Lecture 9 - Arbovirus Encephalitides (rev) (2025) (3)

Arthropod-Borne Viral Encephalitides Overview

  • Arthropod-Borne viruses (arboviruses) are transmitted by arthropods (insects, ticks, sandflies) and can cause Central Nervous System (CNS) diseases.

Taxonomic System for Viruses

  • Viruses categorized by:

    • Morphologic similarities

    • Biochemical similarities

    • Antigenic similarities

    • Genetic similarities

    • Replication schemes

  • This system lacks information on:

    • Transmission (epidemiology)

    • Disease patterns (clinical features)

Importance in Clinical Neurology

  • Understanding epidemiology and clinical features is vital for neurologists.

Alternative Groupings for Arboviruses

  • Arboviruses include a range of viruses that cause CNS diseases, often incorporated into clinical and epidemiological contexts.

Virus Families Containing Arboviruses

  • Key Families:

    • Togaviridae

    • Flaviviridae

    • Bunyaviridae

    • Reoviridae

  • Over 500 arthropod-borne viruses exist, but only a subset causes human diseases.

Arboviral Disease Patterns in Humans

  • Common disease manifestations include:

    • Fever, arthralgia, rash syndromes

    • Viral hemorrhagic fevers

    • Neurologic diseases (encephalitides)

Infections of the Nervous System

  • FAR: Fever arthralgia-rash

  • VHF: Viral hemorrhagic fever

  • CNS: Central nervous system diseases

Encephalitis from Arboviruses

  • Major viruses include:

    • Togaviridae: Alphaviruses (Eastern equine, Western equine, Venezuelan equine encephalitis)

    • Flaviviridae: (West Nile, St. Louis encephalitis, Japanese encephalitis, Zika virus)

    • Bunyaviridae: La Crosse virus

    • Reoviridae: Colorado tick fever virus

Ecology of Arboviruses

  • Humans are incidental hosts, with viruses transmitted primarily among birds or small rodents through vectors (mosquitoes/ticks).

  • Encroachment upon animal cycles can lead to human infection.

  • Bridging vector: Different species may carry the virus to humans.

  • Enzootic and epizootic cycles detail how viruses persist and amplify in animal populations.

General Pathogenesis of Arbovirus CNS Infection

  1. Initial infection occurs through a vector bite.

  2. Virus replication in skin and muscle.

  3. Spread to regional lymph nodes, then into the bloodstream (biphasic viremia).

  4. Virus enters CNS, correlated with viremia extent and viral properties.

Pathological Features

Gross Pathology

  • Congested brain tissue with hemorrhagic spots.

  • Lesions in various brain regions.

Microscopic Pathology

  • Perivascular cuffing and infiltration of immune cells.

  • Neuron destruction and possible demyelination.

  • Inflammatory responses may appear late in infection.

Clinical Features of Arbovirus CNS Infection

General Features

  • Incubation period: 4-8 days.

  • Initial flu-like symptoms (fever, headache, nausea).

  • Potential biphasic fever curve.

Neurologic Symptoms

  • Changes in behavior, seizures, levels of consciousness.

  • Focal neurologic signs: hemiparesis, cranial nerve dysfunction.

Specific Arboviruses

Togaviridae: Alphaviruses

  • Cause fever, arthralgia, and rash (Old World) and encephalitis in humans (New World).

  • Notable viruses include:

    • Eastern Equine Encephalitis (high mortality)

    • Western Equine Encephalitis (low prevalence)

    • Venezuelan Equine Encephalitis (mainly febrile disease)

Flaviviridae: Flaviviruses

  • Known for West Nile Virus and Zika Virus.

  • West Nile Virus: First isolated in 1937 with significant outbreaks from the 1990s onward.

Diagnosis of Arboviral Infections

  • Broad differential with other viral infections.

  • CSF analysis reveals:

    • Lymphocytic pleocytosis

    • Elevated protein

    • Normal glucose content

  • Detection of virus or antibodies critical for diagnosis.

Treatment

  • No established treatment for West Nile encephalitis.

  • Experimental options include:

    • Interferon

    • Ribavirin

    • Human immune globulin

  • Vaccines under development but none currently available for humans.

Zika Virus

  • First isolated in 1947, spread globally, particularly in recently affected regions.

  • Epidemic linked to severe outcomes like microcephaly and Guillain-Barre’ syndrome.

Transmission and Diagnosis of Zika Virus

  • Transmitted by Aedes mosquitoes (not Culex). Human-to-human is possible (mother to child, sexual transmission, blood transfusion).

  • Detection methods similar to other arboviruses (RT-PCR, antibody assays).

Zika Vaccine and Prevention

  • No effective vaccine yet, but several in trials.

  • Prevention emphasizes mosquito bite avoidance, safe sex practices, and eliminating standing water to reduce mosquito breeding.