West Nile Virus

West Nile virus (WNV) testing is used to determine whether someone is currently or has recently been infected with WNV. Testing of symptomatic and seriously ill patients can help distinguish WNV from other conditions (such as bacterial meningitis) causing similar symptoms. WNV testing is also used in the US and Canada to screen units of blood for the virus, to detect WNV infection in the blood of living tissue and organ donors, and to track the spread of WNV through a community and across the country. Detecting the presence of WNV in the community can alert health providers and promote prevention measures.

Testing involves measurement of WNV antibodies, specific proteins created by the body’s immune system in response to a WNV infection, or measurement of WNV nucleic acid, genetic material from the virus itself.

Antibody Testing
There are two types of WNV antibodies: IgM and IgG. IgM antibodies are the first to be produced by the body in response to a WNV infection. They are present in most individuals within 8 days of the initial exposure. Antibody titres continue to rise for a short time period and then will taper off. Eventually, after several months, the IgM antibodies fall below detectible levels.

IgM WNV antibody testing may be performed on the blood or cerebrospinal fluid of symptomatic patients as an initial test. The WNV tests available may be positive both with WNV and with any related flaviviruses (viruses in the same family, such as St. Louis Encephalitis virus and Japanese Encephalitis virus). For this reason, most positive WNV IgM tests must be confirmed by another method before a diagnosis is established. If the IgM test is negative, but symptoms and clinical signs still suggest WNV, the test may be repeated on a new specimen collected a few days later.

IgG WNV antibody testing can be used, along with IgM testing, to help confirm the presence of a recent or previous WNV infection. If the IgG test is positive, then another blood sample should be collected and tested a couple of weeks later.

Since the majority of patients who become infected with WNV have no symptoms and no associated health problems, antibody testing is not used as a general screening test on asymptomatic people.

Nucleic Acid Testing
Nucleic acid testing involves amplifying and measuring the West Nile virus’s genetic material to detect the presence of the virus in blood or tissue. While it can specifically identify the presence of WNV, there must be a certain amount (number of copies) of virus present in the sample in order to detect it. Since humans are incidental hosts of WNV (birds are the primary hosts), virus levels in humans are usually relatively low and do not persist for very long.

Antibody testing may be requested during the WNV season (the peak mosquito season is generally July to October, but in some regions they may be present year-round) and when patients have travelled to areas where WNV is currently present. IgM antibody testing may be primarily requested when a patient has new symptoms suggesting a current WNV infection such as:

• headache
• fever, chills
• nausea, vomiting
• muscular weakness
• skin rash on the back or chest.

Two to four weeks after a positive WNV test, IgM and IgG WNV tests may be ordered on a follow up blood sample. If an initial IgM test is negative but symptoms persist and other conditions are ruled out, another IgM test may be ordered a few days later to determine whether IgM WNV antibodies are now present.

Testing is not usually done on asymptomatic people, but when a blood or organ recipient becomes infected with WNV, both IgM and IgG antibodies may be requested on the donor (who is frequently asymptomatic) to help determine whether they were the source of the infection.

Nucleic acid testing is now routinely used to screen units of donated blood for WNV and may be performed on the blood of tissue and organ donors prior to transplantation.

Antibody Testing
If the IgM WNV antibody is positive in blood or cerebrospinal fluid (CSF) and confirmed by another method, then it is likely that the patient has a current WNV infection, or that they had one in the recent past. If the IgM antibody is detected in the CSF, it suggests that the WNV infection is present in the central nervous system.

If IgM WNV and IgG WNV antibodies are detected in the initial sample, then it is likely that the patient contracted the WNV infection at least 3 weeks prior to the test. If the IgG WNV antibody is positive and the IgM WNV antibody level is low or not detectible, then it is most likely that the patient was previously exposed to WNV but is not currently infected. Also, if WNV IgG antibody titres in subsequent samples continue to rise, this change would indicate a more recent infection. If the WNV IgG antibody levels have not changed or have decreased, this would indicate a past but not recent infection.

The presence of WNV antibodies may indicate an infection, but they cannot be used to predict the severity of an individual patient’s symptoms or their prognosis.

Nucleic Acid Testing
If a nucleic acid test is positive for WNV, then it is likely that the virus is present in the sample tested (donated blood; blood from a living donor; a tissue sample from a human, bird, or other animal; or a mosquito pool sample) and is present in the geographic location where the sample was collected.

A nucleic acid test may be negative for WNV if there is no virus present in the sample tested or if the virus is present in very low (undetectable) numbers. A negative test cannot be used to definitely rule out the presence of WNV.

In some warm areas, WNV is present year-round, but in most regions, it is seasonal – cases occur during the mosquito season. The amount of WNV present depends in part on the number of infected birds and the mosquito population. Prevention depends on controlling individual exposure and on controlling the mosquito population. According to the UK Health Security Agency (as of 20th August 2018), there have been occasional cases of infection in the UK associated with travel. Previously, the main risk of WNV for UK residents has been for those travelling abroad. However, in 2010, the mosquito species responsible for transmission of the virus (between birds, horses and humans) was detected for the first time in the UK since 1944. This finding may increase the risk of WNV being transmitted in the UK.

Nucleic acid testing and viral cultures are used in research settings to identify the strain of virus causing the infection and to study its attributes. Different strains of WNV have been isolated and associated with different epidemics around the world.

Not for humans yet, but there may be one or more vaccines available in the next few years. A vaccine has been developed by mixing West Nile virus with a vaccine for yellow fever, altering the proteins coating the established vaccine. This new vaccine has been successfully tested for safety and effectiveness in animals and is now being tested in humans.

Another potential West Nile virus vaccine that uses an inactive protein (instead of a live virus) also has been developed and undergone some initial testing. It would have the advantage of being able to be given to anyone, even children, pregnant women, or those who are immunosuppressed.