Transmission, Diagnosis Methods, Possible Treatment, and Prevention of Prions - Essay Example

Prions - an Overview Also known as transmissible spongiform encephalopathies, prion diseases are characterized as rapidly progressive and uniformly fatal spectrum of illnesses that particularly affect the brains of human and animals such as cattle, sheep, goats, mink, deer, elk, cats and zoo ungulates. Identified prion diseases in humans include Creutzfeldt-Jakob disease (CJD) and its new variant, Gerstmann-Strausller Scheinker syndrome, fatal familial insomnia, Kuru and Alpers syndrome (Collins, McLean & Masters 2001). The degenerative tissue damage brought about by human prion diseases includes spongiform change, neuronal loss, astrocytosis and amyloid plaque formations (Montagna, Gambetti, Cortelli & Lugaresi 2003). Clinical signs among others include personality changes, psychiatric problems, lack of coordination, steady gait, involuntary jerking movements, unusual sensations, insomnia, confusion and severe mental impairment in the later stages. Those known to infect other vertebrate animals include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cows, chronic wasting disease in American elk and deer, transmissible mink encephalopathy in mink and feline spongiform encephalopathy in cats (Jeffrey, Goodbrand & Goodsir 1995). One of the primary risk factors identified in relation to prion diseases is age. Studies suggest that a general mechanism might produce the remarkable reduction in disease risk as age increases. For example, in a study of scrapie outbreaks, it is observed that incidence of clinical cases peaked in sheep with age ranging from 2 to 3 years. The same age range has been noted in cattle with mad cow and deer with chronic wasting disease (Heisey 2004). In terms of its prevalence in the human population, it is estimated that 1 in 10,000 people are infected with CJD at the time of death. The actual prevalence of prion diseases are very difficult to ascertain due to overlapping symptoms that may lead to misdiagnosis. (Heaphy 2003) Research pertaining to prion diseases is deemed limited by the fact that studying them is substantially hampered by the unconventional properties of the presumed etiologic agent. Moreover, the long incubation period ranging from 34 to 41 years ("Mad cow could be dormant in people" 2006) of the diseases make them more difficult to detect. Moreover, the standard laboratory methods utilized for studying viruses and bacteria may not be applicable in this case (Belay & Telling). However, following reports of the outbreak of BSE, commonly termed as "mad cow" disease, in many European countries coupled with the estimated economic and medical implications of the said epidemic, the scope and nature of research on prion diseases has developed rapidly. This paper focuses on the current advancements in the study of prion diseases specifically in terms of modes of transmission, diagnosis methods, possible treatment and prevention. Modes of Transmission The manner of transmission of prion diseases is of primary concern in view of the protein nature of the prions. Note that unlike other types of infectious diseases which are spread by microbes, prion diseases are caused by misshaped protein, dubbed as prion protein, which transmits the disease between individuals causing brain deterioration (Belkin 2003). Based on recent studies, prion diseases have been considered unique as these can be inherited, sporadically occur or spread through infection. Majority of the prion disease cases are said to occur spontaneously, hence, animals with no prion protein mutation were observed infected. (Collinge 2001) On the other hand, inherited prion disease occurs in animals carrying a rare mutant prion allele. The disease is transmitted when healthy animal consume tainted tissues of other infected animals. The "mad cow" epidemic has been attributed to this mode of transmission as practice of feeding the cattle with processed remains of other cattle, which may have been infected already, became common. (Weissmann 2004) In humans, as in the cases of CJD, the prion diseases have been transmitted when an individual comes in direct contact with affected tissues. Some patients have been infected with the disease after being injected with growth hormone derived from human pituitary glands (Brown et al 2000). Apart from this, prion diseases in humans are also said to be gradually transmitted through consumption of infected animals such as beef as in the cases of CJD in teenagers and young adults in1994 (Lewis 2005). It may also be transmitted through practicing cannibalistic rituals that allow prion proteins to accumulate through generations (Prusiner 2001). For instance, Kuru epidemic among the Fore people of Papua New Guinea was attributed to their funerary ritual of consuming their dead. Another mode of transmission is through the use of contaminated instruments for brain surgery. Prions are substantially resistant to conventional methods of disinfection and sterilization (Belkin 2003). In this regard, discarding of instruments used on identified or prospective prion disease carriers in biohazardous trash for incineration has become common (Brown et al 2000). Blood transfusions may also be another mode of transmitting these diseases ("Second Wave of Mad Cow Disease Possible" 2006). However, this finding is still subject to further tests for confirmation. Diagnosis In the previous years, the diagnosis of prion diseases was mainly based on the occurrence of clinical symptoms which were confirmed through postmortem examination of brain tissue. This means that there were no diagnostic methods for identifying a carrier of the disease during its incubation period until recently (Belkin 2003). With the rapid advancements in prion disease research, myriad diagnostic techniques for each variant to identify abnormal protein have been undertaken. To date, in order to identify a sporadic CJD carrier, medical practitioners would have to do a surgical brain biopsy. For clinical diagnosis of the CJD, the bases include the combination of progressive dementia, myoclonus and multifocal neurological dysfunction. A development in the diagnostics for this prion variant is the assay for 14-3-3 protein in cerebral spinal fluid that is said to have a high sensitivity and specifity for sporadic CJD. ("World Health Organization" 1998) For the new variant of CJD, clinical features established by the World Health Organization (WHO) are early psychiatric symptoms, early persistent paresthesia/dysesthesia, ataxia, chorea or myoclonus, dementia and akinetic mutism. Although the new variant CJD cannot be diagnosed with certainty on clinical criteria alone, findings on a number of confirmed cases showed that the diagnosis of this prion disease should be taken into account in a patient who exhibits progressive neuropsychiatric disorder with at least five out of the six clinical features mentioned. Aside from these methods, experiments conducted by researchers at Jerusalem-based Hadassah University Hospital showed that a precipitable and protease-resistant form of the prion protein could be detected in dialysed urine. This finding further implies that the protease-resistant protein isoform is excreted in urine at the same time it is accumulated in the brain. Hence, they concluded that urine testing for this type of prion protein can be utilized to diagnose prion diseases in humans and animals at terminal phases as well as in the subclinical stages. In line with this promising discovery, the manufacture of diagnostic urine test kits to verify the efficacy of this method has been arranged. (Belkin 2003) Another milestone in the diagnosis of human prion diseases is the finding that tonsils have been observed to be a storage site for prion proteins. In this regard, it is recognised that the tonsil biopsy may be a crucial diagnostic test (Belkin 2003). Treatment As the prion protein still remains to be a mystery, there is still no known treatment for prion diseases. However, as knowledge about prion expands, the means as to how to target these diseases have been established. According to studies, interfering with the conversion of prion protein would seem to be the most attractive therapeutic target. In line with this, a possible treatment strategy would be to stabilize the structure of the prion protein by binding a drug. Another strategy is to modify the action of protein X, which functions as a molecular chaperone. (Prusiner) Furthermore, another possible avenue which potentially leads to formulation of a vaccine or treatment lies in the discovery that abnormally folded proteins that cause the disease expose a side chain of amino acids that properly folded protein does not expose. With this, antibodies particularly coded to this side chain amino acid sequence have been found to stimulate an immune response to the abnormal prions while leaving the normal prions intact. (Weismann 2004) Given the above, it can be seen that much effort would have to be exerted in order to find an effective cure for prion diseases before they spread in epidemic proportions. Prevention To prevent and reduce exposure to prion disease-causing agents, the WHO has banned the use of ruminant tissues in ruminant feed ("World Health Organization" 2002). With this, the organization has also impelled pharmaceutical industry players to avoid the use of materials from animals in which prion diseases naturally occur. In addition, WHO has established a new set of guidelines to relative to the reusing of medical instruments in light of the discovery that the disease may be spread through the utilization of contaminated instruments. It has recommended that instruments suspected to be contaminated should be immersed in sodium hydroxide solution and heated in gravity displacement sterilizer in for 30 minutes. Following such disinfection process, instruments should be cleaned, rinsed in water and subjected to routine sterilization. On the patients' end, they may consider directly inquiring from surgeons if the instruments to be used on them are prion-free. (Belkin 2003) Another crucial preventive measure to be undertaken, as strongly suggested by the WHO, is the conduct of risk assessments in all countries in order to determine the possible exposure of both human and animal population to prion diseases. Works Cited Animal and Plant Health Inspection Service 2000, Veterinary Services, [01 August 2006] Available at: http://www.aphis.usda.gov/lpa/fsheet_faq_notice/fs_ahtse.html Belay, E.D. & Telling, G.C. (eds), Prions and prion diseases: current perspectives, Horizon Bioscience, England. Belkin, N.L. 2003, 'Creutzfeldt-Jakob disease: identifying prions and carriers', AORN Journal, August 2003. Brown, P., et al 2000, "Iatrogenic Creutzfeldt-Jakob disease at the millennium', Neurology, vol. 55, no. 8. Collinge, J. 2001, 'Prion diseases of humans and animals: their causes and molecular basis', Annu Rev Neurosci, vol. 24. Collins, S., McLean, C.A. & Masters, C.L. 2001, 'Gerstmann-Straussler-Sheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies' J Clin Neurosci, vol. 8, no. 5. Heaphy, S. 2003, Prion Diseases, Leicester University, [01 August 2006] Available at: http://www-micro.msb.le.ac.uk/3035/prions.html Heisey, D.M. 2004, Emerging Infectious Diseases, June 2004. Jeffrey, M., Goodbrand, I.A. & Goodsir, C.M. 1995, 'Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure', Micron, vol. 26, no. 3. Lewis, C.E. 2005, 'Prion', Microsoft Encarta Premium Suite 2005. Montagna, P., Gambetti, P., Cortelli, P. & Lugaresi, E. 2003, 'Familial and sporadic fatal insomnia', Lancet Neurol, vol. 2, no. 3. Prusiner, S.B. 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