# Multi-omic approaches to identify novel biomarkers for the diagnosis of syphilis in pregnancy and assessment of treatment response

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $205,000

## Abstract

ABSTRACT
Congenital syphilis (CS) rates are rising exponentially in the United State. Syphilis in pregnancy is associated
with miscarriage, stillbirth, early infant death, low birth weight, and preterm birth. CS is also associated with
other neonatal finding, including skeletal abnormalities, skin rashes, vision and hearing loss, jaundice, severe
anemia, and hepatosplenomegaly. There is an urgent need for improved diagnostic tests in pregnancy, when
timely and adequate treatment is of crucial importance to reduce the risk of CS. Currently, syphilis diagnosis
relies on specific and non-specific serologic assays (treponemal and non-treponemal) that may be inadequate
to accurately distinguish between past infection, current infection, or reinfection. In the highest risk patients,
serology can be difficult to interpret due to lifelong persistence of treponemal antibodies in those with prior
syphilis, incomplete treatment histories, inadequate serologic response after treatment, and reinfection.
Furthermore, the current treatment regimen for late latent syphilis or syphilis of unknown duration in pregnancy
is three weekly, intramuscular doses of penicillin, which is often challenging to administer in a timely manner in
the highest risk patients. Adequate response to treatment is determined by a 4-fold drop in non-treponemal
antibody titer in 3-6 months, which in clinical practice, may be after delivery of the infant depending on
gestational age of infection. A more time-sensitive biomarker of successful treatment during pregnancy would
have a great impact on resource utilization during pregnancy, and aid in the postnatal risk assessment of the
infant. Unbiased metabolomics and proteomics approaches have been increasingly applied to discover novel
biomarkers of disease status and prognosis, as well as treatment. Molecular-based testing for Treponema
pallidum antigens may also be a useful adjunct to traditional serologic testing, especially for more complex
clinical scenarios. These approaches have not been widely applied to syphilis in pregnancy. Here, we propose
to enroll a prospective cohort of pregnant patients with syphilis in Fresno, CA, where the rates of CS in Fresno
are 2.5-times higher than national averages. In the following Aims, we propose to analyze longitudinally
collected samples from pregnant patients diagnosed with syphilis to identify novel biomarkers of syphilis stage,
characterize the prevalence of T. pallidum in oral and vaginal samples at the time of diagnosis through the
application of a new nucleic acid amplification test, and identify proteomic biomarkers in maternal and infant
samples with confirmed CS. The overarching goal of these studies is to discover new candidate
molecules for novel diagnostic markers for syphilis in pregnancy and CS.

## Key facts

- **NIH application ID:** 10979056
- **Project number:** 1R21AI186006-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephanie Lina Gaw
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979056

## Citation

> US National Institutes of Health, RePORTER application 10979056, Multi-omic approaches to identify novel biomarkers for the diagnosis of syphilis in pregnancy and assessment of treatment response (1R21AI186006-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979056. Licensed CC0.

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