State to try to better detect extent of mad-cow diseases

By Sandi Doughton
Seattle Times staff reporter

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Soon after the nation's first mad-cow case was discovered in Washington, Dr. Tom Montine started getting calls from worried people who told him they had eaten beef that may have come from the infected Holstein.

The director of neuropathology at the University of Washington, Montine tried to calm their fears and explain that the chance of getting sick is extremely slight.

But, he wondered privately, what if the worst happens? If some Northwesterners do contract the human form of the brain-wasting disease, would it be properly diagnosed — or mistaken for some other form of dementia?

Washington doesn't require doctors to report mad-cowlike diseases in people, and hospitals have been reluctant to do autopsies on people who might have died from the mysterious infections.

So Montine joined with Harborview Medical Center, the Washington state Department of Health and a top national laboratory to improve surveillance and diagnosis of so-called prion diseases across the region.

The health department is preparing to send letters to all of the state's physicians, asking them to be on the alert for patients who might be suffering from variant Creutzfeldt-Jakob (vCJD) disease, the scientific name for the human version of mad-cow. The agency is also asking doctors to look for likely cases of classical Creutzfeldt-Jakob disease (CJD), a fatal condition similar to mad-cow disease but with no known cause.

With the permission of families, Harborview will perform autopsies for free. The hospital will take special precautions to prevent spread of the infectious agent and ship victims' brains to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland for expert analysis.

Both CJD and vCJD appear to be caused by misfolded proteins called prions. Only by examining brain tissue is it possible to distinguish the two diseases — and detect the human form of mad-cow if it does turn up here.

"I hope that doesn't happen," Montine said. "But if it does, without this system we could miss it."

And even if there are no human mad-cow infections, better diagnosis will improve understanding of CJD and help researchers tease out possible links between the similar, and equally baffling, diseases.
 
That's especially critical because several new studies suggest some cases of CJD, which experts believed had no connection to mad-cow disease, may actually be caused by eating infected meat.

"It's very difficult to rule it out," said Dr. Pierluigi Gambetti, director of the Case Western laboratory. "That's one of the reasons we need better surveillance."

Uphill battle

Gambetti has been campaigning to raise awareness of CJD and persuade more states and institutions to participate in his autopsy program.

"It is really an uphill battle," he said. "People are afraid to do these autopsies, but we're dealing with a disease where autopsies are the only way to get a diagnosis."

Gambetti estimates his lab gets brain tissue from fewer than half of the estimated 300 cases of CJD that occur each year in the United States. That means it's possible human mad-cow cases, or unusual forms of CJD, are going undetected.

"You have to look at all of these cases if you want to protect the American public from these diseases," he said.

Only about 25 states require doctors to report CJD cases. Washington is not among them, although reporting is encouraged. About five or six people in the state die from CJD every year, but fewer than half are autopsied, said health-department spokesman Tim Church.

Some scientists also think CJD may be more common than believed, hidden among millions of people with Alzheimer's disease.

"There are so many questions about this disease that they don't have answers for," said Shoreline resident Sandy Skrinjaric

When her mother died in 2001, doctors told her that classical CJD was almost certainly the cause. But the family didn't know about Gambetti's lab and didn't even consider an autopsy.

Now, Skrinjaric, a former hospice worker, regrets the lack of a definitive diagnosis and wonders whether something her mother ate or was exposed to could have been responsible.

"I think something triggered it. I just don't know what," she said.

Moon suit, extra gloves

Since Washington bolstered its surveillance system after the infected cow was discovered at a Moses Lake slaughterhouse in December, one CJD victim has been autopsied at Harborview, Montine said.

The hands-on work is done by Michael Hobbs, the hospital's autopsy coordinator and a 24-year veteran in the field. Because prions can't be killed by most conventional sterilization techniques, even he was a bit apprehensive.

"Very few people will even do these, because it can be dangerous if you don't take the proper precautions," he said. "I wear a moon suit and about nine pairs of gloves."

There's no evidence prions can spread through the air, but the disease has been transmitted by contaminated surgical instruments and may be spread through blood. So Hobbs works alone, draping off the entire body except the head. The saw blade and scalpel used to remove the brain are treated with formic acid, one of the few substances that can destroy prions.

"I'm very meticulous about how I do things," Hobbs said.

Half of the brain is flash-frozen, the other half preserved in formalin. Both halves are heat-sealed in three plastic bags and shipped to Cleveland in a special container via Federal Express for testing and examination.

So far, the United States' only human mad-cow infection has been a young Florida woman who likely picked up the disease while living in England. Of the approximately 150 people worldwide infected with the human form of mad-cow, nearly 90 percent were from the United Kingdom, where the cattle disease was rampant a decade ago.

If other cases appear here, Gambetti says he's confident his lab will be able to detect them — as long as the victims are autopsied.

But it's also possible that a home-grown version of human mad-cow might look very different from the version that appeared in Britain.

"There's no guarantee it will be the same," he said.

New questions, possible links

Researchers are finding few things are certain when it comes to prion disease, which Gambetti argues makes better diagnosis more important than ever.

Classical CJD was discovered decades before mad-cow disease appeared in England in the 1980s. The conventional wisdom is that the disease arises spontaneously, as a result of genetic mutations or a breakdown in cell processing that allows abnormal proteins to build up and destroy brain cells.

While CJD usually strikes older people, the human form of mad-cow that emerged in the United Kingdom afflicts mainly people in their 20s and 30s.

Symptoms of the two diseases are slightly different: The first signs of CJD are usually memory loss and difficulty walking, and most victims die within six months of onset; vCJD usually begins with psychiatric problems, such as anxiety and depression, and progresses to pain and paralysis that can persist 1-4 years before death.

Under the microscope, the diseases are more distinct. While both cause characteristic holes in brain tissue, the human form of mad-cow is also marked by tangles of plaque.

But last month, Italian researchers reported a new form of mad-cow disease that looks very similar to classical CJD. And last year, British researchers were surprised to find that mice genetically engineered to respond like humans to prion infections came down with a disease similar to classical CJD after being injected with mad-cow prions.

Laura Manuelidis, a Yale University neuropathologist who has studied CJD, is among scientists who say the evidence points to a link between mad-cow and CJD.

"I don't believe that CJD occurs spontaneously," she said. "I think it's absolutely the result of an infection."

There is evidence that the disease can occur more frequently than the one-in-a-million rate usually quoted by experts. In the United Kingdom, the incidence of CJD has doubled since the 1970s. In Switzerland, which has a very comprehensive surveillance program, CJD is turning up in roughly three people out of a million.

In the United States, the rate appears to be steady, but many experts say that could be because surveillance is so limited.

Manuelidis conducted a study that found up to 13 percent of people diagnosed with Alzheimer's disease or other forms of dementia are actually suffering from CJD. Other studies have put the figure as low as 3 percent. With nearly 4 million Americans suffering from Alzheimer's, that could mean 120,000 or more undiagnosed CJD cases.

Including Harborview, Gambetti now has about 20 centers across the country that will perform autopsies on suspected CJD victims. With money from the CDC, his lab pays for the cost of shipping the body to the closest center.

"In the European countries, 70 to 80 percent of CJD cases are autopsied," he said. "That's how they were able to spot vCJD in Britain ... and this is what we should try to achieve here in the U.S."

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com

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