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Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Iatrogenic transmission of prions, the infectious agents of fatal Creutzfeldt-Jakob disease, through inefficiently decontaminated medical instruments remains a critical issue. Harsh chemical treatments are effective, but not suited for routine reprocessing of reusable surgical instruments in medical cleaning and disinfection processes due to material incompatibilities. The identification of mild detergents with activity against prions is therefore of high interest but laborious due to the low throughput of traditional assays measuring prion infectivity. Here, we report the establishment of TESSA (sTainlESs steel-bead Seed Amplification assay), a modified real-time quaking induced cyclic amplification (RT-QuIC) assay that explores the propagation activity of prions with stainless steel beads. TESSA was applied for the screening of about 70 different commercially available and novel formulations and conditions for their prion inactivation efficacy. One hypochlorite-based formulation, two commercially available alkaline formulations and a manual alkaline pre-cleaner were found to be highly effective in inactivating prions under conditions simulating automated washer-disinfector cleaning processes. The efficacy of these formulations was confirmed in vivo in a murine prion infectivity bioassay, yielding a reduction of the prion titer for bead surface adsorbed prions below detectability. Our data suggest that TESSA represents an effective method for a rapid screening of prion-inactivating detergents, and that alkaline and oxidative formulations are promising in reducing the risk of potential iatrogenic prion transmission through insufficiently decontaminated instrument surfaces., Competing Interests: Borer Chemie AG (Zuchwil, Switzerland) is the distributor of the formulations used in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Heinzer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy whose initial description is associated with two German authors, Alfons Maria Jakob and Hans Gerhard Creutzfeldt. As polemic as the issue about the Creutzfeldt's merit in the first description of the disease, is his history during the Third Reich. Some evidence pointed to the idea that he was essentially against the Nazi ideology, though some did not. He was an official member of the SS, but his own wife was convicted by a Nazi court. Some authors have argued that Creutzfeldt helped save many patients during Aktion T4 operation, but, in fact, he could have done more. Even during the post-war period, he sent a letter to authorities reporting the name of a Nazi physician who worked as a medical reviewer at the euthanasia court, but he did not proceed any further when his letter initially failed to start an investigation.

Effective sterilization of reusable instruments contaminated by Creutzfeldt⁻Jakob disease in dental care is a crucial issue for public health. The present cross-sectional study investigated how the recommended procedures for sterilization were implemented by French dental practices in real-world settings. A sample of dental practices was selected in the French Rhône-Alpes region. Data were collected by a self-questionnaire in 2016. Sterilization procedures ( n = 33) were classified into 4 groups: (1) Pre-sterilization cleaning of reusable instruments; (2) Biological verification of sterilization cycles—Monitoring steam sterilization procedures; (3) Autoclave performance and practitioner knowledge of autoclave use; (4) Monitoring and documentation of sterilization procedures—Tracking and tracing the instrumentation. Answers were provided per procedure, along with the global implementation of procedures within a group (over 80% correctly performed). Then it was verified how adherence to procedure groups varied with the size of the dental practice and the proportion of dental assistants within the team. Among the 179 questionnaires available for the analyses, adherence to the recommended procedures of sterilization noticeably varied between practices, from 20.7% to 82.6%. The median percentages of procedures correctly implemented per practice were 58.1%, 50.9%, 69.2% and 58.2%, in Groups 1, 2, 3 and 4, respectively (corresponding percentages for performing over 80% of the procedures in the group: 23.4%, 6.6%, 46.6% and 38.6%). Dental practices ≥ 3 dental units performed significantly better (>80%) procedures of Groups 2 and 4 ( p = 0.01 and p = 0.002, respectively), while no other significant associations emerged. As a rule, practices complied poorly with the recommended procedures, despite partially improved results in bigger practices. Specific training regarding sterilization procedures and a better understanding of the reasons leading to their non-compliance are needed.

Evidence has recently been reported of prion seeding activity in skin tissue from patients with sporadic Creutzfeldt-Jakob disease (sCJD). This is relevant information for infection control measures during surgery. The work uses very sensitive prion assays now available for medical research, and may soon be adapted to related neurodegenerative disorders.

The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10-8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.

Neurodegenerative human CJD and sheep scrapie are diseases caused by several different transmissible encephalopathy (TSE) agents. These infectious agents provoke innate immune responses in the brain, including late-onset abnormal prion protein (PrP-res) amyloid. Agent particles that lack detectable PrP sequences by deep proteomic analysis are highly infectious. Yet these agents, and their unusual resistance to denaturation, are often evaluated by PrP amyloid disruption. To reexamine the intrinsic resistance of TSE agents to denaturation, a paradigm for less resistant viruses and microbes, we developed a rapid and reproducible high yield agent isolation procedure from cultured cells that minimized PrP amyloid and other cellular proteins. Monotypic neuronal GT1 cells infected with the FU-CJD or 22L scrapie agents do not have complex brain changes that can camouflage infectious particles and prevent their disruption, and there are only 2 reports on infectious titers of any human CJD strain treated with chemical denaturants. Infectious titers of both CJD and scrapie were reduced by >4 logs with Thiourea-urea, a treatment not previously tested. A mere 5 min exposure to 4M GdnHCl at 22°C reduced infectivity by >5 logs. Infectious 22L particles were significantly more sensitive to denaturation than FU-CJD particles. A protocol using sonication with these chemical treatments may effectively decontaminate complicated instruments, such as duodenoscopes that harbor additional virulent microbes and biofilms associated with recent iatrogenic infections.

Objective: To summarize the approaches used to manage exposure of patients to inadequately sterilized neurosurgical instruments contaminated as a result of Creutzfeldt-Jakob disease (CJD)., Methods: Information on past CJD exposure incidents reported to the Centers for Disease Control and Prevention (CDC) was aggregated and summarized. In addition, inactivation studies were reviewed, and data from selected publications were provided for reference., Results: Nineteen incidents of patient exposure to potentially CJD-contaminated instruments were reported to the CDC, including 17 that involved intracranial procedures and 2 that involved ophthalmologic procedures. In more than 50% of incidents, the neurosurgical procedures were performed for diagnostic work up of the index patients. At least 12 of the hospitals had multiple neurosurgical sets, and the CJD-contaminated instruments could not be identified in 11 of 19 hospitals. In 12 of 15 hospitals with neurosurgical incidents, a decision was made to notify patients of their potential exposure., Conclusions: Neurosurgical instruments used for treatment of patients with suspected or diagnosed CJD or patients whose diagnosis is unclear should be promptly identified and sterilized using recommended CJD decontamination protocols. Inability to trace instruments complicates appropriate management of exposure incidents. The feasibility of instituting instrument tracking procedures should be considered.

Nation-wide surveillance for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease (CJD) is undertaken by the Australian National Creutzfeldt-Jakob disease Registry (ANCJDR), based at the University of Melbourne. Surveillance has been undertaken since 1993. During this period the unit has evolved and adapted to changes in surveillance practices and requirements, the emergence of new disease subtypes, improvements in diagnostic capabilities and the overall heightened awareness and understanding of CJD and other transmissible spongiform encephalopathies in the health care setting. In 2012, routine surveillance continued. This brief report provides an update on the surveillance data collected by the ANCJDR prospectively from 1993 to December 2012, and retrospectively to 1970. It also highlights the recent release of the revised Australian CJD Infection Control Guidelines., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

Flexible endoscopy is a widely used diagnostic and therapeutic procedure. Contaminated endoscopes are the medical devices frequently associated with outbreaks of health care-associated infections. Accurate reprocessing of flexible endoscopes involves cleaning and high-level disinfection followed by rinsing and drying before storage. Most contemporary flexible endoscopes cannot be heat sterilized and are designed with multiple channels, which are difficult to clean and disinfect. The ability of bacteria to form biofilms on the inner channel surfaces can contribute to failure of the decontamination process. Implementation of microbiological surveillance of endoscope reprocessing is appropriate to detect early colonization and biofilm formation in the endoscope and to prevent contamination and infection in patients after endoscopic procedures. This review presents an overview of the infections and cross-contaminations related to flexible gastrointestinal endoscopy and bronchoscopy and illustrates the impact of biofilm on endoscope reprocessing and postendoscopic infection.

During the last 25 years the safety of blood products has improved dramatically with regard to infectious risk, notably to the threat represented by retroviruses (HIV and human T‑cell lymphotropic virus) and hepatitis B and C viruses. However, both residual and emergent viral infections are still responsible for contaminations in recipients of blood products. Along with other viruses (human herpesvirus‑8, human parvovirus B19, hepatitis A and E viruses, etc.), special attention has recently been paid to emerging arboviruses, such as West Nile virus in North America, and Dengue and Chikungunya viruses in Europe. Another blood‑linked risk, notably in the United Kingdom and France, is the prion agent responsible for the variant form of the Creutzfeldt‑Jakob disease. Hemophilia care has been the model for improvements in the safety and availability of safe blood components free of infectious agents. In this regard, several measures aimed to halt transmission of viruses have been implemented in blood banks, including the exclusion of at‑risk donors, specific sensitive diagnostic tests, leukocyte reduction of labile blood products, and the physical or chemical treatments aiming at nonspecific inactivation of infectious agents potentially present in blood without impairing significantly its physiological properties.

The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic disease until a blood screening test for the detection of preclinical infection is validated for human use.

BSE is a zoonotic disease that caused the emergence of variant Creuzfeldt-Jakob disease in the mid 1990s. The trend of the BSE epidemic in seven European countries was assessed and compared, using Age-Period-Cohort and Reproduction Ratio modelling applied to surveillance data 2001-2007. A strong decline in BSE risk was observed for all countries that applied control measures during the 1990s, starting at different points in time in the different countries. Results were compared with the type and date of the BSE control measures implemented between 1990 and 2001 in each country. Results show that a ban on the feeding of meat and bone meal (MBM) to cattle alone was not sufficient to eliminate BSE. The fading out of the epidemic started shortly after the complementary measures targeted at controlling the risk in MBM. Given the long incubation period, it is still too early to estimate the additional effect of the ban on the feeding of animal protein to all farm animals that started in 2001. These results provide new insights in the risk assessment of BSE for cattle and Humans, which will especially be useful in the context of possible relaxing BSE surveillance and control measures.

The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

Background: The emergence of variant Creutzfeldt-Jakob disease (vCJD) prompted guidelines from the Department of Health that stress the use of disposable and protective equipment. This survey explores current methods of airway management for tonsillectomy in the UK and ascertains anaesthetists' current knowledge and opinions of the guidelines and of vCJD., Methods: Three hundred and five questionnaires were sent to all Royal College tutors across the UK to explore the current practice and adherence to the guidelines., Results: The tracheal tube was the most frequently used airway across all age groups: 87% for <3 yr old, 79% for 3-16 yr old, and 73% for adults. Of the respondents who intubated, 57% protected the laryngoscope blade with a disposable sheath or used a disposable blade, while others used a reusable laryngoscope blade without protection. Fourteen per cent protected the laryngoscope handle, as recommended. When a reusable classic or flexible laryngeal mask airway was used, 45% reused it after routine sterilization. Thirty-eight per cent of respondents were unaware that any recommendations existed, 55% disagreed with them, and 84% were not fully compliant with them. Compliance rates did not differ between the anaesthetists who agreed or disagreed with the recommendations. Overall full compliance was achieved by only 16% of respondents. The most common reason for non-compliance was the lack of protection of the laryngoscope handle., Conclusions: The survey demonstrates widespread non-compliance with and lack of knowledge of, national guidelines.

Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month before the onset of prion disease or after the onset. All ophthalmologists reused surgical instruments that had been incompletely sterilized to eliminate infectious prion protein. Ophthalmologists should be aware of prion diseases as a possible cause of visual symptoms and use disposable instruments whenever possible.

Background: Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease caused by infection with the agent of bovine spongiform encephalopathy. After the recognition of vCJD in the UK in 1996, many nations implemented policies intended to reduce the hypothetical risk of transfusion transmission of vCJD. This was despite the fact that no cases of transfusion transmission had yet been identified. In December 2003, however, the first case of vCJD in a recipient of blood from a vCJD-infected donor was announced. The aim of this study is to ascertain and compare the factors that influenced the motivation for and the design of regulations to prevent transfusion transmission of vCJD in the UK and US prior to the recognition of this case., Methods and Findings: A document search was conducted to identify US and UK governmental policy statements and guidance, transcripts (or minutes when transcripts were not available) of scientific advisory committee meetings, research articles, and editorials published in medical and scientific journals on the topic of vCJD and blood transfusion transmission between March 1996 and December 2003. In addition, 40 interviews were conducted with individuals familiar with the decision-making process and/or the science involved. All documents and transcripts were coded and analyzed according to the methods and principles of grounded theory. Data showed that while resulting policies were based on the available science, social and historical factors played a major role in the motivation for and the design of regulations to protect against transfusion transmission of vCJD. First, recent experience with and collective guilt resulting from the transfusion-transmitted epidemics of HIV/AIDS in both countries served as a major, historically specific impetus for such policies. This history was brought to bear both by hemophilia activists and those charged with regulating blood products in the US and UK. Second, local specificities, such as the recall of blood products for possible vCJD contamination in the UK, contributed to a greater sense of urgency and a speedier implementation of regulations in that country. Third, while the results of scientific studies played a prominent role in the construction of regulations in both nations, this role was shaped by existing social and professional networks. In the UK, early focus on a European study implicating B-lymphocytes as the carrier of prion infectivity in blood led to the introduction of a policy that requires universal leukoreduction of blood components. In the US, early focus on an American study highlighting the ability of plasma to serve as a reservoir of prion infectivity led the FDA and its advisory panel to eschew similar measures., Conclusions: The results of this study yield three important theoretical insights that pertain to the global management of emerging infectious diseases. First, because the perception and management of disease may be shaped by previous experience with disease, especially catastrophic experience, there is always the possibility for over-management of some possible routes of transmission and relative neglect of others. Second, local specificities within a given nation may influence the temporality of decision making, which in turn may influence the choice of disease management policies. Third, a preference for science-based risk management among nations will not necessarily lead to homogeneous policies. This is because the exposure to and interpretation of scientific results depends on the existing social and professional networks within a given nation. Together, these theoretical insights provide a framework for analyzing and anticipating potential conflicts in the international management of emerging infectious diseases. In addition, this study illustrates the utility of qualitative methods in investigating research questions that are difficult to assess through quantitative means.

With the appearance of variant Creutzfeldt-Jakob disease (CJD) and the detection of infectious prions in the peripheral organs of persons with sporadic CJD, the development of decontamination methods that are compatible with medical equipment has become a major issue. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide dramatically reduces the level of prion protein (PrP)(Sc) (the scrapie isoform of PrP) present in homogenates of samples from prion-infected brains, including brain samples from humans with CJD. An animal bioassay confirmed the reduction in prion infectivity, indicating that this novel Cu(2+)-H(2)O(2) formulation has great potential for prion decontamination.

New prion-related disorders have emerged over the past 20 years, of which the most notable in the human context is variant Creutzfeldt-Jakob disease (CJD). This disorder is a challenge to medical and public health professionals seeking early detection and diagnosis, provision of therapy, and support for persons affected and a better understanding of transmission risks. The risk of iatrogenic transmission of the disease remains a significant threat, given the well documented cases of CJD transmission via surgery, organ transplantation, and blood transfusion. This review discusses our current understanding of the prevalence of variant CJD, the distribution of tissue infectivity, and new methods for the decontamination of surgical instruments. A comparison of emerging technologies is provided on the basis of our current perception of surgical risk to identify methods that are likely to provide sufficient safety margins and to stimulate debate about the standards needed to protect against variant CJD and CJD transmission.

Objective: To compare the view at simulated direct laryngoscopy obtained with a standard laryngoscope, with and without a disposable cover and a disposable laryngoscope blade., Design: Randomized non-blinded comparison., Setting: The high-fidelity human patient simulator at the Scottish Clinical Simulation Centre., Participants: Thirty-two anaesthetists with between 11 months and 25 years of experience., Interventions: A randomized comparison of ease of laryngoscopy with each laryngoscope option for simulated easy and difficult laryngoscopy., Main Outcome Measures: The best grade achievable at laryngoscopy (Cormack and Lehane grade) for each laryngoscope, for both easy and difficult laryngoscopy., Results: For the easy setting, 34% (P = 0.001) of anaesthetists graded laryngoscopy more difficult with the covered laryngoscope, and 22% (P = 0.008) with the disposable laryngoscope considered laryngoscopy more difficult than with the standard laryngoscope. For the difficult simulator setting, 69% (P < 0.001) found laryngoscopy more difficult with the covered laryngoscope and 69% (P < 0.001) with the disposable laryngoscope, when compared with the standard laryngoscope. There was no difference between the laryngoscopy grades for the covered and disposable laryngoscope for either easy (P = 0.21) or difficult (P = 0.87) simulation., Conclusions: Single-use equipment, as presently recommended for tonsillectomy surgery by the UK Department of Health, makes laryngoscopy more difficult for anaesthetists.

From 1986 more than 184,000 cattle in the UK and islands (of which >1,880 have been detected by active surveillance using rapid tests) and approaching 5,500 elsewhere have been confirmed with BSE. The original 1988 ban on the use of ruminant-derived protein in ruminant feed has been upgraded and now prohibits the use of any processed animal protein in feed for any farmed food animal. As a result of rigorous enforcement this reinforced ban is now regarded as fully effective from 1 Aug. 1996. Reasons are given for the substantial slippage that occurred initially and for the small but diminishing number of cases that have occurred in cattle born after 1 Aug. 1996. The 1989 offal ban, initially introduced to protect public health, has likewise been progressively strengthened and since 1995 has been effectively enforced by the Meat Hygiene Service, thus protecting the consumer. It is now extended as the specified risk material (SRM) ban throughout the EU. BSE continues to decline towards elimination in the UK and is being dealt with effectively in other Member States of the European Union (EU) and Switzerland with an extensive (and very expensive) range of edicts. The improving situation in the EU has encouraged the EC to draft a TSE Roadmap outlining possible reduction in control measures whilst still protecting the consumer. The situation on a global basis still causes concern as, although cases are less frequent than in the UK, surveillance, legislation and enforcement are not clearly as extensive and effective as in the EU. The risk of primary transmission of BSE to man from cattle to cause variant CJD (vCJD) is examined with reference to up-to-date assessments of bovine tissue infectivity and is now regarded as unlikely in the EU and Switzerland.

The recognition of the first cases of variant Creutzfeldt-Jakob Disease in the United Kingdom (UK) in 1996 and the realisation that this new disease represented the human form of the cattle disease BSE has prompted a considerable investment in research, particularly in the UK, Europe and the United States (US). Much has been learnt about this disease but much is still unknown. Infectivity is not destroyed by conventional sterilisation and disinfection treatment methods. This, combined with the widespread distribution throughout the lymphoid system as well as the central nervous system, raises the spectre of transmission through both surgical and ophthalmological procedures. Reports in 2004 of two likely transfusion-transmitted cases of vCJD suggest the probability of infection through blood transfusion and tissue transplantation. The risk of hospital-based and community-based transmission has not been quantified. To complicate matters even further, there is no suitable ante-mortem screening test or effective treatment for this fatal disease. The incubation period prior to onset of clinical disease is many years and there is good evidence for the existence of subclinical infection and infectivity during this stage. The extent of under-diagnosis and misdiagnosis is probably significant, adding to the risk of human-to-human transmission.

From the spring of 2004 the United Kingdom Blood Services have been importing fresh frozen plasma from United States donors for all neonates and children born after 1 January 1996. The decision to mandate the use of American plasma in this age group was taken by the Department of Health in 2002 as part of its precautionary approach to the risk of transfusion transmitted variant Creutzfeldt-Jakob disease. In this article we explain the background to this decision and explore some of the implications it raises for clinical practice.

Objective: To evaluate the costs and benefits of infection control strategies to prevent the transmission of variant Creutzfeldt-Jakob disease (vCJD) in ophthalmic surgery in Australia., Methods: The reduction in the risk of iatrogenic transmission of vCJD from feasible infection control strategies was calculated using decision analytic models. A static model calculated the direct secondary transmission for surgical eye procedures, and a simple dynamic model estimated the change in the risk of a subsequent sustained epidemic over the longer term. The expected number of vCJD infections, their cost of care and years of life lost and the estimated cost of strategies included the direct costs of infection control measures were calculated taking a health system perspective., Results: The dynamic model (Markov process) predicted that from a hypothetical pool of as many as 100 primary vCJD cases there would be less than five iatrogenic infections in the next 30 years. If there are fewer than five primary cases the model predicted no secondary cases of vCJD. The costs of providing care for a vCJD case is estimated to be about $50,000, subject to considerable uncertainty. The minimum cost for using a partial infection control strategy to prevent an iatrogenic infection is likely to be in the order of several millions of dollars., Conclusions: Substantial public health investment would need to be made in order to reduce a low risk of iatrogenic transmission of vCJD. Given the likely number of cases of iatrogenic infection, and the order of magnitude of the costs of caring for cases of vCJD, it may be difficult to justify the high cost of risk reduction strategies.

Background: The risk compensation theory is a widely used concept in transport economics to analyze driver risk behaviour. This article explores the feasibility of applying the theory in blood transfusion to raise important questions regarding the increased blood safety measures and their possible effects on blood usage (e.g., the appropriateness in transfusion). Further, it presents the findings of a pilot survey of physicians in Canada., Discussion: While studies have attempted to define transfusion appropriateness, this article argues that if the risk compensation theory holds true for transfusion practice, physicians may actually be transfusing more. This may increase the possibility of contracting other unknown risks, such as the variant Creutzfeldt-Jakob Disease (vCJD), as well as increasing the risk of non-infectious transfusion risks, such as transfusion reactions., Summary: A much larger study involving psychosocial assessment of physician decision making process to fully assess physician behaviour within the context of risk compensation theory and transfusion practice in Canada is needed to further explore this area.

In the physical sciences, mathematical theory and experimental investigation have always marched together. Mathematics has been less intrusive in the life sciences, possibly because they have until recently been largely descriptive, lacking the invariance principles and fundamental natural constants of physics. Increasingly in recent decades, however, mathematics has become pervasive in biology, taking many different forms: statistics in experimental design; pattern seeking in bioinformatics; models in evolution, ecology, and epidemiology; and much else. I offer an opinionated overview of such uses--and abuses.

Only one case of a cow infected with bovine spongiform encephalopathy has been reported in Israel. Its publication, in 2002, caused both public and professional concern. The inevitable health policy question raised was whether or not to recommend against consuming beef and what public health measures should be taken. In this article we describe the prion diseases among animals and humans, their interaction and the precautionary procedures that were carried out by the state Veterinary Services and the Ministry of Health since 1988. The BSE case (a 10 year old dairy cow) is believed to be the result of local consumption of infected mammalian meat and bone meal more than a decade earlier. The risk assessment took into consideration that no cases of vCJD (a new variant of Creutzfeldt-Jacob disease) have ever been diagnosed in Israel, as well as the low risk of contamination of the meat due to the religious method of slaughtering performed in the country. The policy decision was to implement a contingency plan prepared in advance. Israel was reclassified from the level II category of geographic risk where BSE is unlikely but not excluded in the herds, to level III where BSE is likely but not confirmed, or confirmed at a lower level. No undue damage to the meat industry has occurred. By the end of 2002, despite the examination of more than 3,800 brains from slaughtered cows older than 3 years, no other cases of BSE have been detected.