—from Epidemiological Bulletin, Vol. 21 No. 4, December 2000

West Nile Virus in the Americas


West Nile Fever is a disease caused by the West Nile (WN) virus, a flavivirus belonging taxonomically to the Japanese Encephalitis serocomplex. It is a vector-borne disease that is transmitted to a wide range of vertebrates by infected mosquitoes. Because of spatial and temporal proximity of avian and human infections, epidemiologists have concluded that transmission follows an enzootic cycle. Birds act as natural reservoir hosts infecting mosquitoes, which in turn infect vertebrates (1).

In humans, the WN virus usually produces either asymptomatic infection or mild febrile illness. Symptoms of infection include fever, headache, and body aches, occasionally with skin rash and swollen lymph glands. More severe infection may be marked by headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, paralysis and rarely death (2). Meningoencephalitis is an occasional complication of this disease. Case definitions of probable and confirmed cases have been developed by the United States Centers of Disease Control and Prevention (CDC) (Table 1).

The WN virus was first isolated from an adult woman in the West Nile District of Uganda in 1937. The first recorded epidemics of West Nile fever occurred in Israel during the 1950’s. During this time, the virus became recognized as a cause of severe human meningoencephalitis. Subsequently, its presence was noted in Egypt, Israel, India and areas of Africa. In 1974, the largest known epidemic caused by WN virus occurred in South Africa. Recent outbreaks of WN viral encephalitis in humans have occurred in Algeria in 1994, Romania in 1996-1997, the Czech Republic in 1997, the Democratic Republic of the Congo in 1998, Russia in 1999, the United States in 1999-2000 and Israel in 2000 (2) (Figure 1).

In the Americas, the first recorded epidemic of WN viral encephalitis occurred in the New York metropolitan area during the late summer of 1999. A total of 62 cases of neurological disease and 7 deaths were reported. In addition to humans, concurrent epizootics occurred in birds and horses especially affecting the American crow (3). During this epidemic/epizootic, the virus was detected in 4 states, Connecticut, Maryland, New Jersey and New York. In 2000, there were 18 cases with 1 death and epizootic activity in birds and/or mosquitoes was recorded in 12 states (Connecticut, Delaware, Maryland, Massachusetts, New Hampshire, New Jersey, New York, North Carolina, Pennsylvania, Rhode Island, Vermont, Virginia) and the District of Columbia (4).

It has not been determined how WN virus was introduced into the Western hemisphere. However, migratory birds are suspected as being principal introductory hosts for several reasons (1): outbreaks of the virus in temperate regions generally occur during late summer or early fall, coinciding with the arrivals of large concentrations of migratory birds; outbreaks often occur among humans living near wetlands where high concentrations of birds come into contact with large numbers of mosquitoes; and antibodies to the virus have been found in the blood of many migratory bird species of temperate regions. In addition to migratory birds, international travel of infected persons to New York, importation of infected birds or mosquitoes are other possible sources of WN virus introduction.

As a result of the 1999 outbreak, U.S. public health officials questioned the preparedness of the public health infrastructure to respond to vector-borne diseases and recognized the ease with which emerging infectious pathogens can move into new geographic areas. Furthermore, public health agencies did not know how far the virus would spread and if it would sustain during the winter season (5). To address these issues, guidelines for an active surveillance system and prevention and control programs were established by the CDC and U.S. Department of Agriculture (USDA) (3).

An enhanced surveillance system is a priority for states along the Atlantic Ocean and Gulf of Mexico. These states, from Massachusetts to Texas, were selected to participate in WN virus surveillance on the basis of having been affected by the 1999 outbreak and/or having high potential to become affected because of bird migration patterns to the south. A major objective of WN virus surveillance is to detect epizootic activity early so that intervention can occur before severe human illnesses (4). From the 1999 outbreak epidemiological findings, WN virus-infected birds were identified before human cases in their same county of residence suggesting that avian surveillance data are sensitive indicators of epizootic transmission and may predict human illness. The emphases on surveillance activities included: the monitoring of arbovirus activity in wild birds, sentinel birds, and dead crows; surveillance of mosquito populations to detect WN virus and other arbovirus activity; passive surveillance for the presence of WN virus outside of the bird-mosquito cycles, as in horses and other animals; and passive surveillance for cases of viral encephalitis (3).

The success of the surveillance activities in the U.S. has depended on the availability of laboratories that can provide diagnostic support. The immunoglobulin M and G enzyme-linked immunosorbent assays (ELISA) are available in public health and veterinary laboratories to provide the first-line testing for human and animal serum and cerebrospinal fluid specimens. Selected public health and reference laboratories have the capabilities to isolate and identify the virus, perform neutralization tests to identify specific flavivirus antibody, and perform immunohistochemistry to detect WN virus in autopsy tissues. All laboratory investigations handling the virus is conducted under bio-safety level 3 containment.

The most effective method to prevent transmission of WN virus or other arboviruses to humans is to reduce human exposure to mosquitoes. Public health services should have capabilities to control mosquito populations by larval control; control of adult mosquito populations by aerial application of insecticides; and educating the public about vector-borne diseases, how they are transmitted and how to prevent or reduce risk of exposure.

Because WN virus is a zoonosis affecting mosquitoes and vertebrates, a close coordination and data exchange between federal, state and local public health, vector control, agriculture and wildlife departments is essential for the success of addressing this vector-borne disease. A functional arbovirus surveillance and response capability with an adequately equipped reference laboratory with trained staff and veterinary/entomology health capacity is required (3).

The decrease in the number of cases of severe human illness from 1999 (62 cases) to 2000 (18 cases) in the U.S. may be attributed to prevention and control measures taken by state and local public health departments. However, previous experience in Europe has shown that incidence of human illness can be variable and outbreaks sporadic. In spite of a decrease in cases, WN virus activity has continued to expand to new locations and will persist. Research of migratory bird patterns shows that “members of one or more avian species that pass through New York and gather in wetlands in large, dense groups potentially reach every part of the southeastern United States, Mexico and Central America, the Caribbean Islands, and South America during their migration south to wintering sites and nearly every part of North America during their migration north to breeding sites” (1) (6) (7). As noted by Blaskovic and Ernek (8), “the role of birds in ecology of arboviruses depends upon whether the migrating vector finds favourable conditions in the new environment and whether the local vectors are capable of transmitting the appropriate virus. The presence of arbovirus antibody in migratory birds indicates only a virus-host interaction but does not explain when and where the infection occurred.” For these reasons, surveillance (mainly of dead birds), prevention activities and mosquito control need to be well established and maintained. Additionally, future research should define criteria for predicting where the virus will go next (1).

Table 1: Case definitions of West Nile Virus Encephalitis
Confirmed Case
Probable Case
Non-Case

A confirmed case of WN encephalitis is defined as a febrile illness associated with neurologic manifestations ranging from headache to aseptic meningitis or encephalitis, plus at least one of the following:

  • Isolation of WNV from or demonstration of WN viral antigen or genomic sequences in, tissue, blood, CSF, or other body fluid; · Demonstration of IgM antibody to WN virus in CSF by IgM-capture EIA.
  • A > 4-fold serial change in plaque-reduction neutralizing (PRNT) antibody titer to WN virus in paired, appropriately timed serum or CSF samples
  • Demonstration of both WN virus-specific IgM (by EIA) and IgG (screened by EIA or HI and confirmed by PRNT) antibody in a single serum specimen.

 


A probable case is defined as a compatible illness (as confirmed case) that does not meet any of the above laboratory criteria, plus at least one of the following:

  • Demonstration of serum IgM antibody against WN virus (by EIA);
  • Demonstration of an elevated titer of WN virus-specific IgG antibody in convalescent-phase serum (screened by EIA or HI and confirmed by PRNT).

A non-case is defined as an illness that doe not meet any of the above laboratory criteria, plus:

  • A negative test for IgM antibody to WNV (by EIA) in serum or CSF collected 8-21 days after onset of illness; and/or
  • A negative test for IgG antibody to WNV (by EIA, HI, or PRNT) in serum collecteed > 22 days after onset of illness.
Note: Although tests of tissues or fluids by PCR, antigen detection, or virus isolation can be used to confirm WN encephalitis cases, they cannot be used to rule-out cases because the negative predictive values of these test methods in this disease are unknown.

References:
(1) Rappole, J., Derrickson, S., Hubalek, Z., Mirgratory Birds and Spread of West Nile Virus in the Western Hemisphere. Emerging Infectious Diseases, 2000; 6:319-327.
(2) Centers for Disease Control and Prevention. West Nile Virus, Division of Vector-Borne Infectious Diseases, 2000.
(3) Centers for Disease Control and Prevention. Epidemic/Epizootic West Nile Virus in the United States: Guidelines for Surveillance, Prevention and Control, 1999.
(4) Centers for Disease Control and Prevention. Update: West Nile Virus Activity - Eastern united States, 2000. Morbidity Mortality Weekly Report, 2000; 49; 1044-1047.
(5) Centers for Disease Control and Prevention. Guidelines for Surveillance, Prevention, and Control of West Nile Virus Infection – United States, Morbidity Mortality Weekly Report, 2000; 49;25-8.
(6) Bull J. Birds of New York State. Garden City (NY): Doubleday; 1974.
(7) Steele KE, Linn MJ., Schoepp RJ, Komar N., Geisbert TW, Manudca RM, et al. Pathology of fatal West Nile virus infections in native and exotic birds during the 1999 outbreak in New York City. Veterinary Pathology 2000; 37:208-24.
(8) Gubler, D.. Surveillance for West Nile Virus in the Americas, PAHO/WHO, Third Meeting of the Surveillance Networks for Emerging Infectious Diseases in the Amazon and Southern Cone Regions, 2000.
(9) Blaskovic D., Ernek E. Birds as hosts of arboviruses in connection of migratory birds and their role in the distribution of arboviruses. Novosibirsk, Russia: Nauka; 1972. p. 161-7.
(10) Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/dvbid/westnile/index.htm , December 2000.

Source: PAHO. Division of Disease Prevention and Control. Communicable Diseases Program (HCP/HCT)

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Epidemiological Bulletin , Vol. 21 No. 4, December 2000