Rabies Poliomyelitis Prion Disease

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RabiesPoliomyelitisPrion Disease

• Nani Kurniani, dr., SpS(K)
• Dept. of Neurology
• Hasan Sadikin Hospital
• Bandung

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Introduction
Rabies

• Is a zoonosis ? encephalitis
• Infect mammals (dogs, bats, wild carnivores)
• Public Health problem
• Etiology Lyssavirus 4 serotypes
• family rhabdoviridae
• Preventable
• Curable?

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Introduction
Rabies

• 100 mortality
• Death 25,000 people/year
• Post exposure prophylaxis 4million people/year
• 90 live in developing countries
• The risk of contracting rabies from a bite wound
  is 5-80
• depend on incidence of rabies in endemic species
  or other terrestrial animals in the region

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Pathogenesis
Rabies

• The virus is believed to be capable of infecting
  all warm-blooded creatures
• Almost all cases of human rabies occur due to the
  bite of an infected animal
• Other possible route of transmission
• Aerosol
• Person-to-person corneal transplantation

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Pathogenesis
Rabies

• Route of infection
• Virus in the saliva of infected animals
• The bite
• Inoculation in local tissue
• Transmission of the virus to the CNS
• Axonal transport
• Direct transmission without prior local
  replication
• Initial local replication followed by transmission

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Pathogenesis
Rabies

• Route of infection
• Rate of transmission 8 20 (up to100) mm/day
• Dorsal root ganglia ? spinal cord ? the brain
• Subsequent widespread infection to limbic system,
  hippocampus, brainstem and cerebellum
• Centrifugal spread back to the peripheral sites ?
  salivary glands, corneal cells ? transmission to
  other person
• At end stage, virtually all organs are involved

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Clinical
Rabies

• History
• History of an animal bite is given ? suspicion
  of rabies!
• In any suspected cases, identify the following
• Nature of the interaction with the animal (eg,
  provoked attack or unexpected)
• Strange animal behavior (eg, nocturnal animal out
  during the daytime)
• Vaccination status of the animal for rabies
• Patients usually come when the sign of
  encephalitis has been present ? difficult to
  obtain anamnesis
• Rabies progresses over 7-14 days
• mean time between initial presentation and death
  16.2 days

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Clinical
Rabies

• Prodrome
• Patients have presented to Emergency Departments
  with nonspecific fever and pharyngitis
• Most prodromes last from 2-10 days
• Initial symptoms of pain or paresthesias at the
  site of bite or scratch begin during the prodrome
• ? The only symptoms
• Fever, headache, and anorexia may also be present

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Clinical
Rabies

• Neurologic stage (2-7 days)
• Aphasia
• Incoordination
• Paresis
• Paralysis
• Mental status changes
• Hyperactivity

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Clinical
Rabies

• Late symptoms
• Hypotension
• Coma
• Disseminated intravascular coagulation (DIC)
• Cardiac arrhythmias
• Cardiac arrest
• Fatality

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Clinical
Rabies

• Physical findings
• High fever with rapidly progressive encephalitis
• Myoclonus
• Increased lacrimation
• Hypersalivation
• Agitation
• Anxiety

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Clinical Presentation
Rabies

• 2 forms of rabies furious and paralytic
• Both forms progress to paralysis of pharyngeal
  and respiratory muscles, seizures, and coma with
  death in 1-3 weeks
• Most common in humans furious form
• Also common in cats
• Many animals, including bats, exhibit dumb rabies
  (paralytic form)

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Diagnostics
Rabies

• Definitive Brain biopsy
• In suspected human cases
• skin biopsy from the nape of the neck
• smear of corneal epithelial cells (less
  preferable)
• Rise in specific neutralizing antibodies by rapid
  fluorescent focus inhibition test (RFFIT)
• often not documented in true rabies cases (have
  died before the 2nd test can be done)
• more useful to ascertain serostatus in immunized
  animals and humans
• Viral culture saliva, CSF, and brain

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Treatment
Rabies

• For the human patients
• Thorough cleaning of all bite and scratch wounds
• soap and water
• and/or 2 benzalkonium chloride
• or povidone/iodine solution for at least 10
  minutes
• Administer human rabies immune globulin (20
  IU/kg)
• as much of the dose as possible infiltrated in
  and around the wound (if wound location allows)
• the rest INTRAMUSCULARLY in the gluteal region
• Equine rabies immunoglobulin may be available ?
  beware of serum sickness and anaphylaxis!

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Treatment
Rabies

• For the human patients
• Wound care as needed, debridement, antibiotic
  administration if needed
• Measures to prevent bacterial infection when
  warranted also are indicated
• Check tetanus status ? Tetanus prophylaxis if
  indicated
• Decision regarding postexposure prophylaxis

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Treatment
Rabies

• For the suspected animals
• Determine rabies immune status of the biting
  animal
• Determine the nature of the interaction
• Uncommon animal behavior
• Provoked attacks are less likely due to rabies
• Quarantine, etc

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Vaccine
Rabies

• Available vaccines
• human diploid cell vaccine (HDCV) ? for I.D.
• rabies vaccine adsorbed (RVA) ? I.M.
• Purified chick embryo cell vaccine ? I.M.
• Immunity lasting approximately 2 years

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Prevention
Rabies

• Prophylaxis is recommended for any routine
  contact with animals at risk.
• Intact skin contact with urine, blood, or feces
  of an animal has not been shown to constitute
  exposure, except in bats
• High risk groups
• Veterinarian
• Rabies diagnostic lab. staff
• Animal handlers
• Wildlife officers
• Any person who lives in (or travel to) endemic
  area

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Prevention
Rabies

• Human rabies immune globulin and vaccine are
  recommended for bites and exposures
• regardless of the period between exposure and
  treatment
• unless the individual is previously vaccinated
  and rabies antibodies can be detected
• Postexposure prophylaxis
• Dosage 1mL IM
• in deltoid or upper outer thigh in infants.
• The 5-dose schedule is as follows
• day 0
• day 3
• day 7
• day 14
• day 28

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Prevention
Rabies

• Factors to be considered before PEP
• Is it an open wound?
• Nature of bites
• provoked bites are less likely to require
  prophylaxis
• Presence of rabies in the locality
• History of vaccination
• Bats?
• PEP is recommended in any contact with bats
• Even in the absence of a bite or scratch

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Prevention
Rabies

• Rabies control
• Notification of cases and destruction of animals
  with signs or bitten by suspected rabid animals
• Quarantine pets that have bitten people
• Mass immunization
• Pets registration

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Poliomyelitis
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Introduction
Poliomyelitis

• Enteroviral infection
• genus enterovirus, family picornaviridae
• 3 types
• Multiplication in GI tract, but are particularly
  neurotropic
• 4 different forms of manifestation
• inapparent infection (90-95)
• abortive poliomyelitis
• nonparalytic poliomyelitis
• paralytic poliomyelitis

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Introduction
Poliomyelitis

• Aggressive immunization programs ? significant ?
  of worldwide prevalence
• Indonesia??
• Mortality more frequently in paralytic form ?
  associated with complications such as respiratory
  failure

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Clinical Presentation
Poliomyelitis

• Inapparent infection and abortive polio
• Nonspecific symptoms, usually resolve within a
  few days (less than 5 days)
• Fever
• Headache
• Nausea
• Vomiting
• Abdominal pain
• Oropharyngeal hyperemia
• Normal neurological examination

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Clinical Presentation
Poliomyelitis

• Nonparalytic poliomyelitis
• Symptoms described above
• AND
• Nuchal rigidity
• More severe headache
• Back and lower extremity pain
• Meningitis with lymphocytic pleocytosis (usually)
  

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Clinical Presentation
Poliomyelitis

• Paralytic poliomyelitis
• Compromise of the motor neurons may be localized
  or widespread
• Frequent finding asymmetric loss of muscle
  function
• involvement of major muscle groups
• Muscle atrophy several weeks later
• Recovery may be complete, partial, or absent
• May involve spinal muscles only
• in more severe form, bulbar involvement

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Clinical Presentation
Poliomyelitis

• Postpoliomyelitis syndrome
• weakness or fatigue involving groups of muscles
  that were initially affected
• May last long

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Diagnostics
Poliomyelitis

• Viral cultures from CSF, stool, and throat
• Acute and convalescent serum for antibody
  concentrations against the 3 polioviruses.
• Confirms the diagnosis if
• IgG titers increase 4 folds
• Positive IgM titer during the acute stage

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Treatment
Poliomyelitis

• Medical Care
• No antivirals are effective
• Treatment is MAINLY supportive
• Analgetics for headache/pain
• Laxative for fecal impaction
• Mechanical ventilation
• For patients with bulbar paralysis

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Treatment
Poliomyelitis

• Tracheostomy if needed
• Catheterization if needed
• Physical therapy (in paralytic form)
• Frequent mobilization to avoid development of
  chronic decubitus ulcerations
• Active and passive motion exercises during the
  convalescent stage

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Prevention
Poliomyelitis

• Oral attenuated poliovirus vaccine
• Has been used since early 1960s
• Major disadvantage vaccine-associated paralytic
  poliomyelitis (VAPP)
• Although attenuated, the virus may occasionally
  become neurotropic ? wild-type virus infection
• Schedule
• 2, 4, and 6 months of age
• PLUS a booster at age 4 years
• A new monovalent oral poliovirus type 1 vaccine
  (mOPV1) was introduced in India in April 2005
• Targeted to eliminate some of the last poliovirus
  reservoirs

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Prognosis
Poliomyelitis

• Bulbar paralytic poliomyelitis
• is associated with the highest rate of
  complications
• mortality rate is as high as 60
• Spinal poliomyelitis less fatal
• Inapparent or abortive poliomyelitis recover
  without significant sequelae

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Prion-related diseases
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Introduction
Prion

• Large group of related neurodegenerative
  conditions
• Affect both animals and humans
• Includes
• Creutzfeldt-Jakob disease (CJD) ? human
• Gerstmann-Sträussler-Scheinker (GSS) ? human
• Bovine spongiform encephalopathy (BSE, or "mad
  cow disease") ? cattle
• Chronic wasting disease (CWD) ? mule deer and elk
• Scrapie ? sheep

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Introduction
Prion

• Prion protein
• abnormal conformation of a host-encoded
  glycoprotein
• can be inherited
• can be transmitted
• can infect normal surroundings
• Long incubation periods
• Once clinical symptoms begin ? rapidly
  progressive
• All prion diseases are fatal
• No effective form of treatment currently

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Introduction
Prion

• 1st description of scrapie ? over 250 years ago
• Manifestation
• Hyperexcitability
• Itching
• Ataxia
• Paralysis ? death
• First transmission was demonstrated in 1943
  within a population of Scottish sheep that was
  accidentally inoculated against a common virus
  using a formalin extract of lymphoid tissue from
  an animal with scrapie

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Pathophysiology
Prion

• Unifying feature
• Similar neuronal loss, gliosis, and
  characteristic spongiform change in the gray
  matter of the CNS
• Amyloid plaques in many of these conditions
• In 10 of patients with CJD amyloid in the
  cerebellum or in the cerebral hemispheres
• In all cases of GSS multicentric cerebellar
  plaques
• Different immunoreactivity with amyloid plaque in
  Alzheimer disease

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Route of Transmission
Prion

• Route of transmission is not clear yet
• Lymphoid organs are believed to be involved in
  the early stages of prion diseases
• Hematogenic spread of prions to the CNS is also
  suggested
• Three cases of vCJD infection associated with
  blood transfusion have also been observed
• Other studies have implicated the distinct CD11c
  dendritic cell population in prion neuroinvasion
• Prions can also reach the brain via the
  parasympathetic vagus nerve

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Epidemiology
Prion

• Mortality/morbidity
• Relentlessly progressive and invariably lead to
  death
• Mean duration of illness
• sporadic CJD 8 months
• vCJD 14 months
• Familial CJD 26 months
• GSS 60 months

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Epidemiology
Prion

• Sex
• No sex preponderance
• Mean age of onset
• Sporadic CJD 62 years
• vCJD 28 years
• Familial CJD, GSS 45-49 years

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Clinical Presentation
Prion

• (sporadic) Creutzfeldt-Jakob disease
• Rapidly progressive multifocal neurological
  dysfunction
• Myoclonic jerks involving either the entire body
  or a limb
• Spontaneous or precipitated by auditory or
  tactile stimuli
• Cerebellar dysfunction also occurs.
• Global severe cognitive impairment in terminal
  stage
• Death in about 8 months.
• Definite, probable and possible CJD

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Diagnostics
Prion

• Initial workup laboratory tests as for dementia
• Rule out other conditions
• toxic and/or metabolic condition that can cause
  dementia
• paraneoplastic syndrome
• Imaging Studies
• MRI is the most important
• PET
• Contrast CT-scan of the chest, abdomen, pelvis to
  rule out malignancy
• EEG
• Characteristic finding periodic or
  pseudoperiodic paroxysms of sharp waves or spikes
  on a slow background

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Diagnostics
Prion

• Lumbar puncture (LP) in all suspected cases
• Check the opening pressure
• cell count, protein, glucose, bacterial cultures,
  viral cultures, VDRL, cryptococcal antigen, and
  acid-fast bacilli (AFB)
• CSF findings
• typically normal in sporadic CJD
• CSF protein may be elevated slightly (never gt100
  mg/dL)
• Patognomonic 14-3-3 protein
• Brain biopsy

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Treatment
Prion

• Medical Care
• Discontinue any medication that could impair
  memory or cause confusion
• Therapeutic interventions are under current
  development
• Consultations
• Neurologist
• Infectious disease specialist
• Diet No dietary restrictions are necessary
• Activity Activity is unrestricted

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Prevention
Prion

• Prion diseases may spread by iatrogenic means
• ? not to reuse EEG and/or electromyography (EMG)
  needles, surgical instruments, and other tools
  that have been exposed to a patient with prion
  disease
• Prion agent is remarkably resistant to
  inactivation ? routine sterilization procedures,
  such as autoclaving, are ineffective

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Prognosis
Prion

• The prionoses are rapidly progressive
• Median survival duration (time from diagnosis to
  death)
• 8 months in sporadic CJD
• 60 months in GSS
• Patients with familial prion-related disease tend
  to have a longer course than those with sporadic
  disease

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