FC5.3
Assessing the Risk of vCJD Transmission by Dentistry; Distribution of
Infectivity in Oral Tissues of VM Mice after Simulated Oral Feeding of
BSE-301V
Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,
MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH1
1Health Protection Agency, Centre for Emergency Preparedness and Response,,
TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3Health
Protection Agency, Centre for Emergency Preparedness and Response,, UK
Background: Ongoing concerns about the prevalence of variant Creutzfeldt
Jakob
Disease (vCJD) in the UK population has heightened concerns about the risks
of iatrogenic transmission of the disease. Although there have been no cases
to
date of transmission by surgery there have been 4 cases involving blood
transfusion.
This study aims to assess the potential of transmission of the disease by
dental
procedures. Whilst the risks are undoubtably low the very large numbers of
procedures
carried out annually have the potential to amplify the risks considerably
and there is
very little data in this area to form the basis for accurate risk
assessments.
Aim(s)/Objective(s): To assess the relative levels of infectivity in oral
tissues from a
murine model following exposure to BSE-301V through the small intestine.
Methods.
The study uses a BSE-301V, VM mouse model as a clinically relevant model for
assessing iatrogenic vCJD transmission between humans. Infectious mouse
brain
homogenate was prepared and inoculated into a loop of the duodenum, to
prevent
direct contamination of the oral tissues. Mice were sacrificed at 3-weekly
intervals and at appearance of clinical symptoms. A range of oral tissues,
including
dental pulp, gingival margin, salivary gland, saliva, lingual tonsil and
trigeminal ganglia,
together with brain and spleen tissues were removed, processed as
homogenates and
reinoculated intracranially (ic.) into indicator mice.
Results: The primary challenge proved to be a very efficient route of
infection with a 100% attack rate and a mean incubation to clinical disease
of 157 ± 17 days
(compared to 120 days for the same titre inoculum ic.). Infectivity was
observed in all
oral and control tissues with varying time-courses and titres estimated from
incubation
period.
Discussion: The results throw new light on the potential routes of
dissemination and
spread of infectivity from the small intestine to the oral cavity and its
implications for
possible iatrogenic transmission of vCJD via dental, endoscopic or other
forms of
surgery.
Conclusion: The data generated from the study provides support for ongoing
risk
assessments to look at the potential for vCJD transmission via dental
procedures
alongside other elements of studies looking at effectiveness of
decontamination and
re-use of dental instruments.
P02.15
Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease
Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5;
Ironside, J6;
Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8; Stressenberger, N9;
Langeveld,
J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13; Andreoletti, O1
1Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’Anatomie
Pathologique
and INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France;
5
Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular &
Clinical
Medicine (Pathology),, National Creutzfeldt-Jakob Disease Surveillance Un,
UK; 7Pitié
Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière, Service de
Biochimie et
Biologie Moléculaire,, France; 9Hôpital Neurologique -Service de
Neurochimie, France;
10CIDC-Lelystad, Netherlands; 11University of Edinburgh, Western General
Hospital,
UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire de
Neuropathologie, France;
13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France
Creutzfeldt-Jakob disease (CJD) cases are currently classified according to
established diagnostic criteria and by the genotype at codon 129 of the PRNP
gene
and the Western blotting of the proteinase K digested abnormal prion protein
that
distinguishes a type 1 and a type 2 profile. These biochemically distinct
PrPres types
have been proposed to represent distinct prion strains. However, since the
cooccurence
of type 1 and type 2 PrPres in the same patient is common, the rationale of
this classification and strain concept as applied to CJD are currently under
discussion.
Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD
(both dura
matter-, and growth hormone-associated) cases, originating from UK and
France, were
systematically investigated, using Western blotting typing, and by two
others
biochemical assays that depend on the behaviour of PrPSc in variable PK
digestion
conditions. As described previously, co-occurrence of type 1 and type 2
PrPres was
found in 30% of the CJD patients examined. However, our novel PK
concentration
dependent assays identified a single uniform PrP type in cases where both
type 1 and
type 2 were present. Moreover, in sCJD four distinct biochemical PrPSc
signatures
were identified by the PK concentration dependent assays and these
correlated to the
current genotype/clinico-pathological sCJD groups. In iCJD the four similar
biochemical signatures were observed, but were not correlated to particular
PRNP 129
polymorphism or Western Blot PrPres patterns. Moreover notable differences
were
observed between PrPSc biochemical properties of French and UK GH-CJD cases,
which could reflect, as already suspected, differences in the causative
agents.
Identification, in sCJD and iCJD, of four different PrPSc phenotypes
irrespective of
patients PRNP polymorphism at codon 129 and Western blot profile provides
new
insights into human prion disease aetiology and could reflects an
unsuspected
diversity of TSE agents in human disease. Further investigations are
currently
underway using animal transmission to correlate agent strain with our new
discriminant
biochemical assays.
see much more ;
PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS
SEPTEMBER 2007
Date: Mon, 24 Sep 2007 21:31:55 -0500
I suggest that you all read the data out about h-BASE and sporadic CJD, GSS,
blood, and some of the other abstracts from the PRION2007. ...
http://lists.ifas.ufl.edu/cgi-bin/wa...&F=&S=&P=19744
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it
today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were
''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007
11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa...mg&T=0&P=19779
see full text 143 pages ;
http://www.prion2007.com/pdf/Prion%2...0Abstracts.pdf
Terry S. Singeltary Sr. Bacliff, Texas