Medical conditions such as cancer and diabetes, and age over 60 years, increase the risk of developing severe symptoms.

[6][7] Headache can be a prominent symptom of WNV fever, meningitis, encephalitis, meningoencephalitis, and it may or may not be present in poliomyelitis-like syndrome.

[21] West Nile virus has been seen to replicate faster and spread more easily to birds at higher temperatures; one of several ways climate change could affect the epidemiology of this disease.

[29] In mammals and several species of birds, the virus does not multiply as readily and so does not develop high viremia during infection.

[28] As a result of the differential infectiousness of hosts, the feeding patterns of mosquitoes play an important role in WNV transmission,[26][27] and they are partly genetically controlled, even within a species.

[32] The US outbreak identified additional transmission methods through blood transfusion,[33] organ transplant,[34] intrauterine exposure,[35] and breast feeding.

[37] As a precautionary measure, the UK's National Blood Service initially ran a test for this disease in donors who donate within 28 days of a visit to the United States, Canada, or the northeastern provinces of Italy, and the Scottish National Blood Transfusion Service[38] asks prospective donors to wait 28 days after returning from North America or the northeastern provinces of Italy before donating.

Mosquito saliva is a pharmacological cocktail of secreted molecules, principally proteins, that can affect vascular constriction, blood coagulation, platelet aggregation, inflammation, and immunity.

[49] Risk factors independently associated with developing a clinical infection with WNV include a suppressed immune system and a patient history of organ transplantation.

[50] For neuroinvasive disease the additional risk factors include older age (>50+), male sex, hypertension, and diabetes mellitus.

Carriers of two mutated copies of CCR5 made up 4.0 to 4.5% of a sample of people with West Nile disease, while the incidence of the gene in the general population is only 1.0%.

A recent history of mosquito bites and an acute febrile illness associated with neurologic signs and symptoms should cause clinical suspicion of WNV.

[57] Diagnosis of West Nile virus infections is generally accomplished by serologic testing of blood serum or cerebrospinal fluid (CSF), which is obtained via a lumbar puncture.

[60] If cases of suspected West Nile virus infection, sera should be collected on both the acute and convalescent phases of the illness.

[62] In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of autopsy tissues can also be useful.

[63] A number of various diseases may present with symptoms similar to those caused by a clinical West Nile virus infection.

Consideration of a differential diagnosis is required when a patient presents with unexplained febrile illness, extreme headache, encephalitis or meningitis.

When using the blood sera of wild birds and sentinel chickens, samples must be tested for the presence of WNV antibodies by use of immunohistochemistry (IHC)[70] or enzyme-linked immunosorbent assay (ELISA).

[11][86] Patients with milder WNF are just as likely as those with more severe manifestations of neuroinvasive disease to experience multiple somatic complaints such as tremor, and dysfunction in motor skills and executive functions for over a year.

[88][89] WNV was first isolated from a feverish 37-year-old woman at Omogo in the West Nile District of Uganda in 1937 during research on yellow fever virus.

[90] A series of serosurveys in 1939 in central Africa found anti-WNV positive results ranging from 1.4% (Congo) to 46.4% (White Nile region, Sudan).

The disease was first noted in horses in Egypt and France in the early 1960s and found to be widespread in southern Europe, southwest Asia and Australia.

[citation needed] The first appearance of WNV in the Western Hemisphere was in 1999[93] with encephalitis reported in humans, dogs, cats, and horses, and the subsequent spread in the United States may be an important milestone in the evolving history of this virus.

The American outbreak began in College Point, Queens in New York City and was later spread to the neighboring states of New Jersey and Connecticut.

[citation needed] In August 2024 in Warsaw the West Nile virus was identified in bodies of dead birds (Corvidae) while investigating an unusually high number of finds.

Morpholino antisense oligos conjugated to cell penetrating peptides have been shown to partially protect mice from WNV disease.

[106] Dr. Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, has urged proactive action, including international collaborations for vaccine and antiviral development, emphasizing that we must not wait for a greater crisis to address this virus.

His call for increased public awareness and scientific research followed his own recovery as a victim of the West Nile virus himself, which he most likely contracted in his Washington, D.C.–based backyard from a mosquito bite.