site in the respiratory tract versus the total number of biologically-active units deposited is a minor aspect of the inherent uncertainty associated with characterizing the biological threat. A detailed discussion of the effect of biothreat uncertainty on biodetector testing is outside the scope of this study, however, a summary is provided in Box 3.1. Briefly stated, evaluating biodetector accuracy is severely constrained by inherent threat uncertainty (e.g., which strain will be encountered, what the particle distribution will be, what the agent will be suspended in). However, high precision in biodetector testing can be achieved by well-controlled system and component testing with simulants and well-chosen threat agent prototypes.

Normalization of Agent Concentration to Health Hazard

Biological activity with respect to the ability to cause an adverse health response is routinely characterized using controlled biological assays. The observed biological end point

BOX 3.1

Precision and Accuracy in Biodetector Testing

The number of different bacteria, viruses, and toxins that can cause adverse health effects is great. For each bacterial and viral type of agent (e.g., the genus and species B. anthracis, VEE virus), myriad strains with varying biological and physical properties occur naturally; anthropogenic effects, from agricultural use of antibiotics to genetic engineering, may alter natural strains. Some infective strains are culturable using artificial media; others will not grow in such an environment. Which specific microorganism will a biodetector actually be confronted with on the battlefield? The mode of aerosol dissemination (e.g., dry or wet dissemination, particle size distribution), suspension media (e.g., addition of fluidizers to prevent clumping, chemicals to absorb killing UV light and potentiate agent biological activity), and natural background materials (e.g., chemical pollutants, pollen, and ambient microbial flora) can greatly affect the nature and health effects of the aerosol cloud. It is not presently possible to fully test and characterize the accuracy of a detector against this vast array and combination of potential agents and aerosol presentations; nor could current detectors identify the entire range of agents, even if such testing were possible. Therefore, biodetector accuracy testing is inherently limited, in contrast to the great precision that can be achieved by employing well-controlled test procedures. A practical and useful level of accuracy can be approached by carefully selecting prototypical strains and bounding key aerosol parameters, such as particle size. A robust understanding of pathogenesis and phylogenetic diversity (e.g., selecting strains with conserved virulence epitopes) for a pathogen is critical to constructing such a practical level of accuracy in biodetection testing.

varies, depending on the mechanism(s) of pathogenicity for the particular agent and the assay system. Results of these assays are often expressed as a statistical function, such as the dose that is lethal, infective, or effective for 50 percent of an exposed population (LD50, ID50, or ED50, respectively). Expressing biological activity as a statistical unit of health consequence provides the opportunity to “normalize” activity units across the spectrum of biothreat agents. One can compare the effects of a set number of LD50 units for several disease-causing microorganisms. For example, in vaccine efficacy testing, vaccine treatment groups are often challenged with 100 LD50 of agent. When articulating the performance of a biodetector, the threshold of detection for any number of agents can be expressed in terms of LD50 units. Converting the actual number of bacteria, viruses, or mass of toxin to units of biological activity provides for greater information

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