Variant Creutzfeldt-Jakob Disease (vCJD) and Gastrointestinal Endoscopy

Variant Creutzfeldt-Jakob disease (vCJD) is a transmissible form of spongiform encephalopathy believed to be contracted from the consumption of bovine spongiform encephalopathy (BSE) infected beef products. To date over 100 individuals have developed this incurable disease. There have been no documented cases of iatrogenic infection, but there is a theoretical risk that surgical procedures could transmit the disease. This review describes the background of the disease and assesses the possible risks of transmission through endoscopic procedures. The risk of transmission by endoscopy is small and probably negligible if suitable procedures are followed. The greatest potential danger arises from healthy individuals who are incubating the disease. Pathological prions (PrP^sc) may be found in lymphatic tissue of these individuals (particularly tonsils), but smaller amounts have been identified in the appendix and Peyer’s patches. These prions are resistant to all forms of conventional sterilization. There is a theoretical risk that biopsy forceps and the operating channel of endoscopes could become contaminated. This review gives recommendations as to how these small risks can be minimized. They include the employment of single-use forceps for biopsies taken from the terminal ileum, greater attention to the maintenance of endoscopic equipment and accessories, more rigorous manual cleaning of endoscopic equipment and the use of well designed, disposable cleaning brushes for the operating channel of the endoscope.

References

• 1 Prusiner S B. Prions.  Proc Natl Acad Sci USA. 1998;  95 13 363-13 383
• 2 Soto C, Saborio G P. Prions: disease propagation and disease therapy by conformational transmission.  Trends in Molecular Medicine. 2001;  7 109-114
• 3 Johnson R T, Gibbs C J. Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies.  N Engl J Med. 1998;  339 1994-2004
• 4 Collee J G, Bradley R. BSE: a decade on-part I.  Lancet. 1997;  349 636-641
• 5 Will R G, Ironside J W, Zeidler M, et al. A new-variant of Creutzfeldt-Jakob disease in the UK.  Lancet. 1996;  347 921-925
• 6 Prusiner S B. Molecular biology of prion diseases.  Science. 1991;  252 1515-1522
• 7 Harris D A. Cellular biology of prion diseases.  Clin Microbiol Rev. 1999;  12 429-444
• 8 Stahl N, Baldwin M A, Teplow D B, Hood L, Gibson B W, Burlingame A L, Prusiner S B. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing.  Biochemistry. 1993;  32 1991-2002
• 9 Pan K M, Baldwin M, Nguyen J, Gasset M, Serhan A, Groth D, Mehlhorn I, Huang Z, Fletterick R J, Cohen P E. Conversion of alpha-helices into β-sheets features in the formation of scrapie prion proteins.  Proc Natl Acad Sci USA. 1993;  90 10 962-10 966
• 10 Raeber A J, Brandner S, Klein M A, Benninger Y, Musahl C, Frigg R, Roeckl C, Fischer M B, Weissmann C, Aguzzi A. Transgenic and knockout mice in research on prion diseases.  Brain Pathol. 1998;  8 715-733
• 11 Cohen F E, Prusiner S B. Pathologic conformations of prion proteins.  Annu Rev Biochem. 1998;  67 793-819
• 12 Kocisko D A. Cell-free formation of protease-resistant prion protein.  Nature. 1994;  370 471-474
• 13 Harper J D, Lansbury P T. Models of amyloid seeding in Alzheimer’s disease and scrapie: mechanistic truths and physiological consequences of the time dependent solubility of amyloid proteins.  Annu Rev Biochem. 1997;  66 385-407
• 14 Ghani A C, Ferguson N M, Donnelly C A, Anderson R M. Predicted vCJD mortality in Great Britain.  Nature. 2000;  406 583-584
• 15 Cousens S, Smith P G, ward H, Everington D, Knight R S, Zeidler M, Smith-Bathgate E A, Macleod M A, Mackenzie J, Will R G. Geographical distribution of variant Creutzfeldt-Jakob disease in Great Britain, 1994 - 2000.  Lancet. 2001;  357 1002-1007
• 16 Lorains J W, Henry C, Agbamu D A, Rossi M, Bishop M, Will R G, Ironside J W. Variant Creutzfeldt-Jakob disease in an elderly patient.  Lancet. 2001;  357 1339-1340
• 17 Shmakov A N, Ghosh S. Prion proteins and the gut: une liaison dangereuse?.  Gut. 2001;  48 443-447
• 18 Kimberlin R H, Walker C A. Pathogenesis of scrapie in mice after intragastric infection.  Virus Res. 1989;  12 213-220
• 19 Beekes M, McBride P A. Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie.  Neurosci Lett. 2000;  278 181-184
• 20 Rieger R, Edenhofer F, Lasmezas C I, Weiss S. The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells.  Nat Med. 1997;  3 1383-1388
• 21 Shmakov A N, Bode J, Kilshaw P J, Ghosh S. Diverse patterns of expression of the 67-kD laminin receptor in human small intestinal mucosa: potential binding sites for prion proteins.  J Pathol. 2000;  191 318-322
• 22 Shmakov A N, McLennan N F, McBride P, Farquhar C F, Bode J, Rennison K A, Ghosh S. Cellular prion protein is expressed in the human enteric nervous system.  Nat Med. 2000;  6 840-841
• 23 Ironside J W, Head M W, Bell J E, McCardle L, Will R G. Laboratory diagnosis of variant Creutzfeldt-Jakob disease.  Histopathology. 2000;  37 1-9
• 24 Hilton D A, Fathers E, Edwards P, Ironside J W, Zajicek J. Prion immunoreactivity in appendix before clinical onset of variant Creutzfeldt-Jakob disease.  Lancet. 1998;  352 703-704
• 25 Wadsworth J D, Joiner S, Hill A F, Campbell T A, Desbruslais M, Luthert P J, Collinge J. Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunobloting assay.  Lancet. 2001;  358 171-180
• 26 Ironside J W, Hilton D A, Ghani A, Johnston N J, Conyers L, McCardle L M, Best D. Retrospective study of prion-protein accumulation in tonsil and appendix tissues.  Lancet. 2000;  355 1693
• 27 Kimberlin R H, Walker C A. Pathogenesis of experimental scrapie. In: Bock G, Marsh J (eds). Novel infectious agents and central nervous system.  Chichester; Wiley 1988: 37-62
• 28 Bruce M E, McConnell I, Will R G, Ironside J W. Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues.  Lancet. 2001;  358 208-209
• 29 Houston F, Foster J D, Chong A, Hunter N, Bostock C J. Transmission of BSE by blood transfusion in sheep.  Lancet. 2000;  356 999
• 30 Lasmezas C I, Fournier J -G, Nouvel V, Boe H, Marce D, Lamoury F, Kopp N, Hauww J -J, Ironside J, Bruce M, Dormont D, Deslys J -P. Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health.  Proc Natl Acad Sci USA. 2001;  98 4142-4147
• 31 Guidelines on cleaning and disinfection in GI endoscopy . Report of the European Society of Gastrointestinal Endoscopy and the European Society of Gastroenterology and Endoscopy Nurses and Associates.  Endoscopy. 2000;  32 77-83
• 32 Hill A F, Butterworth R J, Joiner S, et al. Investigation of variant Creutzfeldt-Jacob disease and other human prion diseases with tonsil biopsy samples.  Lancet. 1999;  353 183-189
• 33 Bons N, Mestre-Frances N, Beli P, et al. Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents.  Proc Natl Acad Sci USA. 1999;  96 4046-4051
• 34 Heggebo R, Press C M, Gunnes G, et al. Distribution of prion protein in the ileal Peyer’s patches of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent.  J Gen Virol. 2000;  81 2327-2337
• 35 Baron H, Safar J, Groth D, DeArmond S J, Prusiner S B. Prions. In: Block SS (ed). Disinfection, sterilization and preservation. New York, Lippincott; Williams & Williams 2001 5th edition: 659-674
• 36 Antloga K, Meszaros J, Malchesky P M, McDonnell G E. Prion disease and medical devices.  ASAIO J. 2000;  46 S69-S72
• 37 Rutala W A, Weber D J. Creutzfeldt-Jakob disease: recommendation for disinfection and sterilization.  Clin Infect Dis. 2001;  32 1348-1356
• 38 Taylor D M. Inactivation of prions by physical and chemical means.  J Hosp Infect. 1999;  43 S69-S76
• 39 Taylor D M. Inactivation of transmissible degenerative encephalopathy agents: a review.  Veterinary Journal. 2000;  159 10-17
• 40 Zobeley E, Flechsig E, Cozzio A, Enari M, Weissmann C. Infectivity of scrapie prions bound to a stainless steel surface.  Mol Med. 1999;  5 240-243
• 41 Brown P, Rohwer R G, Gajdusek D C. Newer data on the inactivation of scrapie virus or Creuttzfeldt-Jakob disease virus in brain tissue.  J Infect Dis. 1986;  153 1145-1148
• 42 Diringer H, Braig H R. Infectivity of unconventional viruses in dura mater.  Lancet. 1989;  1 439-440
• 43 Pruniner S B, McKinlay M P, Bolton D C, et al. Prions: methods for assay, purification, and characterization. In: Maramorosch K, Koprowsk H (eds). Methods in Virology.  New York; Academic Press, 1984 VIII: 293-345
• 44 Taylor D M, Fraser H, McConnell I, et al. Decontamination studies with the agents of bovine spongiform encephalopathy and scrapie.  Arch Virol. 1994;  139 313-326
• 45 World Health Organization .Infection Control Guidelines for Transmissible Spongiform Encephalopathies. 1999
• 46 Systchenko R, Marchetti B, Canard J N, Palazzo L, Ponchon T, Rey J F, Sautereau D. and the Council of the French Society of Gastrointestinal Endoscopy . Guidelines of the French Society of Digestive Endoscopy: Recommendations for setting up cleaning and disinfection procedures in gastrointestinal endoscopy.  Endoscopy. 2000;  32 807-818
• 47 Department of Health, UK (1999) .Variant Creutzfeldt-Jakob disease (vCJD) minimizing the risk of transmission.  London; HSC 1999/178, 13/08/99

Addendum - The European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA)

Recommendation for the Reduction of the Risk of Transmission of Prions in Endoscopy

This document is supplemental to the previously published ESGE/ESGENA Reprocessing Guidelines

Introduction

As there are no known effective means of disinfection or sterilisation following exposure to prions the emphasis in preventing transmission of prions in endoscopy must be on the removal of organic matter from equipment and the prevention of cross contamination of the environment.

I. Staff Safety

Endoscopes and accessories are a potential source of infection. Therefore validated and standardised reprocessing according to manufacturers' recommendations is essential. This requires special training and knowledge. Staff should be trained in care and maintenance of equipment handling of equipment during procedures reprocessing of equipment, including cleaning, disinfection and sterilisation infection control, including potential health risks. Reprocessing of endoscopie equipment should only be undertaken by trained and competent staff. Reprocessing of endoscopie equipment should be undertaken in a separate, dedicated reprocessing room to minimise the risk for other personnel and the general public. During reprocessing of equipment staff should wear protective clothing (gloves, long sleeve moisture resistant gowns, masks/visors) to protect themselves from splashes, aerosols and vapour. A small pipette, pair of tweezers or single-use toothpick should be used to remove biopsy specimens from the biopsy forceps cup (Using a needle increases risk of needle stick injury) or specimens may be removed by agitating the forceps cup in NaCl 0.9%; do not use needles to remove specimens do not dip the biopsy forceps cup directly into formaldehyde solution. (Aldehydes denature and fix organic material. This may impair the subsequent cleaning of forceps.) Rinse the biopsy forceps cups in NaCl 0.9% or tap water before taking the next biopsy in order to avoid re-transfer of organic material into the biopsy valve or endoscope channel.

II. Choice of Accessories

Biopsy forceps Disposable/single use biopsy forceps should be used for ileum biopsies. Disposable biopsy forceps reduce the risk for staff as no reprocessing is required and for patients as they have not been previously exposed to potentially infective organisms during endoscopie or reprocessing procedures. Endoscopie injection needles should be disposable in order to minimise the risk to endoscopy personnel (needle stick injuries) to avoid problematic reprocessing. (The narrow lumen of injection needles does not allow effective reprocessing.) Cytology brushes should be disposable as they cannot be cleaned effectively. Tissue residue may remain on the brush, potentially causing transmission to the next patient (exogenous infection) or incorrect cytological diagnosis. The use of disposable invasive accessories should be encouraged when possible in order to minimise the risk to endoscopy personnel avoid potentially problematic reprocessing. Cleaning brushes should be disposable because brushes cannot be cleaned effectively. Tissue residue may remain on the brush, and be transmitted onto the next piece of equipment reprocessed, with all adherent consequences.

III. Utilisation of Accessories During Endoscopie Procedures

Disposable gauze/sponge should be used when accessories (especially biopsy forceps/invasive accessories) are withdrawn from the instrument channel and removed from the endoscope in order to remove secretions to wipe clean external surfaces of the equipment to avoid splashing while removing accessories from the instrument channel in order to minimise contamination of the environment and staff. A separate instrument table/trolley to deposit accessories during procedures and for the removal of specimens from accessories should be used in order to avoid contamination of surroundings to ensure adequate space for safe handling. Instrument tolleys should be covered with disposable, waterproof sheets which can be discarded after each procedure.

IV. Reprocessing of Equipment

Key points for reprocessing endoscopie equipment are as follows:

Aldehyde containing cleaning agents must not be used for cleaning as they denature and fix proteins, and this may impair effective cleaning. Alkaline detergents or enzymatic type detergent solutions or NON-COAGULATING disinfectants with good cleansing power are recommended for the cleaning of endoscopie accessories. Endoscopie equipment should be reprocessed IMMEDIATELY after removal from the patient in order to avoid the drying and fixation of organic material. Thorough manual cleaning is a prerequisite for effective decontamination. Therefore manual cleaning must always take place before disinfection or sterilisation. Cleaning and rinsing solutions should not be re-used.

Accessories

Manual cleaning is the most important step in the removal of organic material from accessories. This includes thorough cleaning by dismantling of accessories as far as possible (follow manufacturers recommendations) cleaning of external surfaces by using a soft, disposable cloth/sponge and brushes thorough brushing of the biopsy forceps' cups flushing all available channel lumens. Ultrasonic cleaning is essential for the removal of debris from inaccessible spaces of complex accessories such as spiral biopsy forceps: do not overload the tray of the ultrasonic cleaner in order to avoid ultrasound “shadows”/dead space use dedicated ultrasonic solutions (NOT aldehyde containing detergents). Ultrasonic cleaning is recommended for 30 minutes, 35–47kHz, 40–60 °C). After thorough rinsing and drying, endoscopie accessories should be sterilised in accordance with manufacturers' instruction (recommendation: steam autoclave, 134 °C, 5 minutes, pre-vacuum).

Endoscopes

Thorough manual cleaning with detergent remains the most important step of the endoscope reprocessing procedure. This includes cleaning of all external surfaces by using a soft, disposable cloth/sponge, and brushes cleaning of valve ports, channel opening and suction ports with a suitable brush and cotton bud brushing of all accessible channels with a flexible, purposed designed brush. Appropriate sized brushes for each channel have to be used to ensure good contact with the channel walls flushing of all lumen. Select appropriate size and type of cleaning brush in accordance with size and type of endoscope channels. In order to ensure maximum effectiveness of cleaning brushes single use brushes or change of brushes on a daily basis are recommended. All reusable brushes have to be thoroughly cleaned manually, followed by ultrasonic cleaning, and decontaminated (preferably sterilised) after each usage.

V. Automated Reprocessing Systems

Thorough manual cleaning of equipment, especially small equipment channels, is a prerequisite for effective disinfection - independent of whether a manual or automatic reprocessing cycle is performed. The use of automated reprocessing after manual cleaning is recommended in order to provide a standardised and validated reprocessing cycle in a closed environment to minimise staff contact with chemicals and contaminated equipment to minimise the contamination of the environment. Machines may pose an additional infection risk. Therefore they must be cleaned and maintained according to manufacturer's recommendation on a daily base have regular engineering maintenance undergo regular microbiological surveillance. Machines must be capable of self-disinfection and should use bacteria free/sterile rinsing water. Machines should not re-use the cleaning and rinsing water.

The previously published ESGE-ESGENA Guidelines on Cleaning and Disinfection in GI Endoscopy have to be adhered to (Endoscopy 2000; 32: 77-83).