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West Nile Virus Infection: Are You Prepared?


n the United States, the number of cases and geographic range of West Nile virus infection have increased since 1999, when the virus first surfaced in the Western Hemisphere. This year, the virus is expected to spread to all states except Alaska and Hawaii.

BRIAN S. KOLL, MD Albert Einstein College of Medicine

In the United States, the number of cases and geographic range of West Nile virus infection have increased since 1999, when the virus first surfaced in the Western Hemisphere. This year, the virus is expected to spread to all states except Alaska and Hawaii.

Here I focus on what you need to know now to recognize and manage this infection.


The West Nile virus-a mosquito-borne flavivirus closely related to St Louis encephalitis and Japanese encephalitis viruses-was first isolated and identified in 1937 from an infected person in the West Nile district of Uganda. Before the mid-1990s, human outbreaks were infrequent and were reported mainly in groups of soldiers, children, and healthy adults in Israel and Africa. Infection usually resulted in a mild febrile illness.

Since the mid-1990s, the frequency and severity of West Nile virus outbreaks have increased. Outbreaks in Romania, Russia, and Israel involved hundreds of persons who had severe neurologic disease. It is not known whether the change in disease severity and frequency results from differences in the circulating virus's virulence or from changes in the age demographics, background immunity, or prevalence of predisposing chronic conditions in the affected populations.1,2


In August 1999, the first occurrence of West Nile virus in the Western Hemisphere was recognized when an outbreak in New York City resulted in 62 cases of acute encephalitis. During this outbreak, 7 patients died. Mortality among horses and birds was also substantial.3,4

Since 1999, there have been human outbreaks of West Nile virus encephalitis and aseptic meningitis every summer and fall. National surveillance has documented an increasing number of cases of West Nile virus infection (62 persons in 1999, 21 in 2000, 66 in 2001, and 4156 in 2002) occurring in an increasing number of states (1 state in 1999, 3 in 2000, 10 in 2001, and 44 in 2002).1 The 2002 West Nile virus outbreak in the United States was the largest outbreak of arboviral meningoencephalitis ever documented in the Western Hemisphere.

As of mid July 2003, 31 states reported West Nile virus activity in birds, horses, or mosquitoes; in addition, 3 human cases in Texas and South Carolina were reported to the CDC. Up-to-date maps showing the United States distribution of West Nile virus are available at: http://www.cdc.gov/ncidod/dvbid/ westnile/index.htm.


In the United States, West Nile virus is mainly transmitted by infected mosquitoes, primarily members of Culex species. In 2002, several new modes of transmission were documented (see Box on page 1148).

West Nile virus is maintained in an enzootic cycle that involves Culex mosquitoes and bird reservoir hosts. Although birds-particularly crows, ravens, and jays-infected with West Nile virus can become ill or die, most infected birds survive and develop lifelong immunity. Deaths in crows have increased markedly shortly before human cases have appeared.

There is no evidence that a person can acquire West Nile virus infection from handling live or dead infected birds. However, persons should avoid bare-handed contact when handling any dead bird, use gloves or double plastic bags to place the bird carcass in a garbage bag, and contact their local health department for guidance.

In temperate regions, adult mosquitoes begin to emerge in the spring. Viral amplification occurs in the bird-mosquito-bird cycle until early fall. When environmental conditions promote significant amplification, sufficient numbers of "bridge vector" mosquitoes (mosquitoes that bite both humans and birds) become infected in late summer and then pose an infection threat to humans. Year-round transmission is possible in tropical climates.1

Humans, horses, and most other mammals are probably "dead-end" or incidental hosts. Although West Nile virus does not appear to cause extensive illness in dogs or cats, a serosurvey in New York City of dogs in the 1999 epidemic area indicated that dogs are frequently infected.5 Nonetheless, clinical disease from West Nile virus infection has not yet been found in dogs. Cases of disease in horses have been documented, however. About 40% of equine West Nile virus infections result in the death of the horse. There is no documented evidence of animal-to-person transmission of West Nile virus.


The incubation period of West Nile virus infection ranges from 3 to 14 days. Most infected persons have no symptoms. A small number experience mild symptoms that include fever, headache, body aches, rash, and swollen lymph nodes. A serosurvey performed during the 1999 New York City epidemic indicated that fever developed in about 20% of persons infected with West Nile virus; only half of these persons sought medical attention.6

More severe illness-including meningitis and encephalitis-develops in fewer than 1% of infected persons. Of those who have encephalitis, death is estimated to occur in fewer than 1 of 1000.5

First US outbreak: clinical features. During the initial West Nile virus outbreak in New York City, 59 patients with meningoencephalitis were hospitalized. Most patients were at least 50 years old; had encephalitis; and presented with fever, weakness, nausea, vomiting, headache, and altered mental status. Twenty percent of the patients had an erythematous macular, papular, or morbilliform eruption involving the neck, trunk, arms, or legs. Decreased muscle strength and hyporeflexia were noted in a third of affected patients.7

Older age was associated with a substantially higher risk of more severe neurologic disease. An age of 75 years or older was the factor most strongly associated with death; the presence of diabetes mellitus was also significantly associated with death. The overall case-fatality rate was 12%. Infected Culex mosquitoes were the only known vectors in this outbreak.7

The initial outbreak followed a pattern more characteristic of recent outbreaks of encephalitis in areas where the virus is not endemic and where the level of immunity of the population to the West Nile virus is lower (eg, Romania and Russia). In these outbreaks, recognized illness was characterized by severe neurologic disease that affected primarily older adults. In regions where the virus is endemic, outbreaks of milder febrile illness usually occur.7

Paralytic poliomyelitis-like syndrome. Approximately half of hospitalized patients in the United States with West Nile virus infection have severe muscle weakness. This symptom may provide a clue to the diagnosis, especially in the setting of encephalopathy. About 10% of patients in the New York City outbreak had complete flaccid paralysis. In fact, several patients had such profound weakness that they were first thought to have Guillain-Barré syndrome.1,4

Recent findings have shed light on the pathogenesis of the muscle weakness associated with West Nile virus infection. Asymmetric flaccid paralysis and areflexia in the setting of West Nile virus infection had previously been thought to be secondary to Guillain-Barré syndrome or axonal polyneuropathy. Careful study of patients with West Nile virus-associated acute flaccid paralysis-using electrophysiologic, laboratory, and neuroimaging data-has shown that the symptoms may be attributable to involvement of anterior horn cells and motor axons, which causes a syndrome similar to that found in acute poliomyelitis. Evaluation by a neurologist to determine the underlying cause is recommended before instituting empiric therapy for Guillain-Barré syndrome.8,9

Sequelae. Few data exist regarding the long-term morbidity after hospitalization for West Nile virus infection; the evidence available suggests that many patients have substantial morbidity. Among those hospitalized in New York and New Jersey in 2000, more than half had not returned to their previous functional level by discharge and only one third were fully ambulatory. At 1-year follow-up, many patients involved in the 1999 outbreak in New York had frequent, persistent symptoms (fatigue, 67%; memory loss, 50%; difficulty in walking, 49%; muscle weakness, 44%; and depression, 38%).1


Table 1 lists several clues that signal the possibility of West Nile virus infection. If any of these features are present, prompt definitive diagnostic testing is warranted.10

The most sensitive screening test for West Nile virus is the IgM-capture enzyme-linked immunoabsorbent assay (ELISA) for cerebrospinal fluid (CSF) and/or sera. Specimens that test positive for West Nile virus by ELISA require confirmation by plaque reduction neutralization testing (PRNT) to rule out cross-reactivity with other flaviviruses, such as those that cause St Louis encephalitis or dengue. Cross-reactivity is also noted in persons who recently were vaccinated against yellow fever or Japanese encephalitis. PRNT is the most specific test for arthropod-borne flaviviruses.

Data from recent outbreaks suggest testing for West Nile viral RNA by polymerase chain reaction (PCR) assay (by either standard reverse transcriptase or the real-time quantitative method) is not as sensitive as serologic testing. Only 6.9% of patients with laboratory-confirmed cases of West Nile virus infection in New York City (from 2000 to 2002) had positive PCR assays of CSF; in contrast, nearly all (95%) had positive ELISA results.11 CSF testing is most sensitive if performed within 8 days of illness onset, while serologic testing is most sensitive if done within 8 to 14 days. Although it is possible to culture West Nile virus from CSF or brain tissue, low sensitivity prevents the use of culture for routine screening.

Serologic testing is available through local department of health public laboratories and through commercial laboratories. Report any positive test for West Nile virus from a commercial laboratory to the local department of health for confirmatory testing by PRNT.

Serologic testing for patients who have mild symptoms, such as fever and headache, or who have simply been bitten by mosquitoes is neither necessary nor recommended. The likelihood of West Nile virus infection in these patients is extremely low. Since there is no specific antiviral therapy for West Nile virus infection, mildly symptomatic patients do not require diagnostic testing. Advise mildly ill patients to seek medical attention if more severe symptoms-such as confusion, lethargy, muscle weakness, movement disorders, severe headache, stiff neck, or photophobia-develop.


Treatment of West Nile virus infection is supportive. There is currently no known effective antiviral therapy, although high doses of ribavirin and interferon alfa-2b have been found to inhibit West Nile virus replication and cytopathogenicity in human neural cells in vitro.12 However, controlled clinical trials have not been completed for either agent.13 No controlled studies have examined the use of corticosteroids, antiseizure medications, or osmotic agents in the management of West Nile virus encephalitis.1


Although human West Nile virus vaccines are under development, their use is many years away. Therefore, prevention of infection relies on reducing the number of-and minimizing human contact with-mosquitoes.1 Table 2 lists prevention strategies.


REFERENCES:1. Petersen LR, Marfin AA. West Nile virus: a primer for the clinician. Ann Intern Med. 2002;137: 173-179.
2. Hubalek Z. Comparative symptomatology of West Nile virus fever. Lancet. 2001;358:254-255.
3. Outbreak of West Nile-like viral encephalitis-New York, 1999. MMWR. 1999;48:845-849.
4. Asnis DS, Conetta R, Teixeira AA, et al. The West Nile virus outbreak of 1999 in New York: the Flushing Hospital experience. Clin Infect Dis. 2000;30:413-418.
5. Division of Vector-Borne Infectious Diseases: West Nile Virus. CDC Web site. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/index. htm. Accessed July 14, 2003.
6. Mostashari F, Bunning ML, Kitsutani PT, et al. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet. 2001;358:261-264.
7. Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med. 2001;344:1807-1814.
8. Leis AA, Stokic DS, Polk JL, et al. A poliomyelitis-like syndrome from West Nile virus infection. N Engl J Med. 2002;347:1279-1280.
9. Glass JD, Samuels O, Rich MM. Poliomyelitis due to West Nile virus. N Engl J Med. 2002;347: 1280-1281.
10. Tyler KL. West Nile virus encephalitis in America. N Engl J Med. 2001;344:1858-1859.
11. New York City Department of Health. West Nile Virus Surveillance and Control: An Update for Health-care Providers in New York City. New York: City Health Information; 2001:20.
12. Jordan I, Briese T, Fischer N, et al. Ribavirin inhibits the West Nile virus replication and cytopathic effect in neural cells. J Infect Dis. 2000;182:1214-1217.
13. Anderson JF, Rahal JJ. Efficacy of interferon alpha-2b and ribavirin against West Nile virus in vitro [letter]. Emerg Infect Dis. 2002;8:107-108.
14. Update: investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion-Michigan, 2002. MMWR. 2002;51:879.
15. Iwamoto M, Jernigan DB, Guasch A, et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med. 2003;348:2196-2203.
16. Possible West Nile virus transmission to an infant through breast-feeding-Michigan, 2002. MMWR. 2002;51:877-878.
17. CDC. Intrauterine West Nile virus infection-New York, 2002. MMWR. 2002;51:1135-1136.
18. Laboratory-acquired West Nile virus infections-United States, 2002. MMWR. 2002;51:1133-1135.

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