Mad cow blood test could reduce secondary transmission of Creutzfeldt-Jakob disease

You may remember the scare -- infected beef causing brains to become holey and sponge-like, cows being slaughtered and consumers living on edge. The source of this fear was that the ingestion of beef contaminated by bovine spongiform encephalopathy (aka mad cow disease) causes variant Creutzfeldt-Jakob disease (vCJD), a fatal neurodegenerative disease characterized by a long asymptomatic phase during which the infectious agent breaks down brain tissue. Unlike other infectious agents, such as viruses and bacteria, vCJD contains no nuclear DNA and does not illicit an immune response, making the development of diagnostic tests very difficult.

For years, researchers have investigated blood-based measures that could provide a non-invasive clinical diagnosis, as well as a screening measure for donated blood. Early last year, researchers at the Medical Research Prion Council published a report showing their blood-based test had 71 percent sensitivity and 100 percent specificity in a sample of 190 individuals, including healthy controls and patients with vCJD, sporadic CJD, and other neurological diseases. The blood test is now being offered to confirm vCJD diagnosis after a patient has died and is being tested for its ability to provide a diagnosis for the living. A definitive diagnosis could provide closure to individuals suspected of having the disease, allowing them to choose how to approach their days.

Research is currently being conducted to determine the applicability of this test for screening the blood supply. This type of screening is essential because current measures such as leukodepletion, i.e. the removal of white blood cells, reduce but do not eliminate transmissible spongiform encephalopathies in blood. Secondary infection is of particular concern in Britain where estimates suggest that 1-in-4000 may carry the disease. Even though carriers may not develop vCJD, they can still spread the disease through blood and organ donation. While the blood test is promising as a tool for screening, it requires further testing to determine if 1) specificity holds up in larger samples and 2) there is reasonable sensitivity in asymptomatic carriers of vCJD.

Specificity refers to the ability to correctly identify negative samples, i.e. identifying people without vCJD as not having the disease. To determine if the blood based test’s specificity holds up to widespread testing, researchers have begun screening US blood from the Red Cross, which has low vCJD infection rates, to determine false positive rates. High specificity is extremely important for screening because lack of treatment options increases the risks associated with false positives.

If the specificity holds up, then testing of blood in the UK will begin to determine the sensitivity in non-symptomatic individuals. Sensitivity refers to the ability to correctly identify positive samples -- identifying individuals with vCJD as having the disease. Even in confirmed diagnoses, the sensitivity of the blood test only reached 71 percent during the previous research trials. Because levels of abnormal cellular prion protein are much lower in the asymptomatic vs. symptomatic phase, the sensitivity to detect carriers will most likely be lower than the 71 percent seen in the clinical population. This means that a negative screen does not guarantee an individual does not carry the disease. However, if the test identifies a reasonable number of individual carriers, the removal of this infected blood, in combination with current methods such as leukodepletion, could reduce the risk of secondary infection.  

The possibility of identifying carriers through blood screening, however, carries important ethical considerations. UK blood services would be required to tell individuals of a positive vCJD test. Notification that one carries an incurable, neurodegenerative disease would be devastating and many individuals might prefer not to know. The desire to remain in the dark about carrying a fatal neurodegenerative disease can be seen in genetic testing for Huntington’s disease, with around 95 percent of at-risk individuals choosing not to get tested. The implications of positive testing in Huntington’s disease has resulted in strict regulations about who, where, when and how results of genetic testing are undertaken. Similar measures will undoubtedly be required before screening of blood for vCJD can occur.