Early Detection of Congenital Chagas Disease

先天性恰加斯病的早期发现

• 批准号: 8639449
• 负责人: ROBERT H GILMAN
• 金额: $ 57.12万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639449
• 关键词: Acute; American; Americas; Antibodies; Antigens; Area; Back; Beds; Biological Assay; Birth; Blood; Blood Donations; Bolivia; Cessation of life; Chagas Disease; Chronic; Detection; Diagnosis; Disease; Early Diagnosis; Economics; Ensure; Genetic; Hereditary Disease; High Prevalence; High Risk Woman; Hospitals; Hour; Immigrant; Immune; Immune response; Immunoglobulin M; Infant; Infection; Laboratories; Latin America; Left; Life; Mediating; Metabolic Diseases; Methods; Microscopy; Modification; Mothers; Neonatal Screening; Parasite Control; Parasitemia; Parasites; Parasitic Diseases; Persons; Phase; Pregnancy; Risk; Sampling; Schedule; Serologic tests; Specimen; T cell response; Techniques; Testing; Time; Trypanosoma cruzi; Umbilical Cord Blood; United States; Urine; Vertical Disease Transmission; Woman; base; college; congenital infection; cytokine; disorder control; effective therapy; follow-up; girls; high risk; improved; neonate; novel; offspring; point of care; prenatal; programs; public health relevance; screening; transmission process; vector

DESCRIPTION (provided by applicant): Twenty-six percent of new Trypanosoma cruzi infections occur through mother-to-child transmission, and as vector and blood donation control improve, the proportion attributable to congenital infection will grow. An estimated 8 million persons have lifelong T. cruzi infection in Latin America. Approximately 5% of T. cruzi infected women give birth to infected infants at risk of clinically manifest Chagas disease at birth, shortly after birth or later in life. Laboratory-based screening is essential to detect congenital infection, and early detection is important to the most effective treatment. In high-prevalence areas, one promising approach may be universal newborn screening, as is routine for some genetic and metabolic disorders. However, there is no sufficiently sensitive, specific and logistically feasible test to diagnose congenital T. cruzi infection early in life, and current Latin American programs have low completion rates. The current standard for congenital T. cruzi diagnosis throughout Latin America relies on microscopy of concentrated cord blood, followed by serology at 9 months. In our previous study in Bolivia, we found a transmission rate of 6.5% (10/154 infants of infected mothers). However, none of the infected infants were detected by microscopy in cord blood, and only 40% were detected by microscopy in any of the 3 additional specimens collected in the first 30 days (a much more intensive sampling schedule than routine programs can sustain). Because hospitals lack beds, women are often discharged within 12-18 hours of delivery, complicating follow-up efforts. Prenatal screening with current rapid tests had only 90% sensitivity, and mothers with false-negative results seldom brought infants back for follow- up. We found that PCR-positive women were significantly more likely to transmit T. cruzi than seropositive women with negative PCR, and mothers of infected infants had significantly higher parasite loads. PCR detected 89% of infected infants at birth and100% by 30 days. Despite intensive efforts, only 58% of at-risk infants completed 9-month follow-up. We estimate that current screening programs miss more than half of all infected infants. The aim of this application is to develop and evaluate novel techniques (Loop Mediated Isothermal Amplification, antigen detections assays and enhanced IgM assay for antibodies to Shed Acute Phase Antigens), with the ultimate aim of developing a rapid, point-of-care format to test neonates. In addition we will assess the use of prenatal PCR and T. cruzi-specific immune responses to identify the women with the highest risk of transmission, in order to ensure more intensive follow-up of their infants.

描述(申请人提供)：26%的新克氏锥虫感染是通过母婴传播发生的，随着媒介和献血控制的改善，可归因于先天性感染的比例将会增加。据估计，拉丁美洲有800万人终身感染克鲁兹旋毛虫。大约5%的感染克氏毛滴虫的妇女在出生时、出生后不久或晚年生下有临床表现恰加斯病风险的受感染婴儿。以实验室为基础的筛查对于检测先天性感染是必不可少的，而早期检测对于最有效的治疗非常重要。在高发地区，一种有希望的方法可能是普遍的新生儿筛查，这是一些遗传和代谢疾病的常规做法。然而，目前还没有足够灵敏、特异和逻辑上可行的测试来诊断生命早期的先天性旋毛虫感染，而且目前拉丁美洲的项目完成率很低。目前整个拉丁美洲的先天性旋毛虫诊断标准依赖于浓缩脐带血的显微镜检查，然后在9个月时进行血清学检查。在我们之前在玻利维亚进行的研究中，我们发现了6.5%的传播率(感染母亲的154名婴儿中有10名)。然而，没有一名婴儿在脐带血中通过显微镜检测到感染，在最初30天收集的3个额外样本中，只有40%的样本被显微镜检测到(这是一个比常规程序支持的更密集的采样计划)。由于医院缺乏床位，妇女通常在分娩后12-18小时内出院，使后续工作复杂化。目前快速检测的产前筛查只有90%的敏感性，假阴性结果的母亲很少带回婴儿进行随访。我们发现，聚合酶链式反应阳性的妇女比聚合酶链式反应阴性的血清阳性妇女更有可能传播克氏锥虫，感染婴儿的母亲的寄生虫载量明显更高。聚合酶链式反应在出生时检测到89%的感染婴儿，在30天后检测到100%。尽管进行了密集的努力，但只有58%的高危婴儿完成了9个月的随访。我们估计，目前的筛查计划漏掉了一半以上的受感染婴儿。这项应用的目的是开发和评估新的技术(环路介导的等温扩增、抗原检测分析和增强的IgM检测抗体以去除急性时相抗原)，最终目的是开发一种快速、医疗保健的形式来检测新生儿。此外，我们将评估产前聚合酶链式反应和克氏锥虫特异性免疫反应的使用，以确定具有最高传播风险的妇女，以确保对其婴儿进行更密集的随访。