Reducing the risk of transmission of CreutzfeldtJakob disease (CJD) from surgical instruments used for interventional procedures on high-risk tissues

Evidence-based recommendations on reducing the risk of transmission of CreutzfeldtJakob disease (CJD) from surgical instruments used for interventional procedures on high-risk tissues. These procedures on high-risk tissues are intradural surgery on the brain (including the pituitary gland) and spinal cord, neuroendoscopy, and surgery on the retina or optic nerve.

# This guidance is for high-risk tissues
This guidance is for interventional procedures on tissues considered at high risk of transmitting CreutzfeldtJakob disease (CJD). These procedures on high-risk tissues are intradural surgery on the brain (including the pituitary gland) and spinal cord, neuroendoscopy, and surgery on the retina or optic nerve (see appendix D for a complete list).
Note that the abbreviation 'CJD' is used for both sporadic and variant CJD (vCJD), including surgically transmitted CJD (stCJD), unless otherwise specified.
The recommendations do not apply to any interventional procedures done on patients already known to have or thought to be at increased risk of CJD as previously defined by the Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathies subgroup. For these patients and patients in whom the risk of CJD cannot be ascertained by questioning them, or when a diagnosis of CJD cannot be excluded, the Advisory Committee on Dangerous Pathogens' guidance on transmissible spongiform encephalopathy agents: safe working and the prevention of infection must be followed.# Recommendations

# Decontamination
All surgical instruments that come into contact with high-risk tissues during an interventional procedure must be kept moist and separated from other instruments until they are cleaned, and then disinfected and sterilised (decontaminated). This improves the efficacy of the decontamination process and is highly cost effective.

# Set integrity and tracking
Surgical instruments that come into contact with high-risk tissues must not be moved from one set to another and must remain within their individual sets. Maintaining set integrity reduces the risks associated with instrument migration (including infection) and makes it easier to trace instruments back to the patients they were used on.

# Supplementary instruments
Supplementary instruments that come into contact with high-risk tissues must remain within the individual set to which they have been introduced. Supplementary instruments are those that are not part of a specific instrument set. If supplementary instruments are used with different sets, this would compromise set traceability and increases the risks associated with instrument migration.

# Neuroendoscopy
Rigid neuroendoscopes (rather than flexible neuroendoscopes) should be used if possible. They should be of a type that can be steam sterilised and must be thoroughly cleaned and steam sterilised after each use.

# Single-use instruments
The evidence on cost effectiveness does not support using sets of single-use instruments to reduce the risk of CreutzfeldtJakob disease (CJD) transmission.

# Systems specifically for people born after 1996
The evidence on cost effectiveness does not support introducing systems to maintain separate sets of neuroendoscopes and reusable surgical instruments for use on high-risk tissues for people born after 1996.
Removing the requirement to use different instruments on high-risk tissues for people born after 1996 would not markedly increase the risk of surgical transmission of CJD.

# Other relevant guidance
This guidance should be used with:
the Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathies subgroup's previous guidance on transmissible spongiform encephalopathy agents: safe working and the prevention of Infection
the Department of Health and Social Care's Health Technical Memorandum (HTM) 01-01: decontamination of surgical instruments (2016) and corresponding guidance in the devolved administrations' areas.

# Further research
NICE may update this guidance after 3 years or sooner if important new information becomes available, including evidence on:
the epidemiology of CJD, including data on the prevalence of CJD and its infectivity in the UK population
the transmission of CJD by surgical instruments, including cases of CJD in which surgery is a possible route of transmission
the cost effectiveness of single-use instruments for use in interventional procedures on high-risk tissues
commercially available decontamination methods that are safe and cost effective against prions
the systems for, and cost effectiveness of, maintaining set integrity and traceability of instruments.# Indication

# The condition
CreutzfeldtJakob disease (CJD) is a progressive, fatal neurological disease affecting the brain. It is caused by pathological accumulation of a transmissible form of protein called a prion. CJD belongs to a wider group of neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs) that affect both humans and animals. People with CJD typically present with rapidly progressive dementia, usually accompanied by myoclonus and cerebellar ataxia. Most people die within 4 months of disease onset, in a mute and immobile state.

# Epidemiology of CJD
The incidence of any type of CJD (based on published surveillance studies) is 1 to 2 cases per million of the population worldwide. There are 4 aetiological CJD categories:
Sporadic CJD (sCJD) accounts for 85% to 90% of cases worldwide. The aetiology is not known. It has an annual incidence of 1 to 2 deaths per million of population per year. The general rate of age-adjusted detection of sCJD is increasing in the UK. Reasons for this include improved case ascertainment and an ageing population (in which there is a higher incidence).
Inherited (genetic or familial) CJD accounts for 5% to 15% of cases or about 10 deaths in the UK per year. It is associated with pathogenic mutations in the prion protein gene.
Variant CJD (vCJD) is a novel form of human prion disease, first recognised in the UK in 1996. It is believed to result from consumption of food derived from cattle infected with bovine spongiform encephalopathy (BSE), a fatal neurodegenerative disease that causes sponge-like changes in the brain. vCJD is characterised by extensive lymphoreticular tissue involvement and a young age at onset (the mean age at death is 28 years, compared with 66 years for sCJD). The clinical course of vCJD is distinct from that of sCJD. People with vCJD frequently present with sensory and psychiatric symptoms that are uncommon in people with sCJD. They develop progressive neurological signs such as gait disturbance, ataxia and tremor. The median duration of illness is longer than for sCJD (14 months compared with 4 months). By 2016 there had been 178 cases of vCJD in the UK. Three cases are considered to have occurred through blood transfusion and 175 cases were related to dietary exposure to BSE. The prevalence of non-clinical vCJD (abnormal prion accumulation in tissues without clinical symptoms) in the general UK population is estimated to be 240 per million, based on retrospective analyses of appendix specimens. In the UK, between 1988 and 1996, a series of measures were put in place to reduce the risk of people being exposed to BSE. Over the past 8 years there have been 0 or 1 deaths per year in the UK attributed to vCJD.
Iatrogenic CJD (iCJD) accounts for less than 1% of cases each year. It is the transmission of prions through surgical or medical procedures (especially from tissues with the highest concentration of prions, such as brain and posterior eye tissue) or human-derived products (growth hormone, gonadotropin, dura mater grafts and packed red blood cells). Surgically transmitted CJD (stCJD) is theoretically possible through prion-contaminated instruments that have been previously used on patients with CJD. This includes patients who are asymptomatic but infectious because neural tissue has a high infectious load, and there are difficulties in eradicating prions from surgical instruments. The most common causes of iCJD are historic use of human growth hormone and dura mater grafts, according to a review of worldwide iCJD cases published in 2012. In the UK, 85 iCJD cases were identified between 1970 and 2016. Eight were from dura mater grafts, 1 was from human gonadotrophin and 76 were from human growth hormone. There were 4 cases of possible stCJD through contaminated neurosurgical instruments between 1952 and 1974; 3 in the UK and 1 in France. The University of Sheffield's School of Health and Related Research (ScHARR) systematic review indicates that the risk of stCJD is currently low and no cases were reported between 2005 and 2018. However, there is uncertainty about the future risk of stCJD because of the potentially long incubation period of CJD, difficulties in eradicating prions from surgical instruments, the presumed subclinical prevalence in the general population, and high levels of infectivity in the brain. Neurosurgical instruments used on people who are possibly carriers of CJD are handled in accordance with the Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathies risk management subgroup's guidance on safe working and the prevention of infection.
The National CJD Research and Surveillance Unit report the number of deaths per year in the UK attributed to the 4 categories of CJD.

# Incubation periods
Evidence from retrospective data in the ScHARR systematic review shows that the incubation period of iatrogenic CJD ranges from 1 to 42 years with durations towards the shorter end of the range reported in cases of stCJD. Incubation times might be affected by the recipient's genotype and the infecting prion strain or subtype of CJD.

# Infectivity
The infectivity of CJD is likely to be moderated by a number of factors including the recipient's genotype, the infecting prion strain, and the route of transmission. There are limited data about infectious dose or infectious titre in humans. The ID50 is the dose that would give the person receiving it a 50% chance of becoming infected. High values are expressed in log or factor-of-10 terms. For example, 1 g of brain tissue can have an ID50 of 108 (8 log). This means it carries a dose of 100,000,000 ID50. The model assumes that intracranial transfer of 0.01 micrograms of such brain tissue would result in the recipient having a 50% chance of becoming infected with CJD.# Appendix B: Contributors
These organisations provided specialist advice and comments:
CJD Support Network
Child Growth Foundation# Appendix C: Related advisory groups
A number of advisory committees, expert groups and academic units are addressing issues related to CreutzfeldtJakob disease (CJD) including developing the scientific basis of our understanding of the disease, improving decontamination practices across the NHS and minimising the risk of transmission. NICE has made every effort to coordinate with these groups to ensure that this guidance takes account of, and builds on, their work. Some members of the CJD advisory subcommittee are also members of other CJD committees, working groups and academic units. NICE has been represented on some of these groups.
The following is a list of some of the organisations in the UK that either fund surveillance, study or provide advice on the public health aspect of CJD:
Department of Health and Social Care
Medical Research Council Prion Unit at University College London Hospitals' National Prion Clinic
University of Edinburgh National CJD Research & Surveillance Unit
Public Health England
Health Protection Scotland# Appendix D: High-risk procedures
The OPCS4 codes for intradural operations on the brain and spinal cord are shown below.

# Neurosurgery
This list may not be comprehensive.
All purposeful intradural brain and spinal cord surgery are regarded as high-risk and this guidance applies wherever there is contact with or possible contamination by brain or spinal cord tissue.
Extradural surgery, even in the presence of a cerebrospinal fluid leak, is not high risk and this guidance does not apply.
A01 Major excision of tissue of brain
A02 Excision of lesion of tissue of brain
A03 Stereotactic ablation of tissue of brain
A04 Open biopsy of lesion of tissue of brain
A05 Drainage of lesion of tissue of brain
A07 Other open operations on tissue of brain
A08 Other biopsy of lesion of tissue of brain
A09 Neurostimulation of brain
A10 Other operations on tissue of brain
A12 Creation of connection from ventricle of brain
A13 Attention to component of connection from ventricle of brain
A14 Other operation on connection from ventricle of brain
A16 Other open operations on ventricle of brain
A20 Other operations on ventricle of brain
A22 Operations on subarachnoid space of brain
A24 Graft to cranial nerve
A25 Intracranial transection of cranial nerve
A26 Other intracranial destruction of cranial nerve
A29 Excision of lesion of cranial nerve
A30 Repair of cranial nerve
A31 Intracranial stereotactic release of cranial nerve
A32 Other decompression of cranial nerve
A33 Neurostimulation of cranial nerve
A34 Exploration of cranial nerve
A36 Other operations on cranial nerve
A38 Extirpation of lesion of meninges of brain
A39 Repair of dura
A42 Other operations on meninges of brain
B01 Excision of pituitary gland
B02 Destruction of pituitary gland
B04 Other operations on pituitary gland
B06 Operations on the pineal gland
L33 Operations on aneurysm of cerebral artery
L34 Other open operations on cerebral artery
A44.1 Chordectomy of spinal cord
A44.2 Extirpation of lesion of spinal cord NEC
A44.3 Excision of lesion of intradural intramedullary spinal cord
A44.5 Excision of lesion of intradural extramedullary spinal cord
A44.8 Other specified partial extirpation of spinal cord
A44.9 Unspecified partial extirpation of spinal cord
A45.1 Stereotactic chordotomy of spinal cord
A45.2 Open chordotomy of spinal cord NEC
A45.3 Myelotomy of spinal cord
A45.4 Open biopsy of lesion of spinal cord
A45.5 Removal of foreign body from spinal cord
A45.6 Open aspiration of lesion of spinal cord
A45.8 Other specified other open operations on spinal cord
A47.1 Needle destruction of substantia gelatinosa of cervical spinal cord
A47.2 Radiofrequency controlled thermal destruction of spinothalamic tract
A47.3 Percutaneous chordotomy of spinal cord
A47.8 Other specified other destruction of spinal cord
A48.1 Biopsy of lesion of spinal cord NEC
A48.2 Aspiration of lesion of spinal cord
A48.3 Insertion of neurostimulator adjacent to spinal cord
A48.4 Attention to neurostimulator adjacent to spinal cord NEC
A48.6 Removal of neurostimulator adjacent to spinal cord
A48.7 Insertion of neurostimulator electrodes into the spinal cord
A48.8 Other specified other operations on spinal cord
A49.1 Freeing of spinal tether NEC
A49.2 Closure of spinal myelomeningocele
A49.3 Closure of spinal meningocele
A49.4 Complex freeing of spinal tether
A49.8 Other specified repair of spina bifida
A49.9 Unspecified repair of spina bifida
A51.1 Extirpation of lesion of meninges of spinal cord
A51.2 Freeing of adhesions of meninges of spinal cord
A51.3 Biopsy of lesion of meninges of spinal cord
A51.8 Other specified other operations on meninges of spinal cord
A51.9 Unspecified other operations on meninges of spinal cord
A53.1 Cerebrospinal syringostomy
A53.3 Creation of syringoperitoneal shunt
A57.1 Extirpation of lesion of spinal nerve root
A57.6 Reimplantation of spinal nerves into spinal cord

# Posterior eye surgical procedures that are regarded as high-risk posterior segment eye surgery

## Orbit (C01 to C08)
C01 Excision of eye
C03 Insertion of prosthesis of eye
C04 Attention to prosthesis of eye
These orbital operations are only included if the surgery or implant is likely to come into contact with the optic nerve or retinal tissue (for example, evisceration of the eye and intra-orbital implant).

## Operations on optic nerve (A29.1 to A36.4)
A29.1 Excision of lesion of optic nerve
A30.1 Repair of optic nerve
A32.1 Decompression of optic nerve
A34.1 Exploration of optic nerve
A36.4 Radial Optic Neurotomy

# Sclera and iris (C52 to C65)
C54 Buckling operations for attachment of retina

# Retina, other parts of eye and anaesthetics (C79 to C90)
C79 Operations on vitreous body, only when this involves potential contact with the posterior hyaloid face. For example:
Code C7910 for vitrectomy via anterior approach and code C7923 for intravitreal injections are specifically excluded because they are unlikely to come into contact with the posterior hyaloid face.
Code C7920 and code C7922, which potentially could come into contact with the hyaloid face, are included.
C80 Operations on retinal membrane
C81 Photocoagulation of retina for detachment, only when the retina is handled directly
C82 Destruction of lesion of retina, only when the retina is handled directly
Code C82.4 for insertion of radiotherapy plaques is specifically excluded.
C83 Translocation of retina
C84 Other operations on retina
C85 Fixation of retina
C86 Other operations on eye
C88 Destruction of subretinal lesion
C89 Operations on posterior segment of eye
ISBN: 978-1-4731-3605-2