November 1997

Officials downplay concerns

By Greg Gordon
Star Tribune
Washington Bureau Correspondent

Washington, D.C. --- When a test was developed three years ago to detect
the potentially deadly virus hepatitis C, researchers at the Food and
Drug Administration (FDA) made a disturbing discovery.

They found the genetic fingerprint of the virus in batches of a
blood-plasma product that has been used for decades to inoculate U.S.
soldiers and other Americans against hepatitis A and B before they
travel to Third World nations.

Officials at the FDA and the Centers for Disease Control and Prevention
(CDC) say that despite the finding, there is no need to worry about the
safety of those inoculations. Even if the virus got into the inoculants,
the officials contend, its genes were damaged during the manufacturing
process or otherwise neutralized. Some scientists aren't so sure.

And FDA and CDC officials acknowledge that there has been no definitive
research on whether the inoculants could have transmitted hepatitis C, a
disease estimated to have infected 3.9 million Americans.

A number of public-health experts say more studies are needed to prove
that the inoculations were safe and didn't put soldiers and travelers at
risk of contracting the slow-moving, blood-borne virus that is a leading
cause of liver disease.

In a recent report, the General Accounting Office quoted an anonymous
FDA official as saying that although there are no known instances in
which the shots have transmitted the disease, "this is a very scary

Last year, after the FDA ordered that immune globulin inoculants undergo
testing for hepatitis C as a "fail-safe measure," all private
manufacturers pulled their products from the market. Some of these
companies, including Pennsylvania-based Centeon, which was the
military's principal supplier, said they soon will seek FDA approval to
add steps to their production processes that inactivate the virus. The
pharmaceutical industry also recently developed a vaccine for hepatitis
A that eliminates much of the need for the immune globulin.

But Sen. Richard Shelby, R-Ala., has asked the Pentagon to look further
into the possibility that the inoculants may have spread the disease.

In a letter to the Defense Department in May, Shelby said that since the
inoculants weren't virally inactivated, "it is possible that military
personnel sent to Somalia, Panama, Haiti, the Persian Gulf and other
theaters were exposed to hepatitis C through the . . . injections."

In a 1993 Army study, blood tests were taken on 513 soldiers before and
six months after they were inoculated with immune globulin and deployed
in Somalia. The study found that none was infected by the shots, said
coauthor James Writer, an epidemiologist at the Walter Reed Army
Institute of Research. But Writer and other experts said the study's
methodology wouldn't pass scientific muster, in part because it wasn't
known whether the soldiers received tainted inoculants.

After a different immune globulin product was found to have transmitted
the disease in 1994, the CDC tested about 100 civilian travelers who had
received immune globulin shots from lots known to contain hepatitis C
genes. None was infected, said Jay Epstein, the FDA's director of blood
research and review, who vouches for the inoculants' safety.

Dr. John Penner, a Michigan State University hematologist who sits on
the FDA's Advisory Committee on Blood Safety and Availability, said he
cannot recall "any really good studies" on whether immune globulin shots
can transmit hepatitis C.

"It probably needs to be looked at . . . more carefully," he said.
However, if low amounts of the virus in the products infected a small
percentage of people, "we might have a hard time uncovering it," he

Former Surgeon General C. Everett Koop said more research is needed on
all possible transmission routes for hepatitis C - including immune
globulin inoculations.

A mystery

The inoculants have been considered a possible suspect in part because
most scientists view the virus' spread as somewhat of a mystery. As many
as 44 percent of its victims typically report no risk factors - such as
having had a blood transfusion, having shared intravenous needles or
having held a health-care job.

Also, until recently, it has been easy to contaminate immune globulins.
It takes 10,000 to 25,000 blood donations to produce one dose, which can
be tainted by a single infected donor. After tests to detect hepatitis C
were developed in 1990, manufacturers began screening donors for the

Federal health officials and spokesmen for makers of immune globulin
inoculants say that, despite these factors, the products always have
been safe because the manufacturing process kills the virus.

"Intramuscular immune globulin is safe and has never transmitted
hepatitis C or any other infectious disease as licensed in the United
States," said Miriam Alter, the CDC's chief hepatitis epidemiologist.

She said that although many victims reported having no risk factors,
follow-up interviews with a sample group established that all but 1
percent of them had "high-risk drug and sexual behaviors." Alter said
her agency had "miscommunicated" by failing to publicize that follow-up
data, thus leaving the impression that the disease spreads in unknown

Other scientists, even federal officials who say that immune globulins
are safe, are skeptical of such sweeping conclusions. Edward Tabor,
director of the FDA's Division of Transfusion-Transmitted Diseases, said
he is "a little bothered" by the deduction that anyone who has the virus
and has used drugs got it from an infected needle. In many cases, he
said, "you're talking about somebody who experimented with drugs once."

Centeon spokesman Jimmy Hendricks said that since 1992, 11 people have
contended that the company's globulin gave them hepatitis C and that FDA
and company inquiries exonerated the product in each case.

Not tested

If immune globulin inoculants carried the hepatitis C virus in the past,
the military would be a good place to look for victims. The Pentagon
ordered 481,000 doses of the inoculants from 1992 to 1996; the number of
those doses actually administered was unavailable.

Capt. David Trump, an official of the Defense Department's Office of
Health Affairs, said that troops aren't routinely tested for hepatitis C
and that no statistics on the number of infected soldiers exist. But, he
said: "We really don't have any evidence that the military population in
general is different from the civilian population when it comes to
hepatitis C infection."

Army epidemiologist Writer said a 1992 study of random blood samples
from 15,124 active duty personnel found that 1.3 percent tested positive
for hepatitis C - below the national infection rate of 1.5 percent.
Rider didn't know how many of those tested had received globulin shots.

Shelby, a member of the Senate defense appropriations subcommittee, has
inserted language in this year's appropriations bill calling for the
Defense Department to study the rate of hepatitis C among personnel who
received globulin inoculations.

At a warehouse in Rockville, Md., the department has stored millions of
frozen blood samples taken during physical examinations of Army, Navy
and Marine Corps personnel since the mid-1980s to test troops for AIDS.
Air Force blood samples were added recently.

Former Surgeon General Koop said the military should begin screening
troops for hepatitis C. "You've got a demon on your hands," he said.
"You'd better find out where that's coming from if you can."

- Star Tribune intern Andrew Atkins contributed to this report.