Chapter II. Information and Guidance for Clinicians

West Nile virus (WNV) was first isolated and identified in 1937 in a febrile person in the West Nile district of Uganda. Prior to 1999, the virus was found only in the Eastern Hemisphere, with wide distribution in Africa, Asia, the Middle East, and Europe. There were infrequent reports of human outbreaks, mainly associated with mild febrile illnesses, in Israel and Africa. These were mostly in groups of soldiers, children, and healthy adults. One notable outbreak in Israeli nursing homes in 1957 was associated with severe neurologic disease and death.

Since the mid-1990s, the frequency and apparent clinical severity of WNV outbreaks have increased. Outbreaks in Romania (1996), Russia (1999), and Israel (2000) involved hundreds of persons with severe neurologic disease. It is unclear if this apparent change in disease severity and frequency is due to differences in the circulating virus's virulence or to changes in the age structure, background immunity, or prevalence of other predisposing chronic conditions in the affected populations.

National surveillance has documented persons with illness caused by WNV each year since 1999: 62 persons in 1999; 21 in 2000; 66 in 2001; 4,156 in 2002; and 9,862 in 2003. (See Statistics, Surveillance, and Control for current statistics.)

WNV is now an important public health problem in North America. In 2002, for example, CDC received 4,156 reports of human disease cases due to WNV in 44 states. Of these, about 3,000 were central nervous system (CNS) disease cases, and the others were either West Nile fever or clinically uncharacterized. Of the cases of WNV disease of the CNS, nearly 300 (about 10%) were fatal. In addition, many survivors have experienced short-term or long-term sequelae. For data from other years, see Q & A: Statistics on WNV Human Cases.

Peak incidence of human disease in North America occurs in late August and early September.

Predicting the temporal characteristics of future WNV transmission seasons based on limited reports available to date is not possible. Despite this limitation, active ecological surveillance and enhanced passive surveillance for human cases should be encouraged beginning in early spring and continuing through the fall until mosquito activity ceases because of cold weather (where applicable).

West Nile Virus (WNV) Infection

West Nile Virus (WNV) Infection: Information for Clinicians

CDC Fact Sheet
Clinical Features

Mild Infection

Most WNV infections are mild and often clinically unapparent.
Approximately 20% of those infected develop a generally mild illness (West Nile fever).
The incubation period is thought to range from 3 to 14 days.
Symptoms generally last 3 to 6 days.
Reports from earlier outbreaks describe the mild form of WNV infection as a febrile illness of sudden onset often accompanied by

malaise
headache
anorexia
myalgia
nausea
rash
vomiting
lymphadenopathy
eye pain

The full clinical spectrum of West Nile fever has not been determined in the United States.

Severe Infection
Approximately 1 in 150 infections will result in severe neurological disease.
The most significant risk factor for developing severe neurological disease is advanced age. Encephalitis is more commonly reported than meningitis. In recent outbreaks, symptoms occurring among patients hospitalized with severe disease include

fever
gastrointestinal symptoms
weakness
change in mental status

A minority of patients with severe disease developed a maculopapular or morbilliform rash involving the neck, trunk, arms, or legs. Several patients experienced severe muscle weakness and flaccid paralysis. Neurological presentations included

ataxia and extrapyramidal signs
optic neuritis
cranial nerve abnormalities
polyradiculitis
myelitis
seizures

Although not observed in recent outbreaks, myocarditis, pancreatitis, and fulminant hepatitis have been described.

Clinical Suspicion

Diagnosis of WNV infection is based on a high index of clinical suspicion and obtaining specific laboratory tests.
WNV, or other arboviral diseases such as St. Louis encephalitis, should be strongly considered in adults >50 years who develop unexplained encephalitis or meningitis in summer or early fall.
The local presence of WNV enzootic activity or other human cases should further raise suspicion.
Obtaining a recent travel history is also important.
Note: Severe neurological disease due to WNV infection has occurred in patients of all ages. Year-round transmission is possible in some areas. Therefore, WNV should be considered in all persons with unexplained encephalitis and meningitis.

Diagnosis and Reporting

Procedures for submitting diagnostic samples and reporting persons with suspected WNV infection vary among states and jurisdictions. Links to state and local websites are available at
http://www.cdc.gov/ncidod/dvbid/westnile/city_states.htm

Diagnostic Testing

West Nile virus (WNV) testing for patients with encephalitis, meningitis, or other serious central nervous system infections can be obtained through local or state health departments. For WNV diagnosis, public health laboratories usually perform an IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Using this assay, virus-specific IgM can be detected in nearly all cerebrospinal fluid (CSF) and serum specimens received from WNV-infected patients at the time of their clinical presentation. Because serum IgM antibody may persist for more than a year, physicians must determine whether the antibody is the result of a WNV infection in the previous year and unrelated to the current clinical presentation. The following procedures are recommended:

The most conclusive diagnostic method to identify persons with WNV infection of the central nervous system (CNS) is detecting WNV-specific IgM antibody in CSF using MAC-ELISA. This can be done with a CSF specimen obtained during initial clinical presentation. Because IgM antibody does not readily cross the blood-brain barrier, IgM antibody in CSF strongly suggests acute CNS infection

If CSF is not obtained and serum samples are used to make the diagnosis, paired acute- and convalescent-phase serum samples should be acquired. The acute-phase specimen should be obtained during initial clinical presentation and the convalescent-phase specimen should be obtained 7-14 days later. Both samples should be tested with MAC-ELISA.

If a convalescent-phase specimen cannot be obtained, the acute-phase specimen should be tested with MAC-ELISA. If the specimen is IgM-negative, then the illness is very unlikely to be an acute WNV infection. If the specimen is IgM-positive and the illness is clinically compatible, then it may be a recent WNV infection (presuming the test results for IgM antibody to St. Louis encephalitis (SLE) virus are significantly lower or negative; see below).

Ideally, MAC-ELISA testing should be performed, using both WNV and SLE virus. If the MAC-ELISA results for WNV and SLE are similar, it is necessary to use the plaque-reduction neutralization test (PRNT) to confirm either a WNV or SLE virus infection. Note: Patients who have been recently vaccinated against or recently infected with related flaviviruses (e.g., yellow fever, Japanese encephalitis, dengue) may have positive WNV MAC-ELISA results.

Reporting Suspected WNV Infection

Refer to local and state health department reporting requirements: http://www.cdc.gov/ncidod/dvbid/westnile/city_states.htm
WNV encephalitis is on the list of designated nationally notifiable arboviral encephalitides.
Aseptic meningitis is reportable in some jurisdictions.
The timely identification of persons with acute WNV or other arboviral infection may have significant public health implications and will likely augment the public health response to reduce the risk of additional human infections.

Laboratory Findings

Among patients in recent outbreaks
Total leukocyte counts in peripheral blood were mostly normal or elevated, with lymphocytopenia and anemia also occurring.
Hyponatremia was sometimes present, particularly among patients with encephalitis.
Examination of the cerebrospinal fluid (CSF) showed pleocytosis, usually with a predominance of lymphocytes.
Protein was universally elevated.
Glucose was normal.
Computed tomographic scans of the brain mostly did not show evidence of acute disease, but in about one-third of patients, magnetic resonance imaging showed enhancement of the leptomeninges, the periventricular areas, or both.

Treatment

Treatment is supportive, often involving hospitalization, intravenous fluids, respiratory support, and prevention of secondary infections for patients with severe disease.

Ribavirin in high doses and interferon alpha-2b were found to have some activity against WNV in vitro, but no controlled studies have been completed on the use of these or other medications, including steroids, antiseizure drugs, or osmotic agents, in the management of WNV encephalitis.

For additional clinical information, please refer to Petersen LR and Marfin AA, "West Nile Virus: A Primer for the Clinician [Review]" Annals of Internal Medicine (August 6) 2002:137:173-9.

2006 West Nile Virus Activity in the United States
(Reported to CDC as of October 10, 2006)

State	Neuroinvasive	Fever	Unspecified	Total	Fatalities
Alabama	4	0	1	5	0
Arizona	15	14	16	45	3
Arkansas	21	5	0	26	0
California	65	164	13	242	3
Colorado	54	219	0	273	3
Connecticut	6	2	0	8	1
District of Columbia	0	1	0	1	0
Florida	3	0	0	3	0
Georgia	2	4	1	7	1
Idaho	94	542	6	642	10
Illinois	111	55	23	189	9
Indiana	11	5	12	28	0
Iowa	17	12	0	29	0
Kansas	14	10	0	24	3
Kentucky	5	1	0	6	1
Louisiana	66	49	0	115	0
Maryland	2	1	1	4	0
Massachusetts	2	1	0	3	0
Michigan	29	2	6	37	3
Minnesota	29	34	0	63	3
Mississippi	72	79	0	151	6
Missouri	41	9	1	51	2
Montana	10	19	1	30	0
Nebraska	33	123	0	156	1
Nevada	34	73	14	121	1
New Jersey	2	2	1	5	0
New Mexico	1	2	0	3	0
New York	7	3	1	11	2
North Dakota	20	115	0	135	1
Ohio	27	7	0	34	3
Oklahoma	21	12	1	34	5
Oregon	4	42	8	54	0
Pennsylvania	7	1	0	8	2
South Dakota	37	71	0	108	3
Tennessee	7	1	0	8	1
Texas	175	81	0	256	23
Utah	48	88	0	136	4
Virginia	0	0	2	2	0
Washington	0	2	0	2	0
West Virginia	1	0	0	1	0
Wisconsin	10	8	0	18	1
Wyoming	14	36	11	61	2
Totals	1121	1895	119	3135	97

West Nile encephalitis and West Nile meningitis are forms of severe disease that affect a person's nervous system. Encephalitis refers to an inflammation of the brain, meningitis is an inflammation of the membrane around the brain and the spinal cord.

Click here for further explanation of WN meningitis and/or encephalitis.

West Nile fever refers to typically less severe cases that show no evidence of neuroinvasion. WN fever is considered a notifiable disease, however the number of cases reported (as with all diseases) may be limited by whether persons affected seek care, whether laboratory diagnosis is ordered and the extent to which cases are reported to health authorities by the diagnosing physician.

Other Clinical includes persons with clinical manifestations other than WN fever, WN encephalitis or WN meningitis, such as acute flaccid paralysis. Unspecified cases are those for which sufficient clinical information was not provided.

See the case definition (2004) for Neuroinvasive and Non-Neuroinvasive Domestic Arboviral Diseases. From the CDC Epidemiology Program Office.

Total Human Cases Reported to CDC: These numbers reflect both mild and severe human disease cases that occurred and have been reported to ArboNET by state and local health departments since January 1, 2006. ArboNET is the national, electronic surveillance system established by CDC to assist states in tracking West Nile virus and other mosquito-borne viruses. Information regarding 2006 virus/disease activity is posted when such cases are reported to CDC.

Of the 3135 cases, 1121 (36%) were reported as West Nile meningitis or encephalitis (neuroinvasive disease), 1895 (60%) were reported as West Nile fever (milder disease), and 119 (4%) were clinically unspecified at this time. Please refer to state health department web sites for further details regarding state case totals.

Note: The high proportion of neuroinvasive disease cases among reported cases of West Nile virus disease reflects surveillance reporting bias. Serious cases are more likely to be reported than mild cases. Also, the surveillance system is not designed to detect asymptomatic infections. Data from population-based surveys indicate that among all people who become infected with West Nile virus (including people with asymptomatic infections) less than 1% will develop severe neuroinvasive disease. See: 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.

2006 West Nile Virus Activity in the United States
(Reported to CDC as of October 10, 2006)*

Click on the map for a printer friendly version.

*Map shows the distribution of avian,animal, or mosquito infection occurring during 2006 with number of human cases if any, by state. If West Nile virus infection is reported to CDC from any area of a state, that entire state is shaded.

Data table:

As of October 10, 2006 avian, animal or mosquito WNV infections have been reported to CDC ArboNET from the following states: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin, and Wyoming.

Human cases have been reported in Alabama, Arizona, Arkansas, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Jersey, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, West Virginia, Wisconsin, and Wyoming.

Maps detailing county-level human, mosquito, veterinary, avian and sentinel data are published each week on the collaborative USGS/CDC West Nile virus web site: http://westnilemaps.usgs.gov/

____________________________________________________________________________________
Question No.9. Where and when was the West Nile Virus first isolated and identified?

a. Australia in 1890
b. The West Nile district of Uganda in 1937
c. Kenya in 1972
d. South Africa in 1992

Question No.10. How many cases of WNV were documented in the United States in 2003?

a. 62
b. 536
c. 4156
d. 9862

Question No.12. Symptoms from a mild form of WNV infection include the following EXCEPT:

a. Anorexia
b. Hair loss
c. Rash
d. Eye pain

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