Modernizing Perinatal Syphilis Testing

Study Overview
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Brief Summary
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Treponema pallidum is a bacterium that causes the disease syphilis. The primary objective of the study is to evaluate the testing performance of two diagnostic molecular techniques [quantitative polymerase chain reaction (qPCR) and transcription-mediated amplification (TMA)] for the detection of Treponema pallidum in maternal and neonatal specimens from participants with the diagnosis of syphilis using the Centers for Disease Control's (CDC's) Sexually Transmitted Infections (STI) Treatment Guidelines for adult and congenital syphilis.

Official Title
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Modernizing Perinatal Syphilis Testing

Conditions
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Syphilis

Intervention / Treatment
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* Diagnostic Test: Quantitative polymerase chain reaction (qPCR) assay for detection of Treponema pallidum
* Diagnostic Test: Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detection of Treponema pallidum
* Other: Center for Disease Control (CDC) Sexually Transmitted Infections (STI) 2021 Treatment Guidelines for diagnosis of syphilis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal diagnosis of syphilis by 2021 CDC STI guidelines, irrespective of treatment status; AND viable pregnancy with gestational age ≥ 12 weeks OR postpartum ≤ 96 hours from delivery Neonates of pregnancies affected by syphilis ≤ 72 hours of birth Exclusion Criteria: Pregnant individuals and neonates who do not meet the criteria of syphilis (false positive) Planning to move outside of study prior to ND testing

Ages Eligible for Study
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Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Molecular testing for detection of T. pallidum and use of CDC guidelines for diagnosis of syphilis<br> | Diagnostic Test: Quantitative polymerase chain reaction (qPCR) assay for detection of Treponema pallidum<br>* A quantitative polymerase chain reaction (qPCR) assay detects and quantifies DNA in a sample, and the qPCR assay used in this study targets the polA gene of T. pallidum to confirm presence of T. pallidum in a sample. Samples will be collected from the mother/newborn dyad at the time of birth. qPCR data will only be used to determine testing performance and will not be used in clinical management of study participants.<br>Diagnostic Test: Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detection of Treponema pallidum<br>* The Aptima transcription-mediated amplification (TMA) assay used in this study will target RNA of T. pallidum to confirm presence of T. pallidum in a sample. Samples will be collected from the mother/newborn dyad at the time of birth. TMA data will only be used to determine testing performance and will not be used in clinical management of study participants.<br>Other: Center for Disease Control (CDC) Sexually Transmitted Infections (STI) 2021 Treatment Guidelines for diagnosis of syphilis<br>* Using the Center for Disease Control (CDC) Sexually Transmitted Infections (STI) 2021 Treatment Guidelines, new born syphilis infection is categorized by clinical providers at birth as follows: confirmed proven/highly probably, possible congenital syphilis (CS), CS less likely, or CS unlikely. These CS categories are determined using neonatal nontreponemal test results, physical exam of the infant, placental pathology, and maternal serologies and treatment history, and comparison of maternal and neonatal nontreponemal tiers. These data will be collected as part of standard clinical care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of quantitative polymerase chain reaction (qPCR) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 96 hours after birth | 
| Specificity of quantitative polymerase chain reaction (qPCR) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Positive predictive value of quantitative polymerase chain reaction (qPCR) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Negative predictive value of quantitative polymerase chain reaction (qPCR) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Area under the receiver operating characteristic (ROC) curve of quantitative polymerase chain reaction (qPCR) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Sensitivity of Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Specificity of Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Positive predictive value of Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Negative predictive value of Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Area under the receiver operating characteristic (ROC) curve of Aptima Treponema pallidum transcription-mediated amplification (TMA) assay for detecting T. pallidum | Samples will be collected from participants during the following time periods: from the time of birth to up to 72 hours after birth (for neonates) from time of birth up to 96 hours after birth (for mothers) | from the time of birth up to 72 hours after birth | 
| Sensitivity of CDC 2021 STI Treatment Guidelines for diagnosis of syphilis | Clinical data used to diagnose syphilis according the CDC 2021 STI Guidelines will be collected as part of standard clinical care from the time of pregnancy (greater than or equal to 12 weeks gestational age) up to 18 months after birth. | from 12 weeks gestational age up to 18 months after birth | 
| Specificity of CDC 2021 STI Treatment Guidelines for diagnosis of syphilis | Clinical data used to diagnose syphilis according the CDC 2021 STI Guidelines will be collected as part of standard clinical care from the time of pregnancy (greater than or equal to 12 weeks gestational age) up to 18 months after birth. | from 12 weeks gestational age up to 18 months after birth | 
| Positive predictive value of CDC 2021 STI Treatment Guidelines for diagnosis of syphilis | Clinical data used to diagnose syphilis according the CDC 2021 STI Guidelines will be collected as part of standard clinical care from the time of pregnancy (greater than or equal to 12 weeks gestational age) up to 18 months after birth. | from 12 weeks gestational age up to 18 months after birth | 
| Negative predictive value of CDC 2021 STI Treatment Guidelines for diagnosis of syphilis | Clinical data used to diagnose syphilis according the CDC 2021 STI Guidelines will be collected as part of standard clinical care from the time of pregnancy (greater than or equal to 12 weeks gestational age) up to 18 months after birth. | from 12 weeks gestational age up to 18 months after birth | 
| Area under the receiver operating characteristic (ROC) curve of CDC 2021 STI Treatment Guidelines for diagnosis of syphilis | Clinical data used to diagnose syphilis according the CDC 2021 STI Guidelines will be collected as part of standard clinical care from the time of pregnancy (greater than or equal to 12 weeks gestational age) up to 18 months after birth. | from 12 weeks gestational age up to 18 months after birth |