Special Feature

What You Need To Know About West Nile Virus

By Saadia R. Akhtar MD, MSc, Idaho Pulmonary Associates, Boise. Dr. Akhtar does research for Eli Lilly.
This article originally appeared in the January 2007 issue of Critical Care Alert. It was edited by David J. Pierson, MD, and peer reviewed by William Thompson, MD. Dr. Pierson is Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, and Dr. Thompson is Staff Pulmonologist, VA Medical Center; Associate Professor of Medicine, University of Washington. Dr. Pierson and Dr. Thompson report no financial relationships relevant to this field of study.

West nile virus (WNV) infection is a growing epidemic that impacts more persons and more aspects of our health care system yearly. A significant percentage of affected patients require admission to, and care in, an intensive care unit (ICU). Those with the most severe manifestations — meningoencephalitis and/or acute flaccid paralysis — may have prolonged ICU stays with considerable long-term morbidity and mortality. Thus, it is essential that all health care personnel in the critical care community become familiar with WNV.


WNV is a single-stranded RNA virus of the family Flaviviridae, which includes the arboviruses Japanese encephalitis and St. Louis encephalitis viruses. It was first discovered about 70 years ago in Uganda. It was not until the 1990s that it began to spread across the world and ultimately appeared in the United States in 1999.1-2 (The strain found in the United States is genetically almost identical to a strain from the Middle East and has not changed significantly since 1999.) Most human WNV infections occur at the times of peak mosquito activity which in the United States is July through October. However, cases have been reported from April to December. Persons of all ages may be affected.2

Between January 1 and November 28, 2006, 4028 cases of human WNV infection from across the continental United States were reported to the Centers for Disease Control and Prevention (CDC). This number represents a 27-fold increase in cases since 2001. The largest numbers of cases were detected in Idaho (889). Neuroinvasive disease (meningitis, encephalitis, or myelitis) occurred in 34.4% or 1386 of these cases. Overall mortality was 3.4% (135 persons). This year, the median age of affected patients was 51 years and 55% of patients were male. 3


Mosquitoes (of the Culex species) serve as the primary transmitters of WNV. They acquire infection by feeding on infected birds and subsequently transmit the virus by biting humans or other birds and animals. (Birds of more than 100 species may be affected by WNV but the most common hosts are crows, jays and ravens in the Corvidae family.) Although fecal-oral transmission may occur among birds, its significance remains unclear. Humans and other animals do not develop high enough levels of viremia to be carriers of disease that uninfected mosquitoes can acquire: that is, there is no human-to-human transmission by mosquitoes and no animal-to-human transmission. There is, however, WNV transmission via human tissue and body fluids. This includes blood products (packed red cells, platelets and plasma), solid organs (either via organ transplantation or exposure of health care workers during autopsy), and breast milk. Transplacental transmission with devastating fetal outcomes has also been reported although this appears to be rare.4,5

Clinical Features and Outcomes2,4,6-7

The incubation period for human WNV infection is 2-14 days. It is estimated that 80% of infected persons are asymptomatic. The most common clinical presentation is that of a mild flu-like illness or what is termed West Nile fever: general malaise, fever, headache, myalgias and anorexia lasting 3-6 days, but more protracted courses have been described. Lymphadenopathy or a transient erythematous fine maculopapular rash of the face and trunk may be seen. Symptoms resolve fully with supportive care.

Neuroinvasive disease is the next most common manifestation: meningitis, encephalitis and/or myelitis with acute flaccid paralysis are well-described. These are estimated to represent less than 1% of WNV infections.8 Advanced age (> 50 years) is a clear risk factor for development of neuroinvasive disease. There is suggestion that diabetes and alcohol abuse may be factors as well. 9

WNV meningitis resembles other viral meningitides and presents with fever, headache, nausea, vomiting, nuchal rigidity and photophobia. WNV encephalitis may present with all of these plus altered mental status, focal neurological changes and, less commonly, seizures. In WNV encephalitis, tremor is common and other movement disorders have also been reported. WNV acute flaccid paralysis may be symmetric or asymmetric and clinically and pathologically resembles poliomyelitis. There is hypo- or a-reflexia and often bowel and bladder dysfunction. Sensation, however, is intact. Pathology generally reveals destruction of anterior horn cells. Rarely, demyelinating syndromes have been reported. Guillain-Barré syndrome is in the differential and must be ruled out with history, serological testing and, if needed, electromyographic and nerve conduction studies. Finally, WNV has also been reported to cause chorioretinitis and vitritis.8

On routine blood work, patients may have a mild leukocytosis or leukopenia and mild hyponatremia. With neuroinvasive disease, spinal fluid reveals mild to moderate pleocytosis (typically < 500 cells/mm3 although > 2000 have been reported), usually lymphocytic, with elevated protein and normal glucose. Head CT is generally unremarkable. Brain and spine MRI are normal in the majority of patients but in about one-third may reveal leptomeningeal or periventricular enhancement or increased signal on T2-weighted images of the thalamus, basal ganglia, brainstem, or spinal cord.

Rarely, WNV has been reported to cause acute pancreatitis, hepatitis, nephritis, myocarditis, or a septic shock-like syndrome with multisystem organ failure.

Overall, about one-third of patients with WNV infection are hospitalized. In one series from the Colorado experience in 2003, 34-38% of patients with encephalitis or limb weakness required intubation and mechanical ventilation9; in another recent review of WNV-associated acute flaccid paralysis, 54% of patients required ventilatory support.10 ICU lengths of stay for these patients may be quite long (up to 118 days in one study).11 Mortality of those with neuroinvasive disease is up to 7-18% and even higher in patients with acute flaccid paralysis with quadriparesis or those requiring mechanical ventilatory support.7,10,12 Significant neuropsychological impairments remain at 8-12 months of follow-up of patients with WNV neuroinvasive disease, with complaints including general fatigue and weakness, memory loss, cognitive dysfunction, tremor, gait abnormalities, and depression. Those with acute flaccid paralysis in particular appear to have only limited recovery at best. 12-13

Diagnostic Studies4,6

Presence of WNV virus in any body fluid or tissue (usually detected by PCR) confirms the diagnosis of WNV infection. However, the likelihood of isolating the virus is quite low; by the time symptoms of illness develop, only very low levels of viremia are present. For instance, sensitivity of WNV PCR of CSF for patients with neuroinvasive disease is ≤ 50%.

Thus, diagnosis is generally made by detection of serum or CSF antibodies to WNV in the appropriate clinical setting. Measurement of WNV IgM and IgG by antibody capture enzyme linked immunoabsorbent assay (MAC-ELISA) is the recommended method for confirming diagnosis. WNV IgM antibodies become positive by the 8th day of illness in ≥ 90% of patients; it is important to note that they may persist for ≥ 6-12 months. Presence of WNV IgM in the CSF confirms neuroinvasive disease. WNV IgG antibodies begin to appear at one week and are positive by 3 weeks in most infected patients; thus, an increase in titer over this time period is strongly suggestive of acute infection. (The CDC case epidemiological case definitions for WNV infection are listed in the Table 1.)

The duration of viremia, and time to development of antibodies, may be delayed in immunocompromised patients.

There is cross-reactivity between antibodies against WNV and antibodies against other viruses of the Flaviviridae family. Thus, it is important to obtain appropriate clinical history to evaluate for these and to confirm any positive WNV antibody result by MAC-ELISA with further, more specific testing (plaque reduction neutralization assay).


Supportive care is the mainstay of therapy for WNV infection. There have been in vitro or animal studies and anecdotal human reports of therapy with WNV-specific-IV-immunoglobulin, ribavirin, interferon-alpha and corticosteroids. Results have been mixed. At this time there is insufficient evidence to recommend any of these therapies. PREVENTION2,4,7

An equine WNV vaccine was licensed in 2003 and is currently in use. No human vaccine is yet available although studies of candidate vaccines are ongoing.

Avoiding exposure to infected mosquitoes is the primary route of prevention of WNV infection. This is particularly important for persons who are elderly, pregnant, or immunocompromised. Recommended methods include using insect repellent (containing DEET, permethrin, picaridin or oil of lemon eucalyptus), wearing long-sleeved and long-legged clothing, limiting outdoor activity during dusk to dawn (the peak mosquito hours), and using door and window screens on homes and draining standing water to avoid creating mosquito breeding areas. Local mosquito control programs including spraying of large areas with larvicides or insecticides may be necessary in some locations.

The FDA recommends routine screening of blood products for WNV between June 1 and November 30. Furthermore, donors with symptoms of flu-like illness in the week prior to presentation to blood banks are asked to defer donation for one month. Cases of persons who are found to develop WNV infection after donation or persons with WNV illness who received transfusion in the month preceding onset of illness are also investigated in order to identify and remove infected blood products from the supply.


WNV infection is an increasing problem in the United States. Our knowledge of its epidemiology and clinical impact is still developing. Until targeted therapies and a specific preventive vaccine are identified, supportive care remains the mainstay of treatment. It is clear that for now we will continue to encounter WNV infection cases resulting in severe illness, substantial morbidity including need for prolonged critical care services and support for long term neurological deficits, and significant mortality.


1. Nash D, et al. 1999 West Nile Outbreak Response Working Group. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med. 2001;344:1807-1814.

2. Hayes EB, Gubler DJ. West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States. Annu Rev Med. 2006;57:181-194.

3. http://www.cdc.gov/ncidod/dvbid/westnile/index.htm.

4. Sampathkumar P. West Nile virus: Epidemiology, clinical presentation, diagnosis and prevention. Mayo Clin Proc. 2003;78:1137-1144.

5. O'Leary DR, et al. Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics. 2006;117:e537-545.

6. Petersen L, et al. West Nile virus. JAMA. 2003;290:524-528.

7. Tyler KL. West Nile virus infection in the United States. Arch Neurol. 2004;61:1190-1195.

8. Sejvar JJ, Marfin AA. Manifestations of West Nile neuroinvasive disease. Rev Med Virol. 2006;16:209-224.

9. Bode AV, et al. West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003. Clin Infect Dis. 2006;42:1234-1240.

10. Saad M, et al. Acute flaccid paralysis: the spectrum of a newly recognized complication of West Nile virus infection. J Infect. 2005;51:120-127.

11. Fan E, et al. West Nile virus infection in the intensive care unit: a case series and literature review. Can Respir J. 2004;11:354-358.

12. Sejvar JJ, et al. West Nile Virus-associated flaccid paralysis outcome. Emerg Infect Dis. 2006;12:514-516.

13. Sejvar JJ, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA. 2003;290:511-515.

14. Gea-Banacloche J, et al. West Nile virus: pathogenesis and therapeutic options. Ann Intern Med. 2004;140:545-553.

15. Kalil AC, et al. Use of interferon-alpha in patients with West Nile encephalitis: report of 2 cases. Clin Infect Dis. 2005;40:764-766.

16. Anderson JF, Rahal JJ. Efficacy of interferon alpha-2b and ribavirin against West Nile virus in vitro. Emerg Infect Dis. 2002;8:107-108.