Classification
RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.
General Characteristics and Epidemiology
General features of equine encephalitis virus (EEV)
- Family: Togaviridae
- Genus: Alphavirus
- Genome:
- Positive-sense, ssRNA
- 11–12 kb in size
- Properties:
- Enveloped
- Lipid bilayer envelope has viral-encoded glycoproteins E1 and E2.
- Small icosahedral capsid
- Clinically relevant viruses and geographic distribution:
- Eastern equine encephalitis virus (EEEV) complex:
- Eastern equine encephalitis (EEE) virus: North America (Atlantic and Gulf coasts) and the Caribbean
- Madariaga virus: South and Central America
- Western equine encephalitis virus (WEEV): North and South America
- Venezuelan equine encephalitis virus (VEEV): Central and South America
- Eastern equine encephalitis virus (EEEV) complex:
Epidemiology
- In the United States:
- EEEV is the most common of the 3 viruses.
- Infections are rare and sporadic.
- Peak incidence: August and September
- Flooding increases breeding of mosquitoes → ↑ risk of infection
- Both humans and horses can be infected and develop encephalitis.
Pathophysiology
Vector and transmission
- Mosquitoes: primary arthropod vector
- Virus has different reservoirs or amplifying hosts: domestic and wild birds, mammals
- Transmission:
- The virus is maintained by birds and mosquitoes (Culiseta melanura with EEEV infection) in a mosquito-bird-mosquito cycle.
- Viral transmission between vertebrates is facilitated by bridge vectors (other mosquitoes or blood-feeding arthropods).
- Species of mosquitoes that serve as bridge vectors:
- Coquillettidia species
- Aedes species
- Culex species
- Humans are infected by the human-biting bridge vectors.
- While humans can develop illness, they are considered dead-end hosts.
- Viremia in humans is generally insufficient to infect feeding mosquitoes/vectors.
- The virus can also be used as a bioterrorism agent (via aerosol transmission).
Transmission cycles of arboviruses in nature:
Transmission of most arboviruses is covered by 2 major cycles, namely the mosquito-reservoir/host-mosquito cycle and the mosquito vector and humans/dead-end hosts.
Pathogenic features and viral infection
- Infected female mosquito bites human → virus enters the bloodstream → entry into host cells (myeloid or lymphoid cells) via endocytosis
- Envelope E1 and E2 viral proteins:
- Aid in virus attachment and penetration
- E1 can bring about hemagglutination by fusing to membrane lipids
- Viral replication:
- Occurs in the cytoplasm (viremic phase)
- Positive-sense genomic RNA serves as the mRNA.
- Virions mature by budding from plasma membranes → infect other cells
- Neuroinvasion:
- The virus crosses the blood-brain barrier and multiplies in the CNS.
- Leads to neuronal necrosis/neuronophagia and meningeal irritation
- Invasion depends on:
- Level of viremia
- Virulence of strain
- Host immune response
- Age-dependent risk for CNS infection, which is increased in:
- Infants/young children
- Elderly
Electron micrograph of the salivary gland of a mosquito containing the eastern equine encephalitis virus:
The mosquito is infected with the virus when it feeds on the blood of a viremic animal. The virus matures and disseminates in the organs and eventually accumulates in the salivary glands of the mosquito.
Diseases
Minor illness
- 1st phase (from mosquito bite to viral replication in non-neural tissue)
- Incubation period: 4–10 days following a mosquito bite
- 7–10 day prodrome:
- Fever
- Headache
- Nausea/vomiting
- Most cases are subclinical or only produce low-grade fever.
- Patients with minor viral illness (and no CNS involvement) recover within 1–2 weeks.
Major illness
- 2nd phase: viral multiplication in the brain
- Encephalitis or inflammation/swelling of the brain parenchyma affects 2% and 6% of infected adults and children, respectively.
- Signs and symptoms include:
- Headache
- High fever
- Muscle pain
- Photophobia
- Altered mental status
- Seizures and cranial nerve palsies in 50% of patients
- May manifest as bulging fontanelle in infants
- Mortality rate can reach 20%–30% depending on the EEV type and host factors.
- Survivors have severe neurologic sequelae that can include:
- Intellectual impairment
- Epilepsy
- Paralysis
- Deafness
- Blindness
- Signs and symptoms include:
Diagnosis and Management
- Diagnostic approach:
- Clinical findings consistent with encephalitis
- Laboratory findings:
- Leukocytosis
- Hyponatremia
- CSF analysis: pleocytosis, ↑ protein concentration
- Determination of virus:
- Virus-specific IgM: < 4-fold rise in specific antibodies
- Viral antigen or genomic sequences (using PCR assays) in CSF, blood, or tissue
- Imaging: MRI is more sensitive in showing abnormalities (focal lesions in basal ganglia, brainstem, and thalami).
- Treatment: supportive (no specific treatment)
- Prevention:
- Mosquito control
- Avoidance of mosquito bites (protective clothing, mosquito repellants)
References
- Crosby, B., Crespo, M.E. (2020). Venezuelan Equine Encephalitis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, from https://www.ncbi.nlm.nih.gov/books/NBK559332/
- Perng, G., Chen, W. (2013). Arboviral Encephalitis, Encephalitis, Sergey Tkachev, IntechOpen. https://www.intechopen.com/books/encephalitis/arboviral-encephalitis
- Peterson, L. (2021). Arthropod-borne encephalitides. UpToDate. Retrieved Apr 24, 2021, from https://www.uptodate.com/contents/arthropod-borne-encephalitides
- Riedel, S., Hobden, J.A., Miller, S., Morse, S.A., Mietzner, T.A., Detrick, B., Mitchell, T.G., Sakanari, J.A., Hotez, P, Mejia, R. (2019). Arthropod-borne and rodent-borne viral diseases. Jawetz, Melnick & Adelberg’s Medical Microbiology, 28e. McGraw-Hill.
- Ryan, K.J. (Ed.), (2017). Arthropod-borne and other zoonotic viruses. Sherris Medical Microbiology, 7e. McGraw-Hill.
- Simon, L.V., Coffey, R., Fischer, M.A. (2020). Western Equine Encephalitis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, from https://www.ncbi.nlm.nih.gov/books/NBK470228/
