A very nicely researched piece on anthrax;
Anthrax cases bewilder experts
By William J. Broad, Stephen Engelberg, Judith Miller and Sheryl Gay Stolberg
New York Times News Service
The diagnosis of inhalation anthrax in a New York hospital worker who died early Wednesday throws into question many of the assumptions about an outbreak on which the scientific and medical wisdom was already being revised daily, sometimes hourly.
Just a few days ago, it seemed possible that the current spate of anthrax infections could be largely traced to a handful of anthrax-laced letters, in particular a remarkably potent one that wound its way from New Jersey to a Washington mail collection center and then, finally, to the office of Tom Daschle, the Senate Democratic leader.
That now seems increasingly unlikely. And what was striking on Tuesday as officials struggled to explain the latest twist — the infection in the hospital employee, who works in a basement stockroom and neither handles the mail for a living nor appears to have been the target of an anthrax-tainted letter — was their acknowledgment of how much they do not know.
"It is unclear whether this particular instance is part of a pattern of other cases or whether it represents something different," said Dr. Jeffrey Koplan, head of the Centers for Disease Control and Prevention. "We are making no assumptions as to where this exposure occurred."
Since the first case was diagnosed in Florida a month ago, almost every assumption about anthrax has been challenged, if not disproven outright. Finely ground anthrax, it now seems, can form a lethal mist with no more sophisticated a delivery system than an envelope in the mail. Powerful antibiotics, doctors have learned, can offer a fighting chance of survival even after symptoms have appeared. Yet the amount of spores needed to produce inhalation anthrax, the deadliest form of the disease, could be far smaller than previously believed.
The most recent case is even more confounding. Could a wisp of the anthrax mailed to Washington have found its way to the basement of a Manhattan hospital before settling in the lungs of the worker? Were there other letters and, if so, where are they? Or is this latest infection a harbinger that something worse is to come — an anthrax outbreak in which the spores are being spread in some way other than the mail?
The inability of scientists to answer these questions points out how little experience they have with the illness.
Anthrax is an ancient disease, refined in the 20th century into a weapon of war. But there is little human data on how the infection takes hold in individuals or how an outbreak moves through populations.
There is also enormous uncertainty over who might have the capability to produce such a weapon. While only a few nations are known to have made anthrax in the form found in the letter to Daschle, the technology for producing such finely ground particles is now widely available. While it might take more than a Ph.D. in microbiology to make the weapon, it is not beyond the ability of a terrorist group or even a lone individual trained in the arts of pharmacology.
"This is a classic who, what when, where and why," said Dr. Michael T. Osterholm, director of the Center for Infectious Disease Research at the University of Minnesota. He added: "We are going to have to start getting used to this uncertainty in the short term, because it is going to take a while for these cases to be fully investigated."
From a public health standpoint, the troubling, unanswered question about the 61-year-old New York hospital worker, who has been identified as Kathy T. Nguyen, a Vietnamese immigrant, is whether she was what epidemiologists term an "outlier" — someone who fails to fit the pattern of an outbreak and therefore represents a harbinger that an epidemic is about to grow more dire.
"The obvious thing here is, it is not clear what her source of exposure would be," said Stephen S. Morse, director of the Center for Public Health Preparedness at Columbia University. "She doesn't fit the normal pattern. She's not a mail handler who was working in a facility where there was a lot of mail going to the media or government offices or an obvious target."
Before the outlier question can be settled, some old-fashioned disease detective work must be done. Authorities must track Nguyen's habits and whereabouts in the weeks before she became ill — all without her help. They must test for anthrax in her home and workplace; the stockroom where she worked shared space with the hospital mail room until recently. Some tests have already been conducted, and the few results that have come back so far have been negative.
"We are making no assumptions as to where this exposure occurred," Koplan said on Tuesday, "and we have to both investigate and rule out where she worked, did she have other jobs and where else she might have been exposed, what were her patterns of activity."
He added, "And we don't have answers on all of those yet."
In any public health investigation, authorities zero in on the "mode of transmission" — the way a disease is spread. In the case of anthrax, so far, the mode of transmission has been the mail. But anthrax germs are being spread intentionally, not naturally, so officials must be open to the possibility that the mode of transmission may have changed.
One important clue is that the woman has developed inhalation anthrax, which occurs when microscopic spores lodge in a person's lungs. Although experts have theorized in recent weeks that anthrax might be spread when letters cross-contaminate one another in postal facilities, many are skeptical that the woman got infected this way.
One comforting sign, experts say, is that so far, no one else has gotten sick. If someone intentionally released anthrax spores in the hospital or some other place the woman visited, "you would probably see an epicenter of several people being infected," said Dr. Irwin Gelman, an infectious disease expert at Mount Sinai School of Medicine in Manhattan.
So it may take additional anthrax cases — if any emerge — before authorities can determine whether the woman's infection is the result of exposure in the mail or through some other means.
"If you're investigating a serial killer, its very hard to know the pattern of that serial killer after one or two murders," said Osterholm, of the University of Minnesota. "By the seventh or eighth murder, things start to appear in a particular way. As more cases come in, we will learn a lot about the epidemiologic pattern and the risk factors for developing this infection."
On Tuesday, New York City public health officials urged doctors and hospitals to be alert for additional cases of inhalation anthrax. "You need to be watchful for those first cases that don't fit any established pattern," said Morse, of Columbia, "because they may tell you that there is another pattern that you need to be looking for."
In theory, a single letter containing anthrax, like the letter sent to Daschle, could contaminate other letters moving with it through the postal system with enough anthrax to infect a person.
To some, that scenario seems unlikely.
"The whole secondary spread is very dubious to me," said Dr. Philip Brachman, the researcher who did the pioneering studies of anthrax in the United States in the 1950s following an outbreak at a textile mill in New Hampshire. "If you did have an envelope that had spores in it and some of the powder gets out and lands on something else, I'm not sure it becomes aerosolizable. I can envisage large particles coming out, but for them to re-aerosolize in a manner in which they would be inhalable, that would take a tremendous amount of energy. I don't know if that's aerodynamically possible."
But other experts said that, given recent events, spreading of the spores in this way could not be ruled out.
The issue arises because anthrax spores, if properly grown and processed, are incredibly potent. Federal officials have already disclosed that the powder in the Daschle letter was an advanced formulation, with a compound added to keep the anthrax particles from sticking together, enabling them to float more freely, spread more widely and potentially infect more people.
One gram, or one-twenty-eighth of an ounce, of such high-grade anthrax can hold up to 100 billion spores, said Ken Alibek, a former top official of the Soviet germ weapons program who is now president of Advanced Biosystems Inc., a consulting company in Manassas, Va. Estimated conservatively, at 10,000 spores to a lethal dose, one gram in theory could cause about 10 million deaths.
Rep. Mike Pence, R-Ind., whose office last week was found to be contaminated with a few spores, said in an interview that he had been told by federal investigators that the letter sent to Daschle contained two grams of anthrax — enough to make about 20 million lethal doses, assuming it could be distributed with perfect efficiency.
But this letter caused only minor problems in the Senate office building itself, because most of the spores probably stayed put and only a fraction rose into the air, weapons experts said. Moreover, only a tiny fraction of the floating particles were inhaled.
The anthrax in the Daschle letter was found to have contaminated 28 people. None of these people became sick. But federal investigators said the Senate letter may have leaked anthrax in transit from New Jersey and infected postal workers there and in Washington. And perhaps it could have even tainted other letters, spreading the germs to other buildings in Washington.
"If you shake it somehow," Alibek said, a contaminated letter might let loose a lethal puff of anthrax spores. "It's possible to re-aerosolize enough to become infected," he said.
Another possibility, he said, was that a poisoned letter could hold so little anthrax that the spores would be essentially imperceptible. "It might be that you wouldn't see the actual product," Alibek said. "It could be a very tiny amount" but still harbor enough spores so more than one person would come down with the disease.
Alibek said that when he directed the production of mass quantities of anthrax in the Soviet Union, scientists were amazed at its ability to spread. The anthrax he perfected at the Stepnogorsk plant in remote Kazakstan, he noted, was found in many unlikely places.
"We found spores where you would never expect to see them," he said. "We found them in zones of our production building where they were never supposed to be. But you can't control wind direction, and you really can't control their movement."
The scientists did not fall ill, however, "because we had a very powerful vaccine, and we were all vaccinated, repeatedly."
As investigators and scientists study the question of whether tainted letters alone could have caused all of the cases of infection and contamination, they find themselves confronting an array of other possibilities, some more likely than others.
The most improbable would be a large-scale outdoor release of spores by an airplane or sprayer driven around by car or van, experts agreed. Such attacks are hard to pull off successfully, especially in urban areas, because fickle winds, heat effects and other meteorological variables would tend to disperse spores harmlessly. Also, they said, such an attack might produce more cases of anthrax than have been reported so far.
"You'd think there would be more cases by now, because people are so vigilant," said Jonathan B. Tucker, a germ-weapons expert in the Washington office of the Monterey Institute of International Studies. "It seems unlikely that this is the first of a wave of new cases."
But strikes in confined indoor spaces, such as buildings and subways, would be easier, experts said, though they agreed, medical evidence for such attacks is so far lacking.
Moreover, hitting a building through its ventilation system can be risky and highly unreliable, said Ashok Gadgil, a senior scientist at the Lawrence Berkeley National Laboratory in Berkeley, Calif., who studies germ terrorism.
For instance, he said, if the two grams of anthrax powder sent to the Senate in a letter had instead been scattered at the building's air intake, the results could have ranged from catastrophic to nothing at all. The outcome, he said, would depend on the quality of the air system.
"If the filters were good — and that's a big if — two grams of the stuff going into the air intake wouldn't have killed anybody," Gadgil said. "But if they were lousy, it would have killed everyone many times over."(This, of course, assumes that the attack went undetected and that no one received treatment.)
Alibek, the former Soviet germ official, said that medical evidence of a large strike, if it occurred, would emerge within days as patients began streaming into hospital emergency rooms.
"If not, if we see nothing in two or three days, it means the attack was maybe small" and most probably the result of mail contamination, he said, referring to the most recent case of the New York hospital worker.
Steven M. Block, a germ-terror expert at Stanford University, noted that science rests on the philosophical view known as Occam's razor, which holds that the simplest explanation of an event is usually the best and most likely to be correct.
By that logic, he said, it is only after the mails have been ruled out in the New York case as a source of contamination that "we'll have to look for a second source."
Bush administration bioterrorism experts remain befuddled by the origin of the anthrax.
So far, all the anthrax samples discovered have characteristics of the so-called Ames strain, a variety the United States used in its germ weapons program. That suggests the possibility that the anthrax was domestically produced, the experts say. So too, they say, does the presence of silica in the anthrax sent to Daschle. Silica was the additive American bioweapons developers chose to remove electrostatic charges from anthrax spores to prevent them from sticking together. Other countries used different materials.
But those who favor the theory that the anthrax has a foreign source say that both the Ames strain and silica along with other hallmarks of the American program have become well-known to foreign scientists.
While some experts initially argued that only three countries — the United States, the former Soviet Union and Iraq — were known to have made the dangerous, high-grade anthrax powder that floats easily in the air, many others disagreed. They say that the techniques used in those programs are now sufficiently common that a well-trained scientist in a private laboratory could have produced similar results, at home or abroad.
Reluctantly, White House officials have come around to that view.
Experts also agree that the list of countries that could have produced the high-quality anthrax is long and growing. A National Intelligence Council report issued last January concluded that more than a dozen states either have or are actively pursuing germ weapons capabilities. The report identified only Iran, Iraq, Libya, North Korea and Syria, along with Russia. But the Monterey Institute of International Studies has complied a list of 13 countries, including Algeria, China, Egypt, Pakistan, Taiwan and Israel.
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