Research on interventions to help end the syphilis epidemic in gay, bisexual and other men who have sex with men (gbMSM)

• Researchers developed a model to predict the impact of syphilis prevention strategies in B.C.
• The model analyzed the effect of testing, PrEP and DoxyPEP among men who have sex with men
• These interventions could end syphilis as a health concern among this population by 2034

Rates of new syphilis diagnoses have been increasing over the past 20 years. As a result, there is now an epidemic of syphilis across Canada. The initial symptoms of syphilis—a sore or chancre on or inside the genitals, mouth or other parts of the body—may be painless or go unnoticed. The germs that cause syphilis (called treponemes) quickly spread from the site of first contact. These germs can attack nerves in the ears (causing hearing loss) and eyes (causing loss of vision) and over time can cause injury to vital organs, including the brain, bones, heart and circulatory system, liver and kidneys. Syphilis during pregnancy can harm the fetus. Symptoms of syphilis can mimic many other diseases; however, syphilis can be easily diagnosed with a simple blood test. Most people can recover from syphilis with a single course of antibiotic therapy.

Doxycycline taken after sexual exposure

In San Francisco, a well-designed clinical trial among gbMSM and transgender women has found that the use of the antibiotic doxycycline (200 mg) taken within 72 hours of sexual exposure significantly reduced the risk of chlamydia, gonorrhea and syphilis. When doxycycline is used in this way it is called DoxyPEP (PEP stands for post-exposure prophylaxis). As a result of this and other studies, more public health authorities are encouraging healthcare providers to consider prescribing DoxyPEP to sexually active gbMSM.

HIV pre-exposure prophylaxis

A cornerstone of HIV prevention is the use of a combination of drugs (tenofovir + FTC), usually taken once daily, initiated prior to potential sexual exposure. The use of medicines in this way is called HIV pre-exposure prophylaxis (PrEP). Clinical trials have found that PrEP is highly effective (more than 99%) at reducing the risk of HIV. Programs that deploy PrEP involve screening for HIV and other sexually transmitted infections (STIs) prior to initiation of PrEP and at regular intervals (usually every three months). In British Columbia, access to PrEP is subsidized by the Ministry of Health.

Studying syphilis in British Columbia

Researchers in B.C. have been studying the syphilis epidemic in that province. They have accumulated data about the impact of testing and treatment of syphilis, particularly among gbMSM. A team of researchers at the BC Centre for Excellence in HIV/AIDS, the BC Centre for Disease Control (BCCDC), the University of British Columbia and York University (in Toronto) used that data to develop a computer model that simulates the syphilis epidemic. Using this model, the researchers estimated the impact of no intervention or different interventions against the syphilis epidemic in that province in different subgroups of gbMSM. The researchers focused on the following four sub-groups of gbMSM:

1. men who were HIV negative or unaware of their HIV status and for whom PrEP was not recommended
2. men who were HIV negative or unaware of their HIV status for whom PrEP was recommended but who were not taking it
3. men who were HIV negative who were taking PrEP
4. men who were diagnosed with HIV

The researchers modelled the effect of increasing different factors that could have an impact on the syphilis epidemic, such as the following:

• frequency of syphilis screening
• use of DoxyPEP
• use of PrEP (recall that people on PrEP are supposed to be screened for syphilis and other STIs every three months)

The researchers used computers to simulate the syphilis epidemic to the year 2034.

Results

The simulation predicted that if more gbMSM used PrEP in the coming years, the regular syphilis screening that accompanies PrEP engagement would help reduce the spread of this infection by about 50% over the long term. Indeed, the researchers stated that without the continued deployment of PrEP, rates of new cases of syphilis would rise among gbMSM by nearly 170% by 2034.

The researchers found that a combination of interventions in the sub-groups studied would be ideal. Such interventions would include an overall increase in the frequency of syphilis screening and the use of DoxyPEP.

Based on the results of the simulation, the first sub-group that the researchers identified as a priority for sexual health services could be those in group 2—gbMSM who were HIV negative or unaware of their HIV status and for whom PrEP was recommended but who were not taking it. The researchers would first encourage more frequent syphilis screening and the deployment of DoxyPEP, as they are primarily interested in stopping the spread of syphilis. However, it seems logical that after syphilis screening and treatment (when necessary), this sub-group of men could be offered entry to PrEP programs.

The next sub-group identified was group 3—HIV negative gbMSM who are taking PrEP. As these men already undergo frequent syphilis screening (every three months), there would be no change in this. However, the researchers recommended the deployment of DoxyPEP to this group. The fourth group—men with HIV—would be encouraged to test for syphilis more frequently and to use DoxyPEP when needed.

Ending syphilis as a community health issue among gbMSM in British Columbia

Overall, to end syphilis as a community health issue among gbMSM, the researchers underscored the need for more frequent syphilis screening and the deployment of DoxyPEP among sub-groups of gbMSM. If these interventions are scaled up, the computer simulation predicted that by 2034it would be possible to bring about the end of syphilis as a community health issue among gbMSM in B.C.

Increasing the frequency of syphilis screening

Data from B.C. suggests that rates of syphilis testing are not always optimal. For instance, in 2019, among gbMSM in group 1 (HIV negative or did not know their HIV status and for whom PrEP was not recommended), screening for syphilis occurred an average of every nine months. Among gbMSM in group 2 (HIV negative or did not know their HIV status and for whom PrEP was recommended but who had not initiated it), the frequency of syphilis screening was also around every nine months. Even among HIV negative gbMSM who used PrEP, rates of syphilis screening were suboptimal—about every 4.7 months. Among men with HIV, testing for syphilis occurred on average every six months. Thus, it appears that increasing rates of syphilis screening among all sub-groups of gbMSM will be necessary.

The research team recommended consideration of the following interventions that may be useful in some sub-groups who are not frequently engaged in syphilis testing:

• enhanced use of an online STI testing service (called GetChecked Online) offered by the BCCDC
• deployment of test kits that can be used to rapidly and simultaneously screen for HIV and syphilis
• campaigns to encourage gbMSM who would benefit from PrEP to enter PrEP programs (where syphilis screening would be available)

The researchers suggested that the promotion of more frequent syphilis screening and the use of DoxyPEP have the potential to further drive down new cases of syphilis.

The research team noted that the San Francisco Department of Public Health and the Australian Society for HIV, Viral Hepatitis and Sexual Health Medicine have developed guidelines for the use of DoxyPEP. They also found it encouraging that so far evidence suggests that the germs that cause syphilis (Treponema pallidum) are unlikely to develop resistance to doxycycline. The researchers suggested that long-term monitoring of people who use DoxyPEP is required to assess the impact of doxycycline on the potential of key STIs to develop resistance to it.

Although the present simulation explored the effect of DoxyPEP on the syphilis epidemic, it is likely that the antibiotic would have another benefit—a reduced risk for infections with the germs that cause chlamydia and gonorrhea.

Bear in mind

No simulation of reality is perfect, and the present model could be further refined. For instance, the research team acknowledged that certain psychosocial issues help drive the syphilis epidemic among gbMSM. They stated that these issues include the following:

• mental health
• substance use
• violence
• discrimination
• stigma

Unfortunately, the researchers did not have data on these issues to put into their simulation.

Nevertheless, the research by the scientists is encouraging. It shows that it may be possible to drive down rates of new cases of syphilis and ultimately end the syphilis epidemic as a community health issue among gbMSM. For this to happen, more resources will need to be deployed in public health and sexual health programs in B.C. Other regions and cities in Canada and other high-income countries may be able to use the ideas presented by the researchers to model how the syphilis epidemic among gbMSM could be controlled and hopefully ended. Increased syphilis screening, DoxyPEP deployment and the entry of more gbMSM into PrEP programs all have a role to play against syphilis.

—Sean R. Hosein

Resource

Syphilis resources — CATIE

REFERENCES:

1. Zhu J, Takeh BT, David J, et al. Impact of screening and doxycycline prevention on the syphilis epidemic among men who have sex with men in British Columbia: a mathematical modelling study. Lancet Regional Health—Americas. 2024; in press.
2. Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure doxycycline to prevent bacterial sexually transmitted infections. New England Journal of Medicine. 2023 Apr 6;388(14):1296-1306.
3. Vanbaelen T, Manoharan-Basil SS, Kenyon C. 45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis. BMC Infectious Diseases. 2024 Apr 4;24(1):376.  
4. Pitt-Kendall R, Sun S, Hughes S, et al. Investigating the cause of increased tetracycline-resistant Neisseria gonorrhoeae in England, 2016-20. Journal of Antimicrobial Chemotherapy. 2024; in press.
5. Hazra A, McNulty MC, Pyra M, et al. Filling in the Gaps: Updates on Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections. Clinical Infectious Diseases. 2024; in press.
6. Cornelisse VJ, Riley B, Medland NA. Australian consensus statement on doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual and other men who have sex with men. Medical Journal of Australia. 2024; in press.
7. Vanbaelen T, Manoharan-Basil SS, Kenyon C. Doxycycline post-exposure prophylaxis could induce cross-resistance to other classes of antimicrobials in Neisseria gonorrhoeae: an in-silico analysis. Sexually Transmitted Diseases. 2023 Aug 1;50(8):490-493.
8. Mortimer TD, Grad YH. A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance. Clinical Infectious Diseases. 2023 Sep 11;77(5):788-791.
9. Whiley DM, Tickner JA, Kundu RL, et al. Selection of Neisseria gonorrhoeae ceftriaxone resistance using doxycycline post-exposure prophylaxis. Lancet Infectious Diseases. 2023 Aug;23(8):e268-e269.
10. Kong FYS, Kenyon C, Unemo M. Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections. Journal of Antimicrobial Chemotherapy. 2023 Jul 5;78(7):1561-1568.