An antigen-detection assay to diagnose Babesia microti infection

诊断田鼠巴贝斯虫感染的抗原检测方法

• 批准号: 10082042
• 负责人: Michel Ledizet
• 金额: $ 69.21万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-10 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082042
• 关键词: Acute respiratory failure; American; Anaplasmosis; Animals; Antibiotics; Antibodies; Antigens; Babesia; Babesia microti; Babesiosis; Biological; Biological Assay; Black-legged Tick; Blood; Blood Transfusion; Blood donor; Blood specimen; Borrelia microti; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Clinical Sensitivity; Complex; Congestive Heart Failure; DNA; Detection; Development; Diagnosis; Diagnostic Procedure; Diffuse; Disease; Disease model; Elderly; Enzyme-Linked Immunosorbent Assay; Epitopes; Erythrocytes; Evaluation; Goals; Gold; Health; Human; Immunocompetent; Immunocompromised Host; Immunofluorescence Immunologic; Individual; Industry Standard; Infection; Institute of Medicine (U.S.); Kidney Failure; Laboratories; Lead; Longitudinal prospective study; Lyme Disease; Malaria; Methods; Microscopic; Microscopy; Monitor; Monoclonal Antibodies; Mus; Parasitemia; Parasites; Patients; Performance; Phase; Population; Prospective Studies; Proteins; RNA; Recombinant Proteins; Recurrent disease; Red Cross; Relapse; Reporting; Resolution; Retrospective Studies; Risk; Sampling; Sensitivity and Specificity; Serologic tests; Serological; Serum; Signs and Symptoms; Specificity; Statistical Data Interpretation; Symptoms; Techniques; Ticks; Transfusion; Treatment Failure; United States; Vascular blood supply; active method; assay development; base; cohort; cost; design; diagnostic assay; experimental study; flu; granulocyte; human disease; human model; immunosuppressed; infection risk; mortality; mouse model; pathogen; vector tick

PROJECT SUMMARY Human babesiosis is a malaria-like multisystem disease caused primarily by Babesia microti, an emerging apicomplexan parasite that infects and develops within human erythrocytes. The parasite is transmitted to humans by the tick vector Ixodes scapularis and can also be introduced through blood transfusion. Infection can cause flu-like symptoms, and severe infection can be fatal, in particular in the immunosuppressed and the elderly. Current methods for babesiosis diagnosis include microscopy, PCR, IFA and ELISA-based methods that detect antibodies in serum from patients or donors. Each of these methods has major limitations, such as insufficient sensitivity, high complexity, and low throughput. In addition, results from many of these assays remain positive for months or years after resolution of active infection. In Phase I of this project, we have developed a capture ELISA assay that can detect a protein of the parasite, BmGPI12/BmSAI. We have identified pairs of monoclonal antibodies that can be used to capture BmGPI12 in mouse and human samples. Our preliminary results demonstrate that this assay has an excellent sensitivity. Using samples collected from infected mice, a well-established model of human disease, we demonstrated that following successful treatment, our assay gives negative results while PCR and serology remain positive. Thus, our assay may be useful in distinguishing active infection from past exposure. In Phase II of this project, we will further develop this assay with the goal of applying for FDA clearance. We will analyze several hundred animal and human samples to establish important characteristics of the assay including sensitivity and specificity. These Phase II experiments are designed to give us a full understanding of the potential biological indications and commercial usefulness of the assay.

项目总结