Arboviruses, also known as arthropod-borne viruses, refer to a diverse group of viruses that are transmitted via mosquitos, ticks, or sandflies. This group of viruses belongs to the families Togaviridae, Flaviviridae, Bunyaviridae, and Reoviridae. These families have similar RNA genomes that permit mutations that allow them to acclimate to changing environments or host conditions. These viruses are unique as they require vectors for biological transmission to humans. It is important to understand the disease processes caused by these infectious agents, given the increasing frequency of infection and the potential for additional emerging diseases.
Arboviruses can cause multiple neurological diseases, including myelitis, neuritis, myositis, meningitis, and encephalitis. Mortality rates related to these infections increase with the diagnosis of encephalitis. Thus arboviruses are important differentials to consider when evaluating a febrile patient with neurological symptoms. Although arboviruses can cause a wide range of infections, this article will cover major features of the more common arthropod-borne neurotropic viruses that cause endemic and travel-associated encephalitis.
There are many epidemiologic features to consider when evaluating patients for potential etiologic agents of encephalitis. Exposure history, including place of residence, recent travel, insect contact, animal contact, occupation, recreational activities, and diet, can help guide initial diagnostic testing. Additional factors such as age, vaccination history, immune status, and seasonal variation can also help narrow one’s differential. See table 1 for vectors and geographical distribution associated with each virus.
The degree to which arboviruses can cause neuroinvasive disease depends on both host and virus factors. Although several mechanisms have been described, the exact pathway by which arboviruses can enter the central nervous system (CNS) remains unknown. The infection can then both directly and indirectly cause neuronal injury and apoptosis.
Arbovirus infections can vary in clinical presentation. As patients can present with nonspecific symptoms, one's initial differential diagnosis must remain broad. Fevers, headaches, altered mental status, seizures, and focal neurological deficits are common findings in individuals who present with encephalitis. Some infected patients may experience a flu-like illness prior to having any neurological symptoms. Importantly, the combination of fever, headache, and altered mental status can symbolize acute encephalitis syndrome.
Physical exam findings can also assist in determining the cause of a patient's encephalitis. Skin rashes, for example, can be associated with WNV or zika virus. Ocular findings such as chorioretinitis, retinal hemorrhages, and vitreitis can be seen with WNV. Furthermore, certain neurological findings can aid in determining a specific etiology of viral encephalitis. For example, certain flaviviruses such as WNV, SLE virus, and JEV can cause signs and symptoms of parkinsonism. Additionally, these viruses can also cause seizures, cerebellitis, and symptoms of brain stem involvement.
Patients should undergo a lumbar puncture if there are no contraindications to the procedure. Cerebrospinal fluid (CSF) should be sent for cell count and differential, glucose concentration, protein concentration, culture, and gram stain. CSF analysis will typically reveal lymphocytic pleocytosis, normal glucose, and elevated protein with a negative gram stain.
Virus-specific IgM and PCR of CSF and serum are helpful in obtaining a diagnosis when available. It is important to note that cross-reactivity has been demonstrated among flaviviruses. Plaque reduction neutralization testing can be beneficial in these instances.
Neuroimaging studies, preferably magnetic resonance imaging (MRI), should also be considered when evaluating a patient for encephalitis as distinct MRI findings can provide additional guidance in diagnostic testing. For example, MRI findings of diffusion restriction and abnormal signal intensities on T2 and FLAIR imaging can be indicative of WNV. Some studies have reported similar MRI abnormalities with JEV and SLE virus.
Electroencephalograms (EEG) are typically abnormal in patients with viral encephalitis and typically show generalized slowing. In patients with WNV encephalitis, the most common EEG abnormality include diffuse irregular slow waves.
Brain biopsy can be considered in patients with encephalitis with neurological deterioration if other non-invasive test is nonrevealing.
If neuroinvasive disease is suspected or confirmed to be secondary to an arbovirus, management involves supportive care as there are no current antiviral treatment options.
Infection prevention is important to consider in endemic regions and include vector control, personal protective measures, and vaccination when available. The approach for travelers includes avoiding infected areas, reducing exposure to vectors by wearing long clothing and using insect repellant, and considering vaccine if available if traveling to high-risk areas.
Prognosis varies for each virus. Although most infected individuals are asymptomatic and have a complete recovery, mortality rates have been reported from <1% up to 30% with neuroinvasive disease. Patients that recover from neurological manifestations of the infection often have long-term neurological sequelae.
Many patients require hospitalization for supportive care, including respiratory support. Long-term neurological sequelae are common in individuals diagnosed with arthropod-borne encephalitis. For example, previous studies of patients hospitalized with WNV encephalitis have demonstrated neurocognitive deficits and self-reported symptoms ranging from fatigue to neurological symptoms lasting from months to years after the onset of illness.
It is important to be aware of the infectious complications related to arboviruses that can be transmitted via mosquitos and ticks. As no treatment options are available, educating patients on the geographical distribution of these viruses to practice infection prevention is important when traveling to endemic areas. Resources for such information can be found online through the Center for Disease Control (CDC) and the World Health Organization. Using insect repellant, wearing long-sleeved clothing, and checking for ticks can help prevent diseases related to these viruses.
An interprofessional team approach in evaluating patients with symptoms concerning for encephalitis can help facilitate an early diagnosis as appropriate diagnostic testing can be ordered upon the first presentation. Although there are no current treatment options for arbovirus encephalitides, early diagnosis can help identify the need for supportive treatment sooner and prevent any additional invasive testing.
Additionally, it is important to note that many endemic arboviruses are nationally notifiable diseases and should be reported to the CDC via ArboNET, a national surveillance system. This will ensure that appropriate public health measures are taken to identify outbreaks and prevent additional cases of the disease. Furthermore, it provides additional information regarding these viruses in terms of their epidemiology, seasonality, and geographical distribution.
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