A weighted composite dose-response model for human salmonellosis

This article describes the development of a weighted composite dose-respons e model for human salmonellosis. Data from previously reported human challe nge studies were categorized into two different groups representing low and moderately virulent/pathogenic Salmonella strains based on a disease end p oint. Because epidemiological data indicate that some Salmonella strains ar e particularly pathogenic, and in the absence of human feeding study data f or such strains, Shigella dysenteriae was used as a proxy for highly virule nt strains. Three single-hit dose-response models were applied to the human feeding study data and evaluated for best fit using maximum likelihood est imation: (1) the exponential (E-1pop), (2) the two-subpopulation exponentia l (E-2pop), and (3) the Beta-Poisson (BP). Based on the goodness-of-fit tes t, the E-1pop and BP were the best-fit models for low and moderately virule nt/pathogenic Salmonella strains, and the E-2pop and BP models were better for highly virulent/pathogenic strains. Epistemic analysis was conducted by determining the degree of confidence associated with the selected models, which was found to be 50%/50% (E-1pop/BP) for low and moderately pathogenic Salmonella strains, and 9.8%/90.2% (E-2pop/BP) for highly virulent strains . The degree of confidence for each component model and variations in the p roportion of strains within each virulence/pathogenicity category were inco rporated into the overall composite model. This study describes the influen ce of variation in strain virulence and host susceptibility on the shape of the population dose-response relationship.