Pathogens are inoculated peripherally, replicate and disseminate through the bloodstream. In immunocompetent patients, this process is generally associated with seroconversion and results in virus clearance. Thus, most patients who contract an arbovirus infection remain asymptomatic or merely develop flu-like symptoms. Neuroinvasion and AE are more likely in those individuals suffering from an immune system disorder, receiving immunosuppressive medication, and the elderly, and occurs in less than 1% of cases [7].

After an incubation period of a few days, AE patients start to suffer from flu-like symptoms such as fever, headaches, and myalgia. A short period of apparent resolution may pass until additional symptoms manifest, namely nausea, vomiting and meningism with neck stiffness [3]. The onset of neurological symptoms clearly indicates central nervous system involvement, and patients may present with an altered mental status, tremor, myoclonic jerks, seizures, limb weakness, paralysis, and photophobia. Reduced consciousness ranging from somnolence to coma may be observed.

AE-associated symptoms generally persist for few weeks, but may occasionally last several months.

• Pathologist

  Tissue pathways for urological pathology The target primary users of the tissue pathway are trainee and consultant cellular pathologists. These recommendations will also be of value to trainee/qualified biomedical scientists involved in... [evidence.nhs.uk]

Symptoms presented in the case of AE are unspecific. The consideration of anamnestic data is of utmost importance at the time of establishing a list of differential diagnoses. Patients should be queried about recent journeys and stays in endemic areas as described above.

The following diagnostic measures may be undertaken to confirm a tentative diagnosis of AE:

• Proof of seroconversion.
  
• An analysis of cerebrospinal fluid regarding the presence of immunoglobulin-M (IgM) antibodies against either of the pathogens described above, is considered the gold standard for the detection of neuroinvasive arboviruses and AE [8].
• Determination of cerebrospinal fluid/serum antibody ratios, with high ratios indicating central nervous system disease.
• Detection of antigens or nucleic acid by means of molecular biological assays such as polymerase chain reaction, using serum or cerebrospinal fluid samples, (preferred in immunocompromised patients) [9] [10].
• Isolation and culture of arboviruses (although difficult and not routinely performed).

Pathogens pertaining to distinct families of viruses may trigger the following diseases:

• Bunyaviridae: California encephalitis and sandfly fever
• Flaviviridae: Japanese encephalitis, Murray Valley encephalitis, Powassan encephalitis, St. Louis encephalitis, tick-borne encephalitis, and West Nile Encephalitis
• Togaviridae: Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis

Other arboviruses are primarily known to cause systemic febrile disease or hemorrhagic fever, but affected individuals may occasionally develop AE. For instance, this applies to the causative agents of Colorado tick fever, Kyasanur forest disease, and Rift Valley fever [3].

While arboviruses are distributed throughout the world, specific viruses may only be encountered in determined geographic areas. For instance, the distribution of vectors, as well as wild animals that constitute the natural reservoir of these pathogens, may demarcate affected geographic regions. The latter, in turn, are strongly influenced by climatic conditions, and the climate change may entail the expansion of arboviruses [4]. To date, distribution patterns of AE are as follows [5]:

• California encephalitis: North America
• Sandfly fever: Europe, northern Africa, Middle East and South Asia
• Japanese encephalitis: Asia, Pacific islands [6], northern Australia
• Murray Valley encephalitis: Australia
• Powassan encephalitis: North America, Russia
• St. Louis encephalitis: Americas, Europe, and Asia; highest incidence rates reported in the United States
• Tick-borne encephalitis: Europe and Asia
• West Nile fever: worldwide; highest incidence rates reported in northern Africa and the Middle East
• Eastern equine encephalitis: America
• Western equine encephalitis: America
• Venezuelan equine encephalitis: America

Arbovirus is a non-taxonomic term coined to refer to viral pathogens transmitted by arthropods. In detail, humans may contract an infection with an arthropod-borne virus after getting bitten by mosquitoes, flies or ticks. Furthermore, infected organ transplants and blood products constitute possible sources of infection [1] [2]. Patients suffering from an arbovirus infection may present with systemic febrile illness, hemorrhagic fever or encephalitis. Pathogens that may provoke arbovirus encephalitis (AE) and corresponding entities are detailed below.

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10. Penn RG, Guarner J, Sejvar JJ, et al. Persistent neuroinvasive West Nile virus infection in an immunocompromised patient. Clin Infect Dis. 2006; 42(5):680-683.