West Nile virus overview and characteristics

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.

Vertebrate Ecology

West Nile (WN) virus replicates (the correct term is amplified) when the adult mosquito blood-feeds. During this time the virus continually transmits between the mosquito and the host. Infectious mosquitoes carry virus particles in their salivary glands. If the host is the bird, the virus survives and replicates. In turn, mosquitoes become infected when they feed on infected birds, which may circulate the virus in their blood for a few days. Infected mosquitoes can then transmit West Nile virus to humans and animals while biting to take blood. There is a concept called dead-end hosts. (Campbell et al., 2002) This means that some hosts then do not offer an opportunity to infect others. Or they are not sufficiently infected to infect a mosquito following a mosquito bite.

Birds have been the biggest victims of WN virus. It has been detected in at least 138 species of birds. Although birds, particularly crows and jays, infected with WN virus can die or become ill, most infected birds do survive. In 2000, the New York and New Jersey Public Health Departments reported detecting the West Nile virus (WNV) in tissues from wild crows: two crows were found dead in New York and one in New Jersey. These results were confirmed by the Centers for Disease Control (CDC).

Household pets like dogs and cats are typically spared. Only a single case exists where WN virus was isolated from a dog. This was in Botswana in 1982. West Nile virus was isolated from a single dead cat in 1999. In New York City where the WN epidemic struck, some dogs were reported infected. There is no documented evidence of person-to-person or animal-to-person transmission of WN virus. The idea of the dead-end host arises again. There is not enough infection that would allow a host to survive that it becomes a transmitter or carrier of the diseases. It is possible that eating dead infected animals such as birds could infect dogs and cats. However, there have been no documentations of such a case. Cases of WN virus disease in horses have been documented, either by virus isolation or by detection of WN virus-neutralizing antibodies in 1999, 2000, and 2001. (Bunning et al., 2002; Bunning et al., 2001) Approximately 40% of equine WN virus cases results in the death of the horse. Horses most likely become infected with WN virus by the bite of infectious mosquitoes. Through December 2001, CDC has also received a small number of reports of WN virus infection in bats, a chipmunk, a skunk, a squirrel, and a domestic rabbit.

In the past, Louisiana rice farmers suffered due to an infestation of adult stink bugs, which threatened the paddy crop in the mid to late season. The insecticide is being now considered to gauge whether it could kill medically threatening mosquitoes breeding in rice fields. Researchers believe that the timing is right to test the insecticides as anti-mosquito treatments because of the threat of the WN virus. Treatments likely to be tested at varying dosages for their impact on mosquito populations include Methyl parathion, Karate, Mustang Max and Malathion. These insecticides would be applied in varying concentrations using airborne spraying methods. Though rice fields generally aren't considered a major threat for spreading West Nile virus, two mosquitoes typically found in Louisiana rice fields, the Anopheles quadrimaculatus and Psorophora columbiae are considered secondary or minor vectors of West Nile virus. In Louisiana, researchers plan to make detailed mosquito counts in rice fields, identify the types of mosquitoes found and estimate how many larvae grow to adulthood in rice ponds. Light traps and other devices will be used to catch adult mosquitoes and to monitor the growth of larvae. (McClain, 2003)

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.