association

Introduction

Transmissible spongiform encephalopathies or TSEs are a group of diseases that cause rapidly developing degenerative and ultimately fatal disease of the central nervous system. Symptoms of TSEs are difficulty in balance, loss of muscle coordination and, in humans, slurred speech, failing vision, memory loss and dementia. The causative agent is thought to be an infectious protein called a prion. These prion proteins are abnormally shaped and cause other proteins to conform to the same shape, thus causing the brain tissue to develop holes and a characteristic "Swiss cheese" appearance.¹

TSE Diseases

TSEs are found in animals - for example scrapie in sheep and goats, and bovine spongiform encephalopathy (BSE) in cattle (more familiarly known as mad cow disease). TSEs manifest in humans primarily in the form of Creutzfeldt-Jakob disease (CJD) and the more recently identified new variant Creutzfeldt-Jakob disease (vCJD). Other even more rare human forms of TSE are Gerstmann-Straussler-Scheiker disease, fatal familial insomnia, and kuru. The first evidence of the transmissibility of TSEs was evidenced by the kuru epidemic among tribes that practiced ritual cannibalism in New Guinea, eating human brain, among other body parts. When cannibalism stopped in the 1950s, the incidence of kuru virtually disappeared.²

Evidence of Transmission by Blood

Classic CJD infectivity in blood has been demonstrated in lab experiments with rodents both during the asymptomatic incubation phase and during overt disease. In these experiments, blood caused transmission of CJD only via injection directly into brain tissue.³ More recent studies of various tissues and fluids from BSE cattle injected into rodents do not show infectivity from blood. However, in a preliminary report one study showed the transmission via blood transfusion from one BSE-infected sheep to one disease-free sheep. Other sheep similarly transfused in the same experiment did not develop disease.⁴ Further evidence of the lack of infectivity of CJD and vCJD by blood transfusion comes from several epidemiological studies, which included heavily transfused populations and tracing recipients of blood from donors who developed CJD or vCJD. None of the recipients developed these diseases. The most convincing evidence against transmission by transfusion is that no cases have been reported in persons with hemophilia and others who receive large amounts of blood or are transfused on a regular basis. Nevertheless, applying the precaution-ary principle, the FDA has advised additional donor history screening to safeguard against transmission of CJD and vCJD.

Protection of the Blood Supply

The vast majority of CJD cases are sporadic, affecting 1:1,000,000 people worldwide annually. About 10 percent of cases are familial and a small handful of cases are of iatrogenic origin (deep probe EEG leads, dura mater transplant, corneal transplant and injection of human growth hormone). Therefore, questions that address these issues have been added to the donor history form.

With the identification of vCJD in the UK in 1996, the FDA and other national health authorities concluded that the consumption of BSE-infected meat was likely the cause. Concerned over a potential risk to the blood supply, the FDA asked the TSE Advisory Committee to consider appropriate donor deferral criteria for time spent in the United Kingdom (UK). A balance had to be struck between the predicted number of donors deferred for various lengths of time spent in UK countries and maintaining an adequate supply of blood. The period of six months cumulative time spent in the UK between 1980 and 1996 was predicted to defer 2.2% of blood donors nationwide and 3% of donors in the greater New York City area.⁵ This was thought to be a loss that blood centers could absorb. Since implementation of the UK travel restriction in the Spring of 2000, the actual percentage of donors deferred proved to be far less. Nationally only 0.3% of donors were deferred and 0.6 % of donors were deferred in the New York City area.⁶ It is important to recognize, however, that these overt deferrals would not include donors who stopped presenting to donate based on this well publicized criteria for ineligibility. There is also concern that some donors are self deferring incorrectly based on confusion in calculating the time spent in the UK. The ARC and the NYBC plan to do a survey of lapsed donors to determine what percentage have self deferred for this reason and whether they have correctly self deferred.

In January, 2001 the FDA asked the TSE Advisory Committee to review the issue of travel as reports of BSE spread throughout western Europe. New variant CJD is considered an emerging infection because it displays some different features from classic CJD that include marked accumulation of prions in the lymphoid tissues and development of disease at a younger age, possibly indicating a shorter incubation period.

In recent months the number of countries acknowledging BSE expanded to include all of western Europe. Accordingly, the TSE Advisory Committee meeting in January of this year expanded their recommendations to include an aggregate period of time of 10 years spent in France, the Republic of Ireland or Portugal since 1980.

The committee did not recommend extending the deferral of donors to other countries because, unlike France and the Republic of Ireland, no cases of vCJD have been reported in any other country. Portugal is considered a country of concern, as the European Union assigned it to the highest risk category for BSE last year. The Republic of Ireland was assigned borderline status between high and medium risk. This is based on the amount of beef that was imported from the UK and their management of the BSE crisis. Another factor was the concern regarding the effect on the adequate supply of blood in the greater New York City area if the ban on donors was to be expanded to other countries. Approximately 25% of the blood supply for the greater New York City areas is imported from Switzerland, Germany, and the Netherlands.

Donor and Product Management Summary

Below is a chart summarizing donor and product management.

Notes: All CJD or vCJD deferrals are permanent (indefinite). If a donor is not familiar with the term Creutzfeldt-Jakob disease, it may be taken as a negative response.

Future

Until there is greater certainty about the lack of transmissibility of CJD and vCJD via blood transfusions, we will surely continue using donor screening questions to capture potential risk for these diseases. However, since these questions, particularly those focusing on travel, are non- specific and limited as a safety precaution, intensive focus should be on scientific inquiry into whether TSEs are transmissible by blood trans-fusion and on developing a test to screen for TSEs in asymptomatic blood donors.