Brief history
- Ethical considerations in presymptomatic testing for variant CJD


Variant Creutzfeldt-Jakob disease (vCJD) was identified in 1996 as distinct from classical forms of CJD (both sporadic and familial).1 Cumulative evidence strongly supports that vCJD is zoonotically linked to bovine spongiform encephalopathy (BSE).2–4 BSE, CJD, and vCJD are transmissible spongiform encephalopathies (TSEs), a family of invariably fatal neurodegenerative diseases affecting both humans and animals.5 They are associated with the accumulation in affected brains of misfolded, protease resistant conformers (PrPres) of a normal host protein known as the prion protein. There is currently no proven prophylaxis or effective treatment for any form of CJD. The molecular structure of the infectious agent is unknown but is referred to as a prion.2,6

Soon after the recognition of vCJD, the tissue distribution of the disease-associated PrPres of the prion protein was shown to be relatively widespread, including in the peripheral lymphoreticular system, heightening concerns of iatrogenic transmission from blood products and surgical procedures.7 Adding to these concerns, the transmissible agents causing prion diseases are relatively resistant to the routine methods of decontamination and sterilisation used for medical equipment.8,9 Consequently, imperatives exist for the development of a reliable, non-invasive, presymptomatic or early symptomatic diagnostic test.10–12 Research into the development of such tests is well advanced.6,13–15 In-depth evaluation of the ethical implications of such testing is not.

It had been hoped that the primary wave of vCJD had reached its peak in 2000 when the annual death toll rose to 28, a figure not reached since.16 Two critical findings now negate such optimism. The recent realisation of secondary vCJD transmissions through blood products from presymptomatic donors has raised new fears and reinforced exigencies regarding the development of presymptomatic tests.17–19 It is also no longer assumed that vCJD affects only individuals who are homozygous for methionine at codon 129 of the prion protein gene (approximately 33% of the population), leading experts to wonder if the real epidemic is in fact ahead.18,20,21

There is an urgent need to consider the ethical implications of the provision of a screening presymptomatic diagnostic test for vCJD. This is crucial for four reasons: (1) vCJD is likely to be transmissible through invasive surgery; (2) sterilisation against vCJD requires more stringent measures; (3) recent data suggest that the number of people potentially incubating vCJD may be much greater than previously thought; and (4) a presymptomatic or early symptomatic diagnostic test is likely to be available in the near future. Acknowledging each of these facts, we provide an ethical analysis of four possible protocols for test provision, focusing on the need to balance personal autonomy with an obligation to benefit society as a whole. Finally we recommend what we believe to be the best protocol should a presymptomatic test become available.


BSE was first recognised in the UK in 1986.21 Cows suffering from BSE show symptoms of anxiety, restlessness, and aggressive behaviour: "mad cow disease".22 In 1988 a UK working party recommended the compulsory slaughter of all animals showing symptoms of BSE.23 In 1996 vCJD was first described.1 That same year, after advice from the Spongiform Encephalopathy Advisory Committee, the UK government announced that there was a probable link between BSE and vCJD.24 In 1997 the BSE Inquiry was set up, delivering its report in 2000.23

The most common theory on the origins of BSE holds that it was originally transmitted to cows from a sheep prion disease, scrapie, due to cattle feed being supplemented with sheep products.25 It is thought that vCJD then arose in humans as a result of exposure to BSE, most likely through contaminated food.10,26 The clinical features of vCJD are marked by both neurological and psychiatric disturbances. Individuals often present with anxiety, insomnia, and withdrawal.5 Additional clinical features may include delusions, aggression, and auditory and visual hallucinations.27 As the disease progresses, neurological signs such as slurred speech, involuntary movements, and cognitive impairments become evident.5 The average age of onset is 29 years and the duration of the disease ranges from 9 to 35 months.27

Detailed diagnostic criteria for vCJD exist, predicated on the condition representing a neuropsychiatric disorder.28 The criteria include early psychiatric symptoms, persistent sensory symptoms, ataxia, myoclonus or chorea or dystonia, and dementia.28 Electroencephalography and magnetic resonance imaging are important in diagnostic evaluation,28 and tonsil biopsy is also useful for achieving a specific diagnosis of vCJD.29

Less than two decades after the first "mad cow", as of December 6, 2004, it is estimated that 147 people have died from vCJD, with an additional five suspected to be living with the disease.16 The final vCJD case numbers from primary and secondary transmissions will not be clear for some time but it is obvious that a large percentage of the British population have an elevated risk of developing this disease.

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