Wednesday, December 23, 2009

Just nine cases of BSE recorded in Ireland this year

The Irish Times - Thursday, December 24, 2009

Just nine cases of BSE recorded in Ireland this year

SEÁN Mac CONNELL Agriculture Correspondent

IRELAND RECORDED only nine cases of bovine spongiform encephalopathy (BSE) this year compared with 23 cases last year, official figures show.

From a high of 333 cases in 2002, there has been a dramatic fall in the disease of the central nervous system of animals which scientists believe was caused by contaminated animal feed.

The disease was first identified in Britain in the mid-1980s. It took years and multiple human deaths and the slaughter of millions of infected animals in Britain before scientists discovered even tiny amounts of contaminated feed could trigger the disease.

Although the feeding of meat and bone meal to ruminants had been banned in the EU from early in the crisis, contamination of feed had continued at feed mills where there was cross-contamination of cattle feed by feed for other animals. When feed at mills and compounders was segregated, there was a dramatic fall in animal infections.

Since 2002, over 700,000 animals per annum were tested in Ireland up to 2008.

Ireland was on May 30th, 2008, declared by the World Animal Health Organisation as having a “controlled risk for BSE”, which was a significant landmark.

The organs in animals where the disease resides continue to be removed from cattle and destroyed before an animal is processed for human consumption.

Transmissible Spongiform Encephalopathies (including Bovine Spongiform Encephalopathy and Scrapie) in Northern Ireland

Information related to Transmissible Spongiform Encephalopathies (such as Bovine Spongiform Encephalopathy (BSE) and Scrapie) in Northern Ireland.

What is BSE?

It is a brain disease of cattle for which there is no treatment or cure

BSE is confirmed after death of the animal by examining it’s brain tissue

BSE is notifiable and there is a DARD slaughter and compensation scheme in Northern Ireland

Advisory Leaflet on BSE

How many confirmed cases of BSE in cattle have there been in Northern Ireland?

Between 1988 and 2008, a total of 2183 cattle in 1511 herds have been confirmed as cases of BSE.

Confirmed BSE cases in Northern Ireland

What is Scrapie?

Scrapie is a fatal brain disease of sheep.

Scrapie is notifiable

Signs of scrapie should not be ignored, but should be tackled before it becomes a flock problem.

How many confirmed cases of scrapie in sheep have there been in Northern Ireland?

Between 2000 and 2008, a total of 52 sheep in 23 flocks have been confirmed with scrapie.

Number of Scrapie Cases

About BSE in Ireland

Over the period 1990-2008 the average crude annual mortality rates from sporadic CJD per million population were 0.94 in England, 1.08 in Wales, 0.96 in Scotland and 0.58 in Northern Ireland (Table 1). When account is taken of age and sex, the variation in recorded mortality between the different countries is not statistically significant (p=0.4).

Table 1 Deaths from definite and probable sporadic CJD by region and county of death: 1st January 1990 to 31st December 2008


18 (0.58)

CJD, vCJD- Communication Experience in Ireland 1998 – FVIII recall due to donor who had a risk factor for CJD ( Dura matter Transplant) 2004 – UK HPA Risk assessment on products used by 50 people in Ireland 2006 US FDA Risk Assessment on UK Products 2008 – Man with Haemophilia in UK had Prions in his spleen at autopsy

vCJD Cases

Ireland – 4

FX Deficiency - 2004 Concentrates derived from UK Plasma were imported and used in Ireland No Implicated batches used Non UK Plasma product now used

1998 • FVIII recall due to donor who had a risk factor for CJD ( Dura matter Transplant) ( Ireland) • Last year BSE in food chain

vCJD Timeline so far in UK / Ireland 2004 • UK HPA Risk assessment on blood and blood products. • All persons with Haemophilia who used UK plasma derived FVIII or FIX between 1980 and 2001 are assumed to have a 1% additional risk of vCJD infection for public health purposes • These UK products were never imported into or used in the Republic of Ireland • 50 Persons with Haemophilia used UK plasma derived product in the UK or Ireland • 3 Used implicated batches

vCJD 2009 - Ireland Day 1( Sunday 17th Feb) – story broke in UK media Day 2 ( Monday 18th Feb) – Letter signed jointly by Barry White and I H S and sent from both centre and Society to all patients. - Embargoed Press release issued and Press Conference organised for Day 3 - Clinicians began task of personally calling those who had received UK Plasma derived product

The Irish Times - Tuesday, March 3, 2009

Haemophiliac infected with vCJD sparks concern


THE DISCOVERY that a haemophiliac who died in Britain last year had evidence of variant CJD or vCJD infection has led to just over 30 people ringing a helpline specifically set up to respond to the issue. The helpline was aimed at people who had received UK-derived plasma products or had concerns about blood products they received.

Two information meetings were held in Dublin and Cork at the weekend to further allay concerns and were attended by a handful of people.

It emerged two weeks ago that the elderly man, who did not die from vCJD, was infected from a UK plasma-derived product known as Factor VIII. Haemophilia and related bleeding disorders are caused by a lack of clotting factors and are treated by products containing clotting factor concentrate such as Factor VIII.

Since the late 1990s, Ireland has been using a synthetic clotting concentrate.

On hearing the details of the man’s death, the National Haemophilia director Dr Barry White and the Irish Haemophilia Society’s Brian O’Mahony wrote to the 50 Irish patients who had received UK plasma-derived products to inform them of developments.

Only two of those had received a product that was subsequently identified as being at risk of vCJD. Thousands of people in the UK have received products where some of the donors developed vCJD, but none of the recipients have developed symptoms.

There have been 167 cases of vCJD in the UK and four in Ireland since the link between eating infected meat and a new variant of CJD was made in the mid-1990s.

Some nine people who died of vCJD in the UK had donated blood for the manufacture of clotting factor concentrates.



Thirty-one vCJD cases were reported to have been blood donors. Four additional cases who were not reported to have been blood donors were found to be registered with UKBTS. One of these cases was found to have been a blood donor while the other three cases were registered as donors but never made any donations. Twenty-four of the cases have been traced at blood centres including the four additional cases mentioned above. Components from 18 of these individuals were actually issued to hospitals. It has been established that 66 components were transfused to named recipients (44 dead, 22 alive).

Four instances of probable transfusion transmitted infection have been identified. The first recipient (Case 1) developed symptoms of vCJD 6½ years after receiving a transfusion of red cells donated 3½ years before the donor (Donor 1) developed symptoms of vCJD. The second recipient (Case 2) died from a non-neurological disorder 5 years after receiving blood from a donor (Donor 2) who subsequently developed vCJD; protease-resistant prion protein (PrPres) was detected in the spleen but not in the brain. This is the first recorded case in the UK of autopsy detection of presumed pre- or sub-clinical vCJD infection. The third recipient (Case 3) developed symptoms of vCJD 7 years, 10 months after receiving a transfusion of red cells donated about 21 months before the donor (Donor 3) developed symptoms of vCJD. The fourth recipient (Case 4) who also received a transfusion from the same donor as Case 3, developed symptoms of vCJD 8 years, 4 months after receiving a transfusion of red cells donated about 17 months before this donor (Donor 3) developed symptoms of vCJD. (see publications).

These findings strongly suggest that vCJD may be transmitted via blood transfusion. The identification of a third case of vCJD in this small cohort of known recipients of blood from persons incubating vCJD establishes beyond reasonable doubt that blood transfusion is a transmission route.

In the reverse study, 15 vCJD cases were reported to have received blood transfusions in the past. A further case received a blood transfusion after onset of illness. This case is excluded from the figures quoted. Checks revealed that of these 15 cases, one was not transfused, 4 had transfusions which pre-dated available records (pre 1980), and 10 had records of transfusion which could be traced (see vCJD cases who received blood transfusion(s) in the past). These 10 had received 209 donor exposures (with one patient given 103 components), which have been traced to 192 named donors (two of whom had vCJD as described above).

DoH goes for 'do nothing' option on tests for vCJD

Dara Gantly

The IBTS has called on the Department of Health to re-establish an expert advisory group on vCJD to safeguard the blood supply, reports Dara Gantly

The Department of Health believes that a number of ‘significant issues’ need to be addressed before it can consider funding a new test for variant Creutzfeldt Jakob disease (vCJD).

An investigation by Irish Medical Times has revealed that Chief Medical Officer Dr Tony Holohan believes the Department has not received enough scientific evidence on a number of key issues to be in a position to make an adequate assessment of whether prion testing or prion filtration should be adopted to safeguard Ireland’s blood supply.

The Irish Blood Transfusion Service (IBTS) submitted a detailed ‘options appraisal paper’ to the Department in April on the possible avenues open to the Minister for Health on the issue. These include: doing nothing; testing all donations; filtering all donations; filtering blood for younger recipients; combined filtration and testing; or filtering all red cells for children this year until the picture around testing becomes clearer. The cost of these options range from zero (doing nothing) up to E75 million over five years. The ‘doing nothing option’ won out.

Robust decision making

In a letter from the IBTS to Minister Mary Harney the previous month, Chairperson Maura McGrath said the proposals on prion filtration of blood components and a test for vCJD would require ‘robust decision making on the part of the Minister’. However, the Department has informed IMT that more detailed data and documentation on the effectiveness of the different technologies is still required, as well as more information on possible negative impacts, including the potential for ‘false positive’ individuals and a decrease in blood donation levels.

Along with the substantial cost of adopting the technologies — which the IBTS says it cannot meet within its current resources — prion testing may well cause donor distress and loss of donations due to difficult-to-resolve false positives. With no effective treatment or cure for vCJD, there is no diagnostic or prognostic value for an individual in knowing that one has the disease. Filtering, meanwhile, reduces the red cell content of blood units by 20 per cent, the clinical significance of which remains unclear.

The IBTS has ‘urgently’ called on the Minister to re-establish the vCJD Advisory Committee, set up when the Bovine Spongiform Encephalopathy (BSE, or ‘mad cow’ disease) epidemic first emerged in the UK. The Irish independent expert group, chaired by UCD’s Prof Bill Hall, has not met since January 2006.

Speaking to IMT, IBTS CEO Andrew Kelly said: “There needs to be an objective group to look at information that we submit — another voice of advice to the Minister.” However, the Department has rejected the request, despite the IBTS informing the Minister and her Secretary General Michael Scanlan that it was necessary to have such a ‘competent resource’ available to the Department.

While no other country has yet adopted either prion testing or filtration, it is possible that the UK and France, the other two countries most at risk from vCJD, will make a decision later this year. The filter is already in use in clinical studies in Ireland and the UK where it is performing satisfactorily to date and could be now more extensively deployed.

IBTS Medical and Scientific Director Dr Willie Murphy told IMT that use of the filter has been examined as part of a safety study in 20 patients from Cork, and a further hundred units are being transfused in Cavan General Hospital, where the system is in routine use. “We need some more experience in paediatrics, so we plan to use it at Crumlin Hospital, probably starting next month,” Dr Murphy explained. He added that while some ‘caution’ was needed to ensure safety before rolling it out to 100,000 people a year, the IBTS was ready to do so.

Variant CJD, a fatal neurodegenerative disease, is the human form of BSE. The most likely cause is exposure to the BSE agent, most plausibly due to dietary contamination by affected bovine central nervous system tissue. While vCJD transmission by transfusion is very unlikely in Ireland, the risk is not zero.

Over the past 10 years, the IBTS has taken measures to try to offset any risk of transmitting vCJD from blood transfusion, including no longer accepting donations from people who have spent one year or more in the UK between 1980 and 1996.

Replacing cryoprecipitate

It has also: deferred people who have had a blood transfusion in the past; implemented leucodepletion of red cells, platelets and plasma products; replaced plasma for clinical use from Irish donors with virus inactivated plasma from the US; and is currently replacing cryoprecipitate (made from Irish plasma) with fibrinogen concentrate made from US plasma.

The scale of the threat of vCJD, both from diet and blood transfusion, has diminished over the past decade, and any threat that remains is much smaller than once feared. Nevertheless, the IBTS believes some risk remains, and although this is likely to be small, the Service says it is important to maintain its ‘highly proactive stance in relation to this disease’.

Documents obtained through the Freedom of Information Act reveal that the IBTS Board, at its meeting on February 17, received a presentation from its Director of Testing, Dr Joan O’Riordan, on the current state of tests for vCJD. She explained that the best estimate was that there could be one or more infectious donors in the donor population — however there may well be none.

Leucodepletion — the removal of white blood cells from a blood component — may well have been effective in preventing transmission. However, Dr O’Riordan said the IBTS could not be certain of this. An infectious donor in the platelet apheresis panel could be ‘catastrophic’ if leucoreduction hasn’t worked. While this was extremely unlikely, it would be ‘an intolerable risk’ if a feasible test was developed.

Almost a decade has elapsed since the last known transmission of the disease happened in the UK, suggesting that either leucoreduction may be effective in preventing transmission, or that the number of infectious asymptomatic donors is small. However, as experts believe that vCJD can be asymptomatic for about 10 to 16 years, there is no accurate way to determine either how many people could currently be harbouring the disease or the magnitude of future cases.

The incidence of vCJD in Ireland is second to that of the UK, and ahead of France.

Since 1996, a total of 208 patients from 11 countries have been identified. As of June 2008, cases have been reported from the following countries: 167 from the UK (1 per 350,000 population), 23 from France (1 per 3 million), four from Ireland (1 per million), three from the US, three from Spain, two in the Netherlands, two in Portugal, and one each from Canada, Italy, Japan, and Saudi Arabia. Two of the three US cases, two of the four cases from Ireland and the single cases from Canada and Japan were likely exposed to the BSE agent while residing in Britain.

So what are other countries doing? Last month (July 17), the NHS Blood and Transplant (NHSBT) authority in Britain awarded tenders to two companies — Amorfix Life Sciences and Prionics — to supply prion testing of blood donations. Due to the new and still emerging technologies, the NHSBT said it required suppliers to submit their systems for independent evaluation of performance. This evaluation will initially assess the specificity of the assay on 10,000 stored (frozen) plasma samples from blood donations from the UK and the United States. One would not expect to find any positive vCJD in the US samples.

A spokesperson for the NHSBT told IMT that the tender related to evaluation only, and that the decision to roll out this technology would be taken by the UK Department of Health, which is guided by the advisory committee on the Safety of Blood Tissues and Organs (SaBTO).

On prion filtration, reports have suggested that SaBTO believes implementing this would not be cost-effective under the majority of scenarios modelled for risk. The UK government is expected to decide in October whether or not this method should be introduced. In June, Amorfix also announced that it had tested 20,000 blood donations in France — the next country hardest hit by vCJD — using its EP-vCJD blood screening test as part of a large-scale study to demonstrate the feasibility of routine testing of blood donations.

100 per cent specific

At the UK specification of a required sensitivity of 1:100,000 dilution of vCJD brain, the company said its test was 100 per cent specific with no false positive samples on repeat testing. The test performed five times better than required as it was still 100 per cent specific at a sensitivity of 1:500,000 dilution of vCJD brain.

“France has taken a leading role in assessing the feasibility of testing routine blood donations for vCJD by establishing the Amorfix test in two major blood transfusion centres,” explained Dr George Adams, CEO of Amorfix. “The Amorfix test continues to demonstrate its readiness for use by high-risk nations to conduct prevalence studies to assess the safety of their blood supply.”

The IBTS is working closely with the UK and is planning on the basis that a test will become available this year. IBTS CEO Andrew Kelly believes the position should become clearer in the autumn. “We will be seeking a meeting with the Department of Health so that we can make sure we are all clear as to what action needs to be taken and when it needs to be taken to further minimise the risk,” he told IMT. According to correspondence from IBTS Chairperson Maura McGrath to Minister Harney, sent in March, the recent case of the haemophilia patient in the UK who was discovered to have vCJD, at autopsy, confirms that this issue needs to be dealt with ‘at the highest level’ to ensure that appropriate measures are taken to prevent onward transmission from transfusion and from other sources such as surgical instruments and endoscopes.

The Irish Government will obviously be keeping a close eye on developments in both the UK and France. But if either country fully adopts filtration and testing, will Ireland be forced to follow suit? “If we were seen to lag on this then the pressure on the Government would become unbearable,” predicted Dr Murphy. See part two next week for options open to Ireland. Posted in Guests on 21 August 2009 Tags: blood, Department of Health, IBTS

Report to the Board of Directors: Current Status of TSEs and Transfusion Safety

Executive Summary:

There continues to be concern about transmission of variant Creutzfeldt Jakob disease (vCJD) by blood transfusion, with a total of 4 reported cases, plus a potential case of transmission of the prion via a UK-derived plasma derivative, known to have contained potentially infectious donations. Some infections (but no disease) have been found among individuals who are not homozygous for MM at the 129 codon of the PRP gene, raising concern about a possible second wave of disease and an expanded group of potential carriers. There has been no published progress in blood donor testing technologies. One method for prion removal from red cell concentrates has been evaluated by authorities in the UK and Ireland.

Information about transfusion transmitted infectivity:

There have now been a total of four cases of transmission of the vCJD prion by transfusion of blood collected from three donors who subsequently developed vCJD. Three of the cases resulted in the development of vCJD in the recipient, while one was detected in the spleen and one lymph node of a transfused patient who died of other causes. This individual had no symptoms of vCJD (1, 2). Interestingly, he was found to be (MV) heterozygous at codon 129 of the PrP gene. The potential significance of infection among non MM genotypes is discussed briefly below. More recently, evidence of pathologic vCJD prions was found in a hemophilic recipient of F VIII concentrates known to have included plasma from a donor who subsequently developed vCJD (3). Again, the recipient patient was free of vCJD symptoms. Modeling studies imply that the infection was most likely to have come from the plasma products (4).

In a paper published in Transfusion, American Red Cross authors reported on the absence of evidence of transmission of classic CJD from donors who subsequently developed the disease. The study involved lookback on 436 recipients of donations from a total of 36 donors who developed the disease subsequent to their donation, finding no cases of CJD among the recipients. A subset of recipients with exposure histories comparable to the UK cohort of patients exposed to vCJD was shown to be at lower risk of developing CJD: a statistically significant (p = 0.012) observation. This supports the absence of infectivity of classic CJD via transfusion (5).

Risk modeling for recipients of plasma derivatives in the US:

As a result of the finding of the vCJD prion in a hemophilia patient (described above), and the findings of vCJD prions among non MM individuals, the US FDA has revised its model of the vCJD transmission risk for recipients of US-derived plasma derivatives. The new models were presented at a meeting of the Transmissible Spongiform Encephalopathies Advisory Committee in June, 2009. Although the lowest estimated annual per-person risk has risen 5 to 18-fold, it may still be as low as 1 in 12 million and the maximal estimated risk remains unchanged at 1:12,000, the FDA still regards the risk to US patients to be “extremely small”.

Implications of findings of vCJD prions in non MM individuals:

There are several variations at codon 129 of the human PrP gene, resulting in 3 main genotypes, MM, MV and VV, where M signifies methionine and V, valine. To date, all symptomatic cases of vCJD who have been evaluated have been MM homozygous at the 129 codon. Approximately 40% of the UK population has this genotype. However, there have been a number of circumstances (some described above) in which the pathologic prion has been found in asymptomatic individuals with the MV or VV genotype. This has raised two questions. The first is whether there will be a “second wave” of vCJD among individuals with a non MM genotype, perhaps resulting from a much extended incubation period. Second is the question of whether non MM individuals can be infectious carriers of the vCJD prion. This latter concern was included in the newer FDA infectivity model for US-derived plasma derivatives. Both questions await resolution.

Status of interventions against transfusion transmission of TSEs:

No significant progress has been reported in the development of any pre-mortem test that could be used for blood donors or donations, although one of the tests under development has undergone some preliminary clinical evaluatation.

Currently, one manufacturer has an available, CE-marked affinity filter intended for use with leukoreduced red-cell concentrates. The procedure has been evaluated in the UK and Ireland, but no decision has been made with respect to its implementation. A process has also been developed for use in the manufacture of solvent-detergent treated plasma for transfusion.


1. Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt–Jakob disease and blood transfusion: results of the UKTransfusionMedicine Epidemiologic Review study. Vox Sang 2006;91:221-30.

2. Health Protection Agency. CDR weekly, Vol. 16 No 6; 9February 2006. [cited 2009 May]. Available from:

3. Health Protection Agency. Asymptomatic vCJD abnormal prion protein found in a haemophilia patient. [cited June 2009]. Available from:

4. Health Protection Agency. vCJD Risk assessment calculations for a patient with multiple routes of exposure.

5 . Dorsey K, Zou S, Schonberger LB, Sullivan M, Kessler D, Notari E 4th, Fang CT, Dodd RY. Lack of evidence of transfusion transmission of Creutzfeldt–Jakob disease in a US surveillance study. Transfusion 2009;49:977-84.

Prepared by TTD Committee, October, 2009.

Friday, November 20, 2009

SaBTO Advisory Committee on the Safety of Blood, Tissues and Organs Summary of the Eighth Meeting, 27 October 2009

Since variant CJD was first reported in 1996, a total of 217 patients with this disease from 11 countries have been identified. As of October 2009, variant CJD cases have been reported from the following countries: 170 from the United Kingdom, 25 from France, 5 from Spain, 4 from Ireland, 3 from the United States, 3 in the Netherlands, 2 in Portugal, 2 in Italy, and one each from Canada, Japan, and Saudi Arabia. Two of the three U.S. cases, two of the four cases from Ireland and the single cases from Canada and Japan were likely exposed to the BSE agent while residing in the United Kingdom. One of the 25 French cases may also have been infected in the United Kingdom.

There has never been a case of vCJD that did not have a history of exposure within a country where the cattle disease, BSE, was occurring.

It is believed that the persons who have developed vCJD became infected through their consumption of cattle products contaminated with the agent of BSE or in three cases, each reported from the United Kingdom, through receipt of blood from an asymptomatic, infected donor. There is no known treatment of vCJD and it is invariably fatal.



Republic of Ireland 4 (0)

Thursday, December 17, 2009

An Unusual Case of Variant CJD 18 December 2009

Saturday, December 12, 2009


Thursday, March 12, 2009

Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study ?




Tuesday, December 15, 2009

Intraspecies transmission of L-type-like bovine spongiform encephalopathy detected in Japan


Intraspecies transmission of L-type-like bovine spongiform encephalopathy detected in Japan

Shigeo Fukuda 1*, Yoshifumi Iwamaru 2*, Morikazu Imamura 2 , Kentarou Masujin 2 , Yoshihisa Shimizu 2 , Yuichi Matsuura 2 , Yujing Shu 2 , Megumi Kurachi 2 , Kazuo Kasai 2 , Yuichi Murayama 2 , Sadao Onoe 1 , Ken'ichi Hagiwara 3 , Tetsutaro Sata 4 , Shirou Mohri 2 , Takashi Yokoyama 2 and Hiroyuki Okada 2 1 Molecular Biotechnology Laboratory, Hokkaido Animal Research Center, Shintoku, Hokkaido 081-0038, Japan 2 Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kan-nondai, Tsukuba, Ibaraki 305-0856, Japan 3 Departments of Biochemistry and Cell Biology , and 4 Pathology, National Institute of Infectious Diseases, Toyama 1-23-1 Shinjuku-ku, Tokyo, 162-8640, Japan Correspondence Hiroyuki Okada, Prion Disease Research Center, National Institute of Animal Health, Kannonndai 3-1-5, Tsukuba, Ibaraki 305-0856, Japan. Tel & fax: +81-29-838-7757; email:

*These authors contributed equally to this work.

Copyright © 2009 Japanese Society for Bacteriology, Japanese Society for Virology, Japanese Society for Host Defense Research, and Blackwell Publishing Asia Pty Ltd KEYWORDS atypical bovine spongiform encephalopathy • cattle • L-type-like • transmission


It has been assumed that the agent causing BSE in cattle is a uniform strain (classical BSE); however, different neuropathological and molecular phenotypes of BSE (atypical BSE) have been recently reported. We demonstrated the successful transmission of L-type-like atypical BSE detected in Japan (BSE/JP24 isolate) to cattle. Based on the incubation period, neuropathological hallmarks, and molecular properties of the abnormal host prion protein, the characteristics of BSE/JP24 prion were apparently distinguishable from the classical BSE prion and closely resemble those of bovine amyloidotic spongiform encephalopathy prion detected in Italy.


Received 7 May 2009; revised 2 August 2009; accepted 4 August 2009.

DIGITAL OBJECT IDENTIFIER (DOI) 10.1111/j.1348-0421.2009.00169.x About DOI


In Japan, two atypical BSE cases have been identified to date. The first case showed an L-type-like electrophoretic mobility of the unglycosylated PrPSc on western blot analysis (9). The second casewas identified in an aged beef cattle, Japanese Black (BSE/JP24), and showed PrP-positive amyloid plaques in histopathological examination of the brain and a distinct glycoformprofile (10). Although such properties seem to be similar to those reported in a BASE case (7), unlike with the BASE prion, shortening of the incubation periods was observed in bovinized mice serially passaged with the BSE/JP24 prion (11). Thus, it remains controversial whether the BSE/JP24 prion is identical to the BASE prion. These observations prompted us to characterize the phenotypes of the BSE/JP24 prion propagated in its natural host by comparison with those of the classical BSE prion. Hence, we have inoculated with brain homogenates from classical BSE and BSE/JP24 isolates into Holstein cattle and assessed their risk against cattle species.


In summary, we demonstrated the successful transmission of the BSE/JP24 prion to cattle. The BSE/JP24 prion-affected cattle sustained the molecular properties of PK-treated PrPSc as those of the original BSE/JP24 isolate. Although most brain regions except for the medulla oblongata of the original BSE/JP24 isolate were unable to be investigated due to inadequate specimen collection, in comparison to experimentally BSE/JP24 prion-affected cattle, both neuropathological features, such as severe vacuolation in the medulla oblongata at the obex level and the presence of PrPSc plaques, closely resembled each other. Based on molecular properties of PK-treated PrPSc and a detailed comparison of the immunohistochemical and neuropathological properties, the BSE/JP24 prion was distinguishable from those in the classical BSE prion, and appear to be rather similar to the BASE prion (8). Of interest, experimental transmission of the BSE/JP24 prion to cattle induced a shorter incubation period and more severe neuropathological changes compared to the classical BSE prion, suggesting that the BASE and BSE/JP24 prion might be more virulent in cattle species. However, such speculation conflicts with reports that atypical BSE field cases have been mainly found in adult and aged cattle (5). The reason for this discrepancy in incubation periods between experimentally and naturally affected cattle is unknown. These observations may imply that atypical BSE are sporadic forms of BSE. Alternatively, the route of infection and/or prion titer may be attributed to the relatively long incubation period in natural atypical cases. Further studies using orally BSE/JP24 prion-affected cattle will be needed to address this issue.

>>> These observations may imply that atypical BSE are sporadic forms of BSE.

PLEASE SEE BELOW "So far, there is no evidence for spontaneous PrPSc formation in any animal or human TSE."

Prions: Protein Aggregation and Infectious Diseases


Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland


3. Sporadic Creutzfeldt-Jakob disease Approximately 85% of all human prion diseases are sporadic forms of CJD. For sCJD, there is no association with a mutant PRNP allele, nor is there any epidemiological evidence for exposure to a TSE agent through contact with people or animals infected with TSEs. sCJD cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the size and glycoform ratio of proteaseresistant prion protein identified on western blot (type 1 or type 2) (174). Heterozygosity (Met/Val) at PrP codon 129 appears to be associated with a lower risk (378) and/or prolonged incubation time (119, 387). The lack of routine laboratory testing for preclinical diagnosis makes the search for agent sources and other risk factors extremely difficult. At present, the means of acquisition of a TSE agent in these patients remains a mystery. So far, there is no evidence for spontaneous PrPSc formation in any animal or human TSE. In humans, the peak age incidence of sporadic CJD is 55–60 years. However, if spontaneous misfolding were the primary event, one might expect a continuously increasing incidence with age because more time would allow more opportunity for rare misfolding events.


Physiol Rev • VOL 89 • OCTOBER 2009 •

O.11.2 Transmission of bovine-passaged TME prion strain to macaque Emmanuel Comoy1, Juergen Richt2, Valérie Durand1, Sophie Freire1, Evelyne Correia1, Amir Hamir2, Marie- Madeleine Ruchoux1, Paul Brown1, Jean-Philippe Deslys1 1Atomic Energy Commission, France; 2National Animal Disease Center, USA Background: The origin of Transmissible Mink Encephalopathy (TME) remains controversial, with historical evidence for either scrapie or BSE as the source of separate outbreaks. The case for BSE is supported by the experimental transmission of BSE from cattle to mink, whereas scrapie failed to transmit from sheep to mink. Transmission of TME from mink to cynomolgus macaque is inefficient, suggesting a low risk of TSE to human health. Because only typical and atypical BSE prion strains have been shown to be easily transmissible from non-primate to primate species, we have investigated transmissibility to monkeys of a cattle-passaged strain of TME. Objectives: To compare the transmissibility of cattle-passaged TME prions to the transmissibility of other cattle-passaged prions. Methods: Monkeys (cynomolgus macaques) were intra-cerebrally infected with classical BSE, atypical BSE strains (BASE and BSE H), and a cattle-passaged TME strain. Animals were regularly monitored for clinical signs, and extensive biochemical and immunohistochemical studies were performed on lymphoid and neural tissues of animals that have already died. Results and discussion: The animal infected with the cattlepassaged TME strain developed neurological clinical signs after a very short incubation period of 20 months, with a clinical picture that is clearly different from that of BSE/vCJD-infected animals, but similar to that of BASE (the animal is still alive at the time of this writing but post-mortem histopathological and immunohistochemical analyses will provide a more complete characterization of the disease). This new transmission reinforces the notion of human vulnerability to prion diseases passaged through cattle, perhaps due to a low species barrier.

Selected by the scientific committee from the submitted abstracts

O.11.3 Infectivity in skeletal muscle of BASE-infected cattle Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta” Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot. Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE. Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.

Selected by the scientific committee from the submitted abstracts

P.9.21 Molecular characterization of BSE in Canada Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle. Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis. Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE. Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.

P.4.23 Transmission of atypical BSE in humanized mouse models Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined. Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared. Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far. Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed. Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

Subject: Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION

Date: August 24, 2005 at 2:47 pm PST

August 24, 2005

Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION

Greetings APHIS ET AL,

My name is Terry S. Singeltary Sr.

Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009


Thursday, November 05, 2009 9:25 PM

Subject: [BSE-L] re-FOIA REQUEST ON FEED RECALL PRODUCT contaminated with prohibited material Recall # V-258-2009 and Recall # V-256-2009

Tuesday, November 17, 2009


Saturday, December 01, 2007

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model Volume 13, Number 12–December 2007 Research

Monday, November 23, 2009


Wednesday, November 18, 2009

R-CALF: 40 Groups Disagree With USDA's Latest BSE Court Submission

Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans

Wednesday, September 9, 2009

Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics.

Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


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