CJD: Recommendations for Disinfection and Sterilization in Health Care William A. Rutala, Ph.D., M.P.H. University of North Carolina (UNC) Hospitals and.

CJD: Recommendations for Disinfection and Sterilization in Health Care

William A. Rutala, Ph.D., M.P.H.University of North Carolina (UNC) Hospitals

and UNC School of Medicine

CJD: Disinfection and Sterilization Topics

Rationale for US recommendations Epidemiological studies of prion transmission Infectivity of human tissues Efficacy of removing microbes by cleaning Prion inactivation studies

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

Methodology-how methodology affects results

CJD: DISINFECTION AND STERILIZATION Rationale for US recommendations

Epidemiological studies of prion transmission Epidemiological studies of prion transmission via

surgical instruments Infectivity of human tissues Efficacy of removing microbes by cleaning Prion inactivation studies Risk associated with instruments

Transmissibility of Prions Transmission

Not spread by contact (direct, indirect, droplet) or airborne Not spread by the environment Experimentally-all TSEs are transmissible to animals, including

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

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

Iatrogenic Transmission of CJD Contaminated medical instruments

Electrodes in brain (2)Neurosurgical instruments in brain (4)

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




CJD and Medical Devices Six cases of CJD associated with medical devices

2 confirmed cases-depth electrodes; reprocessed by benzene, alcohol and formaldehyde vapor

4 cases-CJD following brain surgery, index CJD identified-1, suspect neurosurgical instruments

Cases occurred before 1980 in Europe No known cases since 1980 and no known failure of

steam sterilization




Risk of CJD Transmission Epidemiologic evidence (eye, brain) linking specific

body tissue or fluids to CJD transmission Experimental evidence in animals demonstrating

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

concentration of CJD tissue or fluid

Risk of CJD TransmissionRisk of Infection TissueHigh Brain (including dura mater), spinal cord, and eye

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

No 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

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




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

inactivation Probability of a device remaining capable of transmitting

disease depends on the initial contamination and effectiveness of C/D/S.

Cleaning results in a 4 log10 reduction of microbes and ~2 log10 reduction in protein contamination




Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants

PrionsSpores

MycobacteriaNon-Enveloped Viruses

FungiBacteria

Enveloped Viruses

Ineffective or Partially-Effective Disinfectants:CJD

Alcohol Ammonia Chlorine dioxide Formalin Glutaraldehyde Hydrogen peroxide Iodophors/Iodine Peracetic acid Phenolics

Ineffective or Partially Effective Processes: CJD

Gases Ethylene oxide Formaldehyde

Physical Dry heat UV Microwave Ionizing Glass bead sterilizers Autoclave at 121oC, 15m

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

Sodium hydroxide 1 N for 1h (variable results)

Sodium hypochorite 5000 ppm for 15m

Guanidine thiocyanate 4M

Phenolic (LpH) 0.9% for 30m

Effective Processes: CJD Autoclave

134oC-138oC for 18m (prevacuum) 132oC for 60m (gravity)

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




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

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

vascular system should be sterile 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?)

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

CJD : potential for secondaryspread through contaminatedsurgical instruments

Risk Assessment: Patient, Tissue, Device Patient

Known or suspected CJD or other TSEs Rapidly progressive dementia Dura mater transplant, HGH injection

Tissue High risk-brain, spinal cord, eyes

Device Critical or semicritical

Examples: CJD D/S High risk patient, high risk tissue, critical/semicritical

device-special prion reprocessing High risk patient, low/no risk tissue, critical/semicritical

device-conventional D/S Low risk patient, high risk tissue, critical/semicritical

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

conventional disinfection

Conclusions Epidemiologic evidence suggests nosocomial CJD

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

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

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

from high risk patients require special prion reprocessing

CJD: Disinfection and Sterilization Conclusions

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

No low temperature sterilization technology effective Four disinfectants (e.g., chlorine) effective (4 log decrease

in LD50 within 1h)

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





Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants

PrionsSpores

MycobacteriaNon-Enveloped Viruses

FungiBacteria

Enveloped Viruses

Prion Inactivation Studies Problems

Investigators used aliquots of brain tissue macerates vs. intact tissue (smearing, drying); weights of tissue (50mg-375mg)

Studies do not reflect reprocessing procedures in a clinical setting (e.g., no cleaning)

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

STERILIZATIONFactors affecting the efficacy of sterilization Bioburden Cleaning Pathogen type Protein and salt Biofilm accumulation Lumen length and diameter Restricted flow

Penicylinders Sterilized by Various Low-Temperature Sterilization Methods

Challenge: 12/88 100%ETO HCFC-ETO Sterrad10% Serum,0.65% Salt(7 organisms, N=63) 97% 60.3% 95.2% 37%No Serum or Salt,(3 organisms, N=27) 100% 100% 96% 100%Alfa et al. Infect Cont Hosp Epidemiol 1996;17:92-100. The three organisms included: E. faecalis, M. chelonei,

B. subtilis spores. The seven organisms included: E. faecalis, P. aeruginosa, E.coli, M. chelonei, B. subtilis spores, B. stearothermophilus spores, B. circulans spores

Lumens Sterilized by VariousLow-Temperature Sterilization Methods

Challenge: 12/88 100%ETO HCFC-ETO Sterrad10% Serum,0.65% Salt(7 organisms, N=63) 44% 39.7% 49.2% 35%No Serum or Salt,(3 organisms, N=27) ND 96.3% 96.3% NDAlfa et al. Infect Cont Hosp Epidemiol 1996;17:92-100. The three organisms included: E. faecalis, M.

chelonei, B. subtilis spores. The seven organisms included: E. faecalis, P. aeruginosa, E.coli, M. chelonei, B. subtilis spores, B. stearothermophilus spores, B. circulans spores

Low-Temperature Sterilization Technologies (LTST)Conclusions

All technologies have limitations LTST (ETO, HP gas plasma) demonstrate a significant

number of failures in presence of serum or salt Salt and serum provide protection for spores and

bacteria Salt and serum combined with a narrow lumen provide

extraordinary protection with LTST

STERILIZATIONFactors affecting the efficacy of sterilization Bioburden Cleaning Pathogen type Protein and salt Biofilm accumulation Lumen length and diameter Restricted flow

Effect of Rinsing with Water on Sterilization Results

Method Inoculate scalpel blade with tissue culture media with 10% fetal

bovine serum containing 1.5x106 Geobacillus stearothermophilus spores dried for 12 hours at room temperature

Removal of Soil and Microorganisms from Medical Devices

Method Inoculate 0.02 ml of FBS containing 106 B.

stearothermophilus spores onto scalpel blade Dry for 30 min at 35oC followed by 30 min at RT Samples placed in distilled water at room

temperature for specified time Chloride, protein and spore concentration measured

Removal of Soil and Microorganisms from Medical DevicesConclusions

Inorganic, organic and microbial contaminants on a device are dramatically reduced during a washing process

96.3% (or 2.5 x 106 organisms) removed from blade in 150 sec

Removal of Soil and Microorganisms from Medical DevicesConclusions

Inorganic, organic and microbial contaminants on a device are dramatically reduced during a washing process

Contact with water for short period of time rapidly leads to the dissolution of salt crystals. Studies in 1950’s and 1960’s show that spores occluded inside crystals were very resistant to sterilization (e.g., ETO, steam).

Minimal cleaning eliminates the effect of salt Simulated use tests that do not include washing would not

represent conditions that exist in use situation

You can cleanwithout sterilization

but you NEVERcan sterilize

without cleaning

Conclusions All sterilization processes effective in killing spores Salt favors crystal formation and impairs sterilization by occlusion of

organisms Cleaning removes salts and proteins and must precede sterilization Failure to clean or ensure exposure of microorganisms to sterilant

(e.g. connectors) could affect effectiveness of sterilization process CJD inactivation studies should be consistent with actual clinical

practice





Thank you

References Alfa MJ, Olson N, DeGagne P, Hizon R. New low temperature

sterilization technologies: Microbicidal activity and clinical efficiency. In Rutala WA, ed. Disinfection, Sterilization, and Antisepsis in Healthcare. Champlain, NY: Polyscience Publications. 1998:67-78.

Rutala WA, Weber DJ. Clinical effectiveness of low-temperature sterilization technologies. Infect Control Hosp Epidemiol 1998;19:798-804.

Jacobs P. Cleaning: principles and benefits. In: Rutala WA, ed. Disinfection, Sterilization, and Antisepsis in Healthcare. Champlain, NY: Polyscience Publications. 1998:165-182.

Disinfection and Sterilization for Prion DiseasesReferences

Rutala WA, Weber DJ. Creutzfeldt-Jakob Disease: Recommendations for Disinfection and Sterilization. Clin Inf Dis 2001;32:1348-1356.

Rutala WA, Weber DJ, and HICPAC. CDC Guideline for Disinfection and Sterilization. In preparation

Weber DJ, Rutala WA. Managing the risks of nosocomial transmission of prion diseases. Current Opinions in Infectious Diseases. 2002;15:421-426.

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.

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

blood or tissue Unlike CJD, vCJD detectable in lymphoid tissues and prior to onset

of clinical illness 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

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

Factors Affecting the Efficacy of LTST Cleaning - Failure to clean results in higher bioburden,

protein load and salt concentration Bioburden - Natural bioburden on surgical devices 100 to

103

Pathogen - Spore forming organisms most resistant Protein - Residual protein decreases efficacy of

sterilization Salt - Residual salt decreases efficacy of sterilization

CJD: Recommendations for Disinfection and Sterilization in Health Care William A. Rutala, Ph.D., M.P.H. University of North Carolina (UNC) Hospitals and.

Documents

cases of cjd

cjd infectivity

iatrogenic transmission

instruments slide

index cjd

neurosurgical instruments

fluid slide

high risk tissues