Agents of Encephalitis

Encephalitis, or inflammation of the brain, can be caused by a variety of infectious agents, including viruses. Arboviruses (arthropod-borne viruses) are a significant cause of encephalitis worldwide, transmitted primarily through the bites of infected mosquitoes and ticks. This section will review the serodiagnosis, epidemiology, and vectors of transmission for some key agents of encephalitis, with a focus on West Nile virus and other arboviruses

General Principles of Arboviral Encephalitis

Arboviruses: A diverse group of viruses transmitted by arthropods (primarily mosquitoes and ticks)
Transmission Cycle: Typically involves a vertebrate reservoir host (e.g., birds, rodents) and an arthropod vector. Humans are often incidental or dead-end hosts
Clinical Manifestations: Range from asymptomatic infection to mild febrile illness to severe encephalitis or meningitis
Diagnosis: Often relies on serological testing to detect antibodies against the virus
Prevention: Vector control measures (e.g., mosquito spraying, personal protective measures) are key

West Nile Virus (WNV)

Serodiagnosis
- WNV IgM: Indicates recent WNV infection. Can persist for several months
- WNV IgG: Indicates past WNV infection. Can cross-react with other flaviviruses (e.g., Zika, dengue)
- Plaque Reduction Neutralization Test (PRNT): A more specific test to confirm WNV infection and differentiate it from other flaviviruses
Clinical Significance
- Most WNV infections are asymptomatic
- Symptomatic infections can cause West Nile fever (fever, headache, fatigue) or neuroinvasive disease (encephalitis, meningitis, paralysis)
- Risk of neuroinvasive disease increases with age and immunocompromising conditions
Epidemiology
- Transmission: Mosquitoes (primarily Culex species)
- Reservoir hosts: Birds
- Geographic distribution: Widespread in North America, Europe, Africa, and Asia
- Seasonality: Peak incidence during summer and fall months when mosquito populations are highest
Vectors of Transmission
- Culex mosquitoes (e.g., Culex pipiens, Culex quinquefasciatus) are the primary vectors

St. Louis Encephalitis Virus (SLEV)

Serodiagnosis
- SLEV IgM: Indicates recent SLEV infection
- SLEV IgG: Indicates past SLEV infection. Can cross-react with other flaviviruses
- Plaque Reduction Neutralization Test (PRNT): Used to confirm SLEV infection and differentiate it from other flaviviruses
Clinical Significance
- Most SLEV infections are asymptomatic
- Symptomatic infections can cause St. Louis encephalitis (fever, headache, stiff neck, altered mental status)
- Risk of severe disease increases with age
Epidemiology
- Transmission: Mosquitoes (primarily Culex species)
- Reservoir hosts: Birds
- Geographic distribution: Primarily in North America (especially the central and eastern United States)
- Seasonality: Peak incidence during summer and fall months
Vectors of Transmission
- Culex mosquitoes (e.g., Culex pipiens, Culex quinquefasciatus) are the primary vectors

La Crosse Virus (LACV)

Serodiagnosis
- LACV IgM: Indicates recent LACV infection
- LACV IgG: Indicates past LACV infection
Clinical Significance
- LACV causes La Crosse encephalitis, primarily in children
- Symptoms include fever, headache, nausea, vomiting, and neurological complications (seizures, coma)
Epidemiology
- Transmission: Mosquitoes (primarily Aedes triseriatus)
- Reservoir hosts: Chipmunks and squirrels
- Geographic distribution: Primarily in the midwestern and eastern United States
- Seasonality: Peak incidence during summer and early fall months
Vectors of Transmission
- Aedes triseriatus (Eastern Treehole Mosquito) is the primary vector

California Encephalitis Virus (CEV) Group

Includes: La Crosse virus (LACV), Jamestown Canyon virus (JCV), Snowshoe hare virus (SSHV), and others
Serodiagnosis: Serological tests can detect antibodies to CEV group viruses, but cross-reactivity can occur. Specific identification may require neutralization assays
Clinical Significance: Causes encephalitis, meningitis, and febrile illnesses
Epidemiology: Geographic distribution varies depending on the specific virus within the group
Vectors of Transmission: Mosquitoes (various Aedes, Culex, and Culiseta species)

Eastern Equine Encephalitis Virus (EEEV)

Serodiagnosis
- EEEV IgM: Indicates recent EEEV infection
- EEEV IgG: Indicates past EEEV infection
Clinical Significance
- EEEV causes Eastern equine encephalitis, a severe and often fatal disease
- Symptoms include fever, headache, stiff neck, seizures, and coma
- High mortality rate and significant neurological sequelae in survivors
Epidemiology
- Transmission: Mosquitoes (primarily Culiseta melanura)
- Reservoir hosts: Birds
- Geographic distribution: Primarily in the eastern United States, along the Gulf Coast, and in parts of Canada and South America
- Seasonality: Peak incidence during summer and early fall months
Vectors of Transmission
- Culiseta melanura is the primary enzootic vector (maintains the virus in bird populations)
- Bridge vectors (e.g., Aedes sollicitans, Coquillettidia perturbans) transmit the virus to humans and horses

Western Equine Encephalitis Virus (WEEV)

Serodiagnosis
- WEEV IgM: Indicates recent WEEV infection
- WEEV IgG: Indicates past WEEV infection
Clinical Significance
- WEEV causes Western equine encephalitis, a less severe disease than EEE
- Symptoms include fever, headache, and neurological complications (encephalitis, meningitis)
Epidemiology
- Transmission: Mosquitoes (primarily Culex tarsalis)
- Reservoir hosts: Birds
- Geographic distribution: Primarily in the western United States and Canada
- Seasonality: Peak incidence during summer months
Vectors of Transmission
- Culex tarsalis is the primary vector

Powassan Virus (POWV)

Serodiagnosis
- POWV IgM: Indicates recent POWV infection
- POWV IgG: Indicates past POWV infection
Clinical Significance
- POWV causes Powassan encephalitis, a rare but serious disease
- Symptoms include fever, headache, stiff neck, seizures, and altered mental status
- Can cause long-term neurological problems or death
Epidemiology
- Transmission: Ticks (primarily Ixodes cookei and Ixodes scapularis)
- Reservoir hosts: Rodents and other small mammals
- Geographic distribution: Primarily in the northeastern and Great Lakes regions of the United States and Canada
- Seasonality: Peak incidence during spring, summer, and fall months when ticks are active
Vectors of Transmission
- Ixodes cookei is the primary vector in the wildlife cycle
- Ixodes scapularis (deer tick or black-legged tick) can transmit the virus to humans

Japanese Encephalitis Virus (JEV)

Serodiagnosis
- JEV IgM: Indicates recent JEV infection
- JEV IgG: Indicates past JEV infection or vaccination
Clinical Significance
- JEV causes Japanese encephalitis, a leading cause of viral encephalitis in Asia
- Symptoms include fever, headache, stiff neck, seizures, and coma
- High mortality rate and significant neurological sequelae in survivors
Epidemiology
- Transmission: Mosquitoes (primarily Culex tritaeniorhynchus)
- Reservoir hosts: Pigs and wading birds
- Geographic distribution: Primarily in Asia and parts of the western Pacific
- Seasonality: Peak incidence during the rainy season when mosquito populations are highest
Vectors of Transmission
- Culex tritaeniorhynchus is the primary vector

Tick-Borne Encephalitis Virus (TBEV)

Serodiagnosis
- TBEV IgM: Indicates recent TBEV infection
- TBEV IgG: Indicates past TBEV infection or vaccination
Clinical Significance
- TBEV causes tick-borne encephalitis, a viral infection of the central nervous system
- Symptoms can range from mild flu-like illness to severe encephalitis or meningitis
Epidemiology
- Transmission: Ticks (primarily Ixodes ricinus in Europe and Ixodes persulcatus in Asia)
- Reservoir hosts: Rodents and other small mammals
- Geographic distribution: Primarily in Europe and Asia
- Seasonality: Peak incidence during spring, summer, and fall months when ticks are active
Vectors of Transmission
- Ixodes ricinus (European castor bean tick)
- Ixodes persulcatus (Taiga tick)

General Diagnostic Approach

Clinical Suspicion: Encephalitis should be suspected in patients with fever, headache, altered mental status, seizures, or other neurological symptoms
CSF Analysis: Cerebrospinal fluid (CSF) should be collected and analyzed for cell count, protein, glucose, and viral PCR
Serological Testing: Serum should be tested for IgM and IgG antibodies against relevant arboviruses
Confirmatory Testing: Plaque Reduction Neutralization Test (PRNT) may be needed to confirm specific diagnosis and differentiate between cross-reacting antibodies
Geographic and Exposure History: Consider the patient’s travel history, outdoor activities, and potential exposure to mosquitoes or ticks

Prevention Strategies

Personal Protective Measures
- Use insect repellent containing DEET, picaridin, or oil of lemon eucalyptus
- Wear long sleeves and pants when outdoors
- Avoid being outdoors during peak mosquito and tick activity
- Use mosquito netting when sleeping outdoors or in unscreened areas
Vector Control
- Mosquito spraying and larviciding
- Tick control measures in residential areas
- Eliminating standing water where mosquitoes can breed
Vaccination
- Vaccines are available for Japanese encephalitis virus (JEV) and tick-borne encephalitis virus (TBEV) for individuals at high risk of exposure

Key Terms

Encephalitis: Inflammation of the brain
Arbovirus: Arthropod-borne virus (transmitted by mosquitoes, ticks, or other arthropods)
Vector: An organism (e.g., mosquito, tick) that transmits a pathogen from one host to another
Reservoir Host: An animal species that harbors a pathogen and serves as a source of infection for vectors
Dead-End Host: A host that can be infected by a pathogen but does not transmit it to other susceptible hosts
Plaque Reduction Neutralization Test (PRNT): A serological assay used to measure neutralizing antibodies against a virus
Neuroinvasive Disease: Disease in which a pathogen invades the central nervous system (brain and spinal cord)
Viremia: The presence of virus in the blood

Viral Pathogens

T. pallidum & B. burgdorferi