Improving diagnostics for toxoplasmosis to support public health interventions

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BBSRC : Gregory Milne : BB/M009513/1Toxoplasmosis is caused by the globally ubiquitous zoonotic protozoan parasite Toxoplama gondii. T. gondii accounts for approximately 190,000 cases of congenital disease in humans each year in addition to exerting a substantial economic burden on agriculture, as a leading cause of spontaneous abortions in small ruminants. Moreover, immunosuppressed human patients are at high risk of reactivation of latent infection and severe, often lethal, disease. Increasing evidence also suggests that T. gondii may be responsible for a considerable burden of neurological disease, including affective disorders like schizophrenia.T. gondii is transmitted (horizontally, from animals to humans) via two main routes: either environmentally, by oocysts (containing infectious sporozoite stages) shed in the faeces of infected cats (or other felids), or via raw or undercooked meat contaminated with infectious bradyzoite cysts. Distinguishing between these transmission routes is relevant to identifying the source of infection in outbreaks, to the design of appropriate public health intervention strategies and potentially also to the prediction of disease sequelae in infected patients.The discovery of a sporozoite-specific protein, called T. gondii embryogenesis-related protein (TgERP), has made distinguishing between transmission routes possible using a serological (blood) test. However, the TgERP assay has hitherto only been successfully implemented in a single laboratory in the United States. The aim of this work is to validate the TgERP serological assay using human and animal serum samples. This will involve isolating TgERP from T. gondii cultures; testing the assay on animal samples with known infection route; maximising the sensitivity and specificity of the test and using the assay to identify the route of transmission from stored human sera samples. Dissemination of the results from this work will be key in facilitating the more widespread use of TgERP serology. This will assist public health practitioners with the implementation of effective measures to counter T. gondii outbreaks and with the design of appropriate intervention strategies to control transmission. Ultimately, validation of TgERP serology could be the first step towards the commercialisation of a point of care assay with a broad scope of clinical, epidemiological and public health utility.