HEALTH TOPICS A TO Z

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal human neurodegenerative condition. As with Creutzfeldt-Jakob disease, vCJD is classified as a Transmissible Spongiform Encephalopathy (TSE) because of characteristic spongy degeneration of the brain and its ability to be transmitted. vCJD is a new disease that was first described in March 1996.

Before the identification of vCJD, CJD was recognized 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 85–90% of CJD cases. Familial cases are associated with a gene mutation and make up 5–10% of all CJD cases. Iatrogenic cases result from the accidental transmission of the causative agent via contaminated surgical equipment or as a result of cornea or dura mater transplants or the administration of human-derived pituitary growth hormones. Less than 5% 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 TSE of cattle called Bovine Spongiform Encephalopathy (BSE).

Total cases

From October 1996 to November 2002, 129 cases of vCJD have been reported in the United Kingdom (UK), six in France and one each in Canada, Ireland, Italy and the United States of America. Insufficient information is available at present to make any well-founded prediction about the future number 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 UK. Some of the patients had been long-standing residents in Wales, Scotland or Northern Ireland.
• As of early November 2002, the CJD surveillance unit for the UK reported 129 cases of vCJD, including 93 confirmed and 24 probable cases. In addition, there are 12 cases where vCJD is strongly suspected, but the diagnosis has not yet been definitively confirmed by post mortem analysis.
• Some of these patients have donated blood. However, to date vCJD has never been known to have developed in a recipient of this blood; study of possible transmission through blood transfusion continues. The UK 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 countries with higher risk of BSE. WHO cautions that donor restrictions such as these may not improve safety in some countries, particularly those still unable to institute measures against known hazards such as HIV, HBV and HCV.

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 and, by the time of death, patients become completely immobile and mute.

Diagnosis

• The clinical presentation, progressive nature of the disease and failure to find any other diagnosis are the hallmarks of vCJD.
• There are no available, completely reliable diagnostic tests for use before the onset of clinical symptoms. However, magnetic resonance scans, tonsillar biopsy and cerebrospinal fluid tests are useful diagnostic tests.
• The brainwave pattern observed during an electroencephalogram was abnormal in most of the vCJD patients, but the wave forms characteristic of sporadic CJD do not occur.
• Currently the diagnosis of vCJD can only be confirmed following pathological examination of the brain. Characteristically, multiple microscopic and abnormal aggregates encircled by holes are seen, resulting in a daisy-like appearance described by the term "florid plaques".

Probable cause

• vCJD is strongly linked with exposure to the BSE agent. BSE is a TSE affecting cattle and was first reported in the UK in 1986. Since that year, about 181 376 cases have been reported in the UK. The number of reports of BSE in the UK began to decline in 1992 and has continuously declined year by year since then. In 2002, only 755 cases were reported in the UK; 891 from the 21 other countries reporting BSE cases.
• The most likely route of exposure was 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 UK, relatively small numbers of BSE cases (in total 3679) have also been reported in native cattle in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Liechtenstein, Luxembourg, Netherlands, Poland, Portugal, Slovakia, Spain and Switzerland. However, all but 206 cases have been reported in six countries — France, Germany, Ireland, Portugal, Spain and Switzerland. Since the introduction of monitoring programmes to detect BSE in dead and slaughtered cattle, 12 countries have found their first native case (Austria, Czech Republic, Finland, Germany, Greece, Israel, Italy, Japan, Poland, Slovakia, Slovenia, Spain).
• Small numbers of cases have also been reported in Canada, the Falkland Islands (Islas Malvinas) and Oman, but solely in animals imported from the UK. The International Office for Epizootic Diseases (OIE) reports these cases on their web site.
• The nature of the TSE agent is being investigated and 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 virus-like and possesses nucleic acids which 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 virus-like agent.

Evidence of vCJD-BSE link

• The hypothesis of a link between vCJD and BSE was first raised because of the association of these two TSEs in time and place. More recent evidence supporting a link, includes identification of pathological features similar to vCJD in brains of macaque monkeys inoculated with BSE. A vCJD-BSE link is further supported by the demonstration that vCJD is associated with a molecular marker that distinguishes it from other forms of CJD and which resembles that seen in BSE transmitted to a number of other species. Studies of the distribution of the infectious agent in the brains of mice artificially infected with tissues from humans with vCJD and cows with BSE showed nearly identical patterns.
• The most recent and powerful evidence comes from studies showing that the transmission characteristics of BSE and vCJD in laboratory mice are almost identical, strongly indicating that they are due to the same causative agent.
• Intensive surveillance in 17 European countries has confirmed the high incidence of vCJD in the UK, the country with the largest potential exposure to BSE. France (with six reported cases) imported relatively large quantities of cattle products from the UK. The case in Ireland lived in the UK. Canada and the United States of America (all with extremely low potential exposure) have confirmed reports of vCJD attributed to exposures that occurred when the case lived in the UK. The Italian case did not live in the UK.
• For the final opinion of the European Union's Scientific Steering Committee on the Geographic Risk of BSE, please see the link at the bottom of this page.
• In conclusion, the most likely cause of vCJD is exposure to the BSE agent, most plausibly due to dietary contamination by affected bovine central nervous system tissue.

Other human TSEs

Other human TSEs include kuru in Papua New Guinea, which is believed to be transmitted in the course of funerary rituals. During these rituals, family members who were preparing the body for burial were exposed, or may even have consumed the brain tissues of people who had died from kuru. Gerstmann-Sträussler-Schenker (GSS) syndrome (occurring in persons with an apparent hereditary predisposition) and fatal insomnia (which occurs in familial and sporadic forms) are the other known human TSEs. 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

Due to strong suspicions of a linkage between vCJD and BSE, the British government made BSE a notifiable disease in June 1988. Shortly afterwards, a statutory ban on the feeding of protein derived from ruminants (e.g. cattle, sheep and goats) to any ruminant was introduced. 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. The list of banned bovine offals was revised and expanded on several occasions as new information became available. In 1994, the EU banned mammalian MBM to ruminants, however, the measures taken, the date of implementation and the extent of enforcement vary from country to country. In 2001, because of the continued risk from cross contamination, the EU introduced a total feed ban (e.g. ban on feeding MBM to all farm animals).

WHO involvement

• Since 1991, WHO has convened 11 scientific consultations on issues related to animal and human TSEs. These meetings have made wide-ranging recommendations aimed at protecting human and animal health.
• In 2001, WHO, FAO and OIE jointly convened a Technical Consultation on BSE: Public Health, Animal Health and Trade.
• As exposure to the BSE agent may extend to populations outside Western Europe, it was recommended that to ascertain the number and distribution of any future cases, global surveillance of CJD and its variants would be required. From 1997–2000, WHO held a series of training courses worldwide, particularly in developing countries, in order to help individual countries establish national surveillance of CJD and its variants. The first workshop, for West African countries, was held in Dakar, Senegal in June 1997. Similar workshops were held in Bangkok for South-east Asian countries (October 1997), in Cairo for North African countries (February 1998) and in China for countries of the Western Pacific (July 1999) and for Eastern and Central European countries in May 2000.
• WHO has revised its training guidelines for surveillance and provides a globally accepted case definition for all forms of human TSEs.

WHO recommendations

To protect human health, WHO has also recommended the following:

• The clinical presentation, progressive nature of the disease and failure to find any other diagnosis are the hallmarks of vCJD.
• There are no available, completely reliable diagnostic tests for use before the onset of clinical symptoms. However, magnetic resonance scans, tonsillar biopsy and cerebrospinal fluid tests are useful diagnostic tests.
• The brainwave pattern observed during an electroencephalogram was abnormal in most of the vCJD patients, but the wave forms characteristic of sporadic CJD do not occur.
• Currently the diagnosis of vCJD can only be confirmed following pathological examination of the brain. Characteristically, multiple microscopic and abnormal aggregates encircled by holes are seen, resulting in a daisy-like appearance described by the term "florid plaques".

• No part or product of any animal which 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 of animal TSE agents. The pharmaceutical industry should ideally avoid the use of bovine materials and materials from other animal species in which TSEs naturally occur. If their use is absolutely necessary, bovine materials should be obtained from countries which have a surveillance system for BSE in place and which report either zero or only sporadic cases of BSE. These precautions apply to the manufacture of cosmetics as well.
• In 1999, a review was conducted of the known information about a number of animal TSEs to try to proactively determine if there are any new TSE threats. Their principle recommendations were to eradicate BSE and to find out if BSE has infected sheep populations.
• Joint WHO/FAO/OIE Technical Consultation on BSE: Public Health, Animal Health and Trade.