Institute Finds 'Paucity' Of Research On Anthrax Vaccine Safety

by Elaine M. Grossman

Inside The Pentagon

April 13, 2000

The National Academy of Sciences' Institute of Medicine last month reported there is insufficient medical research demonstrating the safety of the anthrax vaccine the Pentagon has given to more than 400,000 service members to date under a mandatory program.

"The committee concludes that in the peer-reviewed literature there is inadequate/insufficient evidence to determine whether an association does or does not exist between anthrax vaccination and long-term health outcomes," according to the IOM. "To date, published studies have reported no significant adverse effects of the vaccine, but the literature is limited to a few short-term studies."

The finding comes amid growing concern among service members and on Capitol Hill that the Pentagon has underestimated the number of those vaccinated who have experienced serious or systemic reactions to the shots, as well as the severity of some of those reactions. The Pentagon says about 350 service personnel have refused the shots, and sources say dozens more have gone to desk jobs or left the service voluntarily because of concerns about the vaccine.

The services have court-martialed a number of enlisted personnel who have refused the shots. Yet the Air Force recently dropped its first court-martial proceedings against an officer, Maj. Sonnie Bates, who disobeyed an order to take the vaccine out of concern about lapses in the manufacturing process and possible side effects.

The IOM provided the Pentagon with its initial finding as part of a two-year comprehensive study the Defense Department has requested on the safety and efficacy of the vaccine. The Pentagon hopes to use the data provided by the IOM to better respond to questions raised by Congress, according to a March 30 letter from an institute panel to Marine Corps Maj. Gen. Randall West, the special adviser for biological defense affairs to the under secretary of defense for personnel and readiness.

Although the mandate for the two-year effort is quite broad -- looking in detail at adverse reactions, gender differences, long-term health consequences, validation of the manufacturing process and much more -- the IOM panel offered to provide more quickly findings it has drawn from an ongoing study of the anthrax vaccine for the Department of Veterans Affairs "because of immediate concern over anthrax vaccine safety issues," the letter states.

The IOM panel looked only at primary peer-reviewed literature, although it appears the extent of that literature is limited. The group suggests that much of the Defense Department's own research on this topic has not yet been put to that level of scrutiny.

"The ability of IOM to conduct the more comprehensive study of the anthrax vaccine requested by DOD," states the panel, "assumes that the significant body of work that has been conducted by DOD on this subject will be released for publication in peer-reviewed scientific journals."

To date, there is little evidence in medical research that sheds light on anthrax vaccine safety, especially on a long-term basis, the panel finds.

"There is a paucity of published peer-reviewed literature on the safety of the anthrax vaccine," writes the IOM's Committee on Health Effects Associated with Exposures During the Gulf War.

The panel notes there has been just one randomized peer-reviewed study of the kind of anthrax vaccine used in the United States, known as the 1962 Brachman study. But, the group notes, the vaccine currently used by the Pentagon is different from that studied in the Brachman research, following changes in the strain of anthrax used and the process by which the vaccine is manufactured.

Typical short-term reactions found by the Brachman research included swelling and tenderness at the site of injection. A small number of individuals observed in the tests experienced a systemic reaction described as "malaise" lasting up to 24 hours after injection.

Other short-term studies were conducted as the vaccine was being developed in the 1950s and 1960s. A 1954 study found that less than one percent of vaccinated human subjects reported systemic reactions including mild muscle aches, headaches and malaise lasting one to two days. Under the same study, about two percent of subjects had swelling and itching around the site of the injection.

Anecdotal reports emerging from the field during DOD's vaccination program include possible systemic adverse reactions involving swelling of the limbs, headaches, dizziness, memory loss, nausea, sleep disorders, blackouts, night sweats and chest pain. But the Pentagon says it is aware of only about 600 cases of adverse reactions, most of them minor.

The IOM calls into question the value of the system the Pentagon uses to track adverse reactions from the anthrax vaccine, though. Data from the Defense Department's "Vaccine Adverse Event Reporting System," or VAERS, "are useful as a sentinel for adverse events but are limited in their usefulness for assessing the rate or causality of adverse events since the information may be underreported, incomplete, or duplicative and may not always have been confirmed by medical personnel," states the panel.

Senior Pentagon officials have acknowledged they are uncertain if the current vaccine will produce long-term side effects, but they note that in the three decades the licensed vaccine has been in use, no evidence of problems of that sort has emerged.

The IOM assessment states that "there [was] no long-term follow-up reported on the subjects" in the studies that led to the development of the anthrax vaccine. The IOM committee also observes that the Brachman trials made no effort to study either local or systemic reactions to the vaccine after 48 hours following each shot.

The panel found just one published series of studies that performed long-term follow-up with individuals who received the anthrax vaccine, but the subjects had received other kinds of vaccines as well. No long-term symptoms attributable to the vaccine program were shown by dozens of subjects observed over a 25-year period. But there was "no comparison cohort and no random sampling of employees," leading the IOM to wonder whether the test should have bearing on the safety questions currently at hand.

"The published studies have found transient local and systemic effects . . .of the anthrax vaccine," the IOM concludes. "There have been no studies of the anthrax vaccine in which the long-term health outcomes have been systematically evaluated with active surveillance." Although the panel states such long-term research is rarely carried out for vaccines, it "strongly encourages the development of active monitoring studies that evaluate long-term safety in recipients of the anthrax vaccine."

Whether the IOM's findings will have a chastening effect on the Pentagon leadership is yet to be seen. Last spring, the Pentagon's top physician expressed confidence in the safety of the vaccine in testimony before Congress.

"The Department is confident, as is the Food and Drug Administration (FDA), that the FDA-licensed anthrax vaccine is safe and efficacious for its intended use of immunizing the total force against anthrax," stated Dr. Sue Bailey, the assistant secretary of defense for health affairs, in written testimony provided to the House Government Reform national security subcommittee on March 24, 1999. "The anthrax vaccine has been licensed by the FDA since 1970 and has been recommended for veterinarians, laboratory workers, and livestock handlers in the U.S. for more than 25 years. There have been no long-term side effects reported with the FDA-licensed anthrax vaccine."

Click here: An Assessment of the Safety of the Anthrax Vaccine

http://www.nap.edu/html/anthrax_vaccine/