CONTROL OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES by sdfwerte

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									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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