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During the last 20 years, the safety of blood products increased dramatically with regard to the infectious risk and notably to that represented by retroviruses (HIV and HTLV) and hepatitis B and C viruses. The aim of this review is to identify the residual and emergent viral threats that could be responsible for the occurring of new contaminations in the receivers of blood products. Beside many other viruses (HHV-8, erythrovirus B19, hepatitis A and E viruses...), a special attention has been paid to emerging arbovirus diseases (West Nile virus infection, dengue, chikungunya) that threaten to occur in the French metropolitan area following the implantation in Europe of the mosquito Aedes albopictus, the main vector of dengue and chikungunya in temperate regions. Another blood-linked risk, notably in United Kingdom and France, is the prion agent responsible for the variant form of the Creutzfeldt-Jakob disease. The review is concluded by a brief overview of the measures aimed to control these emergences, including the exclusion of at-risk donors, the diagnostic tests able to detect a specific agent, the leukocyte reduction of labile blood products, and the physical or chemical treatments aiming the nonspecific inactivation of infectious agents potentially present in blood without impairing significantly the physiological properties of blood compounds. The ability to control prospectively the new viral risks linked to blood products is a challenge for the preservation of the confidence of both clinicians and receivers in the safety of blood transfusion., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The latest updates (February 2004 and February 2005) of the analysis of the risk of transmission of the agent of Creutzfeldt-Jakob disease (CJD) by blood and blood products in France firstly reported in 2000, were triggered by the two cases of probable transmission of variant CJD (vCJD) by transfusion reported in the UK, and the notification of two French cases of vCJD who had been blood donors on several occasions before clinical onset. Even though some figures of the quantitative assumption used in the risk analysis have been modified since 2000, the conclusion as regards the risk for blood cellular component is considered unchanged: it can be assumed that one unit of labile blood products will contain more than one infectious unit if the donor is incubating the disease. Therefore, the residual risk of receiving by transfusion one infectious blood unit is depending on the prevalence of subjects incubating the disease in the blood donor population. For this particular aspect, the expected number of clinical vCJD cases to occur in France has been lowered since 2000. However, the worst-case scenario of 300 cases in the next 60 years has been maintained in the risk analysis, leading to the hypothesis that one blood donor per 120,000 could be infectious. In conclusion, the risk of getting one infectious blood unit is considered probable to a level of 1/120,000, but the benefit outweighs the risk if the use of transfusion is restricted to well justified indications and if patients are informed a priori and a posteriori.

Legal obligation to inform the patient does not include theoretical risks. However, due to the very sensitive situation of blood transfusion in France, following the tainted-blood affair, a circular was issued to extend this obligation (1998) to inform the theoretical risk of CJD transmission by blood. Ethically speaking, this raises three questions: Is it beneficial to the patient to be informed on theoretical risk? Is the use of a "circular", less legally binding, appropriate? Finally, what is the situation in other countries? The evolution of the law tends to be more positive in that it no longer involves any theoretical risk.

Bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease (vCJD) belong to a family of similar diseases under the name of transmissible spongiform encephalopathies (TSE). It is demonstrated that the agent responsible for bovine spongiform encephalopathy (BSE) is also responsible for the new variant of Creutzfeldt-Jakob in man. This contribution describes the main characteristics of the two diseases.

Because of the HIV and HCV virus transmission by transfusion during the eighties, there has been a retrospective reflection about the non-application of the precautionary principle, which has appeared only recently in the medical world. Since it was difficult to identify the real cause of the above-cited transmission in France, mainly because of the bad selection of blood donors, we feel we are justified in applying this precautionary principle more and more, in a monopolistic way, for biological security reasons. As a result, the biological research is not limited to looking for a 'degree zero' risk. Whether it concerns the 'PCR', the research of a new potential virus, the excessive fear regarding the transfusion of the new ESB agent, the worry caused by the blood donors who lived in the British Isles, the need for security based upon the precautionary principle is increasing endlessly. It is, however, more reasonable to consider that the precautionary principle should be essence incite a multi-disciplinary reflection involving biological sciences as well as social sciences. The precautionary principle would not make sense if it were not questioned for bad estimations, its harmful influences or its opportunistic use. Transfusion security, which is so important as a goal and as a principle, cannot appeal to the precautionary principle all the time, since the excessive use of this principle would lead to the paradox of not being able to identify the issues anymore.

Three categories of emerging risks are studied: 1) A new variant of Creutzfeld-Jakob disease, different from its sporadic form; limited to the British isles (48 of 51 cases), it affects younger patients, and has a higher duration with a predominance of psychiatric symptoms. Environmental risk factors include a previous stay in the British isles and oral transmission via contaminated food. No link has been made evident between blood component (BC) transfusion and occurrence of the disease. A potential risk exists if its agent is found in blood and peripheral lymphoid tissues and if buffy coat from infected animals has been inoculated intracerebrally. Since 1993, prevention measures have been taken: exclusion of donors with a potential risk as well as transfused donors, systematic leukocyte reduction and implementation of disease surveillance. Excluding donors after a several month-stay in the British Isles is being discussed. 2) Novel hepatitis viruses. Hepatitis G virus (HGV) has been detected in 2-4% of blood donors. Ten percent of patients with chronic non-A-E hepatitis are HGV RNA positive. The incidence of HGV infection is higher than expected from PCR studies. HGV has a high prevalence in the world. Novel DNA non-enveloped virus (TTV) has a normal distribution. Its prevalence varies from 2 to 80%, depending on the country. Although it has not been shown to be aggressive for the liver, prolonged follow-up is required. 3) Human herpes virus 8 (HHV8) is associated with Kaposi's sarcoma in 80% of cases. Its prevalence (0-20%) varies depending on the country. Kaposi's sarcoma has never been reported after BC transfusion. PCR-based viral DNA searches have yielded negative results in 19 poly-transfused subjects. Continuous monitoring is required for recipients at risk (e.g., immunosuppressed). In response to a possible health risk, emerging risks govern the "Precaution Principle", so difficult to implement.

The risk assessment of transmissible spongiform encephalopathies (TSEs or prion diseases) can be managed at three levels: 1. control of source material that could be potentially infected (biological products of human or animal origin, instruments in contact with these products); 2. control of the processes for the purification of biological products and instrument decontamination techniques; 3. evaluation of invasive medical or surgical acts. Highest infectivity is found in central nervous system. TSE agents do resist to almost all usual decontamination procedures. National recommended procedures include sodium hypochlorite 18,500 ppm or sodium hydroxide 1N for 1 hour and autoclaving at at least 134 degrees C for at least 18 min.

Administrative texts published in 1995, 1996 and 1997, have reinforced materiovigilance and impose disinfection precautions for endoscopes. The steps of disinfection of non-sterilizable endoscopes are: preliminary treatment, rinsing, actual disinfection, final rinsing, storage (see: Progrès en Urologie, 1997, 7, 505-507). Each procedure from collection of the endoscope until storage must be defined by written standard operating procedures validated by CLIN. The risk of transmission of Creutzfeld-Jakob disease requires autoclaving, which is only possible, at the present time, with the most recent rigid endoscopes. Until disinfection has become generalized, the traceability of endoscopes (labelling, utilization files) must be established on the model recommended for haemovigilance (circular of 02/04/96).

The occurrence of Creutzfeldt-Jakob disease (CJD) in two teenagers and four dairy farmers in the United-Kingdom has focused attention on the possibility of a causal link between bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease. The BSE epidemic was initiated by the inclusion in the cattle feed of the ruminant-derived protein in 1981/1982. A feed ban of the ruminant-derived protein in 1988 prevented further transmission of the infective agent to cattle by this route. However cases in animals born some years after the feed ban suggest that there has been some continued leakage of BSE infected material into animal feed (and perhaps maternal transmission?). To protect public and animal health, measures have been taken in the United Kingdom, especially prohibition of specified bovine offals in 1989 (extending this ban to thymus and intestine of calves slaughtered for human consumption in 1994). These measures are considered as minimizing the risk of BSE infection. Although the BSE linked risk factors are probably unique to the United Kingdom, it seems necessary to have the same regulations for the calves imported from this country. More, it is crucial that the ongoing surveillance programme of CJD in Europe is sustained.

The long latency time, without any characteristic clinical sign, of transmissible degenerative encephalopathies, the transmissibility of the called "prion" infectious agent, associated with its exceptional resistance to normal inactivation methods, are resulting in accidental transmissions, both human (Creutzfeldt-Jakob disease), and animal (bovine spongiform encephalopathy). Among data about physical and chemical inactivation methods tested, we retain, to avoid professional or iatrogenic transmissions in the laboratory or in hospital, steam autoclaving and sodium hypochlorite or hydroxide treatment. But inactivation shall not be performed using the current processes as regarding parameters such as temperature, concentration and duration of exposure.

The virus of Creutzfeldt Jakob disease differs from conventional viruses in its extraordinary resistance to commonly used physical and chemical methods of decontamination. Autoclaving the virus for 1 hour at 121 degrees C and 2 atmospheres pressure is the most certain means for achieving total inactivation. Exposure to 5 p. 100 hypochlorite for several hours can also totally inactivate the virus, and exposure to phenol or potassium permanganate is probably effective, but as yet insufficiently tested.