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DETERMINING THE INFECTIOUS DOSE-50 FOR WEAPONS-GRADE ANTHRAX IN RHESUS MONKEYS USING A BIOLOGICALLY-BASED MODEL
Citation:
Cicmanec*, J L. DETERMINING THE INFECTIOUS DOSE-50 FOR WEAPONS-GRADE ANTHRAX IN RHESUS MONKEYS USING A BIOLOGICALLY-BASED MODEL. Presented at Society for Risk Analysis Annual Meeting, Baltimore, MD, 12/7-10/2003.
Description:
One of the significant discoveries following the bioterrorist episodes beginning in October 2001 was that a modified form of Bacillus anthracis (Ames strain) was the causative agent. Physical alteration of the inoculum had occurred; the electrostatic charge had been removed and the resulting spores were approximately one micron in diameter. Eight separate inhalation studies have been identified in which non-human primates were used for inhalation exposure to B. anthracis to determine the Infectious Dose50 (Druett 1953, Henderson 1949, Estep 2003, etc.) Depending on the spore particle size and strain used, these values ranged from 4000 to 682,000 spores. Although some studies used spores that were one micron in diameter, conventional spore preparations will aggregate so that many of the inhaled particles will often range from four to twelve microns. The primary advantage that is gained through the use of spores that lack an electrostatic charge is that particles do not clump and essentially all of the inoculum can be deposited directly in the lungs. In order to adjust for the amount of the conventional inoculum in the non-human primate studies that was deposited in nasal passages, pharynx, and tracheobronchial regions, a methodology that has been developed for chemical particulate inhalation exposure (using the MMAD and sigma g) has been used as a model. Conveniently, cadmium chloride and radio-labeled polystyrene microspheres share the same target cell, alveolar macrophages, as anthrax spores. Through the use of ranking the dose response of these two surrogates and zones of deposition in the respiratory tract, similar dosage adjustments can be made for anthrax spores of various particle sizes. Use of this model enables us to predict that the ID50 for the modified form of anthrax is at least 15 to 80 times lower than for conventional spores and that for sensitive subpopulations fewer than 10 spores may cause infection. Comparison of the hose response in guinea pigs that received inhalation doses of varying particle sizes can be used to validate this model. (This presentation does not represent USEPA policy).