Syphilis: genetic study reveals the disease is back

Detailed analysis of the strains provides information on the genetic diversity of the disease, which can lead to vaccine design and antimicrobial resistance

The incidence of syphilis, a silent and systemic disease, declined during the 1980s and 1990s, in part due to safer sex practices in the wake of the HIV/AIDS epidemic. However, the world is experiencing a return of the disease, which continues to cause morbidity and mortality. In the last decade, the increase in incidence may be linked to unrestricted sexual behavior with unprotected contact between multiple partners, including those from the same sex. According to the World Health Organization (WHO), syphilis affects more than 12 million people worldwide. The data are worrying as the presence of Sexually Transmitted Infections (STIs) increases by up to 18 times the risk of a person being infected with HIV.

To better understand the disease, researchers at the London School of Hygiene and Tropical Medicine (LSHTM), the Wellcome Sanger Institute, the UK Health Security Agency and colleagues mapped the recent resurgence of the disease around the world. “Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis” is considered the largest and most comprehensive study of syphilis genomes to date and provides data on how the strains are moving around the world. To do this, the researchers used 726 syphilis samples from 23 countries, which included well-sampled areas such as the United States and Western Europe, as well as poorly sampled regions such as Central Asia, Australia and Africa.

The team found that all samples came from just two deeply branched strains, Nichols and SS14. Both strains are currently circulating in 12 of the 23 countries sampled, and nearly identical samples were present in 14 of those countries. Some rarer sub-lineages were also found, either as singleton strains or strains private to a single country While this can be expected in sparsely sampled and geographically distant locations such as Cuba, Haiti, Mexico and Zimbabwe, research has shown that most of the private sublineages and singleton strains were actually from Canada, the UK or the US, suggesting that deeper sampling elsewhere may also find new diversity.

Dr. Mathew Beale, from the Wellcome Sanger Institute, the studys first author, explains that evidence of widespread transmission of strains between countries was found and that most strains worldwide are extremely similar. “Thats because they share a common source that dates back only a few decades (late 1990s/early 2000s). Although we have also sequenced some older strains, they are not closely related to current syphilis and it seems that new strains of syphilis have replaced the older ones”, he points out. Also according to the researcher, the dominant syphilis strains that infected patients before 1983 are not the same ones that infect today. Our analysis shows a population bottleneck that occurred in the late 1990s that indicates a large decline in the population size of T. pallidum, probably as a result of the HIV/Aids crisis, he highlights. For him, this raises an alert from the public health standpoint. “What is worrying is that the presence of nearly identical samples in several countries suggests that the disease is being transmitted internationally on a regular basis. Syphilis is back and its global,” says Dr. Beale.

Asked what the samples reveal about the origin of the syphilis epidemic and the resurgence of the disease, the researcher says that the current pandemic of the disease seems to be linked to certain strains (sublineages) that emerged during the 1990s and the beginning of 2000s and since then they have spread around the world. “The strains that have spread across many countries in our analysis also tend to be resistant to antibiotics such as azithromycin, a macrolide drug. Its not clear whether this is the reason for the spread – macrolide resistance might allow a particular bacterium to survive the treatment and continue to transmit and spread, but its also possible that the strains were already spreading widely anyway, and because of that, most likely, they may have been exposed to antibiotics,” he points out.

In addition, the researcher points out that there has been a huge change in behavior in recent decades, in terms of how people find sexual partners. The rise of dating apps, chemsex (refers to sex under the influence of psychoactive drugs, a practice that has become popular in recent years) and other factors may have contributed to the rise of many STIs, including syphilis. “Many of these infections can be difficult to detect and diagnose, including syphilis. They are always difficult to eradicate because they depend on human behavior and, of course, people continue to have sex. Safe sex messages, use of protection, regular testing, etc. can help. We know that the HIV crisis of the 1980s and 1990s led to a change in behavior, and we postulate that this was related to the decline in syphilis rates that was occurring around the world at that time. With the development of effective treatments for HIV, and the fact that people may have lost their fear of becoming infected, all of this combined with the impact of dating apps and social media may have led to the current rise in STIs,” concludes Dr. Beale.

The study is a valuable resource for understanding the genetic diversity of T. pallidum that may have implications for vaccine development and drug resistance. Furthermore, the study is important in showing the association with the increase in congenital syphilis, which results from the increase in the general number of cases. A limitation of the study is the very limited number of samples from certain parts of the world, including Latin America. There are no genomes currently available in Brazil and that is why the team is looking for laboratories in Brazil or neighboring countries that are interested in collaborating on the genomics of syphilis.

Brazil: Syphilis cases increase 16 times in 11 years

A total of 64,301 cases of acquired syphilis were registered in Brazil in the first half of 2021 alone, according to the recent Epidemiological Bulletin of the Ministry of Health. The number is 16 times higher than in the entire year of 2010, when 3,936 people were diagnosed with the disease. Men represent more than 62.8% of cases. The Southeast represents 45.1% of cases, followed by the South, with 22.3%, the Northeast with 16.5%, the North with 8.4% and, finally, the Midwest with 7.6%. During this period, 27,213 women had syphilis during pregnancy, most were between 20 and 29 years old. In these first six months, a total of 10,968 children under one year of age had congenital syphilis, and almost all (96.2%) received a positive diagnosis for the disease within one week of life.

Also according to the Epidemiological Bulletin of the disease, in 2020 there were 115,371 cases of acquired syphilis, 61,441 of syphilis in pregnant women and 22,065 of congenital syphilis with 186 deaths. The document points out that 38.8% of the notifications of acquired syphilis occurred in individuals between 20 and 29 years old, and 56.4% of pregnant women were also of this age. In addition, 56.4% of children born with congenital syphilis came from mothers aged between 20 and 29 years.

According to the Bulletin, it is possible to observe that in 2020, compared to 2019, there was a reduction in all rates: 26.6% in the detection rate of acquired syphilis, 9.4% in the incidence rate of congenital syphilis and 0.9% in the detection rate in pregnant women. The reduction in the number of cases may result from an underreporting of cases in the Notifiable Diseases Information System (Sinan) due to the local mobilization of health professionals caused by the pandemic.

Syphilis is curable and its treatment is simple, with one to three doses of penicillin, depending on the stage of the disease, available free of charge from the Unified Health System (SUS). When untreated, the bacteria remain in the body and the disease progresses to the stages of secondary syphilis (when spots, papules and other lesions can occur on the body, including the palms of the hands and soles of the feet, in addition to fever, malaise, headache and swelling) or latent syphilis (asymptomatic phase, when no more signs or symptoms appear). After a latency period, which lasts from two to 40 years, the disease progresses to tertiary syphilis, a serious condition that leads to dysfunction of various organs and can lead to the patients death. It usually presents ulcerated lesions on the skin, in addition to bone, cardiovascular and neurological complications.