Medical Device Link.

MATERIAL MATTERS COLUMN

Writing this column between Christmas and New Year at the end of 2005, it is obvious that medical technology continues to play an enormously important role in our lives and that there will be plenty of issues to discuss during the coming year. The technical developments that we are witnessing in medicine at the moment are profound, especially those that occur at the interface between information technology, advanced materials science and biology. These developments bring with them a myriad of nontechnical issues, for example, health economics and medical ethics. I read in an American newspaper that the United States is in the middle of the biggest hospital construction programme for a century, but the new facilities are so technologically oriented that health-care costs are soaring beyond the reach of most citizens. On the ethical front, we have witnessed the emergence of the apparent “scandal of scientific fraud” following the activities of Professor Hwang Woo Suk in South Korea in embryonic stem cells and cloning. Whatever the outcome of this case, which I shall write about in due course once the details are clearer, it certainly raises questions about the speed of introduction of new medical technologies and the ethical dimensions of the cutting edge of innovative medical science. We also have the spectre of a flu pandemic should the avian version be transmitted to humans.

CJD and blood transfusion

The topic of this month’s column touches on all four of the above issues: technology, cross-species disease transmission, health economics and medical ethics. It is concerned with the long-running debate over the transmission of diseases from animals to humans, especially the spongiform encephalopathies, and includes the question of contamination through the use of surgical instruments. The reason why this is topical again is that a new Scientific Opinion on Creutzfeldt-Jakob Disease (CJD) risks has just been made available by the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) of the European Commission.¹ This is the same source that produced an opinion on nanotechnology, reported in this column in November 2005.²

It will be recalled that a decade or so ago there was great anxiety, especially in Western Europe, following the outbreak of bovine spongiform encephalopathy that affected cattle, particularly in the United Kingdom (UK), and the possibility that this disease could cross species barriers and lead to CJD in humans. There was clear evidence that this could take place, and although the number of cases of so-called variant CJD fell far short of those predicted by some, the mechanisms of potential transmission remained controversial. Because bovine tissues and fluids were used in many areas of medical technology and pharmaceutics, there was a major effort to introduce processes of risk assessment and risk management associated with the use of any animal products in these areas, and most would agree that these processes have been beneficial. The reason why risk management is still a matter of concern is the possibility of the transmission of variant CJD from human to human through medical procedures and products, including blood transfusions, transplants and cell therapies, and through contaminated surgical instruments.

In 2004, two cases were reported in which variant CJD appeared to be transmitted via blood transfusions. These two cases could not be definitely confirmed, but their characteristics led to clear conclusions that there is a substantial risk of disease transmission following transfusion of nonleucodepleted blood from asymptomatic individuals who were incubating variant CJD. The SCENIHR was asked to review this evidence and advise on the levels of risk. Taking into account the eligible blood-donor population in the UK and the procedures for the use of donated blood including pooling of donations, the SCENIHR suggested that the worse case in the UK would be approximately 3750 new infections per year. The current decline in the onset of variant CJD and the low number of cases observed in the older age groups that comprise the majority of blood recipients, suggests that this number is probably a significant over estimate, but it is clear that concerns do exist. One of the difficulties here is that, although there have been considerable advances in test methodologies for prion diseases, no diagnostic system has yet emerged with the level of sensitivity and specificity required for the routine screening of blood.

Surgical instruments

The SCENIHR report discusses at some length the epidemiological and case history aspects of CJD transmission. It makes extremely interesting reading at a time when zoonoses (animal to human transmission) is so potentially important, but discussion of this is beyond the scope of this article. The one area that is highly relevant, however, concerns the iatrogenic transmission of disease associated with surgical procedures (for a review of these iatrogenic effects, see Brown et al.).³ The main factor here is the ability of the prion proteins that are associated with the infectivity of the transmissible spongiform encephalopathies to adhere to a variety of surfaces and to resist both removal during cleaning procedures and eradication by sterilisation. It has to be said that the number of cases where there has been a proven transmission of disease through this route is limited, but the mechanisms of transmission are scientifically valid and the need to follow clear risk management procedures cannot be denied. At the heart of this issue is the re-use of surgical instruments and devices, which clearly affects the ethical and health-economic aspects of the re-use of single-use devices and the technology of cleaning and sterilisation processes. The arguments are, of course, complex and this complexity requires full and sensible risk analysis. This approach is justified in view of the well-known history of the policy in the UK a few years ago to mandate the use of disposable surgical instruments for tonsillectomies because of the theoretically high infectivity of lymphoid tissue, which led to the poorer clinical outcomes associated with some ineffective disposable instruments. In many situations, the routine use of high-quality disposable instruments would be prohibitively expensive, but so could the introduction into hospital practice of new complex cleaning and sterilisation procedures.

David Williams Clinical Engineering Department, Royal Liverpool University Hospital, Liverpool L69 3BX, UK, tel. +44 151 706 5606 fax +44 151 706 5803, e-mail: dfw.ce@liverpool.ac.uk

The danger is real. The report quotes studies in which 10 mg of tissue is left on simple surgical instruments after routine cleaning. There are many variables associated with the cleaning and decontamination procedures, including the nature of the chemicals used, the timing of the procedures and the physical conditions of the exposure. Yet, the fact remains that no procedure for the decontamination of surgical instruments has so far been validated to the extent that its universal introduction can be recommended. The complexity of the situation can be seen from two revealing statements. First, disinfectants with fixative properties such as those containing aldehydes (widely used in other situations) must not be used for the decontamination of instruments suspected to be contaminated with encephalopathy prions, because they tend to stabilise rather than inactivate the prions. Second, drying of instruments before cleaning and decontamination is likely to reduce the effectiveness of the decontamination process. The use of some conventional decontamination solutions such as NaOH and NaOCl was endorsed, and the potential for some recently identified solutions such as guanidium thiocyanate emphasised.

The SCENIHR concluded that to minimise the risk of transmission of CJD from surgical instruments, procedures are recommended based on the probability of the patient under investigation or treatment being infected with any infectious agent. For clinically confirmed cases of variant-CJD patients, potentially contaminated instruments must be destroyed. For patients at high risk, single-use instruments are recommended, but in situations where this is impractical, cleaning plus chemical inactivation plus physical inactivation procedures may be used, depending on the type of procedure (mainly the type of tissue) involved. This provides a good example of a rational risk analysis approach to potential hazards associated with surgical procedures and instruments. The rapidly declining incidence of the onset of variant CJD in the UK and elsewhere in Europe, suggests that this specific issue may only be transient, but considerable lessons have been learnt.

Professor David Williams DSc, FREng is Professor of Tissue Engineering at the University of Liverpool and Director of the UK Centre for Tissue Engineering located in the Universities of Liverpool and Manchester. He is Editor-in-Chief of Biomaterials, the leading journal in the biomaterials field. He is Scientific Director of STEPS, the European Commission Framework VI Programme on a Systems Approach to Tissue Engineering Products and Processes. Professor Williams is also a Managing Partner of Morgan & Masterson LLC, a consulting partnership that focusses on global health-care issues.