Risk of prion disease transmission through blood or serum

Questions are frequently asked as to wether CJD can be transmitted by blood tranfusion or by in vitro fertilization proceedures. There is currently not a clear scientific consensus. Because of the potential transmission, World Health Organization has recommended that individual in the following high risk catagories be permanently excluded as blood donors.

Individuals who have been treated with cadaver derived human pituitary hormones (growth hormone or gonadotropin)
Individuals who have a family history of CJD, GSS, or FFI
Individuals who have recieved a human dura matter graft
Individuals who have symptoms suggesting a possible prion disease

Blood or serum from donors who subsequently develop CJD or other prion disease should be withdrawn from use and destroyed. Different countries have different policies for managing this risk.

The USDA and FDA have set controls such that the American Red Cross currently excludes donors that have lived more than 6 months in countries where BSE (or vCJD) has been identified. This is a broad exclusionary category enacted as a safety precaution.

In September, 2001 the Red Cross will begin excluding donors that have spent 3 months in the United Kingdom (England, Northern Ireland, Scotland, Wales, Isle of Man or the Channel Islands) or 6 months anywhere in Europe since 1980, thus tightening the donor restrictions. Also, donors will be excluded if they received a blood transfusion in the United Kingdom. This restriction may reduce the number of blood donors by 8% (loss of donors approaching half a million of the >6 million US donors).

There were several reasons for these enactments, both for their generality and limitations:

• There is no direct evidence that CJD or vCJD (or BSE) can be transmitted by blood - thus there was need to consider whether the remote (or maybe non-existent) risk of contracting a TSE via donated blood out-weighed the possibility of a 2-3% blood shortage (with the current restrictions) caused by restricting donation (a small albeit significant effect that easily could result in loss of life at the Red Cross supplies half of the blood needed in the US).
• Albeit vCJD is a serious condition, contracting the disease is very rare. Thus, the risk of contacting the disease was considered remote enough not to exclude those living abroad less than 6 months.
• However, the risk of contacting the disease from donors lacking clinical symptoms is possible as vCJD may "hide" in several lymphoid tissues (tonsils, lymph nodes, spleen and Peyers patches of the gut) and it is believed that B lymphocytes (a type of white blood cell found in the circulation) may contain prion proteins. Please note the word may in this latter sentence. Considerable investigation is needed to prove that these tissues or cells can be infectious or that they are safe.
• Thus there is a possibility that donors exposed to vCJD or BSE may be infectious before clinical symptoms arise.
• Until a sensitive and accurate test is available to screen blood from donors, the current ban mentioned above was enacted and the new restrictions will take effect in September.
  

Click for a large (190k) image describing a possible mechanism of TSE infection

Important findings relating to: prion AND (blood OR serum OR plasma)

Weissman, 2001. Following scrapie infection of mice, infectivity is first found in the spleen and later in the brain. T and B lymphocytes of the spleen were infectious. PrP is found on T and B lymphocytes and follicular dendritic cells (FDCs) in the spleen. No infectivity was found in lymphocytes (T or B) within blood of the same mice. Evidence indicates that, albeit they express PrP, that the PrP^Sc found on T and B lymphocytes is derived from FDCs and is not retained on lymphycytes found in the circulation. Thus, infectivity of cells within the spleen does not relate to infectivity of spleen-derived cells found in the circulation.

Hermann, 2001. PrP mRNA was found in peripheral blood mononuclear cells (PBMC) of normal and scrapie sheep as was cell surface PrP. The cellular PrP of both normal and scrapie infected sheep was proteinase K sensitive. Thus despite carrying scrapie, the PrP on circulating cells does not appear to be PrP^Sc but appears to be normal non-infectious PrP.

Fischer, 2000. PrP^Sc but not PrP bind to plasminogen from blood. First factor found that can descriminate between these protein isoforms. Plasminogen may play a role in neuronal excitotoxicity and hence a role in the death of neuronal cells caused by PrP^Sc . This finding may lead to new test for PrP^Sc levels and to better understanding on the pathologic effects of TSE.

Houston, 2000. Whole blood taken from a symptom-free sheep caused scrapie in another sheep following transfusion.