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http://www.nytimes.com/2002/08/13/health/13DOCS.html

West Nile and Its Lessons for Doctors

By LAWRENCE K. ALTMAN, M.D.

ASHINGTON, Aug. 11 — As West Nile fever spreads through the country, it is giving scientists a rare picture of how a virus carves a new ecological niche in a hemisphere where it has never been seen.

Most infectious diseases were presumably present at the creation — or gained a foothold long before the first doctors could determine their origins and chart their spread. We know when smallpox was eradicated from the world (in 1980), but when and where did it first appear? When did it begin to spread to wider areas?

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Theories abound. But there is no proof because the earliest doctors lacked the knowledge and tools. Even today, scientists debate whether AIDS, which was first diagnosed in 1981, is a new disease or a newly recognized old one. The only certainty is that AIDS has infected people in virtually every country.

West Nile is different. It was first recognized in this hemisphere just three years ago, in New York City (although the possibility that it occurred earlier cannot be excluded). And thanks to the alert work of scientists then, doctors now know a great deal about how it can spread.

Two axioms of medicine are that infectious agents respect no borders and that jet travel is likely to help infectious diseases spread into new areas. Yet the first case of West Nile fever in the Western Hemisphere came as a surprise.

That outbreak produced 62 human cases, 7 fatal. Since then, West Nile virus has spread to mosquitoes, birds, animals and humans in 36 states and the District of Columbia.

And this summer, it attained epidemic status, causing brain infection (encephalitis or meningitis) in at least 145 cases in Alabama, Illinois, Indiana, Louisiana, Mississippi, Texas and the District of Columbia.

The 85 human cases in Louisiana, including 7 deaths, make the state the scene of the country's worst West Nile outbreak ever.

Compared with scourges like AIDS and influenza, the virus poses a relatively small danger to public health. It can cause fatal brain damage in humans, but seldom does. Still, the wide swath that West Nile has cut in just three years illustrates how vulnerable the United States is to imported diseases.

The speed with which the initial cases were detected and control measures instituted are cited as evidence of the significant improvement in the public health response to new and emerging diseases.

If alert veterinarians and practicing physicians had not sought to identify the cause of the deaths of crows and of human encephalitis in New York City in 1999, health officials would probably have included the human cases in the large "cause undetermined" category of encephalitis. If West Nile had not been recognized until this year, scientists might have missed the evolving pattern and even concluded that the virus had been here a long time.

Determining the cycles of transmission of the virus among humans, insects, birds and animals is complex, and the maps of those interrelationships are still too sketchy to provide a full understanding of the ecology of West Nile virus in this country. But when scientists knit together the fragmentary information, the charts could be useful for the future.

Already, West Nile has provided some useful, and sometimes painful, information. Most disturbing is the virus's changing face. The frequency of human outbreaks in Europe, the Middle East and this country has risen over the last decade. So, apparently, has the severity of human disease. Also, at 55, the median age of West Nile encephalitis cases in this country this year seems to be a decade lower than in earlier outbreaks.

The strain of West Nile virus spreading in the United States is identical to one that infected geese and humans in Israel, but no one knows how it came here. Large numbers of bird deaths from West Nile disease have occurred concurrently with human cases only in Israel and the United States, said Dr. Lyle R. Petersen, an epidemiologist who specializes in studying insect-borne infections at the Centers for Disease Control and Prevention.

The reasons are unknown, but the phenomenon raises important questions: whether an older strain of the virus may be gaining in virulence, whether it may be a new strain altogether or whether birds in North America are simply more susceptible to West Nile than those in the Eastern Hemisphere.

Knowledge about the West Nile virus dates from 1937, when a healthy 37-year-old woman from Omogo, Uganda, gave blood for a scientific study of sleeping sickness. The virus was identified by injecting her blood into mice, monkeys and other animals at a laboratory in Entebbe, financed by the Rockefeller Foundation in New York City. Dr. K. C. Smithburn and his team that discovered the virus did not know how the woman became infected.

Recognition of the insect's role in spreading West Nile fever came in the 1950's, when the virus was isolated from patients, birds and mosquitoes from sporadic cases, largely in Egypt.

Israeli doctors reported the first epidemics, in 1951. A large outbreak of an illness in the region in 1941 may have been West Nile fever, but documentation is lacking because diagnostic tests were not available. Later outbreaks in Israel involved nursing home patients and soldiers, but West Nile was nearly forgotten there by the end of the 20th century.

Elsewhere, West Nile fever was more of academic than public health interest because most cases were mild and occurred sporadically.

Then in 1996 the face of West Nile fever changed when the first urban epidemic occurred, in Bucharest, Romania. The case total was 393, including 17 deaths. In 1999, at least 318 cases, including 40 deaths, occurred in the Volgograd region of Russia. Additional outbreaks have occurred in the Czech Republic, Israel, Tunisia and elsewhere.

Scientists say the virus can infect a wide variety of animals (except, apparently, goats). But which species of mosquito is most responsible for transmission to humans in the current outbreak in the South is unknown. Entomologists are investigating whether a species of mosquito that bites all day is a greater factor in the outbreaks than other species that tend to bite in the early evening.

The risk that a person will develop severe West Nile fever from the bite of an infected mosquito is low. In a vast majority of cases in which blood tests show that someone has been infected, no symptoms develop.

About 20 percent of infected people experience mild nonspecific symptoms that resemble influenza, making diagnosis difficult without a blood test. Symptoms begin abruptly from three to six days after the bite of an infected mosquito. Initial symptoms can include fever from 102 to 104 degrees, chills, sore throat, nausea and vomiting, headache, conjunctivitis, pain in the back of the eye, backache, muscle and joint aches and malaise. Often a rash appears on the head, trunk and limbs.

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About 1 in 150 ill patients go on to develop a stiff neck, a possible indicator of meningitis, or muscle weakness, a staggered gait or mental confusion, symptoms of encephalitis. (Infected horses have particular difficulty using their rear legs and may be unable to stand without help.)

About half of patients hospitalized for West Nile virus in earlier outbreaks in the United States had severe muscle weakness, a previously unrecognized symptom.

Encephalitis can leave many persistent symptoms among survivors. In 2000, a year after the first group of New York patients became ill with West Nile, two-thirds of those who had been admitted to a hospital were still fatigued; half had memory loss and difficulty walking; 44 percent had muscle weakness; and 38 percent were depressed.

"A lot of these people were very active and went out doing things, which is why they got bitten by mosquitoes, and their lives changed significantly," said Dr. Marcelle Layton, the assistant commissioner of the New York City Department of Health for communicable diseases. In an interview Dr. Layton added that "many people don't realize that this is not an infection that you always get over, especially if you have had encephalitis."

Why so few of those who are infected with West Nile virus become sick and why severe cases tend to develop predominantly among elderly people are only two of the disease's many riddles.

Also, although doctors presume there are no long-term hazards from mild West Nile fever, follow-up studies have not been done to document the point. Health officials may include this aspect in studies now being undertaken in the South.

Prevention requires both public and individual measures. Public health workers are spraying communities to reduce mosquito populations. People are being told to avoid locations where infected mosquito species are biting, install window screens, wear long-sleeved shirts and full length pants and apply mosquito repellents to prevent bites.

But health officials say more study is needed to determine the efficacy and cost-effectiveness of spraying and other preventive measures.

The activity of mosquito-borne diseases like West Nile fever and related infections like St. Louis encephalitis and Eastern encephalitis tends to be unpredictable from year to year.

Although weather data suggest that hot, dry summers promote mosquito-borne human outbreaks, simple generalizations about weather have been poor predictors for St. Louis encephalitis activity in a particular area. West Nile virus is unlikely to be an exception, health officials say.

An additional factor, a committee of the National Research Council wrote last year, is that "the lack of high-quality epidemiologic data for most diseases is a serious obstacle to improving our understanding of climate and disease linkages."

One research aim is to determine the best monitoring systems and clues to predict the probability of occurrence of the disease in a specific place. Another research aim is to determine why sporadic outbreaks are separated by long silent periods.

West Nile virus is here to stay, health officials say. Until a vaccine is developed for humans and a clearer picture emerges of how to stop the virus's spread in nature, West Nile virus is likely to move throughout the Western Hemisphere to cause anxiety, if not major public health problems.

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