Prions (CJD) and Processing of Reusable Medical Products

Copyright © 2004 WA Rutala

Prions (CJD) and Processing of Reusable Medical Products

衛生署疾病管制局

中區傳染病防治醫療網

王任賢指揮官


Prions and Processing of Reusable Medical ProductsTopics

l Rationale for United States recommendationsn Epidemiological studies of prion transmissionn Infectivity of human tissuesn Efficacy of removing microbes by cleaningn Prion inactivation studiesnRisk associated with instruments

l Recommendations to prevent cross-transmission from medical devices contaminated with prions


Transmissible Spongiform Encephalopathies (TSEs) of Humans

lKurulGertsmann-Straussler-Scheinker (GSS)lFatal Familial Insomnia (FFI)lCreutzfeldt-Jakob Disease (CJD)lVariant CJD (vCJD), 1995


CJD


Prions and Processing of Reusable Medical Products

l Rationale for US recommendationsn Epidemiological studies of prion transmissionn Epidemiological studies of prion transmission via

surgical instrumentsn Infectivity of human tissuesn Efficacy of removing microbes by cleaningn Prion inactivation studiesnRisk associated with instruments


Transmissibility of Prionsl Transmissionn Not spread by contact (direct, indirect, droplet) or airbornen Not spread by the environmentn Experimentally-all TSEs are transmissible to animals, including

the inherited formsn Epidemiology of CJD: sporadic-85%; familial-15%; iatrogenic-

1% (primarily transplant of high risk tissues, ~250 cases worldwide)


Iatrogenic Transmission of CJDl Contaminated medical instrumentsnElectrodes in brain (2)nNeurosurgical instruments in brain (4)

l Dura mater grafts (>110) l Corneal grafts (3)l Human growth hormone and gonadotropin (>130)


Prions and Processing of Reusable Medical ProductsHistorical Perspective

l CJD and other TSEs exhibit an unusual resistance to conventional chemical and physical decontamination methods

l Until recently, all medical/surgical instruments from CJD patients received special prion reprocessing

l Draft guidelines of the CDC (Favero, 1995) suggested a risk assessment consider cleaning and prion bioburden that results from contact with infectious tissues


CJD and Medical Devicesl Six cases of CJD associated with medical devicesn 2 confirmed cases-depth electrodes; reprocessed by

benzene, alcohol and formaldehyde vaporn 4 unconfirmed cases-CJD following brain surgery, index

CJD identified-1, suspect neurosurgical instrumentsl Cases occurred from 1953-1980 in UK, France and Switzerlandl No cases since 1980 and no known failure of steam sterilization


Risk of CJD Transmissionl Epidemiologic evidence (eye, brain, pituitary)

linking specific body tissue or fluids to CJD transmissionl Experimental evidence in animals demonstrating

that body tissues or fluids transmit CJDn Infectivity assays a function of the relative

concentration of CJD tissue or fluid


Risk of CJD Transmission

Peripheral nerve, intestine, bone marrow, whole blood, leukocytes, serum, thyroid gland, adrenal gland, heart, skeletal muscle, adipose tissue, gingiva, prostate, testis, tears, nasal mucus, saliva, sputum, urine, feces, semen, vaginal secretions, and milk

No

CSF, liver, lymph node, kidney, lung, spleen, placenta, olfactory epithelium

Low

Brain (including dura mater), spinal cord, and eyeHighTissueRisk of Infection

High-transmission to inoc animals >50%; Low-transmission to inoc animals >10-20% but no epid evidence of human inf


CJD: DISINFECTION AND STERILIZATIONl Effectiveness must consider both removal by cleaning and

inactivationn Probability of a device remaining capable of transmitting

disease depends on the initial contamination and effectiveness of cleaning/disinfection/sterilization.

n Device with 50ug of CJD brain with a titer of 6 log10 LD50/g would have 5 x 104 infectious units


CJD: DISINFECTION AND STERILIZATIONlEffectiveness of cleaningn Cleaning results in a 4 to 6 log10 reduction of microbes and ~2

log10 reduction in protein contaminationn Recent data: alkaline detergents reduce 5 log10 prions (FDA,

2003, J Hosp Infect, 2004); enzymes that digest prions at 70oC reduce 5-6 log10 prions (J Inf Dis, 2003)

n Ideally, in the future new alkaline/enzymatic cleaners and routinely available sterilization processes will lead to sterilization methods for prion-contaminated medical devices


Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants

PrionsSpores

MycobacteriaNon-Enveloped Viruses

FungiBacteria

Enveloped Viruses


Prion Inactivation Studiesl Problemsn Investigators used aliquots of brain tissue macerates vs. intact

tissue (smearing, drying); weights of tissue (50mg-375mg)n Studies do not reflect reprocessing procedures in a clinical

setting (e.g., no cleaning) n Factors that affect results include: strain of prion (22A),

prion conc in brain tissue, animal used, exposure conditions, validation and cycle parameters of sterilizers, resistant subpopulation, different test tissues, different duration of observations, screw cap tubes with tissue (air), etc


Ineffective or Partially-Effective Disinfectants:CJD

l Alcoholl Ammonial Chlorine dioxidel Formalinl Glutaraldehydel Hydrogen peroxidel Iodophors/Iodinel Peracetic acidl Phenolics


CJD: Ineffective DisinfectantsExamples

l Glutaraldehyde (5%)n Partially effective

l Iodine (2%)n ~1 log decrease in 30m

l Hydrogen peroxide (3%)n ~ 1 log decrease in 60m

l Formaldehyde (3.7%)n ~ 1 log decrease in 60m


Ineffective or Partially Effective Processes: CJD

l Gasesn Ethylene oxiden Formaldehyde

l Physicaln Dry heatn UVn Microwaven Ionizingn Glass bead sterilizersn Autoclave at 121oC, 15m


CJD: Ineffective SterilantsExamples

l Steam sterilization (gravity)n 121oC and 132oC-< 4 log10 decrease at 15m

l Ethylene oxiden 88%, 4h

l Glass bead sterilizersn 240oC for 15m

l Dry heatn 160oC for 24h


Effective Disinfectants(>4 log10 decrease in LD50 with 1 hour)

l Sodium hydroxiden 1 N for 1h (variable results)

l Sodium hypochoriten 5000 ppm for 15m

l Guanidine thiocyanaten 4M

l Phenolic (LpH)n 0.9% for 30m


Effective Processes: CJDl Autoclaven 134oC-138oC for 18m (prevacuum) n 132oC for 60m (gravity)

l Combination (chemical exposure then steam autoclave, potentially deleterious to staff, instruments, sterilizer) n Soak in 1N NaOH, autoclave 134oC for 18mn Soak in 1N NaOH, autoclave 121oC for 30m


Disinfection and Sterilizationl EH Spaulding believed how an object will be D/S

depended on the objects intended usen CRITICAL-objects that enter normally sterile tissue or the

vascular system should be sterilen SEMICRITICAL-objects that touch mucous membranes or

skin that is not intact requires a disinfection process (high level disinfection) that kills all but bacterial spores (prions?)

n NONCRITICAL-objects that touch only intact skin require low-level disinfection

CJD : potential for secondaryspread through contaminatedsurgical instruments


Risk Assessmentl High risk patient-certain patients capable of transmitting

infection.l High risk tissue-CJD can be transmitted to laboratory

animals by inoculation of infective material. Iatrogenic episodes of CJD have been associated with these infective materials.

l High risk devices-risk of infection associated with the use of the device.


Risk Assessment: Patient, Tissue, Devicel Patient

n Known CJD or other TSEsn Rapidly progressive dementian Familial history of CJD, GSS, FFIn Patients with mutation in the PrP gene involved in TSEsn History of dura mater transplant, cadaver-derived pituitary hormone

l Tissuen High risk-brain, spinal cord, eyes

l Devicen Critical or semicritical


Examples: CJD D/Sl High risk patient, high risk tissue, critical/semicritical device-

special prion reprocessingl High risk patient, low risk tissue, critical/semicritical device-

conventional D/S or special prion reprocessingl High risk patient, no risk tissue, C/SC device-conventional D/Sl Low risk patient, high risk tissue, critical/semicritical device-

conventional D/Sl High risk patient, high risk tissue, noncritical device-

conventional disinfection


CJD: Instrument Reprocessingl High Risk Tissue, High Risk Patient, Critical/Semicritical

Device-special prion reprocessingnCleaning followed byuNaOH and steam sterilization (e.g., 1N NaOH 1h, 121oC 30

min)u134oC for >18m (prevacuum/porous)u132oC for 1h (gravity)

nDiscard instruments that are difficult to clean


CJD: Instrument Reprocessingl Special prion reprocessing by combination of NaOH and steam sterilization

n Immerse in 1N NaOH for 1 hour; remove and rinse in water, then transfer to an open pan and autoclave for 1 hour

n Immerse in 1N NaOH for 1 hour and heat in a gravity displacementsterilizer at 121oC for 30 minutes

l Combined use of autoclaving in sodium hydroxide has raised concerns of possible damage to autoclaves, and hazards to operators due to the caustic fumes.

l Risk can be minimized by the use of polypropylene containment pans and lids (AJIC 2003; 31:257-60).


CJD: Instrument Reprocessingl No Risk Tissue, High Risk Patient, Critical/Semicritical Devicen These devices can be cleaned and disinfected or sterilized

using conventional protocols of heat or chemical sterilization, or high-level disinfection (HLD for semicritical)

n Endoscopes would be contaminated only with no or low risk materials and hence standard cleaning and HLD protocols would be adequate

l Low Risk Tissue, High Risk Patient, Critical/Semicritical Devicen Conventional D/S or special prion reprocessing


CJD: Environmental Surfacesl High/Low/No Risk Tissue, High Risk Patient, Noncritical

Surface/Devicen Environmental surfaces contaminated with high risk

tissues (autopsy table in contact with brain tissue) should be cleaned and then spot decontaminated with a 1:5 dilution of bleachn Environmental surfaces contaminated with low/no risk

tissue require only standard disinfection


D/S of Medical Devicesl Issuesn Do not allow tissue/body fluids to dry on instruments (e.g., place

in liquid)n Some decontamination procedures (e.g., aldehydes) fix protein

and this may impede effectiveness of processesn Do not exceed 134oCn Clean instruments but prevent exposuren Assess risk of patient, tissue, devicen Choose effective process


Conclusionsl Epidemiologic evidence suggests nosocomial CJD

transmission via medical devices is very rarel Guidelines based on epidemiologic evidence, tissue

infectivity, risk of disease via medical devices, and inactivation data

l Risk assessment based on patient, tissue and devicel Only critical/semicritical devices contacting high risk tissue

from high risk patients require special prion reprocessing


CJD: Disinfection and Sterilization Conclusions

l Cleaning with special prion reprocessingn NaOH and steam sterilization (e.g., 1N NaOH 1h, 121oC 30 m)n 134oC for 18m (prevacuum)n 132oC for 60m (gravity)

l No low temperature sterilization technology effectivel Four disinfectants (e.g., chlorine) effective (3 log decrease

in LD50 within 15 min)


CJD: Sterilization in Health CareUsed Instrument

↓Keep Wet (do not let tissue/fluid dry)

↓Clean (Washer Disinfector)

↓Steam Sterilize (NaOH and SS; 134oC, 18 min)

↓Sterile Instrument


Prevent Patient Exposure to CJD Contaminated Instruments

How do you prevent patient exposure to neurosurgical instruments from a patient who is latter given a diagnosis of CJD?

Hospitals should use the special prion reprocessing precautions for instruments from patients undergoing brain biopsy when a specific lesion has not been demonstrated (e.g., CT, MRI). Alternatively, neurosurgical instruments used in such cases could be disposable or instruments quarantined until pathology excludes CJD.


Variant CJDl Strongly associated with epidemiology of BSE (1983) in UKl BSE amplified by feeding cattle meat and bone meal infected

with BSE (bovine spongiform encephalopathy)l June 2003, 144 cases vCJD (135 in UK, 6 in France, 1 Italy,

Canada, US [latter two cases resided in UK during BSE outbreak])

l Affects young persons (range 13-48y, median 28y)l Clinical course is longerl vCJD and BSE not reported in the United Statesl vCJD and BSE are believed caused by the same prion agent


vCJD: Disinfection and Sterilizationl To date no reports of human-to-human transmission of vCJD by

tissue but a possible case of vCJD by blood transfusionl Unlike CJD, vCJD detectable in lymphoid tissues (e.g., spleen

tonsils) and prior to onset of clinical illnessl Special prion reprocessing (or single use instruments) proposed

in the UK in dental, eye, or tonsillar surgery on high risk patients for CJD or vCJD

l If epidemiological and infectivity data show these tissues represent a transmission risk then special prion reprocessing could be extended to these procedure


Thank you

Prions (CJD) and Processing of Reusable Medical Products

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