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3 Building the Framework for Evaluating Health Hazard
Pages 29-46

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From page 29...
... 3.1 THE FRAMEWORK IN WORDS Biological activity can be described as the concentration of biologically active aerosol particles (BAP) or total biologically active units (BAU)
From page 30...
... 3.1.1 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.
From page 31...
... 3.2 PROPOSED FRAMEWORK FOR EVALUATING AEROSOLIZED BIOTHREAT AGENTS The committee recommends that the following units be adopted as Department of Defense-wide standards: BAULADae. A primary unit of concentration is recommended for biological aerosols that quantifies Biologically Active Units per Liter of Air as a function of aerodynamic diameter (BAULADae)
From page 32...
... An example of the use of this unit in estimating the health hazard for an aerosol challenge with Bacillus anthracis spores would be as follows. An aerosol would be generated having a particle size distribution of 1-3 µm number median aerodynamic diameters; Dae is 1-3µm.
From page 33...
... Even a minimal estimate of health hazard requires accurate measures of lethality and infectivity, which have not been established for all possible biological agents. Furthermore, in a field environment, there is likely to be incomplete knowledge of how many other factors might affect health risk, from weather conditions, to host immune status, to precise strain characteristics.
From page 34...
... ; all aerosols contain particles that are distributed over some range of sizes. To understand the dose response to aerosol exposure we must address the contributions of particles of different sizes by introducing a particle size distribution function.
From page 35...
... Even when an agent is present at dangerous levels, many or even most aerosol particles will be common, agent-free ambient particles, such as dust, pollen, fungal spores, other natural aerosols, emitted primary particles, and secondary aerosols formed from gas phase chemical reactions. The units of n are {number of particles}/{unit volume of air}/{unit of aerodynamic diameter}( i.e., m-3µm-1)
From page 36...
... P I( ν ) Probability of an adverse health outcome originating in region i dNPi Differential probability that a particle with aerodynamic diameter Dae will deposit in region i of the respiratory tract when inhaled at rate Q dNCi Differential number of cells that can be expected to deposit into each region i of the respiratory tract per unit volume of air inhaled if the probability that a particle of diameter Dae contains ν cells (or other agent entities)
From page 37...
... In that case the probability of adverse health outcome would depend on the number of sites where any viable agent deposits. The number of such sites that will be produced in the respiratory tract where infection may develop from deposition of a particle that contains one or more active cells is, per unit volume of air inhaled, dN Si = ∑ Pν (Dae )
From page 38...
... (10) ⎝adverse health outcome ⎠ i=1 The foregoing analysis provides a formalism through which the hazard, measured as a probability of an adverse health outcome, can be related to measurable properties of a bioaerosol cloud, taking into account the size distribution of the aerosol particles, the variation of the composition with particle size, the behavior of particles when inhaled, and the probability that deposited particles will induce an adverse outcome.
From page 39...
... n( Dae , x, y, z , t ) Differential particle size distribution as a function of aerodynamic diameter Dae, space and time ({number of particles} / {m3} / {µm})
From page 40...
... BOX 3.4 Calculation of BAULADae with Available Data Scenario 1 KNOWN: Identified agent is present UNKNOWN: How much of the agent is active Particle size distribution LD50 Worst case scenario: All detected agent is active It can cause illness wherever it deposits Agent is extremely virulent (low dose causes illness) Calculate BAULADae assuming: 1)
From page 41...
... Consequence: Detector will sound alert if agent concentration>LD50 (or other dose level, depending on specific scenario requirement) Scenario 3 KNOWN: Identified agent is present Particle size distribution How much is needed to cause any form of disease How much agent is needed to cause disease at a specific site of deposition UNKNOWN: How much of the agent is active Worst case scenario: All detected agent is active Calculate BAULADae assuming: 1)
From page 42...
... For genome equivalents (Aii) , the measure includes viable and nonviable bacteria and fragments of bacterial DNA in the sample.
From page 43...
... Quantitation in total plaque-forming units (Ai) provides the information needed to assess health hazard because it includes a measure of activity.
From page 44...
... That result, expressed in colony-forming units (CFU) , is directly related to health hazard, because it indicates the dose of bacteria delivered to the respiratory tract that can replicate and cause disease.
From page 45...
... In addition, the analysis of an aliquot of the collection medium by PCR can determine the total number of genome equivalents for a specific bacterial or viral species present in a unit volume of aerosol, and an immunologic test such as ELISA, can be used to measure the amount of specific bacterial, viral, or toxin antigen. However, these methods will almost always overestimate the value of BAULADae for the same aerosol because both active and inactive agent are detected.


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