A shot in the dark?

THOMAS MAIER, "A shot in the dark?", Newsday, November 20, 2005,
Link:
http://www.newsday.com/news/health/ny-enanth024519241nov20,0,6116618.story?coll=ny-health-headlines

America's homeland defense program is spending more than $1 billion on
anthrax vaccines earmarked for wide civilian use despite uncertainty
about their effectiveness and an ongoing debate about potential health
problems, Newsday has found.

The vaccine stockpiling is a key element of the federal Project
BioShield program, which was awarded $5.6 billion in funding in 2004 to
develop drugs and vaccines to protect Americans against biological and
chemical attacks. It constitutes the largest federal effort ever to
protect civilians from an anthrax attack.

In May, BioPort Corp., the only manufacturer currently licensed in the
United States to produce an anthrax vaccine, won a $123-million
contract to make 5 million new doses for the public. And earlier this
month, federal officials doubled their request, saying they wanted to
buy another 5 million doses for approximately the same amount.

Last November, another firm, California-based VaxGen, received an
$877-million contract, plus up to $69 million in other potential fees,
to manufacture 75 million doses of an updated vaccine. The product,
which still lacks approval by the U.S. Food and Drug Administration,
will not be available until 2007, company officials say.

Federal officials say an airborne anthrax attack could kill thousands
of people in an urban setting like New York and tout the vaccines as
key parts of the civilian defense program.

But while a body of scientific research shows that the current vaccine
is effective if administered before skin exposure to anthrax - and the
rate of serious side effects is comparable to other common vaccines -
several public health experts have raised questions about the vaccine's
safety and whether it would work following an airborne attack.

David Ozonoff, a professor at Boston University's School of Public
Health, said there was "scant" evidence the vaccine will work to treat
people who inhale the airborne spores. He said studies show antibiotics
as the most effective treatment, and that the vaccine could cause
potentially serious health problems among civilians.

"The number of doses they are amassing is wildly out of proportion to
any possible threat from anthrax," Ozonoff said. "What the benefits are
is very unclear and there are always [health] risks ... when you
vaccinate a whole lot of people."

Hillel W. Cohen, an epidemiologist at the Albert Einstein College of
Medicine in the Bronx, agreed.

"The only possible benefit of a vaccine is if there's a danger of
exposure and that danger is small because of the technological hurdles
of weaponizing anthrax," Cohen said. " ... It's not something you can
do in your basement."

If an anthrax attack were to occur today, the nation would rely on
stocks of the BioPort vaccine, which, like the VaxGen product, would be
provided in combination with antibiotics.

The only major study of the use of the BioPort vaccine following
inhalation exposure found it ineffective on laboratory animals unless
used in conjunction with antibiotics.

VaxGen also is conducting animal studies of its vaccine, but company
officials say they are not yet certain it will work safely and
effectively on humans exposed to airborne anthrax attacks.

"We'd hopefully achieve a high level of protection, and the alternative
is severe disease," said Harry Keyserling, a pediatrics professor at
Emory University School of Medicine in Atlanta and a key researcher in
early VaxGen trials.

Still, several prominent members of Congress are skeptical of the
amount of federal money going to VaxGen.

"I do question the BioShield acquisition strategy being pursued that
bets 800 million dollars on an untested vaccine ... ," said Rep.
Christopher Shays (R-Conn.), chairman of the House Subcommittee on
National Security, Emerging Threats and International Relations.

"In the event of an attack, we need to know the vaccines and medicines
in the national stockpile are the best modern science can produce,"
Shays said.

The issue of whether the vaccines themselves may cause health problems,
and even death, also remains in dispute.

In documents of the FDA, Newsday found reports of more deaths and
serious health problems among anthrax vaccine takers than previously
reported.

Until late last year, the FDA had listed reports of six deaths and
1,850 "adverse" reactions since 1990, ranging from minor redness at the
inoculation site to severe cardiovascular and respiratory system
problems, that "possibly" were caused by the BioPort vaccine. The
government's monitoring system collects voluntary reports of illness,
but does not determine exact causes.

But in a little-noticed report issued in December, the FDA said 16
deaths were possibly linked to the BioPort vaccine. After Newsday asked
about other fatalities cited in FDA filings, the agency upped the total
number of fatalities possibly linked to the vaccine to 21 - including
one the agency said had been "incorrectly coded" in its database.

The same report tallied more than 4,100 illnesses, including 347 it
characterized as "serious," as possibly associated with the vaccine.

Government officials say the rate of serious illness associated with
anthrax injections is lower than that for other common vaccines such as
influenza, smallpox, tetanus, diphtheria and hepatitis.

About 9 percent of all health problems tied to the BioPort vaccine are
considered "serious," compared to 14 percent for the other vaccines
combined, said the FDA.

"This vaccine is as safe as any," said Kim Brennen Root, a spokeswoman
for BioPort, of Lansing, Mich.

Although humans can contract anthrax poisoning through breaks in the
skin or the gastrointestinal system, the civilian vaccine program is
focused on post-exposure treatment of the deadliest form, inhaled
anthrax. Initial symptoms of inhalation anthrax include mild fever and
muscle aches, but shock, severe breathing problems and often meningitis
then develop, according to the federal Centers for Disease Control and
Prevention.

The BioPort vaccine contains proteins from the anthrax bacteria called
"protective antigen," and once in the bloodstream the vaccine makes the
body produce antibodies to the antigen, so the bacteria can't produce
the anthrax disease. The VaxGen product would work in a similar manner
but with technology utilizing new combinations of genetic material.

Under current plans, contaminated civilians, along with others who
suspect they were exposed, would be offered a regimen of antibiotics
followed by several injections of vaccine.

But while BioPort's FDA license authorizes the vaccine as a
preventative against anthrax contracted through skin exposure, federal
officials have begun efforts to expand that authorization to cover
inhalation anthrax suffered by civilians.

Under the expanded powers in Project BioShield, the BioPort vaccine
could be used following an airborne anthrax attack, even without a
federal license for that use. The VaxGen product also could be
administered to civilians, even if it were still unlicensed.

Federal officials say the catastrophic potential of an anthrax attack
would justify any available medical weapon.

"We know that the consequences of such use could be very grave," the
Department of Homeland Security said of the possibility of an anthrax
attack. But data about whether either of the vaccines would be
effective in treating inhalation anthrax victims are scarce.

As the primary evidence that its vaccine would work for post-exposure,
BioPort cited a 1993 study in the Journal of Infectious Diseases that
was sparked by concerns about anthrax attacks during the Persian Gulf
War.

Tested on monkeys

The researchers, led by Arthur Friedlander of the Army Medical Research
Institute of Infectious Diseases at Fort Detrick in Frederick, Md.,
exposed six groups of 10 Rhesus monkeys each to anthrax contained in a
spray. Subsequent treatment included the BioPort vaccine by itself, the
vaccine in combination with antibiotics or antibiotics alone. Members
of a control group received only saline.

The untreated monkeys had a death rate of 90 percent, while 80 percent
of the monkeys given only the anthrax vaccine died. The groups treated
with the antibiotics Ciprofloxacin or Doxycycline showed death rates of
11 percent and 10 percent, respectively. Another group of animals took
a combination of Doxycycline and the vaccine. All survived.

"This suggests that antibiotic treatment, begun early after exposure,
prevented the infection from fully developing," the study said, adding
that the vaccine "may provide an additional degree of protection
against relapse" by killing spores remaining in the body after
antibiotic treatment.

"We know that antibiotics treat the symptoms of anthrax, but
antibiotics don't kill the spores," said Root, the BioPort spokeswoman.

Beyond that, Friedlander said, the vaccine's effectiveness in treating
humans already exposed to anthrax spores remains uncertain.

The vaccine was "not meant to be given after exposure," Friedlander
said in an interview. "The vaccine alone doesn't protect and we
wouldn't expect it to protect" those contaminated with anthrax.

In touting their vaccine, VaxGen officials also note the limits of
antibiotics.

Lance Ignon, VaxGen's vice president of corporate affairs, noted CDC
recommendations that anthrax patients take antibiotics for only up to
60 days. He said patients often don't follow the prescribed schedule,
while others develop resistance to antibiotics over time or cannot
tolerate them long-term.

Beyond the unanswered questions about efficacy, there is debate about
whether the vaccines themselves are dangerous. Some activists and
military personnel argue that the government is moving too quickly with
plans for a civilian vaccination program, without assurances that the
BioPort and VaxGen vaccines won't cause serious health problems.

"There's been a tremendous amount of spin by the government," said
Meryl Nass, a physician in Maine and director of the Alliance for Human
Research Protection, an advocacy group that has been a long-time critic
of the anthrax vaccine program.

Several deaths reported

The BioPort vaccine was first licensed in 1970, primarily for use by
agricultural workers in danger of skin exposure to anthrax from
animals. The vaccine's health effects have been studied extensively in
recent years, beginning with the 1991 Gulf War when thousands of U.S.
troops rolled up their sleeves for injections.

Most studies have found low levels of serious illness, although
allegations of severe health problems, including several deaths, are
detailed in at least one federal report and in several lawsuits.

A 2002 study by the National Academies' Institute of Medicine examined
the cases of people who took a total of nearly 2 million doses of the
vaccine, primarily in the late 1990s.

Researchers pored over illness reports in examining possible patterns
of long-term health problems and gender differences in reactions to the
vaccine. They said "limited scientific data" suggested that the vaccine
with antibiotics "could provide post-exposure protection" from inhaled
anthrax spores. The vaccine, they said, was "sufficiently safe and
effective."

In 2003, a study by academics from universities including George
Washington in Washington, D.C., and Johns Hopkins in Baltimore reviewed
health problems reported by some of the 500,000 military personnel who
took the vaccine between 1998 and 2001.

The lead researcher, John Sever of George Washington, said in an
interview that the inquiry could find no "unexpectedly high rate" of
serious adverse reaction to the vaccine. The study found six known
deaths at that time were either "unrelated" to the vaccine or
"unclassifiable."

In 2002, however, a U.S. General Accounting Office study of Air
National Guard and Air Force Reserve members who took the vaccine
revealed that 84 percent reported some adverse reaction - more than
double the approximately 30 percent rate reported to the FDA and
included in BioPort's packaging at the time. The preponderance were
minor, but almost 20 percent were considered serious - chills, fever,
nausea and dizziness, with some symptoms lasting more than seven days,
the GAO said.

"The implications were that the vaccine was part of the problem of
getting sick, and we recommended that they should be following up,"
said Nancy Kingsbury, who oversaw the GAO study.

The Army rejected the GAO's call for more active surveillance, saying
it already kept track of and studied health problems linked to anthrax
vaccinations.

Defense Department records show that Army Reservist Spc. Rachel Lacy
took vaccinations for anthrax and smallpox at Fort McCoy in Wisconsin,
while preparing in March 2003 for overseas deployment. Subsequently,
Lacy developed pulmonary and neurological problems that led to
inflammation of her lungs. She died the following month.

Lacy's father, Moses, said he believes the combination of vaccinations
overwhelmed his daughter. "I do think the anthrax vaccine contributed
to my daughter's death," he said.

After reviewing Lacy's case, two federal panels said the evidence
"favored a causal relationship" between her death and the vaccines,
although they could not establish a conclusive link.

Root, the BioPort spokeswoman, denied any link between Lacy's death and
the vaccine.

Other U.S. service members have cited the vaccine's alleged ill effects
in lawsuits challenging the military's compulsory use of the BioPort
vaccine. Hundreds of troops have refused to undergo the vaccine
regimen, and some have faced court-martial.

Three advocacy groups have filed court papers contending that the FDA
improperly granted "emergency authorization" for the military to use
the vaccine against possible airborne anthrax attacks, and ignored
evidence it was unsafe.

Last year, U.S. District Judge Emmet Sullivan, of Washington, D.C.,
temporarily halted the military program, questioning the FDA's approval
of the vaccine for inhalation anthrax cases. Sullivan later allowed the
revival of the inoculation program, after the military made it
voluntary.

Some health problems, including headaches and fatigue, also have
cropped up in early trials of the VaxGen vaccine, company officials
said. However, VaxGen chief executive Lance Gordon called the reported
health problems "not significant" because of the small initial testing
sample.

Last year, U.S. District Judge Emmet Sullivan, of Washington, D.C.,
temporarily halted the military program, questioning the FDA's approval
of the vaccine for inhalation anthrax cases. Sullivan later allowed the
revival of the inoculation program, after the military made it
voluntary.

Some health problems, including headaches and fatigue, also have
cropped up in early trials of the VaxGen vaccine, company officials
said. However, VaxGen chief executive Lance Gordon called the reported
health problems "not significant" because of the small initial testing
sample.

But BioPort's vice president of medical affairs, Tom Waytes, emphasized
VaxGen's early difficulties and said it was time for them "to go back
to the drawing board."

Despite the safety debate, BioPort and VaxGen continue to vie for the
$5.6 billion in Project BioShield money.

This year, BioPort said it has used Jerome Hauer, former acting
assistant secretary of the HHS Office of Public Health and Emergency
Preparedness, as a lobbyist in Washington.

Last year, BioPort hired Louis Sullivan, the former HHS secretary under
President George H.W. Bush, as a consultant to help land a new federal
contract for its anthrax vaccine.

Sullivan said he set up a meeting for the company with government
scientists in October 2004. The following month, BioPort announced it
would be manufacturing 5 million anthrax vaccine doses for the civilian
stockpile.

How the vaccine works: In general, the anthrax vaccine works the same
way as tetanus, rabies and other inoculations.

(A) A vaccine is made from an antigen isolated or produced from the
disease-causing organism. In the case of anthrax, the existing vaccine
is culled from proteins in the bacteria and (B) injected into the
bloodstream. (C) Once it recognizes the antigen, T cells in the immune
system trigger B cells to neutralize it and another type of T cells to
kill it.

The process produces memory cells that remain ready to mount a quick
response against subsequent infection from the same agent. That's why,
for example, a childhood vaccination generally protects against a
disease for a lifetime.

How it's taken

As a preventative, it is taken in six does of 0.5 milliliters each over
an 18-month period. For those already exposed, treatment is antibiotics
with three doses of vaccine.

Side effects

Mild: Soreness, muscle and joint aches, headaches, chills, fever,
fatigue and nausea.

Severe: May range from serious allergic reaction to rarely, death.

Anthrax, in brief

Anthrax spores exist all over the world and become dangerous only when
they make contact with human blood, organs and tissues. There are three
types of anthrax exposure:

1: CUTANEOUS

· Bacteria enter through a break in the skin.

· Handling contaminated animal products, such as meat, wool or hides.

Death is rare if antibiotic therapy is given.

2: GASTROINTESTINAL

· Eating raw, undercooked, contaminated meat.*

Death in 25% to 60% of cases.

3: INHALATIONAL

· Inhaling at least a deep breath of anthrax spores.

If left untreated, death rate is almost 100%; even when treated, 45% to
80% of patient's die.

1.3 million Number of military personnel who have taken vaccines for
anthrax since 1990

5 million+ Number of individual doses supplied since 1990

$123 million Amount BioPort Corp. of Lansing, Mich., is being paid to
make 5 million new doses of its vaccine.

$877 million+ Amount VaxGen, Inc., of Brisbane, Calif., is being paid
to develop 75 million doses of an updated vaccine.

SOURCES: National Health Museum, Department of Defense, Centers for
Disease Control and Prevention, Food and Drug Administration, Anthrax
Vaccine Immunization Program

Researched by J. Stephen Smith

.

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