Arthropod-borne viruses are transmitted to humans by arthropod bites and cause a spectrum of disease, from a mild viral syndrome to encephalitis.

Epidemiology

• Prevalence
  • >300 cases reported annually in U.S.
  • Seasonal occurrence – April to October
• Age – young children and elderly more likely to have severe disease
• Transmission – mosquito bite

Organisms

• More than 500 species of arbovirus exist
• RNA viruses of importance in the U.S. are reviewed here
  • Bunyavirus – California encephalitis (CE) serogroup
    • La Crosse virus
      • Primarily in upper Mississippi River valley
    • Jamestown Canyon virus
      • Upper midwestern states and New York
    • Snowshoe hare virus
      • Southern Canada
    • Mosquito species
      • Aedes triseriatus
  • Flavivirus
    • St. Louis encephalitis
      • Present in nearly all of the U.S.
      • Mosquito species
        • Culex pipiens and C. quinquefasciatus
          • Gulf Coast; Ohio and Mississippi River valleys
        • C. nigripalpus
          • Florida
        • C. tarsalis
          • Western states
    • West Nile virus encephalitis (WNV)
      • Endemic in U.S.
      • Mosquito species
        • C. tarsalis
      • Refer to Dengue fever virus for more information
  • Togaviruses
    • Eastern equine encephalitis (EEE)
      • Present in the eastern half of the U.S.
      • Mosquito species
        • Aedes vexans, Coquillettidia perturbans, Ochlerotatus sollicitans and canadensis
    • Western equine encephalitis (WEE)
      • Present in western and midwestern U.S.
      • Mosquito species
        • C. tarsalis

Risk Factors

• Older age
• Outdoor activity during peak mosquito activity (morning and evening)

Clinical Presentation

• Commonly asymptomatic
• Nonspecific flu-like symptoms/illness 
  • Fever
  • Headache
  • Myalgias
  • Nausea, anorexia
  • Cough
  • Sore throat
• Acute encephalitis (neuro-invasive disease)
  • Lasts a few days to months with slow and sometimes incomplete recovery
  • EEE has more abrupt onset and shorter, more severe course than arbovirus encephalitides
  • Presentation begins as nonspecific illness but progresses to any of the following
    • Cognitive dysfunction
    • Memory impairment
    • Muscle weakness
    • Paralysis
    • Seizures
    • Coma
• WNV
  • Acute flaccid paralysis can also occur with WNV infection
    • Causes poliomyelitis-like syndrome with involvement of anterior horn cells in spinal cord
    • Meningoencephalitis occasionally complicates disease
    • Mortality – 5-20% in affected patients
      • Up to 70% in affected patients >75 years

Treatment

• Supportive care
• Recovery may be prolonged

Indications for Testing

• Patient with meningitis/encephalitis presenting during mosquito season

Laboratory Testing

• Initial testing 
  • CBC with differential – lacks sensitivity/specificity but may aid in ruling out bacterial etiology
  • Cerebrospinal fluid (CSF) 
    • Cell count
    • Gram stain with culture
    • Culture – limited use because of low sensitivity
    • CNS disease – consider ordering multiple panel tests on CSF and serum to rule out other viral illnesses (eg, varicella-zoster virus [VZV], herpes simplex virus [HSV])
    • Protein
    • Glucose
  • Cellular profiles
    • WNV
      • Lymphocytic pleocytosis <1,000 cells/mm³
      • Neutrophils may predominate in early infections
      • Protein – moderately increased
      • Glucose – normal
    • St. Louis encephalitis
      • Lymphocytic pleocytosis <200 cells/mm³
      • Protein – >200 mg/dL in majority
      • Glucose – normal
    • Bunyavirus
      • Lymphocytic pleocytosis <200 cells/mm³
      • Protein – mildly increased
    • Togavirus
      • Lymphocytic pleocytosis 1,200-2,000 cells/mm³
      • Protein – elevated
      • May have increased CSF opening pressure
• Serum or CSF antibody testing
  • Majority of cases are diagnosed by serology
  • Best evidence for infection is a significant change (fourfold increase) in titer on two appropriately timed specimens done at the same laboratory
    • Appropriate timing – acute and convalescent samples at least 2 weeks apart
    • IgG usually negative in first 2 weeks of infection
    • Positive IgG without increase in convalescent sample and/or with negative IgM may indicate past exposure

Imaging Studies

• MRI more sensitive than CT
  • MRI may be normal 
  • Findings vary but include increased T2 signal in basal ganglia, thalamus, and brainstem
  • If patient has focal neurologic signs and symptoms, MRI or CT should be performed prior to lumbar tap

Other Tests

• EEG – if patient has seizures or is comatose
  • May show diffuse slow waves, focal sharp waves, seizures
  • No specific findings for viral encephalitis

Differential Diagnosis

• Infectious
  • Viral
    • HSV
    • VZV
    • Enterovirus
    • Rubeola
    • Rabies
    • Dengue fever
    • Colorado tick fever
  • Bacterial
    • LCM
    • Rickettsia spp
    • Listeria monocytogenes
    • B. burgdorferi
    • T. pallidum
  • Parasitic
    • Acanthamoeba
    • Toxoplasma gondii
    • Plasmodium spp
  • Meningitis
  • Brain abscess
• Tumor
  • Metastatic disease
  • Brain tumor
• Vasculitis
  • Systemic lupus erythematosus
  • Behçet disease
• Demyelinating disease
  • JC virus
  • Paraneoplastic syndrome

Tests generally appear in the order most useful for common clinical situations

Guidelines

• Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 47 (3) :303-327.PubMed

General

• Artsob H, Gubler DJ, Enria DA, Morales MA, Pupo M, Bunning ML, Dudley JP. West Nile Virus in the New World: Trends in the Spread and Proliferation of West Nile Virus in the Western Hemisphere. Zoonoses Public Health. 2009; :-.PubMed
• Davis LE, Beckham JD, Tyler KL. North American encephalitic arboviruses. Neurol Clin.. 2008 Aug; 26 (3) :727-57.PubMed
• Heeney JL. Zoonotic viral diseases and the frontier of early diagnosis, control and prevention. J Intern Med. 2006; 260 (5) :399-408.PubMed
• Lindsey NP, Staples JE, Lehman JA, Fischer M. Surveillance for human West Nile virus disease - United States, 1999-2008. MMWR Surveill Summ. 2010; 59 (2) :1-17.PubMed
• Petersen LR, Hayes EB. West Nile virus in the Americas. Med Clin North Am. 2008; 92 (6) :1307-22, ix.PubMed
• Romero JR, Newland JG. Diagnosis of viral encephalitides: zoonotic-associated viruses. Pediatr Infect Dis J. 2006; 25 (8) :741-742.PubMed
• Sejvar JJ. The evolving epidemiology of viral encephalitis. Curr Opin Neurol. 2006; 19 (4) :350-357.PubMed
• Weaver SC. Evolutionary influences in arboviral disease. Curr Top Microbiol Immunol. 2006; 299 :285-314.PubMed
• Zacks MA, Paessler S. Encephalitic alphaviruses. Vet Microbiol. 2009; :-.PubMed

ARUP Institute for Clinical and Experimental Pathology®

• Baillie GJ, Kolokotronis SO, Waltari E, Maffei JG, Kramer LD, Perkins SL. Phylogenetic and evolutionary analyses of St. Louis encephalitis virus genomes. Mol Phylogenet Evol. 2008; 47 (2) :717-728.PubMed
• Malan AK, Martins TB, Hill HR, Litwin CM. Evaluations of commercial West Nile virus immunoglobulin G (IgG) and IgM enzyme immunoassays show the value of continuous validation. J Clin Microbiol. 2004; 42 (2) :727-733.PubMed
• Malan AK, Stipanovich PJ, Martins TB, Hill HR, Litwin CM. Detection of IgG and IgM to West Nile virus. Development of an immunofluorescence assay. Am J Clin Pathol. 2003; 119 (4) :508-515.PubMed
• Rawlins ML, Swenson EM, Hill HR, Litwin CM. Evaluation of an enzyme immunoassay for detection of immunoglobulin M antibodies to West Nile virus and the importance of background subtraction in detecting nonspecific reactivity. Clin Vaccine Immunol. 2007; 14 (6) :665-668.PubMed
• Welch RJ, Anderson BL, Litwin CM. Evaluation of a new commercial enzyme immunoassay for the detection of IgM antibodies to West Nile virus using a ratio method to eliminate nonspecific reactivity. J Clin Lab Anal. 2008; 22 (5) :362-366.PubMed

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Borrelia burgdorferi
Dengue Fever Virus
Herpes Simplex Virus
Lymphocytic Choriomeningitis
Meningitis, Acute
Neuromyelitis Optica
N-methyl-D-Aspartate (NMDA) type Glutamate Receptor Autoantibody Disorders
Toxoplasma gondii
Varicella-Zoster Virus