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From: TSS ()
Date: August 23, 2007 at 11:30 am PST


T. Baron1, A.G. Biacabe1, A. Bencsik1, J. Jacobs2, J.P.M. Langeveld2, P.L.
Acutis3, M. Polak4, D. Gavier-
Widèn5, A. Buschmann6, M.H. Groschup6, J. A. Richt7
1 AFSSA, Lyon, France; 2 CIDC-Lelystad, Dept.
Bacteriology & TSEs, Lelystad, The
Netherlands, 3 CEA – Istituto Zooprofilattico del Piemonte, Turin, Italy,
Turino, Italy; 4 NVRI, Dept. Virology,
Pulawy, Poland; 5 SVA, Upssala, Sweden; 6FLI-INEID, Riems, Greifswald,
Germany; 7 NADC/USDA, Ames,
Iowa, U.S.A.
Since 2003, some cases of prion diseases in cattle have shown unusual
features as assessed by
molecular characterization of the protease-resistant prion protein (PrPres)
and/or histopathology,
when compared to the unique features of BSE described previously. Similar
cases have now been
recognized in a number of countries, and an overview of the current
situation will be presented. Such
studies have allowed to refine the molecular definition of such cases using
Western blotting, referred
as H-type (Biacabe et al., 2004) or L-type (BASE)(Casalone et al., 2004).
While a single strain of
infectious agent had previously been recognized when BSE was transmitted to
a panel of genetically
defined inbred wild-type mice, the recent unusual findings raised the
question of transmission of prion
disease from such unusual isolates. We could show transmission of prion
disease from unusual BSE
isolates in murine experimental models (including wild-type and transgenic
mouse lines). Most
importantly, data obtained during the characterization of experimentally
infected mice showed
different features when compared to those previously described in mice
infected with typical BSE
isolates. The unusual PrPres molecular features initially described in the
brain of cattle by Western
blot were maintained following transmission of the agent into mice. In this
presentation, the potential
origin of such cases, including the possible existence of “sporadic” forms
of prion diseases in cattle,
will be discussed.

A. Buschmann1, A. Gretzschel1, A.-G. Biacabe2, K. Schiebel3, C. Corona4, C.
Hoffmann1, M. Eiden1, T.
Baron3, M. Casalone4, F. Tagliavini5, J. Langeveld6 and M.H. Groschup1
1 Friedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging
Infectious Diseases, Insel Riems, Germany
2 AFSSA-Lyon, Unite ATNC, Lyon, France
3 Institute for Biochemistry, Universitity Erlangen-Nürnberg, Germany
4 CEA – Instituto Zooprofilattico di Turino, Turin, Italy
5 Instituto Nazionale Neurologico Carlo Besta’ (INNB), Milano, Italy
6 CIDC-Lelystad, Lelystad, The Netherlands
After the detection of BSE in the UK in 1986, it was assumed that BSE only
occurred as a single
strain. However, since 2003 BSE cases of two deviant kinds (L-type and
H-type) have been reported
in France and Italy in animals that were over eight years of age. Therefore
we have re-assesed the
27 German BSE cases that were over eight years of age when the disease was
diagnosed out of the
389 German cases that have been detected between November 2000 and December
2005. This
characterization focused on the determination of the molecular mass (Mr) of
the unglycosylated band
as well as on the glycoprofile of the accumulated PrPP
Sc by immunoblot analysis. We detected one Ltype
case which was characterised by a decreased M of the unglycosylated PrP r
Sc and a unique
glycopattern with almost equal percentages of the di- and monoglycosylated
P fractions as well
as one H-type case with a distinctly elevated Mr molecular mass of this
smallest PrPP
Sc fraction and an
unaltered glycoprofile (using mab L42). Comparative analyses of these two
cases together with
French and Italian cases of the H- and L-types proved that these two cases
indeed belong to the
same groups. Both German isolates were inoculated into bovine PrP transgenic
mice (Tgbov XV
mice). The L-type provoked disease in these mice after very short incubation
times of 183 days as
compared to 230 days after challenge with classical BSE. In contrast, the
H-type has not lead to any
clinical symptoms in the mice after 300 days. Interestingly, the
characteristic immunoblot profile of the
L-type BSE was maintained after passage through Tgbov XV mice. In order to
study the
pathogenesis of these novel BSE strains in their natural host, transmission
studies in 6 months old
calves (i.c. route) have been initiated.

C.Casalone1, C.Corona1, B. Iulini1, C.Porcario1, M.Caramelli1,
J.P.M.Langeveld2, L.J.M. Van Keulen2
1CEA-Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’
Aosta, Via Bologna 148, 10154 Turin,
Italy (
2Department of Bacteriology and TSEs, Central Institute for Animal Disease
Control (CIDC), 8023 AA Lelystad,
The Netherlands
Unusual isolates of BSE have been reported in the past two years in
different European countries and
Japan. Two variant forms of BSE have been reported based on biochemical
analysis of the molecular
mass and glycoform ratio of the pathological prion protein (PrPsc): i) a
type with a lower molecular
mass of the unglycosylated isoform and a distinct glycopattern of PrPres
(L-type or BASE) and (ii) a
type with higher molecular mass of the unglycosylated isoform and a distinct
glycopattern of PrPres
(H-type). From a pathological point of view, a careful description was only
available for the two Italian
cases (L-type) where immunohistochemical analysis revealed an unusual PrPsc
deposition pattern
characterized by the presence of amyloid plaques particularly in the white
matter of olfactory bulb,
frontal and parietal cortex. Here we report the results of a comparative
immunohistochemical study
between an H-type BSE case identified in the Netherlands and the two Italian
L-type or BASE cases,
using a panel of four different antibodies (9A2, 94B4, 12B2, F99/97.6.1). Th
e antibodies used
recognize different linear and conformational epitopes that are dispatched
along the PrP sequence.
The study conducted at the level of the obex and pons indicates that
F99/97.6.1 better discriminates
the two different phenotypes.

D. Gavier-Widén1, L. Renström1, M. Nöremark1, L. Ottander1, B. Klingeborn1,
T. J. Vulin2, Baron2, M. Stack3,
M. Chaplin3, J.P.M. Langeveld4
1SVA, Upssala, Sweden,
2AFSSA, Lyon, France
3VLA, Webridge, UK
4CIDC-Lelystad, Dept. of Bacteriology & TSEs, Leystad, The Netherlands
Bovine spongiform encephalopathy (BSE) is considered to be caused by a
single strain producing a
consistent and homogenous phenotype of disease in cattle. BSE had never been
detected in Sweden
until March 2006, when a 12-years old mixed-Charolais cow was screened
positive using an ELISA
test. The cow was in late pregnancy, had been recumbent and getting up
repeatedly, was finally
unable to rise and was euthanized. Western blot (WB) with Bio-Rad Bovine WB
at SVA confirmed
the case but showed that the unglycosylated band had a higher MW than in
classical BSE. Further
WB analysis was conducted in parallel at the VLA, AFSSA and CIDC-Lelystad.
The VLA, applying
mAb 6H4 in the hybrid, the OIE-SAF, and the NaPTA WB confirmed the results
of SVA and also
demonstrated binding of mAb P4 (specific for WGQGGSH), which is unusual for
cattle. Image
analysis estimated the difference of MW of being approximately 0.75-0.9 kD.
Additionally, it showed
more evenly distributed relative quantities of PrPSc in the di- and
mono-glycosylated bands than in
classical BSE. The AFSSA achieved similar results using a core antibody,
Sha31, for the
discrimination of apparent molecular masses and also showed binding with
mAbs 12B2. CIDCLelystad
showed excellent binding of 12B2 (specific for sequence WGQGG) and higher
level of PK
sensitivity, in contrast to classical BSE cases. IHC on brainstem, with mAbs
F89 and P4 showed a
characteristic widespread fine granular synaptic type of immunostaining of
the neuropil throughout the
grey matter in all the sections. The trigeminal tract nucleus and the
solitary tract nucleus were more
densely and intensively stained, and had also coarser granules. Perineuronal
staining was observed
in a few neurons. Notably, intracellular and glia-associated PrPP
d types were not observed. In
conclusion, the Swedish case shows similarities with previous descriptions
of H-type of BSE.

K. Hagiwara1, Y. Nakamura1, Y. Yamakawa1, Y. Sato2, M. Tobiume2, T. Sata2
and the Expert Committee for
BSE Diagnosis, Ministry of Health, Labour and Welfare (MHLW) 3
Dep. Biochemistry and Cell Biology1 and Pathology2, Natl. Inst. Infectious
Diseases, Shinjuku, Tokyo 162-8640,
Japan, and MHLW, Tokyo 100-8916, Japan 3
An ELISA (Plateria, BioRad) positive specimen of a 14 year-old Japanese
Black cow (beef cattle)
slaughtered in an abattoir was examined by western-blot (WB) and
(IHC) analyses for the confirmation of BSE. Dysstasia had been reported as a
clinical symptom.
Histological examination of the medulla oblongata at the level of obex
showed severe vacuolations in
dorsal nucleus of the vagus, nucleus of the solitary tract and nucleus of
the spinal tract. Granular and
linear deposition of PrPSc was also detected in these areas by IHC analysis.
Thus, histological and
IHC data were compatible with the histopathology of the typical BSE. In the
WB analysis, however,
the amount of the di-glycosylated PK-resitant PrPP
Sc was found to be at approx.35% of the total PrPSc,
and the mono-glycosylated PrPSc was at approx.40%. The WB analyses showed
that PrPSc
distributed widely in the brain with the unchanged glycosylation ratio. Such
a glycosylation-ratio is
distinct from that of the typical BSE agent in which the di-glycosylated
form is dominant (approx.70%)
but, intriguingly, similar to that of the type-2 sporadic CJD agent. No DNA
mutation was detected in
the PrP coding region, except polymorphisms of the codons for Gln78 and
Asn192 being determined
as CAG and AAT, respectively. Judging from the glycosylation-ratio, BSE
prion herein is different
from the typical BSE prion, and the atypical BSE prion found previously in a
Holstein steer in Japan
(ref. 1). Instead, its molecular feature is close, if not identical, to
PrPSc found in the cattle succumbed
to bovine amyloidtic spongiform encephalopathy (ref. 2), and to the sporadic
CJD-like PrPSc in the
mice inoculated with BSE agent (ref. 3).
References: 1) Y. Yamakawa, Jpn.J.Infect.Dis. (2003), 56, 221. 2) C.
Casalone, PNAS (2004), 101, 3065. 3) S.E.
Lloyd, J.Gen.Virol. (2004), 85, 2471.

J. Jacobs1, J.P.M. Langeveld1, A.G. Biacabe2, P.L. Acutis3, M.Mazza3, M.
Polak4, D. Gavier-Widèn5,
A. Buschmann6, M.H. Groschup6, F.G. van Zijderveld1, A. Davidse1, T. Baron2
1CIDC-Lelystad, Dept. Bacteriology & TSEs, Lelystad, The Netherlands,
2AFSSA, Lyon, France;
3CEA – Istituto Zooprofilattico del Piemonte, Turin, Italy, Turino, Italy;
4NVRI, Dept. Virology, Pulawy, Poland;
5SVA, Upssala, Sweden;
6FLI-INEID, Riems, Greifswald, Germany.
Transmissible spongiform encephalopathies (TSEs) exhibit strain specific
properties by their
behaviour in bioassays and in molecular analyses of the disease associated
prion protein (PrPSc).
However, bovine spongiform encephalopathy (BSE) of cattle appeared to be
very homogeneous.
Recently, a limited number of atypical isolates have been identified in
several countries. This asks for
a comparative study to find a firm molecular classification of these cases.
Various conditions of
digestion with proteinase K (PK) and PNGaseF, analysis by Western blot with
a range of epitopedefined
antibodies were explored. Analyses of the disease associated proteinase K
resistant moiety
of PrP (PrPres), as described previously by Biacabe and Casalone, confirmed
existence of two
additional PrPres variants, defined here as type-H and type-L following the
higher and lower position of
the aglycosylated PrPres band in Western blots compared to that in BSE. This
was further confirmed
by varying the biochemical conditions like detergent addition, PK digestion,
and deglycosylation
treatment. The three molecular PrPres types exhibited different migration
patterns, glycoprofile, PKsusceptibilities
and antibody binding. These properties appear independent of geographical
suggesting the general occurrence of these two different PrPres variants in
cattle, possibly all over the
world. A practical procedure for the recognition of these types in brain
tissues has been worked out.117

In June 2006, a USDA official reported that the two native-born U.S. cattle
“atypical” BSE, not the type seen in cattle in Europe or in the other North
cases.6 The implications of this finding, including whether atypical BSE
could be
spread by novel means, or whether existing controls are appropriate, are
unclear at
this time. The USDA official stated at the time that there were no plans to
existing controls, and the department was already in the process of ramping
down its
domestic BSE surveillance activity.
The North American BSE cases prompted widespread debate over the
effectiveness of U.S. (and Canadian) safeguards against BSE. These
generally have been implemented incrementally over a number of years, not
only as
a response to its emergence in Great Britain and spread to other countries,
but also
to evolving scientific evidence about this relatively new disease, its
causes, and
means of transmission. Many animal health experts inside and outside of
government assert that these regulatory developments have not constituted a
“piecemeal” approach to addressing the BSE threat but rather an increasingly
system of overlapping and complementary safeguards.
Some critics, nonetheless, have questioned whether these safeguards are
providing adequate protection against BSE. Also at issue have been whether
costs to taxpayers and industry are justified; whether such steps are
scientifically and will fully restore foreign markets’ confidence in the
safety of U.S.
cattle and beef; and whether other types of regulatory and/or legislative
should be considered, among other questions.

6 Bill Tomson, “Much Still Unknown About Two US BSE Cases,” Dow Jones
June 8, 2006.


[2] Germany: Characterization of atypical BSE
Date: Sun 20 Aug 2006
From: Terry Singeltary
Source: Vet Microbiol., 14 Aug 2006 (E-pub ahead of print) [edited]

Germany: Characterization of an atypical form of bovine spongiform
encephalopathy (BSE)
The following recently published paper is reproduced here because of
its relevance to theories of the origin of new variant CJD, the human
form of BSE.

Title of paper: Atypical BSE in Germany - Proof of transmissibility
and biochemical characterization. By Buschmann A, Gretzschel A,
Biacabe AG, Schiebel K, Corona C, Hoffmann C, Eiden M, Baron T,
Casalone C, Groschup MH. At the Friedrich-Loeffler-Institut (FLI),
Institute for Novel and Emerging Infectious Diseases, Boddenblick 5a,
17493 Greifswald, Insel Riems, Germany.

ABSTRACT. Intensive active surveillance has uncovered 2 atypical
German BSE (bovine spongiform encephalopathy) cases in older cattle
which resemble the 2 different atypical BSE phenotypes that have
recently been described in France (designated H-type) and Italy
(designated L-type or BASE). The H-type is characterized by a
significantly higher molecular size, but a conventional glycopattern
of the proteinase K treated abnormal prion protein (PrP(Sc)), whereas
the L-type PrP(Sc) has only a slightly lower molecular size and a
distinctly different glycopattern.

In this paper, we describe the successful transmission of both German
atypical BSE cases to transgenic mice over-expressing bovine PrP(C).
Upon challenge with the L-type, these mice developed BSE after a
substantially shorter incubation period than any classical BSE
transmission using these mice to date. In contrast, the incubation
period was distinctly prolonged when these mice were challenged with
the H-type. PrP(Sc) accumulating in the brains of these mice were of
the same atypical BSE type that had been used for the transmission.
These atypical cases suggest the possible existence of sporadic BSE
cases in bovines. It is thus feasible that the BSE epidemic in the UK
could have also been initiated by an intraspecies transmission from a
sporadic BSE case.

Terry S. Singeltary Sr.

[Terry Singeltary Sr. has added the comment that these atypical cases
suggest the possible existence of sporadic BSE cases in bovines. It
is thus feasible that the BSE epidemic in the UK could have also been
initiated by an intraspecies transmission from a sporadic BSE case. -

[3] China (Hong Kong SAR): Suspected vCJD case
Date: Thu 31 Aug 2006
From: ProMED-mail
Source: Xinhua News Agency online, Wed 30 Aug 2006 [trans. from
Chinese by Mod.RY, edited]

China (Hong Kong SAR): Suspected 2nd Case of CJD (new var.) now discounted
The Department of Health of the Hong Kong [SAR] government and Bureau
of the Hong Kong Hospital Administration issued a joint statement on
Wed 30 Aug 2006 reporting that a suspected case of variant
Creutzfeldt-Jakob disease (vCJD) was being assessed in Hong Kong. So
far, laboratory test results have proved negative, and it remains
uncertain whether the suspected case is truly a case of vCJD.

The patient is a 23-year old male born in Britain who returned to
Hong Kong at the beginning of April this year [2006]. He became ill
and was unconscious on 6 Apr 2006, when he was admitted to the
Overseas Chinese Hospital in Guangzhou, and was subsequently
transferred to the Prince of Wales Hospital in the Hong Kong SAR for

The patient's condition is critical at the present time due to
necrotic changes in some of his organs. Though the patient shows
clinical symptoms similar to those observed in vCJD,
electroencephalograms (EEC) and magnetic resonance imaging (MRI) do
not correspond with those observed in vCJD. Tonsil tissue samples
were sent by the hospital to Britain for further examination, but
proved negative.

Therefore, so far, there is no definite indication that the patient
is suffering from vCJD. The Bureau of HK Hospital Administration has
stated that vCJD is a rare degenerative disease of brain and is not
contagious. Nevertheless, the hospital's disease control and
prevention authority will follow a set of strict procedures for
disinfection of medical instruments that have been used for
examination and treatment of the patient to avoid transmission to
other patients.

Hong Kong's 1st case of confirmed vCJD was discovered in 2001. The
patient was a 34-year-old woman who had lived in Britain for an
extended period of time and eventually succumbed to the disease in

[Byline: Tang Yun and Kuang Peng]


[There appears to be no positive reason to diagnose the patient's
illness as vCJD. The report, however, is a reminder that there has
been a previous vCJD case in Hong Kong, a fact that has been
overlooked in most accounts of vCJD in the literature. - Mod.CP]


CJD (NEW VAR.) UPDATE 2006 (10)
A ProMED-mail post

ProMED-mail is a program of the
International Society for Infectious Diseases


[These data are accessible via
. -


[2] Correction
Date: Tue 5 Sep 2006
From: "Terry S Singeltary Sr"

Characterization of atypical BSE in Germany: correction
[In the Moderator's comment accompanying the abstract of the paper entitled
"Atypical BSE in Germany-Proof of transmissibility and biochemical
characterization'" by A Buschmannaet et al, (see part [2] of CJD (new var.)
update 2006 (09) 20060904.2519) it was wrongly implied that Terry S
Singeltary Sr endorsed the conclusions of the paper, whereas his comments
were intended merely to highlight the conclusions of the paper. Namely that
the atypical cases suggested the possible existence of sporadic BSE cases
in bovines and perhaps the BSE epidemic in the UK could have also been
initiated by an intraspecies transmission from a sporadic BSE case. I
apologize for inadvertently misrepresenting Terry's views. - Mod.CP]

Terry S Singeltary Sr has written the following. "In fact I disagree with
the spontaneous/sporadic BSE/TSE theory, IF this is what the authors of
this paper meant by 'sporadic BSE' to mean. For one thing, it has never
been proven. IF atypical BSE i.e. BASE is so similar to some sporadic CJDs,
then how did they all of a sudden become spontaneous? Could it not be so
simple as an atypical BSE i.e. BASE was transmitted the same way most of
all of the other BSE cattle were i.e. feed of just an atypical source, thus
causing atypical strain? Why would these animals not develop an atypical
BSE i.e. BASE from the same oral route? WHAT about an atypical strain
mutating to become infectious via a lateral or horizontal mode in the
bovine, as with CWD and scrapie? Also, please explain to me how a distinct
synthetic prion, of a strain that is supposedly unlike any other we have
ever seen, how can this explain 6 different documented phenotypes of
sporadic CJD to date?

It's like trying to explain away all the 6 phenotypes of sporadic CJD with
the spontaneous theory, it's just not scientific. OR, if you render an
atypical TSE of what ever phenotype, in what ever species, of the atypical
strain and feed it to another whatever species, nothing happens x 1 x 2 x 3
x 4 etc passage? This all has been proven?

Please show me these transmission studies? What Prusiner and Soto produced
in vitro did not look like any natural field TSE, and as far as this in
vitro TSE being infectious, well this was questionable too. If this was the
case, then why does CWD not spontaneously happen in geographical areas
where it has never been documented, OR with scrapie, as in scrapie free New
Zealand? If TSE were to arise spontaneously, I don't see how the scientific
arena can dictate which animal TSE can arise spontaneously, and which ones
cannot, without any scientific evidence to support this to date, and by
even suggesting this in this study, was not scientific. The words sporadic
and spontaneous are very confusing in the world literature of human and
animal TSE and, in my opinion, should not be used as terminology of any

Terry S Singeltary Sr


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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


Subject: SEAC New forms of Bovine Spongiform Encephalopathy 1 August 2007
Date: August 5, 2007 at 10:41 am PST

Position Statement


New forms of Bovine Spongiform Encephalopathy


1. SEAC considered the implications of scientific research on recently
identified novel forms of bovine spongiform encephalopathy (BSE).

2. Very low numbers of cattle with abnormal prion proteins (PrPsc) with
different biochemical properties from those normally associated with BSE
have been detected in active surveillance programmes in a number of
countries. SEAC considered (SEAC 97, May 2007) published and unpublished
research relating to these putatively new forms of BSE.

Characterisation of cases

3. Different forms of BSE were initially identified and distinguished from
classical BSE on the basis of their PrPsc profiles in biochemical tests. All
BSE cases identified to date conform to one of three different PrPsc
profiles on western blot tests. The European Union (EU) Community Reference
Laboratory has suggested that cases be classified on the basis of these
profiles as classical, L- or H-type BSE. The key distinguishing features in
western blot tests are the lower concentration of the diglycosylated band
and the slightly lower molecular mass of unglycosylated band of PrPsc in
L-type BSE, and the higher molecular mass of the unglycosylated band in
H-type BSE, compared with classical BSE. A western blot method to
discriminate between the three types of BSE has been developed .

4. All the reported cases of L-4,5,6,7 and H-type7,9,8,9 BSE have been
detected during active surveillance of healthy slaughtered animals or fallen
stock. In the majority of cases, retrospective investigations indicated that
these animals either showed no clinical signs of BSE or showed non-specific
signs such as ataxia and recumbency. As these cases have been detected
following active rather than passive surveillance, it has not been possible
to observe the clinical signs associated with L- or H-type BSE in sufficient
detail to assess whether there are differences in the clinical features
between L-type, H-type and classical BSE. However, a significant distinction
between classical BSE and L- and H-type BSEs is the age distribution of
cases as L- and H-type BSE are found in older cattle with an age range of
5.5 to 19 years. One putative L-type BSE case was aged two years6, however
the BSE typing of this case has not been verified. Around 85% of L- or
H-type BSE cases have been found in animals more than 10 years old, which is
much older than most cases of classical BSE.

5. Neuropathological investigations suggest that PrPsc may be more widely
distributed, with a different brain distribution pattern for L- and H-type
BSE, compared with classical BSE. However, these investigations are limited
by the very low number of animals for which a complete brain has been
available for analysis. There are no data on the peripheral distribution of
PrPsc or infectivity of L- and H-type BSE or on the pathogenesis of these
diseases. However, studies to assess the tissue distribution of infectivity
and PrPsc in animals throughout the incubation period following
intracerebral challenge are underway.


6. As there is no regulatory requirement to specify the type of BSE when
notifying the EU or the World Organisation of Animal Health of BSE cases, it
is not possible to accurately quantify the number of H- or L-type BSE cases
that have occurred world-wide. Information presented to SEAC indicated that
at least 37 cases of L- and H-type BSE have been identified world-wide to
date. These cases are widely distributed geographically with L-type cases
identified in a number of European countries and Japan, and H-type cases
identified in a number of European countries and North America.

7. Due to the different approaches to surveillance between countries,
proportions of animals tested and methods used, which do not necessarily
include systematic molecular typing, these surveillance systems are not
equally capable of detecting L- and H-type BSE. Furthermore, surveillance
procedures, including the most appropriate brain region to sample, have not
been optimised for the detection of L- and H-type BSE. Therefore, it is not
possible to accurately assess and compare the prevalence of L- and H-type
BSE in different countries. Origins and Causes

8. It is not known whether L- or H-type BSE are newly emerging forms of BSE
or whether they have existed for some time and have only come to light
following extensive active surveillance programmes in the EU and elsewhere,
together with the introduction and development of new biochemical tests.
Studies using historic frozen brain samples from cattle collected from
passive surveillance during the early years of the UK BSE epidemic are
underway to investigate whether L- and H-type BSE existed in the UK in the
past. However, if the prevalence of these BSE types was low, these studies
may not identify many, if any, cases.

9. Genetic analyses of a few L- and H-type BSE cases4,5,8,9 have not
identified associations between the occurrence of such cases and known
genetic polymorphisms in the prion protein gene. There are no mutations in
the prion protein gene open reading frame in all, but one, sequenced case.
However, the analyses conducted to date are limited by the small number of
cases and controls analysed. Thus, a genetic cause of the disease cannot be
ruled out.

10. No detailed epidemiological investigations have been conducted to
investigate the possible causes for, or links between, L- and H-type BSE
cases. No geographical clusters of L- and H-type BSE cases have been found
to date. Therefore, it is not possible to rule out feed related,
environmental or spontaneous causes for these types of cases.

Transmission studies

11. Transmission studies5,10,11 have demonstrated that both L- and H-type
BSE are transmissible to other species by the intracerebral route. No
studies have assessed the transmissibility by the oral route. Thus, the
available information shows that it is possible for species other than
cattle to develop these diseases upon infection. However, these data do not
allow an assessment of the susceptibility to infection from the most likely
natural route of exposure.

12. L-type BSE has been transmitted to wild-type, bovinised, ovinised and
humanised mice as well as to cattle and a cynomolgus macaque by
intracerebral inoculation. Incubation periods, clinical signs,
neuropathology as well as the neurological distribution of PrPsc were
distinct from classical BSE13,12. With the exception of transmissions to
wild-type mice, primary transmissions resulted in clinical disease. Although
primary transmission to wild-type mice did not result in clinical disease,
secondary transmissions from some of these animals resulted in clinical
disease. Sub-passage of L-type BSE in wild-type12 and ovinised mice13
suggests that L-type BSE may be converted to an infection of a similar
phenotype to classical BSE. However, further experiments using serial
sub-passages of infections in a range of species are required to more fully
investigate whether L-type BSE may convert to a disease with a classical BSE

13. H-type BSE has been transmitted to wild type, bovinised and ovinised
mice by intracerebral inoculation with incubation periods, neuropathology
and neurological distribution of PrPsc distinct from classical and L-type

14. Studies of intracerebral transmission of H-type BSE to cattle and
cynomolgus macaques . To date, clinical disease has developed from one
intracerebral inoculation of H-type BSE to cattle. Oral transmissions of L-
and H-type to cynomolgus macaques are underway.

Human and animals health implications
15. There are too few data to enable an assessment of the natural
transmissibility of L- and H-type BSE between cattle, or to sheep or goats.
The present feed control measures which prevent feeding of mammalian meat
and bone meal to ruminants would limit the spread of these forms of BSE to
cattle, sheep and goats should they be transmissible to these species by the
oral route.

16. Similarly, the lack of data on the oral transmissibility of L- or H-type
BSE to humanised mice or non-human primates does not allow an assessment of
the human health implications of ingestion of meat from animals infected
with L- or H-type BSE. The differing clinical features of L-type and
classical BSE in the cynomolgus macaque suggest that if L-type BSE were ever
to be transmitted to humans, its clinical presentation may differ from that
of vCJD. It is possible, therefore, that, if transmitted to humans, it could
be identified by continuing surveillance of unusual neurological conditions
in place in the UK.


17. L- and H-type BSE have not yet been fully characterised, however data
from biochemical, neuropathological and transmission studies suggest that L-
and H-type and classical BSE may be distinct strains of prion disease. In
contrast to classical BSE, L- and H-type BSE infections are mostly detected
in animals of older age with most of the infected animals identified to date
over 10 years of age. Although L- and H-type BSE may be diseases that
predominantly affect older cattle, it is possible that infections may occur
at a young age and develop over a long period of time. The origins and
possible routes of transmission, if transmissible under natural conditions,
of L- and H-type BSE are not known. Due to the older age of the cases
identified, wide geographical distribution and their apparent low number, it
is possible they may have arisen spontaneously, however feed borne or
environmental transmission cannot be ruled out.

18. As data on the oral transmissibility of L- and H-type BSE are lacking,
it is not possible to fully assess the animal and human health implications.
However, as the occurrence of L- and H-type BSE appears to be low, and due
to the feed control measures in place, the risk of spread to other cattle,
sheep and goats is likely to be very low assuming that, as with classical
BSE, environmental transmission is negligible. For these reasons, and
because of the BSE control measures in place to protect the food supply,
assuming that the specific risk material controls are similarly effective
for L- and H-type and classical BSE, the risk to human health is likely to
be very low to negligible. However, given the paucity of data on L- and
H-type BSE, a close watching brief should be maintained on the findings of
research in this area.

SEAC July 2007


1SEAC 97 discussion papers available at

2Published and unpublished data from the Institute for Novel and Emerging
Infectious Diseases, Germany presented by Dr M. Groschup, the Instituto
Nazionale Neurologico, Italy presented by Dr F. Tagliavini, the Unite Agents
Transmissibles Non Conventionnels, France presented by Dr T. Baron, the
Istituto Zooprofilattico Sperimentale del Piemonte, Italy presented by Dr P.
Acutis, the National Animal Disease Centre, USA presented by Dr J. Richt,
the National Veterinary Services Laboratories, USA presented by Dr M. Hall,
the Commissariat à L’Energie Atomique, France presented by Professor C.
Lasmezas, the Veterinary Laboratories Agency, UK presented by Dr. L. Terry
and the National Institute of Infectious Diseases, Japan provided by Dr Y.

3Jacobs et al. Molecular discrimination of atypical bovine spongiform
encephalopathy strains from a geographical region spanning a wide area in
europe. J Clin Microbiol. 2007;45(6):1821-9.

4Casalone et al. Identification of a second bovine amyloidotic spongiform
encephalopathy: molecular similarities with sporadic Creutzfeldt-Jakob
disease. Proc Natl Acad Sci U S A. 2004;101(9):3065-70.

5 Buschmann et al. Atypical BSE in Germany--proof of transmissibility and
biochemical characterization. Vet Microbiol. 2006;117(2-4):103-16.

6Yamakawa et al. Expert Committee for BSE Diagnosis, Ministry of Health,
Labour and Welfare of Japan. Atypical proteinase K-resistant prion protein
(PrPres) observed in an apparently healthy 23-month-old Holstein steer. Jpn
J Infect Dis. 2003;56(5-6):221-2.

7Brown et al. On the question of sporadic or atypical bovine spongiform
encephalopathy and Creutzfeldt-Jakob disease. Emerg Infect Dis.

8Biacabe et al. Distinct molecular phenotypes in bovine prion diseases. EMBO
Rep. 2004;5(1):110-5.

9Richt et al. Identification and characterisation of two bovine spongiform
encephalopathy cases diagnosed in the United States. J Vet Diagn Invest

10Capobianco et al. Conversion of the BASE Prion Strain into the BSE Strain:
The Origin of BSE? PLoS Pathog. 2007;3(3):e31

11Baron et al. Transmission of new bovine prion to mice. Emerg Infect Dis.

12Beringue et al. Isolation from cattle of a prion strain distinct from that
causing bovine spongiform encephalopathy. PLoS Pathog. 2006;2(10):e112.

13Beringue et al. A bovine prion acquires an epidemic bovine spongiform
encephalopathy strain-like phenotype on interspecies transmission. J
Neurosci. 2007;27(26):6965-71.

Page updated: 1 August, 2007


18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.


64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.


Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the



3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse

Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.


These results indicate that BASE is transmissible to humans and suggest
that BASE is more virulent than classical BSE in humans.


6:30 Close of Day One

1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...


There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance


He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.



If, on the other hand, atypical BSE continues to occur as typical BSE
disappears, this would be a strong indication that it is indeed sporadic,
and if in addition at least 1 form of what is presently considered as
sporadic CJD (such as the type 2 M/V subtype shown to have a Western blot
signature like BASE) were to increase, this would suggest (although not
prove) a causal relationship (Figure 5).


The Lancet Infectious Diseases 2003; 3:463


Tracking spongiform encephalopathies in North America

Xavier Bosch

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers
ever since. What I have found is that we have not been told the truth. CWD
in deer and elk is a small portion of a much bigger problem.”


adding that, “the cases that we know about are reassuring, because they do
not suggest the appearance of a new variant of CJD in the USA or atypical
features in patients that might be exposed to CWD. However, until we
establish a system that identifies and analyses a high proportion of
suspected prion disease cases we will not know for sure”. The USA should
develop a system modelled on that established in the UK, he points

1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.





MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9

June 2003

BY Philip Yam


Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system
has errors but stated that most of the errors will be confined to the older




By Terry S Singeltary

Bacliff, Texas USA Jan 24, 07

Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518

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