Early Detection of Congenital Chagas Disease

描述（由申请人提供）：26%的新克氏锥虫感染是通过母婴传播发生的，随着病媒和献血控制的改善，先天性感染的比例将增加。估计有800万人患有终身T。拉丁美洲的克氏病毒感染。约5%的T.受克氏病感染的妇女生下的受感染婴儿在出生时、出生后不久或以后有临床表现出查加斯病的风险。以生殖系统为基础的筛查对于发现先天性感染至关重要，早期发现对于最有效的治疗至关重要。在高流行地区，一个有希望的方法可能是普遍的新生儿筛查，因为这是一些遗传和代谢疾病的常规检查。然而，目前还没有足够敏感、特异和逻辑上可行的检测方法来诊断先天性T细胞癌。克鲁兹感染，目前拉丁美洲的方案完成率很低。现行的先天性T。整个拉丁美洲的cruzi诊断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。在我们以前在玻利维亚的研究中，我们发现传播率为6.5%（10/154的婴儿感染的母亲）。然而，在脐带血中没有一个被感染的婴儿被显微镜检测到，在前30天收集的3个额外样本中，只有40%被显微镜检测到（比常规程序可以维持的更密集的采样时间表）。由于医院缺乏床位，妇女往往在分娩后12至18小时内出院，使后续工作复杂化。目前的快速检测产前筛查的敏感性只有90%，假阴性结果的母亲很少带婴儿回来随访。我们发现，PCR阳性的妇女更有可能传播T。Cruzi感染的婴儿的母亲比PCR阴性的血清阳性妇女有更高的寄生虫负荷。PCR在婴儿出生时检出率为89%，30天内检出率为100%。尽管付出了大量努力，但只有58%的高危婴儿完成了9个月的随访。我们估计，目前的筛查计划错过了一半以上的感染婴儿。本申请的目的是开发和评估新技术（环介导等温扩增、抗原检测试验和增强型IgM试验，用于检测脱落急性期抗原抗体），最终目的是开发一种快速的即时检测模式来检测新生儿。此外，我们将评估产前PCR和T。在这方面，我们将采取针对克鲁兹病毒的免疫反应，以确定传播风险最高的妇女，从而确保对其婴儿进行更密集的跟踪。

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.