A shot in the dark? - U.S. presses ahead with $1B plan to fight anthrax despite concerns about the Drugs' Cost and Safety
NEWSDAY
BY THOMAS MAIER, Researched by J. Stephen Smith
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 pe
rcent 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.
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
