As doctors and mosquito experts watch West Nile virus numbers mount, many are speculating that this could be Northern California's big year - the year the virus flares before dropping dramatically in 2006.
That has been one pattern as the disease has expanded north, south and west since its arrival in New York in 1999.
It is not the only pattern. Sometimes the worst year has come later. Sometimes levels of serious cases simmer for years.
The boom-and-bust cycle is not uncommon, but "it can't be taken as a hard and fast rule," said Dr. Dan O'Leary, an epidemiologist with the Centers for Disease Control and Prevention's Division of Vector-Borne Infectious Diseases in Colorado.
A complex tangle of variables, from weather to birds to mosquito control to human immunity, so far makes it impossible to predict how the virus will behave as it becomes an enduring presence in America, O'Leary said.
Others believe that even though West Nile patterns aren't fully consistent, a long-term decline in serious illness, once the disease is entrenched nationwide, seems likely.
When most illnesses carried by mosquitoes reach a new population, the second and third years tend to be high, followed by a steady dampening, said Bruce Eldridge, a University of California, Davis, professor emeritus who has run the UC system's mosquito research program.
Vicki Kramer, who heads the vector-borne disease program for the state Department of Health Services, also expects an eventual drop in West Nile, with its potential for occasionally severe paralysis, encephalitis and other nerve disorders.
"It's not something we can eradicate," Kramer said. Still, "we hope in a decade, certainly, the amount of illness associated with this disease will be much less than it is today."
Several factors could play into an overall decline.
One is human immunity. Researchers are fairly sure that once bitten, people have long-term if not lifelong immunity to the virus.
In parts of Africa, Pakistan and other regions with established West Nile, immunity can reach up to 90 percent of the population, doctors say. They caution that conditions in those regions - from climate to mosquito types to screenless homes and far more time spent outdoors - are so different that immunity in America may never approach that.
We have only the earliest indications about U.S. immune levels in West Nile's wake. A single published study found immunity in 2.6 percent of those living near the 1999 West Nile epicenter in New York City. Unpublished research at other locations has found similar levels of 2 percent to 3 percent immunity at first, O'Leary said.
What's unknown is how much that might grow each year or with each outbreak, because no one has done follow-up work to track West Nile immunity over time, he said.
Then there's bird immunity.
West Nile generally reaches humans from the bite of a mosquito that has bitten an infected bird - but not just any infected bird. It can't be, say, a chicken, which can get West Nile but doesn't build up enough virus in its blood to pass it on to a mosquito.
The most troublesome diseased birds, for human contagion, harbor lots of virus in their blood so they can pass it along to mosquitoes, stay contagious a relatively long time, and live near people in large numbers.
In California, some of the most "competent" birds at offering a bridge from virus to mosquito to human include house sparrows, house finches, crows and western scrub jays, said Nicholas Komar, a research scientist in the CDC infectious disease division.
Komar is interested in the theory that increasing bird immunity could contribute to decreases in human cases of West Nile. He's been working with about a dozen researchers who have caught thousands of house sparrows around northern Colorado towns, drawn blood to check for West Nile, and then looked for correlations in how active the disease was in nearby birds and mosquitoes.
"We set out to do the study in a way to prove that theory that bird immunity explains why we don't have (human) outbreaks two years in a row," he said.
Unfortunately, Komar said, it doesn't seem to explain that at all.
While he has only preliminary data from the first year of an ongoing project, he's finding no correlation between bird immunity and disease levels. His theory is that bird populations turn over so quickly - a house sparrow lives on average about three years - that "immunity fizzles out, it gets diluted, in the bird world."
Beyond the natural evolution of disease and resistance, other things could contribute to a long-term West Nile decline - including a vaccine.
Today, one potential West Nile vaccine, made from genes of West Nile and yellow fever, has been put through an initial phase of human testing in the United States. Its maker, British-based Acambis, hopes it could be approved by 2009.
Federal researchers at the National Institute of Allergy and Infectious Diseases are working on two other vaccine approaches, including one that is in its first phase of human testing in Maryland.
Because people can generate immunity to West Nile, the virus is a good target for a vaccine, said Dr. Gary Nabel, director of the institute's vaccine research center.
"One can be relatively optimistic that within a matter of years, I can't tell you if it would be five or 10, there should be vaccines that do confer protection," he said.
The science, though, is only part of the picture. For a business to create, test and finally produce any vaccine, at costs that easily can top a half-billion dollars, there has to be a market for the product, he said.
If West Nile turns out to jump from spot to spot in America, erupting only occasionally in greater numbers and causing serious disease largely in the elderly, those features could limit demand for a vaccine.
And while people of any age can get West Nile, those hardest hit are often ill or elderly. "Young people, they tend not to get sick" from the virus, said Dr. Roger Baxter, a Kaiser Permanente infectious disease specialist.
The median age of those who died from West Nile in 2002 was 77 1/2, a large analysis of nationwide cases found, although it did note that a 19-year-old was the youngest person to die.
As Northern California struggles with what could become its biggest year for the virus, public health officials stress that even if the disease eventually declines, it is unlikely to disappear.
Many suggest West Nile could become cyclical, flaring anew whenever weather and other conditions are ripe.
Along the way, it also could become a kind of test case, a way for Americans to learn how a new disease takes root on their shores, how long it takes to become widespread and how it best can be resisted.
The lesson won't be wasted, said CDC's Komar, who points out that the world has plenty of other mosquito-borne diseases, some more dangerous than West Nile and some less, that are not known in the United States today. "Presumably as the globe shrinks, more and more of these viruses will have a chance to jump over and say hello," he said.
WEST NILE AT A GLANCE
To reduce the risk of catching West Nile virus, the Sacramento-Yolo Mosquito and Vector Control District recommends:
* Use an effective mosquito repellent containing ingredients such as DEET, Picaridin or oil of lemon eucalyptus.
* Repair tears in door and window screens.
* Drain standing water.
* Wear long pants and long sleeves outdoors when practical.
* Avoid being outside at dawn and dusk, when mosquitoes are most active.
* About 80 percent of people who get West Nile virus have no symptoms, and 19 percent get flulike symptoms that include fever, aches and fatigue.
* Fewer than 1 percent of West Nile victims will contract neuroinvasive disease, symptoms of which can include paralysis of the arms or legs, chronic headaches and chronic fatigue.
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