Anatomy of an Outbreak: West Nile Virus

National Post, Saturday August 19, 2000
James Gathany

NEW YORK, NY – Before Enrico Gabrielli became patient zero for the western hemisphere’s West Nile outbreak, he enjoyed evenings sitting outside in his garden, in an Italian neighbourhood in New York’s northern borough of Queens.

He puttered in his garden, and, like most of us, didn’t worry much about the odd mosquito. The bites are itchy. But mosquitoes are little more than a nuisance of nature. Aren’t they?

A week or so after one of those bites last summer, the well-tanned 60-year-old started feeling ill. On August 12, he went into emergency and was admitted to hospital with complaints of fever, weakness and nausea, which soon progressed into full-blown encephalitis. Three days later, an 80-year-old man, also with a good tan, arrived at Flushing Hospital in Queens with the same symptoms. Then a 75-year old. By the beginning of September, they had been followed by five more.

“Initially we had three people from the same area of Queens, three previously perfectly healthy people, who had roughly the same symptoms,” says Dr. Rick Conetta, director of critical care medicine at Flushing Hospital, the hot zone of last year’s outbreak.

“And just [when] we were realizing these three were the same, we started wondering, ‘Is it some kind of epidemic?’ Then the fourth case came in. Then we knew there must be something going on.”

The toll to date for West Nile in North America is seven fatalities, 65 cases of severe illness and several thousand dead birds. What makes it remarkable is not its speed or its fatality rate — Ebola would spread more quickly and kill an exponentially higher number of victims — but the simple fact that it managed to get here. For that reason, experts on emerging infectious diseases say, New York’s continuing epidemic of West Nile is one of the most stunning events in the history of virology.

West Nile is being considered a harbinger of risk for far more lethal outbreaks. The virus is telling us that the Atlantic Ocean is no barrier preventing the migration of pathogens — the ones lurking, incubating and mutating in foreign jungles — from landing on our shores. “The world is a small place,” says Dr. Ian Lipkin, director of the Emerging Diseases Laboratory at the University of California at Irvine, where last year’s virus was identified as West Nile. “And with increases in global travel and trade, and incursions into wildlife habitats, the urbanization of primitive areas, we’re going to see an increase in the frequency with which infectious agents begin to move about into the remainder of the world.”

“It’s when you introduce a new agent into a new environment that you begin to see outbreaks of severe disease,” he says. “That’s what’s happening in the case of West Nile.”

At about the same time that Enrico Gabrielli was noticing symptoms, New York’s population of crows were dying in unusually high numbers, even for a city that sees so many shot, poisoned, hit by
cars and killed by natural causes.

“Crows were dropping from the sky,” said Dr. Tracey McNamara, head veterinary pathologist with the Wildlife Conservation Society at the Bronx Zoo, about 20 km northwest of Queens.

Then, just after Labour Day, 1999, 24 birds from the zoo’s own population suddenly died.

“We had a trumpeter swan doing the backstroke,” says Dr. McNamara. She also lost seven Chilean flamingoes out of a flock of 40, and Clementine, a bald eagle and the mascot of the zoo.

What Dr. McNamara found most frustrating was trying to make a diagnosis. She ran some tests at the pathology lab at the zoo.

“I got findings that screamed viral encephalitis,” she said, during a tour of her lab, in which shelves are lined with bottled bird parts preserved in formaldehyde. But what she saw was nothing she recognized from the textbooks. And her facilities weren’t sufficiently sophisticated to recognize anything new.

She started sending out specimens to other experts, including wildlife pathologist Ward Stone at the New York State Department of Environment and Conservation, 250 km up the Hudson River in Albany.

Dead birds of all kinds were at the department, arriving in red and white Coleman coolers and piling up outside his necropsy room, where again this year his walk-in freezer is filled waist-high with dead birds waiting to be tested.

Last year Mr. Stone received birds mostly from the southerly counties of New York state, centering around New York City.

“All of a sudden this year, whoosh, it has spread out,” he says, referring to a map of New York state and the surrounding area that is covered with colour-coded push pins indicating where birds have died.

Most of the push-pins are black, for crows, with a fair number of blue for blue jays, red for raptors (birds of prey), yellow for house sparrows and a few green indicating “other.”

“We have a Canada Goose with West Nile this year. It’s one of the greens,” he says.

Though Canada Geese pass freely and often between the two countries, the evidence of West Nile closest to Canada is still a crow, found in the Buffalo suburb of Townawanda.

As Mr. Stone likes to point out, “As the crow flies, that’s not far from Canada.”

“Unfortunately,” says Stone, “my predictions last year turned out to be right. Birds have been the best indicator of where the disease is going.”

But while Mr. Stone was accurate with his prediction about birds being good sentinels of the disease, he had no better luck than anyone else in identifying the disease.

“Nobody could identify the virus because they weren’t set up to identify what they had never seen before in the country,” he said. “Nobody was looking for West Nile.”

“What we’ve got [with West Nile],” he says, “is a new mortality factor for the Western Hemisphere, for birds and humans both.”

Back in Queens, once Flushing Hospital suspected they had an epidemic on their wards in August, they contacted the Department of Health. From there, the New York City Outbreak Investigation Team was deployed.

“Our unit mobilizes for outbreaks almost on a daily basis,” says Dr. Marci Layton, a medical epidemiologist and assistant commissioner at the Department of Health (she was one of several key players in last year’s outbreak that officials at Health Canada invited to a conference last February to develop a Canadian contingency plan for West Nile’s seemingly inevitable migration across the border). “But the team for West Nile was working around the clock,” Dr. Layton says. “And it became a bigger and bigger team over the next month and a half.”

She estimates the team of city and state health officials peaked at several hundred.

There were 75 people per shift on the West Nile information hotline alone. The army also included surveillance workers, going out in the field to find dead birds and collect mosquitoes from dry ice traps that lure them in by mimicking human breath. Officials in neck-to-toe white uniforms sprinkled pesticide pellets to kill mosquito larvae and spray trucks wound through the paths of Central Park — where this year, despite further findings of mosquitoes, and the cancellation of a Philharmonic Symphony Orchestra concert, New Yorkers continue to jog and bike and rollerblade, without even a whiff of bug repellent (300,000 cans of repellent — reportedly all that were on the market at the time — were given out in the city last year for free).

The most crucial members of the Outbreak Investigation Team were the epidemiologists, or disease detectives, such as Dr. Layton. As soon as she got the call from Flushing, she and her team visited the hospital and spent hours examining the patients, combing through charts and taking specimens.

“We also interviewed the families and visited their homes to try to find what these people had in common,” she says. “The only thing they had in common was that they enjoyed spending time outdoors.”

After doing as much in-house medical detective work as they could, the DOH investigators hit a wall, just as the investigation did with the dead birds. At city and state labs, though test results indicated some kind of infectious mosquito-borne disease (the kind of disease that commonly causes encephalitis), health officials came up empty.

At that point, Dr. Layton sent specimens on to the scientist-crowded Center for Disease Control and Prevention in Fort Collins, Colorado.

There, in a biosafety level-three laboratory — where investigators work in negative-pressure biosafety cabinets wearing gowns, masks, gloves and boots, and where they must “shower-out” before re-entering the real world — tests came up positive for St. Louis encephalitis virus (genetically a close cousin of West Nile).

St. Louis itself was very rare in North America and had never before emerged in New York. When the news was announced on Sept. 3 last year, the Mayor took swift action New York was sprayed with mosquito-killing pesticides only two hours later.

While the diagnosis of the St. Louis virus seemed to explain the human epidemic, it didn’t explain what was going on with the birds. According to Dr. McNamara’s continued research at the Bronx Zoo, birds are not known to die of the St Louis virus.

Bronx Zoo samples by now had been sent to the U.S. Department of Agriculture, and the National Veterinary Services laboratories, both without any precise diagnosis.

“With every test that proved negative, the level of concern elevated,” said Dr. McNamara. “[If] it’s not this, it’s not this, it’s not this … Then what is it?”

It wasn’t until the two scenarios merged — when CDC finally agreed to look at the bird specimens, though that was outside its immediate mandate to protect human health and safety — that the diagnosis was changed to West Nile.

West Nile is defined as an arthropod, vector-borne virus. The vector is an insect (the arthropod), in this case a mosquito. West Nile’s host, or the reservoir of the virus, is almost always a bird.

The most common host in the New York outbreak has been the crow, although innumerable species of birds have been affected. Humans are only “incidental hosts,” quite literally caught in the crossfire as the virus moves back and forth from mosquito to bird to mosquito, and so on.

According to Dr. Linda Glasier, a wildlife disease specialist at the U.S. Geological Survey’s National Wildlife Health Center, the return of West Nile for a second season indicates that the virus is increasing its range.

“The number of infected mosquitoes is increasing, they’re biting more birds and making them more infected, then the birds give it to more mosquitoes,” says Dr. Glasier.

“The cycle just keeps increasing until you have so many infected mosquitoes out there that one could much more easily bite a human.”

Based on studies of St. Louis encephalitis, mosquitoes have to be infected at a rate of one in 1,000 for the virus to become a rampant threat to the human population. A similar ratio is estimated to exist for West Nile, although experts say it is almost impossible to trap a large enough sample of the billions of mosquitoes in the area of the outbreak to determine how close the current situation is to that threshold.

Once the virus enters the human blood stream, it can circulate for three to 15 days before the onset of illness.

“A virus is nothing more than some genetic material wrapped up in a protein coat,” explains Dr. Ostroff. “[But] it doesn’t have the machinery it needs to reproduce itself. So what it does is it takes over the machinery inside your cells,” he says. “It invades your cells and makes copies of itself and when it has made enough copies, the cell bursts and dies and out come more copies of the virus.”

“Which cells it takes over is dependent upon the virus,” he says. “Some recognize liver cells, some recognize lymph tissue. West Nile appears to like the central nervous system. That’s why it causes encephalitis.

“The [inflammation of the brain] is the body’s response to the virus there. The body is trying to kill the virus.”

Since there is no treatment for West Nile (nor any vaccine) all that can be done for an infected individual is supportive therapy, such as intravenous fluids and respiratory assistance.

Severe infection or death occurs when the body’s immune system is too weak to wage a successful fight, explaining why the elderly and those with weak immune systems are most at risk.

Of the seven human deaths caused by West Nile in last year’s outbreak, all were elderly. And of the total 58 cases of severe illness to date, most have been over 50.

Another factor in assessing the threat of West Nile is determining how many people have been infected unwittingly, with only mild illness or no symptoms at all. The reported cases, as Dr. Layton describes are only “the tip of the iceberg,” according to a survey conducted in the hot zone of Queen’s after last year’s outbreak.

The question the Department of Health wanted answered was, “In the 9 km epicentre of the epidemic, what percentage of the population actually became infected with West Nile virus?”

Health officials went door-to-door and took anonymous blood samples from volunteers in a mobile health unit van parked on neighbourhood streets. Of the regional population of 46,000, about 700 blood samples were tested at CDC. Based on the results, it was estimated that a maximum of 4.1% of the population had been infected, or approximately 2,000 people.

“That was much lower than expected,” says Dr. Layton, comparing it to an outbreak that occurred simultaneously last year in Russia which made 600 ill and killed 32. Three years earlier, an estimated 90,000 had been infected in Bucharest, Romania, with 373 severe cases.

And where West Nile has become endemic in the Nile Delta region of Egypt (the virus was discovered and named after the West Nile district of Uganda where it was first found in the blood of a woman in 1937), 40% of the population is estimated to have contracted the virus over the course of their lives.

The New York strain of the virus is most likely related to one of these recent outbreaks. DNA evidence, however, showed it to be 99% similar to a virus specimen collected from a goose in Israel in 1998.

How it got from Israel to New York is the matter of some speculation.

One possibility, considered by the CIA, was bioterrorism.

A New Yorker article in the fall of 1999 reported that just four months before the outbreak, CIA officials had heard that Saddam Hussein, the Iraqi president, was planning to use the West Nile virus as a bio-weapon. This was according to a self-described Iraqi defector who went by the name of Mikhael Ramadan.

Mr. Ramadan was said to look like Hussein and allegedly worked for the dictator as a double to foil assassination attempts. In Mr. Ramadan’s autobiography, In the Shadow of Saddam, Mr. Ramadan recounted that it was during his last meeting with Mr. Hussein that he mentioned his plans for West Nile:

“Saddam summoned me to his study. Seldom had I seen him so elated. Unlocking the top right-hand drawer of his desk, he produced a bulky, leather-bound dossier and read extracts from it … the dossier holds details of his ultimate weapon, developed in secret laboratories outside Iraq … Free of UN inspection, the laboratories would develop the SV1417 strain of the West Nile virus — capable of destroying 97% of all life in an urban environment … The target had been selected, Saddam said, ‘but that is not for your innocent ears.'”

The last word on Mr. Ramadan, according to the article, was that he was hiding out somewhere in Canada.

Beyond this unlikely scenario, CDC scientists have been working on a yet-to-be published report, West Nile Virus Origins Project, theorizing on how the continent-hopping virus landed in New York.

The purpose of the project is not to find the smoking gun and take punitive measures.

“The purpose is to assess and prioritize major factors of risk,” says Dr. Daniel Singer, the CDC Epidemic Intelligence Service officer in charge of the study.

There are three obvious possibilities: a mosquito, a bird or a human.

A mosquito seems least likely, with the chances being slim of someone inadvertently packing the infected pest into their luggage on return from a trip to an exotic land, and then unpacking it alive upon arriving home in New York. Then again, scientific experiments have proven that mosquitoes can survive cross-Atlantic flights while travelling in the wheel-well of a plane.

A person is a little more probable. Someone can travel around the globe in 80 hours, never mind 80 days — less than the incubation period for many infectious diseases. According to the CDC study, between 1998 and 1999 1.1 million people travelled to New York from places where West Nile has been found. But the fact that few humans are ever infected with West Nile severely enough to pass it on to a mosquito puts them barely on the study’s top 10 list of carriers.

A bird is the most likely culprit. Species such as the Eurasian Wigeon migrate from breeding grounds in the Old World all the way to the eastern seaboard of North America. And a few birds have been known to get carried across the ocean in tropical storms. Larger numbers, though, are imported, both illegally and legally, for commercial purposes — 5,563 between 1998 and 1999 for pet stores and zoos, and a minority for consumption (most American food-industry poultry comes from Canada). Most birds imported legally undergo a quarantine of at least 30 days at the USDA quarantine warehouses in New York, Miami and Los Angeles.

But even those precautions are not fail-safe, because birds could be infected with West Nile if they were bitten during transit, as they wouldn’t manifest any symptoms for days. And no tests for West Nile exist for healthy birds and animals, again because on the Western Hemisphere, at least, West Nile was thought not to exist.

Although Dr. Singer and his team do not expect to retrace the path of West Nile precisely, they will be able to develop a model from the study that will act as a compass, guiding our response to the infectious disease pathogens that might make their way to our shores in the future — something epidemiologist say is sure to happen.

“This time it happened to be West Nile,” said Harvey Artsob, chief of zoonotic diseases (diseases in animals communicable to humans) at Health Canada’s virology labs in Winnipeg. He’s head of Canada’s only biosafety level-four laboratory, one of only about 15 in the world, where the most lethal pathogens such as Ebola reside.

“Ebola is an example of the worst extreme scenario of an imported disease,” said Dr. Artsob.

“That’s our biggest fear, [an infectious disease] that grows by aerosol [airborne] route. They can travel around the world so quickly from person to person.”

“If you look historically,” he says, “a disease we’ve already had this century that was terribly frightening was the Spanish Flu in 1918 when millions and millions of people died. This is the worst case scenario. The worst type of disease. And we will get pandemic influenza one day again. We will. We know we will. It’s inevitable. We just don’t know when.”

Joshua Lederberg, a Nobel Laureate and professor of microbial genetics and evolution at Rockefeller University ups the ante one notch further.

“The single biggest threat to man’s continued dominance on the planet is the virus.”

That is the Lederberg quotation that fades to black before the beginning of the infectious-disease blockbuster movie Outbreak, a film that virology experts agree is based on some good science and then becomes wildly exaggerated (they nonetheless loved every minute of it).

Dr. Lederberg explains that it is when viruses start misbehaving and wiping out their hosts that things get unpredictable.

“Most viruses settle down and take small bites out of their host, and then both the virus and the host live longer,” he says. “[Viruses] are always walking a tight rope because if they’re not aggressive enough, they can’t establish a foothold, they can’t sink their teeth into you. And if they’re too aggressive and they sink their teeth into a vital organ, then whoops, too bad for both sides.

“When viruses are behaving themselves and playing by the rules, they will have only moderate virulence,” he says. “But every now and then, they are dumb enough, because evolution is unpredictable and mutations are unpredictable, that they will stumble down a path of very high virulence and start wiping things out.”

“Do I think [West Virus is] an important health risk?” asks Dr. Lipkin. “Absolutely. Do I think in the future we may have to be concerned with West Nile becoming the major [mosquito-borne] virus in North America? There is a very good possibility of that. The prediction many of us would have is that this virus is going to become more prolific, more prominent, and be associated with more disease.”

“We have to use our intelligence,” Dr. Lederberg advises. “We have to develop what responses we can. We very badly need to develop better drugs for treating virus infections. We’re very behind on that. We don’t do too badly on vaccines,” he says, “but we need 10 years advance notice.”

Revising his Outbreak quote, Mr. Lederberg says, “I think humans are the biggest threat to human dominance. We’re more likely to kill each other off, because we go about that with such supreme intelligence.”

But barring human stupidity and complacency, he warns, outbreaks of emerging infectious diseases could go a very long way toward wiping out the human race.

After Mr. Gabriella, patient zero, had been to the brink and back due to his bout with West Nile last year, he was rewarded with the dubious honour of being “vaccinated” for a virus that has no vaccine: That is, because he was infected with West Nile virus, and survived, his body has naturally built up the antibodies that give him life-long immunity. Now he would be capable of fighting the virus off, should he have another encounter with an infected mosquito in his garden.

Meanwhile, on the third floor at Flushing Hospital, where Mr. Gabriella fought West Nile a year ago and won, Dr. Conetta again is contending with a critical care unit full of elderly patients exhibiting similar symptoms.

“Things are getting strange here,” he says, finishing off a call with the New York City Department of Health regarding some blood samples he recently sent in.

“This is the real drama,” Dr. Conetta says.

“Families are looking at you asking what’s going on. Last year we had nothing to tell them. We had four critically ill patients in ICU at the same time and all we could tell the patient’s families was that they were very sick but we don’t know what’s going on.”

“This year, when they realize they might be part of an epidemic, they’re shocked,” he says.

“Imagine, being killed by a mosquito.”

Carriers of disease

Two main species of mosquitoes have been discovered as transmitters so far:

– The culex pipiens, “chirping bird” or common house mosquito (also known as the “dirty water mosquito” for its preferred breeding ground), bites only at dusk and dawn, and only attacks humans when they can’t find a bird.

– The tiger mosquito, imported on a shipment of tires from Asia in the 1980s, is known for it vicious appetite for human blood in particular and will bite at any time of day, even in broad daylight.

– The common North American black crow has been identified as the main transmitter of West Nile, receiving it from one mosquito and passing it on to another.

Who discovered it?

Researchers are arguing over who deserves credit for initially identifying the West Nile Virus.

Dr. Lipkin will likewise tell you “I made the first identification of West Nile,” at the Emerging Infectious Diseases Laboratory in California.

Dr. Stephen Ostroff, federal co-ordinator of West Nile operations at CDC, disagrees.

“I wouldn’t say Dr. Lipkin discovered it,” he says. “Some of the findings were through Dr. Lipkin. Some of the findings were through our Infectious Disease Laboratories in Fort Collins. They all sort of came together at the same time.”

It was CDC, however, that had the distinction, during a press conference on Sept. 24, of announcing to the world that West Nile was confirmed to have arrived in the Western Hemisphere.

Other scientists say the identification wouldn’t even have been possible without their persistence early on in getting wildlife samples diagnosed.

“If the pushy pathologist at the Bronx Zoo hadn’t kept knocking on doors, we wouldn’t know the humans and the crows were connected. That’s a sobering thought — we wouldn’t know we had a new virus,” says the zoo’s Dr. McNamara, giving herself a pat on the back.

For his part, Ward Stone says the work he did at Department of Environment and Conservation was unjustly overlooked. He insists that he deserved just as much credit, and he wrote a few blasting memos to the political powers involved to get the recognition he thought was due.