The mosquito-borne illness that has killed three people in New York City may not be St. Louis encephalitis, as experts have thought, but rather a similar disease that has never been diagnosed in the Western Hemisphere, Government scientists said yesterday.

The disease, West Nile virus, was discovered this week in dozens of birds that died in and around the Bronx Zoo this summer. The virus is indigenous to Asia and northern and eastern Africa and occasionally makes its way to Europe, but has never been found in birds or people in this hemisphere, said [Dr. Duane J. Gubler (born 1939)], the director of the division of vector-borne infectious disease at the Federal Centers for Disease Control and Prevention.

Before yesterday, the illness that has infected at least 14 people in New York City and 4 in Westchester County was believed to be St. Louis encephalitis, which was surprising enough because that disease is rarely found outside the Southeastern United States.

Scores of tests will need to be completed before health officials will be able to say for sure whether the infections were caused by some type of West Nile virus or St. Louis encephalitis. Officials at the C.D.C. said they hope to have the tests completed sometime next week.

But the discovery of the West Nile strain in the birds has cast some doubt on the original diagnosis, officials said. ''West Nile virus is closely related to St. Louis encephalitis, the virus we thought was causing the outbreak,'' [Dr. Duane J. Gubler (born 1939)] said. The discovery of the dead birds, he said, ''has caused some confusion as to whether that is true now.''

The finding of the West Nile virus in New York stunned experts, who have no theory so far on how the strain found its way here.

If officials confirm that the disease that sickened New Yorkers was the West Nile virus, it would have no practical effect on those who have fallen sick, or on the efforts to control the disease from spreading. Both illnesses are transmitted from birds to mosquitoes to people by the same type of mosquitoes, and the same insecticide would be used.

The symptoms of both illnesses are virtually the same and are usually mild, though in rare cases they can cause neurological disorders and even death.

Experts said those severe cases -- which generally involve the elderly, children under 5 and those with compromised immune systems -- are even less frequent with West Nile virus.

''The important message to get across is that all the public health and responsive measures implemented are the same,'' said Tom Skinner, a spokesman at the C.D.C.

But from an epidemiological standpoint, the discovery of West Nile virus in New York is remarkable. ''This is exciting,'' Dr. Gubler said. ''We prefer it didn't occur, but it is interesting.''

''What we are seeing in the waning years of the late 20th century is the transport and movement of these viruses in new areas,'' he added. ''And you get a virus moving into a new area, the entire mosquito population is susceptible.''

Yesterday, two elderly women were added to the list of confirmed cases of the mosquito-borne illness. One of the women, who is 90 years old and in critical condition, was the first case to be confirmed in Manhattan since the outbreak began in August. Officials said the woman, who lived near Central Park, apparently contracted the virus in Manhattan, but it was not clear where.

Now, old and new blood samples from people with symptoms, trapped mosquitoes, as well as roughly 450 birds will be examined to see whether the West Nile virus found in the birds was what has caused the New Yorkers to become ill.

It is not surprising that the diagnosis of those who have taken ill could have been mistaken, experts said -- the illnesses appear very similar, and few would have thought to look for an illness whose closest brush with this country was in France in the 1960's. The worst modern outbreak of the West Nile virus was in Romania in 1996, when 90,000 cases were confirmed and 17 people died.

The discovery of the West Nile virus came about in large part by some dogged sleuthing by a head of the department of pathology at the Bronx Zoo, Federal officials said. That pathologist, [Dr. Tracey S. McNamara (born 1954)], said she became concerned in late July when she heard that a large number of crows had been dying around the zoo. Then, birds at the zoo began to go. Over Labor Day weekend, the zoo lost a Guanay Cormorant, three Chilean flamingos, a pheasant and a bald eagle. Because these deaths followed those of some crows, experts strongly doubt that the disease originated in the zoo.

Autopsies of the birds revealed streaking in the heart and brain hemorrhages. An equine encephalitis was suspected, but Dr. McNamara was skeptical, because the emus in her care, which are very susceptible to that illness, were thriving.

When two more flamingos died on Sept. 9, she sent samples to laboratories of the United States Department of Agriculture, which ruled out all the common bird viruses. Stymied, they called in an equine virologist to do further testing. The C.D.C. and doctors at an Army lab in Maryland were also sent samples.

Yesterday, the C.D.C. discovered the West Nile virus link.''Everyone was shocked,'' Dr. McNamara said. ''It's possible it came in with a human being or a smuggled bird, and I am not at all certain it will ever be established how it got here.''

The Mayor's Office of Emergency Management, which has been in charge of the spraying, would not comment on the C.D.C. news.

As Westchester County prepared to continue its spraying last night, many Jewish residents voiced concern that such efforts would interfere with the start of the Succoth holiday, which requires observants to sit in an open air tent or hut to take their evening meal.

Victoria Hochman, a spokeswoman for the Westchester County Executive's office, said the agency was aware of the holiday and had contacted regional Jewish centers, ''but we have decided it is a health emergency and we have to go with the spraying for the good of everyone.'' [...]

The mosquito-borne illness that has killed three people in New York City is not St. Louis encephalitis, but a similar disease that has never before been found in the Western Hemisphere, health officials said early this morning.

Scientists in two states who have been examining brain tissue from the people killed by the outbreak of encephalitis confirmed that it was caused either by West Nile virus, from Africa, or Kunjin virus, a variant that is found only in Australia.

Since last month, 14 people in New York City and Westchester County have been diagnosed with encephalitis, although it was unclear whether the two strains identified today are responsible for all the cases.

An official with the Centers for Disease Control and Prevention in Atlanta, and a researcher at the University of California at Irvine said this morning that the closely related strains had been positively identified in the brain matter of New York City residents killed by encephalitis. Until now, neither strain had been found in birds or people in this hemisphere.

[Dr. Duane J. Gubler (born 1939)], director of the C.D.C.'s division of vector-borne infectious diseases, said that the agency's lab found the West Nile virus in the brain of one of the victims early last week. ''It was a total surprise to us,'' he said. ''There was no reason to suspect that we'd find West Nile here.''

[Dr. Walter Ian Lipkin (born 1952)], the director of the Emerging Diseases Laboratory at the University of California at Irvine, said his colleagues had identified the virus in the brains of three victims from Queens that had been sent to his lab last week. ''It's very odd that they've been found here,'' he said. ''On the other hand, viruses evolve and they have the capacity to adapt themselves.'' Dr. Lipkin emphasized that the genetic difference between West Nile virus and Kunjin virus is so slight that the two are practically the same strain.

Until yesterday, New York health officials said they had found the West Nile virus only in birds that had died in and around the Bronx Zoo. But this morning, after the C.D.C confirmed the discovery of the virus in humans, a state official acknowledged that officials had known about the findings of [Dr. Walter Ian Lipkin (born 1952)] and Dr. Gubler for several days, but wanted to conduct more tests.

John Signor, a State Health Department spokesman, said the ageny was planning to release the information tomorrow after more testing confirmed the earlier findings. ''The identification of a virus is a complex process,'' he said. ''We felt more testing needed to be done.''

Despite the discovery that the encephalitis outbreak had been caused by a different virus, officials said that the public health measures undertaken to date would not change: the spraying of mosquitos and warnings to reduce exposure to the insects remains. Mr. Signor said that the treatment for those already infected with the disease would remain the same.

The Federal Centers for Disease Control and Prevention said Friday night that its scientists had identified a West Nile-like virus in four birds from New York that they had tested in their laboratory in Fort Collins, Colo.

The birds included two flamingos and an Asian pheasant from the Bronx Zoo, and a crow reported to be from Scarsdale, said Kristine Smith, a spokeswoman for the New York State Health Department.

Yesterday, city health officials continued collecting dead birds, which they had started to do on Friday. Special telephone lines and asked residents to call in sightings of dead birds. By 4 P.M. yesterday, the City Health Department had received two dozen reports of dead birds in all five boroughs, and sent out staff members from its pest control division to retrieve specimens, said a spokeswoman, Sandra Mullen.

''The birds will be kept on dry ice and brought to our Bureau of Laboratories,'' she said, adding that most of the dead birds reported were crows, which have been dying in large numbers since the beginning of the outbreak. Health officials in Suffolk County collected five dead crows on Friday, and sent them for analysis to the State Department of Environmental Conservation yesterday, said the director of public health, Mahfouz Zaki.

And after receiving reports at 5:30 P.M. on Friday that earlier samples from dead crows tested positive for an encephalitis-like disease, they sprayed South Huntington and Huntington Station with pesticides.

In Manhattan, a team from the Parks Department swept through Central Park on Friday night searching for dead birds but found none, said Parks Commissioner Henry J. Stern. He said that more teams would be dispatched, but that all park staff members had been notified and were on the lookout.

News that the infection was either West Nile virus or an Australian variant has deepened an epidemiological mystery that began in July with the deaths of numerous crows around the Bronx Zoo.

A pathologist at the zoo, [Dr. Tracey S. McNamara (born 1954)], first noticed that large numbers of crows were dying, reaching 40 by August. Then, birds at the zoo, including a guanay cormorant, three Chilean flamingos, a pheasant and a bald eagle, died.

Though the symptoms of both diseases are similar, and the steps to combat them are the same, the mosquitoes that carry them can differ, health officials said.

Ms. Smith of the State Health Department said the mosquitoes that carry St. Louis encephalitis and West Nile viruses, the Culex pipiens, are generally active from dusk to dawn. But another type of mosquito known to carry the West Nile virus, the Aedes vexans, is also active during the day, she said. [...]

On Sept. 23, nearly three weeks after Mayor Rudolph W. Giuliani announced that New York was being attacked by a mosquito-borne virus often found in the Southern United States, senior Federal health officials convened a conference call to hear some startling news.

The scientist who initially identified the virus as St. Louis encephalitis said he had changed his mind, an official who was present said. It was probably a form of West Nile virus, a disease never before seen in the Western hemisphere.

Stunned by the sudden turn, senior officials at the Federal Centers for Disease Control and Prevention peppered their colleague with questions. Was he sure? What testing was done? Was it repeated?

The officials decided not to inform New York of the new finding immediately. They sent the scientist, [Dr. Duane J. Gubler (born 1939)], back to his laboratory in Fort Collins, Colo., to do more tests. He reconfirmed the conclusion, and the next morning, calls went out to New York City.

Federal public health officials were chagrined but not overly worried by the sudden switch in diagnosis. West Nile virus is slightly less virulent than St. Louis encephalitis, and the city was already eradicating the mosquitoes that transmitted the disease, whatever it was.

But the announcement caused concern among many of the scientists and Government officials who are working to strengthen the nation's defenses against biological warfare. They saw the New York outbreak as a dress rehearsal, a test of how public health officials could detect and deal with the sudden spread of a disease not typically found in the United States. To them, the missed diagnosis was unnerving.

''The encephalitis outbreak in New York is a powerful lesson for public health authorities,'' said Alan P. Zelicoff, a senior scientist at the Federal Center for National Security and Arms Control at Sandia National Laboratories in New Mexico. ''It is a sobering, not so reassuring, demonstration of the inadequacies of the U.S. detection network for emerging diseases.''

Local and Federal officials agree there is much to be learned from New York's experience that can be applied equally to defense against biological warfare and the emerging need to deal with the global spread of virulent disease.

While the public health system performed well in many regards, officials point to several key missteps. For instance, in testing samples from the initial victims, the C.D.C. screened only for six viruses common in this country. The scientists did not test for several that have been linked to foreign epidemics or germ warfare.

In addition, the scientist holding a key clue to the true identity of the virus, a bird specialist who had noticed the unexplained deaths of crows near the Bronx Zoo, could not get anyone at the C.D.C. to return her calls for a week. In the end, she turned to several other Government laboratories, including a military research center, to confirm her suspicions that the C.D.C. had the wrong virus.

Finally, the myriad state, local and Federal agencies involved in the investigation did not always communicate well with one another.

''We've learned about the need for, and benefits of, improvements in laboratory coordination,'' said Scott Lillibridge, who leads the C.D.C.'s Bioterrorism Preparedness and Response Program. ''We've also learned how helpful surveillance can be, particularly in beginning to track the beginning, extent or progress of an infectious disease outbreak.''

Over the past several years, the Federal Government has invested hundreds of millions of dollars on a national program to defend against biological terrorism. Several officials said that in light of New York's experiences, much more money should be invested in the public health systems detecting epidemics.

The Discovery : 2 Elderly Patients Sound an Alarm

On Aug. 23, Dr. Deborah S. Asnis, an infectious disease specialist at Flushing Hospital Medical Center in Queens, called the city's Health Department with some distressing news -- two elderly patients had come in with symptoms that looked like a neurological illness -- fever, muscle weakness and confusion.

[Dr. Marcelle C. Layton (born 1958)], who heads the Health Department's Bureau of Communicable Diseases, told Dr. Asnis to send samples to the State Department of Health, and then called the C.D.C. to warn them that something -- maybe botulism -- was happening in New York City. As the week went on, the number of sick people was starting to mount.

The case was assigned to Dr. Gubler, one of the C.D.C.'s experts on diseases spread by insects. His suspicions focused on St. Louis encephalitis, which is often found in the Southeastern United States.

To confirm his theory, [Dr. Duane J. Gubler (born 1939)], tested the samples for antibodies against six viruses transmitted by insects and commonly found in the United States. The tests came back positive for St. Louis encephalitis, a close relative of West Nile fever.

The C.D.C. announced on Sept. 3 that tests of blood and spinal fluid had confirmed Dr. Gubler's suspicion. The Mayor called a hasty news conference in Queens. His office of emergency management took the helm and began a $6 million campaign to wipe out New York's mosquitoes.

Within days, New York City had practically cornered the nation's supply of insect repellent, and 250,000 brochures about the disease were printed and distributed, along with the free repellent, by 500 city employees.

And New Yorkers quickly began to debate which thing unknown to their region they feared the most -- St. Louis encephalitis, or malathion, the insecticide that began to rain down from clacking helicopters.

At the Bronx Zoo, officials were worrying about what seemed to be a serious, but separate biological event. Since July, zoo officials had been receiving calls from people in the Bronx and Queens about dead birds. Four days after the city's St. Louis encephalitis announcement, several exotic birds at the zoo were dead. But not emus. And that made Tracey S. McNamara nervous.

Dr. McNamara, who is the head of the department of pathology at the zoo, knew that St. Louis encephalitis, which is carried by birds and transmitted through mosquitoes, does not normally kill the birds.

She considered the possibility that the birds were being killed by another common form of encephalitis. But that disease is deadly to emus, which were thriving. Something much more complicated was afoot, she reasoned.

The pathologist took to her lab, spending 12 hours a day analyzing bird samples. What she found was so disturbing, she said, that she called the C.D.C to alert them. The dead birds were bleeding from the brain and had badly damaged hearts. Was a similar virus infecting people?

''We had dead people and dead birds and I thought we needed to pursue this,'' she said.

She also contacted the National Veterinary Services Lab in Ames, Iowa, part of the United States Department of Agriculture, to study the samples. Around the same time, Ward Stone, the chief wildlife pathologist for the State Department of Environmental Conservation, began noticing large numbers of dead crows, and alerted his counterparts in New Jersey and Connecticut that something strange was happening to the local bird population.

While the C.D.C. agreed to take some of Dr. McNamara's samples, agency workers then did not return her daily calls for a week. ''I got voice mail,'' she said. In fairness, she acknowledged, dead people were taking precedence.

But the agency seemed slow to grasp the possible link to the birds' illness. Dr. McNamara is circumspect about criticizing her colleagues at the C.D.C., but she said, ''I would say a lesson to be learned was that there was some tunnel vision.''

In the Federal Government's dress rehearsals of how a city might detect and handle a sudden outbreak of disease, officials had foreseen many different scenarios. But no one had anticipated an outbreak in which crucial evidence would be uncovered by a wildlife specialist.

''How we respond to introduced diseases in the wildlife perspective is not very well resolved,'' said Michael Samuel, a research project leader at the National Wildlife Health Center, a unit of the Department of Interior, which is also researching New York's outbreak. ''I don't know that we as a nation have a contingency plan in place.''

Dr. Stephen Ostroff, the acting deputy director for science and public health at the C.D.C., said that confusion is a normal part of an emerging diseases investigation.

''Anyone who continues to maintain that there was some mistake here doesn't understand the way science proceeds in outbreak investigations,'' Dr. Ostroff said. ''You won't hear any apologies from me.'' He said he was not aware of Dr. McNamara's repeated attempts to reach C.D.C. officials.

The Breakthrough : Military Minds Turn to Outbreak

Back in the Bronx, Dr. McNamara was getting impatient. The veterinary lab in Ames had already exhausted its capabilities, but could not specifically identify the strange virus that was killing the birds.

Dr. McNamara sent more samples to the C.D.C., but she also put in a call to the United States Army Medical Research Institute of Infectious Diseases, looking for a favor.

Could the laboratory, which does not usually get involved with civilian requests, take a peek at her samples? Dr. McNamara, it turned out, had some chits to call in. She had recently attended the wedding of the pathologist who performs such tests. The lab agreed to take a look.

The system was working, after a fashion. The military's finest minds on bioterrorism had turned to New York's outbreak.

On Sept. 21, Dr. McNamara sent the samples to the lab by overnight mail. Within a day, the Army's unit, which is based in Fort Detrick, Md., confirmed that a virus of a very different sort was killing birds.

Meanwhile, the C.D.C. was beginning to make the connections. On the same day, officials at the agency called Dr. McNamara and said they wanted more material. She sent it out that evening.

On Sept. 24, scientists at the Army lab told her that the tests of bird samples for West Nile virus ''really lit up,'' Dr. McNamara said.

The C.D.C., with help from each of the labs involved, had come to the same conclusion. That day, the agency announced that birds were dying in New York City, and a West Nile-like virus was the reason. The scientists strongly suspected that the humans had been killed by the same virus, but had yet to confirm it.

The answer came, strangely enough, from California. The New York State Department of Health, without telling the C.D.C., sent some of the brain tissue from people believed to have died of St. Louis encephalitis to a lab run by [Dr. Walter Ian Lipkin (born 1952)], a scientist at the University of California in Irvine who had bumped into state scientists at a conference in Albany.

On Sept. 24, [Dr. Walter Ian Lipkin (born 1952)] found that a form of West Nile virus -- which the C.D.C. now believes is similar to a strain previously found in Europe -- had sickened the New York patients. Soon after, the C.D.C. reached the same conclusion.

The words ''West Nile virus'' had little significance in New York. But in Washington, they raised red flags among American intelligence officials who follow bioterrorism, an incident reported by this week's New Yorker magazine.

In April, a supposed associate of Saddam Hussein published a book in Britain in which he claimed that the Iraqi leader had threatened in 1997 to unleash a form of West Nile virus against his enemies.

A closer look at the Iraqi biological weapons program found no evidence that Baghdad had ever experimented with the virus and intelligence officials, along with arms inspectors who had visited Iraq's laboratories, concluded the report was baseless.

Last night, the C.D.C. issued a statement saying it believed the West Nile outbreak was the work of ''Mother Nature.''

The eerie coincidence underscored what officials said was a new reality.

''Sadly the world has changed. The threat of bioterrorism is real and growing,'' said Dr. Margaret Hamburg, an assistant secretary at the Department of Health and Human Services who was previously head of the New York City Health Department. ''Whenever a new or unexpected disease emerges in an outbreak such as this, it would be irresponsible not to at least consider the possibility of bioterrorism.''

Congress, the officials said, has been slow to spend money on detecting outbreaks, even as they invest hundreds of millions in other bio-defense efforts and vaccines.

This year, lawmakers for the first time approved $120 million to strengthen the C.D.C.'s programs for education and monitoring disease. However, the $40 million set aside for improving state and local health detection was only disbursed late last month, as a West Nile-like virus was spreading through New York.

''We're spending hundreds of millions on questionable stockpiles of vaccines and antibiotics,'' said Dr. Zelicoff, the scientist at the Sandia Laboratory. ''We should be improving the ability of local public health officials to recognize and report strange illnesses to a central authority that can quickly tell them what to do about it.''

Dr. Gubler is the Director of the Division of Vector-Borne Infectious Diseases of the National Center for Infectious Diseases, the Center for Disease Control and Prevention in Fort Collins, CO. He has academic degrees in entomology and zoology (B.S.) from Utah State University, parasitology (M.S.) from the University of Hawaii, and pathobiology and tropical disease ecology (Sc.D.) from the Johns Hopkins University. Dr. Gubler has spent his career studying vector-borne diseases and has extensive field experience in Asia, the Pacific and Caribbean islands, Central and South America, and Africa. He has worked on dengue and dengue hemorrhagic fever for 29 years, and he co-developed the mosquito inoculation and immunofluorescent techniques that allowed for routine virologic confirmation of clinically diagnosed dengue cases. He used these methods in Southeast Asia to develop the first virologic surveillance for dengue hemorrhagic fever and to help to clarify the clinical spectrum of illness associated with dengue virus infection. Dr. Gubler also pioneered the field of mosquito vector competence and was the first to show that geographic variation in susceptibility to dengue viruses occurred among strains of both Aedes aegypti and Aedes albopictus. In the Caribbean, he directed the development of the CDC dengue laboratory, which now serves as a world reference laboratory for diagnosis, surveillance, prevention, and control of epidemic dengue. During this period, Dr. Gubler pioneered the concept of active disease surveillance and community-based, integrated mosquito control as the most effective approach to preventing epidemic dengue/dengue hemorrhagic fever. Dr. Gubler has coordinated major emergency responses to epidemics of vector-borne diseases, including the 1994 plague epidemic in India and the 1999 West Nile virus epidemic in the northeastern United States. He holds adjunct academic appointments as professor of microbiology at Colorado State University and professor of international health at the Johns Hopkins University School of Public Health and Hygiene. He is a Past President of the American Society of Tropical Medicine and Hygiene.

Please describe the mission of your laboratory in terms of mosquito-borne viruses.

We are responsible for all vector-borne infectious diseases, which include viruses and bacteria. In our division, we have four World Health Organization Collaborating Centers for Reference and Research: one each on arboviruses, plague, Lyme disease, and dengue hemorrhagic fever. Our mission is to monitor these vectorborne infectious diseases around the world, to provide consultation and advice to agencies from the local level to the international level, to conduct surveillance on a global basis, and to provide reference and reagent services for laboratories around the world. We also carry out research on ways to improve surveillance and to develop more effective strategies for prevention and control of these diseases, although we don’t actually implement the control ourselves. Our laboratory-based research, which is primarily applied research, focuses on the development of improved diagnostics and immunogens.

How would you describe the global threat from mosquito-borne viruses in particular?

In terms of vector-borne diseases, you have to look at the current status from the perspective of what has happened over the past 50 years. By about 1970, we had effectively controlled many of the important vector-borne diseases. We went into the 1970s and 1980s in a rather complacent mode, with this effective control behind us. The policy- and decision-makers essentially redirected the resources that had been used for vector-borne diseases to other, higher-priority and competing areas. We saw the support for research on vector-borne diseases dry up during the 1970s, 1980s, and 1990s. Concurrently, during that 30-year period, we also saw many global demographic and societal changes that were conducive to the spread of infectious diseases in general, and vector-borne diseases in particular. In the past 20 years of the 20th century, from about 1980 to the present time, we have seen a dramatic resurgence of infectious diseases. The vector-borne viral diseases are among the most important of those. An example is dengue hemorrhagic fever, which is, without question, the most important vector-borne viral disease of humans. It was effectively controlled 30 years ago, but recently it has spread globally throughout the tropics. In 2001, more than half of the world’s population, between 2.5 and 3 billion people, live in areas of risk for dengue. We estimate that every year there are between 50 and 100 million cases of dengue fever and several hundred thousand cases of dengue hemorrhagic fever, the more severe form of the disease, depending on epidemic activity. Other vector-borne viral diseases provide similar examples; Japanese encephalitis, which has also been resurgent in the past 20 years, is one. It is primarily a Southeast Asian disease, but we have seen it move into West India and Nepal, south into Papua New Guinea and northern Australia, and east into the Pacific. In addition, diseases such as West Nile, which have never been major public health problems, all of a sudden show up in places like New York and the northeastern United States to cause major outbreaks. It is a sign of the times, with the changing demographics and societal behavior, and the increased movement of people, animals, and commodities via modern transportation into areas that do not have the public health infrastructure to deal with vector- borne diseases. We have seen a major increase in epidemic activity associated with many of these viral diseases. For yellow fever, we have the most economical, effective, and safe live virus vaccine available. Yet yellow fever is potentially one of the most important emergent diseases in the next 10 years, primarily because large areas of the American tropics have become reinfested with Ae. aegypti, the principal urban vector. Once urban yellow fever transmission starts in Latin America, we expect this virus to move very rapidly into the Pacific and Asia via modern transportation. Yellow fever could become the next global public health emergency if we don’t do something to reverse that trend. The unfortunate thing is that like dengue hemorrhagic fever in the Americas, we can see it coming and have the ability to prevent its occurrence, but we are sitting by and doing nothing. Arboviral diseases, in general, are among the most important emergent/resurgent infectious diseases that we will have to deal with over the next 10–20 years.

What are the priorities for the CDC?

The National Center for Infectious Diseases, of which we are one division, has developed a plan to deal with emergent infectious diseases. We have four primary areas of focus: surveillance and response, applied research, infrastructure and training, and prevention and control. We have identified a number of priority areas, including vector-borne and zoonotic diseases. Our priority over the next 10 years is to try and develop more effective surveillance, prevention, and control in the United States at the local, state, and federal levels to deal with vector-borne diseases. We are also working closely with international partners to develop more effective surveillance, prevention, and control programs in endemic and enzootic areas outside of the United States. The rationale is that if we can develop better partnerships in endemic areas, we can develop more effective global surveillance, and it would be less likely that diseases would be introduced into the United States and cause major epidemics here. We are focusing on prevention, rather than waiting for the epidemics to occur and then trying to respond to them.

What do you see as the major threats to the United States in terms of vector-borne viral diseases in the next decade?

Right now, the biggest threat would be the geographic spread of West Nile virus. It appears to have become established in this country, and because it is maintained in a mosquito–bird cycle, and a lot of the birds that are infected are migratory, it is possible, if not likely, that this virus will move south, then move back north, and ultimately become established in most of the United States. It has important health implications in terms of human disease, of course, but it also has very important animal implications for the veterinary community. It has a very high fatality rate in horses, for example. The unique thing about this virus is that it has a very broad host range. It infects not only a large number of birds, but also a number of mammals; we don’t yet understand the full implications of the introduction of this virus. The emergence of West Nile virus in the Western Hemisphere also represents an opportunity, a wake-up call, to warn us that we are not prepared for these kinds of introductions and that we must get on with the job of rebuilding the public health infrastructure and the research capacity to deal with vector-borne diseases that were controlled in this country 30 years ago. Other threats include several local viruses that have been here for many years. In dealing with the West Nile virus, we will also deal with them, but I don’t see them as major threats in the future. Of the introduced viruses, we have dengue, which is introduced into this country repeatedly every year, with the numbers of cases introduced dependent on the amount of epidemic activity occurring in tropical areas. In recent years, we have seen increased transmission of dengue in the United States. We have two good vectors for the virus here, Ae. aegypti and Ae. albopictus, so the potential is always there for an outbreak of dengue fever in this country, especially in the southern tier of Gulf Coast states. Another potential problem for the United States is yellow fever. We used to have major outbreaks of both dengue and yellow fever in this country—they are both transmitted by the same mosquitoes in urban areas—so yellow fever is also a potential threat even though we have an effective vaccine for this virus. The key to eliminating the yellow fever threat is to use that vaccine effectively. Ideally, we would like to see the control of the mosquito vectors, but that will probably not happen any time soon. There are other arboviruses that could be introduced into this country. As I said, West Nile virus was a wake-up call, because other closely related viruses could cause similar types of problems— Japanese encephalitis is one of them. We have the mosquito vectors here that can transmit this virus. In addition, three very good mosquito vectors have been introduced into the U.S. since 1980: Ae. albopictus, which came sometime in the early 1980s; Ochlerotatus (Aedes) togoi, which was introduced into the northwest part of the country in the 1990s; and most recently, Ochlerotatus (Aedes) japonicus, which was first detected in 1998. We cannot predict what the next major introduction of an exotic agent might be. West Nile virus was the last virus we expected to be introduced into the United States. The takehome message is that we need to be prepared for the unexpected.

Are vaccines a realistic and reasonable strategy, or should surveillance and mosquito control be the primary approach to prevention?

Let’s take vaccines first. Yes, vaccines are a realistic way to prevent disease, provided they are used properly. The yellow fever vaccine is a good example of a very economical and effective vaccine that is not effectively used. If we have vaccines, and they are not used, they are worthless. If we are going to put money into the development of vaccines, we have to be sure they are going to be used effectively.

What has prevented the yellow fever vaccine from being used effectively?

The main obstacle is competing priorities for limited resources. If you don’t have an endemic disease, then the decision-makers usually take the limited resources and put them into areas where they are needed the most. While that may seem logical, with diseases such as the mosquito-borne diseases, which can resurge so quickly, it doesn’t make sense. This is what happened with malaria as well. It is unlikely that we will ever eradicate the mosquito vectors, so we are always at risk for epidemics of these diseases. We need to educate the policy-makers about this ongoing risk and convince them to maintain the prevention methods indefinitely. If a vaccine is available, we need to maintain a high level of herd immunity in the population to prevent potential future epidemics. If mosquito control is the primary method of prevention, then we need to maintain that infrastructure to prevent transmission. The problem is that in the past 30 years, we have relied too much on surveillance and emergency response, as opposed to disease prevention. Surveillance is a critical component of any prevention strategy, but you must have a follow- up with sustainable programs in place to implement control to prevent subsequent human disease. Once you have an epidemic on your hands, it’s generally too late. We need renewed emphasis on rebuilding capacity for vector-borne diseases, and that requires vector surveillance and understanding which species are present, where they breed, the seasonal distribution, and how these species’ population densities respond to seasonal and other environmental conditions. It also requires surveillance to identify viral activity in the community. It has to be an ongoing program at the local level, and it has to be supported indefinitely. We are not going to eradicate mosquitoes or ticks, but that is not what people want to hear. These days many people want a “quick fix,” a magic bullet. That’s why vaccines are so popular, because they don’t require any responsibility on the part of the individual. We have to go back to the thinking of 50 years ago, when people accepted some responsibility for disease prevention and helped public health authorities. We need the help of the people in the community if we’re going to be successful in developing sustainable prevention programs for vector-borne diseases.

What hope is there for genetic modification of any of these mosquito species to make it more difficult or impossible for them to be vectors for infectious organisms?

There is always that hope. The manipulation of vector species to make them resistant to infection or less effective vectors can take a lot of forms: You can change their blood-feeding habits, for example, or genetically manipulate them so that the virus cannot replicate efficiently if they do become exposed. I certainly don’t discourage research in this area, but having said that, I have to caution people that this gets into the “quick fix” area. This is the type of research that everyone likes to fund, from NIH on down. Millions of dollars have been put into this type of research over the past 30 years, and I would dare anyone to give me one example of where it has had any lasting impact on vector-borne disease transmission. These are very difficult manipulations to achieve, and even though you may be successful in the laboratory, when you put them into the field, it becomes more difficult to get that genetic change into the natural populations. I would strongly urge that there be more of a balance between funding for these kinds of projects and those to develop the basic programs in biology, behavior, prevention, and control that we know will actually work in preventing disease transmission.

I would like to focus more specifically on dengue and West Nile viruses. Beginning with dengue, please describe the current situation in the Americas.

It is depressing. We predicted, as early as 1980, that epidemic dengue would recur and become widespread in the American tropics and that dengue hemorrhagic fever would emerge in the region. Everything that we predicted has come true. Very few countries in the region, with the exception of Cuba, have taken seriously the challenge of developing prevention programs. Even Cuba has had some setbacks in recent years because of economic problems, but they are the only country in the region that effectively prevented and controlled epidemic dengue during the 1980s and most of the 1990s. In the past 30 years, the whole region has become reinfested by the principal urban vector, Ae. aegypti. Compared with the 1920s and 1930s, when there were major epidemics of both dengue and yellow fever in the region, the vector species now occurs in much higher densities in urban areas. There are more automobiles and therefore more tires; we have poor water systems, so people have to store water; and most consumer goods are packaged in nonbiodegradable plastics and tins. All of these make ideal larval habitats and breeding sites. Finally, the human populations are much larger in these urban areas, and the waste management systems in many cities are poor. The end result is a much denser human population living in intimate contact with much higher mosquito populations and, thus, much higher transmission potential for viral diseases like dengue. You add to that the increased movement of people between population centers around the world, who introduce new viruses on a regular basis, and the result is increased epidemic activity caused by all four dengue virus serotypes. This has created what I call hyperendemicity, or the co-circulation of multiple virus serotypes in communities, and that is generally associated with the emergency of dengue hemorrhagic fever. The situation in the Americas in 2001 is not good. We are going to see continued epidemics of dengue and continued dengue hemorrhagic fever, and we’re going to see a lot of people dying of dengue hemorrhagic fever if we do not do something to reverse the trend.

What is being done to control dengue virus?

Very little in the past 30 years. Since about 1970, the emphasis has been on spraying insecticides to control the adult mosquito population. Realizing that this approach does not work and that adulticides have little or no impact on disease transmission, we developed a community-based program in Puerto Rico in the 1980s that focused on larval control. We know that that approach works, because it was used to eradicate Ae. aegypti in the 1940s, 1950s, and 1960s from many countries of the region. The difference in 2001 is that we have large populations of people living in urban centers, and there is no way that any government in the region has the resources to go into every house every 7 days to control the larvae. If we’re going to have sustainable larval control, we will need the help of the people who live in those houses. That is the rationale we used to develop the community-based program that has now become the basis for the global strategy of the World Health Organization. The Pan American Health Organization was among the first to embrace this approach. They developed guidelines for prevention and control of dengue hemorrhagic fever in 1994, held regional meetings with various governments, sent consultants to the countries to help them develop local programs, and followed up by sending review teams out to evaluate the progress. Unfortunately, with all of this work and support, most of the governments still do not have effective prevention and control programs in place. They still essentially wait until epidemics occur and then try to respond to them; the response is always too little and too late.

Has there been any demonstration of a decline of dengue virus due to control methods?

Probably the best example in this region is Cuba, which had a major epidemic of dengue hemorrhagic fever in 1981; they then implemented a mosquito control program. Initially, they used a lot of insecticides, but that really wasn’t necessary. They developed a very effective larval control program that prevented epidemic dengue in Cuba for 16 years, from 1981 to 1997, using the people of the community and a lot of inspectors to follow up and evaluate. Essentially it was a top-down form of mosquito control, which requires central government control; this approach doesn’t work in most democratic countries. But the take-home message is there: if you control the larval mosquitoes, you are going to control adult mosquitoes and prevent transmission; we know that it works. During this period, every country around Cuba had repeated, large epidemics of dengue. We have not effectively demonstrated that the community-based approach works in any other country. The closest to success would be in Puerto Rico, where in 1998 our surveillance system predicted an epidemic of dengue. The epidemic occurred as predicted, and a community- based response was implemented. It appeared that the epidemic was being controlled, when Hurricane Georges hit in the middle of all this. The hurricane terminated the surveillance program and probably also stopped transmission, so we don’t have good data on the results of the program. The other country that has effectively controlled dengue using this approach is Singapore. Singapore put a program in place in 1968, and they went 20 years without any epidemics of dengue. In the mid-1980s, the director of the program retired, and they had a few years when it didn’t function as well as it should have. Even so, they were able to keep the mosquito densities at a low level. The problem with Singapore is that it is surrounded by countries that repeatedly have major epidemics of dengue fever and dengue hemorrhagic fever, with hundreds of thousands of cases. Many immigrant workers go into Singapore on a daily basis, so they have a lot of introduced dengue, resulting in outbreaks during the 1990s.

What is the potential for dengue reaching epidemic levels in the United States?

Dengue is repeatedly introduced into this country every year. Millions of people travel from the United States to dengue-endemic countries in Latin America, Asia, the Pacific, and Africa, and they bring dengue back with them; in recent years, we have seen increased imported dengue. The mosquito vectors that transmit dengue occur in the United States, thus increasing the potential for epidemic transmission. Yet we have not had any major epidemics in this country for over 60 years. I think the reason for that is our lifestyle. We eliminated epidemic dengue and yellow fever in this country, but we did not eliminate the mosquitoes. Although there is reasonably good mosquito control—the mosquito abatement districts do a good job of controlling the mosquito populations—other factors probably played a more important role. These include reliable piped water systems, good waste management, and good housing with air conditioning and screening. We have relegated Ae. aegypti mosquitoes to outdoor peri-domestic habitats, where they do not have as much contact with humans. Human behavior in the United States is also not conducive to transmission. During the peak biting time, when Ae. aegypti feeds, humans are indoors, either eating breakfast in the morning or watching television in the late afternoons and evenings. My feeling is that while we are at risk and there is the potential for an epidemic, I don’t think we are going to see any major epidemics of dengue in this country, as long as we maintain our public health infrastructure and our standard of living.

What are the similarities and differences between dengue and West Nile viruses?

They are similar in the sense that they are both flaviviruses, and they both cause a similar type of illness—a nonspecific viral syndrome— in the majority of infected patients. But there are a lot more differences between these viruses than there are similarities. West Nile is generally a rural disease, whereas dengue is an urban disease. West Nile is maintained in a Culex mosquito–bird cycle, and dengue is maintained in an Aedes–human cycle. There is no good evidence yet, although we don’t discount it, that humans play a role in the transmission cycle of West Nile virus; whether the viremia is high enough for a human to infect mosquito vectors has not been determined. While West Nile is primarily a rural virus, recent epidemics have occurred in urban areas (Bucharest, New York City, Volgograd, and Tel Aviv), so it is adaptable to urban areas. Whether it will persist in urban areas is another question. Our guess is that it will ultimately become enzootic in the United States, primarily in rural areas.

What is the threat of West Nile—the worst-case and best-case scenarios?

Of course, the worst-case scenario would be that it has become established in the United States and will move with the migratory bird population south into the southern coastal states, as well as into the Caribbean and Latin America, and then with spring migrations will be reintroduced back into the United States, into the Midwest and western regions, and ultimately become widespread in the United States. The best-case scenario is that it will act like St. Louis encephalitis virus, which is closely related and has appeared in the northern latitudes. St. Louis encephalitis virus has occurred as far north as Canada, but generally, after outbreaks, the virus persists for a year or two and then disappears. These viruses, St. Louis encephalitis and West Nile, are basically tropical viruses, and their natural cycles are in tropical or subtropical regions. We won’t know what the outcome will be until we have several years of surveillance data behind us.

What is most responsible for new mosquito vectors coming into the United States?

The most likely way these exotic mosquito species are brought into the country is in commodities, through container shipping. We are quite sure that Ae. albopictus and probably Oc. japonicus were introduced by this mechanism, probably in the used automobile or truck tire trade. These mosquitoes love to lay their eggs in used tires. When used tires arrive in the United States, they are often stored in an uncovered area; when it rains, the eggs are flooded, they hatch, and the larvae develop to pupae and adults. I don’t know of a single case in which an exotic mosquito species has been established by the introduction of an adult, but I suppose it is possible.

What are the prospects and strategies for preventing further introductions of mosquitoes?

There are several possibilities. We tried to prevent the introduction of new species after Ae. albopictus was introduced in the 1980s by implementing strict quarantine regulations that required the people who brought in used tires to inspect and fumigate them to kill the eggs. Because there is such a huge trade and so many containers had to be checked, it became unreasonable to enforce that regulation, and it was taken off the books. I think the best way to prevent the establishment of exotic species in the United States is to rebuild the infrastructure in this country at the local level to deal with both pest and vector mosquito species. Any time a new species is introduced, effective surveillance by trained people will detect it immediately, and targeted control can be initiated to eliminate it. That is probably the most cost-effective way of preventing future introductions. It has the side benefit of having professional entomologists who are doing the mosquito surveillance and can implement controls to prevent disease. It also controls pest mosquitos and improves the quality of life for the people in the community.

What specifically is being done to control West Nile virus?

After the 1999 epidemic, we developed guidelines for the surveillance, prevention, and control of West Nile virus in the United States. We implemented those guidelines in the spring of 2000 with supplemental funding from Congress. Unfortunately, it was not enough money to initiate mosquito control, but it was enough to implement surveillance to monitor what was happening. We didn’t even know if West Nile would survive throughout the winter. This winter, we will review the surveillance data from the 2000 transmission season, make further recommendations on the prevention and control of this disease, and help state and local health departments initiate their programs. If we are ever going to prevent human infection with West Nile virus, we have to get on with the business of developing locally based mosquito abatement programs. We need to focus on larval control and not wait until we have activity in an area and then depend on adulticides. There has to be a change in the mentality of the public health officials who are making decisions about vector-based disease control. We have a good model of mosquito abatement districts, especially along the Gulf Coast from Texas to Florida. They are highly professional, are funded through local mill levy tax systems, and are quite effective at doing mosquito surveillance and control.

Is it fair to say that at present there is insufficient trained manpower in the United States to address a threat such as West Nile?

Yes, it is safe to say that. To put this into a historical perspective, you must look back at the types of programs that were in place at the local and state levels and in our universities 30 years ago. In 1970, there were many local mosquito control programs in place, routinely doing mosquito surveillance and control, and there were numerous university-based arbovirus programs that provided the necessary technical expertise and diagnostic support for arboviruses. In 2001, however, you will find that not many states have mosquito surveillance and control programs in place and that either most of the arbovirus programs in the universities have deteriorated to the point where they are small, ineffective programs, or they have been completely eliminated. The first thing we need is for the public and public health officials to realize that if we are going to prevent epidemics of exotic diseases like West Nile, we need to rebuild the infrastructure to deal with mosquito-borne diseases. We are very ill prepared to deal with these kinds of introductions at the beginning of the 21st century.