A serological test to determine strains associated with occular toxoplasmosis

 描述（由申请人提供）：专性细胞内寄生虫弓形虫可感染胎儿并引起先天性弓形虫病。在妊娠早期感染胎儿可导致流产或严重的出生缺陷，如智力迟钝和失明，而在妊娠中期和妊娠晚期感染的新生儿通常出生时没有临床症状。然而，他们中的许多人在以后的生活中会发展成眼部弓形虫病（OT）。除了先天性感染外，急性弓形虫感染也可导致眼部疾病，并且眼弓形虫病被认为是美国和世界上后葡萄膜炎最常见的病因。目前尚不清楚为什么一些感染者会发展成眼部疾病，而另一些人则不会患病，但已知他们感染的特定弓形虫株起着重要作用。如果知道一个人感染了什么菌株，治疗可以与感染的具体情况相匹配;例如，血清分型可以识别感染了非典型菌株的患者，这些患者尚未发展成OT，从而可以改变他们的管理（例如更频繁的眼科检查甚至预防性治疗）。有研究显示，感染非典型菌株的OT患者复发的机会较高，因此可能建议对感染非典型菌株的患者进行长期治疗。此外，一旦弓形虫菌株和疾病表型之间的关联被建立，可以设计实验来确定该菌株的毒性增加的分子基础是什么，这可能最终导致新的治疗方法。眼弓形虫病迫切需要新的治疗方法，因为目前的药物耐受性差，似乎是无效的。该项目的目的是开发一种血清学测试，可以正确地确定患者感染了什么菌株。血清学试验将用于将寄生虫基因型与疾病结果相关联。最后，本项目中提出的检测方法可以告诉我们，决定小鼠中毒株特异性毒力差异的弓形虫蛋白是否也决定人类中毒株特异性毒力差异。这一信息将是非常有用的，因为它可能导致新的药物治疗，目的是预防弓形虫病引起的失明。

 DESCRIPTION (provided by applicant): The obligate intracellular parasite Toxoplasma gondii can infect the fetus and cause congenital toxoplasmosis. Infection of the fetus during the first trimester can result in abortion or severe birth defects such as mental retardation and blindness while neonates infected during the second and third trimester are usually born without clinical symptoms. However, a large number of them will develop ocular toxoplasmosis (OT) later in life. Besides congenital infections, acute Toxoplasma infections can also lead to eye disease and ocular toxoplasmosis is recognized as the most common etiology of posterior uveitis in the United States and in the world. At the moment it is unknown why some infected people will develop ocular disease while others will stay disease free but the specific Toxoplasma strain they are infected is known to play an important role. If it was known what strain a person was infected with the treatment could be matched to the specifics of the infection; for example serotyping could identify patients infected with atypical strains that have not yet developed OT allowing changes in their management (e.g. more frequent eye exams or even prophylactic treatment). It has been shown that OT patients infected with atypical strains have a higher chance of recurrences and therefore long term treatment might be recommended to patients infected with atypical strains. Furthermore, once an association between Toxoplasma strain and disease phenotype is established experiments can be designed to determine what the molecular basis is for the increased virulence of that strain which might ultimately lead to novel therapies. Novel therapies are urgently needed against ocular toxoplasmosis because the current drugs are poorly tolerated and seem to be ineffective. The aim of this project is to develop a serological test that can correctly determine what strain a patient is infected with. Thi serological test will then be used to correlate parasite genotype with disease outcome. Finally, the assays proposed in this project could tell us if the Toxoplasma proteins that determine strain-specific differences in virulence in mice also determine strain- specific differences in virulence in humans. This information would be extremely useful because it could lead to new drug treatments with the aim of preventing blindness caused by toxoplasmosis.