Newly Described Variant of Creutzfeldt-Jakob Disease (V-CJD)

Ten cases of CJD have been identified in the U.K. which appear to represent a new variant of CJD (V-CJD), with a characteristic clinical and neuropathological phenotype (1).

On March 20, 1996, the Spongiform Encephalopathy Advisory Committee (SEAC) advised the government of Great Britain that no known risk factors could account for these cases, e.g., none had a history of potential iatrogenic exposure to CJD through neurosurgery or human-derived growth hormone and none had the known mutations of the prion protein (PrP) gene associated with the inherited form of CJD. The SEAC concluded that although there is no direct evidence; based on current data and in the absence of any credible alternative the most likely explanation at present is that these cases are linked to exposure to BSE before the introduction of the Specified Bovine Offal (SBO) ban in 1989.

In contrast to typical cases of sporadic CJD, this variant form has affected young patients (mean age, 26.3 years) with a relatively long duration of illness (mean, 14.1 months). These unusual clinical features also include an early psychiatric presentation and other behavioral changes with progression to neurological abnormalities. In addition, typical EEG appearances of CJD are absent.

The characteristic neuropathological features are the presence of large numbers of kuru-type PrP amyloid plaques surrounded by a halo of spongiform change in the cerebral cortex and extensive deposition of PrP in all grey matter regions, particularly the cerebellum.

The Centers for Disease Control and Prevention (CDC) monitors the trends and current incidence of CJD in the U.S. by analyzing death certificate data.

Based on this surveillance, during 1979-1993, the annual incidence of CJD remained stable at approximately one case per million persons (2). The age distribution of cases has not changed significantly in contrast to that in the U.K. Five of eight patients who died with V-CJD were less than 30. In comparison, in the U.S., CJD deaths in the age group less than 30 are extremely rare (<5 cases per billion per year).

These relatively stable overall rates for over a decade and the consistently very low rates in the population under 44 years of age provide baselines that would make it possible to detect unusual national increases in the number of CJD deaths, particularly if they occurred in persons under 44 years of age.

CDC is working with its four established Emerging Infections Disease Programs in four states to pilot active surveillance for CJD, including V-CJD.

World Health Organization (WHO) Consultation on Public Health Issues Related to Human and Animal Transmissible Spongiform Encephalopathies, April 2-3, 1996

The group reviewed the clinical and pathological data from 10 cases of V-CJD in the U.K., established a case definition for surveillance of V-CJD, and concluded that although there is no definite link between BSE and V-CJD, the most likely hypothesis for V-CJD is the exposure of the U.K. population to BSE (3). Recommendations to minimize transmission of BSE among animals and for the protection of public health include the following:

1 No part or product of any animal which has shown signs of TSE should enter any food chain (human or animal);

2 All countries should establish continuous surveillance for BSE and V-CJD;

3 All countries should ban the use of ruminant tissue in ruminant feed;

4 With respect to specific products, milk and milk products are considered safe. Likewise, gelatin and tallow are considered safe if processed using methods which have been demonstrated to inactivate infectivity.

5 Measures were outlined to minimize the risks from medicinal products/devices containing bovine materials, e.g., careful selection of source materials; and

6 General research needs were identified, e.g., rapid diagnosis, agent characterization, and epidemiology of TSEs in humans and animals.

 

USDA response actions to BSE have been pro-active. Since BSE is not known to exist in the U.S., the measures taken have been in Prevention, Education, Response, and Surveillance.

To prevent BSE from entering the country, USDA has import restrictions and prohibits certain materials from countries where BSE is known to exist.

APHIS educates veterinary practitioners, veterinary laboratory diagnosticians, industry and producers on the clinical signs and pathology of BSE. We also continue to conduct risk assessments for BSE in the U.S. In 1991, we issued two reports analyzing risk factors associated with BSE in the U.K. and compared these risk factors to the U.S. Since 1991, we’ve updated the BSE risk factor analysis, first in 1993 and as recently as February 1996.

In the area of "Response", APHIS is drafting a "BSE Emergency Disease Guidelines" handbook which defines the responsibilities of State and Federal animal disease control officials and prescribes general and specific procedures for handling an outbreak of BSE in the U.S.

In cooperation with the USDA, Food Safety and Inspection Service, APHIS has had since 1990, a comprehensive active and passive BSE surveillance program. APHIS monitors the remaining cattle imported from the U.K. and as part of targeted or active surveillance for BSE, more than 60 veterinary diagnostic laboratories across the U.S. and USDA’s National Veterinary Services Laboratories continue to examine hundreds of cattle brains each year submitted from adult cattle displaying neurologic signs. As of March 31, 1996, a total of 2, 795 cattle brains have been examined with no evidence of BSE detected.

At a March 28, 1995, APHIS BSE meeting, the following six BSE issue areas and interagency/industry working groups to address these issues were identified:

1 Surveillance and Monitoring

2 Import policies

3 Information and education programs

4 Rendering/feed manufacturing

5 U.K. imports in the U.S.

6 Research needs for TSEs

Regarding BSE, scientific information is coming out daily so we have to always keep an open mind to new information and knowledge. At present, there are limited data and a number of questions regarding BSE.

However, the following is clear —

1 In the U.K. epidemiology supports a common source epidemic linked to animal feed containing contaminated meat and bone meal as a protein source. The causative agent is suspected to be either of sheep or cattle origin;

2 Transmission studies demonstrate oral transmission of BSE and Scrapie to other animal species;

3 Inactivation studies demonstrate that BSE and Scrapie are not inactivated by a wide range of rendering practices; and

4 BSE has not been identified in the United States.

1 Will RG, Ironside JW, Zeibler M, et al. A New Variant of Creutzfeldt-Jakob Disease in the UK. Lancet 1996; 347:921-5

2 CDC. World Health Organization Consultation on Public health Issues Related to Bovine Spongiform Encephalopathy and the Emergence of a New Variant of Creutzfeldt-Jakob Disease. MMWR 1996;45:295-303.

3 WHO. Report of a WHO Consultation on Public Health Issues Related to Human and Animal Transmissible Spongiform Encephalopathies. April 2-3, 1996. WHO/EMC/DIS/ 96.147.