After a period out of the spotlight, Mad Cow disease is again causing a stir. Following the first documented case in this country on December 23, 2003,1 the US government is instituting new preventive measures, and patients may be asking for assurances of safe-ty (see “What to advise patients,” page 565).
Mad Cow’s connection to humans: vCJD
Mad Cow disease is the bovine form of transmissible spongiform encephalopathy (TSE), a disease that can also affect sheep, deer, goats, and humans (Table 1). The causative agent is thought to be an infective protein called a prion, discovered in 1997.
Bovine spongiform encephalopathy (BSE) was first identified in the United Kingdom in 1986 and caused a large outbreak in cattle, which peaked in 1993. Subsequently, it was discovered that BSE could rarely spread to humans, causing a variant of Creutzfeldt-Jakob disease (vCJD) that is universally fatal. As of December 2003, 153 cases of vCJD had been reported worldwide, most in the UK. Confirmation of either the classic or variant form requires pathology examination of brain tissue collected by biopsy or, if a patient has died, at autopsy.2
TABLE 1
Transmissible spongiform encephalopathies
| Species affected | Prion disease | Transmissible to humans? |
|---|---|---|
| Mink | Transmissible mink encephalopathy | No |
| Sheep and goats | Scrapie | Historically no; questionable in newly discovered atypical cases |
| Deer and elk | Chronic wasting disease | Possible (under investigation) |
| Cattle and bison | Bovine spongiform encephalopathy | Yes (variant CJD) |
| Humans | Creutzfeldt-jakob disease; variant CJD, Gerstmann-Straussler-Scheinker disease, Kuru, fatal familial insomnia | Through contaminated medical products, instruments, possibly blood |
Uniqueness of vCJD
In medical school, family physicians learned about classic CJD, which is endemic throughout the world and, in the US, causes an average of 1 death per million people per year. The epidemiology of vCJD and CJD are quite different (Table 2). Because vCJD is a new disease, its incubation period is unknown, but it is likely to be years or decades. In the UK it is thought that exposure to BSE-contaminated food from 1984–86 and the onset of vCJD cases in 1994–96 is consistent with such a long incubation period.
Since 1986, BSE has been identified in 20 European countries, Japan, Israel, Canada, and now the US. The main method of its spread through herds is believed to be the former practice of feeding cattle the meat and bone meal products that, at some point, were contaminated with BSE. In 1997, the US and Canada prohibited the feeding of ruminant meat and bone meal to other ruminants. It is thought that most cases of vCJD are transmitted to people when they eat beef products containing brain or spinal cord material contaminated with BSE.
Neuropathology. Variant CJD deposits plaques, vacuoles, and prion protein in the brain. To date, all persons with vCJD have had methio-nine homozygosity at the polymorphic codon 129 of the prion protein gene, suggesting that persons not carrying this genotype (who make 60% of the population) have increased resistance to the disease. In addition, vCJD and BSE are both dose-dependent infections, so both genetics and exposure may explain why so few human cases have occurred despite the widespread outbreak of BSE in the UK.
TABLE 2
Characteristics distinguishing vCJD from CJD
| Characteristic | UK vCJD | US classic CJD |
|---|---|---|
| Median age at death | 28 (range, 14–74) | 68 (range, 23–97)* |
| Median illness duration (mo) | 13–14 | 4–5 |
| Clinical presentation | Prominent psychiatric/behavioral symptoms; delayed neurologic signs | Dementia; early neurologic signs |
| Periodic sharp waves on EEG | Absent | Often present |
| “Pulvinar sign” on MRI† | Present in >75% of cases | Not reported |
| Presense of “florid plaques” on neuropathology | Present in great numbers | Rare or absent |
| Immunohistochemical analysis of brain tissue | Marked accumulation of PrPres | Variable accumulation |
| Presense of agent in lymphoid tissue | Readily detected | Not readily detected |
| Increased glycoform ratio on immunoblot analysis of PrPres | Present | Not present |
| Genotype at codon 129 of prion protein | Methionine/Methionine | Polymorphic |
| *Surveillance data 1997–2001. | ||
| † High signal in the posterior thalmus. | ||
| CJD; Creutzfeldt-Jakob disease; vCJD, variant CJD; EEG, electoencephalogram; MRI, magnetic resonance imaging; | ||
| PrPres, protease-resistant prion protein. | ||
| Source: Centers for Disease Control and Prevention, MMWR Morb Mortal Wkly Rep 2004; 52:1280–1285.1 | ||
Prevention measures have been updated
Before December 30, 2003, prevention measures in place to prevent BSE in this country were the following:
- Import restrictions on bovine-derived consumer products from high-risk BSE countries (initiated in 1989).
- Prohibition of the use of ruminant derived meat and bone meal in cattle feed (initiated in 1997).
- A surveillance system for BSE that involved annual testing of between 5000 and 20,000 cattle slaughtered for human consumption (out of about 35 million cattle slaughtered per year).
Since December 30, 2003, the US Department of Agriculture (USDA) and Food and Drug Administration (FDA) have added or proposed a number of additional provisions to prevent BSE:
- Defining high-risk materials banned for human consumption, including the entire verte-bral column.
- Banning the use of advanced meat recovery systems on vertebral columns. These systems use brushes and air to blast soft tissue off of bone and led to up to 30% of hamburger sampled to be contaminated with central nervous system tissue.
- Proposing an expanded annual surveillance to include about 200,000 high-risk cattle (sick, suspect, dead) and a random sample of 20,000 normal cattle over 30 months old.