West Nile Virus Looming Health Risk for Americans

WASHINGTON--The first frost has come to the East and, with it, an end to the danger from West Nile virus. But the respite is temporary--because scientists know something now they didn't know last year: The virus is here to stay. Experts are now convinced that West Nile--first identified in the United States in the summer of 1999--will likely spread throughout the nation by 2003, including California.

So while the virus hibernates this winter, researchers who study diseases transmitted to humans by mosquitoes will be very busy.

"This virus is evolving and establishing its niche right in front of us," says Dr. James M. Meegan, a viral diseases expert with the National Institute of Allergy and Infectious Diseases, part of the federal government's National Institutes of Health. "We just don't know how big a public health problem it will be."

They are most eager to find out. Among other things, the federal government is spending $3 million to develop a vaccine to protect against West Nile, and another $7.8 million to study this virus and some of its close relatives. It is also helping local health officials cope. President Clinton recently declared a state of emergency in New York, ordering the Federal Emergency Management Agency to provide up to $5 million for emergency preventive measures in New York City and a long list of affected counties, including Westchester.

The virus, named for the region in Uganda where it first appeared in 1937, had never been seen in the Western Hemisphere until it sickened 62 people and killed seven in New York the summer before last. It infects birds, which are bitten by mosquitoes; the mosquitoes then bite people. In humans, the virus can cause potentially fatal encephalitis, an inflammation of the brain, or meningitis, an inflammation of the lining of the brain and spinal cord. During its first summer, the virus was concentrated primarily in New York. Since then, however, it has crossed into 12 states in the eastern U.S.

While the virus has proved lethal in outbreaks outside this country--most recently in Russia and Israel--it has killed relatively few Americans in the two summers since it took up residence here. Among those infected, it has posed the greatest threat to the very old and the very young. Moreover, it has made far fewer people ill this year than last--only 18--and left one person in a "persistent vegetative state," prompting some experts to question whether the government's response has been excessive.

"Is the government overreacting to West Nile? Probably, given that the risk, even in a worst-case scenario, is very low," says David Ropeik, director of risk communication for the Harvard Center for Risk Analysis.

But the government may have little choice because they "have to establish public trust in the face of headlines that play up the scarier parts of the story." Ropeik adds: "We are clearly spending way more money battling this relatively low risk than we are on higher ones where the spending could do more good."

No one really knows yet how much of a public health threat West Nile will prove to be.

"There have been other epidemics that have snuck up on us. We don't know yet how to rank it in the scheme of other public health concerns about which we know more," says Dr. Robert T. Schooley, head of the division of infectious diseases at the University of Colorado Health Sciences Center.

How Far Will Danger Spread?

Federal health officials defend their efforts in light of West Nile's more serious impact in other countries--this year in Israel, for example, there were nearly 300 cases, with two dozen deaths; in Russia last year, there were about 1,000 cases and 40 deaths.

Thus, experts stress that there's no way to know how widespread the danger will be until the virus extends its reach. Also, West Nile is a close relative of other mosquito-borne viruses that are known to be lethal, such as those that cause St. Louis encephalitis--which most closely resembles West Nile--dengue, Japanese encephalitis and yellow fever.

"This is a new virus, and initially, any new introduction of a virus--whether it's West Nile or Ebola--is going to get a lot of effort upfront to try to understand what's happening," says Dr. John Roehrig, chief of the arbovirus diseases branch for the Centers for Disease Control and Prevention's division of vector-borne infectious diseases in Fort Collins, Colo.

Moreover, he says, appearances can be deceiving. In those places hardest hit by West Nile these past two summers--the Northeast and mid-Atlantic regions--state and local health departments were not as well equipped to deal with mosquito-borne diseases as other states with more experience. They didn't have the laboratories, surveillance and other equipment, for example, or much experience in local control measures--such as spraying. States like California, with a track record in dealing with mosquito-borne infections, already have "an excellent infrastructure," and in those states "the response wouldn't look quite so aggressive as what you're seeing on the East Coast," Roehrig says. In preparation for spring, when West Nile will return, scientists will be studying such issues as whether other species of mosquito can transmit the virus. That could increase the risk, particularly as the virus spreads across the country and many thousands more are potentially exposed to it.

The first mosquitoes to carry West Nile were Culex pipiens, which are nighttime feeders--meaning the primary risk occurred in the evening. A major prevention effort was launched to keep people in affected areas inside after dark, or protected by clothing and insect repellent.

But this year, "other mosquitoes have been shown to be infected with West Nile, and many are Aedes species, which bite during the daytime," says the CDC's Roehrig. "It was not unexpected. But it certainly does change the dynamics of transmission. You can't just say to people: Go indoors at night."

In the Works: Vaccine for Virus

No one knows yet how effective daytime mosquitoes are a transmission, nor whether anyone infected this year was bitten by a daytime feeder. The research, it is hoped, will answer these questions.

On a second front, the development of a vaccine to prevent West Nile infection is part of NIAID's ongoing small-business innovative-research program, which has a "fast track" that combines Phase I trials, which look at safety, and Phase II testing, which studies efficacy. The grant was awarded to a U.S. subsidiary of Peptide Therapeutics Group, of Cambridge, England. The company, OraVax Inc., of Cambridge, Mass., will develop the vaccine using Peptide's already established technology for new vaccines against closely related viruses.

The experimental vaccine will be made from constructing a kind of hybrid virus in which the envelope genes of an existing yellow fever vaccine are replaced with the corresponding genes of the target West Nile virus, creating a yellow fever-West Nile hybrid, or chimera. The virus will be live--but weakened, so as not to cause disease.

This approach has already been used by Peptide to develop vaccines against dengue fever--which is still in preclinical development--and Japanese encephalitis, which is still being tested for safety.

A vaccine is still several years away, and it won't become clear until then who should be inoculated. The most likely candidates include individuals most at risk, and probably also those who spend a lot of time outdoors or who work in wildlife settings.

Possible 'Year-Round Transmission'

As the research continues, CDC and other health officials will be closely tracking the path of the virus. They are especially interested in seeing whether it eventually shows up in Gulf Coast states and South America. This would mean "there could possibly be year-round transmission in the Southern states where the climate is warm during winter months," says the CDC's Roehrig.

It will move west if there is, for example, gradual expansion to such states as Pennsylvania, Ohio and Indiana. If, for example, it does show up in South America or in some Southern states, it could return north in the spring in areas other than the Northeast.

Finally, "as the virus extends its range into other mosquito species, they can be transported in ways other than flight," Roehrig says.

Tires are a likely culprit because mosquitoes often breed in standing water in tires.

"It's not beyond the realm of possibility that a shipment of tires from New York or Pennsylvania, with standing water containing mosquitoes that have West Nile, could could be transported somewhere else in the United States--like California--and they would fly out and set up their transmission cycle," he says.

Harvard's Ropeik predicts that the government's response to West Nile will likely follow a similar path as that of rabies, a deadly but relatively rare virus transmitted through the saliva of infected animals.

"As rabies moved up the East Coast, frightening headlines raised public fear far beyond the actual risk to public health," he says."Officials responded with what may have been an overreaction given the relatively low risk.

"But they established trust, proving they were doing everything they could," he adds. "And then, as the public got used to having rabies around, and realized the risk was low, the headlines went away, people calmed down, and government spending on rabies programs is now more in line with the actual risk."