RabiesPoliomyelitisPrion Disease

Nani Kurniani, dr., SpS(K)Dept. of NeurologyHasan Sadikin HospitalBandung

Introduction

• Is a zoonosis encephalitis

• Infect mammals (dogs, bats, wild carnivores)

• Public Health problem

• Etiology: Lyssavirus – 4 serotypes – family rhabdoviridae

• Preventable

• Curable?

Rabies

Introduction

• 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

Rabies

Pathogenesis

• 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

Rabies

Pathogenesis

• 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

Rabies

Pathogenesis

• 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

Rabies

Clinical

• 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

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

RabiesClinical

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

RabiesClinical

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

RabiesClinical

Clinical

• Physical findings: – High fever with rapidly progressive

encephalitis – Myoclonus – Increased lacrimation – Hypersalivation – Agitation – Anxiety

Rabies

Clinical Presentation

• 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)

Rabies

Diagnostics

• 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

Rabies

Treatment

• 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!

Rabies

Treatment

• 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

Rabies

Treatment

• 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

Rabies

Vaccine

• 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

Rabies

Prevention

• 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

Rabies

Prevention

• 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

Rabies

Prevention

• 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

Rabies

Prevention

• 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

Rabies

Poliomyelitis

Introduction

• 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

Poliomyelitis

Introduction

• Aggressive immunization programs significant ↓ of worldwide prevalence

• Indonesia??

• Mortality: more frequently in paralytic form associated with complications such as respiratory failure

Poliomyelitis

Clinical Presentation

• 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

Poliomyelitis

Clinical Presentation

• Nonparalytic poliomyelitis– Symptoms described above

AND – Nuchal rigidity – More severe headache – Back and lower extremity pain – Meningitis with lymphocytic pleocytosis

(usually)

Poliomyelitis

Clinical Presentation

• 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

Poliomyelitis

Clinical Presentation

• Postpoliomyelitis syndrome– weakness or fatigue involving groups of

muscles that were initially affected– May last long

Poliomyelitis

Diagnostics

• 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

Poliomyelitis

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

• 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

Poliomyelitis

Prevention

• 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

Poliomyelitis

Prognosis

• 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

Poliomyelitis

Prion-related diseases

Introduction

• 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

Prion

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

• 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

Prion

Pathophysiology

• 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

Prion

Route of Transmission

• 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 8 months • vCJD 14 months• Familial CJD 26 months• GSS 60 months

Prion

Epidemiology

• Sex: – No sex preponderance

• Mean age of onset: – Sporadic CJD 62 years– vCJD 28 years – Familial CJD, GSS 45-49 years

Prion

Clinical Presentation

• (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

Prion

Diagnostics

• 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

Prion

Diagnostics

• 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

Prion

Treatment

• 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

Prion

Prevention

• 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

Prion

Prognosis

• 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

Prion