$2.7 million NIH grant to fund first comprehensive syphilis test

(Press-News.org) UNIVERSITY PARK, Pa. — In the United States, syphilis cases rose by nearly 80% between 2018 and 2023, with 209,253 cases reported in the latest year of data. The infection, which can be transmitted sexually or passed from mother to infant during birth, is curable but only if diagnosed quickly. Left untreated, syphilis can progress from painless lesions to brain and cardiovascular damage. Despite the first recorded outbreak of syphilis occurring more than 500 years ago — with some researchers theorizing that it has plagued humans for thousands of years — there still isn’t a way to quickly and reliably test for active syphilis infection, according to Penn State Professor Dipanjan Pan.

Now, with a four-year, $2.7 million grant from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, Pan is setting out to change that. In collaboration with his clinical partners at Penn State Health, Carle Foundation Hospital and University of Alabama Birmingham, Pan aims to develop a one-step confirmatory laboratory test that can definitively diagnose active syphilis infection within 10 minutes.

“The ‘great imitator’ is back! Syphilis is known to mimic symptoms of many other sexually transmitted and infectious diseases, making it difficult to diagnose and treat,” said Pan, the Dorothy Foehr Huck & J. Lloyd Chair Professor in Nanomedicine at Penn State. “Syphilis cases in the United State are increasing at an alarming rate, and the need for a rapid diagnostic test that can quickly inform treatment and management decisions is desperately needed. An accurate diagnosis of syphilis relies on recognizing a constellation of symptoms, reviewing medical and sexual history, and performing multiple laboratory tests.”

When infected, the body makes antibodies to combat the bacterium Treponema pallidum, which causes syphilis. This happens whether a person is symptomatic or not. These antibodies — known as treponemal-specific antibodies — persist in a person for decades, even if the infection never becomes active or after successful treatment of an active infection, so they are not a good indicator of an active infection. The body can also make non-treponemal antibodies in response to active infection, but the reaction is not limited to syphilis, so clinicians must test for both types of antibodies to make a more definitive diagnosis and decide on a treatment plan.

“There are only two syphilis rapid tests approved by the U.S. Food and Drug Administration, but they detect only treponemal-specific antibodies, which could be from a decades-old infection that was already successfully treated,” said Pan, who is also a professor of materials science and engineering and of nuclear engineering.

He explained that definitively diagnosing active syphilis, and deciding on a course of treatment, requires testing for the non-specific non-treponemal antibodies that indicate active infection, preferably with a semi-quantitative result. That means the number of antibodies in the blood sample are counted, a process that takes two to seven days and specialized instruments, so the tests are typically outsourced to a lab instead of the doctor’s office.

“This is necessary to determine appropriate treatment with high sensitivity and low false-positive rates,” said Pan, who is also a member of the Center for Infectious Disease Dynamics in the Huck Institutes for the Life Sciences at Penn State. “Combining treponemal and non-treponemal assays within the same platform will provide a more definitive, stand-alone diagnosis of syphilis.”

The proposed platform makes use of highly sensitive electrochemical sensors to detect changes in current resulting from the direct interaction of both antibody types with biological material released from the bacterium and damaged host cells and the bacterium itself. The sensors — made from graphene, an atomically thin material that is incredibly sensitive to such changes — are capable of both detecting and quantify various proteins or molecules associated with these changes.

In preliminary tests using commercially available blood serum samples, Pan said, the researchers found that the sensors could detect both kinds of antibodies in less than 10 minutes with high sensitivity. This initial work — funded by the Centers for Disease Control and Prevention — was conducted by Pan, Parikshit Moitra, previously a research assistant professor in Pan’s lab and now an assistant professor at the Indian Institute of Science Education and Research in Berhampur, India, and with Ketan Dighe, a graduate student in biomedical engineering at Penn State.

“This is the first study using electrochemical sensor for an integrated assay — or comprehensive test to detect multiple targets — for highly sensitive, rapid, point-of-care detection of both treponemal and non-treponemal antibodies needed to accurately diagnose active syphilis infection,” Pan said. “Our goal is to simultaneously detect and quantify these antibodies, identifying and differentiating active from past cases of syphilis within 10 minutes to fulfill an urgent, unmet global need.”

Upon completing testing and refinement of their platform, Pan said the team plans to build a blood sample extraction device integrated with a simple reader — much like an at-home glucose meter — to produce results in 10 minutes. The study team is actively looking for commercial partners to further develop the platform.

The collaborating investigators include Casey Pinto, a nurse practitioner at Penn State Health and an assistant professor in the Department of Public Health Sciences in the Division of Epidemiology at the Penn State College of Medicine; Carla Rafferty, a family medicine physician at Carle Foundation Hospital; Tor Jensen, managing director of the Biomedical Research Center at Carle Foundation Hospital; and Barbara Van Der Pol, a professor of medicine and public health at the University of Alabama at Birmingham (UAB) and the director of the UAB Infectious Diseases STD Laboratory.

END