A serological test to determine strains associated with ocular toxoplasmosis

确定与眼弓形体病相关菌株的血清学测试

• 批准号: 8891026
• 负责人: JEROEN SAEIJ
• 金额: $ 0.37万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891026
• 关键词: Accounting; Acute; Alleles; Animals; Antibodies; B-Lymphocyte Epitopes; Biological Assay; Blindness; Clinical; Collaborations; Congenital Abnormality; Congenital Toxoplasmosis; Contracts; DNA; Development; Disease; Disease Outcome; Enzyme-Linked Immunosorbent Assay; Epitopes; Etiology; Europe; Eye diseases; Fetus; Fingerprint; First Pregnancy Trimester; Genotype; Haplogroup; Human; Infection; Inflammation; Lead; Life; Link; Mental Retardation; Methods; Molecular; Monitor; Mus; Names; North America; Ocular Toxoplasmosis; Ophthalmic examination and evaluation; Parasites; Patients; Peptides; Persons; Pharmaceutical Preparations; Play; Population; Posterior Uveitis; Prevention; Prophylactic treatment; Proteins; Recurrence; Role; Sampling; Second Pregnancy Trimester; Serologic tests; Serological; Serotyping; Serum; South America; Structure; Symptoms; Testing; Third Pregnancy Trimester; Toxoplasma; Toxoplasma gondii; Toxoplasmosis; Treatment Protocols; Trimethoprim-Sulfamethoxazole; United States; Uveitis; Virulence; Virulence Factors; abortion; base; congenital infection; design; disease phenotype; follow-up; genome sequencing; improved; neonate; novel; obligate intracellular parasite; pancreatic secretory trypsin inhibitor I; prevent; public health relevance; research study; screening

 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.

 描述（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。胎儿在妊娠早期感染可导致流产或严重出生缺陷，如智力低下和失明，而新生儿在妊娠中期感染。妊娠晚期通常出生时没有临床症状，但其中许多人随后会患上眼弓形虫病 (OT)。除了先天性感染外，急性弓形虫感染还可导致眼部疾病，而眼弓形虫病被认为是美国和世界范围内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患上眼病。疾病，而其他人则不会患病，但已知他们所感染的特定弓形虫菌株发挥着重要作用，如果知道一个人感染的是什么菌株，则可以将治疗与感染的具体情况相匹配；例如，血清分型可以识别尚未发展为 OT 的非典型菌株感染患者，从而允许改变其管理（例如更频繁的眼科检查甚至预防性治疗）。事实证明，感染非典型菌株的 OT 患者复发和复发的机会更高。因此，可能会建议感染非典型菌株的患者进行长期治疗。 此外，一旦建立了弓形虫菌株与疾病表型之间的关联，就可以设计实验来确定其毒力增加的分子基础。由于目前的药物耐受性差且似乎无效，因此迫切需要针对眼弓形虫病的新疗法。该项目的目的是开发一种血清学测试，可以正确确定患者的菌株。然后，血清学测试将用于将寄生虫的基因型与疾病结果相关联。最后，该项目中提出的测定可以告诉我们，决定小鼠毒力特异性差异的弓形虫蛋白是否也决定了菌株。人类毒力的具体差异将非常有用，因为它可能导致新的药物治疗，旨在预防弓形虫病引起的失明。