Treponemal Shedding, Load, and Viability, in Women and Men-who-have-sex-with-women-only With Early Infectious Syphilis: Implications for Transmission (SOS Global)

Treponemal Shedding, Load, and Viability, in Women and Men-who-have-sex-with-women Only With Early Infectious Syphilis: Implications for Transmission

How syphilis is transmitted between sexual partners is unclear. Asymptomatic detection i.e. detection of syphilis bacteria (Tp) from anatomical sites without lesions, in patients with syphilis infection, suggests that asymptomatic transmission from these sites may play a role. However, no existing studies have established whether the syphilis bacteria (Tp) detected was viable. This means it is not known if the bacteria at this anatomical site is alive and therefore able to transmit the infection. Further, studies have focused mostly on men who have sex with men, resulting in a lack of evidence regarding anal shedding in men-who-have-sex-with-women only and women (regardless of sexual behaviour), and no data on asymptomatic vaginal shedding in women. This study will explore:

1. Patterns of Tp detection in women and men-who-have-sex-with-women only.
2. Whether detected Tp from each asymptomatic anatomical sites is viable
3. Duration of Tp detection and viability (alive and transmissible bacteria). Patients presenting to a participating sexual health service (overseas only) for management of suspected/confirmed early infectious syphilis will be eligible. During the routine clinical examination, participants will have additional oral and anal swabs, urine, vaginal swab (where relevant), penile skin swab (where relevant) and blood sample collected, in addition to the routine samples taken from the same sites and routine serology collected when syphilis is diagnosed.

Study Overview

• Status: Recruiting
• Conditions: Syphilis
• Intervention / Treatment: Other: No Intervention: Observational Cohort

• Study Type: Observational
• Enrollment (Estimated): 480

Contacts and Locations

• Study Contact: Name: Brigid M Scally; Phone Number: +61399039300; Email: brigid.scally@monash.edu
• Study Contact Backup: Name: Janet Towns; Email: janet.towns@monash.edu

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Active, not recruiting
      • Monash University
• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200443
      • Not yet recruiting
      • Shanghai skin disease hospital
    • Shanghai, Shanghai Municipality, China, 200082
      • Not yet recruiting
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
• South Africa
  • Johannesburg, South Africa, 2192
    • Not yet recruiting
    • National Institute for Communicable Diseases
  • Pretoria, South Africa, 0184
    • Not yet recruiting
    • Foundation for Professional Development
• United Kingdom
  • London, United Kingdom, SE10UN
    • Recruiting
    • Burrell Street Clinic, Guy's and St Thomas'
    • Contact: Michael Marks; Phone Number: +442076368636; Email: michael.marks@lshtm.ac.uk
  • London, United Kingdom, WC1E6JB
    • Recruiting
    • Mortimer Market Centre
    • Contact: Michael Marks; Phone Number: +442076368636; Email: michael.marks@lshtm.ac.uk
  • London, United Kingdom, WC1E7HT
    • Active, not recruiting
    • London School of Hygiene & Tropical Medicine
  • London, United Kingdom, W21DL
    • Recruiting
    • Jefferiss Clinic St Mary's Hospital, Imperial College London
    • Contact: Michael Marks; Phone Number: +442076368636; Email: michael.marks@lshtm.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women and Men-Who-Have-Sex-With-Women-Only with early infectious syphilis

Description

Inclusion Criteria:

- 1. Any cis-woman, cis-MSW, or nonbinary individuals with a penis who have sex with women only, (who meet all other study criteria) 2. Aged ≥18 years of age, 3. At least one sexual partner in the last 12 months 4. One of either:

a. Untreated clinically suspected primary or secondary syphilis. i. Must have rash or lesion(s) clinically suggestive of early infectious syphilis infection.

ii. May have positive PCR result, positive Dark-ground Microscopy result, positive syphilis serology or positive point-of-care syphilis test, but these are not necessary at the time of enrolment.

b. Untreated early latent (no clinical signs indicative of primary or secondary syphilis) syphilis with positive syphilis serology or positive point-of-care test, and one or more of the following(11): i. A documented syphilis seroconversion within the prior 12 months. ii. A sustained (longer than 2 weeks) fourfold or greater increase in the titre in the prior 12 months in a person previously treated for syphilis.

iii. Unequivocal symptoms of primary or secondary syphilis within the prior 12 months.

iv. Contact in the prior 12 months with a sex partner who had untreated primary, secondary, or early latent syphilis.

v. Documented reactive nontreponemal and treponemal tests, and the only possible exposure occurred during the previous 12 months vi. RPR/VDRL titre >= 1:64 5. Be willing and able to complete study procedures, including physical examination 6. Receiving syphilis treatment on the day of recruitment 7. Have sufficient language proficiency to understand the requirements of the study 8. Provide informed consent as per individual site's local ethics requirements

Exclusion Criteria:

1. Men, transwomen, or other people, with a penis, who have had any sexual contact, including kissing, oral sex or anal sex, with men (or any other individual with a penis) in the previous one year.
2. Individuals who have received antibiotic treatment within 1 month prior to enrolment, with the EXCEPTION of metronidazole.
3. Diagnosis of late latent syphilis (>1 year) or latent syphilis of unknown duration.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cis-women with suspected or confirmed primary syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study
Cis-women with suspected or confirmed secondary syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study
Cis-women with confirmed early-latent syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study
Men-who-have-sex-with-women-only with suspected or confirmed primary syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study
Men-who-have-sex-with-women-only with suspected or confirmed secondary syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study
Men-who-have-sex-with-women-only with confirmed early-latent syphilis infection	Other: No Intervention: Observational Cohort; No intervention: Observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Biological Samples Testing Positive for Treponema pallidum DNA by PCR	This outcome measures the presence of Treponema pallidum (Tp) DNA in collected biological samples-including lesion swabs, blood, urine, saliva, and oral/anal/genital swabs-using a validated T. pallidum polymerase chain reaction (Tp PCR) assay. Data will be reported as the number and proportion of samples that test positive, stratified by: sample type,; clinical stage of syphilis,; anatomical site (where applicable),; and participant characteristics relevant to the SOS Global protocol. No scale is used; this is a binary laboratory outcome (PCR positive / PCR negative).	Samples are taken at time of consent - single visit study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Load of Treponema pallidum DNA in Positive Biological Samples by In-house Quantitative PCR (qPCR) assay	This outcome measures the load (copies/mL) of Treponema pallidum (Tp) DNA in collected biological samples-including lesion swabs, blood, urine, saliva, and oral/anal/genital swabs-using an in-house validated quantitative T. pallidum polymerase chain reaction (Tp qPCR) assay. Data will be reported as a comparison in load between anatomical sites and by clinical stage of syphilis.	Samples are taken at time of consent - single visit study
Number of Treponema pallidum-Positive Samples Demonstrating Viable Organisms via Novel In-house Viability Assay	This outcome measures the viability of detected Treponema pallidum in PCR-positive biological samples. Viability is assessed using a novel in-house viability assay. Results will be summarised as the number and proportion of Tp PCR-positive samples that contain viable organisms, stratified by sample type and clinical/epidemiological variables specified in the SOS Global protocol. This outcome focuses on confirming whether Tp organisms in collected specimens are capable of establishing infection, rather than merely detecting genetic material. The viability assessment does not result in a continuous scale; it is a binary laboratory outcome (viable / non-viable).	Samples are collected at time of consent - single study visit

Collaborators and Investigators

• Sponsor: Monash University
• Collaborators: The Alfred; Melbourne Sexual Health Centre
• Investigators: Principal Investigator: Janet Towns, Monash University; Principal Investigator: Marcus Chen, Monash University

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: December 10, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: syphilis; sexual health; syphilis transmission; asymptomatic shedding
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Sexually Transmitted Diseases, Bacterial; Treponemal Infections; Syphilis
• Other Study ID Numbers: MUCTC-24018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Request for data sharing will be considered on a case by case basis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No