Fact Sheet - CJD (Mad Cow Disease)
Transmissible Sponiform Encephalopathies

"If an evil force could devise an agent capable of damaging the human race, he would make it indestructible, distribute it as widely as possible in animal feed so that it would pass to man, and program it to cause disease slowly so that everyone would have been exposed to it before there was any awareness of its presence."
Richard Lacey, British microbiologist

Sterilization-resistant Creutzfeldt-Jakob Disease (CJD) presents a ongoing concern for neurosurgeons and supports the use of disposable tools for intracranial surgery.
 
Pathogenesis

The agent of these diseases is thought to be a protease resistant isomer of a natural protein (prion) that can be inherited or acquired infectiously. The infectious form of the disease is potentially extremely dangerous in that it has the long incubation period of HIV (9 years1), the mortality of rabies (100%), and the environmental persistence of anthrax. Like influenza, this disease agent has shown that it can suddenly jump species barriers, with dramatic increases in incidence. While diagnostic tests are being developed,2 no current treatment or even a commercially available antemortem diagnostic test exists. Like Alzheimer's, this disease exacts an enormous economic and emotional toll, slowly debilitating before it kills. The development of a vaccine is unlikely, as there is no experimental evidence of acquired immunity. Finally, there is some evidence of lateral transmission between animals of the same species.3

While there appears to be a significant but incomplete alimentary barrier to transmission, the agent is very infective in a wide range of species when inoculated directly into nervous tissue. This infectivity, when combined with the agent's remarkable resistance to conventional sterilizing procedures,4,5,6 has resulted in iatrogenic transmission between neurosurgical patients.7 Transmission need not be limited to a single patient; two patients and a chimpanzee were serially infected from a single electrode.8 The infection in the chimp took place over two years after the electrode was last used in humans. The risk for contracting CJD is proportional to the number of surgical procedures9 a person undergoes.
 
Variants of the Disease and Their Incidence
    In Man

    Creutzfeldt-Jakob Disease (CJD): Classical form, sporadic incidence: 1 per million, generally occurring in older patients.10 Actual incidence may be higher: A Yale Univ. School of Medicine Study reports that 6 of 46 cases clinically diagnosed as Alzheimer's were proven at autopsy to be CJD.11

    Genetic forms of TSE: Gerstmann-Straussler-Scheinker (GSS) syndrome and Fatal Familial Insomnia.

    Iatrogenic forms: 51 of 968 children treated in France with Human Growth Hormone became infected with CJD. Infection has been documented via corneal graft transplants and dura mater transplants. The National Institute of Neurological Disorders and Stroke (NIH) documented the transmission of CJD from a middle-aged woman to two younger patients and a chimpanzee via cerebral cortex electrodes, despite repeated cleanings and sterilizations.8 ---Neurosurgical transmission from biopsy patient to trauma patient has also occurred. The new West European BSE variant strikes younger patients; its incidence is much higher than 1 per million but is not yet fully known. In New Guinea, a variant called Kuru causes periodic outbreaks through cannibalistic practices.

    In Animals

    Bovine Spongiform Encephalopathy (BSE): The recent British epidemic reached 1% incidence with approximately 170,000 diagnosed cases.

    Chronic Wasting Disease (CWD) is endemic in elk and mule deer.

    Scrapie is an endemic form of the disease in sheep and goats. It is the source of the BSE outbreak in England via rendered (cooked) meat meal. Forty years of USDA policy of flock slaughtering has not eradicated the disease.

    Transmissible Mink Encephalopathy has been observed in farm mink-fed downer dairy cattle.

    Feline Spongiform Encephalopathy has been transmitted in zoos to a wide range of animals (eland, nyala, oryx, kudu, gemsbok, cheetah, puma, ocelot, ostrich)
     
Preventing CJD during Neurosurgery

 No consensus exists in the literature on surgical instruments sterilization methods adequate to prevent the spread of CJD. Autoclaving at 134º-138ºC for 60 min is not adequate;4 steam autoclaving and even ashing at 360ºC is not effective.6 Solutions of sodium hypochloride4 and quanidine thiocyanate12 offer promise to disrupt the infectious agent. The inadequacy of current sterilization procedures has led some authorities to recommend that "all instruments used for patients with CJD must be destroyed."13 While this policy would be adequate for patients known to have a TSE, the long incubation period, varying clinical presentations, similarity of clinical course to other neurological conditions and the lack of accurate clinical antemortem diagnostic tests make it very difficult to rule out TSE. The re-use of surgical instruments in neurological cases is therefore tantamount to simply gambling that the current surgical patient will not be the one to launch the first cluster of an epidemic.

TSE still has a very low incidence,14 but it is instructive to remember that bubonic plague and HIV were also once rare and of concern only to the unlucky few. Sporadic outbreaks of Kuru, BSE and Transmissible Mink Encephalopathy may be considered sentinel warnings that TSE presents an epidemic risk to the public health similar to rabies. While rabies is contained via an aggressive program of immunizations and public awareness, there exists neither the program nor the vaccine to contain the spread of TSE in this fashion. Until there is a test to rule out TSE in the neurosurgery patient, the surgical spread of the disease can only be halted by preventing the re-use of neurosurgery instruments. The severity of TSE demands the same prophylactic philosophy used for rabies upon an animal bite, and HIV when there is a risk of blood exposure: when in doubt, proceed as if the agent is present.
 

References

 (Abstracts available on Medline at www.ncbi.nlm.nih.gov/PubMed)

  1. Ghani AC, Ferguson NM, Donnelly, CA, Hagenaars, TJ, Anderson, RM, Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain. Proc R Soc Lond B Biol Sci 1998 Dec 22;265(1413):2443-52.
  2. Hill AF, Butterworth RJ, Joiner, S, Jackson, G, Rosser, MN, Frosh, A, Tolley, N, Bell, JE, Spencer, M, King, A, Al-Sarraj, S, Ironside, JW, Lantos, PL, Collinge, J, Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999 Jan 16;353(9148):183-9.
  3. Kirkwood JK, Cunningham AA, Wells, GA, Wilesmith, JW, Barnett, JE, Spongiform encephalopathy in a herd of greater kudu (Tragelaphus strepsiceros): epidemiological observations. Vet Rec 1993 Oct 9;133(15):360-4.
  4. Taylor DM, Fraser H, McConnell I, Brown DA, Brown KL, Lamza KA, Smith GR, Decontamination studies with the agents of bovine spongiform encephalopathy and scrapie. Arch Virol 1994;139(3-4):313-326.
  5. Burger D, Gorham JR, Observation on the remarkable stability of transmissible mink encephalopathy virus. Res Vet Sci 1977 Jan;22(1):131-2.
  6. Brown P, Liberski PP, Wolff, A, Gajdusek, DC, Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications. J Infect Dis 1990 Mar;161(3):467-72.
  7. el Hachimi KH, Chaunu MP, Cervenakova, L, Brown, P, Foncin, JF, Putative neurosurgical transmission of Creutzfeldt-Jakob disease with analysis of donor and recipient: agent strains. C R Acad Sci III 1997 Apr;320(4):319-28.
  8. Gibbs CJ Jr, Asher DM, et.al. Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8.
  9. Collins, S, Law, MG, Fletcher, A, Boyd, A, Kaldor, J, Masters, CL, Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 1999;353(9154):693-7.
  10. "World Health Organization Consultation on Public Health Issues Related to Bovine Spongiform Encephalopathy and the Emergence of a New Variant of Creutzfeldt-Jakob Disease, "Morbidity and Mortality Weekly Report, 12, April, 1996; 295-303.
  11. Manuelidis, EE, Manuelidis, L, "Suggested Links between Different Types of Dementias: Creutzfeldt-Jakob Disease, Alzheimer disease and Retroviral CNS Infections, " Alzheimer Dis Assoc Disord 1989;3(1-2): 100-9.
  12. Manuelidis, L, "Decontamination of Creutzfeldt-Jakob Disease and Other Transmissible Agnets," Neuroviro 1997;3(1):62-65.
  13. Estebe JP, Anesthesia and non-conventional transmissible agents. Ann Fr Anesth Reanim 1997;16(8):955-63.
  14. In the US, CJD is annually identified in the death certificates of 0.9 per million persons. Holman RC, Khan AS, Kent, J, Strine, TW, Schonberger, LB, Epidemiology of Creutzfeldt-Jakob disease in the United States, 1979-1990: analysis of national mortality data. Neuroepidemiology 1995;14(4):174-81.