Neurotropic Viral Infections

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Definitions:
Neurotropic

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can replicate in one or more cell types in CNS

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Neurovirulent

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can cause pathological effect in CNS

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Neuroinvasive

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Can infect CNS from a peripheral site or after establishing infection at an extraneural site

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Encephalitis

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Inflammation of brain and SC

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Meningitis

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Inflammation of membranes of brain and SC

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How does Encephalitis present?

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Acute onset
Febrile
HA
ALtered consciousness
Disorientation
Behavior/Speech disturbances
Neurologic Signs

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What Neurologic Signs are associated with Encephalitis

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Hemiparesis
Seizures
Cranial Nerve Palsies

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Most common causes of Encephalitis in the US vs WW

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US: ~10% herpes
WW: Rabies, Measles, and Jap B

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What is an Arbovirus?

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Virus belonging to several RNA familes using arthropod vectors (usually skeeters, but ticks too)

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Which virus families are arboviruses?

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***Flaviridae
***Togaviridae
Bunyaviridae
Reoviridae

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Types of Flaviridae encephalitis?

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Japanese Encephalitis
St. Louis "
West Nile "
Tick Borne "

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Types of Togaviridae Encephalitis?

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EEE
WEE
VEE

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Which tick borne virus is the only one in the US?

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the colorado tick fever

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Types of pathogenesis of Encephalitis and examples

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Hematogenous: entero and arboviruses

Neuronal:
Rabies, Herpes

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Where does the initiation of the infection that leads to encephalitis normally occur?

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Non-Neural Tissue

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What are the amplifying animals for arboviruses?

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brids
rodents
pigs
bats`

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Who are the dead end hosts?

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humans
domestic-animals

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When do most cases of arbovirus infections occur?

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June-September

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How do the majority of arbovirus infections present?

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asymptomatic, so they don't present

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Where is virus shed in skeeters?

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Salivary glands

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Rx for viral infections?

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No anti-viral Rx
Treat Sx's

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Vaccines for viral infections?

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No FDA approved ones for US viruses
There is a vaccine for Jap E and European Tick Born E
Horse vaccine for EEE, WEE, VEE

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Prevention of viral infections?

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Personal Protective measures
Public Health Measures

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Who are the Flaviviruses?

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SKEETERS
Jap E
St. Louis
West Nile

TICKS
Central European E
Louping Ill
RSSE
Powassan

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Japanese Encephalitis Virus\
Sx's?

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Similar to SLE

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Japanese Encephalitis Virus
Incubation?

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6-16 days

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Japanese Encephalitis Virus
World incidence?

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30-50,000 per year in asia

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Japanese Encephalitis Virus
morbidity and mortality?

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Highest global rates

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Japanese Encephalitis Virus
Geography

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Japan
SE Asia
Korea
Philipines

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Japanese Encephalitis Virus
environmental links?

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Deforestation
Agriculture
Irrigation

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Amplifiers of JE?

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Birds
Pigs

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Japanese Encephalitis Virus
Age/demographics?

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Very young
Very Old
Men>Women

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Unique Sx?

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GI in some pts

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Japanese Encephalitis Virus
Dx?

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ELISA

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Japanese Encephalitis Virus
Mortality

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7-50%

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Japanese Encephalitis Virus
Sequelae?

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30-70%

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St. Louis Encephalitis
Sx's

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aseptic meningitis/encephalitis
Most cases Mild or Asymptomatic

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St. Louis Encephalitis
Deaths?

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2% of kids
22% of elderly

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St. Louis Encephalitis
Rx?

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No Vaccine
No effective therepeutic Drug

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St. Louis Encephalitis
animal host?

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birds

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St. Louis Encephalitis
Unique Ft?

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Dysuria

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St. Louis Encephalitis
mortality

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2-20% (worse in elderly)

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St. Louis Encephalitis
sequelae?

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25%

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West Nile Virus
Cycle of hosts?

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Bird
Skeeter
Bird

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West Nile Virus
who else besides humans may get this?

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Horses

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Transmission of WNV

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Mostly Skeeters
Transfused blood, platelets, FFP
Transplants
Transplacental
Occupational (percutaneous)
Breast Milk??

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West Nile Virus
Demographics

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Older adults, F>M

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West Nile Virus
Unique Fts

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Flu-like illness followed by flaccid paralysis, seizures, ALOC

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West Nile Virus
mortality?

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1-2%

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West Nile Virus
Sequelae?

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25%

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West Nile Virus
% symptomatic?

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20% symptomatic
80% asymptomatic

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West Nile Virus
Clinical Manifestations

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1. WN Fever=self-limited
accompanied by HA, myalgia, rash, GI sx's, eye and abd pain
2. Neuroinvasive WN
Meningoencephalitis
HA
N&V
Confusion
Acute Paralysis
Movement Disorder Syndrome: tremors, myoclonus

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West Nile Virus
Dx

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1. CSF analysis: lymphocytic pleocytosis w/ elevated protein
2. Head CT/MRI: may show meningeal enhancement and parenchymal abnormalities
3. IgM in serum/CSF
4. PCR for viral Ag or nucleic acid in CSF, blood, tissues

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West Nile Virus
Rx?

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supportive

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Who are three Flaviviruses not normally associated with encephalitis?

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Dengue Virus
Yellow Fever Virus
Hep C

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Who is the subclass of Togaviridae we need to know and who is in it?

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Alphavirus Family
EEE
WEE
VEE

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Which one of the Togaviridae's is the baddest?

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EEE...high mortality

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EEE
Ages?

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Young or Old

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EEE
Unique Features?

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WBC in CSF > 1000 (lots)

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EEE
Mortality?

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50-70%

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EEE
Sequelae?

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80% (esp in kids)

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WEE
Ages?

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infants and older adults

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WEE
Mortality

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5-15%

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WEE
sequelae?

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moderate in infants
low in others

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Both EEE and WEE
Rx?

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No Vaccine
No Effective Therapeutic Drug

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VEE
Rx?

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Vaccine is available

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VEE
Unique Feature?

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can be transmitted by aerosol

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What about the Bunyaviruses?

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California and La Crosse
Majority Subclinical

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Who is the Rhabdovirus I need to know?

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RABIES

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Main Rabies Vector WW?

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Dogs

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Main Rabies Vector in US?

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Racoons, Foxes

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Which animal is somewhat immune to the effects of Rabies?

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BATS!

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What seems to be the main culprit of US rabies cases? (or at least a heavy hitter)

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BATS!

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Besides an animal bite, how else might one get Rabies?

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ORGAN TRANSPLANT

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Disease Process of Rabies?

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Centripetal Spread from entry site to CNS
Centrifugal spread from CNS along nerves to tissues

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Rabies' Incubation Period?

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30 days --> 1 year

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What the Prodrome of Rabies like?

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2-10 days
Paresthesias or pain at wound site
Fever
Malaise
N&V
Anorexia

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how long does it take rabies to kill you?

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0-14 days

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Rabies Dx?

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NEGRI BODIES
Encephalitis and myelitis w/ perivascular infiltration

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What are negri bodies?

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Eosinophilic inclusions seen on light microscopy (capsid proteins)

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Rabies Rx?

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PEP=Post-Exposure Prophylaxis

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What does PEP include?

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1. Thorough Disinfection of wound
2. One Rabies Immune Globulin (RIG) dose at site distant from vaccine inoculation
3. 5 scheduled doses of inactivated vaccine

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Which animals do not transmit Rabies?

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Rodents
Rabbits

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Why is Rabies an expensive disease?

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over 18,000 people a year get PEP

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Who are the Paramyxoviruses?

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Mumps
Measles

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Measles
rate of encephalitis?

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1 in 1000

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Measles
Mortality

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10-15%

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Measles
Sequelae

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40%

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What is a future complication of Measles?

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SSPE
Subactute Sclerosing PanEncephalitis

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Rx for measles and mumps?

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VACCINE!