CONTROL OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Content • Introduction – biology, replication of prions and pathology of prion disease • Clinical features • Diagnostic criteria and procedures • Categorisation of patients by risk • Distribution of infectivity in tissues and body fluids CONTROL OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES • Infection control – care of patients, decontamination and quarantining of instruments • CJD Incidents panel • Risk from blood products and look back exercise • Newer methods of decontamination • Therapies • Conclusions TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES DISEASE HOST Scrapie Sheep and goats Kuru Humans Creutzfeldt-Jacob Disease (CJD) Humans [Sporadic / Iatrogenic] Gerstmann-Straussler-Scheinker Humans Syndrome (GSS) [Familial] Bovine Spongiform Encephalopathy Cattle vCJD Humans HUMAN TSEs Incubation Period Duration of (years) illness (months) Kuru 5-30 3-12 CJD 1.5-30 3-4 vCJD ? 14 (approx) THE AGENTS OF TSEs - PRIONS “Infectious” proteins Do not contain nudeic acid Pass through small filters (50nm) Heat resistant Resistant to many chemicals (alcohol, formaldehyde, glutaraldehyde) Resistant to (practical) doses of radiation Resistant to proteases Long “incubation” period REPLICATION OF PRIONS Pr P c Pr Psc (conformational change) PATHOLOGY OF TSE DISEASE Formation of amyloid plaques (brain) Spongiform changes (brain) Abnormal Pr Psc staining by Immunocytochemistry CLINICAL FEATURES (CJD/vCJD) • Personality change • Psychiatric symptoms • Cognitive impairment • Neurological deficits (sensory, motor & ataxia) • Myoclonic jerks (chorea or dystonia, less frequently) CLINICAL FEATURES (CJD/vCJD) cont • Rapid, or unpredictable stepwise, deterioration • Increasing difficulty with communication, mobility, swallowing and continence • Coma • Death DIAGNOSTIC CATEGORIES FOR CJD/vCJD • Definite • Probable • Possible • Diagnosis unclear - CJD/vCJD remains a possibility DIAGNOSTIC CRITERIA Definite cases Confirmed by neuropathological/ immunocytochemical testing DIAGNOSTIC CRITERIA Probable cases (CJD) Rapidly progressive dementia • At least two of four specific symptoms • Plus either: typical EEG TSE associated marker (14-3-3) in CSF DIAGNOSTIC CRITERIA Probable cases (vCJD) • Have a neuropsychiatric disorder (>6 months) with no alternative diagnosis • At least four of five specific symptoms • Pulvinar sign on MRI brain scan DIAGNOSTIC CRITERIA Possible cases (CJD) • Rapidly progressive dementia • At least two of four specific symptoms • And a duration of less than 2 years Possible cases (vCJD) • Have a neuropsychiatric disorder (>6 months) with no alternative diagnosis • At least four of five specific symptoms CATERGORISATION OF PATIENTS BY RISK Symptomatic patients • Fulfil the diagnostic criteria for definite, probable or possible CJD or vCJD • Patients with neurological disease who do not fit the criteria for possible CJD or vCJD but where diagnosis of CJD/vCJD is being actively considered CATEGORISATION OF PATIENTS BY RISK At risk asymptomatic patients At risk from • Iatrogenic exposure ♦Recipient of hormone derived from pituitary glands ♦Individuals who have received a graft of dura mater ♦ Individuals exposed to : instruments used on, receipt of blood, plasma derivities, organs or tissues donated by, a patient who went on to develop CJD or vCJD DIAGNOSTICS PROCEDURES • Lumbar puncture – test CSF for protein 14-3-3 Predictive value in CJD – good Predictive value in vCJD – poor • EEG Useful in CJD but not in vCJD • MRI scan Useful in CJD but not in vCJD Pulvinar sign in posterior thalamus (vCJD) DIAGNOSTICS PROCEDURES (cont) • Tonsil biopsy – vCJD • Brain biopsy (ante-mortem / post mortem) • Genetic testing (familial types of CJD e.g. GSS) SUMMARY OF vCJD CASES – MAY 2005 Deaths from definite cases: 107 Deaths from probable cases: 43 Number of cases of probable vCJD still alive: 5 Total number of cases (dead and alive): 155 DISTRIBUTION OF TSE INFECTIVITY IN HUMAN TISSUES AND BODY FLUIDS Tissue Level of infectivity CJD vCJD Assumed level of Assumed level of Infectivity Infectivity Brain High High Spinal Cord High High Dura mater High High Posterior eye High High Anterior eye Medium Medium and cornea Olfactory Medium Medium epithelium DISTRIBUTION OF TSE INFECTIVITY IN HUMAN TISSUES AND BODY FLUIDS Tissue Level of infectivity CJD vCJD Assumed level of Assumed level of Infectivity Infectivity Tonsil Low Medium Appendix Low Medium Spleen and thymus Low Medium Other lymphoid Low Medium tissues Blood and bone Low Low marrow CSF Low Low CARE OF CJD/vCJD PATIENTS IN HOSPITAL • Patients do NOT (theoretically) require isolation • Infection control team should be contacted from the outset and definitely prior to invasive procedures being performed (e.g. in theatre) • Hazardous specimens should be collected/handled by competent staff wearing gloves & eye protection • Universal precautions should be adhered to SURFACE DECONTAMINATION AND MANAGEMENT OF SPILLAGES • Urine and faeces contamination (non-blood stained) – use of disinfectants unnecessary. Standard cleaning only required. • Spillages of blood and CSF - disinfect with hypochlorite solution (10,000ppm) then clean with detergent and warm water. • High concentration (20,000ppm) hypochlorite unlikely to be practical in a ward situation. Use only in exceptional circumstances (i.e. spillage of high risk material) PRECAUTIONS FOR SURGICAL PROCEDURES ON SYMPTOMATIC, KNOWN OR SUSPECT CJD/vCJD PATIENTS Definite or Probable Possible Procedure Procedure Procedure Procedure involves high involves low risk involves involves high or medium tissues low risk or medium risk risk tissues tissues tissues Dispose of Reprocess (decontaminated) Quarantine instruments by instruments and return to use incineration QUARANTINING OF SURGICAL INSTRUMENTS • ONLY if a DEFINITIVE alternative diagnosis is confirmed may the instruments be reprocessed and returned to routine use • Records must be kept of all decisions • Sterile Service Department must be informed about the decision before instruments are sent for routine reprocessing MANAGEMENT OF INSTRUMENTS AND TISSUES FROM BRAIN BIOPSY PROCEDURES ON PATIENTS WITH PROGRESSIVE NEUROLOGICAL DISORDERS – DOH GUIDELINES [Letter from CMO, May 2004 www.dh.gov.uk] Covers the following: • Clinical assessment of biopsy procedure • Handling of neurological instruments and biopsy tissues • Neuropathological diagnosis and the fate of neuropathological instruments DECONTAMINATION OF INSTRUMENTS USED IN INVESTIGATIVE PROCEDURES NOTE: Refers only to instruments used on possible or at risk patients where there has been no involvement of brain, spinal cord or eye. • Clean instruments thoroughly (at least twice) to remove body fluids prior to disinfection/autoclaving. ♦ Ultrasonic cleaner ♦ Automated thermal washer/disinfector • Autoclave (where possible) 134-137ºC for 18 minutes or 6 successive cycles of 134 - 137ºC for 3 minutes each cycle. SUMMARY OF THE PRECAUTIONS ADVISED FOR THE USE OF ENDOSCOPES IN PATIENTS WITH vCJD Tissue Infectivity Status of patient Symptomatic Asymptomatic Definite/probable Possible/diagnosis At risk iatrogenic unclear High single use OR single use OR single use OR • Brain • Spinal cord destroy after use quarantine pending Quarantine pending diagnosis exclusion of CJD Medium single use OR single us OR single use OR • Olfactory epithelium use dedicated quarantine pending quarantine pending • Lymphoid tissue endoscope OR diagnosis exclusion of CJD destroy after use Low/none detectable no special precautions no special no special precautions •All other tissues precautions CJD INCIDENTS PANEL • Set up by Department of Health • Makes risk assessments • Gives advice on the management of incidents CJD INCIDENTS PANEL Effectiveness of Instrument decontamination • Assume that first washing and autoclaving cycles reduce infectivity on an instrument by at least 105 fold • Subsequent cycles may have less effect. However, assume that by 10th reuse of an instrument the risk of transmitting infection to subsequent patients is close to zero. CJD INCIDENTS PANEL – PATIENTS TO BE INCLUDED IN “CONTACTABLE” GROUP Clinical Procedure in index patient “Contactable” group High risk procedure a) Patient symptomatic or within 1 year First 6 patients of developing symptoms of any type of CJD b) Patient subsequently develops any First 4 patients type of CJD Medium risk procedure Lymphoid tissue procedures in patients First 2 patients who have or subsequently develop vCJD PRECAUTIONARY MEASURES TAKEN BY UK BLOOD SERVICES • Withdrawal and recall of any blood components, plasma products or tissues obtained from any individual who later developed vCJD (December 1997) • Importing plasma from USA to manufacture plasma products (1998) • Removal of white blood cells (leucodepletion) from all blood components (Autumn 1999) • Importing fresh frozen plasma from the USA for patients born on or after 1st January 1996 (Autumn 2002) • Not accepting donations from people who have received a blood transfusion since 1980 (April 2004) PROBABLE TRANSMISSIONS OF vCJD BY BLOOD TRANSFUSION • Patient 1 aged 62 years received 5 units of red cells in 1996, one unit donated by individual who developed vCJD 3 years and 4 months later. • Patient 1 diagnosed with vCJD late 2002. Died 13 months later. • Patient 2 received unit of non-leucodepleted red blood cells from a donor in 1999 who developed vCJD 18 months later. Patient 2 died in 2004 with no evidence of neurological disorder. vCJD prions detected at PM. No pathological features of vCJD. Patient was heterozygous at codon 129 of prion protein gene. LOOK BACK EXERCISE, vCJD AND PLASMA PRODUCTS – SEPTEMBER 2004 • Background: 2 cases of vCJD probably due to blood transfusion • 9 UK plasma donors are now known to have developed vCJD • Recipients of implicated plasma products ♦ patients with bleeding disorders (e.g. haemophilia) ♦ patients with primary immunodeficiency ♦ other patients (e.g. certain neurological conditions, severe burns) LOOK BACK EXERCISE, vCJD AND PLASMA PRODUCTS – SEPTEMBER 2004 (cont’d) • Assessment of risk commissioned by CJD Incidents Panel -1 per cent or greater additional risk categorised as: ♦ High (e.g. one treatment of factor VIII) ♦ Medium (e.g. several infusions of IVIG) ♦ Low (e.g. intramuscular immunoglobulin) – do NOT meet 1% threshold [patients are NOT contacted] NEW METHODS OF DECONTAMINATION • A number of decontamination agents are undergoing research testing • Stainless steel wires are commonly used as a testing platform. Assayed by: ♦ In vitro – western blotting ♦ In vivo – implanted into the brains of hamsters THERAPEUTIC APPROACHES • Currently no proven treatment exists for CJD/vCJD • A few treatments have been tried: ♦ Pentosan Polysulphate ♦ Quinacrine +/- Chlorpromazine • Conventional vaccine approaches unlikely to be successful due to poor immunogenicity of prions. CONCLUSIONS • vCJD poses a threat to the population of the UK although size of the threat is unknown. • Probable spread of vCJD by infected blood products may have exacerbated the problem. • Effective practical decontamination agents are required, particularly for routine purposes. • A practical, sensitive and specific test for vCJD infection in asymptomatically infected individuals is urgently required. • Effective therapies for vCJD disease are also urgently required. • Infection control strategies for vCJD will evolve as more information/data becomes available.
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