Second case of variant Creutzfeldt-Jakob disease infection that was probably caused by blood transfusion

Research reported in The Lancet this week details the second case of variant Creutzfeldt-Jakob disease (vCJD) infection that was probably caused by blood transfusion. The rogue prion responsible for vCJD was identified at postmortem five years after an elderly person received a blood transfusion from a donor who later developed vCJD.

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal human neurodegenerative condition. As with Creutzfeldt-Jakob disease, vCJD is classified as a Transmissible Spongiform Encephalopathy (TSE) because of characteristic spongy degeneration of the brain and its ability to be transmitted. vCJD is a new disease that was first described in March 1996.

The prion that is believed to cause Creutzfeldt-Jakob exhibits an amino acid sequence and configuration which makes it insoluble in water, while the normal protein is highly soluble. So, as the numbers of defective prion proteins propagate and increase exponentially, the process leads to a huge load of insoluble prions in affected cells. This load of proteins disrupts cell function and causes cell death. Once the prion is transmitted, the defective proteins invade the brain like a forest fire and the patient dies within a few months (a few patients live for about 1-2 years). The defective protein can be transmitted by human growth hormone products, corneal grafts or dural grafts (acquired form) or it can be inherited (hereditary form) or appear for the first time in the patient (sporadic form). In the latter two forms the defective protein is not transmitted from an external source but already exists in the genes of the individual.

The first case of vCJD associated with blood transfusion was announced at the end of last year (see Lancet 2004; 363: 417–21). Also identified at that time were 17 people who had received blood donated from donors who later went on to develop vCJD. The case reported today—who did not have clinical symptoms of vCJD and died of other causes—was one of those 17 individuals.

The current case is the first of its kind to identify a heterozygous genotype for the prion protein, suggesting that a larger population of people could become infected. James Ironside, one of the investigators from the CJD Surveillance Unit, Edinburgh,UK, , comments:

“This finding has major implications for future estimations of numbers of vCJD cases in the UK, since individuals with this genotype constitute the largest genetic subgroup in the population. This subgroup might have a different incubation period after exposure to either primary infection by the bovine spongiform encephalopathy (BSE) agent or secondary infection by blood transfusion. A very lengthy incubation period might explain why no clinical cases of vCJD have yet been observed in this subgroup”.

Professor Ironside adds: “This case highlights the need for continuing surveillance for CJD in the UK, and strongly reinforces the role of the autopsy in the investigation and diagnosis of both clinical and preclinical forms of human prion disease”.

An accompanying commentary (p 477) by Kumanan Wilson (Toronto General Hospital) and Maura Rickets (Health Canada) is supportive of UK policies introduced to limit the spread of vCJD. With regard to the blood-transfusion case Dr Wilson comments: “The true clinical and public-health significance, with respect to the issue of whether the individual would have subsequently developed clinically evident vCJD or whether this individual poses a risk for iatrogenic transmission of the disease, remains uncertain. Nevertheless, combined with the animal studies by Houston and Hunter and their colleagues showing transfusion transmission of the disease in preclinical models, and the previous case report of probable transfusion transmission, there now appears to be sufficient evidence that individuals without clinical signs of vCJD harbour, and therefore potentially transmit, the infection”.

A policy of leucoreduction (removal of white blood cells) for blood transfusion to reduce the risk of possible vCJD transmission was introduced in the UK in 1999.

Authors of a second research letter (p 529) highlight how leucoreduction only reduced infectivity by around 40% in an animal model where hamsters were infected with scrapie-infected tissue. Lead investigator Luisa Gregori (VA Maryland Health Care System/University of Maryland, USA) comments:

“Although leucoreduction is a necessary step for removing white-cell-associated TSE infectivity from blood, this process is insufficient to remove the risk from an infected transfusion unit”.

Transmission of vCJD from surgical instruments is another public-health concern, especially as the prion protein responsible for vCJD is resistant to conventional sterilising procedures. In an article in this week’s issue (p 521), Jean Philippe Deslys and colleagues (CEA/DSV/DRM/GIDTIP, France) identify a new technique for disinfecting prion-contaminated medical devices. They report how specific alkaline agents or an original vaporized hydrogen peroxide treatment can be effective decontaminants without damaging delicate medical or surgical instruments; conventional autoclaving alone does not fully reduce transmission risk and can often damage surgical devices. Dr Deslys comments :

“Decontamination of prions from surgical instruments has been a major problem since vCJD was first identified. The results of our study should provide reassurance that practical solutions now exist which can be implemented without delay to reduce risk of prion transmission from medical and surgical instruments”.