Thread: VCJD Infection: A Continuing Threat to Public Health

ProMetic Life Sciences Inc./VCJD Infection: A Continuing Threat to Public Health

LONDON, UNITED KINGDOM -- (Marketwire) -- 02/04/10 -- Variant Creutzfeldt-Jakob Disease ("vCJD") remains 'a very real and continuing threat to public health and recent developments strongly support predictions of second and third waves of long incubation vCJD' commented Dr Robert Rohwer, Director, Molecular Neurovirology Laboratory and Associate Professor of Neurology, University of Maryland, Baltimore, U.S., speaking at today's GovNet Communications' Patient Safety 2010 Conference held at the QEII Conference Centre in London, UK. Dr Rohwer went on to emphasize the urgency of implementing universal protective measures to arrest human to human transmission through blood transfusion and blood products.

Dr Rohwer highlighted recent research and developments showing how vCJD transmission risk remains 'very real'. He discussed the 'significant challenges' associated with detecting the prion in blood and urged implementation of proven infectivity removal technologies to protect blood. He referred to:

+ Research by Prof John Collinge of the National Prion Clinic, published in the Lancet, (December 2009) describing the first patient to succumb to vCJD from a previously unaffected genetic subgroup of the prion protein. Prior to this point, all 215 people who died of vCJD shared a certain version of the prion gene that is present in only one third of the population. This finding strengthens an earlier prediction by Prof Collinge of second and third waves of vCJD in people who were infected over the same period as people in the first wave, but whose genetics result in a longer incubation time. Two thirds of the population is in this group. Incubating cases in this longer incubation group may be spreading the infection through blood and tissue donations and other invasive medical procedures. These new routes of exposure are of special concern because person to person transmissions are expected to be much more efficient than cattle to person transmissions.

+ Research by the Scripps Research Institute, U.S. (January 2010) which revealed that prions evolve (change) to adapt to new environments. In these experiments prions mutated to more virulent strains and developed resistance to drugs used to suppress their propagation.

+ The exceptionally difficult challenge of detecting prions in blood or plasma. While the miniscule amounts of infectivity in blood is enough to cause infections, it has yet to be convincingly detected other than by infection. Normal forms of the prion protein exist in every person and in blood they are 100,000 to 1 million times more concentrated than the infectious forms. Other plasma proteins are a million times more concentrated than even the normal prion protein. In spite of an abundance of ingenuity and tremendous development effort there is still no blood based assay available for vCJD. Most recently (December 2009) one of the most advanced tests failed to detect prions in blood samples from clinical-stage patients who have died and been verified to have vCJD from animal studies. These patients are expected to have the highest concentrations of vCJD infectivity in their blood.

+ The estimation that the number of people incubating vCJD in the general population is anywhere between 1 in 4,000 and 1 in 20,000. These estimates presume a high level of efficiency in identifying incubating cases. In fact the efficiency is undetermined and at present undeterminable. The recent discovery of incubating infections of vCJD in persons who have died of other causes but have prion genotypes that have not previously resulted in clinically recognised cases suggests that the prevalence may be much greater than anticipated.

+ Universal leucodepletion (the removal of white blood cells from donated blood) was adopted by the UK in 1999, in part to diminish the risk from vCJD transmission by blood. Animal studies have since shown that leucodepletion removes only 40-70% of the infectivity in donated blood. The remaining infectivity is more than sufficient to transmit the infection.

Dr. Rohwer summarized: 'Currently, vCJD contaminated blood poses the greatest risk for human to human transmission of vCJD. Moreover, since the transmission is between humans rather than bovine to human and the exposure is by transfusion or injection rather than orally, it is expected to be at least 1,000 times more efficient than transmissions from BSE infected food. This is not a theoretical risk. To date there have been five recognized cases of transfusion transmission of vCJD and one highly probable transmission from a plasma product. The UK collects over 2.1 million blood donations annually (1.8 million in England alone). It is not known how many of these donors are incubating vCJD, but accumulating evidence of long incubation times in genotypes that make up approximately two thirds of the population intimates that it may be far greater than indicated by the cases detected to date.'

Dr Rohwer noted that the UK has been a leader in evaluating new approaches to reducing the risk from vCJD contamination of blood. These have included the P-Capt® prion reduction filter which removes prion infectivity with an efficiency of 99.9% or greater. The UK evaluation programme has led to a recommendation to the UK Department of Health by the Advisory Committee on the Safety of Blood, Tissues and Organs ("SaBTO") to deploy the P-Capt® filter for treatment of red blood cells destined for children born since 1 January 1996. On 27 October 2009 when it made this recommendation, SaBTO indicated that 'the requirement for prion filtration should be reviewed in the event that further data on vCJD prevalence or filter efficacy becomes available'. Dr Rohwer noted that all recent developments warn of a continuing risk from vCJD and that since the greatest risk of human to human transmission is from blood use, timely and universal adoption of the P-Capt® filter is urgently needed to arrest further spread of the disease.

Dr Rohwer welcomed the progress of the Contaminated Blood (Support for Infected and Bereaved Persons) Bill, a private member's bill that is due to receive its Second Reading in the House of Commons on 5 February. The Bill proposes using prion filtration to protect the haemophilia community from receiving blood which could be contaminated with infective prions that cause vCJD but cannot, as yet, be tested.

ENDS
ProMetic Life Sciences Inc./VCJD Infection: A Continuing Threat to Public Health | SYS-CON MEDIA

Br J Haematol. 2012 Aug;158(4):442-52. doi: 10.1111/j.1365-2141.2012.09201.x. Epub 2012 Jul 9.
Dealing with the uncertain risk of variant Creutzfeldt-Jakob disease transmission by coagulation replacement products.

Millar CM, Makris M.
Source

Centre for Haematology, Imperial College London, London, UK.

Abstract

The identification of variant Creutzfeldt-Jakob disease (vCJD) in the UK in 1996 led to significant concerns about the possibility of secondary transmission, however the prevalence of subclinical vCJD and risks of vCJD transmission by plasma are not known. In the UK, public health precautions have been implemented in all recipients of coagulation factor concentrates manufactured from UK plasma pools between 1980 and 2001. The recent demonstration of abnormal prion protein in a spleen sample at autopsy of a UK haemophilic patient who received coagulation factor concentrates to which a donor incubating vCJD had contributed most likely represents the first case of vCJD transmission by coagulation factor concentrates. We review the uncertainties that surround risk of vCJD transmission by coagulation factor concentrates, the challenges in dealing with undefined risks, the rationale behind current policies and the implementation of vCJD surveillance and risk management measures in bleeding disorder patients in the UK.