Common names for disease: Sporadic Creutzfeldt–Jakob disease, new variant Creutzfeldt–Jakob disease, fatal familial insomnia, kuru, Gerstmann–Sträussler–Scheinker disease

Classification: Prion diseases

OCCUPATIONAL SETTING

There are theoretical but unproven risks to healthcare workers including physicians, surgeons, pathologists, nurses, dentists, laboratory technicians, veterinarians, veterinary technicians, agriculture workers, farmers, meat processors, butchers, abattoir workers, and cooks exposed to blood and uncooked animal products.

EXPOSURE (ROUTE)

Transmission of Creutzfeldt–Jakob disease (CJD) from human to human has been reported for patients receiving corneal transplants, dural grafts, and human growth hormone and gonadotropins derived from pooled human cadaver pituitary glands. Transmission has also been linked to inadequately sterilized instruments and stereotactic electrodes. In addition, transmission of kuru by ritual cannibalism has been documented. Although there have been case reports of healthcare personnel, veterinarians, and farmers developing CJD, there is no firm epidemiologic evidence to date to suggest that work in these occupations increases the risk for developing CJD.

A new variant Creutzfeldt–Jakob disease (nvCJD) has been associated with consumption of brain and spinal cord in sausages, hamburger, and other processed meats from cattle with bovine spongiform encephalopathy (BSE), or “mad cow disease,” in the United Kingdom. Transmission of CJD through human blood or blood products has not been documented but is of some concern.

In August 1999 the FDA issued guidelines to reduce the possible risk of transmission of CJD and nvCJD by blood and blood products.¹ As a result, the Red Cross has implemented restrictions on blood donors who have been diagnosed with CJD, have relatives with CJD, received a dura mater (brain covering) transplant, or received human pituitary growth hormone. Potential blood donors who spent a total time of 3 months or more during 1980–1996 in the United Kingdom during the mad cow disease epidemic or who received a blood transfusion in the United Kingdom or France during this time frame are also restricted from blood donation. In addition members of the of the US military, civilian military employees, and dependents of a member of the US military who spent a total time of six months on or associated with a certain military bases during the specified time frames are also restricted from blood donation.

PATHOBIOLOGY

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders that affect both humans and animals. They are distinguished by long incubation periods, characteristic spongiform changes associated with neuronal loss, and a failure to induce an inflammatory response.

A number of transmissible spongiform encephalopathies or prion diseases have been described in animals and humans. Animal diseases include scrapie in sheep and goats, transmissible mink encephalopathy, wasting disease of deer and elk, bovine spongiform encephalopathy, and feline spongiform encephalopathy. Human diseases include sporadic CJD, nvCJD, Kuru, and genetically transmitted familial Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker disease, and fatal familial insomnia.

The causative agents of TSEs are believed to be prions, a small proteinaceous infectious particle. The term “prion protein” (PrP) was coined by Prusiner in 1982 to describe a novel host membrane sialoglycoprotein that caused scrapie in sheep.² This PrP was apparently able to “replicate” without DNA or RNA. The PrP was resistant to treatments that inactivate nucleic acids and viruses including ionizing radiation, alcohol, formalin, proteases, and nucleases. It was inactivated by treatments that disrupt proteins including phenol, detergents autoclaving, and extremes of pH. The protease-resistant protein associated with disease proved to be an isoform of a protease-sensitive normal host cellular protein. The functions of normal prion proteins are still not completely understood. The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Prion diseases are usually rapidly progressive and always fatal.³

DIAGNOSIS

CJD was first described in 1920 and occurs worldwide with an incidence of 0.5–1.5 cases per million population per year. CJD generally occurs between the ages of 50 and 70. The incidence of the disease has been constant over many decades, and there is no apparent geographic or seasonal clustering of the sporadic form. A genetically determined familial variant has also been reported. To date no environmental risk factors for the disease have been identified although dietary factors, exposure to animals, and occupational exposures have been evaluated in epidemiologic studies. Surgeons and pathologists handling infected human brain tissue, as well as abattoir workers and cooks exposed to blood and uncooked animal products do not appear to have an increased risk for disease.^4,5

Patients with CJD complain of fatigue, disordered sleep, decreased appetite, memory loss, and confusion. Focal neurological signs, such as ataxia, aphasia, visual loss, hemiparesis, and amyotrophy are reported. A diagnosis of CJD is suggested by a progressive loss of cognitive abilities, the development of mild chronic jerking, and pyramidal tract, cerebellar, and extrapyramidal signs. During the latter stages of disease, the patient becomes mute and akinetic. The mean survival time is 5 months, and 80% of patients with sporadic disease die within 1 year.⁶

There appear to be no diagnostic peripheral blood abnormalities or abnormalities in the cerebral spinal fluid that are helpful in the diagnosis. The electroencephalogram can be normal early in the disease but has been shown to be abnormal in 90% of patients if repeated during the course of the illness. As the disease progresses, computed tomography may show progressive generalized atrophy, and magnetic resonance imaging may show hyperintense signals in the basal ganglion on T2-weighted images.

Abnormal protein patterns in the cerebral spinal fluid of patients with CJD were found with two-dimensional electrophoresis, but the method was not practical for routine use.⁷ Histological examination of the brain and immunostaining for the abnormal PrP are the gold standards for diagnosis. Spongiform changes accompanied by neuronal loss and gliosis are common features. Amyloid plaques are found in 10% of the brains in the sporadic form of CJD. In contrast, plaques are common in kuru, some of the familial spongiform encephalopathies, and new variant Creutzfeldt–Jakob disease. Tonsillar biopsy has been suggested as a possible pathological diagnostic technique in the living patient, particularly for nvCJD.⁸ A confirmatory diagnosis of CJD requires neuropathological and/or immunodiagnostic testing of brain tissue obtained either at biopsy or autopsy.

In the United States, the National Prion Disease Pathology Surveillance Center (NPDPSC) was established in 1997 at Case Western Reserve University in response to concerns about the transmission to humans of prion diseases, or spongiform encephalopathies, acquired from animals, as well as transmission between humans during medical procedures.

TREATMENT

CJD and the related transmissible spongiform encephalopathies are universally fatal. There is no effective treatment or vaccine.

PREVENTION

Although iatrogenic transmission of CJD has been reported, and possible transmission of bovine spongiform encephalopathy to humans has been proposed, the cause of sporadic CJD that comprises 90% of the cases remains unknown. To date, there does not appear to be an increased risk of transmission from CJD patients or tissues to surgeons, pathologists, dentists, or other healthcare professionals. Nor does there appear to be an increased risk to veterinarians, meat packers, abattoir, or agricultural workers handling infected TSE animals or tissues.

Unlike most other pathogens, prions resist ordinary disinfection and sterilization techniques and can remain infectious for years even in a dried state. Thus, infected spinal fluid and tissue from the brain, spine, and eyes are theoretically of concern. Healthcare personnel caring for patients with CJD should follow universal precautions for blood-borne pathogens. Gloves should be worn when in contact with central nervous system tissue, contaminated instruments, and surfaces and when handling blood and body fluids, particularly CSF. Gowns and plastic aprons are indicated if splattering of blood or tissue is anticipated. Masks or protective goggles should be worn if aerosol generation or splattering is likely to occur, such as in dental or surgical procedures, wound irrigations, postmortem examinations, bronchoscopy, or endoscopy. Needles and other sharp objects should never be clipped, recapped, or removed from disposable syringes. Needles should be disposed of in a puncture-proof, leak-proof, and rigid plastic biohazard container.

Extensive precautions should be taken when handling cerebral spinal fluid and brain tissue. Where practicable disposable instruments are preferable. The Centers for Disease Control and Prevention and the World Health Organization have published guidelines for sterilizing instruments, tissues, or other materials known to contain prions.^9–11

References

1. 1. Food and Drug Administration. Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products, 2016. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM307137.pdf (accessed on July 4, 2016).
2. 2. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science 1982; 216:136–44.
3. 3. Centers for Disease Control and Prevention. Prions. http://www.cdc.gov/prions/index.html (accessed August 24, 2016).
4. 4. Harris-Jones R, Knight R, Will RG, et al. Creutzfeldt-Jakob disease in England and Wales, 1980–1984: a case–control study of potential risk factors. J Neurol Neurosurg Psychiatry 1988; 51:1113–9.
5. 5. Wientjens DP, Davanipour Z, Hofman A, et al. Risk factors for Creutzfeldt-Jacob disease: a reanalysis of the case control studies. Neurobiology 1996; 46:1287–91.
6. 6. Brown P, Gibbs CJ Jr., Rodgers-Johnson P, et al. Human spongiform encephalopathy; the National Institutes of Health series of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 1994; 35:513–29.
7. 7. Harrington MG, Merril CR, Asher DM, et al. Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. New Engl J Med 1986; 315:279–83.
8. 8. Hill AF, Zeidler M, Ironside J, et al. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997; 349:99–100.
9. 9. Centers for Disease Control and Prevention. Creutzfeldt-Jakob Disease Infection-Control Practices. http://www.cdc.gov/prions/cjd/infection-control.html (accessed August 24, 2016).
10. 10. WHO. WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Report of a WHO Consultation, Geneva, Switzerland, March 23–26, 1999.
11. 11. Chosewood LC, Wilson DE, Centers for Disease Control and Prevention, National Institutes of Health. Biosafety in microbiological and biomedical laboratories, 5th edn. HHS Publication no. (CDC) 21-1112, 2009. Washington, DC: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institutes of Health. Section VIII—H: Prion Diseases. Available at: http://www.cdc.gov/biosafety/publications/bmbl5/bmbl.pdf (accessed July 13, 2016).