The annual death toll from vCJD has been falling since its peak of 28 in 2000. In 2004 the number of deaths dropped to just eight.16 Although initial estimates of the total case numbers of vCJD were alarming, they have been revised downwards to a few hundred, creating hope that the worst was over.34 However, recent findings have given rise to uncertainties.
There is now compelling evidence for human to human transmission of vCJD through blood transfusions from presymptomatic donors. It has been reported that a recipient of a labile blood component developed symptoms of vCJD approximately 6.5 years after receiving the transfusion.17 The donor of the red blood cells developed symptoms of vCJD 3.5 years after the donation, raising the likelihood that the infection was transmitted through the transfusion. A second case has been reported in the UK involving a donor who later went on to develop vCJD. The recipient of this blood transfusion died of causes unrelated to vCJD, but postmortem examination revealed the presence of PrPres in the spleen.18
In 2004 up to 4000 individuals were sent letters informing them that they may be at increased risk of carrying vCJD because they had received blood products donated by people who subsequently developed the disease. All recipients were advised to tell their doctors and dentists in order to reduce the possibility of secondary transmission.35
Additional fears of a future "tail" or late expansion of the epidemic come from the discovery that vCJD is no longer assumed to occur only in individuals who are homozygous for methionine at codon 129 of the prion protein gene.18,20 The patient believed to have contracted vCJD through a blood transfusion was found to be heterozygous at codon 129 at postmortem.18 The fear is that those who are homozygous for methionine at codon 129 have shorter incubation periods for vCJD, and those who are heterozygous are not immune to infection, but simply have longer incubation times.13 This would imply a further group of people who are currently infected but still asymptomatic, thus posing additional risks for secondary transmission.36 Individuals who are homozygous at codon 129 are overrepresented in all forms of sporadic and acquired human TSE and heterozygosity has been shown to correlate with longer incubation periods for growth hormone related CJD and kuru.15
Further cause for concern comes from a study of anonymised appendix and tonsil samples, which assessed the presence of PrPres in these tissues.20 An analysis of nearly 13 000 samples found PrPres in three. If these figures are extrapolated to the population of the UK it would indicate that almost 4000 people aged between 10 and 30 years may be asymptomatically harbouring the prion proteins that cause vCJD. However, only one of the three samples resembled the patterns of accumulation usually seen in vCJD. A more recent study of tonsillectomy specimens failed to find a positive case of disease associated prion proteins in 2000 samples, so more research is needed before definitive conclusions can be drawn.37
DEVELOPMENT OF A PRESYMPTOMATIC TEST FOR VCJD
A reliable, non-invasive, presymptomatic or early symptomatic diagnostic test for vCJD could greatly decrease the potential for iatrogenic transmission in humans but is yet to become available.10–12 Many laboratory based approaches are being developed for the screening of vCJD using blood samples and will continue to be refined in the future.15 Technical aspects of the development of such tests have been detailed, as have methods for validation of test results, although the lack of appropriate positive control samples may hamper the latter.6,12 Minimal criteria for the sensitivity and specificity of such testing, the circumstances under which tests should be implemented, and the surrounding ethical issues have been the subject of a recent conference.15 It is predicted that future screening of blood donors for vCJD may include an initial rapid blood screening test followed by a more rigorous confirmatory test and then a genetic test.15
Although it is currently unresolved whether presymptomatically infected persons will invariably manifest illness, these individuals may still pose covert secondary transmission risks in the health care setting. Thus, despite concerns relating to the sensitivity and specificity of any test adopted and the need for the establishment of independent verification methods, the development of a reliable, practicable, presymptomatic diagnostic test would evoke a range of significant ethical concerns.