Improving diagnostics for toxoplasmosis to support public health interventions

BBSRC：Gregory Milne：BB/M009513/1弓形虫病是由全球普遍存在的原生动物寄生虫弓形虫引起的。除了对农业造成巨大经济负担外，每年约有19万人患上弓形虫，这是导致小型反刍动物自然流产的主要原因。此外，免疫抑制的人类患者再次激活潜伏感染和严重的、往往是致命的疾病的风险很高。越来越多的证据还表明，弓形虫可能造成相当大的神经系统疾病负担，包括精神分裂症等情感障碍。弓形虫通过两种主要途径传播：一种是在环境中，通过受感染猫(或其他猫科动物)粪便中的卵囊(含有传染性子孢子期)传播，另一种是通过生的或未煮熟的肉传播，其中含有传染性的缓殖子孢子囊。区分这些传播途径与确定暴发疫情中的感染源、设计适当的公共卫生干预策略有关，还可能与预测感染患者的疾病后遗症有关。一种称为弓形虫胚胎发生相关蛋白(TgERP)的子孢子特异性蛋白的发现使使用血清学(血液)试验区分传播途径成为可能。然而，到目前为止，TgERP检测只在美国的一个实验室成功实施。这项工作的目的是用人和动物的血清样本来验证TgERP血清学检测。这将包括从弓形虫培养物中分离TgERP；在已知感染途径的动物样本上测试该检测方法；最大限度地提高测试的敏感性和特异性，并使用该检测方法从储存的人类血清样本中识别传播途径。传播这项工作的结果将是促进TgERP血清学更广泛使用的关键。这将协助公共卫生从业人员采取有效措施，抗击弓形虫暴发，并制定适当的干预战略，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.