Syphilis in Pregnancy Study (SIPS): Molecular Diagnostics and Maternal and Infant Immune Response to Infection

妊娠期梅毒研究 (SIPS)：分子诊断以及母婴对感染的免疫反应

• 批准号: 10702053
• 负责人: Jodie Ann Dionne
• 金额: $ 70.46万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-23 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702053
• 关键词: Acceleration; Address; Africa; Aftercare; Age; Animals; Antibodies; Antigens; Area; Bacterial Infections; Binding; Biological Assay; Birth; Blood specimen; CD4 Positive T Lymphocytes; Cameroon; Childhood; Clinical; Communicable Diseases; Complement; Congenital Syphilis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Enrollment; Fetus; Flow Cytometry; Future; Generations; Genome; Gestational Age; Goals; HIV; High Prevalence; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Immunoglobulin M; Immunology procedure; Income; Infant; Infection; Integration Host Factors; International; Kinetics; Knowledge; Laboratories; Lesion; Live Birth; Low Birth Weight Infant; Maternal antibody; Maternally-Acquired Immunity; Measures; Mediating; Medical; Modeling; Molecular; Molecular Biology; Molecular Diagnostic Testing; Molecular Immunology; Natural History; Oral; Outcome; Participant; Pathogenesis; Penicillins; Performance; Perinatal; Peripheral Blood Mononuclear Cell; Placenta; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Prospective, cohort study; Proteomics; Public Health; Reaction; Recording of previous events; Role; Sampling; Sampling Studies; Serology; Serum; Specificity; Spontaneous abortion; Swab; Syphilis; T cell response; T-Lymphocyte; Testing; Time; Treponema pallidum; Umbilical Cord Blood; United States; Vertical Transmission; Virulence Factors; Woman; Zambia; adaptive immune response; adverse birth outcomes; adverse outcome; antibody diagnostic; antigen-specific T cells; biomarker identification; case finding; co-infection; cohort; design; diagnostic algorithm; fetal; follow-up; genome sequencing; genomic data; improved; infection rate; insight; molecular diagnostics; multidisciplinary; neonatal death; neonate; novel; parity; placental transfer; pregnant; prevent; reproductive; response; sample collection; screening; stillbirth; success; syphilis vaccine; transmission process; treatment response; vaccine candidate; vaccine development; vaccine trial; whole genome

Project Summary/Abstract Syphilis in women is usually a silent infection caused by Treponema pallidum (T. pallidum) that can efficiently cross the placenta during all stages of pregnancy and infect the fetus. In the absence of timely diagnosis and treatment, the natural history of infection in pregnancy includes adverse birth outcomes in 80% (spontaneous abortion, stillbirth, low birthweight, preterm delivery, congenital syphilis, and neonatal death). Our team and others have documented elevated prevalence of syphilis in pregnancy in Cameroon and Zambia (3-6%) with high HIV coinfection rates (10-40%). Despite public health efforts, syphilis is the leading preventable cause of stillbirth globally and available diagnostic testing has critical limitations in pregnant women and infants. The Syphilis in Pregnancy Study (SIPS): Molecular Diagnostics and Maternal and Infant Immune Response to Infection brings together an international team of experts in perinatal and pediatric clinical infectious diseases, syphilis molecular biology and immunology to address priority questions in the STI field about the natural history of syphilis in pregnancy and vertical transmission. The SIPS team has designed an observational cohort to enroll and follow 750 well-characterized pregnant women with confirmed syphilis and their exposed infants as well as 750 pregnant controls in Cameroon and Zambia with follow up and repeated sample collection through 12 months after delivery. SIPS participants will have pre- and post-treatment blood samples, cord blood, and placentas collected from women, neonates, and infants to assess immune responses in addition to oral and lesion swabs for PCR testing to carry out the following aims: Aim 1: Identify clinical and host factors independently associated with favorable birth outcomes among pregnant women with syphilis; Aim 2: Characterize the adaptive T. pallidum immune response before and after treatment in pregnant women and their exposed infants; Aim 3: Evaluate quantitative PCR (qPCR) testing on oral and lesion swabs to detect T. pallidum and enhance diagnostic testing in pregnancy and neonates. Aim 1 will test the hypothesis that factors associated with robust maternal immunity will be associated with favorable birth outcomes in multivariable models with clinical and host factors. Aim 2 will test the hypothesis that a robust adaptive immune response (humoral immunity and CD4 T cells) will protect against vertical transmission and assess the role of T. pallidum-specific transplacental maternal antibodies in mediating fetal and infant protection. Aim 3 will test our hypothesis that newly developed molecular diagnostic testing of easily collected oral swabs will help refine and improve the diagnosis of syphilis in pregnant women and infants. Our expected outcome is to identify T. pallidum antigens with a role in dissemination, placental attachment, and vertical transmission. Our long-term goals are to advance these newly identified antigens as potential vaccine candidates for reproductive age women and to support syphilis diagnostic testing with highly specific molecular testing and specific antigens that can discern syphilis stage and treatment response in pregnant women and infants.

项目总结/摘要 梅毒通常是一种由梅毒螺旋体（Treponema pallidum，T.苍白球），可以有效地 在怀孕的各个阶段穿过胎盘感染胎儿。如果没有及时诊断， 在治疗中，妊娠期感染的自然史包括80%的不良分娩结局（自发性）。 流产、死胎、低出生体重、早产、先天性梅毒和新生儿死亡）。我们的团队和 其他人记录了喀麦隆和赞比亚妊娠期梅毒的患病率升高（3-6%）， 艾滋病毒合并感染率高（10-40%）。尽管公共卫生努力，梅毒是主要的可预防的原因， 在全球范围内，死产和可用的诊断检测在孕妇和婴儿中具有严重的局限性。的 妊娠期梅毒研究（SIPS）：分子诊断与母婴免疫应答 感染汇集了围产期和儿科临床传染病的国际专家团队， 梅毒分子生物学和免疫学，以解决性传播感染领域有关自然的优先问题 妊娠期梅毒和垂直传播史。SIPS团队设计了一个观测 队列入组并随访750例确诊为梅毒的特征良好的孕妇及其暴露 喀麦隆和赞比亚的750名婴儿以及750名孕妇对照， 在交货后12个月内收集。SIPS参与者将有治疗前和治疗后的血液样本， 从妇女、新生儿和婴儿收集的脐带血和胎盘，以评估 除了口腔和病变拭子进行PCR检测，以实现以下目标：目标1：确定临床和 宿主因素与梅毒孕妇有利的分娩结局独立相关; 目的2：描述自适应T.孕妇治疗前后的苍白球免疫应答 目的3：评价口腔和病变拭子的定量PCR（qPCR）检测， T.梅毒和加强妊娠和新生儿的诊断测试。目标1将检验以下假设： 与强大的母体免疫力相关的因素将与有利的出生结局相关， 具有临床和宿主因素的多变量模型。目标2将测试一个强大的适应性免疫的假设， 免疫应答（体液免疫和CD 4 T细胞）将防止垂直传播，并评估 T.苍白球特异性经胎盘母体抗体介导的胎儿和婴儿保护。目标3将测试 我们的假设是，新开发的分子诊断测试容易收集的口腔拭子将有助于完善 提高孕妇和婴儿梅毒的诊断率。我们的预期结果是确定T。 苍白球抗原在传播、胎盘附着和垂直传播中起作用。我们的长期 我们的目标是将这些新鉴定的抗原作为生殖年龄的潜在候选疫苗 通过高度特异性的分子检测和特异性抗原支持梅毒诊断检测 可以辨别孕妇和婴儿的梅毒阶段和治疗反应。