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How did it get here?
Was it a bird? Was it a plane? Was it Saddam?

Sunday, May 11, 2003
Chicago Tribune
by Jason George

Neither the doctors nor the virus cared about her name.

It was her blood they wanted.

To the physicians, she was an "African woman, aged 37 years," a volunteer for a sleeping sickness study. She reported to the donation center near Omogo, Uganda, with a mild fever but said she felt healthy. So clinicians never bothered to learn more about her when drawing her blood.

Yet when researchers back at the Yellow Fever Research Institute in Entebbe injected her blood serum into 10 mice, the aura of routine vanished. Nine of them died. And by the time the first paper on the unknown virus she carried was published two years later, 52 more mouse tests had been conducted with the blood serum. None of the mice survived.

Although her identity may never be known, the mystery killer in her veins ended up making her native region famous. Doctors decided to name the virus after it.

The year was 1937 and the world and West Nile virus had just been formally introduced.

Over the next 62 years, West Nile would emerge as a significant health risk in Africa, Asia and Europe. But its presence in the U.S. was limited to laboratories and a brief interlude in the 1950s, when it was injected experimentally into New York cancer patients. At no time did it capture the eye of the U.S. media, which only pay attention to African viruses when they are performing the macabre -- Ebola's liquefied-organ effect -- or showing up in the American populace, as with HIV.
And then came the summer of 1999.

West Nile first showed up in New York City, causing 7 deaths and making 62 other people very ill. By the end of the year it had spread to four states. By 2002, the tally had grown to 4,156 cases in 44 states and 284 people dead.

Virologists have been forced to reexamine what they know about West Nile. In a new land, the virus is behaving uncharacteristically, killing more people, birds and animals than it ever has before. Last year saw the largest West Nile encephalitis outbreak on record, according to the Centers for Disease Control and Prevention. New studies also hint that the long-term effects of having a bad case of West Nile are more serious than previously thought.

And there is still the nagging question: How did it get here?

Queens residents were the first to notice it that June four summers ago. Not only were crows suddenly dropping dead, they were stumbling and staggering into cars and each other, giving the streets the appearance of an avian French Quarter.

By August the crow deaths were in the hundreds. The problem, said a state pathologist, was probably pesticide poisoning or fungal pneumonia.

Only when carcasses started turning up on the grounds of the Bronx Zoo, operated by the Wildlife Conservation Society, did the actual source of the disease come to light. The zoo's veterinary pathologist, Dr. Tracey McNamara, is openly critical of the New York state officials who were studying the crow problem. "You had people doing these tests whose only knowledge of a bird is the Thanksgiving turkey," she says.

Not inclined to accept the fungal or pesticide theories, McNamara started conducting her own examinations of the dead crows. "I needed to know," she says.

Meanwhile, a 60-year-old man was admitted to Flushing Hospital in Queens. Doctors initially suspected pneumonia. While they were treating him for that, the virus was quickly turning a healthy, active man into one who could not even identify his wife.

As his unusual symptoms -- muscle weakness, high fever, confusion -- worsened, three more patients were admitted with similar problems. For a small hospital to have its intensive-care unit half-full of people fading away from an unknown cause was odd, says Dr. Deborah Asnis, chief of infectious disease at Flushing Hospital.

The doctors were stumped. The only links between the patients, who had begun dying, were that they were older and spent lots of time outdoors.

"Initially, it was very hard to explain to the family members why their relative was so ill," Asnis says. "We didn't have a good explanation."

She reported the cases to the New York City Department of Health, which launched and investigation to find out what was loose in Queens.

Within days, the U.S. Center for Disease Control and Prevention (CDC) announced that the culprit was St. Louis encephalitis, a viral disease found throughout much of the United States and transmitted by mosquitoes, with birds acting as reservoir hosts.

But McNamara, who was becoming convinced that the bird and human deaths were connected, was skeptical. Birds are not supposed to get encephalitis and die from St. Louis. And McNamara was seeing encephalitic-type lesions when looking at the crows.

Over Labor Day, the virus jumped from crows into the zoo's resident bird population, killing a zoo favorite, an American bald eagle. McNamara offered her samples to the CDC, but as the agency does not deal with birds, the offer was refused. "I said, 'Maybe it's a mosquito-born virus other than St. Louis.' But the CDC hung up on me," she recalls.

In the next few weeks, McNamara would be the catalyst leading to identification of the real disease agent. She called the U. S. Army Medical Research Institute at Ft. Detrick, Md. She sent her bird samples to various labs around the country. And in the end, her pestering got results. A team at the University of California, Irvine, led by molecular researcher Dr. Ian Lipkin, named West Nile virus as the agent that had killed both humans and birds.

American researchers now began reading up on the unfamiliar virus. West Nile had recently troubled Eastern Europe too. In 1996 an epidemic in Romania affected 90,000 people and killed 17. In 1999, 40 people in Russia died of it.

But scientists would later conclude the strongest similarity to the U.S. outbreak was one the year before in a flock of Israeli geese. How the geese could be connected to the U.S. cases became the million-dollar question.

That West Nile was causing illness came as no surprise. But its intensity did. After the virus was discovered in 1937, it was soon seen in several countries in Africa, but in these areas it has been less virulent than the recent cases in the U.S. and Europe.

Studies in Egypt during the early 1950s, conducted by a U.S. Navy lab and administered by the University of Chicago, found that although most Egyptians over the age of 20 tested positive for having had the virus sometime in their lives, sickness beyond a mild fever was rare. A more recent study in Egypt by the same lab came to the same conclusion. "We don't see any disease with West Nile. Everybody's got antibodies" or signs of past infection, said a U.S. military researcher who headed the four-year study.

Egypt's neighbor, Israel, had its first confirmed outbreak of West Nile in 1951. Sporadic outbreaks followed in the 1970s and 80s, but then it faded away, leading the Israelis to abandon a research program that tracked the disease. "It was a lot of work, so they said why should they keep this testing?" says Ella Mendelson, director of the Central Virology Laboratory in Israel's Ministry of Health.

But in 1997, and again in 1998, flocks of domestic geese in Israel began getting sick from West Nile and authorities put it back on their agenda again.

In the summer of 1999, while the New York bird population was starting to get sick, a retired Tel Aviv engineer entered a hospital in Israel with a mild fever. The 75-year-old was also confused and disoriented. Four days later, as his condition deteriorated, his wife was admitted to the same hospital with similar symptoms. She ended up dying after a month. He died several months later. Both had tested positive for West Nile.

It is not known how both got the disease, but it is assumed the same mosquito bit them. West Nile is not believed to be transmittable human-to-human.

In the months that followed, a group of Israeli and American doctors made a startling discovery. The virus that caused the deaths in New York and those of the Israeli couple were closely related. The researchers found that the West Nile virus in the Israeli husband and the virus in the American humans and animals had a genetic similarity of 99.8 percent, considered very high. And the Israeli man's brain sample and a sample from the 1998 Israeli geese was a 99.9 percent match.

In short, they're all "almost identical," says Dr. Lester M. Shulman, head of Molecular and Environmental Virology at the Israeli Central Virology Laboratory.

It was one of those instances where more information created more questions. Doctors now knew the American and Israeli cases were connected, but in what way?

Although there is little agreement on exactly how it got here, West Nile had to arrive in one of two ways: either in an unwitting infected host or by someone bringing it in intentionally.

According to the leading theories, an infected person or animal traveled to the U.S. and was bitten by a mosquito here, starting the cycle that keeps the virus circulating. But if true, it was an amazing journey that required several unlikely events to come together successfully.

If a human was the unknowing host, that person would have had to become infected in a country where this rare strain of West Nile was present. That would not necessarily be Israel, the only other place outside America where it has been found thus far. An estimated 150 million birds fly over Israel every year, any one of which could have taken the virus to another country in Africa or Europe, giving it to mosquitoes there and then people.

Wherever the human was infected, though, he or she would have had to pack rather quickly. The virus can only be transferred in a stage called "viremia." A West Nile infection can cause chronic problems, but it is only in this initial window of viremia that one can transfer it. Scientists disagree about how long viremia lasts in humans, but most say two to three days after being infected. For birds and animals, it's usually a bit longer. Birds also display higher levels of the virus in their blood than humans do after becoming infected.

"The person got on the plane in the viremia stage and -- even though the viremia in people may be low, especially lower than birds -- they could still transfer it," says Dr. Thomas Monath, formerly director of the CDC's lab in Fort Collins, Co., which handles West Nile.

New evidence adds some weight to this theory. Titres, or levels of the virus in the blood, seem higher in the American-Israeli strain than in others, meaning it's more likely that a mosquito becomes infected after biting a West Nile-positive person in Chicago than a positive human in Cairo. Greater blood titres might also be the reason that almost 50 people acquired West Nile after receiving infected blood or organs last year.

Other apparent cases of transfer, through breastfeeding and a confirmed case last December of a mother giving it to her unborn daughter, show that the virus levels are definitely suited for transfer when great amounts of blood are exchanged.

Once infected, the host would most likely have had to travel to the New York City area. The deceased Israeli couple did not visit the U.S. during the summer of 1999, according to Dr. Michael Giladi, their Israeli doctor. They had not even left the Tel Aviv area in the preceding five years. And, except for their son, who traveled to Germany a month before the father got sick, they had not recently been in close contact with anyone who might travel abroad. So the human transfer was not directly from them.

Could someone else have been infected and spread it to America? It's possible, but no one besides the couple was diagnosed with this strain in 1999, outside of those who acquired it in the U.S.

So if it wasn't them, was it an animal or a bird?

The most popular answer given by public health officials is that birds are to blame. But a close analysis of how birds are shipped and how they migrate reveals that something statistically akin to winning the lottery needed to happen for birds to be responsible for West Nile's U.S. appearance.

Before letting a bird into the U.S., border officials require a certificate from a veterinarian affirming the bird's health. On arrival, most birds are then quarantined for 30 days, during which time they are tested for various diseases (West Nile was not one of these in 1999, and it still isn't today).

There are only three places in the U.S. where birds are quarantined. One is in New York, not far from Flushing Hospital or JFK International and LaGuardia airports. But a virus that infects a bird being shipped to the U.S. has completed only half its journey once it gets here. The bird must be bitten again by a mosquito, presumably in the New York area, and this mosquito must then spread the virus by biting and infecting U.S. birds. This presupposes that a mosquito got into the quarantine building, bit the infected bird, then flew out again.

Some people argue that the carrier was a smuggled bird -- out of reach of U.S. inspectors. It's possible, but a stretch. In fiscal year 2001 (there are no statistics from 1999), the USDA seized only three live birds from passengers coming from Europe and Africa, hardly a sign that there is a large smuggling problem. And again, the smuggled bird would need to have been bitten by a mosquito in the New York area, and this mosquito would then have had to spread it to a U.S. bird.

Then there is the idea that a bird migrated or got blown accidentally across the Atlantic, but ornithologists scoff at this theory. Only one bird, the Northern Wheatear, regularly migrates across the Atlantic, wintering in North Africa and breeding mostly in Canada. "But it is a very rare bird in the United States," says Kevin J. McGowan a professor with the Cornell Laboratory of Ornithology.

The possibility that a bird was swept across the Atlantic accidentally is even more unlikely. A stray from Africa or the Middle East has never been documented in America and only occasionally do birds make a wrong turn when they are leaving Europe, McGowan said.

Clemson University's Sidney Gauthreaux, who studies bird migrations, says a transatlantic trip could be done by a bird in the 3 to 7 days that viremia lasts, if the bird had help from the wind.

"[But] chances are that birds don't move much when they are viremic," points out McGowan.

Despite the bird-crossing-the-Atlantic theory seeming like a long shot at best, scientists still support it, if half-heartedly.

So what about a mosquito? Could that have been the culprit? The idea that one of the insects flew into a foreign airport and down the ramp onto a plane, then flew off the plane at, say, JFK and out into the New York air is a little hard for most scientists to accept.

Less improbable, but not by much, is that an infected mosquito entered a plane's cabin overseas and then bit someone. The obstacle here is that the bitee would have had to be bitten again by a New York mosquito within the two to three days of human viremia.

A mosquito could have flown into a plane's cargo hold or been packaged accidentally in a shipment. Insects found inside luggage or packages are killed when they are found, said a USDA spokesman. But not every container is always checked, and if a mosquito were in the cargo hold it could just fly out when the doors were opened.

Still, a mosquito surviving at sub-zero temperatures on a long trans-Atlantic flight would be quite a feat.

Nevertheless, it's possible, says Wayne A. Rowley, an Iowa State entomology professor who also studies mosquitoes for the CDC. But Rowley does not think that this is what happened. He subscribes to a more sinister idea -- terrorism.

Though the FBI and CIA looked into the terrorism suggestion in 1999 and found no evidence of a plot, some people say that what we now know about the strain in question makes the possibility worth re-examining.

After someone sent anthrax around the U.S. in the fall of 2001, scientists were unable to determine exactly where it came from because that strain of anthrax was a common one found in labs all over the world. But the West Nile strain in the U.S. is not common. It has been seen only here and in Israel. It is different than previous known strains in U.S and European labs, even distinct from West Nile samples that Iraq acquired in the 1980s from the CDC and a private U.S. company.

That the Iraqi samples are different doesn't take Saddam off the hook in conspiracy theorists' eyes. A 1999 book by an alleged Iraqi defector recounted Hussein's "plan" to use West Nile as a bioweapon. In the book "In the Shadow of Saddam," author Mikhael Ramadam wrote that Hussein told him he was going to release a strain of West Nile on a "Third World population centre" that could destroy 97 percent of all life.

What troubled the U.S. intelligence community was that the book appeared months before the U.S. outbreak of West Nile.

There are several serious holes in the Ramadan story. First, neither the CDC nor the CIA found evidence of manufacturing or "weaponizing" within the American-Israeli strain. What that means is that this strain of West Nile is not more dangerous because some scientists made it tougher and meaner, it's just this way naturally.

Another point is that West Nile, while increasingly severe, has come nowhere near infecting, much less killing, 97 percent of a population anywhere. Last year, 6.5 percent of the confirmed U.S. human cases resulted in death, but even that number is greatly inflated and misleading. There were probably tens, if not hundreds, of thousands of people whose only connection to their infection was a mild fever, some aches or even no symptoms at all.

Still another problem is the reliability of the author, "Mikhael Ramadan," whom no one seems to be able to locate. Ramadan has never come forward to back up his claims or spoken in public since publication.

On the other hand, it would be strange to fabricate a plot of mass destruction based on a virus that has spent most of the 20th century being a mere nuisance. There are many other viruses -- 74 related flaviviruses alone. So why would Ramadam, or Saddam Hussein, pick West Nile?

The Ramadan book makes most experts throw up their arms.

"You have to say this is just irrelevant," says Monath. "But it is curious."

There is one more argument against West Nile being the result of bioterrorism. Public health officials in 1999 publicly questioned why someone would chose West Nile instead of, say, smallpox, which is highly contagious and often fatal.

But West Nile has a lot of advantages over smallpox as a weapon, others point out.

"It's not something that [could be traced to] only two labs in the world, so it would be very difficult to find out who was behind it. You could just release it and say, "Let's see what happens," says Manfred Green, director of the Israeli Center for Disease Control, who believes terrorism is "highly unlikely."

"And if that is the case," he says, "it's been very successful. Look at the way they have managed to do something to the United States. I mean, if you think about the damage it's caused, just economic damage, it's been enormous."

It is very difficult to determine how much West Nile has cost the U.S., but it is arguably in the many millions of dollars. The 1999 outbreak in New York alone cost an estimated $10 million, not including losses as a result of export bans that year on horses from the New York area to the European Union and poultry to Mexico.

Rowley, who has studied mosquitoes for 35 years, said spreading West Nile here on purpose would not be difficult.

"It would be the easiest thing in the world," he says, "to bring an ice cream cart of infected mosquitoes to someplace."

If the terrorism hypothesis is rejected, what's left is the theory favored by the CDC: that something infected with this unique strain of West Nile came to New York City. There, it was either bitten or bit something, spreading the virus.

Few scientists will openly confront the weaknesses of the leading theories.

"It is a cop-out answer to an extent, but the alternative is that somebody brought it here on purpose and many don't want to go there," Rowley said. "Certainly the CDC doesn't want to go there."

There are those who have talked about the possibility that West Nile could have been something like a dress rehearsal for a more dangerous weapon to follow.

"Let's assume they release some mosquitoes in some area, they infect some local bird. It could be a test run to see how to start a chain reaction. So maybe the next step now is 'Well, let's take something that is more problematic," Green said.

McNamara, no longer with the Bronx Zoo, is one of the few people involved in the hunt for West Nile who does not espouse a theory on the mystery. "We will never know," she says. "The investigation started long after the initial event."

"The fact that it is identical to a strain that popped up in Israel is a bit disconcerting but you have to remember that we import pathogens wholesale on a daily basis -- in container ships, planes, people."

As a scientist, McNamara is trained to find and examine data. But in the puzzle of West Nile, its arrival in the U.S. will probably remain a missing piece.



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