Mad cows & Englishmen: Variant CJD emerges in UK

CDC looking, but no cases seen yet in U.S.

No case has yet appeared in the United States, but medical experts are forecasting a possible epidemic of new variant Creutzfeldt-Jakob disease (nvCJD) in the United Kingdom. The uniformly fatal infection has been strongly linked to consuming meat contaminated with bovine spongiform encephalopathy (BSE) — widely known as "mad cow" disease.

"There is a real concern of an epidemic in England, where 900,000 cattle were eaten during the incubation period [of BSE] and potentially millions of people were exposed," says Richard T. Johnson, MD, professor of neurology, microbiology and neuroscience at Johns Hopkins University in Baltimore. "That may occur over the next 10 or 20 years — it’s a long incubation period. People have made estimates as high a 100,000, but there will probably be [at least] over a thousand people who come down with this disease in England."

From 1995 through early August 2000, 79 human cases of nvCJD were reported in the United King-dom, three in France, and one in Ireland. Recent data show an increasing trend for the epidemic of nvCJD in the United Kingdom, according to the Centers for Disease Control and Prevention in the United States.¹ The CDC is looking for signs of the pathogen in U.S. mortality data, and the agency has alerted the American Association of Neuro-pathologists to report any cases of nvCJD.

Different from classic sporadic’ disease

New variant CJD is not to be confused with traditional or "sporadic" Creutzfeldt-Jakob disease, a neurological disorder that has occurred throughout the world and the United States for years at a rate of about one case per million people. In contrast to the sporadic form of CJD, nvCJD in the United Kingdom predominantly strikes younger people (median age at death: 27.5 years as of October 2000). The disease has atypical clinical features, with prominent psychiatric or sensory symptoms at the time of clinical presentation and delayed onset of neurological abnormalities.

The recent cases of the new variant strain have probably been incubating in the English population for years, before problems were discovered in cattle, Johnson says. "What happened in England was the outbreak was at full blast — incubation-wise — before they recognized it. That shouldn’t happen here. We have the rules in place already to prevent widespread [transmission of BSE via beef supply]."

Still, Johnson expects a case of nvCJD to eventually appear in the United States. "A lot of us have been exposed to meat in Europe over the last 10 years," Johnson says. "And there is a great likelihood that U.S. troops stationed in Europe were exposed to contaminated meat, so a human is probably going to come down with it someday in this country. But we’re not talking about an epidemic."

The full transmission story on nvCJD is still being written, but initial lines of investigation suggest it is may be more transmissible than sporadic CJD. "The evidence is suggestive that this is transmitted by mouth, which is not a way [sporadic CJD] seems to transmit," Johnson says. "It seems the likeliest transmission [of nvCJD] is from beef. If that is the case, then it seems to be more readily transmitted. The other thing is that [nvCJD] is present in the tonsular tissue and in white cells within the intestinal tract, which makes people concerned that there is a possibility at least that blood could be contaminated."

Indeed, animal studies by an nvCJD researcher in the United Kingdom found evidence the patho-gen could spread from the brain and reach infectivity levels in the spleen and tonsils.²

"It is possible that occasionally nvCJD will be transmitted accidentally from person to person, but if this occurs at a low frequency it may not lead to a long-term establishment of the disease in the human population," says Moira Bruce, MD, a researcher at the Institute for Animal Health neuropathogenesis unit in Edinburgh, UK. Though the disease does not spread easily between people, nvCJD could present new challenges for infection control professionals trying to prevent nosocomial transmission via surgical instruments.

"[nvCJD] is likely to be more of a risk than sporadic CJD because there is a more extensive involvement of noncentral nervous system tissues in nvCJD," Bruce notes. "Therefore, there is possibly a greater chance of contamination of surgical instruments, etc."

Little data are available yet on health care transmission of nvCJD, but the traditional, sporadic CJD has been linked to nosocomial or "iaterogenic" transmission in more than 250 patients worldwide. The cases have been traced back to the use of contaminated human growth hormone, dura mater and corneal grafts, or neurosurgical equipment. Of the six cases linked to the use of contaminated equipment, four were associated with neurosurgical instruments, and two with stereotactic EEG depth electrodes. The equipment-related cases occurred before the routine implementation of sterilization procedures currently used in health care facilities. No such equipment cases have been reported since 1976, and no transmission of CJD has been linked to environmental surfaces, the CDC reports.

Traditional CJD has proven difficult to re-move from surgical instruments, and presumably the new variant strain will be just as vexing a sterilization issue. Beyond that, what about the possibility that nvCJD could be transmitted by a needlestick?

"Previous work in rodent models has shown that animals can be infected by subcutaneous injection or through scarified skin," Bruce says. "The efficiency of these routes is quite low, but the experiments do suggest that needlestick injuries might be a problem, if the needle were heavily contaminated, for example, with brain tissue. Blood is not likely to be a problem in this respect because, if there is any infectivity in blood, it is likely to be there at a very much lower level."

Though studies in animals have shown that there are low levels of nvCJD infectivity in blood, transmission has occurred when larger volumes of blood are involved, Bruce says. For example, a sheep was experimentally infected with BSE and then used as a blood donor. "A large volume of blood was transfused intravenously into another sheep, which subsequently developed BSE," Bruce tells Hospital Infection Control. "This shows that, theoretically, there may be a risk of transmitting nvCJD by blood transfusion."

References

1. Centers for Disease Control and Prevention. Web site: http://www.cdc.gov/ncidod/hip/INFECT/CJD.htm.

2. Bruce ME, McConnel RG, Ironside JW. Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues. Lancet 2001; 358:208-209.