West Nile virus transmission, epidemiology, and viral classification

West Nile Virus

In recent years, every summer, the threat of West Nile (WN) virus has become the scourge of the temperate regions of Europe and North America. (Abramovitz, 2004) The virus presents a threat to the human and animal population -- especially the bird population. Symptoms of WN viral infection range from mild fevers and aches, to encephalitis (inflammation of the spinal cord and brain). The latter can be fatal. In 1937, a woman in Uganda complaining of a fever was the first known case of West Nile virus. In the 1950s, it was found in Egypt, hence the name. In 1957, some elderly people succumbed to the disease in Israel. Later, in the 1960s, in Egypt and France, an infection in horses came to be recognized as West Nile viral in nature. The WN virus appeared in North America in 1999, though it is not known where in the U.S. It originated. Symptoms of encephalitis were first reported in humans and horses. Its spread was then vast. This is an important lesson in the study of the evolution of the virus. All in all, WN virus outbreaks have been reported (besides the United States and Canada) in Africa, Europe, the Middle East, west and central Asia, Oceania.

Recent (well documented) outbreaks of WN virus 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 1999-2001, and Israel in 2000. Epizootics of disease in horses occurred in Morocco in 1996, Italy in 1998, the United States in 1999-2001, and France in 2000 and in birds in Israel in 1997-2001 and in the United States in 1999-2002. In the U.S. from 1999 through December 23, 2002, WN virus has been documented in all states except Alaska, Arizona, Hawaii, Nevada and Oregon.

Entomology

Arthropod-borne viruses, also known as arboviruses, are carried by insects (arthropods -- jointed feet). These viruses survive in nature through biological transmission between vertebrate hosts by insects that feed on blood. Common examples of these include mosquitoes, sand flies and ticks. Vertebrates can become infected when an infected arthropod bites them to take a blood meal. The complex life cycle of the virus usually remain undetected until humans encroach on a natural focus, or the virus escapes this focus via a secondary vector or vertebrate host as the result of some ecologic change. In the United States, infected mosquitoes, primarily members of the Culex species, transmit West Nile virus. (Margulies, 2003)

Virology

WN virus belongs to the viral family Flaviviridae and the Genus Flavivirus Japanese Encephalitis Antigenic Complex. This complex (family) includes other viruses (besides West Nile) Alfuy, Cacipacore, Japanese encephalitis, Koutango, Kunjin, Murray Valley encephalitis, St. Louis encephalitis, Rocio, Stratford, Usutu and Yaounde viruses. This family of viruses shared a common size, which ranges between 40 to 60 nm (1nm = 10-9 meters). They are enveloped viruses and have icosahedral (20-sided symmetry). The virus is a single RNA (ribonucleic acid) strand ranging between 10,000 to 11,000 nucleotide bases pairs.

Symptoms of WN virus

Most people who are infected with the West Nile virus will not have any type of illness. Only 20% of those infected show signs of infection. The incubation period for the virus after initial entry into the blood stream is between three and fourteen days. These symptoms range from mild to severe Symptoms generally last from three to six days. In cases of severe symptoms where encephalitis and other neurological disorders occur the resulting symptoms -- primary and secondary -- may last from several weeks to months. In the case of neurological disorders, the effects of the infection might also be permanent. It is estimated that 1 in 150 persons infected with the West Nile virus will develop a more severe form of disease. The mild symptoms include fever, headache, and body aches, occasionally with a skin rash on the trunk of the body and swollen lymph glands. Other mild symptoms include general malaise, anorexia, nausea, vomiting, eye pain, headache and myalgia. The symptoms of severe infection (West Nile encephalitis or meningitis) include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. (WestNileFever.com, 2003)

The most significant risk factor for developing severe neurological disease is advanced age.

Encephalitis is more commonly reported than meningitis. In some patients gastrointestinal symptoms manifested. In other rare cases, muscle weakness or mild paralyses were also reported. In patients that presented neurological symptoms: ataxia, cranial nerve abnormalities, myelitis, optic neuritis, polyradiculitis and seizures were reported. In the past, though not recently, myocarditis, pancreatitis, and fulminant hepatitis were also reported. (Doron et al., 2003)

Presumably, once infected, the body develops antibodies and lymphocytes (memory white blood cells) that the body produced to combat the virus. These cells will provide lifetime immunity or at least immunity for many years.

Diagnosis and Reporting

The risk of being infected is low. Less than 1% of people who are bitten by mosquitoes develop any symptoms of the disease and relatively few mosquitoes actually carry WNV. The risk of infection increases depending upon the level of outdoor activity. People who spend a lot of time outdoors are more likely to be bitten by an infected mosquito. Age is an important consideration: People over the age of 50 are more likely to develop serious symptoms of WNV if they do get sick and should take special care to avoid mosquito bites. Risk through medical procedures is also low. The risk of getting WNV through blood transfusions and organ transplants is very small (CDC, Possible West Nile Virus Transmission to an Infant through Breast-Feeding - Michigan, 2002, 2002)

West Nile virus infection can be suspected in a person based on clinical symptoms and patient history. Laboratory testing is required for a confirmed diagnosis. The most commonly used WNV laboratory test measures antibodies that that are produced very early in the infected person. These antibodies, called IgM antibodies. These antibodies can be measured in blood or cerebrospinal fluid (CSF). CSF is the fluid surrounding the brain and spinal cord. This test may not be positive when symptoms first occur; however, the test is positive in most infected people within eight days of onset of symptoms. Since IgM antibody does not cross the blood-brain barrier, IgM antibody in CSF strongly suggests central nervous system infection. Detection of IgM antibody to WNV in serum or cerebral spinal fluid (CSF) collected within 8 days of illness onset using the IgM Antibody Capture Enzyme-Linked Immuno-Sorbent Assay, abbreviated MAC-ELISA.

The test for the West Nile virus antibody is conducted by the Center for Disease control, governmental and private laboratories. The CDC is generally in charge of disseminating information related to WN virus infections. It maintains a constantly updated database and website. The CDC is often also called upon to certify results from other laboratories. This is important because the CDC is responsible for general health awareness and safety of the public as regards these issues. The CDC has an "ArboNet" Surveillance System (http://www.phppo.cdc.gov/han/Documents/AlertDocs/OldAlerts/90.asp) for exactly this reason. A state may also perform or ask CDC to perform an additional, different test on a specimen. This latter test is called the Plaque Reduction Neutralization Test (PRNT). This test is performed after the initial diagnosis is made. This test is performed when initial cases of WNV are reported. Since many of the WN virus symptoms could be due to other non-related reasons, PRNT is conducted when the IgM antibody tests are not definitive if the laboratory lacks the right equipment or statistical results prove too erroneous. One of the non-related infections with similar symptoms to a WN virus infection is the St. Louis encephalitis virus. (Creech, 1977) PRNT takes longer to conduct. Patients who have been recently vaccinated against or recently infected with related flaviviruses like yellow fever, Japanese encephalitis and/or dengue WNV MAC-ELISA false-positive result. The PRNT test involves the laboratory amplification of the virus. This test is considered absolutely essential before a case of human infection is declared.

Treatment and Prevention

West Nile virus vaccine for horses was recently licensed, but its effectiveness is unknown. In the case of human WN encephalitis, no vaccine is currently available. However, several companies are in the process of developing one. Researchers have recently reported of a vaccine APHIS that has been proven successful in treating West Nile infections. However, pending FDA approval, the treatment efficacy can be considered rudimentary at best. Failing a cure all for WN viral infection, treatment is supportive. It depends on the severity of the symptoms. Treatment modalities often involve 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. Steroids and anti-seizure drugs have also been tested. But no controlled studies have been completed on the use of these or other medications.

In order to prevent the spread of the diseases people are asked not to handle dead birds with their bare hands, especially during seasonal increase in risk factors. The major preventable option is to prevent being bitten by mosquitoes. This means that areas where mosquitoes are likely to reproduce and grow should be eliminated or at least decreased. These are areas o f stagnant water or potted plants, which need frequent watering. People who are prone to long periods of outdoor activities are advised to wear clothing that would reduce exposure. DEET, the major ingredient in insect repellants is recommended by the CDC. N, N-diethyl-m-toluamide (DEET) (Fradin, 1998) The CDC recommends the use of insect repellants with the usual warnings that they should be applied externally; avoiding areas of cuts and bruises and those applications should be performed under adult supervision.

Since the blood stream is the first point of infection, numerous questions have been raised due to fears of being transfused by infected blood. The CDC avers that in 2003, all blood banks will be screened for West Nile virus. In addition, blood banks will not take donations from people who have fever and headache in the week before they donate blood. The screening tests are in place at all of the nation's blood banks. State and local public health departments will report cases of West Nile virus infection in patients who have received blood transfusions in the 4 weeks before they got sick to the blood collection agency that collected the donation and to CDC. This would help in updating ArboNet the national database where information about cases of West Nile virus is kept. In addition, cases of West Nile virus infection in people who donated blood in the 2 weeks preceding illness onset should also be reported to CDC and blood collection agencies where the sick person donated blood. The blood collection agency will destroy potentially infectious units of blood.

The new screening methods will allow blood banks to destroy potentially infectious blood before it is given to anyone. To reduce the number of donations from potentially infected people, blood banks will refuse to accept blood from people with recent fever and headaches. In addition, public health departments and blood banks will cooperate to identify and destroy blood products (if necessary) from donors who develop a West Nile viral illness after they give blood. If someone becomes ill after a transfusion, blood banks will destroy the blood products taken from the donor of the transfused blood. Prompt reporting of these cases will help facilitate withdrawal of potentially infected blood components. (Gubler et al., 2000)

The Role of the CDC in West Nile Virus

ArboNET is a comprehensive database of every bit of information related to the West Nile virus. (http://www.cdc.gov/)The information is disseminated almost daily (with yearly summaries) through the CDC website. Following are summaries from the year 2000 and the most recent report from the CDC. This gives an idea of the evolution of the diseases, its seasonal occurrence, the human factors and statistics. This information is important because it is a measure of the official effort to minimize the effect of the disease. In 2002, the reported numbers of human and animal infections increased. The geographic range of WN virus activities also expanded significantly.

In an effort to collate the information and conduct testing, specimens from ill humans and animals, dead birds, captive sentinel animals (mostly chickens), wild-caught birds, and mosquitoes were collected by state and local public health departments and other cooperating state and federal agencies. These were tested for WNV or WNV-specific antibody. This activity was reported for 2,289 counties in 44 states and the District of Columbia (DC) compared with 359 counties in 27 states and DC in 2001. (CDC, 2001) The WNV virus was detected for the first time in 1,929 U.S. counties and 16 states. In 2002, a total of 3,389 human cases of WNV disease were reported, compared with 149 during 1999 -- 2001, and large numbers of WNV-infected birds, equines, and mosquitoes also were reported.

In 2002, of the 3,389 reported cases of human WNV-associated illness, 2,354 (69%) persons had West Nile meningoencephalitis, 704 (21%) had West Nile fever (WNF), and 331 (10%) had an unspecified illness. Human cases were reported from 619 counties in 37 states and DC; five states (Illinois [774 cases], Michigan [475], Ohio [409], Louisiana [319], and Indiana [202]) accounted for 2,179 (64%) cases. Four of these five states (Illinois [492], Michigan [437], Ohio [277], and Louisiana [202]) together with Texas [164] accounted for 1,572 (67%) reported WNME cases. Illness onset dates ranged from June 10 to November 4 and the epidemic peak of WNME cases occurred during the week ending August 24. Illness onset dates ranged from June 10 to November 4 in southern states and from July 10 to October 28 in northern states. The epidemic peak of WNME cases occurred 1 week earlier in southern states than in northern states.

This report summarizes West Nile virus (WNV) most recent surveillance data reported to CDC through ArboNET as of July 23, 2003. During the reporting week of July 17 -- 23, six human cases of WNV infection were reported from five states (Iowa, Minnesota, Ohio, South Dakota, and Texas). During the same period, WNV infections were reported in 309 dead crows and related species, 69 other dead birds, 12 horses, and 144 mosquito pools. During 2003, a total of 11 human cases of WNV infection were been reported from Texas (5), Alabama (0), Iowa (1), Minnesota (1), Ohio (1), South Carolina (1), and South Dakota (1). Among these cases, seven (64%) occurred among men; the median age was 70 years (range: 42 -- 80 years), and the dates of illness onset ranged from May 29 to July 13. In addition, 551 dead crows and 150 other dead birds with WNV infection were reported from 34 states; 55 WNV infections in horses have been reported from 16 states (Alabama, Arkansas, Colorado, Georgia, Kansas, Kentucky, Minnesota, Missouri, Nebraska, New Mexico, North Carolina, North Dakota, Oklahoma, Texas, Wisconsin, and Wyoming), and one WNV infection was reported in a dog (South Dakota). During 2003, WNV seroconversions have been reported in 56 sentinel chicken flocks from Florida, Iowa, and North Carolina. South Dakota reported three seropositive sentinel horses; 327 WNV-positive mosquito pools have been reported from 15 states (Colorado, Georgia, Illinois, Indiana, Kansas, Maryland, Massachusetts, Michigan, Mississippi, Nebraska, New Jersey, South Dakota, Texas, Virginia, and Wisconsin).

Conclusion

Based on the above CDC reports, it appears that West Nile virus is here to stay. But with proper precautions and the fact that the odds are on the side of the infected individual if proper treatment and prevention modes are put in place, the diseases will seize to be a problem. One has to recognize the importance of the West Nile virus. It is a single protein molecule. It could mutate to a more benign or virulent form. Research has to be carried to ensure that the right insecticides and vaccines be developed. The work on behalf of the rice farmers of LA is a step in the right direction. But care should also be taken that the chemicals used for treatment and prevention be used judiciously.