Definition

Acute brain inflammation resulting from infection with arboviruses, which are mainly transmitted via infected mosquitoes or ticks. These viruses, belonging to families such as Flaviviridae, Togaviridae, Bunyaviridae, and Reoviridae, are maintained in natural cycles involving blood-feeding arthropods and vertebrate hosts.

Description

• It occurs mainly in summer and early fall.
• It can vary from asymptomatic or mild febrile illness to severe neuroinvasive disease, including encephalitis, meningitis, or acute flaccid paralysis.
• All cases of nationally notifiable diseases are monitored through the CDC’s ArboNET surveillance system.

Classification by causative virus (CDC categories)

• Flaviviridae (Flaviviruses)
  • West Nile virus (WNV) is the most prevalent arboviral encephalitis in the United States.
  • St. Louis encephalitis virus (SLEV).
  • Virus Powassan (POWV).
• Togaviridae (Alphaviruses)
  • Eastern equine encephalitis virus (EEEV).
  • Western equine encephalitis virus (WEEV).
  • Venezuelan equine encephalitis virus (VEEV) is rare in the U.S. but more common in Central and South America.
• Bunyaviridae
  • La Crosse virus (LACV).
  • Jamestown Canyon virus (JCV).
  • California serogroup viruses.

Epidemiology

Incidence/Prevalence

• West Nile Virus (WNV):
  • Since 1999, over 56,000 cases have been reported in the U.S., including more than 25,000 neuroinvasive cases (CDC, 2023).
  • The annual incidence of neuroinvasive WNV disease ranges from 0.4 to 1.0 cases per 100,000 people, varying each year.
• Other arboviruses:
  • LACV occurs in about 50 to 100 cases each year, mainly impacting children in the Midwest and Appalachia.
  • EEEV: Rare, with about 4 to 15 cases annually, but it has a high fatality rate of approximately 30–40%.
  • SLEV: Occasional outbreaks, mainly in the Midwest and South.
  • POWV: Increasing recognition, with about 20–30 cases annually, mainly in the Northeast and Great Lakes regions.

Age

• WNV: The risk of neuroinvasive disease increases sharply with age, peaking in adults over 60 years.
• LACV mainly impacts children under 16 years old.
• EEEV causes severe disease in all age groups, with children and older adults facing a higher risk of poor outcomes.
• POWV is most frequently observed in older adults.

Gender

• Slight male predominance in WNV and other arboviral neuroinvasive diseases, possibly due to more outdoor exposure.
• LACV exhibits a similar male bias in the cases reported.

Race

• CDC surveillance data indicate that arboviral encephalitis affects people across all racial and ethnic groups. However, the incidence rates are more closely associated with regional factors and exposure risks than with race alone.

Risk factors

• General
  • Geographic exposure:
    • Residence or travel in endemic regions (e.g., U.S. Midwest and Gulf Coast, South Asia, Africa, Latin America)
  • Seasonal variation:
    • Summer and early fall (peak mosquito activity)
  • Outdoor activity:
    • Camping, farming, hiking, military deployment
  • Vector exposure:
    • Mosquitoes (e.g., Culex, Aedes), ticks (e.g., Ixodes)
  • Lack of protective measures:
    • Lack of insect repellent, inadequate clothing, and poor housing screens.
    • Poor sanitation or stagnant water near the residence
  • Occupational risk:
    • Forestry, agriculture, entomology, wildlife biology
  • Low vaccination coverage:
    • For Japanese encephalitis or yellow fever (if applicable)
• Physiological
  • Extremes of age:
  • Children <5 years and adults >65 years
    • Immunocompromised status:
    • HIV/AIDS, transplant recipients, chemotherapy, corticosteroid use
  • Pregnancy:
    • Increased susceptibility and risk of fetal transmission (e.g., Zika)
    • Pre-existing neurologic disease:
    • Epilepsy, cerebral palsy, prior stroke
  • Chronic comorbidities:
    • Diabetes mellitus, renal failure, liver disease
  • Genetic predisposition:
    • HLA-linked immune response variations (under investigation)
  • Nutritional deficiencies:
    • Thiamine, protein-energy malnutrition (especially in children)
  • Recent viral illness:
    • May predispose individuals to immune-mediated encephalitis.

Etiology

• Flaviviruses (Flaviviridae):
  • West Nile virus (WNV)
  • St. Louis encephalitis virus (SLEV)
• Alphaviruses (Togaviridae):
  • Eastern equine encephalitis virus (EEEV)
  • Western equine encephalitis virus (WEEV)
  • Venezuelan equine encephalitis virus (VEEV)
• Pathophysiology
  • Viral Entry:
    • Virus enters through a mosquito bite.
    • Initial replication takes place at the bite site and nearby lymph nodes.
  • Viremia:
    • Virus spreads through the bloodstream.
  • Neuroinvasion:
  • Virus crosses the blood-brain barrier (BBB) via:
    • Direct endothelial infection
    • Trojan horse mechanism (infected immune cells)
    • BBB disruption due to inflammation
  • CNS Infection:
    • Virus infects neurons and glial cells.
  • Leads to:
    • Neuronal death
    • Inflammation
    • Cerebral edema
    • Increased intracranial pressure
  • Clinical Manifestations:
    • Fever, headache, confusion
    • Seizures, coma, paralysis

History

• Primary Complaint
  • Fever, severe headache, and confusion have lasted for the past three days.
• History of Present Illness (HPI)
  • Onset: Sudden, following mild fever, malaise, and myalgia.
  • Progression: Headache worsens, followed by nausea, photophobia, and alterations in mental state.
  • Neurological symptoms encompass confusion, memory problems, speech challenges, and sometimes seizures or focal weakness.
  • Associated symptoms include rash(more common with Zika and other flaviviruses, less frequent with WNV), tremors, muscle weakness, or flaccid paralysis.
  • Timeline: Symptoms typically appear within 3 to 14 days after a mosquito or tick bite.
• Past Medical History
  • Chronic illnesses like diabetes, hypertension, and immunosuppression increase the risk of severe disease.
• Family and Social History
  • Outdoor lifestyle, residing near wooded or swampy areas, and the presence of stagnant water close to the home.
  • Outdoor workers such as farmers, construction workers, and park rangers are at higher risk.

Physical findings on examination

• General Appearance:
  • Ill-looking, febrile, lethargic, or obtunded
  • Photophobia and neck stiffness (meningeal signs)
  • Rash (e.g., maculopapular in Zika, West Nile)
• Vital Signs:
  • Fever >101°F (38.3°C)
  • Tachycardia or bradycardia
  • Hypotension (late or systemic involvement)
  • Respiratory distress
• Neurologic Examination:
  • Altered mental status: confusion, delirium, coma
  • Seizures or postictal state
  • Focal deficits: hemiparesis, cranial nerve palsies
  • Ataxia, tremor, and myoclonus (especially related to West Nile)
  • Hyperreflexia or flaccid paralysis
  • Positive Babinski sign
  • Nuchal rigidity, Kernig’s and Brudzinski’s signs
• Ophthalmologic:
  • Papilledema (raised ICP)
  • Conjunctivitis (Zika virus)
  • Retinal hemorrhages or chorioretinitis
• Dermatologic:
  • Maculopapular rash (Zika, Dengue overlap)
  • Petechiae or purpura (if thrombocytopenia)
  • Tick bite site (Powassan virus)
• Cardiopulmonary:
  • Normal or signs of aspiration pneumonia
  • Arrhythmias (autonomic dysfunction)

Laboratory Tests

• Baseline Panels:
  • CBC with differential
  • Leukocytosis or lymphopenia
  • CMP (electrolytes, renal, hepatic)
  • Hyponatremia (SIADH), transaminitis
• Inflammatory & Infectious Markers:
  • CRP, ESR — indicators of nonspecific inflammation
  • Procalcitonin — used to rule out bacterial coinfection
  • Blood cultures — if febrile or septic
• CSF Analysis (Lumbar Puncture):
  • Opening pressure is elevated in cerebral edema.
  • Cell count: lymphocytic pleocytosis
  • Protein: elevated
  • Glucose: normal or mildly decreased
  • CSF PCR — virus-specific tests (e.g., West Nile, EEE, Zika)
  • CSF IgM ELISA — confirm neuroinvasive arboviral infection
• Serologic Testing:
  • Serum IgM and IgG — arboviral panels (West Nile, Zika, EEE)
  • Paired acute/convalescent titers — confirm diagnosis
  • Zika virus RT-PCR — especially in pregnancy
• Other Virologic Studies:
  • Nasopharyngeal swab — for respiratory symptoms
  • Urine or saliva PCR — Zika virus detection
  • Tick/mosquito exposure documentation — epidemiological relevance

Diagnostic Tests

• Neurodiagnostic Support:
  • EEG — seizure activity or encephalopathy
  • MRI brain — inflammation, edema, hydrocephalus
  • CT head — rule out hemorrhage or mass effect

Differential Diagnosis

• Infectious Encephalitis:
  • Herpes simplex virus encephalitis
  • Varicella-zoster virus encephalitis
  • Cytomegalovirus encephalitis
  • HIV-associated neurocognitive disorder
  • Bacterial meningoencephalitis
  • Fungal CNS infections
  • Tuberculous meningitis
• Post-Infectious/Autoimmune:
  • Acute disseminated encephalomyelitis
  • Anti-NMDA receptor encephalitis
  • Hashimoto’s encephalopathy
• Toxic-Metabolic Encephalopathy:
  • Hepatic encephalopathy
  • Uremic encephalopathy
  • Hypoglycemia-induced encephalopathy
  • Drug-induced CNS toxicity
• Structural/Neoplastic:
  • Primary CNS lymphoma
  • Glioblastoma or astrocytoma
  • Paraneoplastic encephalitis
• Vascular:
  • Ischemic stroke with altered sensorium
  • Cerebral venous sinus thrombosis
  • Hypertensive encephalopathy

General treatment items

• Supportive Care:
  • IV fluids for hydration and perfusion
  • Antipyretics (e.g., acetaminophen) for fever
  • Electrolyte correction (e.g., hyponatremia caused by SIADH)
  • Nutritional support (oral or enteral as needed)
• Seizure Management:
  • Levetiracetam or phenytoin for acute seizures
  • Benzodiazepines for status epilepticus
  • EEG monitoring for altered sensorium or seizure risk
• Neuroprotection:
  • Head elevation and ICP control in cases of cerebral edema.
  • Avoid hypotension and hypoxia
  • Sedation for agitation or ICP elevation
• Respiratory Support:
  • Oxygen therapy or mechanical ventilation if necessary
  • Airway protection in comatose patients
• Antiviral/Immunotherapy (limited role):
  • No FDA-approved antivirals for most arboviruses.
  • Consider IVIG or interferon (off-label, case-by-case)
  • Ribavirin: ineffective against arboviral encephalitis
• Rehabilitation:
  • Physical therapy for motor deficits
  • Occupational therapy for ADLs
  • Speech therapy for aphasia or dysphagia
  • Neuropsychological support for cognitive recovery
• Public Health Measures:
  • Notify local/state health department
  • Vector control and exposure documentation
  • Education on prevention and long-term follow-up.

Surgical Interventions

• General Note:
  • Arboviral encephalitis is primarily managed medically.
  • Surgical interventions are uncommon and typically reserved for complications.

Adjunctive Therapies

• Immunomodulatory Therapies:
  • Intravenous immunoglobulin (IVIG)
  • Consider in severe neuroinvasive cases (off-label)
  • May help modulate immune response and reduce inflammation
• Corticosteroids:
  • Limited evidence; may be applicable for cerebral edema or autoimmune overlap.
  • Dexamethasone or methylprednisolone pulse therapy (case-by-case)
• Neuroprotective Strategies:
  • N-acetylcysteine (NAC)
  • Antioxidant support in encephalopathy (experimental use)
• Antiviral Exploration (non-standardized):
  • Interferon-alpha or beta
  • Investigational use in certain arboviruses (e.g., West Nile, Zika)
• Ribavirin:
  • Not effective against most arboviruses; avoid unless there is a specific indication.
• Rehabilitation & Cognitive Support:
  • Cognitive Behavioural Therapy (CBT) for Post-Viral Depression and Anxiety
  • Neuropsychological rehabilitation for memory, attention, and executive functions
  • Occupational therapy for ADLs and fine motor recovery

Medications indicated with specific doses

Toxoids

• Not Applicable

Immunoglobulins

• Not Applicable

Vasodilators

• Not Applicable

Thrombolytic agents

• Not Applicable

Dietary or Activity restrictions

• Dietary Restrictions:
  • No specific dietary restrictions related to arboviruses.
  • Encourage:
    • High-protein, nutrient-rich meals for recovery
    • Adequate hydration (2–3 L/day unless contraindicated)
    • Electrolyte-rich fluids in case of SIADH or hyponatremia
  • Avoid:
    • Alcohol — may worsen CNS symptoms or interfere with medications
    • Excess caffeine — may exacerbate anxiety or insomnia
    • Aspiration risk foods (e.g., thin liquids, dry solids) if dysphagia is present.
• Activity Restrictions:
  • Bed rest during the acute phase (fever, altered sensorium)
  • Gradual mobilization once stable.
  • Passive to active range-of-motion exercises
  • Supervised ambulation if ataxia or weakness
  • Avoid:
    • Driving until seizure-free and cleared by neurology.
    • Strenuous activity until full neuro recovery
    • Screen time overload may worsen headaches or fatigue

Disposition

Admission Criteria

• Neurologic Instability:
  • Altered mental status (GCS < 15)
  • New-onset seizures or status epilepticus
  • Focal neurologic deficits (e.g., hemiparesis, aphasia)
  • Coma or unresponsiveness
• Respiratory or Systemic Compromise:
  • Hypoxia or respiratory distress
  • Autonomic instability (e.g., bradycardia, hypotension)
  • Fever > 102°F with rigors or delirium
• CSF or Imaging Findings:
  • CSF pleocytosis with elevated protein
  • Positive PCR or IgM result for arbovirus
  • MRI/CT indicating encephalitic changes or cerebral edema
• High-Risk Populations:
  • Age <5 or >65 years
  • Immunocompromised individuals (e.g., transplant patients, HIV-positive, undergoing chemotherapy)
  • Pregnant patients with suspected Zika or West Nile virus exposure
• Disposition Needs:
  • ICU: coma, seizures, respiratory failure, brainstem signs
  • Neurology or Infectious Disease service: confirmed neuroinvasive disease
  • Isolation: if Zika or another transmissible arbovirus is suspected
• Social & Safety Considerations:
  • Inability to self-monitor or access care
  • No reliable caregiver or home support
  • Public health reporting and vector exposure documentation

Discharge criteria

• Neurologic Stability:
  • Alert and oriented (baseline or improved)
  • No new focal deficits
  • Seizure-free for ≥24–48 hours
  • Stable GCS ≥14 without ICP concerns
• Systemic Recovery:
  • Afebrile for at least 24 hours without the use of antipyretics
  • Hemodynamically stable (BP, HR, RR within normal limits)
  • No respiratory distress; SpO₂ ≥94% on room air
• Functional Readiness:
  • Tolerating oral intake
  • Ambulating or mobilizing with or without assistance
  • Able to perform basic ADLs or has caregiver support.

Monitoring

• Neurologic Monitoring:
  • Serial Glasgow Coma Scale (GCS) assessments
  • Seizure watch: EEG if altered sensorium or convulsions
  • Focal deficit tracking: motor/sensory exams every shift
  • Monitor intracranial pressure (ICP) in comatose or unstable patients.
• Laboratory Monitoring:
  • CBC with differential — leukocytosis or lymphopenia
  • CMP — hyponatremia (SIADH), transaminitis
  • CSF analysis — pleocytosis, elevated protein, normal glucose.
  • PCR or IgM serology — virus-specific confirmation
• Imaging:
  • MRI brain — preferred for encephalitic changes
  • CT head — rule out hemorrhage or hydrocephalus
  • Repeat imaging if clinical deterioration occurs.
• Respiratory & Systemic Monitoring:
  • Pulse oximetry and ABG — risk of respiratory failure
  • Chest X-ray — aspiration or secondary pneumonia
  • Cardiac telemetry — autonomic instability
• Infectious Disease & Public Health:
  • Notify local/state health department
  • Record travel history and vector exposure

Patient Education

• Goals: Encourage prevention of arboviral infections by raising awareness about mosquito and tick control methods.
• Support early recognition of neuroinvasive symptoms. Encourage follow-up and rehab if neurological issues develop.
• Enhance quality of life by practicing self-management and receiving supportive care.
• General Education: Teach families to recognize early warning signs such as severe headache, high fever, stiff neck, confusion, weakness, or seizures, and seek prompt medical care.
  • Highlight that treatment is supportive: hospitalization, IV fluids, seizure control, and respiratory support if needed.
• Action Plan for Patients & Families:
  • Apply repellent before outdoor activities. Check children for mosquito bites. Avoid outdoor exposure during dusk and dawn.
  • Seek emergency care for neurological signs (confusion, paralysis, seizures). Keep a record of symptom onset for healthcare providers. Conduct diagnostic tests (blood, CSF) as advised.

Complications

• Neurologic Complications:
  • Seizure disorder
  • Status epilepticus
  • Acute flaccid paralysis
  • Spasticity or dystonia
  • Cognitive impairment
  • Encephalopathy
  • Hydrocephalus - post-inflammatory
  • Brainstem dysfunction - respiratory compromise
• Systemic Complications:
  • Respiratory failure
  • SIADH and hyponatremia
  • Rhabdomyolysis
  • Multiorgan dysfunction — rare, fulminant cases
  • A secondary bacterial infection
• Pediatric-Specific:
  • Developmental delay
  • Microcephaly - Zika virus
  • Hearing loss
  • Cerebral palsy
• Pregnancy-Related:
  • Congenital viral syndrome
  • Intrauterine growth restriction
  • Spontaneous abortion
• Post-Infectious Sequelae:
  • Chronic fatigue
  • Depression, anxiety
  • Sleep disturbances
  • Persistent headache
  • Functional disability - requiring rehab

Prevention

• Vector Control:
  • Remove standing water (for example, buckets, tyres, birdbaths)
  • Apply larvicides to stagnant water sources
  • Community-wide mosquito abatement programs
  • Tick habitat management (brush clearing and acaricides)
• Personal Protection:
  • Use EPA-approved insect repellents (e.g., DEET, picaridin, IR3535)
  • Wear long sleeves, pants, and socks in endemic areas.
  • Avoid outdoor activity during peak mosquito hours (dusk to dawn).
  • Use permethrin-treated clothing and gear
• Environmental Measures:
  • Install window and door screens
  • Use air conditioning when possible
  • Use insecticide-treated bed nets when sleeping in high-risk areas
• Travel Precautions:
  • Check CDC travel advisories for arboviral outbreaks
  • Avoid travelling to endemic areas during peak transmission seasons.
  • Practice mosquito avoidance in tropical and subtropical areas
• Vaccination (where applicable):
  • Japanese encephalitis vaccine (for travellers to Asia)
  • Yellow fever vaccine (for endemic areas in Africa and South America)
  • No licensed vaccines for West Nile, EEE, or Zika in the U.S. (as of 2025)
• Pregnancy-Specific Guidance:
  • Avoid travelling to Zika-endemic regions during pregnancy.
  • Use condoms or abstain if your partner has travelled to a Zika-risk area.
  • Prenatal screening for congenital arboviral exposure

Prognosis

• General Prognosis:
  • Variable; depends on virus type, host factors, and timing of care.
  • Mortality rates vary from less than 1% (West Nile) to over 30% (Eastern equine encephalitis).
• Favorable Prognostic Indicators:
  • Early diagnosis and supportive care
  • Mild neurologic symptoms
  • Age 15–50 years
  • Immunocompetent status
• Poor Prognostic Indicators:
  • Coma or seizures at presentation
  • Extremes of age (<5 or >65 years)
  • Immunosuppression
  • Delayed hospitalization
  • MRI: diffuse cerebral edema or haemorrhage
• Long-Term Sequelae:
  • Cognitive impairment
  • Seizure disorder
  • Motor deficits (e.g., spasticity, flaccid paralysis)
  • Psychiatric symptoms (depression, anxiety)
  • Fatigue and post-viral syndrome

Associated conditions

• Primary Neurologic Associations:
  • Viral meningitis
  • Acute flaccid paralysis
  • Status epilepticus
  • Cerebral edema
  • Encephalopathy, unspecified
  • Guillain-Barré syndrome - post-arboviral trigger
• Systemic Complications:
  • Sepsis - secondary bacterial infection
  • Acute respiratory failure
• Pediatric-Specific Associations:
  • Microcephaly - Zika virus
  • Developmental delay
  • Seizure disorder
• Pregnancy-Related Associations:
  • Congenital viral infections - Zika, West Nile
  • Spontaneous abortion related to arboviral exposure
  • Intrauterine growth restriction

Synonyms

• Arboviral meningoencephalitis
• Arthropod-borne viral encephalitis
• Vector-borne viral encephalitis
• Viral encephalitis due to arbovirus
• Acute arboviral encephalitis

ICD-10-CM

• A85.2 - Arthropod-borne viral encephalitis, unspecified

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