Between March 1998 and March 2002, 525,000 US military personnel were vaccinated against anthrax. In the case of an outbreak, this vaccine could be extended to civilians, as occurred in December 2001.

The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of physicians and scientists set up to monitor the safety of vaccination, will publish its first paper in the May issue of Pharmacoepidemiology and Drug Safety, available online on 26th April, showing that reports submitted to the Vaccine Adverse Reporting System (VAERS) over a two-year period did not indicate a high frequency or unusual pattern of serious vaccine-related reactions.

Anthrax is a serious disease caused by the bacterium Bacillus anthracis. It is of special concern because spores can easily be weaponized. Recent illnesses and deaths in the US associated with anthrax spores in the mail further underscore the grave potential this bacterium has as an instrument of bioterrorism.

The Anthrax vaccine is made from a sterile filtrate of a microaeorophilic culture of an attenuated, nonencapsulated, nonproteolytic strain of B. anthracis. The culture filtrate is adsorbed to aluminium hydroxide to create the final vaccine, which is known as Anthrax Vaccine Adsorbed (AVA).

AVA is administered as a primary series of 6 subcutaneous injections followed by annual booster injections. Since military vaccination programs were initiated in 1999 there have been many circumstantial rumors about the safety of the vaccine.

In an accompanying editorial, Neal Halsey, Director of the Institute for Vaccine Safety, comments, "The public must be confident that vaccines are made as safe as possible in order to maintain the high levels of acceptance that are necessary to control the disease." He adds, "this report should help address and reduce many of these concerns."

The Anthrax Vaccine Expert Committee (AVEC) reviewed and medically evaluated 602 reports of adverse events submitted to the Vaccine Adverse Event Reporting System (VAERS). This was correlated with information from the immunization records maintained by the Defense Medical Surveillance System, allowing the committee to profile adverse events with respect to person, location, receipt of other drugs and vaccine lot.

Committee Chair and lead author John Sever said, "A question of paramount interest was whether a review of this initial set of 602 VAERS reports would find an excessive number of medically important adverse events attributable to AVA."

That was not the case. There were no deaths among those reports and only 7 of 34 reported serious adverse events were judged by the committee to fit the WHO causality categories of probable or very likely/certain to be caused by the vaccine.

Six were local injection site reactions, all of which involved a period of hospitalization but were resolved completely. They were rated as very likely/certain consequences of vaccination.

Furthermore, it appears that the local reactogenicity of this vaccine can be quite substantial, since nearly half of the VAERS reports cited some degree of local reaction.

"A particularly significant finding is that some vaccinees with injection-site inflammation also experienced distal paresthesia," said Sever. "We concluded that in some cases administration of the vaccine as a subcutaneous injection in the region of the triceps apparently resulted in direct trauma to the underlying ulnar nerve or delayed-onset compression neuropathy due to localized inflammation. Subcutaneous injection of AVA over the inferior deltoid could eliminate the risk of such injuries and is recommended."

A tentative causality rating of probable was assigned to a single systemic serious adverse event, a case of bronchiolitis obliterans organizing pneumonia (BOOP) in a person who experienced an injection-site reaction and an unspecified diffuse rash after the first dose of vaccine. One day after a subsequent dose, this person developed progressive hives and shortness of breath which continued and was diagnosed as BOOP.

Cultures of bronchial samples for bacteria and fungi were negative, as were serological assays for rubella, adenovirus, mycoplasma, RF, ANA and ANCA.

Some experts, including Neal Halsey, "do not believe the committee can assign a causality rating of probable for BOOP because based upon the information that was available for their review it was virtually impossible to rule out all other possible infections and contributing factors that could have caused this illness."

However, John Sever points out that the "objective of the committee was to look for signals that adverse events which might be attributable to the vaccine are occurring at an elevated rate and warrant further investigation. By assigning a tentative assessment of causality we are not saying that the vaccine is responsible for this event, but it should be subjected to a more extended study."

A focused survey of the reports, done in response to concern that the anthrax vaccine might be associated with increased risk of a chronic illness characterized by fatigue, sleep disturbance, neurologic complaints, cognitive dysfunction and other symptoms, found only 5 that described such a "multi-symptom syndrome" and none of these appeared to be causally related to vaccination.

The authors conclude, "None of the other patterns found in this review of VAERS reports suggests that the adsorbed anthrax vaccine is unsuitable for certain subpopulations or that any particular lot of the vaccine is unsafe."

(Reference: "Safety of Anthrax Vaccine" by John L. Sever, Alan I. Brenner, Arnold D. Gale, Jerry M. Lyle, Lawrence H. Moulton, David J. West, Pharmacoepidemiology & Drug Safety, 11, 3, 189-202 pp. "Anthrax Vaccine and Causality Assessment from Individual Case Reports" by Neal A. Halsey, Pharmacoepidemiology & Drug Safety, 11, 3, 185-187 pp.)

Pharmacoepidemiology and Drug Safety is published monthly by John Wiley & Sons, Chichester, England.

23-Apr-2002