Canada bans tourist blood
Swiss BSE testing Q&A
Two more French cases
Top vet defends actions during BSE crisis
Amino acid may signal onset of Alzheimer's
Nevada testing deer and elk for CWD
Mad cow inquiry denied access to interview tapes
British ``mad cow'' cases seen declining, govt says
More BSE in Holland
Oct. 15, 1998 (UPI)TORONTO -- An independent council of health experts says people who have lived in Britain since 1980 should not be permitted to contribute blood or plasma to the Canadian Blood Services.
The Bayer Advisory Council on Bioethics said today it made the recommendation to avoid the risk of transmission of mad cow disease, or Creutzfeldt-Jakob disease, a fatal cattle malady that erupted in Britain in the 1980s.
The council's chairman, Dr. Burleigh Trevor-Deutsch, says there is no evidence yet that any form of Creutzfeldt-Jakob disease is transmitted among humans through blood, but the council is making the recommendation as a precaution.
He recalled the early 1980s, when thousands of Canadians contracted AIDS or hepatitis C through untested blood received from the Red Cross. The Red Cross recently handed over responsibility for receiving blood donations to the newly formed Canadian Blood Services.
The council recommends that "any persons who, at any time since 1980, have lived in a geographic area such as the United Kingdom that have a significant incidence of Creutzfeldt-Jakob disease or bovine spongiform encephalopathy, not be permitted to contribute blood or plasma until the potential risk can be evaluated."
It says there is an "urgent need to investigate all aspects of CJD through mandatory reporting and registration" and calls for more scientific research, "given the need to know more about the disease." The council has released a report on its own study, carried out since December 1997, on the hypothetical risk of transmission of mad cow disease among humans through blood or blood products.
October 15, 1998 CBC radioTORONTO -- CBC radio said that the Bayer Corporation Advisory Council on Bioethics wants Canada's new blood agency to ban blood donors who have lived in Britain anytime since 1980. The panel is concerned that people who ate British beef could carry a form of Creutzfeldt Jakob - the human brain disorder sometimes related to mad cow disease.
Burleigh Trevor-Deutsch, the head of the Advisory Council, said people in the United Kingdom may have been exposed to mad cow disease, which was known to be present in some British beef before the government took action against it in the mid-1990s. Trevor-Deutsch said they should not be allowed to contribute blood in Canada because large numbers of people could eventually become infected. The risk has already forced Britain to import all of its plasma from outside the country.
The article went on to say that the Bayer Corporation makes most of the blood products used in Canada but the new Canadian Blood Services says refusing plasma products from Britons would result in a severe blood shortage in Canada. A spokesman said the agency would then have to import blood from the United States, a country that hasn't banned British donors.
Canada Newswire October 16, 1998OTTAWA -- Earlier today, the Bayer Advisory Council on Bioethics released its report ``Creutzfeldt-Jakob Disease, Blood and Blood Products: A Bioethics Framework.'' Included in the document am 23 recommendations.
Canadian Blood Services (CBS), which assumed responsiblity for Canada's blood system in all provinces and territoires outside of Quebec on September 28, 1998, is well aware of the issues related to classical Creutzfeldt-Jakob Disease (CJD) and new variant CJD (nvCJD).
Canada has, had policies in place since 1995 aimed at deferring donors thought to be at risk for transmitting classical CJD, which does exist as a disease entity in Canada. The United States Food and Drug Administration recently relaxed criteria, used to defer these donors.
With regard to nvCJD, this disease has never been reported in North America and remains confined to Britain, with one case in France. There is also no evidence of transfusion transmissibility of CJD in any form.
The Bayer Advisory Council's recommendation to stop collecting blood and plasma from individuals who have resided in Britain since 1980 would have major implications for those Canadians who rely on blood products on an ongoing basis. Such a decision will reduce our supply of blood products and will necessitate importing additional quantities of blood and plasma products from countries such as the United States which do not have restrictions in place for nvCJD. Furthermore, no European countries have implemented this restriction. Based on what is known today, the potentiel reduction in supply would pose a greater risk than any collection of blood from individuals who have resided in Britain.
CBS believes global standards are required to address the impact of CJD because blood products are purchased on the international market. Like many countries, Canada is not self sufficient in blood products.
The Canadian Blood Services Board of Directors' Science, Safety and Ethics Committee, in cooperation with the National Blood Safety Council and Health Canada, will continue to respond to the CJD issue and to all emerging or potential pathogens. The Bayer Advisory Council's views will contribute to our deliberations over the next few months. The CBS Board of Directors and management team are committed to the reliable supply and safety of blood and blood products for Canadians.
"The last sentence of the third paragraph "The United States Food and Drug Administration recently relaxed criteria, used to defer these donors" is incorrect. According to the September 8, 1998--Change to the Guidance Entitled "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) by Blood and Blood Products", the FDA has NOT made any changes to the CJD blood/plasma donor screening process. Any donors who disclose CJD risk factors still have their donation deferred."
"The only change in the CJD policy is in the retrieval, quarantine, destruction, and notification for plasma derivatives from donors who reveal post-donation CJD risk factors. This policy change only affects plasma derivatives and does not affect blood or blood components, which are still withdrawn if the donor reveals post-donation CJD risk factors."
BBC News Online: UK Friday, October 16, 1998A panel of Canadian scientists is recommending a ban on blood donors who have lived in the UK in a move to stamp out the human form of "mad cow" disease. The committee said people who have eaten British beef since 1980 could carry a form of Creutzfeldt-Jacob's Disease (CJD). It recommends a blanket ban covering the last 18 years because it says it is almost impossible to predict who will become infected. And it says there is no easy way to separate those who have eaten beef in that time from those who have not.
Scientists speculate that BSE could be linked to the appearance of a new form of CJD, known as new variant CJD (nvCJD). The European Union banned worldwide exports of British beef in March 1996 after the government admitted that there was a probable link between BSE and nvCJD. The UK's National Blood Service said the report was a matter for the Canadian government, but that there was no reason to stop people giving blood in Britain.
The measures include removing all the white cells from blood before it is used (in a process called leukodepletion) and importing blood plasma from the US. So far 27 people have died in Britain of the human variant of BSE, which was particularly prevalent among cattle in the UK.
Marcus G. Doherr, Dr. med. vet., Ph.D. c/o Epidemiology Unit, P.O. Box Inst. of Virology and Immunoprophylaxis (IVI) CH-3147 Mittelhaeusern / SwitzerlandQuestion: systematic testing implies substantial costs and, even in a BSE-free population, a certain proportion of false-positive animals. From what data do you conclude that tests like that from Prionics produce false positive results?
Answer: Basically every test system produces false-positive (and false negative) results if you test a large enough number of disease-free (resp. diseased) animals. This is due to the natural biological variation inherent in the system(s) involved.
As for the Prionics Western Blot, the following information can be provided by the Swiss reference lab:
We have validated the Prionics Western Blot in the Swiss TSE reference lab using large numbers of blinded samples from confirmed positive and negative animals. The sensitivity was 95.4% and specificity 98.9%. False negatives and false positive test results, when compared to results of the immunocytochemistry and histopathology, were due to:
1. inadequate sampling (in view of the inequal distribution of the PrP accumulation in the CNS it is important to sample the correct anatomical area)
2. insufficient stringency of protease digestion.
Meanwhile, these technical shorthcomings have been corrected during the validation stage. Thus as the test stands now, both sensitivity and specificity approach 100%. Nevertheless, due to the variability inherent in the biological systems involved, error can never be completely prevented and a policy has been established for further examination of all Western Blot positives.
At the time of sampling, the brainstem is taken by a suction device. A small sample is used for the test. In case of a positive test result, the medulla is fixed in formalin for PrP immunocytochemistry with another antibody to confirm the Western Blot result. When IHC is negative, a third test consisting of sensitive histoblot test for PrP based on a third antibody is applied.
A case is considered positive when the Prionics check is confirmed with either one of the back up techniques. Since the expected number of both true and false positives by now is very low in Switzerland, the required back up effort is very limited to solve the problem of the false positives. The number of false negatives remains unknown in view of the fact that PrP accumulation can only be detected in the later stages of the incubation period.
A full manuscript with the results of the Prionics Western Blot validation is in preparation under the lead authorship of the Prionics scientists ( Marc Vandevelde and Marcus Doherr, Swiss TSE reference lab).
Question: how can you know that a herd is BSE-free when the best available tests only give positive results during the last about six months of the incubation time?
Answer: This is a very valid question, and two key points that will make the proof of disease freedom extremely difficult are the long incubation period for BSE and the absence of reliable ante-mortem tests for the disease. There are a few countries worldwide that are internationally accepted to be free of BSE. The problem certainly needs to be approached from at least two sides:
A. Prevention of new infection of cattle All routes of (re-)introduction of the disease into a country or region and (re-)circulation of potentially infectious material within the susceptible cattle population need to be detected and closed/prevented. This, in my opinion, is possible for BSE with the collaboration of all parties involved.
B. Detection of disease if present in the cattle population. A high awareness for (early) clinical signs of BSE among cattle owners and veterinarians, combined with a high interest of reporting suspect cases for confirmation. Follow-up and close supervision of high-risk animals (imports from endemic regions, herd mates of confirmed cases etc.). Testing (at slaughter) of all animals from high-risk cohorts and random sampling and testing of animals from the general population. Research to develop diagnostic tests for detection of earlier stages of the disease and for reliable ante-mortem diagnosis.
The whole scheme should be maintained for an extended period of time. Simulation modelling might help to determine how large the number of cattle sampled needs to be. In addition it might provide estimates on how long, starting from the point in time when one can be certain that new infections in a cattle population has been successfully prevented, one has to maintain the high degree of surveillance and sampling/testing to be relatively sure (statistically speaking) that a country or region is (again) free of BSE.
Question: how does one evaluate the issue of evaluation the sensitivity and specificity of a diagnostic test like the Prionics Western Blot? Answer: One part of the evaluation of any diagnostic test is always comparing the results of the "new" test to the results of a gold standard test system. The results of this comparison, expressed as the sensitivity (probability of getting a positive test result from a gold-standard-positive individual) and the specificity (probability of getting a test negative result from a gold-standard-negative individual) of the test, depend on the test but also on the choice of the gold standard. Sensitivity and specificity are RELATIVE measures on how a new procedure performs in comparison to the "truth" as defined by the gold standard. And even the "truth" can be wrong....
A non-BSE example: Assume you have developed a new serologic test to detect antibodies against disease x. What would be your negative gold standard: individuals that never (to your knowledge) were exposed to the agent causing x (i.e. from a disease-free region) with abscense of any clinical signs indicative of x and with negative test results in the standard test procedures. This still is not perfect but the best one can do to select disease-negative animals for the estimation of the new test's specificity.
How about the positive gold standard: One would try to get serum samples from animals (experimentally) infected with x that after inocculation demonstrated clinical signs indicative of x and that in addition showed seroconversion as proven by the routine test protocols. But now comes the critical point: What exactly is your definition of positivity (where is your cutoff): the known exposure to the agent (experimental inocculation), the known clinical infection (presence of clinical signs) or the confirmed seroconversion (as shown by other tests). If your new test is measuring antibody titers (seroconversion) and your positive gold standard is known exposure (experimental inocculation) then the test sensitivity will be very low for all animals that are between day 0 and, say, day 14-21 (seroconversion period) post inocculation. On the opposite, if your positive gold standard is "inocculation and confirmed seroconversion by standard procedures" and you test only animals +21 days post inocculation, then your new test, if it is worth the money, should have a very high sensitivity.
Both estimates (SE and SP) are experimental data and will not hold when appying the new test to a population in which we have individuals in all possible stages of incubation, clinical disease, recovery and seroconversion.
Back to BSE: the best negative gold standard we came up with were animals, old enough to have developed brain lesions and clinical disease in case of infection, from geographic regions at current free of BSE and with now clinical, histopathological and immunocytochemical signs of the disease (not all individuals in the pool met these inclusion criteria, but all were negative in the standard test procedures). The best positive gold standard that was available were animals with clinical signs consistant with BSE, histopathological changes and PrP(Sc) accumulation in the brain (IHC). For these two gold standard populations, the Prionics Western Blot performed very well and we therefore concluded that the sensitivity and specificity of the test is almost 100% (but with the lower limit on the 95% confidence interval below 100% since these are estimates based on samples of limited size).
In conclusion, if the inclusion criteria for gold standards are properly stated then I see no reason why one should not present the validation data the way it was done in our case. We did not claim that the test would perform well on BSE-incubating animals too young to have substantial PrP(Sc) accumulation in the CNS. For this cohort the sensitivity of the Prionics western blot certainly is very low, similar to the sensitivity of an antibody-detecting test when applied on infected animals before 14 days post infection (i.e. seroconversion).
Listserve 12 Oct 98Two French new cases of 'mad cow' disease have been detected in France in September and October 1998 : the first in the French "departement" of Nord, and the second in Orne:
Deux nouveaux d'ESB en France:
- Le 42e cas d'ESB a ÈtÈ diagnostiquÈ en France fin septembre et dÈcelÈ dans le dÈpartement du Nord ; il s'agit d'un animal de 3 ans environ.
- le 43e cas rÈpertoriÈ en France depuis 1990 est donc le 12e cas mis en Èvidence en 1998. L'animal atteint est une vache laitiËre du dÈpartement de l'Orne, nÈe en juin 1994 dans un Èlevage de ce dÈpartement. Il a ÈtÈ procÈdÈ ý l'Èlimination et ý la destruction totale de ce troupeau de 138 bovins.
PA News By Paul Peachey, PA NewsThe Government's top vet during the BSE crisis today defended himself against claims of a cover-up over the full risk to humans of mad cow disease. In a detailed statement to the official inquiry, Keith Meldrum told of his "extreme concern" in 1995 over flagrant breaches of a Government ban on potentially dangerous offal introduced six years earlier. Throughout the 269-page submission, Mr Meldrum said he had pressed for an open policy with the public.
He has been accused of toning down the extent of the risk to the public but claimed that MAFF policy was not to "generate unwanted publicity" that could hit the industry. Yet the document indicated top people at MAFF took years to discover what one vet said was "widespread and flagrant" flouting of regulations by abattoirs over their treatment of carcasses.
Mr Meldrum, the former chief veterinary officer, said four cases were discovered in 1995 where the spinal cord had not been properly removed. Mr Meldrum said: "I expressed my extreme concern that spinal cord could be finding its way into the human food chain putting the consumer at risk and undermining public confidence in the measures that had been taken by Government to protect the consumer."
But Professor Sir Kenneth Calman, the Government's former chief medical officer, criticised Mr Meldrum for failing to tell him about the cases which had started emerging three months earlier. He has already accused Mr Meldrum at the London inquiry of playing down the dangers of the four cases. Sir Kenneth told a MAFF official that the episode "did not help confidence between departments", according to Mr Meldrum's statement.
The friction between the two departments and the lack of communication between the top men has been viewed as a key failing that magnified the scale of the beef crisis. However, Mr Meldrum claimed his relationship with the Department of Health was "extremely open". He added: "I tried to give Dr Calman as much warning as possible of any new findings."
Mr Meldrum details the controls imposed on abattoirs and a 1995 ministry report warns how their procedures would have to improve or "put the future of the whole industry at risk including their part of it". Mr Meldrum, who retired in 1997, is due to give evidence to the inquiry on Monday.
He said that he had experienced no problems in dealing openly with ministers including Mr Gummer, William Waldegrave and Gillian Shephard. He said: "There was no difficulty. There was openness, frank discussion, reliance upon the judgment of each other and we worked as a team. "I had no difficulty getting access to ministers, talking to them, exchanging views and ensuring that every issue was given fullest consideration."
Mr Meldrum defended the Government's response to the early stages of the BSE crisis, describing some measures taken as "inspirational". Policies introduced in the late 1980s, such as the ban of feeding animal remains to cows, might have succeeded in eradicating the disease had they been more rigorously enforced, he suggested.
He said: "For my part, I believe that the measures necessary to control and eradicate BSE were put in place and that some of the measures were inspirational, facing as we were a new and totally unknown disease, where so many questions remained unanswered." The feed ban prevented a large number of BSE cases, but was undermined by cross-contamination in feed mills, he told the inquiry. Mr Meldrum continues his evidence tomorrow.
Sheila McKechnie, director of the Consumers' Association, said later: "When the inquiry was set up, we asked that it be given legal powers to gain access to vital documents. "If evidence is being withheld, there is a danger that the effectiveness of the inquiry will be undermined. "The only way to restore public confidence in the handling of food safety is to ensure complete disclosure by the Government of all relevant information."
October 19, 1998 Reuters News ServiceDURHAM, N.C. - High amounts of an amino acid commonly found in the blood of elderly people may be associated with Alzheimer's disease, researchers reported Sunday.
"These findings are important because they provide a testable hypothesis that it may be possible to prevent Alzheimer's disease from developing in a portion of potential sufferers" since the amino acid can be lowered by taking folic acid, A. David Smith, one of the researchers, said.
But he cautioned that people should not take extra folic acid without consulting a physician. Smith and Robert Clarke, both of Oxford University in Britain, discussed their findings in papers released at an American Medical Association conference at Duke University Medical Center. They reported on a study of 164 patients aged 55 and older who had Alzheimer's-type dementia. They found elevated levels of homocysteine in the patients' blood. Higher levels of the amino acid are common, increase with age and have also been linked to an increased risk of heart disease and stroke, the researchers said.
"Low blood levels of folate and vitamin B-12 and elevated homocysteine levels were associated with Alzheimer's disease," the study said. "The stability of homocysteine levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies," said the report, published in the Archives of Neurology.
In an editorial in that journal, Ramon Diaz-Arrastia of the University of Texas Southwestern Medical Center in Dallas said the report "raises as many questions as it answers." "Although it may be premature to advocate populationwide programs to screen for (elevated levels of the acid), neurologists may want to add measures of homocysteine levels to the battery of blood tests that are routinely done in usually futile searches for reversible factors that predispose to dementia," Diaz-Arrastia wrote.
AP 11 Oct 98State biologists are launching a study to determine whether deer or elk in Nevada have been infected with a malady -- similar to 'mad cow disease' -- that has turnedup in other Western states.
"We want to stress that there is nothing to indicate that the disease is in Nevada," said Gregg Tanner game bureau chief for the Nevada Division of Wildlife. "This is simple a concerted effort to confirm that we do not have it because of its potential ramifications."
... Deer infected with it show changes in behavior, including a lack of fear of humans. In later stages, the animals may wander aimlessly or spend unusual amounts of time with their ears and head drooping.
"It is the wildlife version of mad cow disease," said Chris Healy, wildlife division spokesman. ...Nevada biologists plan to analyze brain tissue samples for at least 500 deer and elk killed by hunters in the coming season.
Wildlife officials said there is some concern that elk and deer might be able to transmit the disease to cattle but there is no evidence of that so far.
Brain tissue samples will be collected at game meat processing plats, field contacts with hnters and hunter check stations. They must come from deer at least 18 months old which have eeen dead for 24 hours or less...
Tanner suggested hunters not shoot an animal that is acting abnormal or looks sick. He said it is always a good idea to wear rubber gloves when field dressing any big game and recommends minimizing contact with the brains and spinal column of deer and elk. David Rice, the diveision's chief conservation educator, said those recomendations are intended as extra safety precautions.
October 19, 1998 PA News Andrew WoodcockThe inquiry into the BSE crisis has been denied access to a taped interview with the government's former head vet, in which he discusses how ministers including John Gummer handled the problem, after ex-Chief Veterinary Officer, Keith Meldrum, refused to release the tape, the first time a request for documentation by the inquiry team under Lord Justice Philips has been turned down.
The revelation came at the end of a day in which Mr Meldrum had denied taking part in any cover up over BSE and told the inquiry that he had always believed in being open with the public about safety risks connected with food. Mr Meldrum was cited as telling the inquiry that the interview - conducted in 1993 by researchers from the University of Surrey, Department of Psychology, investigating the communication of risk to the public - had been carried out on condition of strict confidentiality and that he had declined to release it because it contained personal information about his family and colleagues and comments about ministers which he would prefer not to be become public.
He added that he would review his decision overnight, stating, "I have listened to the tape and comments on that tape are of a very personal nature, about my family, about myself, about my colleagues and so forth. Since the interview was conducted on the basis of confidentiality, I have some difficulty now in releasing all of it. I have no wish to see comments about previous ministers, about how I viewed Mr Gummer and his ability, for instance, to put over a message to the public - I think it was extremely good - coming out. It was very much a personal view of the various situations and some of that tape was very personal and relates to my family."
The inquiry secretariat does not have the power to demand production of the tape, which is presently held by the Ministry of Agriculture's Food Safety Directorate, which commissioned the research.
However, Downing Street wrote to all government departments at the outset of the inquiry asking them to cooperate fully with Lord Justice Philips and his team. It is thought likely that negotiations will take place to expurgate details which Mr Meldrum regards as personal. It also emerged today that the inquiry secretariat was unaware of the existence of a report into the BSE scandal drawn up in 1996 by MAFF official David North until a report in the Daily Express today revealed its existence.
Mr Meldrum was cited as denying today that communication breakdowns within the Government had magnified the scale of the BSE epidemic, stating, "Those who would suggest that we tended to adopt policies that would favour the agricultural industry and to some extent therefore endanger the consumer would be totally wrong. ... MAFF had an open policy and attempted as far as we were able to keep the public, the scientific community and international authorities fully informed about all aspects of BSE."
He further insisted that it was the job of the Chief Medical Officer, not the Chief Veterinary Officer, to inform the public about dangers to human health, noting, "I took the view then and I take it now that it is not the responsibility of the CVO to give advice to the consumer on the safety of beef or bovine products. That was the responsibility, I believe, of the CMO and his advisers and the Advisory Committee."
Reuters World Report 21 Oct 98LONDON - The number of British cattle suffering from BSE or mad cow disease is set to fall from nearly 3,000 this year to below 1,000 in 2000, the government said on Wednesday. Junior Agriculture Minister Jeff Rooker said in a written parliamentary answer that a computer prediction showed the epidemic of Bovine Spongiform Encephalopathy (BSE), which led to a ban on British beef exports, would continue to decline.
The model predicts between 2,685 and 2,891 cases in Great Britain, excluding Northern Ireland, in 1998. Next year the total will fall to between 1,223 and 1,741 cases, and in 2000 the number will be between 451 and 784 cases. Northern Ireland, from which beef exports have resumed, will have 20 cases this year, 12 cases next year and six in 2000.
The British government is hoping to persuade the European Union to allow a resumption of beef exports next year. The ban was imposed because of a suspected link to the deadly new variant Creutzfeldt-Jacob Disease (CJD), which has killed 27 people in Britain.
Rooker said it was impossible to estimate the level the epidemic would reach after 2000 because "by this time there will be random, unpredictable effects, particularly arising from cases occurring with long incubation periods."
Comment (webmaster): according to this model, the scrapie epidemic should have died out in 1748. Instead, it is still going strong 250 years later. Note that subclinical and preclinical cases are not counted in the model, even though these animals can be extremely infectious.
23 Oct 98 correspondenceThe 4th case of BSE has been diagnosed at a farm in Heeten (Raalte; mid-east of the Netherlands). The cow 'Trix 9' was 6 years of age and born in 1991. All 85 flockmates and 5 goats are culled and diagnosed for signs of TSE. All cows born in the same year as well as the whole family line will be traced and kulled for TSE diagnosis.