A New Season of West Nile Virus

Two years do not a trend make, but it does seem that with each passing summer, the number of human West Nile virus cases tends to decline. That said, there is no reason to relax. No one can predict reliably from year to year whether this, or any other mosquito-borne viral illness, might come back to infect humans, says Jim Miller, West Nile coordinator for New York City. "West Nile has been well documented since it was introduced here two years ago. It's a totally new virus in this part of the world, and I don't think we've reached a point yet where it's stabilized." Many factors affect the spread of West Nile: which particular mosquito species are infected, weather conditions, rain--especially conditions that cause areas to flood and then dry up again--and how much pesticide is sprayed. This year, epidemiologists are on alert in all 48 contiguous states, and some believe the virus will spread and become endemic, though not necessarily severe, throughout the United States and the Americas. "There are no natural barriers to the spread of this virus in the U.S., so it is anticipated it will spread across the United States and down into Central and South America," says Margo Brinton, a professor of biology at Georgia State University. "On the edge of the spread, where new individuals will be infected, there will be a lot of birds ... and mammals [dying], and there will be human cases." The good news is that in regions where the virus has been active, "there will be a number of immune cases," she adds. For example, 60 percent of the crows tested for the disease "showed evidence they were previously infected but survived. Survivors are not good hosts." And, like other mosquito-borne viruses, such as St. Louis encephalitis and Eastern Equine encephalitis, the numbers can vary widely from year to year. "For the most part, it will become endemic [to the United States], but it will be a normal infection. Just because the virus is in the mosquito or bird population, doesn't mean that humans are at great risk," she says. Israel has not been as fortunate as the United States. West Nile reached epidemic proportions in animals and humans this past year; health officials reported 417 serologically confirmed human cases, 28 of them fatal.1 Israel is the suspected country of origin for the 1999 New York infiltration. A remarkable similarity between a West Nile virus DNA sequence and that of a virus found in a goose in Israel in 1998 suggested that a bird might have transported West Nile virus.2 The Israeli situation creates a definite cause for concern, says W. Ian Lipkin, a University of California, Irvine, neuroscientist who developed genetic techniques to amplify West Nile viral fragments in the human brain. His research helped clinch the final link between human and avian infection.3 Lipkin, currently the Louise Turner Arnold professor of neuroscience at UC-Irvine, says, "Nothing is known about the basis for the large increase [in recent cases] in Israel, except that there was substantial morbidity and mortality.... We're talking about a very large problem." Lipkin believes the pathogenesis and even the basic molecular biology of West Nile and other encephalitis-causing viruses are poorly understood. "Two-thirds of encephalitis cases in this country are never diagnosed as being associated with a specific infectious agent," he says. Scientists "cannot identify the basis for encephalitis despite molecular and serological techniques, animal inoculations, and virus isolation." Lipkin says his lab will continue to investigate the disease's causes and mechanisms. "We focus on the same things [we did] during the initial West Nile outbreak," he says. "We're studying the basic biology of West Nile and how it replicates. We're continuing to develop new, rapid, high-throughput methods for identifying infectious agents and investigating their role in ... acute and chronic disease." Richard French, veterinary pathologist "at the Connecticut Veterinary Diagnostic Lab, University of Connecticut, doubts the Israeli epidemic will be replicated here. "It's not the same. Israel is not a predictor for what's happening in the U.S.," he asserts. "There is a difference in the mosquito species involved, and one vector may be better than another." French cites the incidence of another arbovirus, Eastern Equine encephalitis, as a better indicator of unpredictability. "Even that disease is quite variable: one year we may not see it at all; the following year we'll significant numbers, so there's no good predictor of what's going to take place." West Nile appeared earlier in birds this year than in years past. This is worrisome to French. "The first positive animal showed up in Connecticut on April 4, and one of the earliest avian cases in New Jersey showed up April 30. This was really unexpected," he says. "This is a disease that we would expect to see in early July and be a problem in later summer and into fall. But [the earlier dates] raise some concerns because of the way this disease works." Scientists now believe the virus survives the winter by hibernating in adult mosquito populations. "One possibility is that the disease has been building up in the ... last two years," French says. "This could account for a higher number of affected mosquitoes. We still don't know what the vertebrate reservoir is [i.e., the numbers of infected birds and animals], and without knowing that, it's difficult to identify what role the reservoir might be playing in the spread of the disease. However, just the fact that we're seeing it show up earlier in birds can be an indicator--we could see more (activity) later in the season." A number of states and regions have significantly increased larva sightings, French reports. West Nile spread to 12 states last year from its early concentration in the New York tri-state area in 1999. "It may be an endemic disease now," he speculates. "It's just too early to predict." Wider Spread, But Growing Immunity? Virus migration and illness patterns are complex, though severe clinical symptoms are rare, says Georgia State's Brinton. "The typical pattern for [humans] is that only one percent who get infected actually get clinically ill, and of those who are ill, only one percent get serious enough disease that results in death," Brinton says. New York City's Miller cites different rates of occurrence: "One out of 150 people infected actually have symptoms," he says. Only one out of every 150 affected get severe illness, which can start as a severe headache and fever. However, Miller adds, "none of these symptoms are unique to West Nile. Several other types of meningitis and encephalitis caused by enteroviruses display similar symptoms." Flu-like symptoms are the common result, but only a very few develop the severe brain and spinal cord inflammations that can result in coma and death. Brinton is now looking at genes in mice hosts that suppress virus replication--so called resistance genes. "This may help us look at genetically susceptible individuals who might be severely affected by the infection," she explains. "Certainly, older people are more at risk for contracting serious diseases, but given that, there are always a few individuals at different ages and even young ages who may have genetic susceptibility." Health officials and drug companies continue to fight West Nile. The strategy has changed from spraying populated areas for adult mosquitoes to aggressively testing for and killing virus-carrying larvae using Bacillus sphaericus-related agents, which attack the larvae's digestive system and destroy it before hatching. Early stage larvicides are now thought to be much more effective in preventing virus amplification than adult-stage spraying. In addition, virtually all states have mounted aggressive surveillance of mosquitoes, birds, and mammals. The Centers for Disease Control and Prevention has set up the ARBONET and West Nile surveillance guidelines through which states can track movements of the virus, mostly through reporting and serological testing of dead birds.4 Scientific researchers and drug companies are at work on other human prescriptions. Among them is a recombinant DNA vaccine that has shown early promise in tests on mice and horses, according to Lipkin. "One of the problems here is that when anyone presents with advanced [encephalitis disease], the damage is already done," he says. A Cambridge, Mass.-based drug company, Acambis Inc., is working to develop a yellow fever vector live-virus vaccine against West Nile, according to Juan Arroyo, a principal investigator. The vaccine, now in preclinical phase, uses a yellow fever backbone and an envelope gene inserted from West Nile virus to create positive immunities. "The vaccine uses yellow fever YF17D strain, a positive strand RNA virus vaccine, to produce chimeras and ... induce a protective immune response against viruses of the same family (i.e., Japanese encephalitis [JE] and dengue viruses)," Arroyo reports in an abstract presented recently at a positive strand RNA symposium in Paris.5 "Chimeric virus products prepared against JE and dengue are in or are nearing clinical trials, respectively," he writes. "The success of this recombinant technology, combined with the emergence of West Nile virus in the New World, prompted the rapid development of a live-virus attenuated vaccine against West Nile." This vaccine has a long round of testing ahead before it can be distributed for humans. In the meantime, encephalitis remains extremely difficult to treat, and most West Nile experts believe the best treatment is prevention. Arielle Emmett (arielleem@snip.net) is a contributing editor for The Scientist. Ricki Lewis also contributed to this report. References 1. C. Banet, "Phylogenetic relationships of West Nile viruses isolated in Israel in 2000," Kimron Veterinary Institute and H. Shiba hospital. 2. J.X.-J. et al., "Genetic analysis of the West Nile New York 1999 encephalitis virus," Lancet, 354:1971-2, 1999. 3. T. Briesel, et al., "Identification of a Kunjin/West Nile-like favivirus in brains of New York encephalitis patients," Lancet, 354:1261-2, 1999. 4. Centers for Disease and Prevention Control, "Epidemic/Epizootic West Nile Virus in the United States: Guidelines for Surveillance, Prevention and Control," March 2000, available at: www.cdc.gov/ncidod/dvbid/arbovirus_pubs.htm 5. J. Arroyo et al., "Yellow fever vector live-virus vaccine against West Nile Virus," Acambis Inc., Cambridge MA 02139 Learning More About A Little-Known Disease By Ricki Lewis As the New York City area faces another year with West Nile virus on the list of summertime ills, the public health climate has changed noticeably from panic to preparedness, armed with data from the past two seasons. One thing learned: as infectious diseases go, West Nile virus isn't that huge a threat to humans. The encephalitis is rare, and people can dampen mosquito populations and protect themselves. But investigating West Nile virus offers an opportunity to observe evolution of an infection that intimately involves several types of organisms. Says Bryon Backenson, director of the arthropod-borne disease program at the New York State Department of Health: "We must find out as much as we can when we can. West Nile has not yet reached equilibrium, as has Lyme disease. It's still spreading. It would be irresponsible of us not to put as much emphasis as we can on a new disease." Backenson made his comments at a June 14 New York State Department of Health news conference. The New York State Department of Health laboratories at Wadsworth, the nearby Arbovirus Research Laboratory at Griffin Labs in Guilderland, and the State Department of Environmental Conservation's Wildlife Pathology Unit in Delmar are ground zero for investigating the West Nile outbreak. The goals for summer 2001: prevent mosquito breeding and alert citizens to report dead birds. Early Efforts Reveal Route of Infection The West Nile virus saga began in late summer 1999, when James Rahal, a physician at New York Hospital Medical Center, Queens, noted eight cases with an unusual triad of symptoms: high fever, altered mental status, and severe muscle weakness.1,2 Public health officials identified an arthropod-borne viral infection, which epidemiologists first attributed to St. Louis encephalitis. But once bird deaths entered the picture, they knew the infection was unfamiliar because the St. Louis virus doesn't kill birds. Investigators eventually discovered that the virus was originally identified in West Nile, Uganda, in 1937. Statistics suggest that severe human illness from the viral infection could be on the wane. In that initial season, 62 people fell ill, and seven died.3 In 2000, 21 people became seriously ill and two died. The story is much bleaker for birds. Virtually all species are infected, and it is devastating in some. After the first year, public health officials began tracking all involved species, finding antibody evidence of the virus in 1,263 birds, 366 mosquito pools, and 26 mammals, including horses, rabbits, squirrels, chipmunks, bats and cats. As of June 25, state health departments reported: two infected birds in New York; 29 in New Jersey, along with two infected mosquito pools; at least one bird in Maryland and one in Connecticut. Much of the first season focused on identifying the players and their relationships. Researchers implicated 10 of the 70 species of mosquitoes native to New York, notes Backenson. Species in genus Culex favor birds, whereas Aedes mosquitoes have more eclectic tastes. A timetable emerged. Researchers found that in May, Culex pipiens and Culex restuans infect a wide variety of birds. "This is the amplification cycle before the spillover into other species," explains Backenson. By late July, Culex salinarius mosquitoes pick up the virus in birds and can transmit it to humans. From August until September, Aedes and Ochlerostatus mosquitoes join the party by biting horses. Other mammals become infected along the way too. This year, investigators have noticed an odd phenomenon. "In all instances where we've had dead crows tested positive for West Nile, we've had a swimming pool," says Rod Schmidt, superintendent of the Middlesex County, N.J., Mosquito Extermination Commission, in an interview. The infected mosquitoes apparently breed either in pool covers or in pool water. "It's definitely become a suburban disease," he comments. Many questions remain for this season. "Is the virus only in adult birds? What other species do the different mosquito types eat? Can other arthropods spread the virus?" asks Backenson. One project under way is a collaboration between the Wadsworth facility, NASA, and Oxford University to analyze satellite data from areas where the virus is found and crows are dying, to see if researchers can predict risks for people in certain geographic areas. Counting Crows Studying mosquitoes is difficult because their numbers are vast. "Looking for mosquitoes is like the needle in the haystack. Birds, in contrast, self-select by falling out of the sky," Backenson says. Tracking birds also is turning out to be more informative than probing pooled mosquitoes. One valuable piece of information to come from the past two years is that human infection follows increases in bird deaths, particularly crows. The New York state data show concentric rings of decreasing numbers of dead birds with increasing distance from New York City. The high "dead crow density"--or the number of dead birds per square mile--correlated to numbers of human cases in the city, with occasional cases in suburbs and none in upstate New York. Counting dead birds to predict human disease might be decidedly low-tech in this era of DNA chip-based diagnostics, but the evidence from last year is compelling enough that it should help to minimize human cases this year. "The dead crow density measurement is the best indicator of a human outbreak," says Millicent Eidson, state public health veterinarian and associate professor of epidemiology at the State University of New York at Albany School of Public Health. "It requires no equipment, special training, or laboratory tests. The number of birds directly correlates to the number of people, and it doesn't falsely predict human cases." Last year, dead birds provided the first confirmation of the virus in 60 of New York's 62 counties. In one county the virus appeared in mosquitoes first, and in the other, not at all. At the Delmar facility, wildlife pathologist Ward Stone oversees three bird dissectors in a small necropsy room. "Last year, we had more than 250 birds a day delivered in July and August just to look for West Nile," Stone says. An unexpected benefit of the many bird dissections is discovery of other conditions. Last year, Stone found new forms of avian pox and malaria that turned up in the hunt for West Nile deaths. Stone has compiled a staggering diversity of winged victims of West Nile virus, including woodthrush, yellow-billed cuckoos, flickers, hummingbirds, and caged birds such as macaws. By far the most severely affected birds are the common American crows, with a 100 percent mortality rate, followed by fish crows, ravens, and blue jays. "We're not sure which birds are the most threatened, besides crows. We're very concerned about what West Nile virus will do to bird populations," Stone says. The crows will survive, he adds, because of their large populations, but other species might not fare as well. "Robins have several nests per season. They could be hit hard, but there are enough of them so that after a few generations, the population remaining will be resistant. The bald eagle is another story. It has a small population and a long time to maturity, so it is much more vulnerable," Stone says. Middlesex County, which harbors at least 60 different mosquito species, had, at 276, the largest numbers of dead crows anywhere in the country last year. West Nile seems to be moving south and west of New York City down to Staten Island and into Middlesex County and beyond, Schmidt says. Last year, there were more than 1,200 positively identified dead birds in New Jersey alone. A Rare Illness in Humans Epidemiologists still do not know just how common West Nile encephalitis is in humans. They estimate that for every recognized case, 150 or more individuals are also infected, but with mild or no symptoms.2 To estimate infection prevalence, the New York State Department of Health tested 1,705 people from Staten Island and Suffolk County for antibodies indicating recent infection. Five people were infected; two of these reported headaches, the other three no symptoms at all. And although it makes sense that vulnerable population groups might be children or the immunosuppressed, this is apparently not the case. "The only risk factor for serious illness from West Nile virus infection is being over age 50," emphasizes New York State Commissioner of Health Antonia C. Novello. The rarity of serious reaction to West Nile virus in humans has prompted a re-evaluation of the necessity of pesticide spraying. In New York State in 2000, 14 people became sick from the virus, but 22 reported adverse effects from associated pesticide spraying to the state's pesticide poisoning registry, says Nancy Kim, director of the division of environmental health assessment at the Wadsworth Center. "The genie is out of the bottle. West Nile is everywhere. So spraying is only necessary if there is imminent risk to human health. It is a last resort." Ricki Lewis (rickilewis@nasw.org) is a contributing editor for The Scientist. Arielle Emmett also contributed to this report. References 1. R.L. Lewis, "West Nile virus--part 2?" The Scientist, 14:1, April 17, 2000. 2. K.L. Tyler, "West Nile virus encephalitis in America," The New England Journal of Medicine, 344:1858-9, June 14, 2001. 3. D. Nash et al., "The outbreak of West Nile virus infection in the New York City area in 1999," The New England Journal of Medicine, 344:1807-14, June 14, 2001.

A New Season of West Nile Virus

Interested in reading more?

Become a Member of