New prion inactivation treatment presented

Developed through collaboration between D-Gen and DuPont, the prion disinfectant Rely+On Prion Inactivator is reported to significantly and rapidly reduce the potential risk of variant CJD (vCJD) transmission via surgical instruments and medical devices with a single-step, pH neutral, ten minute pre-soak procedure.

It is said to provide hospital sterilisation units with an effective treatment for sterilisation-resistant prions in an easy-to-use format. Its efficacy means that the equivalent of a 1,000,000 fold reduction in prion infectivity could be achieved on surgical instruments, which in turn equates to a potential reduction in the risk of accidental transmission of vCJD of up to 1,000,000 fold.

The need for an effective prion decontamination method has become a formidable public health challenge. Recent NICE guidance and a CMO letter have emphasised the Department of Health’s concerns for the potential of secondary vCJD infections occurring in the NHS. CNS and posterior eye surgery carry the greatest risk of infectivity although individuals silently carrying vCJD infection are known to harbour infectivity in a range of so-called lymphoreticular tissues that are present all over the body.

A recent Department of Health survey of hospital SSD units showed that despite carrying out full decontamination and sterilisation procedures, surgical instruments retain relatively large amounts of residual protein. Prion proteins bind avidly to steel and such steel surfaces are known to be still infectious after conventional sterilisation and decontamination procedures.

Of greatest concern, infective prions can resist both extensive autoclaving and treatment with formaldehyde and alcohol. In one notable case, an accidental transmission of CJD occurred via an EEG brain electrode, confirming that prions retain infectivity even after numerous routine sterilisation procedures.

Groundbreaking work at the MRC Prion Unit, directed by Professor John Collinge and funded by the UK Department of Health, led to the development of novel enzymatic methods to destroy prions on metal surfaces.1 This laboratory research work has now been developed into a practical system for easy use in hospitals.

Cell bioassay

Dr Jackson also presented data on Rely+On Prion Inactivator and a new cell bioassay developed in collaboration with D-Gen and the MRC Prion Unit for the assessment of prion decontamination/ infectivity. The cell bioassay uses prions sourced from the RML strain that are more resistant to proteolytic enzymes than vCJD prions and therefore represents a more stringent model for the assessment of enzymatic decontamination methods.

D-Gen’s extensive assessment of Rely+On Prion Inactivator and various experimental formulations using the highly sensitive cell bioassay demonstrated that two proteolytic enzymes are most effective at prion destruction. Data demonstrates that the cell bioassay is 100 times more sensitive than the previous gold standard mouse bioassay that has the added disadvantage of taking more than four months to complete.

Commenting on the Rely+On Prion Inactivator launch, the technical director at DuPont, Dr Vince Croud explained: “With activity against prions and conventional microbial pathogens, plus the key advantage of the single-step procedure, the new product is formulated to provide good instrument compatibility having a neutral pH, a reasonably low temperature of use and a short contact time. The public health benefits of using Rely+On Prion Inactivator will result in a quantifiable and significant reduction in the risk of accidental transmission of vCJD.” 

Prion studies information

In 2003, a prevalence study was carried out to quantify the risks of secondary vCJD infections arising from surgery and tissue donation using appendix material.2 The study suggested that between 49 and 692 people per million may be asymptomatic vCJD carriers in the UK, although this could be an underestimate.3 Although there have been no reports of vCJD being acquired through the use of contaminated surgical instruments or medical devices to date, vCJD has been transmitted via contaminated transfusion products suggesting that iatrogenic cases of transmission will be identified in the future.4,5,6

Furthermore, two recent studies of terminal ileum7 and rectal tissue8 – both tissues frequently examined and biopsied using non-autoclavable endoscopes and colonoscopes – observed that although the levels of prion infectivity were low, approximately 1% of those in brain tissues, innoculation of transgenic mice with infected rectal homogenates resulted in the efficient transmission of prion disease.

In addition to the concerns raised from studies showing high levels of prion infectivity in the tissues of vCJD patients, surgical steel is a major source of infectivity.9,10 Surgical steel-bound prions transmit disease with remarkable efficiency and prions adhere very strongly to other materials such as plastics.

References

1 Jackson G.S., McKintosh E., Flechsig E. et al. An enzyme-detergent method for effective prion decontamination of surgical steel. J Gen Virol 86, 869-878 (2005).

2 Hilton D.A., Ghani A.C., Conyers L. et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 2004; 203: 733-739.

3 Joiner S., Linehan J., Brandner S. et al. Irregular presence of abnormal prion protein in appendix in variant Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2002; 73: 597- 598.

4 Llewelyn C.A., Hewitt P.E., Knight R.S.G. et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004, 363: 417-421.

5 Peden A.H., Head M.W., Ritchie D.L. et al. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004, 364: 527-529.

6 Wroe S.J., Pal S., Siddique D. et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 368, 2061-2067 (2006).

7 Joiner S., Linehan J., Brandner S. et al. High levels of disease related prion protein in the ileum in variant Creutzfeldt-Jakob disease. Gut 2005.

8 Wadsworth J.D., Joiner S., Fox K. et al. Prion infectivity in vCJD rectum. Gut 2006.

9 Zobeley E., Flechsig E., Cozzio A. et al. Infectivity of scrapie prions bound to a stainless steel surface. Molecular Medicine 1999, 5: 240-243.

10 Flechsig E., Hegyi I., Enari M. et al. Transmission of scrapie by steel-surfacebound- prions. Mol Med 2001; 7: 679-684.