Central Hospital Pharmacy
The possible transmission of Creutzfeldt–Jakob disease (CJD) to humans via food products containing the bovine spongiform encephalitis (BSE) agent was first identified in 1996, with the first “new variant” CJD (vCJD) observed in the UK. Independently of this observation, French authorities had started taking compulsory measures in 1994–5 for the prevention of CJD transmission among patients undergoing invasive surgery. The rationale for these precautions was not the fear of BSE transmission to humans but the observation of iatrogenic CJD resulting from the use of extracted growth hormone, the rate of which was higher in France than in other European countries. These measures were taken in the form of a circular from the General Office of Health, the equivalent in France of the health service circulars in the UK NHS. The first French circular involved specific precautions that complemented usual rules of good practice, such as the use of questionnaires to collect the medical history of patients about to undergo surgery or invasive examinations (eg, neurosurgery, injection of extracted growth hormone, implantation of dura mater), identification of neurological or psychiatric pathologies, identification of families with sporadic or genetic CJD.
In 2001 and 2003, two specific circulars were published in order to include possible vCJD contamination of a population potentially larger than just children treated with growth hormone. The particular pathogenesis of vCJD causes specific risks for digestive and bronchial endoscopy(1,2) and for transfusions, since patients receiving red cells containing leukocytes from vCJD-bearing donors were observed in the UK.(3,4) In France, a new specific category of patients at risk was thus defined: those receiving labile blood products in the past (see Table 1). All the procedures described included highly classical precautions, similar to those used in UK. The results have thus far been judged as good, since no iatrogenic transmission of CJD has been observed in France, but should be regarded with care because undetected patients could be in the course of the disease, whose incubation period is longer than the observation interval. The results are less satisfying in terms of compliance and acceptance in care services. Taking into account the latest experimental work and the observed epidemiological advancement of vCJD, it seems that a new period in sterilisation can be started, with several minor variations, to simplify existing procedures.
Organisation of sterilisation and disinfection in France
The system implemented in France takes into account the organisational particularities of our country, in particular the obligation to sterilise reusable medical devices under the responsibility of a pharmacist. The liquid cold sterilisation of reusable heat-sensitive material by immersion in a disinfectant solution or by gas-plasma is also part of this obligation on pharmacy services, but it is called “high-level disinfection” and not “cold sterilisation”, as in most countries.
On the other hand, the treatment of flexible endoscopes for gastrointestinal or bronchial examinations, even though using the same solutions, generally containing glutaraldehyde or peroxides, is called ”simple disinfection”, whether done manually or by machine. This treatment is not under pharmacy responsibility but under that of the medical department conducting the procedure. Regardless of these responsibilities, the entire procedure is, of course, approved by the CLIN (commission to prevent nosocomial infections), obligatory in each public or private hospital, and is regularly inspected by regional health authorities.
Double cleaning and questionnaires
Double cleaning before disinfection of flexible endoscopes became obligatory in the 2003 circular in France. This choice was made because of the impossibility of correctly obtaining a questionnaire from patients and the nonapplicability of inactivating prion treatments in endoscopes. Since peracetic acid and glutaraldehyde are not considered as very effective treatments to prevent prion infections, double cleaning involving so-called “French cycles” for endoscope-cleaners gets around this double deficit of identifying patients at risk and the limited efficacy of the disinfectant. An endoscope used purposely or by error on a CJD patient is destroyed after the procedure even though the risk of transmission is very low, except for a biopsy or highly traumatic endoscopy. The double-cleaning system is also used for sterilisation operations when an at-risk procedure is conducted with medical devices that cannot withstand recommended prion inactivation procedures. This precaution is reassuring for those in positions of responsibility, is not very restrictive and could be extended to the reprocessing of all medical devices reusable in neurosurgery (including deep surgery of the eyes, except for cataracts). This would compensate for the compliance difficulties of questionnaires, aiming to identify patients at risk: in some cases it is obviously not possible to collect the required information when the clinical or psychological state of patients prevents them responding (such as unknown family history if the person is alone; or identification of neurological clinical signs associated with intellectual or psychiatric problems difficult to declare, even by third parties who may not always be capable of judging people close to them).
The result of this is that the questionnaires are not all filled out in certain emergency or intensive care situations or, depending on the type of establishment, are filled out at low rates (20–60%). As a consequence, the number of identified CJD cases after invasive procedures and use of medical devices without any precautions is high, about 40% in France, part of the 80–110 cases of CJD confirmed after death. These “too late” identified CJD cases are not included in the 800–1,000 annual declarations of suspicion. French practitioners would like to simplify these identification processes, perhaps limiting observations of signs of dementia to the age of 65 as suggested in UK, and reinforcing standard double-cleaning techniques for treating instruments used in procedures at risk.(5)
The next revision of the circulars should also take into account the new classification of tissues as a function of their infection risk in humans, as published by the World Health Organization (WHO) in August 2006. The previous references date to 1999, based on the classification made by analogy to infecting capacity observed not in humans but in ovine scrapie. Tissues at a high risk of being infected should be considered for which the prion protein PrPres is systematically found in afflicted patients (CJD and/or vCJD), or for whom secondary transmission is proven. The brain is the reference tissue for this first category, and procedures on these tissues lead to high instrument contamination. On the other hand, and even though the tonsils and appendix have been identified as PrPres positive in cases of vCJD, ablation procedures of these lymphoid tissues are rapid and not highly contaminating for instruments, which are to be considered as moderate- or low-risk procedures, such as those on the cornea, thymus, peripheral nerves, blood and skeletal muscles. As to the choice of the disinfectant products, French practice over the past five years has been to favour the use of peracetic acid for disinfections over that of glutaraldehyde or diluted chlorine-containing solutions. The 2001 circular gave preference to peracetic acid, placing it with other products with partial efficacy, while glutaraldehyde was demoted to Group I, with ineffective products. This is the opposite classification to the WHO recommendations. The French rejection of glutaraldehyde was based on previous observations made on formaldehyde, declared to bind proteins, with negative effects.
After this circular, glutaraldehyde was progressively replaced by peracetic acid in French hospitals. In terms of the prion risk, this choice has not been proven effective since peracetic acid has no clear-cut inactivation of the infectious capacity. Nevertheless, many products on the market containing peroxide should be used more and more in France, since they act rapidly on other infectious agents and leave no toxic residues on instruments, or volatile residues in the atmosphere. In the medium term, instruments, especially optical ones, retain their good condition longer because of the nondamaging detachment of proteins and contaminants. In comparison with chlorine derivatives, even diluted ones, there is an absence of corrosion.
Methods used to control the risk of iatrogenic disease by prion transmission via infected instruments are heading towards simpler procedures. They are very similar in countries with the same risk and can progress, with benefits in efficacy and shorter disinfection or sterilisation times. This will be made possible by a better understanding of the infection capacity of tissues, a higher sensitivity of methods for detecting infectious capacity and improved biological examination of patients before death. In addition, practical experimentation with inactivation techniques is made possible and reliable. Furthermore, precise evaluations of the number of predictable cases of vCJD, more limited in France and UK than that which had previously been announced, and the efficacy of measures taken since 1994 in those two countries, should lead to the acceptance of general procedures within the scope of infection control, able to be harmonised across Europe.
- Taylor DM. Inactivation of prions by physical and chemical means. J Hosp Inf 1999;43:569-76.
- Darbord JC. Importance of cleaning for reprocessing endoscopes and thermolabiles sterile medical devices: French use and regulations. J Hosp Inf 2004;56:540-3.
- Llewelyn CA, et al. Possible transmission of variant Creutzfeldt–Jakob disease by blood transfusion. Lancet 2004;363:417-21.
- Peden AH, et al. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterzygous patient. Lancet 2004;364:527-9.
- Mead S, et al. Questionnaire to reduce the risk of iatrogenic prion disease transmission. J Hosp Inf 2005;60:378-81.
- Vadrot C, Darbord JC. Quantitative evaluation of prion inactivation comparing steam sterilisation and chemical sterilants: proposed method for test-standardization. J Hosp Inf 2006;64:143-8.