Vet Pathologist Wants Program
To Screen For Mad Cow Disease

By David Bowser

AMARILLO — Don Montgomery is one pen rider feedyard owners listen to.

From his early years in the Eastern Texas Panhandle, Montgomery moved to Amarillo where he graduated from Amarillo High School. He worked as a pen rider in a feedlot before going on to earn his veterinary medical degree, then a Ph.D. in veterinary pathology.

Today, he is Donald L. Montgomery, D.V.M., Ph.D., and head of diagnostic pathology at the Texas Veterinary Medical Diagnostic Laboratory here. He is an expert in neuropathology, which includes the area of transmissible spongiform encephalopathies.

One of those is so-called "mad cow" disease.

TSEs are a diverse group of central nervous system diseases that affect both man and animal.

TSEs that affect humans, Montgomery says, can be divided into familial or inherited TSEs and sporadic or acquired TSEs. Familial TSEs include Gerstmann-Strausler-Scheinker disease, fatal familial insomnia, and familial Creutzfeldt-Jakob disease, while sporadic TSEs include Creutzfeldt-Jakob disease and Kuru. Creutzfeldt-Jakob disease, or CJD, can be further broken down to sporadic, iatrogenic and "new variant" strains.

Kuru has some relevance to BSE or "mad cow," Montgomery says, since it is propagated by ritualistic cannibalism.

"This disease was much more common in women and children because they were the ones who ate the brain," Montgomery notes.

(CJD has a similar connection, at least in some jungle villages of Papua New Guinea. There family members for generations have consumed the brains of deceased elders in a funeral ritual that presumably was intended to pass on accumulated wisdom. It passed on CJD instead, and the subsequent prevalence of the disease within certain families initially led researchers to believe it was inherited. — Ed.)

TSEs in animals include scrapie, transmissible mink encephalopathy, chronic wasting disease of elk and deer, and bovine spongiform encephalopathy.

Montgomery says there have been reports of TSEs among elk and mule deer populations in a restricted area from northeastern Colorado into southeastern Wyoming. There have also been two recent reports of infected elk in captive herds in South Dakota and Oklahoma.

"Traditional views of infectious disease such as those caused by viruses, bacteria, etc., would dictate that the infectious agent must contain nucleic acid for replication," Montgomery says.

At one time, TSEs were classified as viral diseases, but they are not, Montgomery says.

TSEs are caused by unconventional agents in that no nucleic acid has ever been demonstrated, and these agents are resistant to treatments that would degrade nucleic acids.

Although there are two theories, the prion theory and the viral theory, the consensus today is tending toward the prion theory.

"Prions are normal proteins found in all animals and also in man," Montgomery explains. "Proteins are made from set sequences of amino acids that comprise the growing blocks of these proteins. Normal proteins can be broken down in a pattern. The most widely accepted theory is that these diseases are caused by abnormal forms of prion proteins."

The abnormal proteins are highly resistant to degradation, he says.

"Once an abnormal prion protein gains access to an individual's body or brain, it causes a conformational change in the protein that makes it very resistant to change."

Studies with mice have shown that even after infected tissues have been burned, extracts injected into healthy animals can still produce the disease.

TSEs characteristically have very long incubation periods.

"The incubation period is measured in years," he says. "BSE has an incubation period of as little as 18 months and as long as eight years. The onset is very insidious. There is no successful treatment. The disease is 100 percent fatal."

Complicating research and surveillance efforts is that until recently — and even now, only in one specific instance so far — there has been no antemortem diagnostic test for TSEs. That means suspected victims cannot be clinically diagnosed until after they have died.

Dealing specifically with BSE, symptoms include behavioral changes in the animal, hypersensitivity to light, touch and sound, motor dysfunction, decreased milk production (81 percent of the cases have been in dairy herds), poor body condition and salivation.

Montgomery says cattle appear panic-stricken, restless, nervous and aggressive.

"Grinding of the teeth is very frequent," he says.

While the name draws pictures of a cow’s brain with holes like a piece of Swiss cheese in it, Montgomery says there are no changes obvious to the naked eye. But under a microscope, lesions are visible. There is formation of vacuoles in neurons and brain substance.

"The brain doesn't appear all that different," Montgomery explains. "To the naked eye there are no specific abnormalities visible. Where the disease gets its name is that there are these so-called spongy changes, but they're of a microscopic nature."

With scrapie or Kuru there is a plaque buildup.

Readily available diagnostic tests for confirmation are limited to microscopic examination of brain, Montgomery says, although there is a possible new test for scrapie using eyelid biopsy.

"Other than scrapie, there are no tests to diagnose TSE," Montgomery says. "For some reason, sheep with scrapie deposit abnormal prion protein in their eyelids. For the others, diagnosis requires examination of the brain tissue."

Accumulations of abnormal prion proteins in the cerebral spinal cord can be used for a presumptive diagnosis, but confirmation requires microscopic examination of the brain itself, hardly a practical option in a living animal.

Not all animals are susceptible to TSE, Montgomery says.

"It seems like the body's own prion protein presence is a must for susceptibility to TSE," he explains.

There appears to be a species barrier in transmissibility as well as differences in genetic susceptibility.

"There are certain differences in the sequence of the prion protein between species," Montgomery says. "The greater the differences in the amino acid sequences between species, the more unlikely the disease can be transmitted. There is also genetic resistance within species. There are differences in prion proteins between different humans and different cows, making some animals and some humans more susceptible to the disease."

The origin of BSE is thought to be the feeding of scrapie-infected biproducts to cattle, coupled with changes in rendering practices, though another theory holds that BSE was always present at undetectable levels and that outbreaks resulted from rendering and feeding practices. There is also a theory that there have been spontaneous mutations in the bovine prion gene.

BSE was first identified in the early 1980s. The first reported case, in July 1988, lead to a ruminant feed ban the following month.

More than 171,000 cases of BSE have been reported, 70 to 80 percent of them in dairy herds. In these herds there was a four percent incidence on 70 percent of the farms involved. The incidence seems to have peaked in 1992-93, Montgomery says, and there is some thought that the disease will die out by 2001.

There is a slight chance BSE can be transmitted orally, and it can be transmitted genetically from the mother cow, although it is estimated that such transmission is not sufficient to maintain the current number of cases.

With regard to BSE and sporadic CJD, the worldwide incidence is about one case in one million population. The mode of acquisition or transmission is unknown, Montgomery says. About 85 percent of the patients with the disease have sporadic CJD. There is no evidence of increased incidence due to occupational exposure. Sporadic CJD usually affects people 40 to 60 years of age.

"The mode of acquisition or the mode of transmission is entirely unknown," Montgomery acknowledges.

Regarding BSE and "new variant" CJD, the first cases were reported in 1995.

"There have been 27 cases reported in Great Britain," Montgomery says, three in 1995, 10 in 1996 and 10 in 1997.

"There have been four in 1998 so far," he says. "There are those who say this is the beginning of an epidemic, but only time will tell. I certainly hope not. Looking at 1998, it certainly doesn't appear that there will be a severe outbreak."

New variant CJD differs from the sporadic form in several ways, he says. New variant exhibits a younger age of onset.

"The usual age is about 29 years," Montgomery notes.

Initial symptoms of new variant are behavioral, where with the sporadic form of CJD, it is dementia. Patients with new variant tend to live longer, but not much so. They tend to live 10 to 12 months compared to seven to nine months for the sporadic form.

"But these do seem to be very separate and distinct diseases," Montgomery says.

In addition to the 27 cases in Great Britain, there has been one from France. The clustering of cases of new variant CJD in Britain, the country with by far the highest incidence of BSE, would suggest a close correlation between the two diseases, Montgomery says.

"Experimental evidence would suggest that new variant CJD is possibly related to BSE," he continues, but he cautions: "No matter what anybody says, this association has not been confirmed."

Studies done with mice in 1996 and 1997 would suggest that people are susceptible to BSE, but that does not prove that the new variant CJD is the result of BSE, Montgomery says.

"The evidence is there, and this may be as close as we can determine, to be quite honest with you, in drawing an association between BSE and new variant CJD," he says.

Montgomery says finding such diseases in the U.S. would be devastating. There have been no cases of BSE reported in the United States nor have there been any reports of new variant CJD in the United States, but that makes it all the more important to watch for it, Montgomery contends.

"It's very important that we employ a rigorous pattern of surveillance throughout the coming years," he insists. "Public perception, right or wrong, is as important or more important than sound scientific fact. We've seen this certainly in our own community."
Montgomery says the industry needs to develop new ways to assess infectivity.

"We need new, easy, cheaper diagnostic tests in earlier stages," he says. He also wants to see effective therapies developed.

"We need to understand the biology of these diseases," Montgomery stresses.

The outbreak of BSE in Great Britain and the publicity it received did heighten the interest of the general public and the scientific community in learning more about these kinds of diseases," he says.

"We know more now than we did a few years ago," Montgomery points out, but he acknowledges that there is still a lot to learn.

Since these diseases can have a profound impact on national and international politics, food safety issues, animal rights groups and international trade barriers, Montgomery says surveillance is critical, particularly among producers.

An effective and credible surveillance system for BSE requires that a representative number of brains from animals showing clinical neuralgic signs be submitted for microscopic examination.

"It is the producer who is best situated to identify these animals and arrange for their submission to the diagnostic labs," he says. "The animals, heads or brains can be submitted directly or certainly through your veterinarian."

The requirements are that the animal should be at least 18 months old to qualify for the surveillance program, certain portions of the brain stem must be available for examination, and pertinent clinical data including age, sex, breed if known, and clinical signs should be submitted with the samples.

"It starts with the producers," he says.