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Research in Italy Turns Up a New Form of Mad Cow Disease
February 17, 2004
By DONALD G. McNEIL Jr.
A new form of mad cow disease has been found in Italy, according to a study released yesterday, and scientists believe that it may be the cause of some cases of human brain-wasting disease.
While the strain has been found in only two Italian cows, both apparently healthy, scientists in Europe and the United States said it should provide new impetus in Washington for the Department of Agriculture to adopt the more sensitive rapid tests used in Europe because it may not show up in those used in the United States.
Along with the Italian study, there have been recent reports of unusual types of mad cow disease in France and Japan, and scientists say the discovery of new forms suggests that many cases of "sporadic" human disease - by far the most common kind, responsible for about 300 deaths a year in the United States - are not spontaneous at all, but come from eating animals.
The brain-destroying diseases involve prions – misfolded proteins that are believed somehow to induce other proteins to fold incorrectly, leaving patches of useless debris and holes that turn brains to sponge.
The study, by a team from universities in Turin, Verona, Brescia and Milan, was edited by Dr. Stanley B. Prusiner, who won a 1997 Nobel Prize for his prion work. It appears this week in The Proceedings of the National Academy of Sciences.
Two American experts not involved in the study said the findings were sobering. Dr. Pierluigi Gambetti, director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, called the report "very convincing." Dr. Paul Brown, a prion expert at the National Institutes of Health, said it "opens the possibility of a second strain of the agent in circulation - and that's probably not good news."
Current American testing focuses only on finding the prion that causes bovine spongiform encephalopathy in cows and "variant" Creutzfeldt-Jakob disease in humans.
But the disease found in two aged dairy cows in Italy is so different that its discoverers gave it a new name, bovine amyloidotic spongiform encephalopathy, or BASE, because it forms amyloid plaques in the brain - round, dark clumps of sticky protein junk.
"We don't know if this disease is passed to humans," said Dr. Salvatore Monaco, a neurologist at the G. B. Rossi Polyclinic in Verona and an author of the study. "But it is very similar to a subtype that causes sporadic C.J.D. in humans."
In the past, some people with cases diagnosed as sporadic have said they ate squirrel brains, pig brains or raw meat, but no link to a different prion was established, said Dr. Michael C. Hansen, who studies prion diseases for Consumers Union. Recently, he said, a new prion strain closely related to a French strain of scrapie, a sheep disease, was found in a French cow.
Both the Italian cows, one 15 years old and one 11, appeared healthy. Their unusual strain was discovered only because Italy tests all cattle over 30 months old slaughtered for human food. By last August, it had tested 1.6 million and found 103 that tested positive for prions.
Finding a new strain in apparently healthy cattle "suggests that all surveillance should be like we do in Italy," Dr. Monaco said.
Many American prion experts concur. The United States now plans to test only 40,000 cows this year, focusing on those too sick to walk, and using an immunohistochemistry test that takes about eight days and is "much less sensitive, "Dr. Gambetti said, than tests used in Europe that take only hours.
Besides forming plaques, the strain differs in that it appears in much older cattle. Most cows with the well-known strain die before they are 10. Also, the new prions collect in different parts of the brain - the olfactory bulb and thalamus, rather than the brain stem. The two cows also had relatively fewer "holes."
Those characteristics resemble the ones found in about 30 percent of humans who have the sporadic form of Creutzfeldt-Jakob disease.
In the United States, about one person per million develops and dies of the sporadic form each year, meaning that there are usually about 300 cases in the country. (For unknown reasons, Italy has nearly two cases per million; Switzerland has about three.)
Only one person in the United States has had variant Creutzfeldt-Jakob, the human form of mad cow disease, which was first described in the 1990's and has killed about 150 Europeans; she grew up in Britain and was probably infected there.
Most sporadic cases are among the elderly, while in Britain the variant form struck many people under 30. Victims of both rapidly develop staggering, memory loss and dementia, fall into comas and die.
Dr. Brown said the discovery did not suggest that many humans were suffering from undiagnosed illness. If that was the case, he said, the number of sporadic cases found in Britain since 1994 should have shot up; they have not.
The sporadic form has been assumed to arise spontaneously because there has been no other obvious cause, said Dr. Laura Manuelidis, a Yale neuropathologist who studies the disease.
But human cases from several countries produce different symptoms when injected into susceptible mice, showing that there are several human strains.
Dr. Manuelidis is skeptical of the conventional wisdom that prions, which contain no DNA or RNA, can transmit infections. She believes that a slow-acting virus, not yet discovered, may be the cause.
To make her point that such infections may have been crossing species well before mad cows created a scandal in Britain a decade ago, she read from an old report she has posted on her office door.
It is from an 1883 issue of the Medical Veterinary Review: A veterinarian named Serraet from southwest France describes a cow he saw die of the symptoms of scrapie, which had then been known in sheep for 100 years: itching, nervousness, partial paralysis and, ultimately, coma.
Dr. Serraet ends with a suggestion: "I would advise the managers of cattle abattoirs to sell the meat only to lower-class butcher shops."
Copyright 2004 The New York Times Company
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