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From: TSS ()
Subject: On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease
Date: November 7, 2006 at 1:57 pm PST


On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease

Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda Detwiler§

Strategies to investigate the possible existence of sporadic

bovine spongiform encephalopathy (BSE) require

systematic testing programs to identify cases in countries

considered to have little or no risk for orally acquired disease,

or to detect a stable occurrence of atypical cases in

countries in which orally acquired disease is disappearing.

To achieve 95% statistical confidence that the prevalence

of sporadic BSE is no greater than 1 per million (i.e., the

annual incidence of sporadic Creutzfeldt-Jakob disease

[CJD] in humans) would require negative tests in 3 million

randomly selected older cattle. A link between BSE and

sporadic CJD has been suggested on the basis of laboratory

studies but is unsupported by epidemiologic observation.

Such a link might yet be established by the discovery

of a specific molecular marker or of particular combinations

of trends over time of typical and atypical BSE and various

subtypes of sporadic CJD, as their numbers are influenced

by a continuation of current public health measures that

exclude high-risk bovine tissues from the animal and

human food chains.

Bovine spongiform encephalopathy (BSE) was first recognized

in 1986 in the United Kingdom and quickly

reached epidemic proportions, affecting >30,000 cattle per

year by 1992. Because of continuing exportation of both

live cattle and meat and bone meal rendered from the carcasses

of slaughtered cattle, the disease spread throughout

most of Europe and a few non-European countries. By

2006, 20 years after its first appearance in the United

Kingdom, the disease had been reported in an additional

24 countries (1).

Beginning toward the end of the 1980s in the United

Kingdom, and in the 1990s in other countries, numerous

regulations were enacted to minimize the entry of contaminated

tissues into both the animal and human food chains

and to eliminate the international spread of disease. These

measures have been extraordinarily successful, to the

extent that no new countries have been added to the list

during the past year and the number of new cases has dramatically

diminished in most countries in which BSE has

appeared (the situation in some countries with insufficient

surveillance remains unclear).

Although the origin of the epidemic is thought to have

been caused by a species-crossing contamination by sheep

scrapie during the course of rendering and recycling carcass

meat and bone meal as cattle feed, an alternative

hypothesis suggested an origin in a similarly recycled case

of spontaneously occurring disease in cattle. The pros and

cons of these competing ideas have been argued elsewhere

(2,3), and neither will ever be convincingly proved or disproved.

Thus, the phenomenon of spontaneous disease

remained in limbo until the recent discovery of “atypical”

strains of BSE reopened the question. In this article we

consider the importance of atypical BSE within the overall

concept of sporadic (spontaneous) disease and whether

such cases, if they exist, could account for at least some

cases of apparently sporadic Creutzfeldt-Jakob (CJD) in


Sporadic BSE

Obviously, the ideal country in which to examine the

question of sporadic BSE would have a large national herd

that was guaranteed never to have been exposed to environmental

sources of infection. Such an ideal will never be

realized. Until recently, the United States appeared to have

at least approached the ideal by having a large national

*Bethesda, Maryland, USA; †National Institutes of Health,

Bethesda, Maryland, USA; ‡University of Verona, Verona, Italy;

and §Virginia-Maryland Regional College of Veterinary Medicine,

College Park, Maryland, USA

1816 Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006

herd, an adequate testing program, and an apparently small

risk for contamination by imported cattle or cattle feed.

That position was made vulnerable in late 2003 by the discovery

of a case of BSE imported from Canada and was

eliminated altogether by the subsequent discovery of 2

indigenously infected animals in widely separate regions

of the country. Although the 2 indigenous cases might represent

sporadic disease, the continuing identification of

cases in western Canada, coupled with a history of substantial

numbers of cattle imported from Canada into the

United States (both indigenous US animals had the same

molecular “signature” as the most recent Canadian case),

makes it difficult to ignore the possibility of undetected

instances of feed contamination from imported and recycled

infectious carcasses.

At present, the 2 best countries in which to undertake

testing programs would be Argentina and Australia; both

have large national herds (≈50 million and 30 million animals,

respectively), and both are considered to be free of

orally acquired BSE infections, on the basis of importation

history, nutritional practices, and adequacy of surveillance

(4). Even in these countries, however, the discovery of a

case of BSE could not be guaranteed to be spontaneous

because of the widespread global distribution of potentially

infected cattle and cattle feed and the vagaries of international

trade: imperfect record keeping, lack of

compliance, and just plain deception.

By way of illustration, an incident occurred many years

ago that involved a particularly bulky shipment labeled as

a pesticide. The large quantity seemed unusual to the customs

inspector, who opened it and discovered that the shipment

contained meat and bone meal destined to be spread

on fields to inhibit grazing by deer, a serious agricultural

pest. Thus, a study of sporadic BSE would only be truly

convincing if no cases were identified.

Moreover, the criteria for answering the question of

sporadic BSE are different than for orally acquired BSE.

Most importantly, we do not know at what age sporadic

cases of BSE might occur, but they are unlikely to be in the

3- to 5-year-old age group in which orally acquired BSE is

most prevalent. If the age distribution of sporadic disease

in cattle were to mimic that of sporadic CJD in humans, it

would not peak until 14–20 years of age (the last third of

the ≈20-year natural life span of a cow). Substantial numbers

of such older cattle do not exist, and thus it may never

be possible to state with assurance that spontaneous BSE

does not occur.

Even if we accept this practical constraint, we can still

take advantage of the fact that in many countries a proportion

of the total slaughter population consists of breeding

stock and dairy cows that are culled at >7 years of age, and

animals that go directly to rendering plants or die “on

farm” further increase this number. Argentina, for example,

with a national herd of ≈50 million cattle, in 2005

recorded nearly 1.4 million deaths from slaughter and natural

causes in animals >7 years (L. Mascitelli, pers.


Approximately 10% of cases of sporadic CJD occur in

patients 25–50 years of age; this age in humans corresponds

to the middle third of a cow’s normal life span, or

7–13 years of age (Figure 1). If the age distribution of sporadic

BSE followed the same pattern, negative test results

in a total of ≈3 million animals randomly selected from

this group would allow us to be 95% confident that sporadic

BSE is not present at a prevalence >1 per million,

and ≈4.5 million negative animals would raise the level of

confidence to 99%. Larger numbers of BSE-negative animals

would be required to achieve these levels of confidence

for a maximum prevalence <1 per 10 million cattle

(Table 1, Figure 2).

Even the least rigorous negative result—a prevalence

not greater than that of sporadic CJD in humans, or 1 per

million—would require several years to achieve, and it is

perhaps unrealistic to suppose that the motivation to prolong

the testing program will endure much beyond the

global disappearance of orally acquired BSE and variant

CJD. Nevertheless, to the degree that testing older as well

as younger adult animals approached these numbers, both

statistical and consumer confidence would increase, and at

the very least provide reassurance that the occurrence of

sporadic disease must be exceedingly rare, with little likelihood

of posing a risk to either human or animal nutrition.

Atypical BSE

Because of its contemporary nature, the study of atypical

BSE is very much a work in progress, with comparatively

little published data and many unknowns. The first 2

cases to be identified were a serendipitous discovery made

in the course of an unrelated experimental study that

required a detailed neuropathologic and immunochemical

Figure 2. Maximum prevalence according to number of negative

cattle at 95% (solid line) and 99% (dashed line) confidence levels.

See Table 1 for exact numbers and statistical method.

Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006 1817

examination of the entire brain (5). The absence of clinical

signs in these older animals, the unusual distribution of

PrPTSE, together with amyloid plaques, and a Western blot

pattern that differed from the stereotypic pattern seen in

typical BSE left little doubt about the probability that a

new “atypical strain” had been identified (bovine amyloidotic

spongiform encephalopathy[BASE]).

Although no further cases were found in nearly 200 cattle

examined in Italy, the initiation of Western blot studies

of animals in other countries with screening test programs

began to yield additional atypical patterns (Table 2, Figure

3) (6–14; P. Lind, pers. comm.). Two major patterns have

been described, named L (resembling the original Italian

case pattern with a lower molecular weight than typical

BSE) and H (for a distinct pattern first seen in France with

a higher molecular weight than typical BSE). It is not yet

clear whether other mixed patterns result from technical

procedures in different laboratories or whether a more

complicated scheme of classification will evolve as more

atypical patterns are discovered.

In addition, Western blots of PrPTSE are a fragile basis

on which to define a BSE phenotype. Little or no information

is available about either the clinical status or neuropathologic

features of these animals. We know that cases

have occurred in different breeds and PrP genotypes, and

we also know that very few of the animals have had the

typical clinical picture of BSE (behavioral disturbances,

sensory signs, ataxia, and tremors), but a cloud of ambiguity

surrounds the clinical picture even in those animals for

which an extensive post-hoc investigation was undertaken.

The fact that few detailed neuropathologic results are

available is explained by the need to preserve at least a full

half brain for examination, which is presently not done in

any of the various countries that have screening test programs.

In the future, the brain as well as the carcass must

be retained in cold storage until the test results are known.

The frequency of atypical cases is another unknown.

Published (7,12) and unpublished (11,13) observations

indicate that in some countries it might be as high as

5%–10% of the total number of older animals diagnosed

by rapid screening tests (e.g., 2/27 in Germany, and 1/9 in

Canada), which would seem to be a surprisingly high proportion

of spontaneously occurring cases. However, data

are not yet sufficient to estimate the overall prevalence of

atypical BSE, i.e., cases per million tested animals of all


In this context, a word is in order about the US testing

program. After the discovery of the first (imported) cow in

2003, the magnitude of testing was much increased, reaching

a level of >400,000 tests in 2005 (Figure 4). Neither of

the 2 more recently indigenously infected older animals,

with ambiguous or no clinical features, would have been

detected without such testing, and neither would have been

identified as atypical without confirmatory Western blots.

Despite these facts, surveillance has now been decimated

to 40,000 annual tests (USDA news release no. 0255.06,

July 20, 2006) and invites the accusation that the United

1818 Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006

States will never know the true status of its involvement

with BSE.

In short, a great deal of further work will need to be

done before the phenotypic features and prevalence of

atypical BSE are understood. More than a single strain

may have been present from the beginning of the epidemic,

but this possibility has been overlooked by virtue of the

absence of widespread Western blot confirmatory testing

of positive screening test results. These new phenotypes

may be found, at least in part, to result from infections at

an older age by a typical BSE agent, rather than neonatal

infections with new “strains” of BSE. Neither alternative

has yet been investigated.

Sporadic CJD

The possibility that at least some cases of apparently

sporadic CJD might be due to infection by sporadic cases

of BSE cannot be dismissed outright. Screening programs

needed to identify sporadic BSE have yet to be implemented,

and we know from already extant testing programs that

at least a proportion of infected animals have no symptoms

and thus would never be identified in the absence of systematic

testing. Thus, sporadic BSE (or for that matter,

sporadic disease in any mammalian species) might be

occurring on a regular basis at perhaps the same annual

frequency as sporadic CJD in humans, that is, in the range

of 1 case per million animals.

Whether humans might be more susceptible to atypical

forms of BSE cannot be answered at this time.

Experimentally transmitted BASE shows shorter incubation

periods than BSE in at least 1 breed of cattle,

bovinized transgenic mice, and Cynomolgus monkeys

(12,13). In humanized transgenic mice, BASE transmitted,

whereas typical BSE did not transmit (13). Paradoxically,

the other major phenotype (H) showed an unusually long

incubation period in bovinized transgenic mice (12).

The limited experimental evidence bearing on a possible

relationship between BSE and sporadic CJD is difficult

to interpret. The original atypical BASE strain of BSE had

a molecular protein signature very similar to that of 1 subtype

(type 2 M/V) of sporadic CJD in humans (5).

In another study, a strain of typical BSE injected into

humanized mice encoding valine at codon 129 showed a

Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006 1819

glycopattern indistinguishable from the same subtype of

sporadic CJD (15). In a third study, the glycopatterns of

both the H and L strains of atypical BSE evidently did not

resemble any of the known sporadic CJD subtypes (12).

To these molecular biology observations can be added

the epidemiologic data accumulated during the past 30

years. The hypothesis that at least some cases of apparently

sporadic CJD are due to unrecognized BSE infections

cannot be formally refuted, but if correct, we might expect

by now to have some epidemiologic evidence linking BSE

to at least 1 cluster of apparently sporadic cases of CJD.

Although only a few clusters have been found (and still

fewer published), every proposed cluster that has been

investigated has failed to show any common exposure to

bovines. For that matter, no common exposure has been

shown to any environmental vehicles of infection, including

the consumption of foodstuffs from bovine, ovine, and

porcine sources, the 3 livestock species known to be susceptible

to transmissible spongiform encephalopathies.

Additional negative evidence comes from several large

case-control studies in which no statistically significant

dietary differences were observed between patients with

sporadic CJD and controls (16,17).

On the other hand, the difficulty of establishing a link

between BSE and CJD may be compounded by our ignorance

of the infectious parameters of a sporadic form of

BSE (e.g., host range, tissue distribution of infectivity,

route of transmission, minimum infectious dose for

humans, whether single or multiple). Presumably, these

parameters would resemble those of variant CJD' that is,

high infectivity central nervous system and lymphoreticular

tissues of an infected cow find their way into products

consumed by humans. Transmissions that might have

occurred in the past would be difficult to detect because

meat products are generally not distributed in a way that

results in detectable geographic clusters.

Barring the discovery of a specific molecular signature

(as in variant CJD), the most convincing clue to an association

will come from the observation of trends over time of

the incidence of typical and atypical BSE and of sporadic

and variant CJD. With 4 diseases, each of which could

have increasing, unchanging, or decreasing trends, there

could be 81 (34) possible different combinations. However,

it is highly likely that the trends for typical BSE and variant

CJD will both decrease in parallel as feed bans continue

to interrupt recycled contamination. The remaining

combinations are thus reduced to 9 (32), and some of them

could be highly informative.

For example, if the incidence of atypical BSE declines

in parallel with that of typical BSE, its candidacy as a sporadic

form of disease would be eliminated (because sporadic

disease would not be influenced by current measures

to prevent oral infection). 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).

Recognition of the different forms of BSE and CJD

depends upon continuing systematic testing for both

bovines and humans, but bovine testing will be vulnerable

Figure 5. Diagram of 2 possible informative trends in the incidence

of bovine spongiform encephalopathy (BSE) and Creutzfeld-Jakob

disease (CJD). The left panel shows the likely trends of typical

BSE and variant CJD (vCJD). The right upper panel shows 1 possible

pair of trends of atypical BSE and sporadic CJD (sCJD)

that might occur in conjunction with the typical BSE/vCJD trends,

and would be consistent with the interpretation that atypical BSE

is not sporadic and not related to sCJD. The right lower panel

shows a second possible associated pair of trends consistent with

the interpretation that atypical BSE is sporadic and might also be

related to the type 2 M/V subset of apparently sCJD.

1820 Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006

to heavy pressure from industry to dismantle the program

as the commercial impact of declining BSE cases ceases to

be an issue. Industry should be aware, however, of the

implications of sporadic BSE. Its occurrence would necessitate

the indefinite retention of all of the public health

measures that exclude high-risk bovine tissues from the

animal and human food chains, whereas its nonoccurrence

would permit tissues that are now destroyed to be used as

before, once orally acquired BSE has disappeared.


We thank Victoria E. Bridges and Chris Kopral for providing

data about annual cattle slaughter numbers from the Food

Safety and Inspection Service of the US Department of

Agriculture (USDA) and for estimates of cattle dying on farms

from data supplied by the National Animal Health Monitoring

System, Animal and Plant Inspection Services, Veterinary

Service, USDA.

This study was funded in part by grant # 4AN/F10 “Studio

dei meccanismi patogenetici delle malattie neurodegenerative per

la diagnosi e lo sviluppo di approcci terapeutici” from the Istituto

Superiore di Sanità, Rome, Italy

Dr Brown has recently retired after a 41-year career in the

Laboratory of CNS Studies at the National Institutes of Health,

where he focused on studying transmissible spongiform



1. World Organization for Animal Health. Bovine spongiform

encephalopathy. Geographical distribution of countries that reported

BSE confirmed cases since 1989 [cited 2006 Oct 24]. Available


2. Brown P, Bradley R, Detwiler L, Dormont D, Hunter N, Wells GAH,

et al. Transmissible spongiform encephalopathy as a zoonotic disease.

International Life Sciences Institute (ILSI) Europe Report

Series. Brussels: ILSI Press; 2003.

3. Horn GM, Bobrow ME, Bruce M, Goedert M, McLean A, Webster J.

Review of the origin of BSE 2001, London: Stationery Office; 2001.

4. World Organization for Animal Health. Bovine spongiform

encephalopathy. Recognition of the bovine spongiform encephalopathy

status of member countries [cited 2006 Oct 24]. Available


5. Casalone C, Zanusso G, Acutis P, Ferrari S, Capucci L, Tagliavini F,

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;101:3065–70.

6. Danish Institute for Food and Veterinary Research [cited 2006 Oct.

24]. Available from


7. Polak M, Rozek W, Rola J, Zmudzinski JF. Prion protein glycoforms

from BSE cases in Poland. Bulletin of the Veterinary Institute of

Pulawy. 2004;48:201–5.

8. De Bosschere H, Roels S, Vanopdenbosch E. Atypical case of bovine

spongiform encephalopathy in an East-Flemish cow in Belgium. Int

J Appl Res Vet Med. 2004;2:52–4. Available from http://www.jarvm.


9. Yamakawa Y, Hagiwara K, Nohtomi K, Nakamurua Y, Nishijima M,

Higuchi Y, et al. Atypical proteinase K-resistant prion protein

(PrPrres) observed in an apparently healthy 23-month-old Holstein

steer. Jpn J Infect Dis. 2003;56:221–2.

10. Biacabe AG, Laplanche JL, Ryder S, Baron T. Distinct molecular phenotypes

in bovine prion diseases. EMBO Rep. 2004;5:110–4.

11. Canadian Food Inspection Agency. Report on the investigation of the

sixth case of bovine spongiformencephalopathy (BSE) in Canada

[cited 2006 Oct]. Available from


12. Buschmann A, Gretzshel A, Biacabe AG, Schiebel K, Corona C,

Hoffmann C, et al. Atypical BSE in Germany—proof of transmissibility

and biochemical characterization. Vet Microbiol. 2006;


13. Book of abstracts. Prion 2006, International Conference on Prion

Diseases of NeuroPrion, Network of Excellence, Turin, Italy, 2006

Oct 3–6 [cited 2006 Oct 24]. Available from http://www.

14. Seuberlich T, Botteron C, Wenker C, Café-Marçal V, Oevermann A,

Haase B, et al. Spongiform encephalopathy in a miniature zebu.

Emerg Infect Dis. 2006;12:xxx–xxx. [THIS ISSUE]

15. Wadsworth JDF, Asante EA, Desbruslais M, Linehan JM, Joiner S,

Gowland I, et al. Human prion protein with valine 129 prevents

expression of variant CJD phenotype. Science. 2004;306:1793–6.

16. Wientjens DP, Davanipour Z, Hofman A, Kondo K, Matthews WB,

Will RG, et al. Risk factors for Creutzfeldt-Jakob disease: a reanalysis

of case control studies. Neurology. 1996;46:1267–91.

17. Van Duijn CM, Delasnerie-Lauprêtre N, Masullo C, Zerr I, de Silva

R, Wientjens DPWM, et al. Case-control study of risk factors of

Creutzfeldt-Jakob disease in Europe during 1993–1995. Lancet.


Address for correspondence: Paul Brown, 7815 Exeter Rd, Bethesda, MD

20814, USA; email:

Emerging Infectious Diseases • • Vol. 12, No. 12, December 2006 1821

Case 1:06-cv-00544-JR Document 14-9 Filed 11/03/2006 Page 47 of 47

P.S. some of the charts, graphs, tables etc. i was not able to forward in plain text. ...TSS

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 collection.

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

A ProMED-mail post

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

[The definition of the designations deaths, definite cases, probable
vCJD cases, and the case definitions can be found by accessing the
Department of Health website or by reference to a previous
ProMED-mail post in this thread (for example, CJD (new var.) - UK:
update March 2002 20020305.3693).

Data on vCJD cases from other parts of the world are now included in
these updates whenever available.

Also, data on other forms of CJD (sporadic, iatrogenic, familial and
GSS) are now included when they have some relevance to the incidence
and etiology of vCJD. - Mod.CP]

In this update:

[1] UK: Department of Health monthly CJD statistics, Mon 6 Nov 2006
[2] EUROCJD data as of 31 Oct 2006
[3] France: novel prion strain

[1] UK: Department of Health monthly CJD statistics, Mon 6 Nov 2006
Date: Mon 6 Nov 2006
From: ProMED-mail
Source: UK Department of Health, Monthly Creutzfeldt-Jakob Disease
Statistics [edited]

The Department of Health is today [Mon 6 Nov 2006] issuing the latest
information about the numbers of known cases of Creutzfeldt-Jakob
disease. This includes cases of variant Creutzfeldt-Jakob disease
[abbreviated in ProMED-mail as CJD (new var.) or vCJD], the form of
the disease thought to be linked to BSE (bovine spongiform encephalopathy).

Definite and probable CJD cases in the UK, as of Fri 3 Nov 2006:
Summary of vCJD cases - deaths
Deaths from definite vCJD (confirmed): 112
Deaths from probable vCJD (without neuropathological confirmation): 46
Deaths from probable vCJD (neuropathological confirmation pending): 0
Number of deaths from definite or probable vCJD (as above): 158

Summary of vCJD cases - alive
Number of probable vCJD cases still alive: 6

Number of definite or probable vCJD (dead and alive): 164

(The next table will be published on Mon 4 Dec 2006).

Since the previous monthly statistics were released on Mon 6 Nov
2006, the total number of deaths from definite vCJD has increased by
2 and stands at 158, and the overall total number of definite or
probable vCJD cases (dead and alive) has increased by 2, making the
overall total 164.

These data are consistent with the view that the vCJD outbreak in the
UK is in decline. The total number of deaths due to vCJD in the UK is
now 158. The peak number of deaths was 28 in the year 2000, followed
by 20 in 2001, 17 in 2002, 18 in 2003, and 9 in 2004, 5 in 2005. The
number of deaths due to definite or probable vCJD in the UK during
the 1st 10 months of 2006 has risen to 5.

Totals for all types of CJD cases in the UK in 2005 and 2006
As of 3 Nov 2006, in the UK in the year 2005, there were 122
referrals of suspected CJD, and there were 65 deaths from sporadic
CJD, 6 from familial CJD, 3 from iatrogenic CJD, 6 GSS
(Gerstmann-Straussler-Scheinker) syndrome cases, and 5 deaths from vCJD.

The corresponding figures so far for the 1st 10 months of 2006 are:
87 referrals, 48 deaths from sporadic CJD, 5 from vCJD, 4 from
familial CJD, 3 from GSS and one from iatrogenic CJD.

During the period 1995, when vCJD was 1st diagnosed, up to the
present, there have been 946 deaths from all forms of CJD, including
the 158 deaths attributable to definite or probable vCJD.

[These data are accessible via


[2] EUROCJD data as of 31 Oct 2006
Date: Tue 31 Oct 2006
From: ProMED-mail
Source: EUROCJD [edited]

The European And Allied Countries Collaborative Study Group of CJD (EUCJD)
This web-site includes information from 2 projects funded by the
European Commission. The EUROCJD project started in 1993 and compares
data from national registries in Australia, Austria, Canada, France,
Germany, Italy, the Netherlands, Slovakia, Spain, Switzerland and the
UK. The NEUROCJD project started in 1998 after the European Union
Council recommended that epidemiological surveillance of CJD should
be extended to all member states. The member states involved in this
project are Belgium, Denmark, Finland, Greece, Iceland, Ireland,
Israel, Norway and Portugal. Both projects are coordinated from the
National CJD Surveillance Unit based in Edinburgh.

Current data as of October 2006
Country / Total No. of Primary cases (No. alive) / Cumulative
residence in UK (>6 months) / Secondary transmission by blood transfusion

United Kingdom / 162 (6) / 164 / 2 (0)

France / 21 (2) / 1 / 0

Republic of Ireland / 4 (1) / 2 / 0

Italy / 1 (0) / 0 / 0

USA / 2 (0) / 2 / 0

Canada / 1 (0) / 1 / 0

Saudi Arabia / 1 (1) / 0 / 0

Japan / 1* (0) / 0 / 0

Portugal / 1 (1) / 0 / 0

Spain / 1 (0) / 0 / 0

Total / 197 (12) / - / 2

* Residence in the UK for 24 days


[3] France: novel prion strain
Date: Thu 12 Oct 2006
From: Terry Singeltary
Source: PLoS Pathogens 2(10); published ahead of print [edited]

Terry S. Singeltary Sr. has drawn ProMED-mail's attention to the
following paper published ahead of print in PLoS Pathogens, which
although not directly featuring vCJD, he considers is relevant to
understanding the origin of the BSE outbreak in cattle and vCJD in
humans. He comments that this research indicates that different prion
disease phenotypes result from inoculation of cattle with 2
temporally separated sources of sheep scrapie from Great Britain.

The paper is entitled "Isolation from Cattle of a Prion Strain
Distinct from That Causing Bovine Spongiform Encephalopathy" and is
authored by Vincent Beringue and 10 others. The abstract reads as follows:

"To date, bovine spongiform encephalopathy (BSE) and its human
counterpart, variant Creutzfeldt-Jakob disease, have been associated
with a single prion strain. This strain is characterized by a unique
and remarkably stable biochemical profile of abnormal
protease-resistant prion protein (PrP(res)) isolated from brains of
affected animals or humans. However, alternate PrP(res) signatures in
cattle have recently been discovered through large-scale screening.
To test whether these also represent separate prion strains, we
inoculated French cattle isolates characterized by a PrP(res) of
higher apparent molecular mass, called H-type, into transgenic mice
expressing bovine or ovine PrP. All mice developed neurological
symptoms and succumbed to these isolates, showing that these
represent a novel strain of infectious prions. Importantly, this
agent exhibited strain-specific features clearly distinct from that
of BSE agent inoculated to the same mice, which were retained on
further passage. Moreover, it also differed from all sheep scrapie
isolates passaged so far in ovine PrP-expressing mice. Our findings
therefore raise the possibility that either various prion strains may
exist in cattle, or that the BSE agent has undergone divergent
evolution in some animals."

The authors' synopsis of their paper reads as follows: Prions are
unconventional agents of proteic nature that are formed of abnormal
conformations of the host-encoded prion protein (PrP). They cause
fatal neurodegenerative diseases in both animals and humans and can
be transmitted between species, as exemplified in humans by the
emergence of variant Creutzfeldt-Jakob disease following the epidemic
of bovine spongiform encephalopathy (BSE) in the United Kingdom.
Since diagnosis of prion infection is only possible once the central
nervous system has been invaded, brains of slaughtered or fallen
cattle are routinely screened in Europe to protect the consumers from
BSE. This has unexpectedly led to the discovery of unprecedented PrP
conformations that were distinct from the single one associated so
far with BSE or BSE-related diseases. To precisely determine their
etiology, the authors have studied the transmissibility of these new
conformations, termed H-type, to transgenic mice expressing either
bovine or ovine PrP. They show that these cases are highly pathogenic
for these mice. The authors also demonstrate that they are not
directly related to the agent involved in the BSE epidemic,
supporting the view for isolation of a new prion strain from cattle,
whose prevalence and associated zoonotic risk should be carefully
monitored in the future."

Terry S. Singeltary Sr

[see also:
CJD (new var.) update 2006 (10) 20061002.2820
CJD (new var.) update 2006 (09) 20060904.2519
CJD (new var.) update 2006 (08) 20060807.2207
CJD (new var.) update 2006 (07) 20060703.1831
CJD (new var.) - Netherlands: 2nd case 20060623.1741
CJD (new var.) update 2006 (06) 20060605.1566
CJD (new var.) update 2006 (05) 20060508.1332
CJD (new var.) update 2006 (04) 20060404.1005
CJD (new var.) update 2006 (03) 20060306.0728
CJD (new var.) - UK: 3rd transfusion-related case 20060209.0432
CJD (new var.) update 2006 (02) 20060206.0386
CJD (new var.) update 2006 (01) 20060111.0101
CJD (new var.) update 2006 20060111.0101
CJD (new var.) update 2005 (12) 20051209.3547
CJD (new var.) update 2005 (11) 20051108.3270
CJD (new var.) update 2005 (10) 20051006.2916
CJD (new var.) update 2005 (05) 20050505.1243
CJD (new var.) - UK: update 2005 (01) 20050111.0095
CJD, genetic susceptibility 20041112.3064
CJD (new var.) - UK: update 2004 (14) 20041206.3242
CJD (new var.) - UK: update 2004 (01) 20040106.0064
CJD (new var.) - France: 8th case 20041022.2864
CJD (new var.) - France: 9th case 20041123.3138
CJD (new var.), blood supply - UK 20040318.0758
CJD (new var.), carrier frequency study - UK 20040521.1365
CJD (new var.) - UK: update 2003 (13) 20031216.3072
CJD (new var.) - UK: update 2003 (01) 20030108.0057
CJD (new var.) - UK: update Dec 2002 20021207.5997
CJD (new var.) - UK: update Jan 2002 20020111.3223
CJD (new var.), incidence & trends - UK (02) 20011124.2875
CJD (new var.), incidence & trends - UK 20011115.2816
CJD (new var.) - UK: reassessment 20011029.2671
CJD (new var.) - UK: update Oct 2001 20011005.2419
CJD (new var.) - UK: regional variation (02) 20010907.2145
CJD (new var.) - UK: update Sep 2001 20010906.2134
CJD (new var.) - UK: update Aug 2001 20010808.1872
CJD (new var.) - UK: 9th Annual Report 20010628.1231
CJD (new var.) - UK: update June 2001 20010622.1188
CJD (new var.) - UK: update 3 Jan 2001 20010104.0025]

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Full Text

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

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




Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518

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