Prions are proteinaceous infectious particles containing, apparently, no genetic material. They are known to cause diseases called transmissible spongiform encephalopathies (TSEs), neurodegenerative diseases with long incubation periods but rapid progressions once they begin. The human TSEs are Creutzfeldt-Jakob disease (CJD), Gerstmann-Strussler-Scheinker disease, and fatal familial insomnia. TSEs are also found in animals and include a disease called scrapie in sheep and goats, transmissible mink encephalopathy, and bovine spongiform encephalopathy (BSE). This last disease is commonly known as mad cow disease and has been in the headlines in recent years due to its apparent link to a variant form of CJD human disease in Great Britain.
▶ Signs and Symptoms of CJD
Symptoms of CJD include altered behavior, dementia, memory loss, impaired senses, delirium, and premature senility. Uncontrollable muscle contractions continue until death, which usually occurs within 1 year of diagnosis.
▶ Causative Agent of CJD
The transmissible agent in CJD is a prion. In some forms of the disease, it involved the transformation of a normal host protein (called PrP), a protein that is supposed to function to help the brain develop normally , and that has recently been found to protect against Alzheimer’s disease. vCJD involves a mutation that alters the structure of this protein.
Once this happens, the abnormal PrP itself becomes catalytic and able to spontaneously convert other normal human PrP proteins into the abnormal form. This becomes a self-propagating chain reaction that creates a massive accumulation of altered PrP, leading to plaques, spongiform damage (that is, holes in the brain), and severe loss of brain function. Using the term transmissible agent may be a bit misleading, however, as some cases of CJD arise through genetic mutation of the PrP gene, which can be a heritable trait. So it seems that although one can acquire a defective PrP protein via transmission, one can also have an altered PrP gene passed on through heredity.
It is thought that 10% to 15% of CJD cases are inherited in this way. They are termed familial CJD. Another form of CJD is termed sporadic CJD, which is the most mysterious and the most common. Up to 85% of CJD cases are of this type. Prions are incredibly hardy “pathogens.” They are highly resistant to chemicals, radiation, and heat. They can withstand prolonged autoclaving.
▶ Pathogenesis and Virulence Factors
Autopsies of the brain of CJD patients reveal spongiform lesions as well as tangled protein fi bers (neurofibrillary tangles) and enlarged astroglial cells. These changes affect the gray matter of the CNS and seem to be caused by the massive accumulation of altered PrP , which may be toxic to neurons. The altered PrPs apparently stimulate no host immune response.
▶ Transmission and Epidemiology
Direct or indirect contact with infected brain tissue or cerebro spinal fluid has been thought to be necessary for prion transmission. Familial CJD and sporadic CJD are most common in elderly people. In the late 1990s, it became apparent that humans were contracting a variant form of CJD (vCJD) after ingesting meat from cattle that had been affl icted by bovine spongiform encephalopathy. Presumably meat products had been contaminated with fluid or tissues infected with the prion.
Cases of this disease have centered around Great Britain, where many cows were found to have BSE. As of late 2009, a total of 217 people worldwide have contracted the disease, 170 of them in the United Kingdom. There have been 3 cases in the United States, two of which are thought to have been picked up during travel to the United Kingdom. The median age at death of patients with vCJD is 28 years. In contrast, the median age at death of patients with other forms of CJD is 68 years. Health care professionals should be aware of the possibility of CJD in patients, especially when surgical procedures are performed, as cases have been reported of transmission of CJD via contaminated surgical instruments. Due to the heat and chemical resistance of prions, normal disinfection and sterilization procedures are usually not sufficient to eliminate them from instruments and surfaces.
The latest CDC guidelines for handling of CJD patients in a health care environment should be consulted. CJD has also been transmitted through corneal grafts and administration of contaminated human growth hormone. In 2003, a British patient died of CJD after receiving a blood transfusion in 1996 from a donor who had CJD. Experiments suggest that vCJD seems to be more transmissible through blood than classic CJD. For that reason, blood donation programs screen for possible exposure to BSE by asking about travel and residence history.
▶ Culture and Diagnosis
It is very difficult to diagnose CJD. Definitive diagnosis requires examination of biopsied brain or nervous tissue, and this procedure is usually considered too risky because of both the trauma induced in the patient and the undesirability of contaminating surgical instruments and operating rooms. Electroencephalograms and magnetic resonance imaging can provide important clues. A new test to distinguish abnormally folded proteins from correctly folded proteins may yield improved diagnostics for cattle very soon and within a few years for humans. The tests can only be performed after death, however.
▶ Prevention and/or Treatment
Prevention of this disease relies on avoiding infected tissues. Avoiding vCJD entails not ingesting tainted meats. No known treatment exists for either form of CJD, and patients inevitably die. Medical intervention focuses on easing symptoms and making the patient as comfortable as possible.