title: Bayesian development of a dose-response model for Aspergillus fumigatus and invasive aspergillosis.
abstract: Invasive aspergillosis (IA) is a major cause of mortality in immunocompromized hosts, most often consecutive to the inhalation of spores of Aspergillus. However, the relationship between Aspergillus concentration in the air and probability of IA is not quantitatively known. In this study, this relationship was examined in a murine model of IA. Immunosuppressed Balb/c mice were exposed for 60 minutes at day 0 to an aerosol of A. fumigatus spores (Af293 strain). At day 10, IA was assessed in mice by quantitative culture of the lungs and galactomannan dosage. Fifteen separate nebulizations with varying spore concentrations were performed. Rates of IA ranged from 0% to 100% according to spore concentrations. The dose-response relationship between probability of infection and spore exposure was approximated using the exponential model and the more flexible beta-Poisson model. Prior distributions of the parameters of the models were proposed then updated with data in a Bayesian framework. Both models yielded close median dose-responses of the posterior distributions for the main parameter of the model, but with different dispersions, either when the exposure dose was the concentration in the nebulized suspension or was the estimated quantity of spores inhaled by a mouse during the experiment. The median quantity of inhaled spores that infected 50% of mice was estimated at 1.8 × 10(4) and 3.2 × 10(4) viable spores in the exponential and beta-Poisson models, respectively. This study provides dose-response parameters for quantitative assessment of the relationship between airborne exposure to the reference A. fumigatus strain and probability of IA in immunocompromized hosts.
authors: Université Paris Diderot, Sorbonne Paris Cité, EA 3520, Paris, France. christopher.leleu@hotmail.fr
authors: Christopher
authors: C
authors: Leleu
authors: Jean
authors: J
authors: Menotti
authors: Pascale
authors: P
authors: Meneceur
authors: Firas
authors: F
authors: Choukri
authors: Annie
authors: A
authors: Sulahian
authors: Yves Jean-François
authors: YJ
authors: Garin
authors: Jean-Baptiste
authors: JB
authors: Denis
authors: Francis
authors: F
authors: Derouin
mesh_terms: D000465:Algorithms; D000818:Animals; D001228:Aspergillosis / Q000382:microbiology* / Q000635:transmission*; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001499:Bayes Theorem; D005260:Female; D016867:Immunocompromised Host; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015233:Models, Statistical; D016012:Poisson Distribution; D011336:Probability; D018570:Risk Assessment; D013172:Spores, Fungal / Q000378:metabolism; D013997:Time Factors
keywords: Aspergillosis; Aspergillus fumigates; Bayesian inference; dose-response; mouse model