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VARIANT CREUTZFELDT-JAKOB DISEASE—
WILL IT COME TO AMERICA?
LONDON—There is growing concern that variant Creutzfeldt-Jakob disease (vCJD) is not going to remain a disease confined to the United Kingdom. Since the establishment in 1993 of a surveillance system for all forms of CJD, France, the Republic of Ireland, and China (Hong Kong) have all reported isolated appearances of the disease. Bovine spongiform encephalopathy (BSE), the putative cause of vCJD, has been found in Greece, and concern has been expressed about infected cattle herds elsewhere, including the United States, leading John Collinge, MD, of St. Mary’s Hospital in London to describe vCJD as “an evolving epidemic.” He delivered his remarks at the 17th World Congress of Neurology.
EUROGENESIS
Updating the statistics on the elevating circulation of vCJD, Robert Will, MD, of the University of Edinburgh, said that “as of May 2001, 100 cases of vCJD had been identified in the UK, and statistical analysis has shown that the numbers of cases are clearly increasing with time.” Additionally, the European Union, which funds the surveillance system for CJD in conjunction with Australia, Canada, Iceland, Israel, Norway, and Switzerland, reported a case in the Republic of Ireland and one in Hong Kong (the first reported in any Asian nation). Both cases involved individuals who had previously resided in the UK. “The Irish case had lived in the UK during the 1980s, when human exposure to BSE was likely to have been significant,” noted Dr. Will. However, three cases of vCJD were also reported in France, and none of those had visited the UK, a fact that suggests “exposure to indigenous BSE or perhaps to bovine exports from the UK.”
Dr. Will added that it cannot yet be conjectured how many cases will ultimately be reported, or from which other countries. At this point, he said, the main risk factors for vCJD are residence in the UK and a young age. The mean age at death from vCJD is 29, although one case has been reported in a 74-year-old. There may also be a genetic susceptibility factor. All the tested cases exhibited methionine homozygosity at codon 129 of the prion protein gene. At the same time, Dr. Will conceded, “it is possible that genetic variation may influence the incubation period, and cases with genotypes other than methionine homozygous may yet be identified.”
MEANWHILE, ACROSS THE POND …
While there is now “compelling evidence” that vCJD is caused by the agent of BSE, the US Food and Drug Administration has expressed concerns about the “possibility of transmission of infection from person to person through the use of blood or blood products or from contaminated surgical instruments,” said Dr. Will.
It has long been known that sporadic CJD may be transmitted by procedures performed on the brain with instruments unwittingly used on patients with CJD. A new finding, however, is that surgery on parts of the lymphatic system, such as tonsillectomies or splenectomies, also pose a risk for transmission of these abnormal prions. Professor Adriano Aguzzi, from the University of Zurich, explained that this is a result of the neuro-invasion process that occurs in vCJD. The ingested infectious prions first invade the lymphatics, including the tonsils and spleen, in their march toward the brain.
Dr. Will added that because of the lengthy incubation period of vCJD, whether the agent is transmissible by blood might not be known with any certainty for many years. In light of this, the US and Canada have both introduced precautionary “exclusion criteria” for blood donations from individuals who worked and traveled extensively in the UK during the 1980s.
DIAGNOSIS DILEMMAS
The possibility of person-to-person transmission emphasizes the need for a diagnostic test that would detect vCJD at its earliest stages, commented Dr. Collinge, who is head of England’s National Prion Clinic. The disease, which occurs mostly in young people, is commonly misdiagnosed in its early stages as some sort of psychiatric disorder. Initially, patients with vCJD usually show anxiety, depression, withdrawal, and behavioral changes. Patients may also report persistent pain or other odd sensations in the face or limbs. After several weeks or months, a neurologic diagnosis is evident, as the person develops ataxia and progressive dementia.
“We want clinicians to refer [patients] to us at an early stage, even when the diagnosis may be unclear,” Dr. Collinge stressed. Diagnostic facilities offering a full range of tests, including molecular genetic analysis and tonsil biopsy with prion protein gene analysis, will be required in order to establish the proper diagnosis. Fulfilling that role in the US is the National Prion Disease Pathology Surveillance Center, which was established in 1997 at the Division of Neuropathy of Case Western Reserve University in Cleveland, to monitor the possible occurrence of vCJD in this country.
“Progress in understanding the disease process and uncovering potential approaches to treat and prevent prion diseases must go hand in hand with diagnostic procedures,” Professor Aguzzi added. Work on a diagnostic test based on plasminogen binding, which can differentiate between normal and abnormal prions, is already under way, he said, and the Swiss-based company Serono has reported that it has developed a method of ultrasonic prion sorting, although the company has not yet manufactured a commercial test for either humans or cattle.
NR
—Jean McCann
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