With syphilis, it’s yesterday once more

“I don’t know if my colleague Jonathan Volk is in the audience,” says the sexually transmitted infection expert, clinician, and writer, Ina Park. “But every time he gets a consultation, he just picks up the phone and says, ‘It’s syphilis.’”

She is kidding, mostly. But these days the call would be right more often than it used to be. Syphilis rates are spiking alarmingly in a wide variety of locales around the world.

Park, author of Strange Bedfellows, a sweeping nonfiction survey and history of sexually-transmitted infection, was addressing a global audience online and a large crowd of scientists, clinicians, and public health advocates that gathered in Denver on March 4, at the 2024 Conference on Retroviruses and Opportunistic Infections. And she’s putting her fingers on a pressing need.

The recent jump in cases has been well-documented and reported, but researchers would like to see more progress in answering questions about syphilis and addressing its diagnosis, treatment, and prevention.

“We have a very syphilis-informed group in this room, but out there in the community a lot of people may not recognize syphilis,” Park says. She argues that routine screening for syphilis is not happening in low- and middle-income countries outside of pregnancy care. Even then it can be missed: as ‘the great imitator,’ syphilis can be difficult to diagnose.

So back, then, is an unwelcome guest. According to a team of researchers, it is one of the oldest known recorded infections. And controversy over its further development tends to start with Columbus.

Syphilis is caused by a corkscrew-shaped microorganism called Treponema pallidum. It is a gram-negative bacterium, and infection is most often transmitted through sexual contact with lesions that allow Treponema into the bloodstream. It can also be passed from mother to child in utero, what is referred to as congenital syphilis.

Once transmitted, it progresses in stages. The primary stage lasts only a few weeks with a small lesion (often painless and in difficult-to-see places) before fading from view. The secondary stage occurs when the pathogen reaches deeper tissues and can present with a rash over the body or on the soles of the feet, in some cases. Untreated, it moves into the latent stage, in which a diagnosis can only be made by a blood test or by giving birth to a child with congenital syphilis. Serology tests are 100% effective for secondary-stage syphilis, but if there are no symptoms, there may be no clear prompt to do them. Late-stage syphilis can cause severe heart and neural problems, blindness, deafness, and even death.

Infection numbers have risen and fallen in waves over the years, but recent figures have whipped higher and higher, starting from a point where it looked like syphilis had been quelled for good. The last syphilis peak came at the time of the first surfacing of HIV/AIDS in the early 1980s along with an explosion of crack cocaine use. From that point syphilis case numbers plunged until, Park says, they started a slow ascent.

It’s hard to pinpoint the actual cause of the recent spike in syphilis cases, but one cause is certainly the fact that prevention and screening initiatives for syphilis waned over time, as did more widespread condom use. Public health agencies also struggled to do more with decreased dedicated funding.

Whatever the reasons, it’s been a steady rise over the years. By 2013, the drive to eliminate syphilis in the U.S. was given up as new cases neared 20,000. By 2022, the annual figure was over 50,000, the highest since the 1950s. Global figures echo these trends, with 6.3 million new cases in 2016 and 7.1 million new cases in 2020. By 2019, there were a total of 49.7 million prevalent cases worldwide — an increase of 60% over the last three decades. Rates of congenital syphilis are also on the rise.

“We’re in the middle of a congenital syphilis epidemic with a tenfold increase in cases in the past 10 years compared to perinatal transmission of HIV,” says Angelica Espinosa Miranda, an epidemiologist, gynecology specialist, and sexually transmitted infection expert in the Brazilian health ministry. Landon Myer of the University of Cape Town and a chairperson at this year’s CROI also called out congenital syphilis. “We think this is a huge public health crisis that is being ignored,” he says. “It speaks to a whole set of failures across the public health system and we really want to highlight it.”

But there are also signs of renewed energy for syphilis research and prevention. In October 2023 the U.S. Centers for Disease Control and Prevention gave its limited backing to the use of the antibiotic doxycycline following unprotected sex among gay and bisexual men and transgender women, based on data from several studies. The U.S. National Institute of Allergy and Infectious Diseases (NIAID) is also supporting an effort at the University of North Carolina, Chapel Hill, to collect lab samples of syphilis taken at all stages of infection to build up a biorepository to boost novel diagnostics research for congenital and adult-acquired infection. NIAID is also supporting ongoing research for syphilis vaccine development, though Treponema pallidum is historically a difficult pathogen to work with, as described by Carlos Ávila Nieto at IrsiCaixa AIDS Research Institute and colleagues.

But there’s been recent progress in characterizing Treponema pallidum’s outer protein membrane, giving rise to hope that it can be better targeted with antigens. Jeffrey Klausner, who participated in organizing an early pilot study on doxycycline, recently reviewed the state of the field for syphilis vaccine development. “We have multiple bacterial vaccines and vaccines for sexually transmitted infections,” he says, “but the investment into syphilis vaccines has been minimal.”

For now, syphilis continues to present a thorny problem. It is simply treated with penicillin, but there are penicillin shortages. Doxycycline appears to be a promising morning-after fix, but some researchers worry about the potential for fostering microbial resistance. Yet progress in diagnostics, including development of convenient rapid tests such as the dual HIV-syphilis rapid test approved last March by Health Canada, and vaccine research could potentially reverse current trends in battling this age-old foe.

Michael Dumiak, based in Berlin, reports on global science, public health, and technology.

Read more:

• Scientists using genomic sequencing to track syphilis outbreaks, Melbourne.
• Survey of clinicians and their concern about antimicrobial resistance and doxycycline.
• Current prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe.