NIH funds 3 syphilis diagnostics projects

The U.S. National Institute of Allergy and Infectious Diseases has awarded grants to fund three University of Washington School of Medicine projects to develop better diagnostic tests for syphilis.

The grants are part of efforts by the National Institutes of Health to address the recent surge in the United States of syphilis infections, which topped 207,000 cases in 2022, the highest recorded since the 1950s, according to Centers for Disease Control and Prevention statistics.

Prompt diagnosis of syphilis is essential because, if diagnosed early, the infection can be easily treated with penicillin. Untreated, however, the infection can cause devastating damage to the brain, heart and other organs. During pregnancy, syphilis can cause severe congenital abnormalities, stillbirth and neonatal death.

Diagnosis is difficult because the bacterium that causes syphilis, Treponema pallidum, cannot be grown in clinical laboratories and is even too difficult to grow in a specialty research laboratory. That makes it difficult to directly detect its presence in a sample. Therefore, testing relies on the use on decades-old tests that look for the presence of antibodies against the bacteria.

These tests are limited because they cannot reliably determine whether the antibodies are due to an active or a resolved infection. Nor can they reliably confirm whether a course of antibiotics has cleared the bacteria.

The tests being developed by UW Medicine researchers use state-of-the-art DNA-based technology to directly detect and characterize the bacterium. The grants have been awarded to the laboratories of Dr. Stephen Salipante, professor of laboratory medicine and pathology, Dr. Joshua Lieberman, assistant professor of laboratory medicine and pathology, and Dr. Alexander Greninger, professor of laboratory medicine and pathology.

To improve detection of Treponema pallidum, Salipante’s laboratory will create small DNA molecules, called aptamers, that can be designed to glow when they bind to specific proteins on the syphilis bacteria. This makes it possible to detect very low levels of the bacteria in a sample collected from a patient during a clinic visit.

 “An aptamer test could provide a rapid, ultra-sensitive, point-of-care detection assay for syphilis,” Salipante said. “If we can make them very robust, inexpensive and easy-to-use, then they could be offered at urgent care clinics and providers’ offices anywhere, making it possible to rapidly diagnose and treat infection.”

Lieberman’s laboratory will use the funds to develop a DNA amplification technology, called multiplex loop-mediated amplification, as a test that can quickly determine whether the bacteria in a patient’s specimen have genes that enable them to resist certain antibiotics.

 “We want to create a test that can be done in the clinic where the patient is being seen that says: whether this is syphilis, yes/no, and whether it is antibiotic-resistant, yes/no — within an hour,” Lieberman said.

Greninger’s lab aims to use the funds to make it possible to sequence the complete genomes of syphilis strains from small samples by using a technique called tiling amplicon sequencing.

Greninger warned that the U.S. syphilis outbreak is likely to get worse before it gets better.

“Rapid genomic sequencing should make it easier for public health officers and epidemiologists to track the spread of strains in the community, detect the emergence of new strains and conduct contact tracing to curtail outbreaks,” he said.

National Institute of Allergy and Infectious Disease grants, totaling $2.4 million, also went to seven other research groups working on syphilis diagnostics, according to a Sept. 3  NIH news release. 

The UW Medicine grants are: R21 AI184749-01, R21 AI185726-01 and R21 AI184484-01.

written by Michael McCarthy

The colorized electron micrograph of syphilis on this page was created at the National Institutes of Allergy and Infectious Diseases and is licensed under Creative Commons 2.0 via Flickr.

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