Author(s): Les Baillie 1
anthrax; antibiotics; bioterrorism; human countermeasures; vaccine
A large-scale bioterrorist attack with Bacillus anthracis , the causative agent of anthrax, against an unprotected population would result in considerable morbidity and mortality. Strategies to mitigate the impact of such an event need to be developed urgently. While pre-exposure immunization would significantly reduce the impact of a covert attack, the implementation of an effective universal vaccination program would face many challenges, notably the identification of a vaccine capable of protecting all sectors of society. Any future vaccine for the general population is likely to be just one component of a multilayered integrated response to the threat.
B. anthracis is a Gram-positive spore-forming member of the Bacillus cereus group. It owes its pathogenicity to the production of two principal virulence factors, a tripartite toxin and an antiphagocytic capsule  . Both factors are plasmid encoded: the toxin genes are located on pXO1, while the genes encoding the peptide capsule are carried on pXO2. Both plasmids can be transferred into other members of the B . cereus group leading to the suggestion that B. anthracis is simply an extremely aggressive form of B. cereus  .
The threat posed by anthrax depends on where in the world you live. In regions where animal husbandry is the primary focus of economic activity, and veterinary services are minimal, the disease still represents a significant burden to animal and human health  . However, in economically developed countries where the animal form of the disease has largely been eliminated, concern centers around the use of the pathogen as an agent of bioterrorism. Indeed, it is the ability of the bacterium to form resistant spores capable of surviving explosive dissemination and infecting via the lungs that has resulted in its development as a biological weapon  . The technology required to produce and handle B. anthracis spores is relatively simple compared with that needed to manipulate nuclear material; this could make the pathogen an attractive option to terrorist organizations  . The simultaneous infection of large numbers of individuals could overwhelm the healthcare resources of even the most economically developed societies  .
Indeed, the ability of even a small-scale release to cause harm and disruption was amply demonstrated during the US mail attacks in 2001, which resulted in the infection of 22 individuals, five of whom died. It was estimated that during this relatively small-scale attack, more than 30,000 individuals were given ciprofloxacin prophylaxis for over 60 days at an estimated cost of over US$2 billion  .
Antibiotic treatment is effective providing it is started early and the bacterium is susceptible. Unfortunately, as infection progresses it reaches a stage at which antibiotics are no longer effective owing to the accumulation of lethal concentrations of toxin  . In addition, strains of the pathogen that are resistant to multiple antibiotics have been reported  . A more effective means of mitigating the impact of a surprise terrorist attack, therefore, could be to immunize the general public in advance. While immunization is widely recognized as...