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http://www.timesonline.co.uk/article/0,,2-1435630,00.html

January 12, 2005

Scientists predict just 70 more deaths from vCJD

By Mark Henderson, Science Correspondent ONLY 70 more people are likely to die from the human form of mad cow disease from infected beef, according to the most comprehensive study of the condition to date. Britain’s outbreak of variant Creutzfeldt-Jakob disease (vCJD) has probably peaked and the 147 deaths so far make up two thirds of the final toll, scientists said yesterday.

The findings dispel fears of a vCJD timebomb, which were raised last year when research suggested that up to 3,800 people might be infected with the incurable brain disorder.

A more precise analysis of these results indicates that only a small fraction of this number will contract the disease and die. The study has cut the estimated number of those carrying the rogue prion proteins that cause vCJD to 3,000, and calculates that just 70 will develop the full-blown condition.

The rest - about 93 per cent of the total infected with prions by eating beef - will remain carriers but stay healthy. They might, though, transmit the disease by giving blood.

Even under the worst outcome, no more than another 363 clinical cases of vCJD contracted from BSE-infected beef are likely. More people could still develop the disease through contaminated blood transfusions.

The estimates, by Paul Clarke and Azra Ghani of Imperial Colledge, London, add to a growing consensus among epidemiologists and doctors that the human impact of the BSE crisis will be much smaller than initially feared.

When vCJD first appeared in 1995, projections suggested that it might kill 500,000 people. The number of deaths has declined sharply from a peak of 28 in 2000 to just eight recorded last year. A further five patients are still alive.

This trend had led experts to predict that the ultimate total would be numbered in hundreds rather than thousands, but research at Derriford Hospital in Plymouth published last May triggered concern that this could be an underestimate.

The study of appendix and tonsil tissue from more than 12,500 people found signs of vCJD in three of them, which when extrapolated to the entire population suggested that there could be 3,800 carriers.

Dr Ghani, who was part of the team that made that estimate, said that the figure was a “rough back-of-the-envelope calculation”, and that the new work is a much better reflection of the likely shape of the disease’s spread.

In the study, published in the journal Proceedings of the Royal Society, the researchers sought to explain the discrepancy between the projections from the tissue samples and current death trends.

They found that the best explanation was that most people infected with prions would not develop the disease.

“The most plausible reason is that a very, very high proportion of those who are infected would not develop the disease,” Dr Ghani said. “We have seen this happen in animal studies, and it is the explanation that best fits the data.”

Asked whether she thought that the outbreak had peaked, she said: “I think that’s the case for consumption of beef. There is still uncertainty about secondary transmission via blood transfusions, though.”

Every clinical case of vCJD reported has occurred in people with particular genetic attributes, and there is concern that people with different DNA profiles could be susceptible after a longer incubation period.

The study considered this possibility, but found that even if true the total number of future cases is likely to be just 363. “If other genotypes are susceptible, it could potentially increase the clinical cases fivefold, but it is still not on the scale of the appendix survey,” Dr Ghani said.


Also - from the BBC Jan 12 2005

'vCJD timebomb' fears discounted

High numbers of future deaths in the UK from the human form of mad cow disease are unlikely, researchers have said.

The Imperial College team 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% of the population, have been affected.

Tonsil samples

There have been 148 deaths from new-variant Creutzfeldt-Jakob disease (vCJD) since the condition was first seen in 1995.

There is little chance of large numbers of vCJD infections from primary transmission
Dr Azra Ghani, Imperial College
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 nine last year.

But researchers who tested 12,674 appendix and tonsil samples found three showed signs of apparent vCJD, indicating around 3,800 people could ultimately be affected.

However, only one of the three positive samples actually matched those taken from people who had been diagnosed with the clinical disease.

Interpretation of the other two samples was less certain because they did not look like scientists expected them to.

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, they used computer programmes 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 last year, 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 with other gene variants 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.

Blood transfusions

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 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.

But Frances Hall, of the Human BSE Foundation said she would rather see researchers focus on developing a test that could pick up early signs of the test in those who were affected.

"I don't think estimates of numbers makes a lot of difference to people who have been affected, or people who are worried about it."