The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health has awarded grants for 10 projects to improve diagnostic tools for congenital and adult syphilis — conditions currently diagnosed with a series of tests, each with limited accuracy . The Centers for Disease Control and Prevention (CDC) estimates that cases of adult syphilis and congenital syphilis increased by 80% and 183%, respectively, between 2018 and 2022—a crisis that prompted the US Department of Health and Human Services (HHS) to create a national task force to deal with the epidemic.
Antibiotics for syphilis work, but outdated tests make it very difficult to ensure people are properly diagnosed and fully treated. Advanced diagnostics could improve syphilis care and also enhance our ability to measure the effectiveness of syphilis vaccine candidates and other prevention methods.”
Jeanne M. Marrazzo, MD, MPH, NIAID Director;
Syphilis is a common sexually transmitted infection caused by the bacterium Trembling pale. It can cause neurological and organ damage in adults, as well as birth defects, stillbirth and neonatal death. The CDC reports that the incidence of syphilis in the US has increased since 2000, marked by a sharp increase in cases since 2019 and an escalating number in medically underserved populations.
The current syphilis testing algorithm requires at least two antibody-based tests, which are based on decades-old technology. These tests are unable to reliably distinguish antibodies from active versus resolved syphilis infection. They also cannot consistently confirm whether a course of antibiotics has successfully cleared T. pallidum bacteria from the body. Fortunately, modern molecular techniques, such as nucleic acid amplification systems and platforms that detect pathogen fragments, are now used for other infectious diseases and could be adapted for the diagnosis of syphilis.
New NIAID grants explore a range of immunological and diagnostic concepts, including basic research to improve understanding of infant immune responses to syphilis, innovative tests to identify different parts T. pallidum genomic material in infants and adults, measures of antibiotic resistance in Strains of T. pallidumand testing platforms that are feasible to use at the point of care rather than in an off-site laboratory. With a cumulative funding of $2.4 million distributed among the recipients, the awards are as follows:
Magic Lifescience, Inc., Mountain View, California
Project Title: Development of a Novel Syphilis Molecular Diagnostic Assay for a Point-of-Care Multiplex Genital Ulcer Panel Test on Giant Magnetoresistive Biosensors
Principal Investigator: Elaine Ng, Ph.D. (early stage researcher)
Grant: 1 R21 AI185972-01
Research at Nationwide Children’s, Columbus, Ohio
Project title: Interrogation of infant immune responses for diagnosis of congenital syphilis infection
Principal Investigator: Masako Shimamura, MD
Grant: 1 R21 AI186003-01
University of California San Francisco
Project title: Multi-omic approaches to identify novel biomarkers for the diagnosis of syphilis in pregnancy and assessment of treatment response
Principal Investigator: Stephanie Gaw, MD, Ph.D.
Grant: 1 R21AI186006-01
University of Texas at Austin
Project title: A triad approach to improved diagnostics for maternal and congenital syphilis
Principal Investigator: Sanchita Bhadra, Ph.D. (early-stage investigator) with Randolph Hubach, Ph.D., MPH (Purdue University)
Grant: 1 R21 AI185965-01
University of Texas Southwestern Medical Center, Dallas
Project title: Preanalytical factors affecting molecular testing for congenital syphilis
Principal Investigator: Jeffrey Sorelle, MD with Emily Adhikari, MD
Grant: 1 R21 AI185968-01
University of Victoria, British Columbia, Canada
Project title: Development of a direct diagnostic test for infectious and congenital syphilis
Principal Investigator: Caroline Cameron, Ph.D.
Grant: 1 R21 AI186005-01
University of Washington, Seattle
Project title: Rapid and ultrasensitive aptamer-based detection technologies for T. pallidum
Principal Investigator: Stephen Salipante, MD, Ph.D.
Grant: 1 R21 AI184484-01
University of Washington, Seattle
Project Title: Rapid Point-of-Care Detection T. pallidum resistance to macrolides and tetracyclines with loop-mediated multiple amplification (LAMP)
Principal Investigator: Joshua Lieberman, MD, Ph.D. (early stage researcher)
Grant: 1 R21 AI184749-01
University of Washington, Seattle
Project title: Sensitive Trembling pale genome recovery by tiling amplicon sequencing
Principal Investigator: Alexander Greninger, MD, Ph.D., MS, M.Phil.
Grant: 1 R21 AI185726-01
Virginia Polytechnic Institute and State University, Blacksburg
Project title: Released peptidoglycan fragments are a biomarker for the early stages of syphilis
Principal Investigator: Brandon Jutras, Ph.D.
Grant: 1 R21 AI185998-01
