Improving diagnostics for toxoplasmosis to support public health interventions

弓形虫病是由全球普遍存在的人畜共患原虫弓形虫引起的。弓形虫除了对农业造成巨大的经济负担外，每年还造成约19万例人类先天性疾病，是小反刍动物自然流产的主要原因。此外，免疫抑制的人类患者处于潜伏感染再激活和严重（通常是致命的）疾病的高风险中。越来越多的证据还表明，弓形虫可能是神经系统疾病（包括精神分裂症等情感性障碍）负担的罪魁祸首。弓形虫通过两种主要途径（从动物向人类的水平传播）传播：一种是环境传播，即通过受感染猫（或其他猫科动物）粪便中的卵囊（含感染性孢子虫阶段）传播，另一种是通过被传染性慢殖孢子虫囊污染的生的或未煮熟的肉传播。区分这些传播途径与确定疫情中的感染源、设计适当的公共卫生干预战略以及可能对受感染患者的疾病后遗症进行预测有关。一种被称为弓形虫胚胎发生相关蛋白（TgERP）的孢子体特异性蛋白的发现，使得利用血清学（血液）测试区分传播途径成为可能。然而，迄今为止，TgERP分析仅在美国的一个实验室成功实施。本工作的目的是利用人和动物血清样本验证TgERP血清学分析。这将涉及从弓形虫培养物中分离TgERP；对已知感染途径的动物样本进行检测；最大限度地提高检测的敏感性和特异性，并利用该检测方法从储存的人血清样本中确定传播途径。传播这项工作的结果将是促进更广泛使用TgERP血清学的关键。这将有助于公共卫生从业人员采取有效措施应对弓形虫疫情，并设计适当的干预战略以控制传播。最终，TgERP血清学的验证可能是迈向具有广泛临床、流行病学和公共卫生效用的护理点检测商业化的第一步。

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.