Viral CNS infections Flashcards
What is encephalitis and how is it different from meningitis? What are some symptoms?
inflammation of the brain itself - meningitis symptoms + mental status changes
seizures, decreased consciousness, confusion
What is myelitis?
focal neurological signs localized to spinal cord
- inflammation of the white/grey matter of the spinal cord
What are some results from a CSF sample that would indicate that you have a viral meningitis case? (4)
- Gram stain negative
- Lymphocytic pleocytosis (increase) (WBC 100 to 1,000)
- Occasionally increased red blood cells (RBC) (ex: HSV)
- Increased protein, normal glucose
What is the typical presentation of a viral meningitis infection?
- typically acute (except with rabies but that’s more encephalitis)
- healthy people are affected but it is more common in immunocompromised individuals
- Frequently occurs as meningoencephalitis
What is meningoencephalitis?
condition that simultaneously resembles both meningitis and encephalitis
What are 4 main viral causes of CNS infections?
- Enterovirus
- HSV-1 and HSV-2
- Arbovirus
- Rabies
What are 4 (less common) viral causes of CNS infections
- Other herpes viruses like EBV, VZV, CMV
- Measles virus
- Lymphocytic choriomeningitis virus (LCMV)
- Human immunodeficiency virus (HIV)
What family does Enterovirus belong to? what are 2 other members of this family?
Picornaviridae
Other members: rhinovirus and hepatitis A
What is the genome/structure of Enterovirus
ssRNA (+ sense) and non enveloped
What kind of virus is enterovirus
A respiratory virus
What % of viral meningitis is caused by Enterovirus?
30-50%
What are the typical clinical manifestations of a CNS infection by Enterovirus? How long? Is the infection widespread or tissue localized?
Usually respiratory symptoms with severe headaches and photophobia that can last for over a week
Can infect lots of different tissues
are there antivirals/ a vaccine for Enterovirus?
no
What are the steps of diagnosing someone with a CNS infection with Enterovirus?
- Clinical suspicion/epidemiology
- CSF specimen profile (normal glucose and high protein)
- do RT-PCR on the CSF specimen
What is the treatment for someone with a CNS infection with Enterovirus?
just symptom management - pain control and hydration
What family of virus do HSV-1 and HSV-2 belong to?
Herpesviridae
What type of genome/structure do HSV1 and 2 have?
dsDNA and enveloped
HSV-1 and HSV-2 are the most common cause of..?
sporadic viral encephalitis in North America
do HSV 1 and 2 show seasonal distribution?
no, sporadic
What is the mortality rate of encephalitis infections with HSV (without treatment)
high, around 70%
What is most commonly the cause of the encephalitis pathogenicity of HSV?
not usually the primary exposure (mucocutaneous, oral/genital) but reactivation (from latency in sensory ganglion)
What are some symptoms of HSV caused encephalitis? (4)
- Fever/headache
- Neurological changes/ focal symptoms (ie. temporal lobe will light up on examination)
- Seizures and mental status changes frequent
- Long-term neurological sequelae possible
What can result in a fatal dissemination of HSV throughout the body?
Immunodeficiency
Temporal lobe activation on an MRI is consistent with…
HSV encephalitis
Where does HSV establish a latent/dormant stage?
in the trigeminal ganglion
At what stage: primary infection, latency, and reactivation, is a CNS infection likely to occur?
Reactivation
HSV-2 (genital herpes) establishes a latent infection where?
in the dorsal root ganglia
How does HSV-2 cause encephalitis?
Because the dorsal root ganglia are so closely associated with the spinal cord, HSV can infect there and travel up to the brain
What are some rough diagnostic steps in determining a CNS infection with HSV?
- Clinical suspicions
- Diagnostic imaging –> MRI looking for temporal lobe activation
- CSF profile
- PCR of the CSF
What is useless in terms of tests for determining a CNS infection with HSV? why?
Serology because the patient will already have circulating antibody from the initial infection
What would the CSF profile of someone with an HSV CNS infection look like? (what 3 things is it high in)
High lymphocytes, increased RBCs common, high protein
What is the treatment for a suspected HSV CNS infection?
antivirals (acyclovir)
- given empirically if infection suspected
What is the first step in the activation of acyclovir?
Phosphorylation by viral kinase ( thymidine kinase)
What are the next two activation steps of acyclovir? what does them? what is the end product?
phosphorylation by two host kinases, end product is a triphosphate (nucleotide analogue).
What happens once the acyclovir is in the active form?
incorporated into the growing nucleic acid and halts elongation process
What are two points of resistance that viruses can develop to acyclovir?
HSV thymidine kinase or HSV DNA polymerase mutations
What are two alternate drugs to acyclovir? why is either of them used?
- cidofovir (TK not required)
2. foscarnet (pyrophosphate analog)
What does Arbovirus mean?
arthropod borne virus
What are two major vectors of arboviruses?
Mosquitos and ticks
How many registered arboviruses are there? how many of them are human pathogens?
over 500 registered
over 130 are pathogenic to humans
What is a vector?
biting insect or tick (usually) that transmits a disease/parasite from one animal to another
How many virus families are there in the Arboviruses?
6
What were the 3 families of arboviruses we mentioned in lecture? What type of genome do they each have?
- Flaviviruses (ssRNA +)
- Togaviruses (ssRNA -)
- Bunyaviruses (ssRNA -)
What are 6 important members of the Flavivirus family?
Zika, Dengue fever, Yellow Fever, West Nile, St. Louis encephalitis, Japanese encephalitis virus
What are 3 important members of the Togavirus family?
- Eastern equine encephalitis virus (EEE)
- Western equine encephalitis virus (WEE)
- Chikungunya virus
What are 2 important members of the Bunyavirus family?
La Cross Virus
Rift Valley Fever Virus
What 4 arboviruses cause Encephalitis in humans ?
West Nile virus (WNV)
Japanese encephalitis virus
Eastern equine encephalitis virus
La Crosse virus
What are 2 primary symptoms/clinical manifestations of an Arbovirus infection
- typically starts of with vague “viral syndrome”
2. Can progress to fever, headache, seizures
What kind of CNS inflammation is common with Arboviruses?
Typically presents as a meningoencephalitis
What impacts the severity and incidence of arbovirus CNS infection?
depends on both the virus and the host
What kind of distribution do arboviruses have? What controls this?
Both seasonal and geographical
Based on distribution of both host and reservoir
What is a reservoir?
An organism or population that directly or indirectly transmits a pathogen while being virtually immune to its effects
During what season do you tend to see high instances of arbovirus infection?
Seasons with lots of rain b/c more rain = more mosquitos
In the Epidemic (or urban) cycle, who acts as the reservoir?
humans
In the Epidemic (or urban) cycle, who acts as the vector? What are 2 examples of viruses
mosquito: A. aegypti for dengue and yellow fevers
In the Ezoonotic (sylvatic or jungle cycle), who acts as the reservoir?
tend to be a vertebrate - harbours the virus with no ill effects
In the Ezoonotic (sylvatic or jungle cycle), who acts as the vector? What effect does this have?
Mosquito: A. aegypti
tends to amplify the virus as the reservoir hosts are not affected
In the Ezoonotic cycle, how do humans fit in?
Incidental hosts
When humans are acting as incidental hosts, can there be human to human spread? Can it be passed to vectors again?
No person-to-person spread
Viremia not sufficient in humans to be picked up by the insect vectors
What is an example of a virus spread through an ezoonotic cycle?
West nile virus
What is the reservoir for WNV?
birds
In the Epizoonitic (rural) cycle, who acts as the reservoir?
wild birds
In the Epizoonitic (rural) cycle, who acts as the vector?
Culex sp. mosquito
In the Epizoonitic (rural) cycle, where is the virus normally being passed between?
Between the domestic animals and the vector
in the Epizoonotic cycle, where do outbreaks normally occur?
in the animals
In the Epizoonotic cycle, who acts as the amplifying host?
humans
What are 3 examples of viruses spread through an Epizoonotic cycle?
- Japanese Encephalitis Virus (JEV)
- Western Encephalitis Virus (WEV)
- St. Louis Encephalitis Virus
What 3 factors are considered in making a diagnosis of an arbovirus infection? What testing can be useful?
- Clinical suspicion - social history/exposure/travel
- CSF profile
- CSF PCR and serology can be useful
What would be expected from a CSF sample of someone infected with an arbovirus?
High WBC count and high protein
What treatment is given to someone with an arbovirus CNS infection?
Largely supportive, pretty much always fatal
What two arboviruses are there vaccines for? what type of vaccine are they?
- JEV - inactivated vaccine
2. Yellow Fever Virus - live attenuated
What are two forms of more large scale prevention of arboviruses?
- Control of vector (mosquito)
2. Personal protection: Insect repellent/nets/clothing
What family of viruses does Rabies belong to? What type of genome and structure does it have?
Family: Rhabdoviridae
Large enveloped virus, ssRNA (-)
Rabies is most common in…?
developing nations - poor rural communities, mostly in Africa and Asia
What is the mode of transmission of rabies
Through the bite of an infected animal, the virus is in the saliva
What are common vectors of Rabies in North America
bats, skunks, raccoons, and foxes
What is a behavioural trait of rabies infected animals?
Show no fear to humans, act very agitated
Also are scared of water
What does rabies virus have a high affinity for? What is the term for this ?
neurotropic – has affinity for nerve cells or tissue
What tissues are infected following an bite from a rabid animal ?
brain (eventually), salivary glands and sensory nerves to skin are infected
What is the progression of Rabies virus like in humans?
Long incubation period (weeks)
Temporal pattern of presentation
- ie. time it takes to develop severe neurological symptoms will be dependent on how far away the bite site is from the brain
What are 4 symptoms of a rabies infection?
- Fever
- Agitation
- Hydrophobia = fear of water
- Painful spasms followed by excessive saliva
Where is the best place to take a biopsy for a rabies test?
the skin at the back of the neck
What two types of tests are done on rabies test specimens?
PCR and DFA
When is serology useful for rabies testing?
to test and see if someone is immune or not
What is the treatment for a suspected rabies infection?
washing of the wound site and injection of preformed anti-rabies antibodies
