of four transfusion-related
infections of vCJD and an apparently silent infection in an hemophiliac patient.
Asymptomatic incubation periods in prion diseases can extend over decades in
humans. We present here unexpected results of experiments evaluating blood
transmission risk in a non-human primate model.
Material and Methods, Cynomolgus macaques were inoculated with brain or
blood specimens from vCJD infected humans or monkeys. Neuropathological and
biochemical findings were obtained using current methods used for human
patients.
Results, Thirteen out of 23 primates exposed to various human or macaque
blood products exhibited a previously undescribed myelopathic syndrome, devoid
of the classical features of prion disease, notably abnormal prion protein
(PrPres) deposition, whereas the 14 corresponding brain-inoculated donor animals
and 1 transfused animal exhibited the classical vCJD pattern. In passage
experiments, plasma transfusion induced the same atypical phenotype after two
years (again, with no detectable PrPres), whereas the intracerebral inoculation
of spinal cord led to a typical prion disease with cerebral spongiosis and
PrPres accumulation in the brain of the primate recipient. Interestingly,
passage experiments in transgenic mice were largely unsuccessful.
In another experiment designed to test the efficacy of antiprion filters,
three recipients of filtered red blood cells suspended in plasma are still
healthy 4.5 y after transfusion whereas the recipients of unfiltered inocula
died after 2.5 y with the atypical neurological profile.
Conclusion. We describe a new fatal neurological myelopathic syndrome in
monkeys exposed to various vCJD/BSE-infected blood components.
Secondary transmission in primates confirms
(I) the transmissibility of this myelopathy, and
(2) its prion origin which could not be diagnosed as such in the first
recipients.
This myelopathy might be compared in some respects to certain forms of
human lower motor neuron disease, including neuromyelitis optica, the flail arm
syndrome of amyotrophic lateral sclerosis (ALS), and the recently described
FOSMN (facial onset sensory and motor neuronopathy) syndrome.
Sunday, September 1, 2013
Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy
We previously described the biochemical similarities between PrPres derived
from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations
suggest a link between these two uncommon prion phenotypes in a primate model
(it is to note that such a link has not been observed in other models less
relevant from the human situation as hamsters or transgenic mice overexpressing
ovine PrP [28]). We speculate that a group of related animal prion strains
(L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion
diseases in humans with a type 2 PrPres molecular signature (and more
specifically type 2B for vCJD)
snip...
Together with previous experiments performed in ovinized and bovinized
transgenic mice and hamsters [8,9] indicating similarities between TME and
L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME
outbreaks in North America and Europe during the mid-1900s.
TSS
posted by Terry S. Singeltary Sr. at
11:47 AM
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