CATIE News

• Scientists are studying the possibility of pre- and post-exposure prophylaxis for syphilis
• Such an approach would entail antibiotics taken before or immediately after exposure
• 44% of gay and bi men said they would take syphilis PrEP; 60% would take syphilis PEP

Rates of common sexually transmitted infections (STIs)—chlamydia, gonorrhea and syphilis—have been increasing over the past 20 years in Canada and other high-income countries. All three infections can have serious health consequences; in particular, the germs that cause syphilis can cause complex multistage disease and can affect vital organs such as the brain, heart and so on. Some sexually active gay, bisexual and other men who have sex with men (MSM) have been hard hit by the surge in STIs. Ways to decrease STI risk are urgently needed.

In clinical trials, a pill containing two anti-HIV medicines (tenofovir DF and FTC; sold as Truvada and in generic formulations) has been extremely effective at reducing the risk for HIV when used as directed. Taking medicines in this way is called HIV pre-exposure prophylaxis (PrEP). Although the combination of tenofovir DF and FTC is approved for HIV prevention, there is no similar prevention strategy that has been sanctioned by STI societies or regulatory agencies for syphilis.

Questions about preventing syphilis

Scientists in Toronto and Vancouver surveyed MSM in both cities to find out about their views on the use of the antibiotic doxycycline taken either before or after sex to reduce the risk of developing syphilis. The survey of 424 mostly young men found that around 60% were willing to take an antibiotic to reduce their syphilis risk. This finding is noteworthy, as syphilis is an important health issue and large clinical trials will be needed in the future to explore the potential role of doxycycline in syphilis prevention among MSM. The survey also captured other interesting information, some of which is detailed later in this CATIE News bulletin.

Study details

Scientists recruited 424 participants from community-based sexual health clinics in Toronto and Vancouver. The study questionnaires were self-administered and anonymous. The brief average profile of participants upon entering the study was as follows:

• age – 31 years (many were between 26 and 39 years)
• most identified as male (99.8%) and gay (88%); one person identified as transgender male
• 7% disclosed that they were HIV positive

Although participants were asked many questions, two key issues were phrased in the following ways:

• “Syphilis PrEP would involve taking one antibiotic pill everyday to prevent syphilis, and potentially chlamydia. It might cause side effects in some people such as mild stomach upset, and might increase the chance that future infections of all kinds could be harder to treat because of drug resistance (not just STIs). It would involve doing bloodwork and seeing a doctor every three months. If this strategy were approved in Canada and available to you, would you take it?”
• In the case of syphilis post-exposure prophylaxis (PEP), the text was similar, except for this definition: “Syphilis PEP would involve taking two antibiotic pills within 24 hours after sex.”

Key findings

A majority of participants (60%) indicated that they would be willing to use syphilis PEP. In contrast, about 44% of participants indicated that they would be willing to take syphilis PrEP.

Other issues

The scientists stated that “few participants had ever heard of antibiotic-based prophylaxis prior to completing the questionnaire (13%). However, most were familiar with the concept of antimicrobial resistance, particularly that some bacteria are becoming harder to treat with antibiotics (89%) and can acquire resistance via antibiotic misuse (89%).”

Another finding was that 55% of participants felt that they were at risk for syphilis.

Willingness to use syphilis PrEP

Analysis revealed that the people most likely to use syphilis PrEP had the following features/characteristics:

• were very concerned about getting STIs
• had used HIV PrEP
• had previously been diagnosed with different STIs
• agreed with the statement “I am at risk for syphilis”

Younger people seemed less willing to use syphilis PrEP.

Willingness to use syphilis PEP

Analysis revealed that the people most likely to use syphilis PEP had a higher number of previously diagnosed STIs than people who were unwilling to use it.

Bear in mind

The rates of willingness to use syphilis PEP were relatively high (60%) vs. syphilis PrEP (44%). The scientists attributed this difference to a desire to take fewer pills.

According to the scientists, part of the unwillingness to take syphilis PEP or PrEP may be due to participants underestimating their risk for syphilis. Other studies in England, the Netherlands and the United States have found that many people—regardless of age—underestimate their potential risk for acquiring STIs. The Canadian scientists stated that these findings “underscore the need for interventions to aid individuals in accurately understanding these probabilities.”

For the future

Scientists in Vancouver are conducting a pilot study of the antibiotic doxycycline taken once daily by people who are also talking HIV PrEP. This study is designed to assess whether it is possible to recruit and retain volunteers for a potential larger study of STI PrEP in the future. The pilot study will also assess other issues, such as adherence to doxycycline, potential side effects, effectiveness in preventing key STIs, and the development of resistance to this antibiotic among bacteria that normally live in the gut. The results from this study are expected in the autumn of 2020. If the results are favourable, hopefully the Vancouver scientists will be able to raise funds for a larger study to better understand doxycycline’s potential in reducing the risk of STIs, especially syphilis.

Resources

Canadian guidelines on STIs – Management and treatment of syphilis

Syphilis – Public Health Agency of Canada

Syphilis – British Columbia Centre for Disease Control

La prise en charge et le traitement de la syphilis chez les adultes infectés par le virus de l'immunodéficience humaine (VIH) – Guide pour les professionnels de la santé du Québec – Version résumée –  Ministère de la Santé et des Services sociaux du Québec

Syphilis - BMJ

Syphilis – CATIE Factsheet

Montreal doctors report on cases of syphilis affecting the eyes – CATIE News

British Columbia — Increasing cases of syphilis affecting the eye – CATIE News

Syphilis cases on the rise among HIV-positive people in Calgary – CATIE news

American doctors focus on cases of ocular syphilis – CATIE News

More cases of ocular syphilis reported in the United States – CATIE News

—Sean R. Hosein

REFERENCES:

1. Fusca L, Hull M, Ross P, et al. High interest in syphilis pre- and post-exposure prophylaxis among gay, bisexual and other men who have sex with men in Vancouver and Toronto. Sexually Transmitted Diseases. 2020; in press.
2. Grant JS, Stafylis C, Celum C, et al. Doxycycline prophylaxis for bacterial sexually transmitted infections. Clinical Infectious Diseases. 2020; in press.
3. Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infectious Diseases. 2018;18(3):308–317.
4. Peyriere H, Makinson A, Marchandin H, Reynes J. Doxycycline in the management of sexually transmitted infections. Journal of Antimicrobial Chemotherapy. 2018;73(3):553–563.
5. Vadboncoeur J, Labbé AC, Fortin C, et al. Ocular syphilis: case series (2000-2015) from 2 tertiary care centres in Montreal, Canada. Canadian Journal of Ophthalmology. 2020; in press.
6. Eslami M, Noureddin G, Pakzad-Vaezi K, et al. Resurgence of ocular syphilis in British Columbia between 2013-2016: a retrospective chart review. Canadian Journal of Ophthalmology. 2020; in press.
7. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Annals of Internal Medicine. 1988 Dec 1;109(11):855-62.
8. Singh AE. Ocular and neurosyphilis: epidemiology and approach to management. Current Opinion in Infectious Diseases. 2020 Feb;33(1):66-72.
9. Bazewicz M, Lhoir S, Makhoul D, et al. Neurosyphilis cerebrospinal fluid findings in patients with ocular syphilis. Ocular Immunology and Inflammation. 2019 Oct 24:1-7.
10. Hamze H, Ryan V, Cumming E, et al. HIV seropositivity and early syphilis stage associated with ocular syphilis diagnosis: A case-control study in British Columbia, Canada, 2010-2018. Clinical Infectious Diseases. 2020; in press.
11. Landry T, Smyczek P, Cooper R, et al. Retrospective review of tertiary and neurosyphilis cases in Alberta, 1973-2017. BMJ Open. 2019 Jun 22;9(6):e025995.
12. Clifton S, Mercer CH, Sonnenberg P, et al. STI risk perception in the British population and how it relates to sexual behaviour and STI healthcare use: Findings from a cross-sectional survey (Natsal-3). EClinicalMedicine. 2018;2-3:29–36.
13. Syme ML, Cohn TJ, Barnack-Tavlaris J. A comparison of actual and perceived sexual risk among older adults. Journal of Sex Research. 2017;54(2):149–160.
14. Wolfers M, de Zwart O, Kok G. Adolescents in The Netherlands underestimate risk for sexually transmitted infections and deny the need for sexually transmitted infection testing. AIDS Patient Care STDS. 2011;25(5):311–319.