Study raises new fears over human toll from mad cow disease
Agence France Presse
PARIS - The final human toll from mad-cow disease could be higher than is conventionally thought because of a potential risk from blood transfusion, a new study says.
Variant Creutzfeldt-Jakob disease (vCJD) was identified 10 years ago as the human form of mad-cow disease, a fatal disorder in which a rogue prion protein called PrPSc proliferates in the brain, turning it spongy.
The fear then was that vCJD would inflict a nightmarish toll, especially in Britain, where millions of people were exposed to beef from infected cows.
Over the years, estimates of the final toll have fallen sharply, from hundreds of thousands to the mere hundreds.
But the big unknowns are how long vCJD takes to incubate before its symptoms become visible and whether some people are genetically more at risk than others.
Seeking to explore this, researchers in Scotland looked at a part of the human genome -- variations on a stretch called codon 129 -- that can affect the transformation of the normal PrP prion into the malevolent PrPSc.
They created several lines of mice that had been genetically modified to produce the key variations in human codon 129.
These variations are called methionine (MM), methionine-valine (MV) and valine (VV).
The modified mice were then injected with infected brain cells that came from cases of either vCJD or the animal equivalent, bovine spongiform encephalopathy (BSE).
All three types of mice became infected with the vCJD, beginning with the MM variant, followed by the MV and VV types. But none became infected with BSE.
The team says the findings are mixed news.
On the one side, it suggests there is a significant "species barrier" that could protect people who ate BSE-tainted beef.
On the other, all codon-129 variants were infected by the vCJD samples, and the disease took a long time to incubate before the lab mice started to fall sick.
In other words, people could have received the vCJD prions through blood transfusions but it could take many years yet before they show symptoms of the disease, according to this theory.
And because they themselves carry PrPSc, yet do not know it, they themselves could hand it on to others through blood donations.
"Transmission of BSE to humans is probably restricted by the presence of a significant species barrier," say the authors, led by Jean Manson, a professor at the Institute for Animal Health in Edinburgh.
"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 pre-clinical disease is predicted by these models, which may represent a risk for further disease transmission."
The study does not offer a new estimate for vCJD mortality, given that even now, 10 years after the disease was identified and tough measures taken to stop BSE among cattle, it is impossible to say whether PrPSc is still entering blood banks.
In a commentary, published in the same journal, French researcher Corinne Lasmezas warns against extrapolating results on lab mice to humans, given their different physiology.
And she notes that the rodents had received the prions by an injection directly into the brain, whereas humans receive blood transfusions through a vein or artery, which means that any infectious agent still has to penetrate the brain's protective membrane.
The number of confirmed and suspected vCJD cases presently stands at 189, comprising 160 in Britain, 17 in France and 12 elsewhere, according to the latest official tallies. Only two cases are known to have occurred through blood transfusion.
So far, all cases vCJD have arisen among people with the MM genotype, a variant that occurs among 40 percent of Caucasians, which suggests that the MV and VV variants may confer some protection, says Lasmezas.
