A paperfluidic molecular diagnostic for Trichomonas vaginalis

摘要/摘要 滴虫病，一种由原生动物阴道毛滴虫引起的可治愈的性传播疾病（STD） (TV)估计是世界上最常见的非病毒性性病。在美国，估计有3.7 感染人数超过了衣原体和淋病的总和。 虽然只有大约30%的人出现任何症状，但那些没有症状的人仍然可以感染其他人。 未经治疗的电视感染可导致严重的后果，如盆腔炎，不孕症，和宫颈癌。 癌由于TV感染的高流行率，CDC建议对所有寻求阴道护理的妇女进行检测。 对所有无症状的艾滋病毒阳性妇女进行出院和常规筛查， 感染风险高或在高流行率环境中。然而，虽然核酸扩增测试（NAAT）进行 尿液或生殖器拭子样本上的病毒检测已成为TV诊断的标准护理（CDC指南）， 目前还没有可以在护理点（POC）进行的快速、廉价的TV NAAT。 一种廉价、快速、对尿液和阴道拭子样本均表现良好的电视POC NAAT， 对临床决策有直接影响。在POC进行的快速检测将增加治疗 通过在初次就诊时提供结果来确定治疗率，从而可以开具治疗处方。一个POC NAAT与高 尿液和阴道拭子样本的敏感性将提供优于现有诊断方法的独特诊断优势。 快速抗原检测试验（仅批准用于拭子）和当前TV NAAT（仅在集中式 实验室设置）。 在这里，我们建议开发一种能够检测TV的高灵敏度和特异性的纸流体NAAT平台， 在尿液和拭子样本中，并提供使用波士顿临床标本的初步性能数据 儿童医院（BCH）先前通过自动NAAT（APTIMA）测试。我们将开发一个双模块 paperfluidic设备，利用我们创新的样品浓缩技术， 电视瞄准并提高我们的敏感度。通过在第一模块中浓缩输入的尿样， 第二个下游NAAT模块中的浓缩样品，我们的目标是降低 并增加TV测定的灵敏度。我们的最终目标是建立一个快速，廉价的电视测试， 灵敏度和特异性类似于自动NAAT，但可以在POC实施。这项工作 有可能导致我们如何筛查和管理电视疾病的范式转变。

Summary/Abstract Trichomoniasis, a curable sexually-transmitted disease (STD) caused by the protozoan Trichomonas vaginalis (TV), is estimated to be the most common non-viral STD world-wide. In the United States, an estimated 3.7 million people have the infection, more than chlamydia and gonorrhea combined. Although only about 30% develop any symptoms, those who do not have symptoms can still infect others. Untreated TV infection can lead to severe consequences like pelvic inflammatory disease, infertility, and cervical cancer. Due to high prevalence of TV infection, the CDC recommends testing all women seeking care for vaginal discharge and routine screening in all asymptomatic HIV-positive women, in addition to screening in persons at high risk for infection or in high-prevalence settings. However, while nucleic amplification tests (NAAT) performed on urine or genital swab specimens have become standard of care for TV diagnosis (CDC guideline), there currently are no rapid, inexpensive TV NAATs that can be performed at the point-of care (POC). An inexpensive, rapid, POC NAAT for TV that performed well on both urine and vaginal swab samples would have an immediate impact on clinical decision making. A rapid test performed at POC would increase treatment rates by delivering the results at the initial visit, allowing treatment to be prescribed. A POC NAAT with high sensitivity in both urine and vaginal swab samples would provide distinct diagnostic advantages over existing rapid antigen detection tests (approved for swabs only) and current TV NAATs (available only in centralized laboratory settings). Here, we propose to develop a highly sensitive and specific paperfluidic NAAT platform capable of detecting TV in urine and swab samples, and provide preliminary performance data using clinical specimens from Boston Children’s Hospital (BCH) previously tested by automated NAAT (APTIMA). We will develop a dual-module paperfluidic device that leverages our innovative sample concentration technique to enrich the concentration of TV targets and improve our sensitivity. By concentrating the input urine sample in the first module then assaying the concentrated sample in the second, downstream NAAT module, we aim to decrease the limit of detection of and increase the sensitivity of the TV assay. Our ultimate goal is to create a rapid, and inexpensive TV test with sensitivity and specificity similar to that of automated NAAT, but that can be implemented at POC. This work has the potential to lead to a paradigm shift in how we screen for, and thus manage, TV disease.