Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach

Summary

Several guidelines recommend specific treatments for endoscopes, procedures of quarantine for endoscopes, or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of Creutzfeldt–Jakob disease (CJD) or variant CJD (vCJD) but vary in many details. This study therefore reviewed guidelines on reprocessing flexible endoscopes after use in patients with suspected or confirmed prion disease. In addition, a literature search was performed in Medline on prion, CJD, vCJD, chemical inactivation, transmission healthcare, epidemiology healthcare, concentration tissue human and endoscope. Thus far, no case of CJD or vCJD transmitted by flexible endoscope has been reported. In animals it has been shown that oral uptake of 0.1–5 g of bovine spongiform encephalopathy (BSE)-infected brain homogenate is necessary for transmission. The maximum prion concentration in other tissues (e.g., terminal ileum) is at least 100-fold lower. Automated cleaning of endoscopes alone results in very low total residual protein ≤5.6 mg per duodenoscopes. Recommendations vary between countries, sometimes with additional cleaning, use of alkaline cleaners, no use of cleaners with fixative properties, use of disinfectants without fixative properties or single-use disinfectants. Sodium hydroxide (1 M) and sodium hypochlorite (10,000 and 25,000 mg/L) are very effective in preventing transmission via contaminated wires implanted into animal brains, but their relevance for endoscopes is questionable. Based on circumstantial evidence, it is proposed to consider validated reprocessing as appropriate in the case of delayed suspected prion disease when immediate bedside cleaning, routine use of alkaline cleaners, no fixative agents anywhere prior to disinfection and single use brushes and cleaning solutions can be assured.

Introduction

Prion diseases in humans comprise Creutzfeldt–Jakob disease (CJD), variably protease-sensitive prionopathy, Gerstmann–Sträussler–Scheinker disease, fatal familial insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in which conformational changes in the prion protein are thought to be the central pathophysiologic event. The majority of cases of human prion diseases occur worldwide in the form of sporadic CJD [1]. Up until 2016 there were 491 incidents of iatrogenic transmission of CJD, largely resulting from prion-contaminated growth hormone (238 cases) and dura mater grafts (238 cases). Four cases were reported after gonadotropin treatment, four were transmitted by surgical instruments in the 1950s (UK and France), three by blood transfusion, two by corneal transplant and two by electroencephalogram (EEG) depth electrode [2]. An analysis of 65 CJD blood donors along with 826 of their blood recipients showed that there is no evidence of CJD transfusion transmission in 3934 person years of follow-up; this risk remains theoretical to date [3].

Prion diseases occur in iatrogenic and zoonotic forms (iatrogenic CJD and variant CJD (vCJD), respectively), adding a public health dimension to their management [1], [4]. A review published in 2017 showed that more than 20 years after identification of the first vCJD patients, only five cases were known that were probable consequences of iatrogenic vCJD transmission, all in the UK, and all associated with blood and blood products. These cases were caused by transfusion of non-leukocyte-depleted erythrocyte concentrates or by treatment involving large amounts of pooled plasma from the UK that were known to include donations from persons who later showed development of vCJD. None of the 220 other vCJD cases identified worldwide has been linked to any other medical or dental procedure [5].

From 1987 the number of bovine spongiform encephalopathy (BSE) cases increased dramatically in the UK, reaching approximately 37,000 new cases in 1992 [4]. With a delay of 8 years, human cases of vCJD were detected and also increased with 28 new cases in 2000 [4]. That is why a transmission by oral uptake of BSE prions was considered to be a possible cause of vCJD. Flexible endoscopes are typically classified as semi-critical items and reprocessed according to validated protocols [6]. In order to eliminate any possible risk of prion transmission via flexible endoscopes, several national and international guidelines have recommended specific treatments for endoscopes, procedures of quarantine for endoscopes or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of CJD or vCJD. They were based on the existing evidence and plausible assumptions at that time. Especially in suspected cases, it may be difficult to clearly distinguish between CJD and vCJD. In addition, some details of the recommendations appear to be questionable and vary largely between countries. This study therefore reviewed major national guidelines on endoscope reprocessing in relation to confirmed, probable or suspected prion disease, the type and impact of endoscopy procedure and its anatomical sites, the evidence of the efficacy of various treatments for prion inactivation including their test methods, data on the concentration of prion protein in various tissues, and finally evaluated their practical plausibility based on current evidence and experience.