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/文摘