Transcript Rabies Poliomyelitis Prion Disease

Rabies
Poliomyelitis
Prion Disease
Nani Kurniani, dr., SpS(K)
Dept. of Neurology
Hasan Sadikin Hospital
Bandung
Introduction
• Is a zoonosis  encephalitis
• Infect mammals (dogs, bats, wild
carnivores)
• Public Health problem
• Etiology: Lyssavirus – 4 serotypes
– family rhabdoviridae
• Preventable
• Curable?
Rabies
Introduction
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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
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
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
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
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
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
Clinical
• Neurologic stage (2-7 days)
– Aphasia
– Incoordination
– Paresis
– Paralysis
– Mental status changes
– Hyperactivity
Rabies
Clinical
Rabies
• Late symptoms
– Hypotension
– Coma
– Disseminated intravascular coagulation (DIC)
– Cardiac arrhythmias
– Cardiac arrest
– Fatality
Clinical
• Physical findings:
– High fever with rapidly progressive
encephalitis
– Myoclonus
– Increased lacrimation
– Hypersalivation
– Agitation
– Anxiety
Rabies
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)
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
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!
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
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
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
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:
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Veterinarian
Rabies diagnostic lab. staff
Animal handlers
Wildlife officers
Any person who lives in (or travel to) endemic area
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:
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day 0
day 3
day 7
day 14
day 28
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
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
Poliomyelitis
Introduction
Poliomyelitis
• Enteroviral infection
– genus enterovirus, family picornaviridae
– 3 types
• Multiplication in GI tract, but are particularly
neurotropic
• 4 different forms of manifestation:
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inapparent infection (90-95%)
abortive poliomyelitis
nonparalytic poliomyelitis
paralytic poliomyelitis
Introduction
Poliomyelitis
• Aggressive immunization programs 
significant ↓ of worldwide prevalence
• Indonesia??
• Mortality: more frequently in paralytic form
 associated with complications such as
respiratory failure
Clinical Presentation
Poliomyelitis
• Inapparent infection and abortive polio
– Nonspecific symptoms, usually resolve within
a few days (less than 5 days):
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Fever
Headache
Nausea
Vomiting
Abdominal pain
Oropharyngeal hyperemia
– Normal neurological examination
Clinical Presentation
Poliomyelitis
• Nonparalytic poliomyelitis
– Symptoms described above
AND
– Nuchal rigidity
– More severe headache
– Back and lower extremity pain
– Meningitis with lymphocytic pleocytosis
(usually)
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
Clinical Presentation
Poliomyelitis
• Postpoliomyelitis syndrome
– weakness or fatigue involving groups of
muscles that were initially affected
– May last long
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
Treatment
• 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
Poliomyelitis
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
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
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
Prion-related diseases
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
Introduction
• 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
Prion
Introduction
Prion
• 1st description of scrapie  over 250 years ago
• Manifestation:
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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
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
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
Prion
Epidemiology
• Mortality/morbidity:
– Relentlessly progressive and invariably
lead to death
– Mean duration of illness:
• sporadic CJD
• vCJD
• Familial CJD
• GSS
8 months
14 months
26 months
60 months
Prion
Epidemiology
• Sex:
– No sex preponderance
• Mean age of onset:
– Sporadic CJD
– vCJD
– Familial CJD, GSS
62 years
28 years
45-49 years
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
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Cerebellar dysfunction also occurs.
Global severe cognitive impairment in terminal stage
Death in about 8 months.
Definite, probable and possible CJD
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
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 >100 mg/dL)
– Patognomonic: 14-3-3 protein
• Brain biopsy
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
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
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