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What is the Best Response to an Anthrax Attack?

By Eric Toner, M.D. and Richard Waldhorn, M.D., April 26, 2005

If a large scale aerosol attack with anthrax occurs over a large city, what would be the most effective response strategy? How many lives could be saved and at what cost? Is it better to treat with antibiotics, vaccinate, or do both? Is it cost effective to vaccinate the public prior to an attack?

These questions were addressed in a recent article by Fowler and colleagues in a paper in The Annals of Internal Medicine (2005;142:601-610). The authors used an analytic model to predict the cost in lives and dollars of both pre-attack vaccination and four post-attack strategies (do nothing, vaccinate, use antibiotics, antibiotic plus vaccination). They ran many different scenarios using different assumptions about both the likelihood of an attack and the number of cases that would result. They also looked at different antibiotics, and they assumed that only 3 out of the usual 6 doses of the current anthrax vaccine could be administered. Finally, the authors presumed that mechanisms to deliver vaccine and antibiotics on a large scale exist and will work, and they presumed that in the best case there is time to administer vaccine and prophylactic antibiotics before the onset of symptoms.

Their results indicated that in the most reasonable scenario, the best strategy is to use a combination of post-exposure antibiotics and vaccination because the combination was more effective in saving lives and more cost effective than either approach alone. Pre-exposure vaccination saved lives and was cost effective only when a person's likelihood of contracting anthrax was quite high, meaning that the annual risk of an attack multiplied by an individual?s likelihood of getting sick after an attack was greater than one in 200. The likelihood of illness would be expected to increase significantly if mass vaccination or prophylaxis is not possible.

In an accompanying editorial, G. Webb discusses some of the problems inherent in the modeling approach taken by Fowler and colleagues (Ann Intern Med 2005:142:668-669). Webb notes the following limitations: 1. The authors focused on a model based on just one city; 2. They underestimated the social impact of an attack on the effectiveness of the medical infrastructure; 3. They assumed the federal government will be willing to fully deploy the Strategic National Stockpile in one city, which, because of policy and political considerations, may not be true.

Dr. Webb's reasonable critique not withstanding, and assuming that pre-release vaccination is a political nonstarter and that post attack prophylaxis and vaccination is logistically feasible, the conclusion drawn by Dr. Fowler and colleagues that antibiotics plus vaccination is the best response to an anthrax attack is important.

Ebola and Plague Vaccines on the Horizon

By Michael Mair, M.P.H. and Eric Toner, M.D.

Currently there is no vaccine available for either plague or ebola, two of the agents on the Category A list of biological weapons. This week there was news of significant progress in closing this gap.

Ebola: On April 14, 2005, Crucell N.V. announced that it had signed a contract with the Vaccine Research Center (VRC), of the National Institute of Allergy and Infectious Diseases (NIAID) for the manufacture of a vaccine against ebola. Under the terms of the contract, Crucell will manufacture up to ten clinical lots of its PER.C6®-based ebola vaccine in its facility. The vaccine will be used for Phase I and early Phase II clinical testing. The PER.C6®-based ebola vaccine is a recombinant vaccine expressing ebola virus proteins based on Crucell's proprietary adenoviral vectors and produced using Crucell's PER.C6® technology.

Testing in animals has shown that this vaccine is effective in preventing ebola infection. Researchers at VCR and the United States Army Medical Research Institute of Infectious Diseases (USAMRID) reported in Nature in 2003 that a single dose of the vaccine provided macaque monkeys with 100% protection from the ebola virus. Crucell reported that further studies confirmed the results of the study published in Nature. There is no word yet on a start date for clinical trials with this vaccine.

Plague: On April 15, 2005, the U.S. Department of Defense (DoD) announced that it entered into a cooperative agreement with the Canadian Department of National Defense and the Secretary of State for Defense of the United Kingdom (UK) to develop a vaccine to protect against plague.

Under the agreement, the two vaccines that are currently being developed in the UK and the DoD will be evaluated in Phase I clinical trials, and one will be selected for continued development based on the results. The DoD's candidate plague vaccine contains the F1 and V plague antigens linked together as a fusion protein. The University of Kentucky is conducting a Phase I clinical trial sponsored by DynPort Vaccine Company. The UK 's candidate plague vaccine is a purified subunit vaccine containing recombinant F1 and V plague antigens which are mixed together. This vaccine is under development by Avecia Biotechnology and is expected to enter into Phase I clinical testing in late 2005. Results from both trials are expected in late 2006.