Analysis of Dose-Response in Guinea Pigs Following Inhalation Exposure to Legionella Pneumophila. T. W. Armstrong and C. N. Haas, ExxonMobil Biomedical Sciences, Inc. and Drexel University
Legionnaires’ Disease (LD) is an atypical pneumonia caused by bacteria of the genus Legionella, and is most commonly caused by the species L. pneumophila (Lp). LD, first reported in 1976, continues to be a significant human health problem in the USA and in many other countries. Legionella are commonly found at widely ranging counts in water from many sources such as surface waters and cooling tower basin water. Despite the continuing incidence of LD, the quantitative nature of the infectious dose-response in humans remains open to question. Post-1976, much research on exposure to the organism using various animal models was completed. The guinea pig has been the most commonly reported test species in published reports on aerosol exposure to Lp. These reports, in a quantitative microbial risk assessment (QMRA) framework, may yield insights into the risk of human disease from exposure to Lp. Yet, analyses applying QMRA techniques on the multiple published data sets for lethality and infectivity of Lp in guinea pigs are not reported in the literature. We report results from dose-response modeling for lethality and infectivity of Lp in guinea pigs using multiple published experimental data sets. The dose-response models we report results for are: beta-Poisson (approximate and exact forms), exponential, log-probit, log-logistic and Weibull. We present a comparison of the model results, with an emphasis on projected low-dose responses.
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