October 2004

West Nile Virus

Overview

People who contract West Nile virus usually experience only mild symptoms—fever, headache, body aches, skin rash, and swollen lymph glands. However, if West Nile virus enters the brain, it can cause life-threatening encephalitis (inflammation of the brain) or meningitis (inflammation of the lining of the brain and spinal cord). Most cases of disease occur in elderly people and those with impaired immune systems. Recent cases have shown that West Nile virus can be transmitted through blood transfusions and organ transplants from West Nile virus-infected donors. Doctors also believe it is possible for West Nile virus to be transmitted from a mother to her unborn child, and through breast milk.

The first step in the transmission cycle of West Nile virus occurs when a mosquito bites an infected bird or other infected animal. Crows are commonly associated with the virus because they are highly susceptible to infection. Scientists have identified more than 138 bird species that can be infected, and more than 43 mosquito species that can transmit West Nile virus. Although the virus primarily cycles between mosquitoes and birds, infected female mosquitoes also can transmit West Nile virus through their bites to humans and other “incidental hosts” such as horses. With so many susceptible hosts to amplify the virus and so many types of mosquitoes to transmit it, West Nile virus has spread rapidly across the United States.

West Nile virus was first isolated in Uganda in 1937. Today it is most commonly found in Africa, West Asia, Europe, and the Middle East. In 1999, it was found in the Western Hemisphere for the first time in the New York City area. In early spring 2000, it appeared again in birds and mosquitoes and then spread to other parts of the eastern United States. By 2004, the virus had been found in birds and mosquitoes in every state except Alaska and Hawaii.

Between 1999 and 2001, West Nile virus caused 149 cases of disease, including 18 deaths, according to the Centers for Disease Control and Prevention (CDC). Spreading west and south, the virus killed more than 280 people in 2002 and more than 260 in 2003. Human cases have now been reported from coast to coast and in Canada. See the CDC Web site for the most recent numbers of reported human cases of West Nile virus infection in the United States.

No specific vaccines or treatments exist for West Nile virus. Faced with a potentially deadly illness spreading quickly across the United States, scientists and public health officials have accelerated research on developing tools to prevent and treat West Nile disease. The National Institute of Allergy and Infectious Diseases (NIAID) supports research on West Nile disease through its comprehensive emerging infectious disease program, which supports research on bacterial, viral, and other types of disease-causing microbes.

NIAID supports basic research at universities to better understand the infection in animals and humans, the virus itself, and the environmental factors that influence disease emergence. For example, researchers are

• determining how the virus replicates and spreads throughout the body in order to develop vaccines and drugs to prevent and treat disease
• determining which viral proteins contribute to the virus’ ability to cause disease
• investigating how the immune system responds in the most serious form of the disease, West Nile encephalitis
• studying whether migrating bird populations carry the virus to points in Central and South America. The emergence of West Nile virus in these new areas, which harbor abundant mosquito populations, could set up conditions for a potentially severe epidemic.
• examining the ecology and year-to-year maintenance of mosquito-borne encephalitis viruses, and how genetic variation affects spread and virulence of the virus
• working to better understand other insects and ticks that transmit other flaviviruses. Such an understanding will allow improved monitoring and surveillance, and enable development and preliminary testing of strategies to control carriers of the virus.

RESEARCH TO PREVENT WEST NILE DISEASE

NIAID supports the development of several West Nile virus vaccine approaches, including chimeric vaccines (which combine genes from more than one virus into a single vaccine), naked DNA vaccines, and vaccines containing cocktails of individual West Nile proteins.

In November 2003, Acambis, a biotechnology company with vaccine development laboratories in Cambridge, MA, started the first human clinical trial of a West Nile virus vaccine. The Acambis vaccine is based on work performed under a fast-track project funded by NIAID in 2000. Scientists based the vaccine from one already licensed for preventing yellow fever, which is caused by another flavivirus.

Called a chimeric virus vaccine, the Acambis vaccine contains genes from two different viruses—yellow fever and West Nile. Researchers replaced some of the yellow fever virus genes with genes for a surface protein of West Nile virus. They are also developing similar chimeric vaccines for dengue fever and for Japanese encephalitis. The Acambis West Nile vaccine performed well in hamsters, mice, monkeys, and horses, and has now entered human clinical trials.

NIAID intramural scientists pioneered the concept of creating chimeric vaccines for flaviviruses in 1992. These scientists, led by Dr. Brian Murphy, also have now developed a chimeric West Nile vaccine and tested it in monkeys with promising results. This experimental vaccine, which uses dengue virus as a backbone to carry West Nile virus genes, is planned, pending Food and Drug Administration approval, to enter Phase I human trials by early 2005. (See this August 2003 NIAID press release for more details.)

Led by Dr. Gary Nabel, researchers at the NIAID Vaccine Research Center are also developing a vaccine for West Nile virus. This vaccine is made from a short circular piece of West Nile DNA modified to produce West Nile proteins. Researchers are evaluating the vaccine in animal models. If successful, it could proceed to early phase human clinical trials by 2005, pending Food and Drug Administration approval.

In 2002, NIAID-supported researchers developed a hamster model of West Nile virus infection that closely mimics human disease. This animal model has proved useful in evaluating ways to prevent serious complications associated with this emerging infectious disease. Using the hamster model, researchers were able to determine that prior infection with other related viruses may provide complete or partial immunity to West Nile virus.

RESEARCH ON WEST NILE TREATMENTS

No specific therapies for West Nile infection currently exist; supportive care is generally the only treatment for infected patients. NIAID supports research to test antiviral drugs and other therapies to prevent or treat severe complications of West Nile virus infection that may develop, such as encephalitis and meningitis.

NIAID currently funds a nationwide clinical trial to test whether antibodies from people who have recovered from West Nile infection can be used to treat those with severe West Nile neurologic disease. Investigators are comparing this treatment to placebo treatments to assess safety and to determine whether these antibodies help overcome the severe disease symptoms. More information on this clinical trial is available on the NIAID Collaborative Antiviral Study Group Web site.

Because drugs are effective against related viruses in laboratory tests, scientists are optimistic that they will be able to develop drugs to treat West Nile disease. NIAID funds investigators who screen chemical compounds for possible effectiveness against West Nile virus. Promising antiviral drugs will be tested in hamster or mouse models. These animal models allow scientists to evaluate a drug’s safety and efficacy before possible human trials. More than 1,000 drugs have been screened, and about 2 to 3 percent have shown promise for additional testing in animals.

In addition, NIAID clinicians are studying how West Nile disease progresses in people who have or are at risk of developing its most serious complications. This research study, conducted through the Collaborative Antiviral Study Group and at the National Institutes of Health Clinical Center, measures neurological function of people hospitalized with West Nile virus and will continue to monitor them as they recover. Data collected in this study will give doctors a better understanding of West Nile encephalitis and will assist in designing better treatments for this form of West Nile disease.

RESEARCH TO IMPROVE DIAGNOSIS OF WEST NILE

NIAID also sponsors research to develop methods that will more quickly and accurately detect West Nile virus in humans, animals, and mosquitoes. NIAID has awarded Small Business Innovation Research grants to small biotechnology companies to support development of new diagnostic tests for West Nile virus. At least one such test under development shows promise for more accurate diagnosis of West Nile virus in people and animals. NIAID also funds academic investigators to work on tests to detect West Nile virus and West Nile virus antibodies in people, mosquitoes, and donated blood.

RESEARCH RESOURCES

NIAID funds the World Reference Center for Emerging Viruses and Arboviruses at the University of Texas Medical Branch at Galveston. This international program characterizes numerous viruses spread by mosquitoes, ticks, and other insects and animals to people and domestic animals. It also investigates the epidemiology of the diseases these viruses cause. The center stores various strains of the West Nile virus as well as samples of sera containing West Nile virus antibodies. Qualified researchers in the United States and other countries may request samples for use in experiments.

Sets of West Nile peptides will be made available in fall 2004 through the NIAID Biodefense and Emerging Infections Research Resources Program. The peptides will be useful for vaccine research as well as immunological research to assess the body’s response following exposure to West Nile virus. NIAID has expanded its funding of West Nile virus research in academic and private sector laboratories. This includes establishing two Emerging Viral Diseases Research Centers in New York and Texas with collaborating laboratories in Colorado, Massachusetts, and several other states. These centers will focus on West Nile and other emerging viruses.

OTHER RESOURCES

Other federal agencies are involved in research on West Nile virus and protecting public health from West Nile disease. See the links below for more information.

Centers for Disease Control and Prevention

Food and Drug Administration

National Library of Medicine

U.S. Department of Agriculture Animal and Plant Health Inspection Service

U.S. Geological Survey

U.S. Environmental Protection Agency

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

U.S. Department of Health and Human Services

Department of Health and Human Services

National Institutes of Health (NIH) Bethesda, Maryland 20892

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