Mad Cow/CJD Update
From Patricia Doyle, PhD
In this update:
[1] UK DOH vCJD monthly statistics - as of 7 Feb 2005; one more case
[2] UK - estimate of future cases reduced to 70
[3] [4] & [5] Inflammation and prion movement
[6] SEAC position paper - maternal transmission
[7] Blood supply - new technology for removal of prions
Date: Fri 11 Feb 2005
From: ProMED-mail <>
Source: UK Department of Health, Monthly Creutzfeldt-Jakob Disease
Statistics, Press release, Mon 7 Feb 2005 [edited]
[The UK Department of Health web-site has been revised, and the monthly new variant Creutzfeldt-Jakob disease statistics are now appended to the table "Creutzfeldt-Jakob disease in the UK by Calendar Year (since 1990)" which can be accessed at
The definition of the designations deaths, definite cases, probable vCJD cases, and, the case definitions can be found by accessing the Department of Health web-site or by reference to a previous ProMED-mail post (for example, CJD (new var.) - UK: update Mar 2002 20020305.3693)
The incidence of variant Creutzfeldt-Jakob disease, abbreviated CJD (new var.) or vCJD in ProMED-mail, in the UK appears to have plateaued, or perhaps to be in decline. Therefore, since many of the reports appearing in the update are only peripherally related to the situation in the UK, the opportunity is being taken to drop the designation UK from the title of this thread. - Mod.CP]
Monthly Variant Creutzfeldt-Jakob Disease Statistics as of Mon 10 Jan 2005
The UK Department of Health is today [Mon 7 Feb 2005] issuing the
latest information about the numbers of known cases of
Creutzfeldt-Jakob disease. This includes cases of variant
Creutzfeldt-Jakob disease (vCJD), the form of the disease thought to
be linked to BSE. The position is as follows:
Definite and probable CJD cases in the UK:
Summary of vCJD cases - Deaths
Deaths from definite vCJD (confirmed): 106
Deaths from probable vCJD (without neuropathological confirmation): 41
Deaths from probable vCJD (neuropathological confirmation pending): 1
Total number of deaths from definite or probable vCJD (as above): 148
Summary of vCJD cases - Alive
Number of probable vCJD cases still alive: 6
Number of definite or probable vCJD (dead and alive): 154
(The next update will be published on Mon 7 Mar 2005)
[Since the previous monthly statistics were released on Mon 11 Jan 2004, the number of deaths from definite vCJD is unchanged at 106, and the total number of deaths from definite or probable vCJD is unchanged and remains 148. The number of probable vCJD cases still alive has increased from 5 to 6. Therefore the overall total number of definite or probable vCJD cases has increased by one since 11 Jan 2004 to 154.
As of 4 Feb 2005, so far this year in the UK there have been 8 referrals of suspected CJD; and there have been 4 deaths from sporadic CJD, one from GSS, and none from Familial, iatrogenic or variant CJD. - Mod.CP]
Date: Wed 12 Jan 2005
From: ProMED-mail <>
Source: BBC News online, Health, Wed 12 Jan 2005 [edited]
"vCJD Timebomb" Fears Discounted
High numbers of future deaths in the UK from the human form [variant Creutzfeldt-Jakob disease of mad cow disease (bovine spongiform encephalopathy)] are unlikely, researchers have said. The Imperial College team [now] calculate there will be around 70 future deaths. They say the worst-case scenario could see another 600 deaths, but that this is unlikely. The research, which appears in the Journal of the Royal Society, said thousands of people could carry vCJD, but show no symptoms.
The higher forecast is based on the possibility that people from different genetic subgroups could be affected by vCJD. So far, people of only one genetic subgroup, which accounts for 40 percent of the population, have been affected. There have been 148 deaths from new-variant Creutzfeldt-Jakob disease (vCJD) since the condition was first seen in 1995. Research pointed to eating meat contaminated with bovine spongiform encephalopathy (BSE) as the cause. Over the last decade, scientists have been working to evaluate what the full extent of the vCJD epidemic will be. Deaths have been declining from their peak of 28 in 2000 to 9 in 2004.
But researchers who tested 12 674 appendix and tonsil samples found that 3 showed signs of apparent vCJD, indicating around 3800 people could ultimately be affected. However, only one of the 3 positive samples actually matched those taken from people who had been diagnosed with the clinical disease. Interpretation of the other 2 samples was less certain because they did not look [precisely] as scientists expected. The Imperial College team suggest this could mean that some people could be infected with vCJD, but not develop symptoms. If this was the case, looking at the population who would have eaten infected meat, computer programmes were used to estimate there could be a total of around 70 deaths from vCJD.
In addition, the Imperial team considered research into the genetics of those who could be affected. Until 2004, all of those affected had been from one genetic subgroup. But it was then revealed that someone with a different genetic make-up had probably become infected with vCJD after a blood transfusion. The researchers say that in this worst-case scenario -- if people of other genotypes are equally as susceptible as those in the original subgroup, but have a longer incubation period for vCJD -- there could be a total of around 600 deaths from vCJD.
Dr Azra Ghani, from Imperial College, said: "Since 2000 there has been a decline in the number of clinical cases reported. One reason for the discrepancy between the high estimated number of positive tests and low number of actual recorded clinical cases could be that infected individuals do not go on to develop clinical disease in their lifetime." However, the researchers say they have been unable to calculate how many vCJD cases could result in the future from blood transfusions from people who do not know they are carriers of the disease.
Dr Ghani said: "Although our results indicate there is little chance of large numbers of vCJD infections from primary transmission, we have not taken into account the possibility of additional cases infected by blood transfusion. This could result in more clinical cases emerging at a later date."
The CJD Surveillance Unit said predicting the extent of vCJD was very difficult, but said the more research was carried out, the more accurate predictions could be.
Date: Thu 20 Jan 2005
From: Terry S. Singeltary Sr. <>
Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions
[The following is the summary of a paper by Mathias Heikenwalder and 8 others, published in Science online, 10.1126/science.1106460, Thu 20 Jan 2005
This paper describes work that illustrates that chronic inflammatory conditions may affect and expand the natural and iatrogenic transmission of prions - Mod.CP]
Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with 5 inflammatory diseases of kidney, pancreas or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin upregulation and ectopic induction of PrPC-expressing FDC-M1+ cells, whereas inflamed organs of mice lacking lymphotoxin-alpha or its receptor accumulate neither PrPSc nor infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.
Date: Thu 20 Jan 2005
From: Terry S. Singeltary Sr. <>
Source: Reuters News Agency, Thu 20 Jan 2005
Study Finds Illness May Promote Spread Of Mad Cow Prion
(Reuters) -- The agent that transmits mad cow disease and related diseases may spread further in the body of an animal suffering from certain illnesses, scientists said on Thu 20 Jan 2005. Their finding raises the question of whether measures aimed at curbing the spread of mad cow disease, or bovine spongiform encephalopathy (BSE), are adequate, the researchers said.
Tests on mice showed that prions, the protein-like fragments that transmit BSE and related diseases [e.g. variant Creutzfeldt-Jakob disease in humans], can show up in organs they are not supposed to if the mouse has an inflammatory condition. Scientists have believed that BSE-causing prions are limited to the brain, spleen, spinal cord and lymph tissue, although some tests have suggested blood and muscle tissue may also harbor the prions. The latest study, published in the journal Science, suggests prions may also sometimes be found in the kidney, pancreas and liver. "We administered prions to mice with 5 inflammatory diseases of kidney, pancreas or liver," wrote the researchers, led by top prion expert Dr. Adriano Aguzzi of the University Hospital of Zurich in Switzerland.
Aguzzi and colleagues in Britain and the United States inoculated specially bred mice with prions and checked to see if the prions spread in their bodies when the mice had an inflammatory condition. This is because other studies had suggested that prions might be attracted to immune system inflammatory cells. "In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs," the researchers wrote.
BSE peaked in British cattle herds in the mid-1990s, and a few cases have been reported in other countries. Canada reported its 3rd case this month. People who eat BSE-infected beef products can develop a related human brain disease called variant Creutzfeldt-Jakob disease or vCJD. There is no treatment or cure. [As of 4 Feb 2005, so far in the UK for the year 2005 there have 8 referrals of suspected CJD; and there have been 8 deaths from sporadic CJC, one from GSS and none from familial, iatrogenic or variant CJD. - Mod.CP]. It has killed 148 Britons, and 5 [now 6] Britons are alive with the disease, according to the British Department of Health's monthly report on the disease. The World Health Organization says it has reports of 6 cases in France, one in Ireland, one in Italy, one in Canada and one in the United States [and one in Japan: see; ProMED-mail post "CJD (new var.) - Japan: death 20050204.0381" - Mod.CP]
Experts believed BSE first appeared when cattle were fed improperly rendered remains of sheep infected with scrapie, a related disease. In 1997, the United States and Canada imposed animal feed bans, and have mandated the removal of materials believed to carry infectious prions. These include the skull, brain, nerves attached to the brain, eyes, tonsils, spinal cord and attached nerves, plus a portion of the small intestine. The study suggests that even symptom-free animals may also have prions in their liver, kidney, and pancreas.
Terry S. Singeltary Sr.
Date: Fri 21 Jan 2005
From: ProMED-mail <>
Souce: New York Times, Fri 21 Jan 2005 [edited]
Study Finds Broader Reach For Mad Cow Proteins
By Sandra Blakeslee
NY Times
Mad cow disease has long been thought to occur in just the brains and nervous systems of infected animals. But scientists are reporting today that the proteins thought to cause the disease can travel to other organs as well. The research is based on experiments with mice, but if it is borne out in other species, it may suggest that no part of an infected animal is safe to eat. The disease leads to a fatal brain disease in humans [variant Creutzfeldt-Jakob disease].
In the mouse experiments, reported in the journal Science [see [3] above], researchers in Switzerland found that prions, proteins that are the infectious agent in mad cow disease, follow immune cells, called lymphocytes, in the body. When mice were given chronic infectious diseases of the liver, kidney and pancreas and then inoculated with prions, the prions made their way to the infected organs. Dr. Adriano Aguzzi, a neuropathologist at the University Hospital in Zurich, who led the experiments, said this meant that cows and sheep infected with prions could harbor the disease in any inflamed organ.
But Dr. David R. Smith, a veterinarian at the University of Nebraska, said the research did not raise alarms about American beef. For one thing, he said, livestock with obvious signs of systemic infection, like a fever, are not allowed into the food supply. And most American cattle are slaughtered while they are young and at reduced risk of infection.
Many countries, including the United States, require the removal of skulls, brains, eyes, spinal cords and other nervous tissues from slaughtered animals because prions are known to accumulate in those tissues. Even in countries with mad cow disease, mainly in Europe, meat is considered safe if those tissues are removed, Dr. Aguzzi said. But the disease could spread more readily if infections are not obvious or if inspections are sloppily done, he said.
Date: Fri 4 Feb 2005
From: Terry S. Singeltary Sr. <>
Source: Spongiform Encephalopathy Advisory Committee (SEAC), Position
Paper, January 2005 [edited]
Position Statement: Maternal Transmission of variant Creutzfeldt-Jakob disease
1. The Chief Medical Officer for England asked SEAC to consider current evidence and comment on the potential transmission of variant Creutzfeldt-Jakob disease (vCJD) from mother to child via human breast milk. In utero transmission was also considered. The committee also commented on the scientific basis of a risk reduction measure for possible transmission of vCJD via banked breast milk.
2. No diagnostic test is currently available for the detection of abnormal PrP in milk. Research is under way to develop tests to screen for the possible presence of abnormal prion protein (PrP) in milk samples from cattle experimentally infected with BSE [A joint FSA/SEAC milk working group is monitoring and providing advice on this research carried out at the Veterinary Laboratories Agency.] These modified tests may also be applicable to human milk. However, it is not yet clear when/if a reliable test will be available.
3. A small number of breast milk banks in the UK supply highly vulnerable premature babies for whom no milk may be available from the mother. A model developed by the Department of Health to assess the effect of pooling breast milk from multiple donors on the possible risks of transmission of vCJD via breast milk banks was considered.
4. There is some, albeit limited, published epidemiological and experimental research on maternal transmission of prion diseases. There are also unpublished surveillance data of children born to vCJD cases from the National CJD Surveillance Unit and UK surveillance of neurological illness in children which might inform on potential risks of maternal transmission.
Breast milk banks:
5. There is no evidence that vCJD infectivity has ever been transmitted through breast milk. However, a theoretical risk exists. Modelling studies clearly show that the practice of pooling breast milk increases the number of donors to which a recipient is exposed and thereby increases the potential risk of an infant receiving milk contaminated with vCJD infectivity. The theoretical risk of infection can be minimised by not pooling the milk, by the use of individual hand operated breast milk pumps for single donors, and by the use of single-use sterilised bottles for collection. In addition, available evidence suggests that infection/inflammation of the breast results in increased lymphocytes in milk and therefore increased risk of infectivity. This risk would be minimised if milk from donors showing signs of infection were not used.
6. The committee suggested that, if practicable, milk could be stored for an appropriate period of time to allow the health status of donors to be monitored, before it is released. However, information was not available to the committee on whether long-term storage of human milk is detrimental to its nutritional quality. Maternal transmission
7. There is evidence from animal studies for low-level maternal transmission of prions in cattle and sheep. This transmission may occur in utero, via milk and/or perinatally. However, the possibility that this putative maternal transmission might have been due to another mode of transmission, for example through a contaminated environment or feed, cannot be ruled out.
8. In contrast, in humans there is no evidence for maternal transmission in cases of familial prion disease, other than the transfer of a mutant form of the PrP gene, and there is no evidence of maternal transmission of Kuru [a chronic, progressive, uniformly fatal nervous system disorder caused by prions, associated with cannibalism among the Fore tribe and neighboring peoples in New Guinea. - CopyEd.PG]. However, compared with other human prion diseases vCJD may pose a greater risk because of the greater involvement of the lymphoreticular system in vCJD pathogenesis. Although, breast tissue (and placenta) from a single vCJD case tested negative for PrPvCJD, transfer of infectivity to breast milk may depend on the physiological status of the mammary gland. Similar tests or infectivity bioassays have not been conducted on breast tissue from lactating patients with vCJD.
9. A published study suggesting transmission of sCJD in colostrum (ref. 1) was considered unreliable because tissues not normally associated with high levels of infectivity (blood and placenta) showed equivalent infectivity to that of the brain in this study.
10. Analysis of prospective surveillance data of UK children born to mothers with, or that had subsequently developed clinical vCJD, provide no evidence for maternal transmission of vCJD. However, the number of cases is very small and the incubation period of vCJD, if transmitted from mother to child, is unknown and so the children may yet be too young to have developed symptoms.
11. The phenotype of BSE infection in humans expressing PrP genotypes other than M/M at codon 129 is not known. Given recently published studies in mice expressing the human PrP gene (ref. 2), which suggest that the human PrP genotype may affect disease phenotype, the committee considered it very important that undiagnosed neurological diseases be carefully monitored. In this respect, amongst others, it is recommended that the careful monitoring of neurological illnesses through the PIND surveillance of children (ref. 3) continue.
12. In summary, there is currently no epidemiological evidence for maternal transmission of vCJD, including transmission via breast milk. However, there is a hypothetical risk. Although available evidence is limited and mostly indirect rather than direct, this risk, if any, appears to be low. As a risk cannot be excluded, a watching brief should be maintained.
(1) Tamai Y et al. Demonstration of the transmissible agent in tissue from a pregnant woman with CJD. New Eng J Med 1992 327, 649.
(2) Wadsworth et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science. 2004 306, 1793-1796.
(3) Devereux G et al. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Arch DisChild. 2004 89, 8-12.
Terry S. Singeltary Sr.
Date: Wed 9 Feb 2005
From: ProMED-mail <>
Source: Medical News Today, Wed 9 Feb 2005 [edited]
Removing prions that cause mad cow in humans from blood
Assessing the risk of potential exposure to variant Creutzfeldt-Jakob Disease (vCJD), the human form of 'mad cow disease', from blood transfusion was the focus of the Food & Drug Administration (FDA) Transmissible Spongiform Encephalopathies (TSEs) Advisory Committee in Silver Spring, Maryland today. In response to the Committee's encouragement that new technologies should be considered that might lead to greater reduction of risk while not deferring many donors unnecessarily, Pall Corporation presented the latest scientific data on its new prion reduction technology.
The Leukotrap Affinity Prion Reduction Filter, expected to be launched commercially in Europe this spring, removes infectious prions from red cells, the most widely transfused blood component. Prions are associated with causing vCJD and other fatal neurodegenerative diseases, known as TSEs.
Sam Coker PhD, Principal Scientist and Technical Director of Pall Medical, acknowledged the public health community's heightened concern about the possibility of a 2nd wave of mad cow disease in humans of unknown magnitude globally, including North America. Japan is the latest nation to confirm a human case of mad cow disease.
The Pall Leukotrap Affinity Prion Reduction Filter was developed in response to these problems as part of the Company's mission to help ensure safety of the blood supply. It can remove leukocytes and all types of prions -- both cell and non cell-associated -- from blood prior to transfusion in a single step. Dr. Coker presented an overview of the key study results that show that the novel technology concurrently reduces leukocytes and prions with a 99 percent reduction of the infectious agent. He concluded that the new filter could be used to remove different strains of infectious prions, including those that cause vCJD.
He reviewed a study that found that the new filter reduces the human form of vCJD prions from red cells below the limit of detection of the western blot assay, the gold standard of prion detection. He also discussed a study with the infectious scrapie prion that causes disease in sheep, which showed that the new filter removed all the infectious prions below the limit of detection of the western blot assay.
Dr. Coker described in detail an animal infectivity study comparing filtered and unfiltered blood infected with scrapie prion. After the 300-day study, 3 of the 18 control hamsters that received the unfiltered blood developed scrapie. Only 2 of these animals had displayed clinical signs of the disease. None of the hamsters receiving filtered blood developed scrapie.
[ProMED-mail has no commercial or other association with Pall Medical. The information is relayed in the public interest. - Mod.CP]
Patricia A. Doyle, PhD
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