CREUTZFELDT JAKOB DISEASE: A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014 with increasing trends of incidence and mortality

A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014

Yoshito Nishimura, Ko Harada, Toshihiro Koyama, Hideharu Hagiya & Fumio Otsuka

Abstract

In the era of hyper-ageing, Creutzfeldt–Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005–2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4–5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7–8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

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Discussion

Our study revealed an increase in the absolute number of deaths, mortality rates, and incidence rates associated with CJD—even after age-adjustment—in Japan between 2005 and 2014. The significantly increasing trends in the CJD-associated mortality and incidence rates were especially prominent in the older age groups. Previous surveillance data and reviews have described that comparable increasing trends in both mortality and incidence of CJD have been observed globally. According to the latest report from the Creutzfeldt–Jakob Disease International Surveillance Network, annual mortality rates of sCJD had risen in the most participating countries from 1993 to 201821. In European countries including the Czech Republic, Slovakia, and the United Kingdom, increases in the sCJD incidence have been reported22,23,24. According to these studies and the current data, it should be noted that Japan might have had higher CJD incidence (more than 4.5 per million in 2014) than other countries. While CJD has been considered a rare disease, the phenomenon of population ageing may trigger a rise in the incidence of CJD and the attendant socioeconomic and healthcare burdens.

According to the previous CJD-associated mortality analysis conducted from 1979 to 2004 in Japan20, the crude mortality rate reached a peak of 1.3 per million in 2004. Our analysis indicates that the steep trend has continued, with 4.1 cases of CJD per million accounted for in 2014 (Supplementary Table S1). While the number of CJD-associated deaths was highest in the 70–79 years age group from 1979 to 2004 in Japan, our crude mortality analysis showed a predominant upward trend among individuals of over 80 years of age, indicating a shift in the CJD disease burden to the more aged population. Concerning the age-adjusted mortality, our results show a continuously increasing trend across the study period, with an APC of 3.7% among men and of 2.9% among females. These results agree with those found by Doi et al., with an age-adjusted mortality of 3.1% among men and 3.9% among women. This increasing trend suggests that CJD will soon aggravate the disease burden in the hyper-ageing Japanese society.

The increased CJD-associated mortality rates could be explained by the rise in the rate of CJD incidence. The prognosis of CJD is considered poor, with uniform fatality and a median life expectancy of about 6 months after diagnosis worldwide25,26. Hence, as was observed in the present study, the mortality and incidence rates are almost identical. Various factors could account for the increase in the rates of CJD incidence: e.g., increased awareness of the disease1, improvement in the accuracy of diagnostic tests2, and demographic changes characteristic of a hyper-ageing society. While the upward trends in the rates of mortality and incidence may be partly attributable to improvements in diagnosis, we propose the ageing of the population as an important contributor to the CJD trends in Japan.

According to the Japanese national statistics, the population of individuals of over 65 years of age was 35.58 million in 2018, accounting for 28.1% of the whole population27. The Japanese surveillance data indicates that approximately 80% of the CJD patients in Japan were sCJD, which is more common among older individuals28. Hence, if the increased CJD-related incidence and mortality are primarily attributable to sCJD, it follows that both rates would rise as the population ages. These observations are compatible with our study results, which suggest that the number of CJD-associated deaths was highest in the age groups of 70–74 and 75–79 years. From a pathophysiological perspective, age may increase the rate of prion protein conversion: the etiological agent of prion diseases, including CJD6,7,29. Also, in our study population, women experienced higher CJD-associated deaths and incidence than men, although it has been generally considered that there is no gender predilection for CJD12. A possible explanation for the differences in CJD according to sex may be postmenopausal decreased serum oestrogen levels, which could facilitate the maintenance of cellular pathological prion protein30. Hence, the cellular mechanism underlying prion diseases also suggests that the incidence and mortality of sCJD would increase in ageing populations.

Considering that dementia has been reported in almost all cases of CJD in Japan28, the increasing incidence of CJD is even more alarming. According to the latest WHO statistics, about 50 million people in the world are estimated to have dementia31, imposing a substantial worldwide socioeconomic burden; the global social costs due to dementia were estimated to be 1.1% of the global gross domestic product in 201532. Approximately 4.7 million people were living with dementia in Japan in 2015. This figure is projected to rapidly increase to 7 million people by 202533. Recognising the pressing global concern about dementia, the G20 Health Ministers stressed the importance of developing national strategies to improve the quality of care and life of the patients with dementia as well those of their caregivers17. It should further be noted that Japanese patients with CJD were reported to have a longer life expectancy (20.9 months on average) following diagnosis than those from other countries (approximately 6 months as noted above)28, which would pose additional socioeconomic impacts on the patients’ caregivers if the mortality and incidence rates continue to rise at the current rates34. While CJD still remains a rare disease, the trends identified by the present study warrant attention by public health authorities and indicate the need for effective policy measures to mitigate the disease burden of CJD, from caregiver’s perspectives in particular.

While this study benefits from being the first to use national vital statistics and surveillance data to perform a joinpoint regression analysis of trends in CJD-associated incidence and mortality in Japan, it is subject to several limitations. First, as we analysed the causes of death based on the information provided by death certificates, we may have underestimated the CJD-associated death rates. Second, the rate of CJD incidences could have been further underestimated due to the voluntary nature of the CJD surveillance. Third, we used a specific ICD-10 code (A81.0 “Creutzfeldt–Jakob disease”) from the vital statistics to obtain our data, which made it impossible to determine the accuracy of the recorded causes of death. Specifically, the patients with CJD may have a number of complications, such as infections, heart failure, and respiratory failure, common in the older populations. Hence, the attribution of the cause of death to CJD may have been recorded inappropriately in some cases. Despite the limitations, our present study underscores the significantly increasing trends in CJD-associated mortality and incidence across a 10-year period in the era of ageing.

In conclusion, we revealed the increasing trends of CJD-associated incidence and mortality using joinpoint regression analysis. The extent of increase was greater among individuals older than 70 years of age; hence, the increased rated of CJD-associated incidence and mortality may not only be attributable to increased disease awareness but also be attributable to the increasingly ageing population. The severe socioeconomic burdens on caregivers imposed by CJD-induced dementia also warrant the attention of policymakers and stress the need for a mitigative action plan with particular focus on preparations to handle an increase in the prevalence of dementia.

https://www.nature.com/articles/s41598-020-72519-0

Application for Negligible BSE Risk Status September, 2012

Overview of BSE Preventive and Control Measures Implemented in Japan While 36 BSE cases have been confirmed in Japan in total so far, no case has been identified in the domestic cattle population born in and after February 2002. This supports appropriateness and effectiveness of the BSE control measures currently implemented in Japan. These measures include the followings:

https://www.maff.go.jp/e/policies/ap_health/animal/attach/pdf/bseoie-2.pdf

BSE JAPAN

https://www.maff.go.jp/result.html?cx=015840603635610229114%3Ad5nyfxhiq78&ie=UTF-8&q=bovine+spongiform+encephalopathy+japan&sa=Search&siteurl=www.maff.go.jp%2Fe%2Fdata%2Fstat%2F93th%2Findex.html&ref=www.maff.go.jp%2Fe%2Fdata%2Fstat%2Findex.html&ss=1902j1612308j7#gsc.tab=0&gsc.q=bovine%20spongiform%20encephalopathy&gsc.sort=date

PRION JAPAN

https://www.mhlw.go.jp/site_kensaku_english.html?q=PRION

CREUTZFELDT JAKOB DISEASE JAPAN

https://www.mhlw.go.jp/site_kensaku_english.html?q=CREUTZFELDT%20JAKOB%20DISEASE

OIE BSE World Cases? LOL!

https://www.oie.int/en/animal-health-in-the-world/bse-specific-data/number-of-reported-cases-worldwide-excluding-the-united-kingdom/

Alternative BSE Risk Assessment Methodology for Beef and Beef Offal Imported into Japan

Yasuhiro YOSHIKAWA1)*, Motohiro HORIUCHI2), Naotaka ISHIGURO3), Mutsuyo KADOHIRA4), Satoshi KAI5), Hidehiro MIZUSAWA6), Chisato NAGATA7), Takashi ONODERA8), Tetsutaro SATA9), Toshiyuki TSUTSUI10), Masahito YAMADA11) and Shigeki YAMAMOTO12)

1)School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan

2)Laboratory of Veterinary Hygiene, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060–0818, Japan

3)Laboratory of Food and Environmental Hygiene, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, Gifu 501–1193, Japan

4)Department of Life Science and Agriculture, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080–8555, Japan

5)Faculty of Business, Marketing and Distribution, Nakamura Gakuen University, Fukuoka, Fukuoka 814–0198, Japan

6)Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113–8619, Japan

7)Department of Epidemiology & Preventive Medicine, Graduate School of Medicine, Gifu University, Gifu 501–1193, Japan

8)Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1–1–1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan

9)Department of Pathology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162–8640, Japan

10)Epidemiological Research Team, National Institute of Animal Health, Tsukuba, Ibaraki 305–0856, Japan

11)Department of Neurology and Neurobiology of Aging, Graduate School of Medical Science, Kanazawa University, Kanazawa 920–8640, Japan

12)Division of Biomedical Food Research, National Institute of Health, Yoga, Setagaya-ku, Tokyo 158–8501, Japan

(Received 11 September 2010/Accepted 31 October 2011/Published online in J-STAGE 14 November 2011)

Abstract.

The Food Safety Commission (FSC) of Japan, established in July 2003, has its own initiative to conduct risk assessments on food stuffs known as “self-tasking assessment”. Within this framework, the FSC decided to conduct a risk assessment of beef and beef offal imported into Japan from countries with no previous BSE reports; thus, a methodology was formed to suit to this purpose. This methodology was partly based on the previous assessments of Japanese domestic beef and beef imported from U.S.A./Canada, but some modifications were made. Other organizations’ assessment methods, such as those used for BSE status assessment in live cattle by the OIE and EFSA’s GBR, were also consulted. In this review, the authors introduce this alternative methodology, which reflects (1) the risk of live cattle in the assessed country including temporal risks of BSE invasion and domestic propagation, with the assessment results verified by surveillance data, and (2) the risk of beef and beef offal consisting of cumulative BSE risk by types of slaughtering and meat production processes implemented and the status of mechanically recovered meat production. Other possible influencing factors such as atypical BSE cases were also reviewed. The key characteristic of the current assessment is a combination of the time-sequential risk level of live cattle and qualitative risk level of meat production at present in an assessed country.

KEY WORDS: beef, BSE, importation, prion diseases, risk assessment.

*Correspondence to: Yoshikawa, Y., School of Veterinary Medicine, Kitasato University, 23–35–1 Higashi, Towada, Aomori 034–8628, Japan. e-mail: ayyoshi@mail.ecc.u-tokyo.ac.jp or yyoshikawa@cis.ac.jp Authors’ notes: The authors, except for the first author, are listed alphabetically. This article is based on the discussion at a Prion Expert Committee meeting. ©2012 The Japanese Society of Veterinary Science

doi: 10.1292/jvms.10-0393; J. Vet. Med. Sci. 74(8): 959–968, 2012

More than 20 years have passed since BSE was officially recognized in the U.K. Now, there is prominent evidence showing the efficacy of a real feed ban and the abolishment of using meat and bone meal (MBM) derived from mammals in feeds for mammals. The total number of BSEpositive cases in the world last year was less than that of one day when the BSE outbreak was at its peak in the U.K. from 1992 through 1993. However, the U.K. continued to spread the sources of BSE pathogens, such as live cattle and animal feeds, to two dozen countries, resulting in a cumulative number of more than 220 variant CJD patients in the world [9].

Currently, Japan imports beef and beef offal from the U.S.A. and Canada, two countries that have previously experienced BSE cases and for which the Food Safety Commission (FSC) in Japan has already assessed the BSE risks of their beef and beef offal. Besides these two countries, Japan also imports beef and beef offal from other countries where no BSE cases have been reported so far. However, some of these countries were categorized as Geographical BSE Risk (GBR) category III by the European Food Safety Agency (EFSA). According to EFSA’s definition, countries are designated as GBR category III either because they are estimated to have a reasonably high possibility of having BSE cases that have not been detected or because they have had a few confirmed cases of BSE. Among exporters to Japan, there are also countries that have simply not been assessed by EFSA’s GBR.

Japanese risk managers presently request importers of beef and beef offal from the above countries to submit official health certificates confirming that the cattle are of healthy origin and also ask that they refrain from importing specified risk materials (SRM). Although the health certificates are confirmed at quarantine stations, there are currently no measures to clarify the exclusion of SRM among beef products imported. There is also uncertainty over potential risks of imported beef and beef offal due to insufficient availability of data related to BSE prevalence and anti-BSE countermeasures in the above-mentioned countries.

The FSC in Japan conducts risk assessments at the request of risk managers, or alternatively, it can also conduct assessments on its own initiative, termed “self-tasking assessment”. The process of hazard selection for self-tasking assessment is as follows. The Expert Committee for Planning collects information and screens the possible assessment subjects based on the degree of public concern in Japan, based on demands for information collection either due to increasing necessity for developing hazards or based on items that are heavily requested for assessment. Selected subjects are then discussed for potential assessment at the Commission’s opinion exchange meetings, and finally, the FSC officially adopts the hazards of choice to be the next subject of selftasking assessment.

Risk assessment of beef and beef offal imported into Japan was among the most requested items during public meetings and other occasions hosted by the FSC. Behind these requests, there seemed to be public concern over uncertainty about BSE risks in beef and beef products imported from countries other than the U.S.A. and Canada. With this situation, the FSC decided to conduct “risk assessment of beef and beef offal imported into Japan” as its self-tasking assessment.

The current assessment conducted by the Prion Expert Committee (PEC) of the FSC in Japan is based on the following concepts: (1) presently, the worldwide BSE prevalence is in the trend of decline; (2) this risk assessment is essentially different from the rest of the BSE-related risk assessments previously conducted by the FSC, in that the assessed countries are only those that have not previously reported BSE cases; (3) previous risk assessments of beef and beef products from the U.S.A. and Canada were conducted by comparing their risks with that of Japanese beef and beef products so that the assessment was based on the relativity; and (4) it was foreseen to be based on the data submitted by each assessed country on a voluntary basis. Subsequently, assuming that there may be certain limitations concerning data availability and submission, the PEC decided to largely conduct this assessment on a qualitative basis but to strive to make it as quantitative as possible.

It was with this background that the PEC firstly developed an alternative assessment method suited to the current situation and then carried out BSE risk assessment for imported beef and beef offal according to this method. In this review, the authors describe the structure and logic of this assessment method. A sample assessment result is provided at the end of this article to enhance readers’ understanding.

PRINCIPLES OF THE CURRENT RISK ASSESSMENT

The methodology for the current risk assessment was developed based on the previously used models for risk assessments of Japanese domestic beef and for US/Canadian beef imported into Japan [5, 6]. OIE’s risk assessment criteria for BSE status and the EFSA GBR method were also referred to [8, 11]. The PEC for the current assessment aimed to deliver the overall conclusion as a science-based comprehensive assessment defined by time periods and based on a combination of the following risk aspects: ...

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Recently, there have been a few cases of irregular forms of BSE (atypical BSE) reported apart from classical BSE in Europe, Japan and the U.S.A. These reports of atypical BSE indicated variation in molecular sizes of abnormal prion proteins (PrPSc) among cases, and eventually two major sizes of proteins were designated as the H and L types. Most of the atypical BSE cases were found in aged cattle over 8 years old, but a remarkable exception exists in Japan, where a steer only 23 months old was reported to have been infected with atypical BSE (the 8th BSE case in Japan). When this exception was excluded, the detection ages of atypical BSE cases ranged from 6.3 to 18 years old. The average detection ages for the H and L types were 11.8 and 11.6 years old, respectively [3].

To the best of the authors’ knowledge, there have been about 40 cases of atypical BSE reported worldwide, yet the OIE does not require distinction between classical and atypical BSE cases in member countries for their reports, while the EFSA only recently referred to case reporting by classical/atypical recognition in its 2009 scientific opinion. These situations seem to further obscure the clear number of atypical BSE cases occurring in the world.

The origin of atypical BSE has not yet been determined. According to EFSA’s scientific opinion published in 2008, all the cases of atypical BSE were reported with birth dates before the real feed ban in January 2001 in Europe. Therefore, the possibility of these atypical cases being attributed to contaminated feeds, just as in classical BSE, cannot be completely denied. On the other hand, data of atypical BSE cases (both the H and L types) in France did not show any reasonable correlation between birth year and frequency of occurrence, as was indicated in classical BSE cases, thus raising the possible interpretation of atypical BSE being sporadic isolated cases of prion disease [3].

Based on the data accumulated in France, the frequencies of atypical BSE cases per 1 million tested adult cattle were estimated to be 0.41 and 0.35 cases for the H and L types, respectively (1.9 and 1.7 cases for the H and L-types, respectively, when limiting the sampling to tested cattle over 8 years old). In Japan, a total of 10 million cattle including fallen stock and slaughtered cattle were tested for BSE, and the results showed no positive cases of the H type and 2 positive cases (case 8, a 23-month-old steer; case 24, a 169-month-old Japanese black cow) of the L type of atypical BSE. These data indicate that Japan has prevalence frequencies of 0 and 0.2 cases of the H and L types of atypical BSE per 1 million cattle including tested fallen stock and slaughtered cattle (zero and approximately 1.5 cases of the H and L types respectively, when limiting the sampling to tested slaughtered cattle over 8 years old).

Atypical BSE of both the H and L types was confirmed to be transmissible by intracerebral inoculation in transgenic mice expressing alleles of bovine or ovine PrP genes and of inbred mice. However, for transgenic mice expressing human prion protein, the L type but not the H type could be transmitted according to the previously published reports (recently, it was reported that H type also transmissible to the humanized transgenic mice). There have also been reports of glycosylation pattern transformation from L-type BASE3 PrPSc-like type to more of the classical BSE PrPSc type. This phenomenon was observed during passage using inbred and transgenic TgVR2 mice. As for the atypical cases of BSE confirmed in Japan, the 24th case of BSE was determined to have had the atypical L type at the detection age of 169 months old, and its sample was successfully transmitted to transgenic mice expressing bovine prion protein. However, transmission of a sample from the other case of atypical L-type BSE confirmed in Japan (the 8th case; detected at the age of 23-month-old) was reported to be unsuccessful in transgenic mice expressing bovine prion protein. The reason for this inconsistency is not clear at this time, although the possible presence of a limitation in the amount of prion protein accumulated in the subject’s brain sample or that the inoculated volume was too low to reach the detection limit cannot be excluded.

A recent report has shown that the atypical L type of BSE has a higher degree of potential for pathogenicity than that its classical counterpart because incubation periods are shorter in atypical BSE transmitted to transgenic mice expressing human prion protein, suggesting that atypical BSE possibly has a higher degree of pathogenicity when compared to its classical counterpart [7].

In contrast to classical BSE, the systemic distribution of abnormal prion protein in atypical BSE cases is barely known. Therefore, it is unclear whether the brainstem is truly the optimal part for sampling and testing in H/L type detection. Likewise, information regarding the infectivity distribution of atypical BSE is scarce in bovine peripheral tissues and body fluid. All together, the lack of essential data hinders, to a certain extent, evaluation of the relative risk-reducing effects of various SRM removal measures for cattle.

Based on the currently available data concerning the potential risks for humans of atypical BSE and prevalence of atypical BSE, it may be too extreme to deny the risk of MRM, especially in MRM derived from aged cattle. However, the degree of influence of the presence of atypical BSE on our concept of the MRM risk will be limited to a low level under the circumstances with presently available knowledge and our discussion. In the meantime, one must also be reminded of the fact that only a limited amount of data is currently available concerning atypical BSE. A proper amount of dis cretion should be used when interpreting these data to avoid unnecessary confusion. Further research and accumulation of data will bring additional insight into the mechanism, pathogenicity and transmission potential of atypical BSE, for which further assessment may become necessary in the future.

To gain the final result of this assessment, the periodic BSE risk status of a country (the sum of invasive BSE risk and domestic stability) and efficacy of present BSE riskreducing measures at meat processing lines were combined and used as an indicator of comprehensive likelihood of BSE prion contamination in beef and beef offal imported into Japan. Surveillance data were used to verify reliability of the assessment. Finally, a summary of each country was expressed in schematic figures (an example is shown in Fig. 4). In Fig. 4, a model country’s invasive risk was ranked as high (from 1986–2005) but was reduced to the middle level from 2006 onwards. The efficacy of feed ban (domestic stability) was unstable during 1986–1989 but improved to the middle level (1990–1996), to the stable level (1997–2000) and then to the very stable level (2001-until now). Current risk reduction efficacy at meat processing lines, determined by factors such as the definition of SRM, compulsory removal of SRM by law, and HACCP/SSOP procedures were good and verified and were therefore rated as ◎. BSE testing at slaughterhouse (>30 months), proper slaughtering procedures such as avoidance of air stunning and pithing were verified as ◎. All together, the overall risk reduction was extremely effective.

The final assessment for this model country was as follows: the domestic BSE exposure/propagation risk was low, and risk reduction at meat processing lines was extremely effective; therefore, the risk of BSE contamination of beef and beef offal imported from this assessed country was considered to be negligible.

RISK ASSESSMENT OF BEEF AND BEEF OFFAL IMPORTED INTO JAPAN

https://www.jstage.jst.go.jp/article/jvms/74/8/74_10-0393/_pdf

https://bovineprp.blogspot.com/2012/01/importation-of-whole-cuts-of-boneless.html

ZOONOSIS OF SCRAPIE TSE PRION

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

***is the third potentially zoonotic PD (with BSE and L-type BSE),

***thus questioning the origin of human sporadic cases.

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

===============

***thus questioning the origin of human sporadic cases***

===============

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

==============

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efﬁciency comparable to that of cattle BSE. While the efﬁciency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

***> why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.

***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.

***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY

https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***

Transmission of scrapie prions to primate after an extended silent incubation period

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

https://www.nature.com/articles/srep11573

Japan BSE Bovine Spongiform Encephalopathy TSE Prion, some history as follows;

Comparative analysis of Japanese and foreign L-type BSE prions

Kentaro Masujin,Ritsuko Miwa,Hiroyuki Okada,Shirou Mohri &Takashi Yokoyama

https://www.tandfonline.com/doi/full/10.4161/pri.6.1.18429

Published Date: 2003-10-08 23:50:00 Subject: PRO/AH> BSE - Japan (05): atypical Archive Number: 20031008.2526

BSE - JAPAN (05): ATYPICAL

**************************

A ProMED-mail post <http://www.promedmail.org> ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org>

[1]

Date: Wed, 8 Oct 2003

From: Terry S. Singeltary Sr. <flounder@wt.net> [edited]

[The statement in the news item cited in the said posting, that "the 8th case of the brain-wasting illness found in Japan is believed to be the world's youngest carrier of the disease"], is wrong.

There have been several cases of clinical BSE in British cattle under 30 months, and it is therefore hardly possible to think that cattle under 30 months have virtually no risk of having BSE.

In 1988 the youngest case was 24, the 2nd youngest 27 months old.

In 1989 the youngest case was 21 and other 4 cases only 24 months old.

In 1990 there were 2 cases only 24 and one only 26 months old.

In 1991 the youngest case was 24 and other 3 cases were only 26 months old.

In 1992 the youngest case was 20 (!), the 2nd youngest 26 months old.

In 1993 there was a 29-month-old case.

In 1995 a 24-month-old case.

In 1996 one British BSE case was 29 months old.

See: <http://www.defra.gov.uk/animalh/bse/bse-statistics/bse/yng-old.html>.

******

[2]

Date: Wed, 8 Oct 2003

From: Laurence Gleeson <Laurence.Gleeson@csiro>

I expect that ProMED will continue to monitor this situation, as the statement that "the abnormal prions found in the bull were of a different type from those of any of the mad cow infection cases reported worldwide so far" is very thought-provoking.

Since this animal was presumably normal and detected by routine post-slaughter screening, it then might be worth clarifying whether the amount of material [from the animal] now available for further studies [might be] limited. The statement and the case have such profound implications that it would seem almost incumbent on the authorities to provide material to an international reference laboratory for confirmation and mouse susceptibility/pathology studies.

Further enquiries of the Japanese authorities would be most helpful to all of us with a keen interest in the prevention and control of this disease.

Laurence J Gleeson Principal Research Scientist CSIRO Livestock Industries Australian Animal Health Laboratory <Laurence.Gleeson@csiro>

******

[3]

Date: Wed, 8 Oct 2003

From: Timothy A Snider/vpb/Cvm <tsnider@cvm.okstate.edu>

A couple of quick questions for the moderator or the readership of ProMED- mail as a whole:

1. If one had a spontaneous BSE case (something analogous to GSS or FFI in humans), how would one know it?

2. What features of current diagnostic modalities in BSE (whether it be immunohistochemistry, western blotting, etc.) define the prion as exogenous or infectious instead of (hypothetically) spontaneous?

These questions are not entirely germane to the currently discussed Japanese case, but I believe they are relevant on a larger scale.

Timothy A. Snider, DVM Lecturer, Anatomic Pathology 250 McElroy Hall College of Veterinary Medicine Oklahoma State University Stillwater, OK 74078 <tsnider@okstate.edu>

******

[4]

Date: Wed, 8 Oct 2003 From: ProMED-mail <promed@promedmail.org> Source: The Financial Times, 8 Oct 2003 [edited] <http://news.ft.com/servlet/ContentServer?pagename=FT.com/

StoryFT/FullStory&c=StoryFT&cid=1059480417800>

Japan finds possible new type of mad cow disease

------------------------------------------------

Japanese scientists launched an investigation yesterday into a possible new strain of BSE, or "mad cow disease", after a bullock was discovered to have contracted the fatal illness. Scientists as well as experts on farming and food met last night to investigate the case and discuss measures to curb the spread of the disease. A confirmed new strain of mad cow disease would be a setback for Japan's cattle and beef industries, which have struggled to win public confidence after the first case was discovered in Japan 2 years ago.

The case differs from previous incidents of bovine spongiform encephalopathy because tests on the animal showed that prions, the self-replicating protein that cause the disease, were arranged in different patterns from past cases.The bullock was also only 23 months old, making it the 2nd-youngest [no, 3rd -- see [1] above. - Mod.JW] animal to have contracted the disease. Also, while initial tests concluded that the animal had fallen victim to BSE, secondary tests all proved negative. The bullock was born one month after Japan banned the use of meat-and-bone meal, which is regarded as the main route of infection.

It is Japan's 8th recorded case of BSE. Chikara Sakaguchi, health minister, said: "The commonly held view is that young [cattle] are not infected [with BSE] but this has proved otherwise. We want to examine whether our current screening system can catch this new type of BSE."

The case is being followed in other countries, notably Britain where the disease first appeared. The UK ministry of agriculture said: "We are watching this with interest but need more information before commenting."

In a recent similar case in Britain involving sheep, scientists are still trying to explain unusual prions that were discovered. BSE was first diagnosed in Britain in 1986 and has since been discovered in several European countries. Japan became the first country outside Europe to have the disease, which has now also been discovered in Canada. The discovery of BSE in a 23-month-old animal could cause widespread concern. In the UK, tests are performed only on animals 24 months or older. However, the removal from the food chain of high-risk body material such as brains and nerve tissue is believed to have cut most of the risk of the infection being passed on.

This latest case of BSE in Japan is likely to bolster Tokyo's contention that all Canadian cattle should be tested for BSE before Japan resumes beef imports from Canada. It could also have repercussions in countries where BSE has recently been found, such as Canada, as well as in countries such as the UK, where the disease is thought to be under control. About 150 people worldwide have died from variant Creutzfeldt-Jakob disease, which is linked to BSE.

[Byline: Bayan Rahman in Tokyo and John Mason in London]

-- ProMED-mail

<promed@promedmail.org>

See Also

BSE - Japan: confirmed (03) 20011002.2392

BSE? - Japan: confirmed (02) 20010925.2337

BSE? - Japan: confirmed 20010923.2303

BSE? - Japan (03) 20010920.2281

Date:22 Nov 2001

From:ProMED-mail <promed@promedmail.org>

Source: Xinhua News Agency, 21 Nov 2001 [edited

Second mad cow case found in Japan's Hokkaido

---------------------------------------------

The Japanese government said on Wednesday that it has found the second confirmed case of mad cow disease (bovine spongiform encephalopathy; BSE) in Japan through a continuing nationwide inspection of all cows. The second cow confirmed infected with the disease was found at a meat inspection center in Hokkaido, north eastern Japan, the Health, Labor and Welfare Ministry said.

Japan's first case of BSE was confirmed by the Ministry of Agriculture, Forestry and Fisheries on 22 September. Following the confirmation of the brain-wasting illness found in Chiba Prefecture, east of Tokyo, the Health Ministry began a nationwide screening of all cows for human consumption on 18 October.

BSE is said to be caused by meat and bone meal (MBM), a protein feed made from the crushed internal organs, skin, and bones of cows. Early this month, beef prices at Tokyo's central wholesale market had returned to nearly the same levels as last year after the government declared domestic beef free of mad cow disease.

******

Date: 21 Nov 2001

From: M Cosgriff <mcosgriff@hotmail.com>

To: ProMED-mail <promed@promedmail.org>

Source: Associated Press [edited <http://ap.tbo.com/ap/breaking/MGAI4HLPAUC.html>

A Holstein cow on the island of Hokkaido has contracted mad cow disease (bovine spongiform encephalopathy), officials said on Wednesday. This, the second confirmed case in Japan, was one of 728 animals given a routine test on the island. The Japanese government [has tried to stem fears by stating that the animal had not been to market.

Japan is the only country in Asia where BSE appears to have spread. The first case was a 5 year old cow apparently infected from contaminated feed. Since then, the government gives mandatory inspections prior to market, and has banned imports of feed made with recycled animal parts and bones.

******

Date: 21 Nov 2001

From: Akira GOTO <ak_goto@yahoo.co.jp>

Source: Kyodo News(online)[edited

<http://home.kyodo.co.jp/all/display.jsp?an=20011121118>

Health ministry finds second mad cow case in Hokkaido

--------------------------------------------------

The second cow confirmed infected with BSE was a 67 month old female Holstein cow raised by a farmer in the village of Sarufutsu in northern Hokkaido, but its place of birth is not known, according to the Hokkaido government. It was slaughtered on Monday.

The cow was suspected of having the disease in an initial test and then tested positive in a confirmation test at Obihiro University of Agriculture and Veterinary Medicine on Wednesday morning, according to the ministry. The meat, internal organs, and all other parts of the cow have not been shipped, the health ministry said. The cow will be disposed of after official confirmation of the results later in the day.

The local government said it has started tracing all the cows shipped by the Hokkaido farmer who currently has about 70 cows. The cow confirmed to have the disease was one of 2 cows the farmer took to a processing center to be slaughtered, but the other cow has tested negative, it added. The ministry said it has stopped the shipment and the distribution of around 30 cows slaughtered after the cow confirmed of having the disease was slaughtered, in addition to all of the farmer's cows.

The health ministry will investigate the contamination route along with the Ministry of Agriculture, Forestry and Fisheries and other institutions. Prime Minister Junichiro Koizumi told reporters at his official residence, "It must be understood that the cow in question will not be put on the market. We must take steps so as not to trigger worries [among the public". Health minister Chikara Sakaguchi said, "It is extremely regrettable" that another cow has been found with the disease, but added, "It is good that we have been conducting strict tests with the determination that we must not have one single (infected cow) reach the dining table of citizens." He added: "The problem is what the (cow's) feed was in the past. It (the disease) will not spread from this cow (to other cows)."

On 22 Sep, the agriculture ministry confirmed Japan's first case of the deadly disease -- the first outside Europe. [That case was a clinical one. - Mod.AS. On 18 Oct, the health ministry began a nationwide screening of all cows for human consumption, following the confirmed discovery of Japan's first case of the brain-wasting illness, found in Chiba Prefecture in September. Around 88 000 cows had been tested as of Tuesday, according to the health ministry. About 1.3 million cows are processed for consumption every year.

The Hokkaido farmer reportedly did not feed the cow MBM, according to the Hokkaido government. It is still not known how the first cow became infected with the disease. Early this month, beef prices at Tokyo's central wholesale market had returned to nearly the same levels as last year, after the government declared domestic beef free of mad-cow disease 18 October.

******

Date: Wed, 21 Nov 2001

From: Tadahiro INOUE <chujo@affrc.go.jp>

Source: The Mainichi Daily News (Mainichi Interactive) [edited <http://mdn.mainichi.co.jp/news/20011121p2a00m0dm013000c.html> CNN.com Asia [edited

<http://asia.cnn.com/2001/WORLD/asiapcf/east/11/20/japan.madcow.second/index.html> Yomiuri Shimbun [edited

<http://www.yomiuri.co.jp/index-e.htm>

Second BSE case confirmed in Japan

-----------------------------------

The Health, Labor and Welfare Ministry confirmed Wednesday 21 Nov 2001 that the dairy cow in Hokkaido, northern part of Japan, has tested positive for bovine spongiform encephalopathy (BSE) in both primary ELISA (enzyme linked immunosorbent assay) as well as the follow up tests (Western blot method) for the disease. The cow was born in April 1996, about the same time as the government advised farmers against feeding cattle with meat and bone meal (MBM), which is suspected of causing BSE. The cow that was earlier confirmed to have had the disease was also born around the same date.

ProMED-mail

<promed@promedmail.org>

[BSE has been confirmed and reported, as of November 2001, in 16 European countries. Japan is the only country outside Europe with confirmed cases of the disease, and one of few Asian countries that have taken steps to determine their BSE status by means of a surveillance in line with the requirements of chapter 2.13.3 of the Office International des Epizooties International Code. The prompt handling of the case, following the laboratory Western blot confirmation of the initial ELISA test -- according to the media, within 24 hours -- is remarkable. - Mod.AS .....................mpp/as/pg/sh

*##########################################################*

http://www.aphanet.ascp.promedmail.org/post/20011123.2873

Gov't panel confirms 4th Japanese cow infected with BSE

Date: 13 May 2002

http://www.hfma.promedmail.org/post/20020515.4210

Published Date: 2001-09-12 23:50:00 Subject: PRO/AH/EDR> BSE? - Japan Archive Number: 20010912.2197

BSE? - JAPAN

************

A ProMED-mail post <http://www.promedmail.org> ProMED-mail, a program of the International Society for Infectious Diseases <http://www.isid.org>

[1]

Date: 12 Sep 2001

From: Kaz Matsuki <kmat@tka.att.ne.jp> [edited]

A possible case of mad cow disease was reported on 10 Sep 2001 for the first time in Japan. The Agriculture, Forestry and Fisheries Ministry in Japan said at the news conference the suspected case was a 5-year-old female Holstein from a dairy farm in Chiba prefecture, east of Tokyo. The cow was found unable to stand up straight in August. The first test conducted by the National Institute of Animal Health in Germany turned out to be negative. However, subsequent necropsy revealed tiny holes in her brain, and the second test was positive. The ministry insisted it was too early to conclude the disease was mad cow (BSE, Bovine Spongiform Encephalopathy).

The animal was destroyed and burned. Other cows at the same farm have been isolated. No human case of variant Creutzfeldt-Jacob disease has been reported in Japan. Kazumasa Matsuki, M.D. Tokyo Metropolitan Government Japan <kmat@tka.att.ne.jp>

******

[2]

Date: 10 Sep 2001

From: Dr. Tadahiro Inoue <chujo@affrc.go.j> Source: OIE News flash 11/09/2001 [edited]

<http://www.oie.int/eng/info/alerte/en_jpn110901.HTM>

Suspicion of bovine spongiform encephalopathy in Japan

------------------------------------------------------

Information received on 10 Sep 2001 from Dr Shigeo Miyajima, Director of Animal Health Division, Ministry of Agriculture, Forestry and Fisheries, Tokyo:

A 5-year-old Holstein cow kept on a dairy farm in Chiba prefecture was slaughtered on 6 Aug 2001 at an abattoir.

As the cow had dystaxia, a brain sample was taken and sent to the National Institute of Animal Health (NIAH) and subjected to Prionics Check test with a negative result on 15 Aug 2001.

A brain sample from this cow was also sent to the prefecture Livestock Hygiene Service Center and subjected to histopathological examination and found to have vacuoles on 24 Aug 2001. The same brain sample was sent to the NIAH on 6 Sep 2001 for histopathological examination with the same result, and subjected to immunohistochemical examination with a positive result on 10 Sep 2001. Control measures: immediately after bovine spongiform encephalopathy was suspected, the herd was been placed under quarantine by the prefecture veterinary inspector.

******

[3]

Date: 12 Sep 2001

From: Akira Goto <ak_goto@yahoo.co.jp> Source: Press release of the Ministry of Agriculture, Forestry and Fisheries of Japan (written in Japanese*) [edited] <http://www.maff.go.jp/work/press010910-01.html>

* Case description summarized and translated by Akira Goto; this is NOT the official translation.

Detection of a suspected case of bovine spongiform encephalopathy (BSE)

Place: Chiba prefecture

Number of suspected case(s): 1

Case 1: Milk cow (Holstein), female, 5 years old

Signs: difficulties in standing

Destroyed and reported to the health officials: 6 Aug 2001

Test results:

(a) "prionics test": negative (15 Aug 2001)

(b) histopathology of the brain tissue: vacuoles are found (24 Aug 2001)

******

[4]

Date: 12 Sep 2001

From: M. Cosgriff <mcosgriff@hotmail.com> and Akira GOTO <ak_goto@yahoo.co.jp>

Source: Reuters and The Mainichi Daily News (Mainichi Interactive) [edited]

<http://mdn.mainichi.co.jp/news/archive/200109/10/20010910p2a00m0dm023001c.h tml>

Mad-cow disease outbreak hits Chiba

-----------------------------------

A cow suspected of suffering from mad-cow disease has been found in Chiba Prefecture, the Agriculture, Forestry and Fisheries Ministry said Monday. If confirmed, this will be the first time that a cow suffering from the disease has been discovered in Japan, ministry officials said.

At the instruction of the ministry, the 5-year-old female cow, kept by a dairy farmer in the prefecture, was euthanized to prevent the disease from spreading. The ministry is withholding the identity of the farmer.

The cow showed symptoms typical of mad-cow disease, such as difficulties in standing, in early August, prompting the Chiba Prefectural Government and the semi-governmental National Institute of Animal Health to examine the cow. The ministry has extracted part of the cow's brain and intends to commission British and Swiss research institutes specializing in the disease to examine the brain.

The source of the disease in Japan has yet to be confirmed, but experts say it may have come from imports of risky feed from Britain, a repeat of the process believed to have spread BSE from UK herds to other European countries. The disease is caused when cattle eat infected meat-and-bone meal, or crushed animal carcasses, and cases have been uncovered across Europe, most of which have been blamed on Britain.

Japan imported animal feedstuffs, including meat-and-bone meal at the peak of the UK mad cow crisis in 1990, but banned such imports in 1996. But the nation's food and agriculture industry was bracing for a possible crisis as some experts warned the disease, whose human variant (vCJD) is thought to have killed more than 100 people in Britain, could be more widespread. Scientists believe milk is unlikely to spread the disease. ProMED-mail

<promed@promedmail.org> [Additional reports of this situation were received from Claudio Maierovitch Pessanha Henriques and Shamsudeen Fagbo. ProMED-mail appreciates the efforts of all who called this apparent emergence of BSE in Japan to our attention. - Mod.ES] .......................tg/pg/es

*##########################################################*

http://ww.promedmail.org/post/20010912.2197

http://www.hfma.promedmail.org/post/20020914.5305

Published Date: 2003-01-19 23:50:00

Subject: PRO/AH> BSE - Japan

Archive Number: 20030119.0181

BSE - JAPAN

**********

A ProMED-mail post <http://www.promedmail.org> ProMED-mail is a program of the International Society for Infectious Diseases <http://www.isid.org>

Date: Sun 19 Jan 2003

From: ProMED-mail <promed@promedmail.org>

Source: Kyodo News, [Sun 19 Jan 2003] [edited]

<http://home.kyodo.co.jp/all/display.jsp?an=20030119085>

Japan confirms 6th case of mad cow disease

-----------------------------------------------------------------

Japan reported its sixth case of bovine spongiform encephalopathy (BSE) or mad cow disease on Sun, 19 Jan 2003 after it confirmed the brain-wasting illness in a cow in Wakayama Prefecture, the Health, Labor and Welfare Ministry said. The Holstein cow from the town of Shibecha in Hokkaido was found to have been infected with the disease.

Wakayama city officials said after an initial test that they asked the National Institute of Infectious Diseases in Tokyo for more detailed BSE tests, which confirmed the cow, born in 1996, was infected with BSE. More conclusive results will become available as early as Monday, they said. 5 cows had been confirmed infected with BSE in Japan since the [first case of the] disease was discovered in Chiba Prefecture in September 2001. One more BSE case each was discovered in Hokkaido and Gunma prefectures in November 2001, a fourth case again in Hokkaido in May 2002, and a fifth case in Kanagawa Prefecture in August 2002.

Of the 6 BSE-infected cows born between December 1995 and April 1996, 4 were born in Hokkaido, and one each was born in Gunma and Kanagawa prefectures, ministry officials said.

The ministry has carried out BSE tests on all cattle for human consumption since October 2001. The latest case emerged after beef consumption began to pick up after a sharp drop in beef sales due to shaken public confidence in the meat industry.

ProMED-mail

<promed@promedmail.org>

[Obtaining the figures on the number of tests allegedly carried out by the Japanese authorities "on all cattle for human consumption since Oct 2001" will be helpful. (In the comprehensive table on BSE tests worldwide, 10 000 tests in Japan are reported for 2001, but no data are available for 2002: <http://ourworld.cs.com/j1braakman/index.htm?f=fs>)

The BSE issue had a striking effect upon the national dairy and beef industries and upon their markets; it had its political ramifications and obviously attracts great attention in Japan. A symposium on BSE, held on 4 Jul 2002 in Tokyo, organized by the OIE, the Japanese Livestock Technology Association and the Japanese Ministry of Agriculture, was attended by about 650 participants.

A comprehensive report on the Japanese investigations into the epidemiology of BSE in Japan has been published on 1 Nov 2002 in ProMED-mail's posting 20021101.5677. The said report, as well as several earlier postings, referred, among others, to the possible role which imported animal-feed ingredients -- including animal fat, intended for calf-milk-replacers -- might have played a role in the introduction of BSE into Japan. The same issue has been subject to discussions and investigations in other countries such as Denmark, Finland, and Austria, and reviewed by ProMED-mail. The possible role of fat products in animal feed is undergoing an extended study by the Scientific Steering Committee (SSC) of the EU, which has adopted -- in September 2002 -- the methodology and input parameters to be used for quantitatively assessing the residual BSE risk in tallow (as well as in gelatin and dicalcium phosphate). During its meeting of 7-8 Nov 2002, the SSC members came to the conclusion that the application of the method requires extensive computing capacity and appropriate software and cannot be done as part of the "homework" of the members of a Working Group. The Secretariat informed the SSC that it had proposed to the Health and Consumer Directorate General that this work be contracted out and that it had launched the corresponding administrative procedure.

The results of these studies are anticipated with great interest. - Mod.AS]

http://www.hfma.promedmail.org/post/20030119.0181

Published Date: 2006-04-27 00:00:00

Subject: PRO/AH/EDR> BSE update 2006 (01)

Archive Number: 20060427.1231

BSE UPDATE 2006 (01)

********************

A ProMED-mail post

<http://www.promedmail.org>

ProMED-mail is a program of the

International Society for Infectious Diseases

<http://www.isid.org>

In this update:

[1] International BSE cases update, 24 Apr 2006

[2] FAO assessment

[3] Estonia, suspicion denied

[4] Japan, contaminated MBM consumed

******

[1] International BSE cases update, 7 Dec 2004

Date: Wed 8 Dec 2004

From: ProMED-mail <promed@promedmail.org>

Source: European Union and Office International des Epizooties data (see comment) [edited]

BSE confirmed cases, 2001 - 2005 (OIE update 24 Apr 2006)

---------------------------------------------------------

Country / 2001 / 02 / 03 / 04 / 05 / (06) / total since 2001

Austria / 1 / 0 / 0 / 0 / 1 / 0 / (-) / 1

Belgium / 46 / 38 / 15 / 11 / 2 / (-) / 112

Canada / 0 / 0 / 2 / 1 / 1 / (1) / 5

Czech Republic / 2 / 2 / 4 / 7 / 8 / (-) / 23

Denmark / 6 / 3 / 2 / 1 / 0 / (-) / 13

Finland / 1 / 0 / 0 / 0 / 0 / (-) / 1

France / 274 / 239 / 137 / 54 / 18 / (-) / 722

Germany / 125 / 106 / 54 / 65 / ... / (-) / 350

Greece / 1 / 0 / 0 / 0 / ... / (-) / 1

Ireland / 246 / 333 / 183 / 126 / 69 / (21) / 978

Israel / 0 / 1 / 0 / 0 / 0 / (-) / 1

Italy / 48 / 38 / 29 / 7 / 7 / (-) / 129

Japan / 3 / 2 / 4 / 5 / 7 / (4) / 25

Liechtenstein* / 0 / 0 / 0 / 0 / ... / (-) / 0

Luxembourg / 0 / 1 / 0 / 0 / 1 / (0) / 2

Netherlands / 20 / 24 / 19 / 6 / ... / (-) / 69

Poland / 0 / 4 / 5 / 11 / 19 / (-) / 39

Portugal / 110 / 86 / 133 / 92 / 37 / (-) / 458

Slovakia / 5 / 6 / 2 / 7 / ... / (-) / 20

Slovenia / 1 / 1 / 1 / 2 / 1 / (-) / 6

Spain / 82 / 127 / 167 / 137 / 75 / (-) / 588

Switzerland / 42 / 24 / 21 / 3** / 3 / (1) / 94

UK / 1202 / 1144 / 611 / 343 / 225 / (-) / 3525

United States / 0 / 0 / 1*** / 0 / 1 / (1) / 2

* 2 cases recorded in 1998

** Including a case in a zoo zebu

*** An imported case (from Canada; this case is included also in the Canadian statistics).

These data have been derived and compiled from OIE's BSE table, updated 27 Apr 2006 <http://oie.int/eng/info/en_esbmonde.htm>.

Key: (-), for 2006, means no reports yet available.

(...), for other years, means no data available.

During 2005, the decline in BSE incidence continued in most affected countries [see 2]. Exceptions were seen in the Czech Republic, Japan and Poland, where the trend of slight increase proceeded.

ProMED-mail

<promed@promedmail.org>

[A table showing the annual incidence (number of indigenous cases per million bovines aged over 24 months) of BSE in OIE Member Countries that have reported cases, excluding the United Kingdom, is available at <http://oie.int/eng/info/en_esbincidence.htm>.

Media news about suspected first BSE cases in Croatia and Estonia have been published by the media in February and April 2006, respectively. So far, these case remain suspected, not confirmed. - Mod.AS]

******

[2] FAO assessment

Date: Thu, 27 Apr 2006

From: ProMED-mail <promed@promedmail.org>

Source:FAO news release 06/24e, 23 Mar 2006 [edited]

<http://www.fao.org/newsroom/en/news/2006/1000258/index.html>

Cases of bovine spongiform encepalopathy (BSE) or "mad cow disease" worldwide are declining, according to the UN Food and Agriculture Organization (FAO). They have been dropping at the rate of some 50 per cent a year over the past 3 years, the Organization said today.

Amid the current international alarm over avian flu, it is good news that the battle against another worrying disease is being won.

In 2005, just 474 animals died of BSE around the world, compared with 878

in 2004 and 1646 in 2003, and against a peak of several tens of thousands in 1992, according to figures collected by the Paris-based World Animal Health Organization (OIE), with which FAO works closely.

Only 5 human deaths resulting from variant Creutzfeldt-Jakob Disease (vCJD), believed to be the human form of BSE, were reported worldwide in 2005. All of them were in the United Kingdom -- the country most affected by the disease -- where 9 deaths were registered in 2004 and 18 in 2003.

Andrew Speedy, an FAO animal production expert, commented: "It is quite clear that BSE is declining and that the measures introduced to stop the disease are effective. But further success depends on our continuing to apply those measures worldwide."

FAO insists on the importance of a scientific approach to detect and control the disease, ensuring it is eradicated in affected countries -- and kept out of unaffected ones.

FAO, together with Swiss experts, has been running courses for specialists from countries as far afield as Serbia, Egypt, Vietnam, Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay, and Paraguay on BSE diagnosis, surveillance and prevention in the animal feed and meat industries. Also vital, said Speedy, is a tracking system that allows animals to be identified all the way from birth to shopping basket. This has been adopted across Europe but has yet to be implemented partially or fully in a number of other countries.

Christopher Matthews Information Officer, FAO <christopher.matthews@fao.org>

******

[3] Estonia, suspicion denied

Date: Thu, 27 Apr 2006

From: Mary Marshall <tropical.forestry@btinternet.com>

Source: Reuters alertnet, 26 Apr 2006 [edited]

<http://www.alertnet.org/thenews/newsdesk/L26272361.htm>

Estonian authorities said on Wednesday that tests for mad cow disease had proved negative in the case of a dead 11 year old animal earlier suspected of being the country's 1st case of BSE [see 20060426.1211]. "There is no case. Of course, this is a big relief for us," Ago Partel,director of the Veterinary and Food Authority, told Reuters.

Earlier this week Agriculture Ministry officials announced that the disease might have been detected in the cow after a routine test at a slaughterhouse. If confirmed, it would have been the country's first case of BSE (bovine spongiform encephalopathy), a disease that destroys the brains of cattle. The cow was from a farm in Jogevamaa county, south eastern Estonia.

BSE was discovered in Britain in 1986 and devastated the country's beef industry. Individual cases of BSE have recently been found in Japan, Canada and the United States.

More than 160 people have died from the human form of the disease, variant Creutzfeldt-Jakob Disease, believed to be contracted by eating meat from infected cattle.

ProMED-mail

<promed@promedmail.org>

[Preferably, the final verdict in a dubious case should be obtained from an OIE BSE reference laboratory. These are: - Dr Danny Matthews, VLA, Weybridge, New Haw, Addlestone, Surrey, UK; - Prof Andreas Zurbriggen, Institute of Animal Neurology, University of Bern, Switzerland; - Dr Takashi Yokoyama, National Institute of Animal Health, National Agricultural Research Organization, Tsukuba, Ibaraki, Japan. - Mod.AS]

******

[4] Japan, contaminated MBM consumed

Date: Thu, 27 Apr 2006

From: Mary Marshall <tropical.forestry@btinternet.com>

Source: UPI via Monstersandritics.com, 10 Feb 2006 [edited]

<http://news.monstersandcritics.com/asiapacific/article_1096137.php>

A cow that died in March 2006 as Japan's 22nd confirmed case of mad cow disease had been fed meat-and-bone meal (MBM), a Japanese official has said. This is the first known use of MBM in Japan since it was banned in 2001 due to suspicions that it causes mad cow disease, formally called bovine spongiform encephalopathy. The case also marks the first time the feed's use has been linked to a mad cow-infected animal in Japan, Kyodo News reported on Thursday.

The 64 month old cow, which died in January 2006 in Hokkaido, Japan's northernmost island, was fed the meal until September 2001, while it was less than 1 year old. In October 2001, the central government imposed a ban on MBM.

The meal was found to be contained in a mixed ration called the CP Supplement made from meat and bones from chickens, pigs and cows. The Hokkaido government has designated 45 cows, fed the same meal at the same farm where the cow died in March 2006, as suspected disease carriers and will destroy them.

ProMED-mail

<promed@promedmail.org>

http://beta.promedmail.org/post/20060427.1231

Subject: Japan confirms 25th case of mad cow disease in a 5-year-old Holstein

From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>

Reply To: Bovine Spongiform Encephalopathy <BSE-L@LISTS.AEGEE.ORG>

Date: Wed, 19 Apr 2006 08:36:42 -0500

Content-Type: text/plain Parts/Attachments: text/plain (109 lines)

##################### Bovine Spongiform Encephalopathy #####################

Subject: Japan confirms 25th case of mad cow disease in a 5-year-old Holstein Date: April 19, 2006 at 6:07 am PST

Japan confirms 25th case of mad cow disease Japan has confirmed its 25th case of mad cow disease in a 5-year-old Holstein, officials said Wednesday.

Meat inspectors in Okayama Prefecture found late Monday that a dairy cow, intended to be slaughtered for meat, had tested positive for the disease. The ministry had initially announced the cow to be 6 years old.

A panel of Health Ministry experts confirmed the infection Wednesday, according to ministry official Kenichi Watanabe.

Japan, which conducts mad cow tests on all cattle killed for meat, has confirmed 25 cases since 2001, including four cases this year, Watanabe said.

The news comes as the U.S. and Japan discuss possible safeguards against the brain-wasting disease that might allow Tokyo to resume U.S. beef imports.

Japan in January reintroduced a ban on American beef products after a U.S. veal shipment was found to contain prohibited spinal bones.

That came just a month after Tokyo eased a previous ban two-year-long ban, imposed in 2003 after the discovery of the first case of mad cow disease in the American herd -- but only for meat from cows aged 20 months or younger with risky body parts removed.

Mad cow is a degenerative nerve disease in cattle. Eating contaminated meat products has been linked to the rare but fatal human variant, Creutzfeldt-Jakob disease, which causes brain tissues to waste.

There have been three confirmed cases of the disease in the U.S. Tests for the disease are much less stringent in the U.S. (AP)

http://mdn.mainichi-msn.co.jp/business/news/20060419p2g00m0bu038000c.html

Subject: Japan confirms 26th mad cow disease case

From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>

Reply To: Bovine Spongiform Encephalopathy <BSE-L@LISTS.AEGEE.ORG>

Date: Sat, 13 May 2006 09:17:41 -0500

Content-Type: text/plain Parts/Attachments: text/plain (39 lines)

##################### Bovine Spongiform Encephalopathy #####################

Subject: Japan confirms 26th mad cow disease case

Date: May 13, 2006 at 6:46 am PST

Japan confirms 26th mad cow disease case

Tokyo - Japan has confirmed its 26th mad cow disease case, this one in a 5-year-old Holstein in the country's north, the Agriculture Ministry said on Saturday.

Meat inspectors in the northern prefecture (state) of Hokkaido found on Thursday that a dairy cow tested positive for the disease, the ministry said in a statement.

A panel of Agriculture Ministry experts confirmed the infection Saturday, according to ministry official Akiko Suzuki.

"All meat, internal organs and parts from this cattle will be incinerated, and there is no danger that they will be circulated in the market," the ministry statement said.

The confirmation comes as Japanese and US officials are set to meet as early as next week to discuss lifting Tokyo's ban on American beef, the countries said earlier this week.

Japan initially banned US beef in December 2003, following the first discovery of mad cow disease in the United States.

That ban was eased last December to allow the importation of meat from cows aged 20 months or less - seen as posing a lower risk of having the disease - but the ban was later tightened following the faulty beef shipment in January.

Mad cow disease, or bovine spongiform encephalopathy, is a degenerative nerve disease in cattle. Eating contaminated meat products has been linked to the rare but fatal human variant Creutzfeldt-Jakob disease.

There have been three confirmed cases of the disease in the US.

http://www.news24.com/News24/World/News/0,,2-10-1462_1932248,00.html

http://mdn.mainichi-msn.co.jp/national/news/20060513p2a00m0na015000c.html

The 11th BSE case in Japan

PrPSc was also detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve). ...

we also know that ;

Results PrPSc was present in the brain tissue of all patients. In addition, we found PrPSc in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle samples. Three patients had PrPSc in both spleen and muscle specimens. Patients with extraneural PrPSc had a significantly longer duration of disease and were more likely to have uncommon molecular variants of sporadic CreutzfeldtJakob disease than were patients without extraneural PrPSc.

and we now know that ;

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

www.sciencexpress.org / 26 January 2006 / Page 1 / 10.1126/science.1122864

we have known that prions were in skeletal muscle ;

http://europa.eu.int/comm/food/fs/sc/ssc/out254_en.pdf

https://web.archive.org/web/20090506011912/http://www.bseinquiry.gov.uk/files/yb/1990/01/19009001.pdf

http://www.pnas.org/cgi/content/ful...53&stored_search=&FIRSTINDEX=0&fdate=1/1/2002

MONDAY, JUNE 19, 2017

PRION 2017 P20 Descriptive epidemiology of human prion diseases in Japan: a prospective 16-year surveillance study

Japan Prion Disease Increasing Annually to 2.3 patients per 1 million populations in 2014

http://creutzfeldt-jakob-disease.blogspot.com/2017/06/prion-2017-p20-descriptive-epidemiology.html

https://vcjd.blogspot.com/2017/06/prion-2017-conference-abstract-p61-vcjd.html

MONDAY, APRIL 27, 2009

The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD) Case Report

Case Report The first Japanese patient with variant Creutzfeldt-Jakob disease (vCJD)

Akiyo Shinde, 1 Takenobu Kunieda, 1 Yoshimi Kinoshita, 1 Reika Wate, 1 Satoshi Nakano, 1 Hidefumi Ito, 1 Masahito Yamada, 2 Tetsuyuki Kitamoto, 3 Yosikazu Nakamura, 4 Sadayuki Matsumoto 5 and Hirofumi Kusaka 1 1 Department of Neurology, Kansai Medical University, Moriguchi, 2 Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, 3 Division of CJD Science and Technology, Department of Prion Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University Graduate School of Medicine, Sendai, 4 Department of Public Health – Inquiry, Jichi Medical University, Shimotsuke, and 5 Department of Neurology, Kitano Hospital, Osaka, Japan Correspondence to Akiyo Shinde, md, Department of Neurology, Kansai Medical University, Fumizono-cho 10-15, Moriguchi 570-8506, Japan. Email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000276/!x-usc:mailto:shindea@takii.kmu.ac.jp This case was presented in a preliminary form in the annual meeting of Japanese Neuropathological Association in Tokyo, 2008.

ABSTRACT

Eleven years after a brief visit to some European countries, a 48-year-old Japanese man developed writing difficulty, irritability and general fatigue. Then he complained of dysesthetic pains in his legs, for which benzodiazepines were prescribed. However, at the time pulvinar sign was retrospectively confirmed on brain MRI. Eighteen months after the onset, his gait became ataxic with rapid deterioration of mental status over the following several months. Thirty-one months after the onset, he became akinetic and mute with periodic synchronous discharges on EEG, and died at the age of 51. The total clinical course was approximately 43 months. Pathological examination revealed the characteristic alterations of spongiform encephalopathy, severe in the thalamus, moderate but widely spread in the cerebral cortices, and moderate in the cerebellum. Abundant amyloid plaques were easily identified in the cerebral cortex and the cerebellum on HE staining. Immunohistochemistry for abnormal prion protein (PrPsc) confirmed amyloid plaques in several forms, such as florid, uni- and multi-centric plaques as well as perineuronal and periaxonal deposits in the basal ganglia and synaptic patterns in the thalami. A Western blotting study identified type 2B protease-resistant PrP. This is the first Japanese patient who was definitely diagnosed as variant Creutzfeldt-Jakob disease (vCJD). The pathological findings were similar to those of previous reports of vCJD in the UK. However, the changes were much more severe both in degree and distribution, probably due to a longer duration of the illness than those in the UK.

--------------------------------------------------------------------------------

Received 5 November 2008; revised and accepted 7 January 2009.

DIGITAL OBJECT IDENTIFIER (DOI) 10.1111/j.1440-1789.2009.01006.x About DOI

http://www3.interscience.wiley.com/journal/122241574/abstract?CRETRY=1&SRETRY=0

http://www.ncbi.nlm.nih.gov/pubmed/19389077?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

----- Original Message -----

From: "TERRY SINGELTARY" <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000276/!x-usc:mailto:flounder9@VERIZON.NET>

To: <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000276/!x-usc:mailto:BSE-L@LISTS.AEGEE.ORG>

Sent: Tuesday, March 10, 2009 9:03 PM

Subject: [BSE-L] JAPAN-Local governments to carry on BSE testing despite subsidy cuts

-------------------- mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000276/!x-usc:mailto:BSE-L@LISTS.AEGEE.ORG --------------------

11/03/2009 00:54:58

Japan-BSE Testing.

JAPAN-Local governments to carry on BSE testing despite subsidy cuts

Every local government across the country with meat inspection facilities will continue to test all beef cows for mad cow disease during the next fiscal year, a Mainichi survey has found.

The finding comes despite the central government's abolition of about 200 million yen in annual subsidies to local governments for bovine spongiform encephalopathy (BSE) tests. Japan is the only country where all beef cows are tested for the disease.

In August 2005, the Health, Labor and Welfare Ministry deemed that there is no need for BSE tests on cows 20 months old or younger, on the grounds that no cow born before January 2002 has been found infected with BSE and that there is little chance of finding BSE in such young cows even if they have been infected.

Nevertheless, the ministry had extended subsidies to local governments conducting BSE tests on all beef cows until July last year.

Officials in charge at all 77 prefectural and municipal governments that have beef inspection facilities said they will continue BSE tests on all beef cows in fiscal 2009.

Among the reasons given was the need to "maintain the brand image of their locally produced beef" and "prevent confusion in the marketing process."

However, 30 government bodies said that there was no discussion on whether to continue testing. The survey also suggested that governments tend to abide by the policy of their peers and requests from local residents.

"It would take a lot of nerve to stop it while other prefectures are continuing it," said an official at the Akita Prefectural Government.

"We'd like to stop it but we can't gain support from local residents," a Miyagi Prefectural Government representative said. An official at the Yokohama Municipal Government said that the national government needs to take the initiative in convincing the public of the safety of beef.

The Toyohashi Municipal Government in Aichi Prefecture called on the national government to organize a nationwide BSE testing system. "Since beef is marketed in widespread areas, there is no point in conducting inspections on them unless they are coordinated.."

The government has also applied with the World Organization for Animal Health to raise its evaluation of Japan's BSE countermeasures from the lowest level of "a country whose BSE risk is unknown" to the middle level of "a country having a controlled BSE risk.."

Japan filed the application after it was decided to abolish a practice called "pithing" at all meat treatment centers across the country by the end of this fiscal year. In pithing, a wire is inserted into the cow's head to destroy the brains and spinal marrow and to prevent them from thrashing around. The practice is feared to raise the risk of BSE infections.

The government expects its application to be approved at a general meeting of the organization to be held in May this year.

http://www.farminguk.com/news/Japan-BSE-Testing.12958.asp

I applaud Japans effort to continue to try and eradicate BSE (TSE) i.e. mad cow from their herds. A far cry as to what the USDA has done here in the USA. they did just the opposite. the truth hurts sometimes when reality sets in $$$

WITHOUT a doubt, IF the USA, Canada, and Mexico can have a terribly flawed favorable rating, even though they are BSE GBR risk factor III, and even at that it was on flawed data, with all this, why not Japan being as controlled as the USA and North America ??? it's all about money is it not $$$ that's what Prusiner et al told the hearing committee in California ;

DAMNING TESTIMONY FROM STANLEY PRUSINER THE NOBEL PEACE PRIZE WINNER ON PRIONS SPEAKING ABOUT ANN VENEMAN

''they don't wanna know, the dont' care''

http://maddeer.org/video/embedded/prusinerclip.html

----- Original Message -----

From: TERRY SINGELTARY

To: mailto:BSE-L@LISTS.AEGEE.ORG

Cc:

Sent: Friday, March 06, 2009 4:27 PM

Subject: Risk of Introduction of BSE into Japan by the Historical Importation of Live Cattle from the United Kingdom

Journal of Veterinary Medical Science

Vol. 71 (2009) , No. 2 February pp.133-138

Risk of Introduction of BSE into Japan by the Historical Importation of Live Cattle from the United Kingdom

Katsuaki SUGIURA1), Toyoko KUSAMA1), Tomotaro YOSHIDA1), Naoki SHINODA1) and Takashi ONODERA2)

1) Food and Agricultural Materials Inspection Center 2) Department of Molecular Immunology, University of Tokyo

(Received 10-Mar-2008) (Accepted 3-Sep-2008)

ABSTRACT. All cattle imported from the United Kingdom to Japan since 1980 and slaughtered before 2002 were traced (n=33), and the number of cattle that were possibly infected with BSE and entered the animal feed chain was calculated. Because there was no effective system to avoid recycling of the BSE agent via animal feed until the early 1990s, of the 33 cattle imported from the UK into Japan, most probably 7 or 8 were infected and entered the animal feed chain, 2 of which entered the animal feed chain in each of 1992 and 1993. In terms of infectivity, 400-550 cattle oral ID50 of the BSE agent entered the feed chain in each of these years. The amount of infectivity that entered the feed chain in 1989, 1991 and 1995 was smaller but still substantial, suggesting that the BSE agent might have entered the Japanese feed chain in any of these years.

KEY WORDS: bovine spongiform encephalopathy (BSE), import risk analysis, Japan, live cattle, simulation

snip...

http://www.jstage.jst.go.jp/article/jvms/71/2/133/_pdf

REFERENCES

http://www.jstage.jst.go.jp/article/jvms/71/2/71_133/_cit

Risk of Introduction of BSE into Japan by the Historical Importation of Live Cattle from the United Kingdom

http://bseusa.blogspot.com/2009/03/risk-of-introduction-of-bse-into-japan.html

SEE FULL TEXT HERE ;

Tuesday, March 10, 2009

JAPAN-Local governments to carry on BSE testing despite subsidy cuts

http://madcowtesting.blogspot.com/2009/03/japan-local-governments-to-carry-on-bse.html

https://cjdusa.blogspot.com/2009/04/first-japanese-patient-with-variant.html

PrPSc distribution of a natural case of bovine spongiform encephalopathy

Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu Imamura, Takashi Yokoyama and Morikazu Shinagawa Priori Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856 Japan gan@affrc.go.jp

Abstract

Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes progressive neurodegeneration of the central nervous system. Infectivity of BSE agent is accompanied with an abnormal isoform of prion protein (PrPSc).

The specified risk materials (SRM) are tissues potentially carrying BSE infectivity. The following tissues are designated as SRM in Japan: the skull including the brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral column excluding the vertebrae of the tail, spinal cord, distal illeum. For a risk management step, the use of SRM in both animal feed or human food has been prohibited. However, detailed PrPSc distribution remains obscure in BSE cattle and it has caused controversies about definitions of SRM. Therefore we have examined PrPSc distribution in a BSE cattle by Western blotting to reassess definitions of SRM.

The 11th BSE case in Japan was detected in fallen stock surveillance. The carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of tissue samples were homogenized. Following collagenase treatment, samples were digested with proteinase K. After digestion, PrPSc was precipitated by sodium phosphotungstate (PTA). The pellets were subjected to Western blotting using the standard procedure. Anti-prion protein monoclonal antibody (mAb) T2 conjugated horseradish peroxidase was used for the detection of PrPSc.

PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve). Our results suggest that the currently accepted definitions of SRM in BSE cattle may need to be reexamined.

T. Kitamoto (Ed.)PRIONSFood and Drug Safety

================

ALSO from the International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004; Bovine spongiform encephalopathy (BSE) in Japan

snip...

"Furthermore, current studies into transmission of cases of BSE that are atypical or that develop in young cattle are expected to amplify the BSE prion"

NO. Date conf. Farm Birth place and Date Age at diagnosis

1. 8. 2003.10.6. Fukushima Tochigi 2001.10.13. 23

2. 9. 2003.11.4. Hiroshima Hyogo 2002.1.13. 21

Test results

# 8b, 9c cows Elisa Positive, WB Positive, IHC negative, histopathology negative

b = atypical BSE case

c = case of BSE in a young animal

b,c, No PrPSc on IHC, and no spongiform change on histology

International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004.

Page 6 of 98

8/3/2006

Tetsuyuki Kitamoto Professor and Chairman Department of Prion Research Tohoku University School of Medicine 2-1 SeiryoAoba-ku, Sendai 980-8575, JAPAN TEL +81-22-717-8147 FAX +81-22-717-8148 e-mail; kitamoto@mail.tains.tohoku.ac.jp Symposium Secretariat Kyomi Sasaki TEL +81-22-717-8233 FAX +81-22-717-7656 e-mail: kvomi-sasaki@mail.tains.tohoku.ac.ip

=================================

Atypical Proteinase K-Resistant Prion Protein (PrPres) observed in an Apparently Healthy 23-Month-Old Holstein Steer

Jpn. J. Infect. Dis., 56, 221-222, 2003

Laboratory and Epidemiology Communications

Atypical Proteinase K-Resistant Prion Protein (PrPres) Observed in an Apparently Healthy 23-Month-Old Holstein Steer

Yoshio Yamakawa*, KenÕichi Hagiwara, Kyoko Nohtomi, Yuko Nakamura, Masahiro Nishizima ,Yoshimi Higuchi1, Yuko Sato1, Tetsutaro Sata1 and the Expert Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare of Japan2

Department of Biochemistry & Cell Biology and 1Department of Pathology, National Institute of Infectious Diseases, Tokyo 162- 8640 and 2Miistry of Health, Labour and Welfare, Tokyo 100-8916

Communicated by Tetsutaro Sata

(Accepted December 2, 2003)

*Corresponding author: Mailing address: Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 1628640, Japan. Tel: +81-3-5285-1111, Fax: +81-3-5285-1157, E-mail: yamakawa@nih.go.jp

Since October 18, 2001, 'bovine spongiform encephalopathy (BSE) examination for all cattle slaughtered at abattoirs in the country' has been mandated in Japan by the Ministry of Health, Labour and Welfare (MHLW). 'Plateria' ELISA-kit (Bio-Rad Laboratories, Hercules, Calif., USA) is routinely used at abattoirs for detecting proteinase K (PK)-resistant prion protein (PrPSc) in the obex region. Samples positive according to the ELISA screening are further subjected to Western blot (WB) and histologic and immunohistochemical examination (IHC) at the National Institute of Infectious Diseases (NIID) or Obihiro University. If PrPSc is detected either by WB or by IHC, the cattle are diagnosed as BSE. The diagnosis is approved by the Expert Committee for BSE Diagnosis, MHLW. From October 18, 2001 to September 30, 2003, approximately 2.5 million cattle were screened at abattoirs. A hundred and ten specimens positive according to ELISA were subjected to WB/IHC. Seven showed positive by both WB and IHC, all exhibiting the typical electrophoretic profile of a high content of the di-glycosylated molecular form of PrPSc (1-3) and the distinctive granular deposition of PrPSc in neuronal cells and neuropil of the dorsal nucleus of vagus.

An ELISA-positive specimen from a 23 month-old Holstein steer slaughtered on September 29, 2003, in Ibaraki Prefecture (Ibaraki case) was sent to the NIID for confirmation. The animal was reportedly healthy before slaughter. The OD titer in ELISA was slightly higher than the 'cut-off' level given by the manufacturer. The histology showed no spongiform changes and IHC revealed no signal of PrPSc accumulation typical for BSE. However, WB analysis of the homogenate that was prepared from the obex region and used for ELISA revealed a small amount of PrPSc with an electrophoretic profile different from that of typical BSEassociated PrPSc (1-3). The characteristics were (i) low content of the di-glycosylated molecular form of PrPSc, (ii) a faster migration of the non-glycosylated form of PrPSc on SDS-PAGE, and (iii) less resistance against PK digestion as compared with an authentic PrPSc specimen derived from an 83-month-old Holstein (Wakayama case) (Fig. 1). Table 1 summarizes the relative amounts of three distinctive glycoforms (di-, mono, non-glycosylated) of PrPSc calculated by densitometric analysis of the blot shown in Fig. 1. As 2.5 mg wet weight obex-equivalent homogenate of the Ibaraki case (Fig. 1, lane 4) gave slightly stronger band intensities of PrPSc than an 8 mg wet weight obex-equivqlent homogenate of a typical BSE-affected Wakayama case (Fig. 1, lane 2), the amount of PrPSc accumulated in the Ibaraki case was calculated to be 1/500 - 1/1000 of the Wakayama case. In the Ibaraki case, the PrPSc bands were not detectable in the homogenates of the proximal surrounding region of the obex. These findings were consistent with the low OD value in ELISA, i.e., 0.2 -0.3 for the Ibaraki case versus over 3.0 for the Wakayama case. The DNA sequence of the PrP coding region of the Ibaraki case was the same as that appearing in the database (GenBank accession number: AJ298878). More recently, we encountered another case that resembled the Ibaraki case. It was a 21- monthold Holstein steer from Hiroshima Prefecture. WB showed typical BSE-specific PrPSc deposition though IHC did not detect positive signals of PrPSc (data not shown).

Though the clinical onset of BSE is usually at around 5 years of age or later, a 20-month-old case showing the clinical signs has been reported (4). Variant forms of BSE similar to our cases, i.e., with atypical histopathological and/or biochemical phenotype, have been recently reported in Italy (5) and in France (6). Such variant BSE was not associated with mutations in the prion protein (PrP) coding region as in our case (5,6). The Ministry of Agriculture, Forestry and Fisheries of Japan (MAFF) announced a ban of feeding ruminants with meat bone meal (MBM) on September 18, 2001, and a complete ban was made on October 15 of the same year. According to the recent MAFF report, the previous seven cases of BSE in Japan were cattle born in 1995 - 1996 and possibly fed with cross-contaminated feed. However, the two cattle in this report were born after the complete ban. Whether contaminated MBM was implicated in the present cases remains to be investigated.

REFERENCES

Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J. and Hill, A. F. (1996): Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature, 383, 685

690. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. J. (1997): Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature, 389, 498-501. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C. L., Gowland, I. and Collinge, J. (1997): The same prion strain causes vCJD and BSE. Nature, 389, 448-450. Matravers, W., Bridgeman, J. and Smith, M.-F. (ed.)(2000): The BSE Inquiry. p. 37. vol. 16. The Stationery Office Ltd., Norwich, UK. Casalone, C., Zanusso, G., Acutis, P. L., Crescio, M. I., Corona, C., Ferrari, S., Capobianco, R., Tagliavini, F., Monaco, S. and Caramelli, M. (2003): Identification of a novel molecular and neuropathological BSE phenotype in Italy. International Conference on Prion Disease: from basic research to intervention concepts. Gasreig, Munhen, October 8-10. Bicaba, A. G., Laplanche, J. L., Ryder, S. and Baron, T. (2003): A molecular variant of bovine spongiform encephalopatie. International Conference on Prion Disease: from basic research to intervention concepts. Gasreig, Munhen, October 8-10. Asante, E. A., Linehan, J. M., Desbruslais, M., Joiner, S., Gowland, I., Wood, A. L., Welch, J., Hill, A. F., Lloyd, S. E., Wadsworth, J. D. F. and Collinge, J. (2002). BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J., 21, 6358-6366.

SEE SLIDES IN PDF FILE;

http://www.nih.go.jp/JJID/56/221.pdf

http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.230.8886&rep=rep1&type=pdf

Subject: Risk assessment consuming beef and internal organs regulated by the beef export verification program of USA, Canada, to Japan cattle Date: April 19, 2006 at 6:37 am PST

Risk assessment concerning

“the comparability between risks of consuming beef and

internal organs regulated by the beef export verification

program of the United States/Canada and risks of

consuming beef and internal organs of Japanese cattle”

December 2005

Food Safety Commission, Japan

snip...

2.3 Verfication by surveillance

Verification and comparison of subjects and the testing techniques

Surveillance in the United States

BSE inspection in the United States has been aimed at surveillance, and histopathological tests have been

conducted since May 1990 on cattle aged 24 months or older and with central nervous system

manifestation or abasia 46). The Animal and Plant Health Inspection Service (APHIS) and the National

Veterinary Services Laboratories (NVSL) have introduced an immunohistochemical (IHC) method since

1993 65) 66). The number of tested cattle between 1990 and 2001 was 16,829 67). The number of subject

cattle have increased since 2002 to approximately 20,000 high-risk cattle annually, and 57,654 heads of

cattle were inspected using histopathological tests and the IHC method between 2002 and May 31, 2004

67). As a result, the first BSE case in the United States was discovered in December 2003. The subsequent

epidemiological study reported that this cow was not born in the United States but was imported from

Canada 68). After this incidence, according to the advice of the international inspection team, an

expanded surveillance began since June 2004 69). In this expanded surveillance, ELISA (enzyme-linked

immunosorbent assay) was used in primary test, and the IHC method was used in confirmatory test as

before. The number of inspected cattle amount to 383,477 as of July 3, 2005 70). Among them, the

second BSE case in the United States was detected in June 2005 71).

Note: Breakdown between 1990 and 1993 is unknown (reference data for the consultation in the United States (29))

In the expanded surveillance, a commercial Plateria kit is introduced for the ELISA method (primary

test) 72), and is used in a total of 13 institutes including the NVSL and 12 voluntarily participating State

Veterinary Diagnostic Laboratories (SVDL) 73). The ELISA method was conducted on 369,467 heads of

cattle by May 29, 2005, of which three were tested inconclusive 74), but were tested negative by the IHC

method, which was conducted as the confirmatory test.

In June 2005, the Office of Inspector General (OIG) demanded confirmatory tests of these three by the

Western Blot (WB method). The above diagnosis institutes lacked both a facility and experience of the

WB method, thus the National Animal Disease Center (NADC) performed the test, and one was revealed

positive. This sample was also tested positive by both the WB and IHC methods at the Veterinary

Laboratories Agency (VLA) in Britain. In the United States, the IHC method was performed again using

a different antibody, and a positive result was obtained at this time 71) 75). The ELISA had not been

conducted before the expanded surveillance in June 2004, neither had the WB method before May 2005.

Thus, unlike the young cattle and atypical cases detected by the ELISA and WB method in Japan (tested

negative by the IHC method), undetectable BSE cases might have been overlooked by the IHC method in

the United States. As a result, the WB method described in the OIE Manual of Standards has been added

to the confirmatory test since June 2005 76), however, no official document on details about the WB

method that will be introduced in the United States has been presented to the Prion Expert Committee to

date.

Thus, the surveillance in the United States might have detected more BSE cattle than reported.

Surveillance in Canada

Canada initiated a surveillance program in 1992. The aim was to identify the presence of BSE in Canada.

Several thousands of cattle with central nervous system manifestation or abasia were examined between

1992 and 2003 77) 78). In 1993, BSE infection was confirmed in one cow imported from Britain, and the

cow was disposed of without being used in food or feed. At that time, all the cattle imported from Britain

was disposed of, and a BSE testing by IHC method took place, but all the cattle were tested negative 79).

After the discovery of a BSE cow in May 2003 (the first case in Canada), the aim of the surveillance

shifted to the assessment of BSE prevalence in adult cattle, and the expanded surveillance began after the

ELISA was introduced in January 2004. In 2004, 23,550 heads of cattle were inspected, and 30,000 are

scheduled for inspection annually after 2005 (20,949 were inspected between January 2005 and April 18,

2005). As a result of the initiative, the second case in Canada was discovered on January 2, 2005, and

the third case on January 11, 2005 77).

Histopathological tests and the IHC method have been introduced to the BSE surveillance in Canada

since 1992 and 1994, respectively 79). After the discovery of the first case in Canada, the WB method

was introduced in September 2003, and the ELISA in 2004 79). Currently, a simple WB method and the

ELISA are performed at state veterinary pathology laboratory, which belong to the TSE inspection

organization network, and 6 CFIA network facilities. Positive samples are then sent to the BSE Reference

Laboratory in the National Centre for Foreign Animal Diseases (NCFAD) for confirmatory test by the

IHC method. However, the WB method is used when the brain stem (obex) cannot be identified

anatomically due to sample conditions, or when conflicting results are obtained by a rapid test and the

IHC test 78) 80).

Surveillance in Japan

In Japan, surveillance by histopathological tests of cattle with central nervous system manifestation and

others in farms is under operation since 1996 81). Between 1996 and 2001, 2,247 heads of cattle were

tested, and the first BSE-positive case was discovered in September 2001 81).

Subsequently, test objects and number of cattle expanded sequentially, and as a general rule, dead cattle

that are 24 months or older have been included in test objects since April 2003 81). Accordingly, blanket

testing of dead cattle aged 24 months or older began in April 2004 81).

The ELISA is performed as a primary test at livestock hygiene service centers, and positive samples are

tested using the WB method and the IHC method at the National Institute of Animal Health 82). A final

diagnosis is made by expert members at the technical research meeting of the risk management

organization 82).

By the end of September 2005, 202,398 high-risk cattle (those with central nervous system manifestation

and dead cattle aged 24 months or older) were tested by the ELISA, and 4 positive cases were detected by

the IHC and WB methods. In addition, 788 suspected cases were tested using the ELISA by 2005 (by the

time when the 20th case of BSE-positive in Japan was discovered), but no positive cases were detected.

In October 2001, BSE screening tests of all slaughtered cattle in slaughterhouses began in order to

prevent use of BSE-positive animals in food 12). Primary test is performed by the ELISA, then

confirmatory test by the WB method, pathological tests, the IHC method. In BSE testing of slaughtered

cattle of all ages, the ELISA is performed as primary test at 114 meat inspection stations throughout

Japan (this year’s plan), and positive cases are subjected to secondary test at 3 confirmatory testing

laboratories in Japan by the WB method (National Institute of Infectious Diseases and Hokkaido

University) and by pathological tests and the IHC method (National Institute of Infectious Diseases and

Obihiro University of Agriculture and Veterinary Medicine) 12). By October 31, 2005, 4,974,937 heads of

cattle were tested, of which 15 were diagnosed BSE-positive in “the Expert Committee of BSE

Diagnosis” of the MHLW 83). The results of this screening test at slaughterhouses are also useful as

surveillance data to comprehend the status of BSE contamination correctly.

Apparently, improvement of surveillance by adding subject animals, number of subject animals, and test

methods, will enable detection of more BSE-positive cattlein many countries, besides in the United States

and Canada.

snip...

5 Conclusions

The past domestic risk assessment could virtually demonstrate the effectiveness and other aspects of the

BSE measures, thus assessments have been conducted based on them. However, since the present

consultation was conducted outside Japan, assessment of risks of beef and others in the United States and

Canada must be based on the assessment of the principles stated in documents, the some data from risk

management organizations, and the supplemental remarks of expert members. Thus, it must be taken into

account that there were also unclear aspects. In addition, assessment had to be conducted under the

assumption that the Beef Export Verification Program was observed.

Many points remained unclear in the data from the United States and Canada both in quality and in

quantity, and assessment had to be conducted with the assumption that the management measures are

observed. Thus, we must say that it is difficult to assess scientifically the comparability of the BSE risks

in the United Sates/Canada. On the other hand, assuming that the Beef Export Verification Program

presented by the risk management organization (mandatory SRM removal in all cattle, export limitation

of age to 20 months or younger, etc.) is observed, the difference in the risk levels of beef and others

derived from cattle in the United Sates/Canada and those in Japan is considered very small.

The risk management organization holds the responsibility to confirm these assumptions, and if the

assumptions are not observed, the results of assessment will be different from the ones presented.

If the risk management organization decides to take measures to lift the import ban after consideration of

the above-mentioned, the Prion Expert Committee is obliged to receive reports on the effectiveness of the

Beef Export Verification Program and the results of assessment of compliance with the Program from the

management organization, provided that the assessment was conducted based on the assumptions.

Subsequently, the management organization is obliged to report to the public.

6 Supplementary items for conclusion

To respond to the present consultation, two points should be emphasized. Firstly, as described in the

history of the consultation, the responsibilities of the risk assessment organization and the risk

management organization must be defined. When the risk management organization judges and

implements measures according to the present verdict, the organization must be accountable of the results

to the public, and must hold the responsibility of ensuring compliance with the Beef Export Verification

Program by the exporting countries in lifting the import ban.

Secondly, to respond to the present consultation, the Prion Expert Committee of the Food Safety

Commission compared the differences in the domestic measures in Japan, the United Sates, and Canada.

The consultation demands risk assessment, assuming additional conditions for the Beef Export

Verification Program for Japan, and the risk assessment was also assessed, assuming the compliance with

the Beef Export Verification Program. Thus, establishment of hardware and software for observance of

the Beef Export Verification Program and its inspection are most critical. In case the Beef Export

Verification Program is not observed, the assessment results are invalid.

We would like to add the following points that were controversial in the course of the risk assessment:

In terms of SRM removal, the current status of surveillance in slaughterhouses in the United States and

Canada is unknown, and the effectiveness of the warranty of good safety by the risk management

organization remains uncertain. In particular, contamination of pieces of spinal cord into beef and others

can be a risk factor, even in a small amount. In such a case, as for SRM removal, it is unclear whether the

risks of beef and others derived from cattle in the United States and Canada are comparable with those in

Japan. Thus, the inspection system for spinal cord removal must be reinforced.

To accurately comprehend the BSE contamination status in the United States and Canada, and to

implement proper management measures, sufficient surveillance of cattle, including healthy animals,

must be expanded and maintained. Even if the management measures become effective to some extent,

and the epidemic becomes discontinued and localized, or sporadic, at least continuous surveillance of all

high-risk cattle must be maintained.

To prevent BSE exposure and propagation in the United States and Canada, ban on the use of SRMs,

which account for 99.4% infectivity of BSE prion, is essential. The use of SRM must be banned not only

in feed for cattle but also in feed of other animals, which might cause cross-contamination.

The present risk assessment was conducted under the assumption that the Beef Export Verification

Program for Japan was observed. Thus, the management organizations must assure the compliance. The

risk management organization must establish a system that assures proper implementation of riskmitigation

measures for beef and internal organs that are exported from the United States/Canada to

Japan. An accreditation system of slaughterhouses of beef and others exported to Japan as well as a

management system, including periodical official on-the-spot inspection of these facilities, are

considered effective.

Even if the risk management organization decides to lift the export ban, import should be suspended

when management measures are not properly observed, such as when certificate of the birth age in

months is absent, SRMs are improperly removed, and there is a possible mix-up with beef derived from

cattle aged 21 months or older during slaughtering and distribution, all of which lead to a serious

situation of undeniable risks to humans.

snip...

http://www.fsc.go.jp/sonota/bse-risk-assessment-concerning.pdf

UK live cattle Exports

https://web.archive.org/web/20090506002229/http://www.bseinquiry.gov.uk/files/mb/m11f/tab11.pdf

UK MBM Exports

https://web.archive.org/web/20060517075218/http://www.bseinquiry.gov.uk/files/mb/m11g/tab05.pdf

USA TSE PRION

THURSDAY, AUGUST 20, 2020

Why is USDA "only" BSE TSE Prion testing 25,000 samples a year?

https://animalhealthreportpriontse.blogspot.com/2020/08/why-is-usda-only-bse-tse-prion-testing.html

PLOS ONE Journal

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

http://www.plosone.org/annotation/listThread.action?root=86610

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply

http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143

FDA's FAILED MAD COW FEED POLICY, IN LIVING COLOR!

***> cattle, pigs, sheep, cwd, tse, prion, oh my!

***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).

Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733407/DEFRA_QRA_TSE_in_cervids_June2018_v1.pdf

http://chronic-wasting-disease.blogspot.com/2012/08/susceptibility-of-cattle-to-agent-of.html

***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;

BSE TESTING (failed terribly and proven to be a sham)

BSE SURVEILLANCE (failed terribly and proven to be a sham)

BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)

these are facts folks. trump et al just admitted it with the feed ban.

see;

FDA Reports on VFD Compliance

John Maday

August 30, 2019 09:46 AM VFD-Form 007 (640x427)

Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.

https://www.fda.gov/media/130382/download

SUNDAY, SEPTEMBER 1, 2019

***> FDA Reports on VFD Compliance

https://bovineprp.blogspot.com/2019/09/fda-reports-on-vfd-compliance.html

MONDAY, AUGUST 24, 2020

Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease

https://chronic-wasting-disease.blogspot.com/2020/08/very-low-oral-exposure-to-prions-of.html

THURSDAY, SEPTEMBER 24, 2020

The emergence of classical BSE from atypical/ Nor98 scrapie

https://nor-98.blogspot.com/2020/09/the-emergence-of-classical-bse-from.html

Monday, September 14, 2020

Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom

https://camelusprp.blogspot.com/2020/09/assessing-aggregated-probability-of.html

Tuesday, September 15, 2020

Mad Camel Disease CPD TSE Prion dromedary camels (Camelus dromedarius) is spreading

https://camelusprp.blogspot.com/2020/09/mad-camel-disease-cpd-tse-prion.html

THURSDAY, SEPTEMBER 24, 2020

ARKANSAS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE 845 Cases Positive To Date

https://chronic-wasting-disease.blogspot.com/2020/09/arkansas-chronic-wasting-disease-cwd.html

THURSDAY, SEPTEMBER 10, 2020

Saskatchewan, Canada, Chronic Wasting Disease CWD TSE Prion

https://chronic-wasting-disease.blogspot.com/2020/09/saskatchewan-canada-chronic-wasting.html

FRIDAY, SEPTEMBER 11, 2020

Norway Skrantesjuke CWD TSE Prion detected on reindeer buck from Hardangervidda

https://chronic-wasting-disease.blogspot.com/2020/09/norway-skrantesjuke-cwd-tse-prion.html

SATURDAY, MARCH 10, 2018

Dura Mater Graft–Associated Creutzfeldt-Jakob Disease — Japan, 1975–2017 Update

http://cjdmadcowbaseoct2007.blogspot.com/2018/03/

http://creutzfeldt-jakob-disease.blogspot.com/2020/01/man-died-of-cjd-30-years-after-brain.html

WEDNESDAY, SEPTEMBER 02, 2020

Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components Guidance for Industry

https://creutzfeldt-jakob-disease.blogspot.com/2020/09/recommendations-to-reduce-possible-risk.html

TUESDAY, AUGUST 18, 2020

Sheep Scrapie, Bovine BSE, Cervid CWD, ZOONOSIS, TSE Prion Roundup August 18, 2020

https://transmissiblespongiformencephalopathy.blogspot.com/2020/08/sheep-scrapie-bovine-bse-cervid-cwd.html

THURSDAY, AUGUST 20, 2020

Why is USDA "only" BSE TSE Prion testing 25,000 samples a year?

https://animalhealthreportpriontse.blogspot.com/2020/08/why-is-usda-only-bse-tse-prion-testing.html

Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.

JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001

JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

http://jama.jamanetwork.com/article.aspx?articleid=1031186

Terry S. Singeltary Sr.