April 15, 2004


 New form of BSE sparks discussion

Posted April 1, 2004 

Italian researchers say they have identified a new form of bovine spongiform encephalopathy that they have coined bovine amyloidotic spongiform encephalopathy or BASE. The study, reported in the March 2 issue of the Proceedings of the National Academy of Sciences, has sparked discussion in veterinary and medical communities.

Between January 2001 and August 2003, a BSE surveillance program in Italy identified 103 cases from 1,638,275 tested brain samples. When scientists tested for the abnormal prion that causes BSE, they found two samples that contained an unfamiliar prion.

The new prion causes accumulations of amyloid brain plaques, similar to plaques seen in Alzheimer's disease, instead of creating holes in the brain, the way BSE usually manifests itself. Past studies have shown that about 5 percent of cows with BSE, however, have amyloid plaques.

The BASE prion has fewer sugars attached to it and is also found in different areas of the brain. The previously identified BSE prion affects the brain stem and lower part of the brain; the new form is found in higher areas of the brain, such as the thalamus and olfactory bulb, and barely affects the brain stem.

Identifying areas of the brain impacted by a disease can lead to clues as to which nerves might carry the disease, possibly illuminating the transmission route. Because BASE does not affect nerves connected to the digestive tract, the Italian researchers hypothesize it was not transmitted through contaminated feed. They say the disease may have been transmitted through the air or another peripheral route.

Dr. William Hueston, director of the Center for Animal Health and Food Safety at the University of Minnesota, says he wouldn't rule out any route of transmission at this point.

"As cattle investigate their surrounding, they actually aggressively smell things, just as dogs do. They also investigate their surroundings with their tongue. They stick their tongue out and touch things, and then they flick their tongue inside their nose," said Dr. Hueston, an expert on BSE. "I wouldn't jump to air right away." The disease could also be a spontaneous event.

Interestingly, the BASE prion protein appears similar to some isolates from human sporadic classical Creutzfeldt-Jakob disease. Sporadic CJD accounts for 85 percent to 90 percent of CJD cases, and researchers say the new prion could be related to a subset of sCJD cases.

"It is possible that the BASE strain could be responsible for the ataxic sCJD variant seen in MV subjects with type 2 protein," said Salvatore Monaco, MD, an author of the PNAS study and a professor of neurology at Policlinico G.B. Rossi in Verona, Italy. One of the six types of sporadic CJD, M/V2, shows similarities to BASE in glycosylation and particle size. Previously, only the new variant strain of CJD was thought to have a link to BSE.

Dr. Hueston says that, while the study certainly suggests the identified prion causes a new strain of BSE, he'd like to see the findings corroborated by other scientists. With the current information available, a link between the new form of BSE and sCJD is only speculation. If there is a link, it's highly unlikely that it will explain all sporadic CJD, since the disease is seen around the world.

"Even in countries where dietary exposure to any type of meat products is limited, you still see (sporadic) CJD, so that would certainly argue against this being the sole explanation," Dr. Hueston said. "Even in countries where we see a huge amount of BSE, no European country—with the possible exception of Switzerland—has shown overall rates of sporadic classical Creutzfeldt-Jakob disease greater than what we see in the rest of the world."

At press time, researchers were in the process of looking more closely at the sCJD prion and two types of BSE prions. "We have passed the disease to mice and cattle and we are waiting for results," Dr. Monaco said. The Italian researchers say that strict epidemiologic surveillance of cattle TSE and CJD based on molecular criteria is needed.

Dr. Hueston says the new study should certainly "encourage BSE investigators to examine testing methods that can detect a full range of transmissible spongiform encephalopathy diseases." Putting the study in the grand scheme of things, however, a new BSE form shouldn't be a surprise.

"It's been quite unique that, to date, all of the BSE that has been identified up to this point was a single strain," Dr. Hueston said. "If people start looking for disease more aggressively, they are going to find more disease, regardless of whether it is influenza or Salmonella (infection), or whatever. We will discover (different) aspects of it, new strains, unique characteristics, or perhaps, differences.

We need to continue to look at strategies to determine what might be different strains of cattle prion diseases. This will stimulate people looking to see if they can find this different strain in different places and (to) characterize how frequently it occurs."