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West Nile Virus (WNV)


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Published: September 2012

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West Nile virus infection first appeared in the United States in 1999. Since that time, West Nile infections are found in all 48 contiguous states and have caused illness in >30,000 people, including potentially life-threatening disease. Dr. Pritt describes clinical presentation, diagnosis, and prevention of West Nile virus infection.

Presenter: Bobbi Pritt, MD

  • Associate Professor of Laboratory Medicine and Pathology and Microbiology
  • Director of the Clinical Parasitology and Initial Processing Laboratories
  • Director of vector-borne disease molecular testing and a consultant in the Division of Clinical Microbiology

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Today we’re going to be talking about West Nile virus, a mosquito-borne virus that is currently infecting many people in the United States.

Before we begin, I would like to state that I have no disclosures, and that I will not be discussing any off-label usages of drugs or devices.

I’d now like to start with some background information about this important virus. West Nile virus is a single-stranded virus containing RNA as its only form of nucleic acid. The basic structure of this virus is shown on the right, demonstrating its nucleic acid surrounded by a protective protein capsid and lipid envelop. West Nile virus is a member of the Flaviviridae family, which includes other flaviviruses such as dengue virus and Japanese encephalitis virus.

West Nile virus is mainly transmitted through the bite of an infected mosquito and mostly involves birds as primary hosts. However, the virus can also infect humans or horses, causing serious illness and even death. Humans are considered incidental or “dead end” hosts since the levels of viremia do not typically become high enough to allow transmission of the virus to another mosquito.

In addition to mosquito bites, there are other, less common, means of transmission.
Blood transfusion is an important method of transmission, and donor blood units are now screened for the virus prior to transfusion. This has substantially reduced the risk of West Nile virus infection from blood transfusion. There are also rare reports of transmission from organ transplantation, breast feeding, from mother to child during pregnancy, and occupational exposure in laboratory workers. Of note, the virus is not transmitted by casual contact, including touching or kissing an infected person and there is no evidence that it is transmitted by handling dead birds, although glove use is advised in that situation.

West Nile virus has been with us for quite some time. It was first recognized in the West Nile district of Uganda, Africa in 1937, and was subsequently recognized as an endemic infection in Africa, Asia, and the Middle East. However, it did not appear in the United States until 1999 and it reached epidemic proportions in 2002. It is now found in all 48 contiguous states and it causes a seasonal illness in temperate climates (usually in the late summer and early fall) or year round disease in the southern United States and it potentially causes serious, life-threatening disease. West Nile virus has caused illness in >30,000 people in the United States to date. Most recently, there has been an increase in disease involving the central nervous system in 2012. This form of disease is called neuroinvasive disease and carries a high associated morbidity and mortality.

On this next slide, you can see the annual incidence of neuroinvasive disease caused by West Nile virus in the United States. Note that the number of cases for 2012 already exceeds the number of annual cases seen in the past 4 years, despite the fact that this graph only represents data up until August of 2012.

Here is a map showing the breakdown of cases by state, showing that several states, including Texas, are bearing the brunt of the neuroinvasive disease.

In fact, numerically, Texas has the highest number of total and neuroinvasive cases, as shown here, followed by Mississippi and South Dakota. This slide shows the tops10 states that have the highest number of cases so far for 2012.

So, how do patients present when they are infected with West Nile virus? Well, fortunately, most infected individuals are asymptomatic. However, approximately 20% of infected individuals will develop a mild infection called West Nile fever, which includes the following symptoms such as fever, headache, body aches, and fatigue. Less commonly, patients may also have a skin rash and swollen lymph nodes. Symptoms can last for days to weeks, even in otherwise healthy individuals.

Most worrisome, however, is the severe form of the infection, which is estimated to occur in 1 of every 150 infected individuals. The signs and symptoms of severe disease are
high fever, severe headache, stiff neck, muscle tremors, lack of coordination, convulsions, disorientation, confusion, partial paralysis or sudden weakness, and even coma and death. The risk factors for severe disease include an age over 60 years, diabetes, hypertension, chronic alcohol abuse, history of malignancy, and chronic kidney disease.

Therefore, accurate diagnosis of West Nile virus infection is essential for determining the appropriate clinical management of the patient.  The clinical symptoms are nonspecific by themselves, and therefore the use of laboratory diagnostics is required. Therefore, it is important to understand the different modalities available for diagnosis since they have varying utility in different phases of the disease: Serology and PCR are the most commonly used methods for laboratory diagnosis. Culture is also an option, but it is not widely available and not performed in the routine clinical laboratory. There is also histopathology with immunohistochemistry that can be used especially for fatal cases, and this is typically performed at the CDC.

This next slide shows the progression of West Nile virus infection and how the different laboratory methods can be put to use at various times of the illness. First, it is essential to mention that there is an incubation period of 2 to 15 days after the bite of an infected mosquito, during which time the patient is asymptomatic. However, the patient will soon become viremic, and viral RNA can be detected in the patient’s blood at this time. Meanwhile, the patient’s immune system will start to develop an immune response to the virus. By day 8, there is typically a detectable virus specific IgM response, followed several days later by a detectable IgG response. During the viremic stage, PCR can be used to detect viral RNA in the patient’s blood. RNA can also be detectable in the spinal fluid if the central nervous system is involved. However, note that the viremic period overlaps significantly with the incubation period, so it is very possible that the patient will be completely asymptomatic during this time and not present to their physician for testing. For this reason, the role of PCR is limited in the diagnosis of West Nile virus infection to the very early stages of illness. Instead, serology is the test of choice throughout most of the patient’s illness.

As mentioned previously, IgM antibodies become detectable in serum
approximately 8 days postinfection. However, it is very likely that they will be negative before this time and so if West Nile virus is strongly suspected, but serum antibodies tests drawn early in infection are negative, then serum can be redrawn several days later for additional antibody testing. IgM antibodies will remain detectable for 1 to 2 months following infection, even after the patient has cleared their infection and fully recovered. In comparison to IgM antibodies, IgG antibodies can be detected later on in the disease, with a rise in IgG titers typically seen if serum samples are drawn on days 7 and then again between days 14 to 21 of illness. Finally, detection of IgM and IgG antibodies in the CSF is the preferred method for documenting CSF disease. However, serologic cross-reactivity with other closely related viruses may cause false-positive results so serologic testing for these other viruses might also be indicated.

In general, PCR testing is less useful than serology, due to low level, transient viremia that overlaps with the asymptomatic incubation phase. However, PCR may be useful for: early disease, before IgM levels are detectable; for detection of virus in immunocompromised patients, in which RNA may persist for longer periods of time; and for screening donor blood units prior to transfusion. PCR can also be used for postmortem studies, when West Nile virus is the suspected cause of the patient’s death.

Unfortunately, there is no specific antiviral treatment available for West Nile infection.
Instead, patients are treated with supportive therapy including IV fluids and breathing assistance if necessary. Because West Nile virus infection can be severe and there are no effective antiviral therapies, prevention is key!

Prevention is best accomplished by using an insect repellent that has been registered by the U.S. Environmental Protection Agency, such as DEET or picaridin. Permethrin can also be used on treated clothing and gear, and many products can be purchased that are already impregnated with this insecticide. Use of a repellent is especially important when spending time outside during the times of peak mosquito activity, such as dawn and dusk. Other protective measures such as wearing long pants and a long-sleeved shirt when outdoors can be quite effective. And, in the community, individuals can take steps to decrease mosquito breeding sites, such as removing sources of standing water like old tires, wading pools and bird baths. And some communities that are especially hard hit with the current West Nile virus epidemic are using techniques such as aerial spraying of insecticides.

So, in summary, West Nile virus disease is endemic in the United States and causes seasonal outbreaks, and the size of the annual outbreak is unpredictable. Also, there is no specific antiviral treatment available. Therefore, preventing mosquito bites is the most important measure that individuals can take to protect themselves from West Nile virus infection. Finally, diagnosis is important for patient care and for epidemiologic studies and is performed using a combination of clinical symptoms and classic laboratory methods such as serology. Thank you for your time.