Variant Creutzfeldt-Jakob Disease (vCJD)

Variant CJD (vCJD) is a rare, degenerative, fatal brain disorder in humans. Although experience with this new disease is limited, evidence to date indicates that there has never been a case of vCJD transmitted through direct contact of one person with another. However, a case of probable transmission of vCJD through transfusion of blood components from an asymptomatic donor who subsequently developed the disease has been reported.

Since variant CJD was first reported in 1996, a total of 229 patients with this disease from 12 countries have been identified. As of June 2, 2014, variant CJD cases have been reported from the following countries: 177 from the United Kingdom, 27 from France, 5 from Spain, 4 from Ireland, 4 from the United States, 3 in the Netherlands, 2 in Portugal, 2 in Italy, 2 in Canada and one each from Japan, Saudi Arabia, and Taiwan. Two of the four U.S. cases, two of the four cases from Ireland, one of the two cases from Canada, and the single case from Japan were likely exposed to the BSE agent while residing in the United Kingdom.

There has never been a case of vCJD that did not have a history of exposure within a country where the cattle disease, BSE, was occurring.

It is believed that the persons who have developed vCJD became infected through their consumption of cattle products contaminated with the agent of BSE or in three cases, each reported from the United Kingdom, through receipt of blood from an asymptomatic, infected donor. There is no known treatment of vCJD and it is invariably fatal.

This variant form of CJD should not be confused with the classic form of CJD that is endemic throughout the world, including the United States. There are several important differences between these two forms of the disease. The median age at death of patients with classic CJD in the United States, for example, is 68 years, and very few cases occur in persons under 30 years of age. In contrast, the median age at death of patients with vCJD in the United Kingdom is 28 years.

vCJD can be confirmed only through examination of brain tissue obtained by biopsy or at autopsy, but a "probable case" of vCJD can be diagnosed on the basis of clinical criteria developed in the United Kingdom.

The incubation period for vCJD is unknown because it is a new disease. However, it is likely that ultimately this incubation period will be measured in terms of many years or decades. In other words, whenever a person develops vCJD from consuming a BSE-contaminated product, he or she likely would have consumed that product many years or a decade or more earlier.

In contrast to classic CJD, vCJD in the United Kingdom predominantly affects younger people, has atypical clinical features, with prominent psychiatric or sensory symptoms at the time of clinical presentation and delayed onset of neurologic abnormalities, including ataxia within weeks or months, dementia and myoclonus late in the illness, a duration of illness of at least 6 months, and a diffusely abnormal non-diagnostic electroencephalogram.

The BSE epidemic in the United Kingdom reached its peak incidence in January 1993 at almost 1,000 new cases per week. The outbreak may have resulted from the feeding of scrapie-containing sheep meat-and-bone meal to cattle. There is strong evidence and general agreement that the outbreak was amplified by feeding rendered bovine meat-and-bone meal to young calves.

The possibility that BSE can spread to humans has focused increased attention on the desirability of enhancing national surveillance for Creutzfeldt-Jakob disease (CJD) in the United States in order to detect variant CJD. Improving methods to detect classic CJD, such as increasing the number of autopsies on patients with suspected prion disease, enhances the ability to identify cases of variant CJD.

The Centers for Disease Control and Prevention (CDC) monitors the trends and current incidence of classic CJD in the United States through several surveillance mechanisms. The oldest and most systematic method includes analyzing death certificate information from U.S. multiple cause-of-death data, compiled by the National Center for Health Statistics, CDC. During 1979-2003 the average annual age adjusted death rates of classic CJD have remained relatively stable. Moreover, deaths from non-iatrogenic CJD in persons aged <30 years in the United States remain extremely rare (<5 cases per 1 billion per year). In contrast, in the United Kingdom, over half of the patients who died with vCJD were in this young age group.

In addition, CDC collects, reviews and when indicated, actively investigates reports by health care personnel or institutions of possible iatrogenic CJD and variant CJD cases. Finally and very importantly, in 1996-97, CDC established, in collaboration with the American Association of Neuropathologists, the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, which performs special diagnostic tests for prion diseases, including post-mortem tests that can detect vCJD.

Four cases of vCJD have been reported from the United States. By convention, variant CJD cases are ascribed to the country of initial symptom onset, regardless of where the exposure occurred. There is strong evidence that suggests that two of the four cases were exposed to the BSE agent in the United Kingdom and that the third was exposed while living in Saudi Arabia. The history of the fourth patient, including extensive travel to Europe and the Middle East, supports the likelihood that infection occurred outside the United States.

The first patient was born in the United Kingdom in the late 1970's and lived there until a move to Florida in 1992. The patient had onset of symptoms in November 2001 and died in June of 2004. The patient never donated or received blood, plasma, or organs, never received human growth hormone, nor did the patient ever have major surgery other than having wisdom teeth extracted in 2001. Additionally, there was no family history of CJD.

The second patient resided in Texas during 2001-2005. Symptoms began in early 2005 while the patient was in Texas. He then returned to the United Kingdom, where his illness progressed, and a diagnosis of variant CJD was made. The diagnosis was confirmed neuropathologically at the time of the patient's death. While living in the United States, the patient had no history of hospitalization, of having invasive medical procedures, or of donation or receipt of blood and blood products. The patient almost certainly acquired the disease in the United Kingdom. He was born in the United Kingdom and lived there throughout the defined period of risk (1980-1996) for human exposure to the agent of bovine spongiform encephalopathy (BSE, commonly known as "mad cow" disease). His stay in the United States was too brief relative to what is known about the incubation period for variant CJD.

The third patient was born and raised in Saudi Arabia and has lived in the United States since late 2005. The patient occasionally stayed in the United States for up to 3 months at a time since 2001 and there was a shorter visit in 1989. The patient's onset of symptoms occurred in Spring 2006. In late November 2006, the Clinical Prion Research Team at the University of California San Francisco Memory and Aging Center confirmed the vCJD clinical diagnosis by pathologic study of adenoid and brain biopsy tissues. The patient has no history of receipt of blood, a past neurosurgical procedure, or residing in or visiting countries of Europe. Based on the patient's history, the occurrence of a previously reported Saudi case of vCJD attributed to likely consumption of BSE-contaminated cattle products in Saudi Arabia, and the expected greater than 7 year incubation period for food-related vCJD, this U.S. case-patient was most likely infected from contaminated cattle products consumed as a child when living in Saudi Arabia. The patient has no history of donating blood and the public health investigation has identified no known risk of transmission to U.S. residents from this patient.

The fourth patient died in Texas in May 2014. Laboratory tests confirmed a diagnosis of variant CJD. The confirmation was made when laboratory results from an autopsy of the patient's brain tested positive for variant CJD.

To prevent BSE from entering the United States, severe restrictions were placed on the importation of live ruminants, such as cattle, sheep, and goats, and certain ruminant products from countries where BSE was known to exist. These restrictions were later extended to include importation of ruminants and certain ruminant products from all European countries.

Because the use of ruminant tissue in ruminant feed was probably a necessary factor responsible for the BSE outbreak in the United Kingdom and because of the current evidence for possible transmission of BSE to humans, the U.S. Food and Drug Administration instituted a ruminant feed ban in June 1997 that became fully effective as of October 1997. As of October 26, 2009, a regulation issued by FDA in April 2009 came into effect establishing an enhanced BSE-related feed ban in the U.S. This enhanced feed ban will further harmonize BSE feed control measures in the U.S. with those in Canada (see below). In addition, FDA continues to enforce its important 1997 mammalian-to-ruminant feed ban through its BSE inspection and BSE feed testing programs.

As of July 12, 2007, an enhanced BSE-related feed ban came into effect in Canada. CFIA established this ban to more effectively prevent and quickly eliminate BSE from Canada. The enhanced ban prohibits most proteins, including potentially BSE infectious tissues known as "specified risk materials" (SRM) from all animal feeds, pet foods, and fertilizers, not just from cattle feed as required by the ban instituted in 1997. The 1997 feed ban in Canada was similar to the feed ban instituted in the United States that same year. As recently reported by CFIA, removing SRM from the entire animal feed system addresses risks associated with the potential contamination of cattle feed during production, distribution, storage, and use. Applying the same measure to pet food and fertilizer materials addresses the possible exposure of cattle and other susceptible animals to these products. With this ban in place, CFIA expects BSE should be eliminated from the Canadian cattle herd by about the year 2017.

In late 2001, the Harvard Center for Risk Assessment study of various scenarios involving BSE in the U.S. concluded that the FDA ruminant feed rule provides a major defense against this disease.