It's also our duty to take advantage of the opportunity to get vaccine data--Dr. Helms, ACIP

[Guest guest]

Government's shot in the darkThe anthrax vaccine: Government's shot in

the dark

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By Sanjay Bhatt, Palm Beach Post Staff Writer

Sunday, December 30, 2001

The federal government has embarked on an experiment on humans to

discover whether a vaccine can protect civilians against future

anthrax attacks.

For scientists to reach conclusions about the vaccine's effectiveness

after an attack, however, anthrax must bring down more people.

A significant number of the 3,000 people who turned down the vaccine

must fall ill or die from the disease to prove inoculation is

effective. Or if the 58 civilians who have received the vaccine so far

contract the disease anyway, officials will know it doesn't work.

The experiment is the latest illustration of how the nation is

learning as it goes in the war on terrorism, despite official

pronouncements soon after Sept. 11 that the government was prepared

for bioterrorism.

Three months after the anthrax attacks, the federal Centers for

Disease Control and Prevention in Atlanta cannot offer clear

recommendations for disease prevention to the general public, or even

to the people exposed to the disease -- a stark reality that came into

focus on Dec. 15, when the nation's top medical minds convened in

Washington, D.C., to debate moving forward with the experiment.

" When occasions like this occur, as devastating as they are, not only

is it the duty of the Public Health Service to protect the public . .

.. it's also our duty to take advantage of the opportunity to figure

out how to handle such an emergency better in the future, " said Dr.

Helms, speaking for an advisory committee that shapes federal

recommendations on all vaccines.

The emergency's scope: This year, five people have died from

inhalational anthrax and six others are recovering from it -- 11 cases

in a few months, compared with 18 U.S. cases reported during the

previous 100 years. Another 11 people who contracted the skin form of

anthrax are fine.

Officials have determined all but two of this year's cases were

infected through anthrax-laced mail, a ubiquitous weapon that

inflicted far more fear than fatalities: More than 10,000 Americans

endured weeks of the gut-wrenching antibiotic Cipro to kill a

potential infection, and suspicious mail closed the U.S. Supreme Court

and Senate buildings for record spans.

From the 22 anthrax cases, this much seems clear -- though nothing is

certain yet:

Spores mixed with certain chemical powders can be dispersed widely

from a sealed or open envelope and float through the air like a gas.

Those who contracted inhalational anthrax in 2001 were older adults,

ranging from age 43 to 94.

Early treatment of the disease with antibiotics and supportive care

vastly improves the chances of survival.

If antibiotics can save those potentially infected with anthrax, why

experiment on humans with a vaccine?

For one, putting thousands of people on antibiotics for months isn't a

practical solution because some cannot tolerate the side effects. And

such a massive antibiotic assault could cause the lethal germ to

become resistant to medicine's own atomic bomb.

In addition, antibiotics attack only the reproductive form of the

anthrax germ, thus preventing it from producing toxins and damaging

organs. Prior to this " vegetative " form, the germ is in its dormant

" spore " form and not affected by antibiotics.

" We've never done this before, " explained Dr. Larry Bush, the Atlantis

infectious disease specialist who sounded the alarm in October on the

anthrax outbreak. " Now they're off prophylaxis (antibiotics), so we'll

find out if it works. "

The concern is that spores could lay silent in the lungs for months

and not germinate -- thus escaping the antibiotics.

With this in mind, the foremost experts assembled on Dec. 15 in the

auditorium of the prestigious National Academy of Sciences to discuss

the benefits and risks of offering the vaccine for the first time to c

ivilians attacked with anthrax.

Inadequate data

All eyes were on Dr. Koplan, a public health superstar who'd

helped conquer smallpox and control HIV. The tall and trim director of

the CDC was entering his fourth year on the job in October when the

anthrax outbreak occurred.

Facing those seated that December morning, Koplan recognized there was

" inadequate data " to recommend the vaccine to victims, but he undercut

critics with a blunt disclaimer.

" Rarely do we have all the information we need when we have to make

public health decisions, " he said. What became clear that day was how

shallow our experts' knowledge base was and how its foundations were

constantly shifting.

The prime reason: Federal research on anthrax as a weapon essentially

came to a halt in 1969 as part of a non-proliferation pact signed with

the Soviet Union. The latter cheated on a massive scale, the United

States would learn more than a decade later.

The 1991 discovery, after the Persian Gulf War, that Iraqi dictator

Saddam Hussein had produced weapons-grade anthrax resurrected federal

support for research.

Scientists at the December meeting appeared to have more studies to

show the vaccine improved the chances of surviving inhalational

anthrax -- or that the benefits outweighed the risks.

The main benefit of vaccination: training the body's immune system to

recognize the germ's lethal toxins and fight off an infection. The

vaccine is licensed by the U.S. Food and Drug Administration for use

only before anthrax exposure.

The main risk: exposing a diverse group of civilians, some with

chronic illnesses, to a vaccine that has been tested mainly in healthy

soldiers. The rate of allergic reactions and potentially more serious

side effects could be higher.

The decision on whether the benefit outweighs the risk hinged on the

likelihood that anthrax spores survive in the body past the 60 days of

antibiotics.

On this question, scant animal research since the 1940s suggests that

anthrax spores might survive in the human lungs for long periods

before being destroyed or causing infection.

" We don't know why it's cleared or how it's cleared, but we know its

dormancy can be for long periods of time, " said Col. Art Friedlander

of the U.S. Army Medical Research Institute of Infectious Diseases.

In one of the early monkey studies, 15 percent to 20 percent of the

initial dose of spores remained 42 days after exposure. At 75 days, 1

percent of the spores were still present, and at the 100th day, trace

amounts.

Dr. D.A. , who now heads the U.S. Office of Public Health

Preparedness, found in studies of monkeys that if antibiotics were

discontinued 20 days after anthrax exposure, they died. Those monkeys

that received penicillin and vaccination after being exposed survived.

In a key 1966 study, viable spores were found in all " apparently

healthy " monkeys in the two-month period following exposure, said Dr.

Greg , chief of infectious diseases at Walter Army Medical

Center in Washington, D.C. One monkey that was taken off antibiotics

died 98 days after exposure.

" So all these things were somewhat disconcerting to us, that possibly

some of our highly exposed people may develop inhalation anthrax down

the line, " said.

While the monkey is considered the best model for studying disease in

humans, the studies are not perfectly applicable because they were

done using wet aerosols, not the dry powders seen in letters sent to

two senators and a news network anchor.

" If that has any effect on the time to germination, it probably

prolongs it, " Phil of the U.S. Department of Health and Human

Services said of the dry powder.

On the other hand, no more inhalational anthrax cases have been

reported nationwide since Nov. 21, despite the fact that large numbers

of people exposed to the germ didn't stick to their 60-day antibiotics

regimen.

Also, no anthrax cases were reported beyond 43 days after people were

exposed in 1979 to a cloud of anthrax spores from a Russian bioweapons

factory, the largest inhalational anthrax outbreak in history.

" Knowing that there is probably not great risk of those individuals

getting inhalation anthrax, I probably would have a great deal of

difficulty recommending to an individual patient that they take the

vaccine at this point, " said Dr. Larry Siegel of the Washington, D.C.,

health department.

Then there's a U.S. military study, done after the Gulf War, that

offers mixed interpretations.

Sixty monkeys were exposed to low doses of anthrax. Some were given no

treatment, others various kinds of antibiotics only, and the rest

antibiotics and two doses of vaccine. The treatments, which included

ciprofloxacin and doxycycline, were stopped at 30 days.

None of the nine monkeys that had taken doxycycline and vaccine

succumbed to anthrax. But five monkeys who received only antibiotics

died six to 28 days after the drugs were stopped. The differences

between the vaccinated and unvaccinated monkeys weren't statistically

significant. But the disparity clearly worried scientists at the

meeting.

Three-and-a-half months after the initial exposure, researchers

sprayed the survivors and some fresh monkeys with 50 times the average

lethal anthrax dose. Only the monkeys that had taken vaccine survived.

" One reason to offer vaccine to the postal workers is that there is a

continuing threat of anthrax coming through the mail, " Siegel said.

Diminished public confidence

While the government's experiment meets ethics guidelines for human

trials, public health officials knew the vaccine would be a tough sell

because of diminished public confidence in the CDC. The agency made

several initial assurances concerning anthrax that later proved wrong:

It said that spores couldn't infect people from inside an envelope. It

also said that blood tests would help pinpoint who was exposed.

Moreover, the federal government has a history of conducting human

trials on unknowing participants, including radiation tests on people

in the 1950s and the Tuskegee Syphilis Study on black men from 1932 to

1972 in Macon County, Ala.

The purpose of the Tuskegee study, which was supervised by the CDC,

was to see how the syphilis germ destroys the body. In the late

stages, the germ can cause paralysis, gradual blindness and dementia.

According to the Tuskegee University's Center for Bioethics in

Research & Health Care, the men who enrolled in the study were never

told they had the disease. Government officials informed them they had

" bad blood " and that they would be treated at no cost. Instead, not

only were they given placebos, but they were systematically prevented

from having penicillin even after it was shown to be a quick and

effective cure for syphilis in the 1940s. For this, the poor, rural

and uneducated men received hot meals on the days scientists visited,

free rides to the hospital affiliated with Tuskegee Institute and $50

for burial insurance.

Now, some people have doubts about what motivated the government's

anthrax vaccine study.

" With the Cipro we felt like lab rats, " said J.D. , a reporter

for AMI's tabloid The Globe, who chose not to take the vaccine or any

more antibiotics. " They don't even know all the side effects of this

vaccine. "

Those like who have stopped taking antibiotics will not be

tracked by the CDC but have been given emergency numbers to call if

they fall sick. Those who take the vaccine in three doses over a month

will be monitored for two years, CDC officials said.

It could take that long for the jigsaw puzzle dumped on America in

October to be put together and understood.

Nagging questions

Other unanswered questions include whether a weaponized anthrax letter

can contaminate other pieces of mail during the sorting process to

create a broader threat to the public beyond its addressed recipient.

Cross-contamination has emerged as the leading theory for how

94-year-old Ottilie Lundgren of Oxford, Conn., became fatally

infected. She was not a mail, government or media worker, and

investigators didn't find spores in her home.

Once tainted letters are delivered, it's unclear what it takes to make

the spores airborne again. Lundgren reportedly tore her mail in half

before throwing it away, CDC officials say, and that act could have

sent spores into the air.

Another question is how to identify those exposed before they become

ill and diagnose them correctly in the early stage. Nasal swabs can

miss people who were exposed, and blood tests done on Boca Raton's

American Media Inc. employees haven't made sense, officials say.

And the early stage of the disease can be confused with the flu

because no definitive tests are available. That's why one infected

postal worker in Washington, D.C., area was sent home from a hospital

a day before he died.

While antibiotics kill the anthrax germ, there is no approved

treatment to counteract the toxin produced by the germ. That's why

those in the disease's late stage seldom recover. Circulating toxin

leaves damage in its wake. Blood pressure drops rapidly. The organs

become swollen and starved of oxygen.

Near the end of the December meeting, someone also complained that

" monkeys are in extremely short supply. " The nation's experts

adjourned at 1:30 p.m. that Saturday.

" I think this is a perfect way to summarize our deliberations today, "

said Dr. Gerberding, a top CDC official. " We are listening and

we are learning. "

Three days later, the CDC announced it would offer the vaccine to

those who handled anthrax-positive letters, who worked in a place

where someone contracted the disease or who worked somewhere that was

heavily contaminated. Forty-eight hours later, 48 Capitol Hill

staffers were the first victims to receive the vaccine, prompting an

outcry from Florida public health officials, whose patients had

stopped taking antibiotics before the Congressional staff.

Six postal workers from the Washington, D.C., sorting plant also chose

to be inoculated. They and other candidates in the Northeast will have

until Jan. 7 to make a final decision about taking the vaccine.

But the 1,000 people connected with American Media Inc.'s Boca Raton

headquarters would receive only a one-time offer.

They had to take the first dose within two weeks of discontinuing

antibiotics for the vaccine to be effective, CDC officials said. And

they received the offer a week after the research meeting -- the

weekend before Christmas.

Health officials expected some 200 people to come to a Delray Beach

clinic for counseling, but only 62 showed up. Thirty-eight opted to

take 40 more days of antibiotics.

Only four decided to take the vaccine.

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