Epidemic Strains of Syphilis Have a Common and Recent Ancestor

One of the most dangerous aspects of antibiotic resistance is that the bacterial pathogens largely mitigated by antibiotic drugs in recent decades have reemerged as public health threats. As syphilis rates have risen in recent years, researchers in a new study have traced the origins of today’s epidemic back to a common bacterial ancestor.

Syphilis is caused by Treponema pallidum bacteria, which can cause infectious genital sores that spread the disease through sexual contact. The bumps are painless and appear in the primary stage of the infection, and symptoms appear on average within 21 days of infection; however, they may take up to 90 days to appear. In the secondary stage, a body rash that does not itch may appear on the palms of the hands, bottoms of the feet, or on other parts of the body. Ocular syphilis can occur at any stage and can cause vision impairment or blindness. Without treatment, symptoms disappear and the infection goes into a latent stage that can last for years, although the bacteria remain in the body. In its late stages, syphilis ravages the internal organs and can result in death.

For more than a decade, rates of primary- and secondary-stage syphilis in the United States have been on the rise, more than doubling since the lowest reported rate of 2.1 cases per 100,000 in population in 2000 to 5.3 cases per 100,000 in 2013. According to the Centers for Disease Control and Prevention (CDC), rates of ocular syphilis as well as congenital syphilis have resurged in this epidemic. Sexually transmitted diseases (STDs) are on the rise worldwide, with an estimated 5.6 million people infected with syphilis each year, along with 131 million new chlamydia infections and 78 million gonorrhea infections, according to the World Health Organization (WHO).

A new study led by researchers at the University of Zurich traced the genetic lineage of circulating syphilis strains to understand the disease’s reemergence. In the paper, published in the journal Nature Microbiology, the authors noted that while syphilis infections in their early stages are still curable with the recommended treatment of a single dose of long-acting benzathine penicillin G, strains of the pathogen infecting people today have shown resistance to the second-line drug azithromycin, which is used as an alternative when the first-line drug is unavailable. To understand the evolutionary origins and the genetic patterns of today’s strains, the research team used new DNA capture and whole-genome sequencing techniques to study 70 clinical and laboratory samples of T. pallidum bacterium from 13 countries; these samples included strains that that cause syphilis as well as those that cause yaws and bejel infections.

Through analyzing bacterial genomes, the researchers discovered an azithromycin-resistant pandemic strain cluster named SS14- Ω, which emerged from an ancestor strain in the mid-twentieth century after the onset of antibiotic use in medical treatment. “The good news is that, so far, no Treponema strains have been detected that are resistant to penicillin, the first-line antibiotic for syphilis treatment,” said the study’s first author Natasha Arora, PhD, in a recent press release. “Our findings highlight the need to study more extensively the predominant strain type in the contemporary epidemic.”

While antibiotic resistance has emerged as a barrier to treatment in the larger gonorrhea epidemic, the authors hope that in studying the epidemiology of syphilis they can shed light on today’s epidemic and the development of antibiotic resistance in T. pallidum. “There have been many questions regarding the origin of syphilis since its appearance on the world stage 500 years ago,” said study author Homayoun C. Bagheri, PhD. “By combining an evolutionary and an epidemiological approach, we were able to decipher the genetic relation between strains infecting individuals today, and also trace the emergence of a pandemic cluster with high frequency of antibiotic resistance.”