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Title:   Author  item
                                            GUO, MIAO - University Of Marylanditem
                                            MISHRA, ABHNAV - University Of Marylanditem
                                            BUCHANAN, ROBERT - University Of Marylanditem
                                            Dubey, Jitenderitem
                                            Hill, Doloresitem
                                            GAMBLE, RAY - National Academy Of Sciences - United Statesitem
                                            JONES, JEFFERY - Centers For Disease Control And Prevention (CDC) - United Statesitem
                                            DU, XIANZHI - University Of Marylanditem
                                            PRADHAN, ABNI - University Of Maryland
  Submitted to: Journal of Risk Assessment
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/12/2015
                                    Publication  Date: 10/19/2015
                                    Citation: Guo, M., Mishra, A., Buchanan, R., Dubey, J.P., Hill, D.E., Gamble, R., Jones, J., Du, X., Pradhan, A. 2015. Development of the dose-response relationship for human toxoplasma gondii infection associated with meat consumption. Journal of Risk Assessment. 36(5):926-38.Interpretive Summary: Human toxoplasmosis accounts for an estimated one-fifth of all diagnosed foodborne infections in the United States, and one fifth of the economic costs attributable to any foodborne pathogen. Pregnant women and their fetuses are exposed to elevated health risks. Currently there is no dose response study for human toxoplasmosis and none is warranted on ethical grounds. The best available dose response studies are with rats and mice. In the present study authors have attempted to develop a rodent model to assess risk to humans consuming meat infected with Toxoplasma. These results will be useful for veterinarians, parasitologists, immunologists, and epidemiologists interested in understanding transmission risks attributable to the environmental stage of the agent of toxoplasmosis.
                                Technical Abstract: Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States.A substantial portion of human T. gondii infections may be acquired through the consumption of meats. The dose-response relationship for human exposures to T. gondii-infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose-response models based on animal studies, and to compute scaling factors so that animal-derived models can predict T. gondii infection in humans. Relevant published studies were collected, and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four, sigmoidal-shaped mathematical models, and model parameters were estimated using maximum likelihood. Data from a mouse study were selected to develop the dose-response relationship. Exponential and beta-Poisson models, which predicted similar responses, were selected as reasonable dose-response models based on their simplicity, biological plausibility and goodness-of-fit. Confidence intervals on parameters were estimated by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse-derived models were validated against data for the dose-infection relationship in rat. A human dose-response model was developed as P (d) = 1-exp (-0.0015×0.005×d) or P (d) = 1-(1+d×0.003/582.414)-1.479. Both models predict the response of healthy, immunocompetent people to eating T. gondii-infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen.  Further validation, and specific consideration of groups at elevated risk (such as during pregnancy) warrant further attention.


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