Rabies Poliomyelitis Prion Disease

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

2. Introduction Rabies • Is a zoonosis  encephalitis • Infect mammals (dogs, bats, wild carnivores) • Public Health problem • Etiology: Lyssavirus – 4 serotypes • family rhabdoviridae • Preventable • Curable?

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

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

10. Clinical Rabies • Late symptoms • Hypotension • Coma • Disseminated intravascular coagulation (DIC) • Cardiac arrhythmias • Cardiac arrest • Fatality

11. Clinical Rabies • Physical findings: • High fever with rapidly progressive encephalitis • Myoclonus • Increased lacrimation • Hypersalivation • Agitation • Anxiety

12. 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)

13. 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

14. 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!

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Poliomyelitis

23. 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

24. Introduction Poliomyelitis • Aggressive immunization programs  significant ↓ of worldwide prevalence • Indonesia?? • Mortality: more frequently in paralytic form  associated with complications such as respiratory failure

25. 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

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

27. 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

28. Clinical Presentation Poliomyelitis • Postpoliomyelitis syndrome • weakness or fatigue involving groups of muscles that were initially affected • May last long

29. 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

30. 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

31. 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

32. 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

33. 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

34. Prion-related diseases

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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