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The spongiform encephalopathies: prion diseases.

Abstract: The spongiform encephalopathies may be caused by prions, infectious pathogens that differ from all other infectious agents in that they do not have deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Very difficult to inactivate, they are composed of an abnormal protein. It is believed by many that prions cause sporatic and genetic neurodegenerative diseases, including scrapie and bovine spongiform encephalopathy in animals and kuru, fatal familial insomnia, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease in humans. Another, the new variant CJD in humans in England, is an example of a breech in the species barrier between humans and animals. Transmitted primarily via exposure to infected brain or spinal cord tissue or blood, there have been numerous iatrogenic cases from contaminated pituitary hormones, surgical equipment, dural grafts, corneal transplants and others. All facets of blood product manufacturing have been affected. Nurses should be aware of the latest developments, and able to practice infection control while providing the best patient/family information possible.

Introduction

Prions are unusual infectious particles. Unlike viruses, bacteria, fungi and parasites, they contain no deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Instead, they are a type of protein normally found within cells in humans and other organisms. In some cases, however, the the prions can change into a disease-causing form. These prions in turn appear to convert other, normal proteins to the abnormal shape. Many scientists now believe this process leads to several dementing diseases in humans, including Creutzfeldt-Jakob disease (CJD). Similar diseases in animals include bovine spongiform encephalopathy or "mad cow disease" in cattle and scrapie in sheep. This article discusses prion diseases, their devastating effects on patients and families and infection control concerns.

Case Study

Mrs. Smith, a 63 year-old female, was in her usual state of good health until she had a sudden onset of tremors during sleep which woke her. In addition, Mrs. Smith and her family had been noticing she was forgetful and had slurred speech. These mild symptoms continued until the day of hospital admission one week later, when the patient reported another episode of tremulousness, incontinence and nausea without vomiting. She specifically denied any headache, fevers or neck stiffness, previous neurologic complaints or changes in strength in any of her extremities. However, she did report some unusual visual and tactile hallucinations in which colors didn't seem right and familiar objects felt unusual. Her medical or family history was not significant. Nonetheless, she was admitted for a diagnostic workup for acute encephalopathy. A computed tomography (CT) scan, magnetic resonance imaging (MRI) scan and electroencephalogram (EEG) were essentially negative. She was discharged home on an antiepileptic medication to control the tremulousness.

Unfortunately, Mrs. Smith's condition continued to rapidly fail and within weeks she became unable to walk or care for herself. She became increasingly confused and the day before the second admission, did not recognize one of her daughters. Nursing staff members found her cheerful and cooperative but her face seemed frozen in a lopsided smile. She would stop talking mid-sentence and stare into space. She had multiple twitches of her hands, legs and feet. She held herself in a very stiff kind of position with her left hand in what could be seen as a possible decerebrate position. Unable to feed herself, she needed to be reminded to chew and swallow. At times she was incontinent. Total care was required at this time.

As part of further diagnostic screening, a heavy metal and toxicology screen were done which were negative. Only the EEG was abnormal with diffuse slowing; the CT and MRI scans again were normal. An environmental and occupational history search were negative.

Within three weeks, Mrs. Smith had deteriorated with rigid extremities and myoclonic jerks. Her dementia rapidly progressed to unresponsiveness. She underwent a right frontal craniotomy with brain biopsy which was positive for CJD. She was transferred to a long-term care facility where she expired within a year, never regaining consciousness.

Prion Diseases

In 1970, the transmissible spongiform encephalopathies, so named because they frequently cause the brain to become riddled with holes, were thought to be caused by infectious agents called slow viruses. (19,26) Distinguished as noninflammatory degenerative diseases with long incubation periods, they produced characteristic spongiform changes associated with neuronal loss in the brain. (30) In 1982, Stanley Prusiner, a neurologist researcher, proposed the prion theory. He theorized that the infectious agent is a neurotropic rogue protein, and named it "prion," a proteinaceous infectious particle. Seemingly, these agents attack the brain but are invisible to the immune system, eliciting no immune response. Theoretically, prions may highjack production of normal proteins in the brain and increase amyloid protein. (30)

Unlike any infectious agent known, prions may multiply in an incredible way by inducing normal protein molecules to change shape and purpose. In support of this theory, mutations in the human PrP gene on chromosome 20 have been found in familial prion diseases. (34) Worldwide research is occurring as there is no vaccine and no known treatment. The hallmark common to all of the prion diseases, whether sporadic, dominantly inherited, or acquired by infection, is that they involve the aberrant metabolism of the prion protein. (28)

Some scientists still consider Prusiner's prion theory unproven because purified prions have not been shown to cause disease. There are other unanswered questions and some researchers still suspect that a slow-acting virus plays a hidden role in the infectious process.

In humans, the prion diseases include CJD, Kuru, familial fatal insomnia (FFI) and Gerstmann-Straussler-Scheinker syndrome (GSS). In animals, prion diseases include scrapie in sheep, bovine spongiform encephalopathy (BSE) (mad cow disease) in cows, transmissible mink encephalopathy in mink and chronic wasting disease in deer and elk. Some of these diseases have been caused by feeding cows offal (animal tissue discarded by slaughterhouses) that is rendered by a process that permits the melted fat to be collected as tallow and leaves the residual solids to be pulverized into meat and bone meal. In humans, the species barrier may have been breached with the new variant Creutzfeldt-Jakob disease cases in England. It is surmised that the outbreak started when cattle were fed with meat and bone meal from scrapie-infected sheep and somehow the infectious agent was then transmitted for the first time to humans. Prior to this time, humans did not contract the disease from animals. (29)

Kuru

In 1957, Gajdusek studied among the Fore people of remote New Guinea. There he found many people with cerebellar dysfunction, ataxia, lack of coordination, profound tremor, hyperreflexia and dementia. Death usually occurred with in one year. The disease was not transmitted by casual contact; nursing mothers didn't infect their babies. At the National Institutes of Health, Gajdusek was able to transmit the disease to monkeys proving it to be infectious. It was found that cannibalism, especially with brain consumption, was the source of infection. The disease has nearly been eliminated by outlawing the practice of cannibalism. (19)

Familial Fatal Insomnia

First reported in 1986, familial fatal insomnia (FFI) is a hereditary prion disease. There is a mutation at codon 178 of the prion protein gene. At onset there is sleep loss, then hallucinations, tachycardia, hyperthermia and deterioration to coma. In one Italian family, 29 out of 288 persons covering six studied generations had the disease. (24) Very rare thus far, the world total is only nine families including one in Chicago. (30)

Gerstmann-Straussler-Scheinker Syndrome

This is an autosomal dominant, also very rare, prion protein gene codon 102 mutation. There are thirty known families with this disease around the world. Onset occurs around forty years of age. Findings include cerebellar ataxia, pyramidal signs, loss of knee and ankle jerks and progressive dementia leading to death in 2-10 years. (30) Pathological spongiform changes and amyloid plaque depositions are found in the cerebellum, cerebrum and brain stem. The EEG usually does not show periodicity, only diffuse slowing. Diagnosis can be achieved by prion gene analysis. (10)

Creutzfeldt-Jakob Disease

In 1920, Creutzfeldt described a progressive, dementing illness and in 1921 Jakob, described four patients with similar signs. The disease is very rare, occurring at a rate of one per one million worldwide. It is not spread by casual contact; conjugal cases are rare. There is some clustering of cases in Tunisia/Libyan Jews, and natives of Slovakia and Chile. (19) Questionable food practices have been described for these groups, such as lightly cooked scrapie-infected sheep brain and eyes; however, these cases have proven to be hereditary. Other cases may have a genetic predisposition. Familial cases of CJD have a mutation on the prion protein gene at codon 200 and account for 15% of all CJD disease. (24)

Symptoms of CJD start with changes in mental status, progressing to dementia and particularly characteristic, myoclonus. There is often a typical EEG with paroxysmal bursts of high-voltage slow waves. (19) Changes in white blood cell counts, cerebrospinal fluid (CSF), sedimentation rates and fever are noticeably absent. Subtypes include: (35)

* subacute- this is the type most common, with rapid deterioration.

* chronic- accounting for 8% of cases has a longer duration of 4-16 years

* amyotrophic- accounting for 5% of cases, with slower progression ending also with dementia

Recently, the detection of 14-3-3 protein in cerebrospinal fluid has shown a high sensitivity and specificity in patients suspected of having CJD. (21) However the test is positive only when the patient is symptomatic and is not a predictive test. The diagnosis is confirmed only by brain biopsy or by autopsy. Typical brain changes found include spongiform degeneration, gliosis and neuronal loss in the absence of an inflammatory reaction. When present, amyloid plaques that stain with PrP antibodies are diagnostic. (28,29)

New Variant Creutzfeldt-Jakob Disease

Mad cow disease, or bovine spongiform encephalopathy (BSE), first appeared in Britain's herds about 10 years ago. Scientists think cattle got the disease by eating feed contaminated with scrapie-infected sheep tissue added as a protein supplement. It is believed that BSE has spread to humans with 21 or more new variant Creutzfeldt-Jakob disease (nvCJD) cases in England primarily among the young. (6,12)

Atypical clinical features are seen including prominent behavior changes at the time of clinical presentation with subsequent onset of neurologic abnormalities, including ataxia within weeks or months, dementia and myoclonus late in the illness. Duration of illness is at least 6 months; nondiagnostic EEG changes are seen. (36) Testing biopsied tonsil tissue for the prion protein (PrP) marker may be used to confirm diagnosis. (23)

Iatrogenic Creutzfeldt Jakob Disease

Iatrogenic transmission of CJD has been reported from corneal transplantation, implantation of dura mater or electrodes in the brain and use of contaminated surgical instruments. (6,7,8) More recently, new cases have been reported after blood transfusion but CJD transmissibility through the transfusion of blood or blood products is controversial. (16) Still, revision of policies and procedures worldwide affecting all facets of blood product manufacturing from blood collection to transfusion are transpiring. (31) Transmission after liver transplantation has also been reported. (13) Also, Defebvre reports CJD in a patient who, during a thoracic surgery procedure, had embolization of intercostal arteries with lyophilized cadaveric dura mater. (4) Fewer than 20 cases of CJD linked to dura mater allografts had been reported world-wide until recently. Now Japan has acknowledged 43 cases over the past ten years. (33)

Pituitary hormones, derived from cadaver donors, were administered between 1963 and 1985 as pituitary gonadotropins (hPG) to infertile women and as growth hormone (hGH) to children with pituitary insufficiency. This source of pituitary hormones was abandoned in most countries in 1985 when two hGH recipients died in the USA from CJD. (17) TO date, there have been 16 deaths from CJD among approximately 8,000 hGH recipients in the United States for whom the National Hormone and Pituitary Program (NHPP) provided growth hormone. The rate of occurrence of new cases has averaged between one and two per year since the risk of CJD was recognized in 1985. (27) There is a potential for more cases due to the long incubation period. Five women treated for infertility in Australia have died from CJD contracted via hPG as a source of follicle-stimulating hormone, given to promote fertility. (17) Around the world, there are a total of approximately 100 deaths from contaminated pituitary hormones that have caused CJD.

Health Care Workers

Determining relevant antecedent events for an infectious illness with a very long incubation period is fraught with difficulty. Nevertheless, there have been at least 24 health care workers reported with CJD. These include six physicians, a pathologist, three dentists, a dental surgeon, nine nurses, three nursing assistants and two histopathology technicians. (3) Risk appears to be particularly associated with contact with cerebrospinal fluid or central nervous system tissue. (5) Guidelines have been established for the handling of blood and tissue specimen collection, surgical procedures and the performance of autopsies (Table 1). (15,8,32)

Nurses in the operating room are at particular risk of exposure to brain or spinal cord tissue or blood. It is best to use as many disposable items as possible. As a result of the extreme resistance of prions to normal sterilization procedures, current recommendations from England are to destroy neurosurgical instruments used in patients with CJD. (23,18) Although the disease is not spread by casual contact, stringently following universal precautions is required by nursing personnel (Table 2). Any patient must be considered infectious until proven otherwise.

Practical experience with these patients in the end stages of disease have shown many possibilities for the spread of infection. Usually they have to be suctioned frequently, need frequent mouth care, have tube feedings and diarrhea and other attendant difficulties of terminal patient care. (25) Consistently practicing universal precautions with every patient may help prevent disease transmission.

Patient/Family Education

Families ask many questions. In the words of a family member, "To watch a loved family member go through such a horrific experience is total torture and to feel as though I know nothing is so frustrating." At the very least, nursing staff members should explain new tests and procedures in simple terms, share knowledge about the prion diseases and explain infection control concerns. The family's need for information is great and any explanations will help to decrease their anxiety.

In addition, the family must be supported through the grieving process. If the family asks about organ donation, it should be explained it is not an option because of the risk that the disease will be transmitted. (9) It's likely that the family will need help with end-of-life decisions which have been thrust upon them so abruptly. (4) Involving support services such as clergy and social services help create a larger base of support. (2)

With the diagnoses of any prion disease, there is little information to give. Often the cause is not known, no effective treatment has been found and even the diagnosis is unproven until after the patient has died. (2) There are resources available for additional information if desired (Table 3).

Summary

Prions, once dismissed as an impossibility, have now gained wide recognition as extraordinary agents that cause a number of infectious, genetic and spontaneous disorders. (30) Prions have apparently crossed the species barrier between animals and humans creating new variant CJD and endangering food supplies. Iatrogenic cases continue to be troublesome. Blood supplies must be screened for CJD. Nurses are challenged to meet the needs of patients and families with these devastating, hopeless illnesses; patient/family education become a top priority. It behooves nurses to be aware of the latest research on these prion diseases, transmissible spongiform encephalopathies, so resistant to disinfectants and thus difficult to eradicate and control.

[FIGURE 1 OMITTED]
Table 1. Guidelines for Decontamination,
Sterilization, Handling of Equipment
and Materials Used for CJD Patients

1. Use as many disposable items as possible. Disposable drapes for
procedures or in surgery should have excellent barrier qualities to
prevent strike through.

2. Wear protective eye wear and gloves when coming in close contact
with body fluids and blood, especially central nervous system tissue.
Wear goggles when suctioning.

3. Wash hands thoroughly with soap and water or detergent after any
contact with the patient even when the contact does not involve
handling blood, percutaneous fluid or body tissues.

4. Irrigate any percutaneous exposure to blood, CSF and tissue
(particularly brain tissue) immediately with 0.5% sodium hypochlorite
(household bleach diluted 1: 10) and water. Keep in mind bleach is
destructive to human tissue, instruments and fabrics.

5. Label all specimens sent to the laboratory from CJD patients as
"Biohazardous."

6. Sterilize all potentially contaminated materials in a gravity
displacement autoclave at 132 degrees C for a least one hour before
discarding, cleaning, or resterilizing. It is preferred that
contaminated materials be autoclaved in a prevacuum autoclave at
134-138 degrees for 1 hour.

7. Immerse all reusable equipment that came in direct contact with the
patient in 1 N sodium hydroxide for one hour at room temperature. An
alternate method is to immerse all reusable equipment coming in contact
with the patient in 5% sodium hypochlorite (full-strength household
bleach) for two hours. Full-strength solution will damage instruments.
This extended contact time ensures deactivation of agents.

8. If possible destroy instruments and incinerate. Otherwise, autoclave
all instruments before they are washed. After sterilization,
instruments can be cleaned following the usual process and
resterilized.

9. Disinfect all surfaces of the operating room with 5% sodium
hypochlorite, then clean routinely.

10. Bag and label all linens and disposable materials with "Biohazard"
labels so that they can be handled safely by housekeeping and laundry
personnel.

11. Organ or tissue donation is not acceptable for the patient with
Creutzfeldt-Jakob disease.

12. Request visitors to wash hands well.

Source: Adapted from Bailes B: Ceutzfeldt-Jakob disease: A fatal
neurodegenerative transmissible disorder. AORN Journal 1990:52:976-985.
Committee on Health Care Issues, American Neurological Association:
Precautions in handling tissue, fluids and other contaminated
materials from patients with suspected Creutzfeldt-Jakob Disease. Ann
Neurol 1986; 19:75-77. Used with permission.

Table 2. Sterilization Procedures for Creutzfeldt-Jakob
Disease Tissues and Contaminated Materials

Fully Effective (Recommended) Procedures
 Steam autoclaving at 132[degrees]C for 1 hour
 Immersion in 1N sodium hydroxide for 1 hour at room temperature

Partially Effective Procedures
 Steam autoclaving at either 121[degrees]C or 132[degrees] for 15-30
 minutes
 Immersion in 1N sodium hydroxide for 15 minutes, or lower
 concentrations (less than 0.5N) for 1 hour
 Immersion in undiluted bleach, or up to 1:10 dilution for 1 hour

Ineffective Procedures
 Boiling, ultraviolet irradiation, ethylene oxide, sterilization,
 ethanol, formalin, beta-propiolactone, detergents, quaternary
 ammonium compounds, Lysol, alcoholic iodine, acetone, potassium
 permanganate

Used with permission from: Rosenberg RN, White CL, Brown P et al:
Precautions in handling tissues, fluids and other contaminated
materials from patients with documented or suspected
Cruetzfeldt-Jakob Disease. Ann Neurol 1986; 19(1):75-77

Table 3. Resources for Families/Patients

Creutzfeldt-Jakob Disease
Foundation
PO Box 611625
North Miami, Florida
33261-1625

Internet:
http://members.aol.com/crjakob
http://www.medicinenet.com/
http://www.mad-cow.org/
http://www.healthfinder.gov


References

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(2.) Belcaster A: Creutzfeldt-Jakob disease: A family centered approach. Crit Care Nurse 1994; 14(4):38-43.

(3.) Berger J, Noble D: CJD in a physician: A review of the disorder in health care workers. Neurology 1993; 43:205-206.

(4.) Brazell VJ: The human side of "Mad Cow disease." RN 1997; 60(1):32-34.

(5.) Brown P. Preece MA, Will RG: Friendly fire in medicine: Hormones, homografts, and Ceutzfeldt-Jakob disease. Lancet 1992; 340:24-27.

(6.) Brown P: The risk of bovine spongiform encephalopathy ("Mad Cow Disease") to human health. JAMA 1997; 278:12.

(7.) Centers for Disease Control and Prevention: Rapidly progressive dementia in a patient who received a cadaveric dura mater graft. MMWR 1987; 36(4):49-50,55.

(8.) Centers for Disease Control: Update: CJD in a second patient who received a cadaveric dura mater graft. MMWR 1989: 38:37-38,43.

(9.) Chipps E, Paulson G: Creutzfeldt-Jakob disease: A review. J Neurosci Nurs 1994; 28(4):219-223.

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(11.) Committee on Health Care Issues, American Neurological Association: Precautions in handling tissue, fluids and other contaminated materials from patients with suspected Creutzfeldt-Jakob Disease. Ann Neurol 1986; 19:75-77.

(12.) Conner S: Reporting of new variant Creutzfeldt-Jakob disease cases in lay press. Lancet 1997; 349:1704.

(13.) Creange A, Gray F, Ceasaro P et al: Creutzfeldt-Jakob disease after liver transplantation. Ann Neurol 1995; 38:269-272.

(14.) Defebvre L, Destee A, Caron J, et al: Creutzfeldt-Jakob Disease after an embolization of intercostal arteries with cadaveric dura mater suggesting a systemic transmission of the prion agent. Neurology 1997; 48: 1470-1471.

(15.) Dormont D: How to limit the spread of Creutzfeldt-Jakob Disease. Infection Control and Hospital Epidemiology 1996; 17(8):521-528.

(16.) Dumble LJ, Klein R: Transmission of Creutzfeldt-Jakob Disease by blood transfusion. (Letter to the Editor.) Lancet 1993; 341:768.

(17.) Dumble LJ, Klein R: Creutzfeldt-Jakob Disease legacy for Australian women treated with human pituitary gonadotropins. Lancet 1992; 340:847-848.

(18.) Farrington M: Use of surgical instruments in Creutzfeldt-Jakob Disease. Lancet 1995; 345; 194.

(19.) Gajdusek DC, Gibbs CJ, Asher DM et al: Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (CJD). New Eng J Med 1977; 297(23):1253-1257.

(20.) Johnson R: Emerging viral infections. Arch Neurol 1996; 53:18-22.

(21.) Joynt R, Kurlan R: Neurology. JAMA 1997; 277:23:1873-1874.

(22.) Hatch G, Kenney K, Gibbs CJ et al: The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. New Eng J Med 1995; 335:924-930.

(23.) Hill A, Zeidler M, Ironside J, Collinge J: Diagnosis of new variant CJD by tonsil biopsy. Lancet 1997; 349:99-100.

(24.) Medori R, Tritschler H, LeBlanc A et al: Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. New Eng J Med 1992; 326(7):444-449.

(25.) Mocsny N: Precautions prevent spread of Creutzfeldt-Jakob disease. J Neurosci Nurs 1991; 23(2):111-119.

(26.) Mocsny N: Slow virus infections of the central nervous system. J Rehab Nurs 1989; 14(3):130-132.

(27.) National Institute of Digestive Disease and Kidney, NIH: Pages 1-10 in: Information for Recipients of NHPP Growth Hormone. US Dept Health Human Services 1997.

(28.) Prusiner SB, Hsiao KK: Human prion diseases. Ann Neurol 1994; 35(4):385-395.

(29.) Pruisner SB: Molecular biology of prion diseases. Science 1991; 252(14):1515-1521.

(30.) Prusiner SB: Prion diseases. Sci Am 1995;272:48-57.

(31.) Ricketts MN, Cashman N, Stratton E et al: Is Creutzfeldt-Jakob disease transmitted in blood? Emerging Infectious Diseases 1997;3(2):50-62.

(32.) Rosenburg RN, White CL III, Brown P et al: Precautions in handling tissues, fluids, and other contaminated materials from patients with documented or suspected Creutzfeldt-Jakob Disease. Ann Neurol 1986; 19:75-77.

(33.) Triendl R: Creutzfeldt-Jakob disease link prompts ban on brain tissue use. Nature 1997; 387:5.

(34.) Van Gool WA, Hensels GW, Hoogerwaard EM et al: Hypokinesia and presenile dementia in a Dutch family with a novel insertion in the prion protein gene. Brain 1995; 118:1565-1571.

(35.) Wallace M: Creutzfeldt-Jakob Disease assessment and management. J Gerontol Nurs 1993; 19(11):15-22.

(36.) Will RG, Ironside JW, Zeidler M et al: A new variant of Creutzfeldt-Jakob Disease in the UK. Lancet 1996; 347:921-925

Questions or comments about this article may be directed to Noreen Mocsny, RN, MEd, 707 Park Avenue, Cincinnati, Ohio 45246. Now retired, she was a staff nurse for med/surg, neurology and outpatient clinics at the Veterans Affair Medical Center in Cincinnati, Ohio.
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Geographic Code:1USA
Date:Oct 1, 1998
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