La Crosse virus (LACV) is a mosquito-borne orthobunyavirus first isolated in 1960 from brain tissue of a child with encephalitis from La Crosse, Wisconsin.1-3 It is in the California serogroup and closely related to Jamestown Canyon, snowshoe hare, and California encephalitis viruses.1,2 La Crosse virus is primarily transmitted by Aedes triseraitus (eastern tree hole mosquito), with small deciduous forest mammals (e.g., chipmunks and gray squirrels) serving as the main amplifying hosts (Figure 1).1,2,4
Figure 1.
La Crosse virus life cycle.
La Crosse virus is endemic throughout much of the Midwest, Appalachian, Mid-Atlantic, and Southeast regions of the U.S.1,2 Most reported LACV disease cases (> 80%) are residents of 4 states (North Carolina, Ohio, Tennessee, and West Virginia).1,2 Interestingly, human seropositivity rates can vary dramatically between counties (or even neighborhoods), suggesting endemicity can be quite localized.2,4 Cases primarily occur from June to October, though they have been reported at other times in subtropical regions.1,2,5 Similar to other arboviral diseases, reported cases are more likely to be male (∼60%).1,2 Unlike other arboviral diseases, LACV disease preferentially affects children and teenagers (∼90% of reported cases are < 20 years old).1,2,5 Although the exact reason is unknown, animal models have demonstrated that the susceptibility of endothelial cells to LACV infection and the strength of the type-1 interferon response vary with age.6,7
While many LACV infections are thought to be asymptomatic, infection may result in a febrile illness, meningitis, and/or encephalitis.1,2,5,8 Approximately 70 neuroinvasive disease cases are reported each year in the U.S. with an annual incidence of 0.1–0.6 per 100 000 per year in the most affected states.1,2 The most common presentation of LACV neuroinvasive disease is encephalitis (∼80%) followed by meningitis (∼20%). 2 Fever, headache, and/or vomiting frequently occur.1,5,8 Seizures are common, and status epilepticus has been reported.1,5,8 While acute flaccid paralysis had initially been reported in one jurisdiction, this was later found to be upper motor neuron weakness (presumably from brain lesions) instead. 8 Cerebrospinal fluid (CSF)analysis often shows a lymphocytic pleocytosis with normal glucose and elevated protein.1,5 Hyponatremia can occur. 5 Neuroimaging is normal in the majority of cases, although some patients may have multifocal or diffuse cerebral edema and/or cortical enhancement. 5
Diagnosis is usually made by serology (i.e., a positive LACV-specific IgM test in serum and/or CSF).1,2 In the correct geographic, temporal, and epidemiologic setting, this can identify a probable case. However, because of significant antibody cross-reactivity among the California serogroup viruses, confirmation should be made through plaque reduction neutralization tests.1,2 Nucleic acid amplification, histopathology with immunohistochemistry, or viral culture of autopsy tissues may provide a diagnosis in fatal cases. 1
Despite active research into antiviral drugs for LACV infection, no agents are currently recommended.9,10 Management includes supportive care with early treatment of seizures, hyperthermia, hyponatremia, and any cerebral edema.1,5 While LACV infection is rarely fatal (< 1%), long-term neurologic sequelae such as epilepsy, hemiparesis, or cognitive/neurobehavioral abnormalities can result.1,2,5,8
Vaccination against LACV has been studied in animals, but no human clinical trials have been conducted so far.11-13 La Crosse virus infection can be prevented by avoiding mosquito bites (e.g., wearing insect repellant, wearing long-sleeved shirts and pants, using air conditioning or window screens when indoors) and dumping outdoor containers with standing water to reduce mosquito breeding sites. 1 Clinicians can contact their local and/or state health departments for questions regarding LACV disease or for assistance with confirmatory diagnostic testing.
Footnotes
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iD
Daniel M. Pastula https://orcid.org/0000-0001-9342-4459
References
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