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From: TSS ()
Subject: Predicting susceptibility and incubation time of human-to-human transmission of vCJD
Date: March 27, 2006 at 6:24 am PST

Lancet Neurology DOI:10.1016/S1474-4422(06)70413-6

Predicting susceptibility and incubation time of human-to-human transmission of vCJD
MT Bishop a, P Hart b, L Aitchison b, HN Baybutt b, C Plinston b, V Thomson b, NL Tuzi b, MW Head a, JW Ironside a, RG Will a and JC Manson b

Summary
Background
Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility.

Methods
Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease.

Findings
BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV.

Interpretation
Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.

Affiliations

a. National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Edinburgh, UK
b. Institute for Animal Health, Neuropathogenesis Unit, King's Buildings, Edinburgh, UK

Correspondence to: Prof J C Manson, Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, King's Buildings, West Mains Road, Edinburgh EH9 3JF, UK

http://www.thelancet.com/journals/laneur/article/PIIS1474442206704136/abstract?isEOP=true

27 March 2006
Of mice and men... and vCJD
Destination Journal: The Lancet Neurology

Variant Creutzfeldt-Jakob Disease (vCJD) has become a serious public-health concern in Europe, especially in the UK, since it was first described in 1996. This new prion disease in human beings, acquired by ingestion of food contaminated by the bovine spongiform encephalopathy (BSE) agent, has raised new questions not only about food safety, but also about the possibility that human prion diseases could be transmitted from human to human. .....


http://www.thelancet.com/journals/laneur/article/PIIS1474442206704148/fulltext?isEOP=true

Scientists warn of high rate of vCJD infection

Polly Curtis, health correspondent
Monday March 27, 2006
The Guardian


A "significant level" of the population could be unknowingly infected with variant CJD, according to scientists whose study reveals the disease to be more easily transmitted than previously thought.
The debate about the number of people infected by vCJD - the human form of BSE - has ranged from estimates of a few hundred to hundreds of thousands.

Some people are understood to be more genetically susceptible to the disease but the study published today by Lancet Neurology shows that mice with all variations of the gene involved were susceptible to different degrees to vCJD passed on through infected blood transfusions.

The paper concludes: "All individuals ... could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public health issue."
The study confirms that the likelihood of transmission from animal to human via infected meat is low, but suggests human to human transmission through infected blood products and surgical equipment is more likely than previously thought.

The National CJD Surveillance Unit and the Institute for Animal Health in Edinburgh said there had been 161 reported cases of vCJD in the UK.

The degenerative brain disease causes progressive dementia, and is in most cases fatal. The incubation period is believed to be up to 15 years.

It is believed that the number of infections through infected meat has been reduced dramatically since safety measures were introduced in the 1990s.

But scientists fear a second wave of cases could be on the way, from people accidentally infected through contaminated surgical instruments or blood transfusion.

The government is considering ways of screening people during postmortems to see whether they are carriers in an effort to see how much hidden vCJD there is.

http://www.guardian.co.uk/bse/article/0,,1740397,00.html

Scots team finds dormant CJD could emerge to claim many more lives
LOUISE GRAY
New study claims vCJD may lie dormant without symptoms
Disease may also be contracted by blood transfusion
Fears that underlying vCJD may lead to second wave of deaths
Key quote
"You cannot rule out the possibility there may be some effect of BSE on people who have so far shown no effect" - PROF HUGH PENNINGTON

Story in full FAR more people could be at risk of contracting the human form of mad cow disease than previously thought after new evidence emerged that the condition could lie dormant for years before developing.

A long incubation period for the disease, together with an ability to pass it on through blood transfusions and surgical instruments, has the potential to create a "significant public health issue", scientists from Edinburgh said.

Through studies on mice, they concluded that variant Creutzfeldt Jakob Disease (vCJD) could lie in the body for many years without showing any symptoms.

Due to long incubation times for the disease, a "significant level" of underlying vCJD may already be present in the population, they said.

The number of deaths from vCJD rose steadily from 1995 to a peak of 28 in 2000, since when fatalities have fallen, leading many to conclude the worst had passed.

But the latest research suggests a second peak is still to come and the disease could claim many more lives.

The disease, believed to be passed from cattle to humans through eating meat infected with BSE during the 1980s and 90s, has killed 154 people in Britain to date, according to the vCJD Surveillance Unit at the Western General Hospital. Six people are still fighting the disease.

Until now, those who have died from the disease have been of a particular gene type - the MM genotype.

However, through studies on mice, scientists at the Institute for Animal Health in Edinburgh concluded that variant vCJD could also be found in other genotypes but lie in the body for many years without showing any symptoms.

This means a "significant level" of underlying vCJD may already be present in the population without knowledge.

The experts also found that vCJD could be passed from human to human through secondary transmission - such as blood transfusions and contaminated surgical equipment - in all genotypes.

The study, published on-line today by The Lancet Neurology, said the fact people may not know they are carrying the disease in its dormant form means it could be spread through blood transfusion to which all genotypes are susceptible.

"All individuals... could be susceptible to secondary transmission of vCJD through routes such as blood transfusion," the scientists warn in the study. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public health issue."

Last November, about 50 people who received blood transfusions were warned they may have been exposed to vCJD.

In July, a similar warning was issued to about 100 blood donors whose blood was given to three people who later developed the disease.

Professor Hugh Pennington, the president of the Society of General Microbiology, said there could be a second wave of fatalities if more genotypes are affected but not yet coming down with symptoms. "You cannot rule out the possibility there may be some effect of BSE on people who have so far shown no effect," he said.

But, people with longer incubation periods are likely to be less susceptible to the disease and Prof Pennington thought a second wave would have begun to show.

More likely is the risk of unknowingly transmitting the infection. This would increase the risk to the population as a whole, but it is impossible to say how many people would die as a result.

"I do not think anybody could put a figure on it," said Prof Pennington.

Graham Steel, co-founder of the vCJD Alliance, whose brother died of the disease, said it was "not welcome news".

"This [is] certainly a 'warning sign' that should be taken with utmost seriousness," he said.

Marc Leighton Turner, a clinical director for the Scottish National Blood Transfusion Service, said the findings were of concern. "It may well be that people of all types of gene type have been infected but it is predominantly the MM gene type who have died of the disease, which suggests there may be a significant number of people in the general population who have been infected but who do not have the disease and indeed may never have the disease. This is a concern for us in the blood transfusion service and surgeons as they may be a source of secondary transmission."

Delusions, loss of mobility, and a young life cut short by this terrible illness
DONNA McIntyre was a successful young woman when signs of the human form of mad cow disease began to emerge.

Two months before her 21st birthday, the receptionist disappeared from her flat in Aberdeen. When she resurfaced, she was clearly ill. She had been living on the streets and had become delusional.

Donna was a meat-eater and liked her burgers and pies but her family never expected this to cause such a terrible illness. Over the next few months Donna lost her speech and mobility.

She died of vCJD aged 22, 12 months after she was diagnosed with the illness, in August 2001.

Malcolm Savidge, the former Labour MP for Aberdeen North who supported Donna's family through that difficult time, said it was always unclear whether it would be "hundreds or hundreds of thousands" affected by BSE-infected meat.

After the recent fall in deaths he was hopeful it would remain low, but the new research has led to fresh uncertainty.

"We have to be aware of the possibility that there may be still be a further terrible toll taken. But we must hope that is not going to be the case," he said.

http://news.scotsman.com/index.cfm?id=470922006

TSS




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