Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents Appropriate Use of Animal Models (2006) / Chapter Skim
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2 Selection or Development of an Animal Model
2 Selection or Development of an Animal Model
Pages 11-20
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From page 11... ...
The Animal Models for Testing Interventions against Aerosolized Bioterrorism Agents Workshop (held July 6th 7th, 2005) focused on inhalation of a subset of these agents, the so-called select agents.
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. Pharmacokinetic considerations Human Human Pathogen disease exposure Pathogen Interspecies Natural history of disease Route of exposure Virulence factors extrapolation Susceptible subpopulations Exposure dose Dose to critical targetsPathogen strain Therapeutic Animal Pathogen intervention disease exposure Pathogen Efficacy Experimental Safety animal model FIGURE 2-1 Factors that need to be considered when selecting an appropriate animal model.
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From page 13... ...
. The ability to identify useful medical countermeasures for the treatment or prevention of disease associated with bioterrorism agents will depend on a robust knowledge of the pathogen and of the host response to that pathogen.
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. Thus the failure of alternative animal models, including other nonhuman primate models, to develop infection following HIV-1 infection has limited development of vaccines and other immunization approaches for this virus (Hu 2005)
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. Species differences in nasal airway anatomy and airflow patterns influence the relationship between exposure concentration and pathogen dose delivered to either the lung or nasal cavity.
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But in laboratory mammals, including nonhuman primates and rodents, the pleura of the lung are thin and the extent of interlobular connective tissue, if any, is modest. In the human lower respiratory tract, there are seven generations of bronchi, and the tracheobronchial branching system is relatively symmetrical (i.e., the
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From page 17... ...
line the tracheobronchial airways of mammalian species, the percentage of these cell types may differ markedly among these species and needs to be taken into consideration when selecting an animal model for inhalation studies. A striking example is the percentage of mucous goblet cells that are found in surface epithelium lining the tracheobronchial airways of human and nonhuman primates compared to the corresponding fraction in laboratory rodents (mice and rats)
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Jarabek and others (2005; 1995) reviewed particle dosimetric adjustments for interspecies extrapolations, which underscore the importance of using quantitative morphometric measurements as input for mechanistic computer codes that calculate regional particle deposition.
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It is clear that for the species and strains to be used in countermeasure research, additional information is needed on differences in respiratory-tract anatomy and particle deposition. The Committee recommends that additional data on experimental-animal airway anatomy and particle deposition and clearance be acquired to aid in developing new animal models and performing extrapolations to human populations.
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