Commentary: Questions on West Nile Virus

Aug. 29, 2001 -- Outbreaks of encephalitis from the "West Nile" virus are not getting the proper scientific attention. The scope of the research is too narrow.

The potential importance of polluted and unhealthy environments in which West Nile virus outbreaks often occur is being ignored due to lack of funding and scientific indifference.

It's noteworthy that West Nile virus is typically described by scientists as a rare, mild and usually harmless infection in humans, affecting mostly the elderly. In birds, however, the virus has been highly touted as a killer.

Like Canaries in a Mine

Traditionally, birds have been viewed as sentinels for toxic environments, the canary in the mine being the most famous example.

What if some degree of the damage to birds and humans now attributed solely to the virus is actually triggered by harsh environmental factors that need to be addressed?

To date, attempts to prevent West Nile outbreaks have often relied on the spraying of mosquitoes. This is controversial and raises the possibility of further polluting a toxic environment that is already causing harm and contributing to the outbreaks.

Robert McLean is one of several federal scientists prominently involved in West Nile virus studies who understands the importance of also investigating environmental factors in the emergence of new diseases. For instance, some studies seem to show that toxic air pollution could potentially enhance the activity of a virus and make it churn out more copies of itself.

"Because we don't have the resources, we're missing the opportunity to look at many different factors that may be going on with West Nile," he said. As director of the Wisconsin-based National Wildlife Health Center of the U.S. Geological Survey, McLean now spends most of his time diagnosing and studying dead crows and other wildlife that turn up positive for a West Nile virus infection.

Dr. Ian Lipkin of Columbia University, who has played an important role in identifying the genetics of the West Nile virus, is an infectious disease scientist who thinks beyond microbes. He too believes that an understanding of disease comes from probing the relationship between environmental factors, including viruses and toxic substances, and the genetic endowment of individuals.

To Lipkin, it makes perfect sense to want to know more about how, say, "an unhealthy environment might break down immunity in both birds and humans and make them more susceptible to viral infection. It's worthy to pursue this."

Searching and Tracking

Even so, when all is said and done, both McLean and Lipkin are still focused on the biology and behavior of the virus. That's where the research action has been since the outbreaks began in New York City in the summer of 1999.

Much of the public health effort is aimed at tracking and identifying mosquitoes that transmit the virus, tracking and diagnosing dead birds, particularly crows, for signs of the virus and monitoring human blood samples for signs of infection.

Symptoms of human infection are said to include fever, headache, and body aches. The rare serious cases can involve inflammation of the brain, causing stupor, tremors, convulsions, paralysis and death.

In 1999, seven people who died and 62 people who became ill turned up positive for the virus. Last year, there were 21 cases, including two deaths.

So far this year, at least ten people, including four in Florida, one in Georgia and five in the New York City area have turned up positive.

Last month, a study published in The Lancet estimated on the basis of sample blood tests and interviews that 8,200 people in the New York City area in 1999 came down with asymptomatic West Nile infections and about 1,700 experienced some flu-like symptoms.

Ozone and the Immune System

Valuable clues have not been investigated about the possible role of air quality in the outbreaks that began in the New York area in 1999. Outbreaks have since occurred in other regions of the country.

The summer of 1999 in New York City was extremely hot and, according to the New York State Department of Environmental Conservation (DEC), the smog was the worst in more than a decade. Smog includes ozone, which forms in the air from other toxic substances, including nitrogen oxides and volatile organic compounds.

It is scientifically established that ozone can affect the body's immune system so that the ability to fight infection may be impaired. It also can cause damage to the brain and lungs.

Steady Flow of Dead Crows

As New Yorkers baked in the heat that summer and were exposed to high levels of ozone, veterinarians and pathologists began to receive calls about unusual numbers of bird deaths.

In Delmar, near Albany, a veteran wildlife expert at the DEC's wildlife pathology unit, Ward Stone, began to receive a steady flow of dead crows, the most he had seen in 30 years.

He figured the heat and the lack of rain had somehow exposed old pesticides in soil and vegetation. It seemed the birds were being poisoned.

Stone then requested the standard type of toxicology testing. In looking for pesticide residues, it is routine to check for low levels of the enzyme cholinesterase. It has become standard practice that even if there are very little or no pesticide residues found in the birds, if the cholinesterase levels are low, then it is deemed likely that the death was due to pesticide poisoning.

On the basis of the tests, he began to theorize that the epidemic of dead birds was likely due to pesticides.

Stone didn't request tests to determine if bad air quality was playing a role in the bird deaths even though high ozone levels can also affect cholinesterase levels.

"We don't order those tests because there are no funds to do that kind of work," he said.

In fact, Stone couldn't recall anyone in his line of work doing air toxicology tests on birds.

When Stone's conclusions about pesticides and dead birds were about ready to be released in a DEC report, a human mystery disease was given an identity.

New York Mayor Rudolph Giuliani held a press conference on Sept. 3, 1999, to announce that scientists at the Centers for Disease Control and Prevention in Atlanta had identified the St. Louis encephalitis (SLE) virus, which is transmitted by mosquitoes, as the culprit in the hospitalizations of several elderly patients. They initially had high fever, headaches and altered mental status and gradually showed signs of brain inflammation.

Soon helicopters and trucks began spraying areas of New York City with the highly toxic insecticide, malathion.

With several scientific groups conducting further genetic tests, it was soon agreed that the culprit was actually West Nile virus and not SLE, Kunjin virus, which was also a major suspect, is another member of this family.

Indifference?

But air quality was not deemed to be an important factor for study among those scientists working on West Nile virus.

This indifference smacked of short-sightedness and arrogance to Jim West, a researcher who works with NoSpray Coalition, an environmental group that has been in the forefront of New York area protests against the spraying of insecticides.

West, 54, is not a scientist. He has music talent in his background and a solid block of engineering courses. Translation: he is mainly self-taught when it comes to biology and toxicology.

He decided to begin mapping the relationship between dead crows and ozone levels (see Web link at right.)

Consulting New York State records and ozone maps from the Environmental Protection Agency (EPA), he noticed that there was a strong correlation between areas of high ozone levels and dead birds that turned up positive for West Nile virus.

West understands that strong correlations do not necessarily mean the relationship is a causal one.

"But this correlation continues to this very day," he said, adding that "anyone studying these publicly available maps and health department documents would have to wonder why the correlations are so strong and should want to further investigate."

Environmental Efforts and Ozone

As one of many examples, he points out that the first seven of eight dead positive crows were found this year in New Jersey's Middlesex county, which happens to be near oil refineries.

West probed further. He set his research sights on a chemical called MTBE (methyl tertiary butyl ether) put into so-called reformulated gasoline as part of a federal effort to make gas burn cleaner.

Some critics believe that MTBE may be even more harmful than ozone. According to Peter Joseph, a toxicologist at the University of Pennsylvania, "symptoms vary widely as MTBE can affect the nervous system, breathing, the heart and trigger allergies."

To date, states are at various stages of reconsidering use of the chemical. A New York State ban on MTBE will go into effect in 2004.

Factoring in Ecological Context

West discovered that those New York City area counties with MTBE-reformulated gasoline reported that 117 dead crows were positive for West Nile virus. The other counties without the MTBE only reported 2 positives. The counties by then had tested about 570 dead birds.

Breaking the data down further, he found that in those MTBE-using counties designated as severe air pollution areas by the EPA, the percentage of positives of those birds tested was 24 times the number found in moderate- and less-polluted counties.

"Jim West's got some good ideas, but he's not a scientist," said Stone, who has met with West at the state pathology unit in Delmar and finds his modeling plausible. "Yes, we certainly need to take a look at air pollution, but I don't think that it has anything to do with West Nile-related morbidity."

Technology Linking Dead Birds and West Nile

Sean Ahearn, director of Hunter College's Center for the Analysis and Research of Spatial Information, offers another perspective. " I think it is extremely important to factor in air pollution and even MTBE because they may harm the immune system and make it easier for an infection to take hold."

Ahearn and his colleagues run a computer project for the City of New York that uses a sophisticated formula to chart clusters of dead birds across the city. Still in its testing phase, it is helping the city to link non-random dead bird clusters to pools of mosquitoes that show signs of the West Nile virus and then to possibly predict where human infection has a high probability of occurring.

"The next phase of the project will be to factor in the ecological context, things like air quality and weather," Ahearn said. "I think this is the only logical way to go."

Virus Takes the Blame

Stephen Guptil of the geographic sciences branch of the U.S. Geological Survey agrees. He too says that his unit may consider mapping an air quality layer in their tracking of West Nile events.

"We may find via this tracking that higher ozone levels lead to greater susceptibility to replicate more virus," Guptil said.

Maybe so, but is there more to this than meets the eye? Guptil is assuming that only the virus (whatever the amount of viral replication) leads to harm, either in crows or humans.

That assumption may turn out to be premature.

In a paper published in the journal Science on Dec. 17, 1999, the authors claimed they had isolated the West Nile virus. It's since been widely accepted (as Guptil does) that whenever the "virus" is injected into, say, a crow, and the crow dies, it means that here is proof positive that the cause of West Nile disease is solely the virus.

That conclusion suggests to many scientists that you might as well forget about any environmental factors being necessary in causing West Nile-associated illness. Some scientists, including Lipkin and McLean, allow for the possibility that environmental factors might enhance the opportunities for infection.

Either way, the virus remains the culprit.

Filtering Out the Virus

John F. Anderson, the director of the Connecticut Agricultural Experiment station in New Haven and the lead author of the study, explained that his group ground up mosquitoes and the brains of dead crows and after several steps eventually filtered out the virus.He used a filter of 0.22 micrometers because he wanted to "exclude bacteria and fungi" from the culture.

The purpose of isolating a virus is to ensure that viral particles are pure and therefore separated from everything else, including possibly harmful materials from the very cells they infect. That way you are reassured that further tests may tap the virus as the likely cause of an illness.

But was a filter of 0.22 micrometers small enough, given that a West Nile viral particle is said to be 0.04 micrometers, about six times smaller than the filter? In other words, there is enough room for cellular matter to move through the pores along with the West Nile viral particle. That cellular matter could incorporate the biochemical products of other toxic insults, including those from the environment, to the organism.

"Yes, small molecules [from tissue] can pass through," Anderson admitted, but didn't think this might be a problem of any kind.

"We don't have a purified form of the virus," said Robert McLean matter-of-factly. "Cellular material could interact with the virus to enhance the replication of viral particles."

What McLean left unsaid was the possibility that the cellular material itself could be sufficiently toxic to cause damage to tissue, with or without the virus.

Clearing the Air

The fact is, no one knows. The West Nile virus was never purified. I find no evidence anywhere in the scientific literature that the rules of virus purification and isolation were followed thoroughly.

Add to this potentially serious omission the scientific indifference to the possible role of the environment in what is being called "West Nile" illness and death.

So what does this all suggest?

A major error in understanding why many birds and some individuals are becoming ill?

An unnecessary and costly West Nile virus industry, consisting of drug development, vaccine-making, public health fiefdoms, fights for status and funding, and so on?

It would help to clarify the situation if we could get some serious air toxicology research underway. That shouldn't be too much to ask.