Variant Creutzfeldt-Jakob Disease--Information from the World Health Organization.

In June 2001, the World Health Organization (WHO) revised its fact sheet on variant Creutzfeldt-Jakob disease (vCJD). The information below is adapted from the fact sheet.

Background

Variant Creutzfeldt-Jakob disease is a rare and fatal human neurodegenerative condition. Like Creutzfeldt-Jakob disease (CJD), vCJD is classified as a transmissible spongiform encephalopathy (TSE) because it causes a characteristic spongy degeneration of the brain that can be transmitted. This disease is a new one and was first described in March 1996.

Before the identification of vCJD, CJD was known to exist in only three forms. Sporadic cases, which have an unknown cause and occur throughout the world at the rate of about one per million people, account for 85 to 90 percent of CJD cases. Familial cases are associated with a gene mutation and make up five to 10 percent of all CJD cases. latrogenic cases result from the accidental transmission of the causative agent via contaminated surgical equipment during cornea or dura mater transplants, or through the administration of human-derived pituitary growth hormones. Fewer than five percent of CJD cases are iatrogenic.

In contrast to the traditional forms of CJD, vCJD has affected younger patients (average age 29 years, as opposed to 65 years), has a relatively longer duration of illness (median of 14 months as opposed to 4.5 months), and is strongly linked to exposure, probably through food, to a cattle TSE called bovine spongiform encephalopathy (BSE).

Total Cases

From October 1996 to early June 2001, there have been 101 cases of vCJD reported in the United Kingdom, three in France, and one in the Republic of Ireland. The information available at present is not sufficient for a well-founded prediction about future numbers of vCJD cases.

Epidemiology

The first person to develop symptoms of what turned out to be vCJD became ill in January 1994. Most people who have developed vCJD have lived in the United Kingdom. Some of the patients had been long-standing residents of Wales, Scotland, or Northern Ireland.

Some of these patients have donated blood. To date, however, vCJD has not been known to have developed in a recipient of this blood; study of possible transmission through blood transfusion continues. The United Kingdom no longer sources plasma from its inhabitants and, as a further precautionary measure, has instituted leukocyte reduction (removal of white blood cells) from blood transfusions. Some countries have prohibited donations of blood from persons who have resided in the United Kingdom for longer than six months or for one year.

Clinical Features

Early in the illness, patients usually experience psychiatric symptoms, which most commonly take the form of depression or, less often, a schizophrenia-like psychosis. Unusual sensory symptoms, such as "stickiness" of the skin, have been experienced by half of the cases early in the illness. Neurological signs, including unsteadiness, difficulty walking, and involuntary movements, develop as the illness progresses. By the time of death, patients have become completely immobile and mute.

Diagnosis

The clinical presentation, the progressive nature of the disease, and failure to find any other diagnosis are the hallmarks of vCJD.

No completely reliable diagnostic tests are available for use before the onset of clinical symptoms. Magnetic resonance (MRI) scans, tonsillar biopsies, and cerebrospinal-fluid (CSF) tests may, however, be useful.

The brainwave patterns observed during electroencephalograms (EEGs) were abnormal in most of the vCJD patients, but the wave forms characteristic of sporadic CJD did not occur.

Currently, the diagnosis of vCJD can be confirmed only after pathological examination of the brain. Characteristically, multiple microscopic and abnormal aggregates encircled by holes are seen, giving a daisylike appearance described as "florid plaques."

Probable Cause

Occurrence of vCJD is strongly linked with exposure to the BSE agent. BSE was first reported in the United Kingdom in 1986. Since that year, about 180,900 cases have been reported in the United Kingdom. The number of reports in the United Kingdom began to decline in 1992 and has declined year by year since then.

The most likely-route of exposure is through bovine-based food, although infectivity is mainly found in the brain and spinal cord of clinically ill animals over two years of age.

Since 1989, when the first BSE case was reported outside the United Kingdom, relatively small numbers of BSE cases (approximately 1,900 in total) have been reported in native cattle in Belgium, Denmark, France, Germany, the Republic of Ireland, Italy, Liechtenstein, Luxembourg, the Netherlands, Portugal, Spain, and Switzerland. All but a couple dozen of those cases have been reported in just six countries--France, Germany, Ireland, Portugal, Spain, and Switzerland. Small numbers of cases have also been reported in Canada, the Falkland Islands (Islas Malvinas), and Oman, but solely in animals imported from the United Kingdom. The International Office for Epizootic Diseases (OIE) reports these cases on its Web site at [less than]www.oie.int[greater than].

The nature of the TSE agent is still a matter of debate. According to the prion theory, the agent is composed largely, if not entirely, of a self-replicating protein, referred to as a prion. Another theory argues that the agent is viruslike and possesses nucleic acids that carry genetic information. Although strong evidence collected over the past decade supports the prion theory, the ability of the TSE agent to form multiple strains is more easily explained by a viruslike agent.

Other Human TSEs

Other human TSEs include kuru in Papua New Guinea, which is believed to be transmitted in the course of funerary rituals involving brains of corpses; Gerstmann-Straussler-schenker syndrome (occurring in persons with an apparent hereditary predisposition); and fatal familial and sporadic insomnia. CJD is the most common of all the human TSEs and is the disease most commonly mistaken for vCJD.

Measures Taken to Protect Public Health

The British government made BSE a notifiable disease in June 1988. Shortly afterwards, a statutory ban was introduced on the feeding of protein derived from ruminants (e.g., cattle, sheep, and goats) to any ruminant. The use in the food chain of bovine offals considered to pose a potential risk to humans was also banned in the UK in 1989, and the list of banned bovine offals was revised and expanded on several occasions as new information became available. In other countries, measures taken, dates of implementation, and the extent of enforcement vary.

WHO Recommendations

WHO has recommended the following precautions to protect human health:

* No part or product of any animal that has shown signs of a TSE should enter any (human or animal) food chain.

* Countries should not permit tissues that are likely to contain the BSE agent to enter any (human or animal) food chain.

* All countries should ban the use of ruminant tissues in ruminant feed.

* Human and veterinary vaccines prepared from bovine materials may carry the risk of transmission. Ideally the pharmaceutical industry should avoid the use of bovine materials and materials from other animal species in which TSEs naturally occur. If the use of such materials is absolutely necessary, bovine materials should be obtained from countries that have a surveillance system for BSE in place and that report either zero or only sporadic cases of BSE. These precautions apply to the manufacture of cosmetics as well.

Further Information

In 1999 a review was conducted of the information known about a number of animal TSEs. The purpose was to proactively determine if there are any new TSE threats. The principle recommendations were to eradicate BSE and to find out if BSE has infected sheep populations. The WHO recommendations are available under the heading "TSE" at [less than]http://www.who.int/emc-documents/[greater than].