A reversible silicone ring worn by male partners as an adjunct to optimise the durability of benzathine penicillin G (BPG) treatment in women with syphilis: a feasibility, acceptability, safety and mechanistic pilot in Ugandan men
A fully designed feasibility, acceptability, safety and mechanistic pilot proposed to assess 8-week wear of a reversible silicone ring in men attending VMMC services in Uganda — ready to execute pending funding, with a top-tier Ugandan investigator team assembled and the study site confirmed at Rakai.
8 million new syphilis infections annually worldwide, despite benzathine penicillin G (BPG) being efficacious, affordable, and widely recommended.
WHO 2022 · Korenromp 2019Standard partner notification achieves male partner treatment in only 1.1–18.3% of index cases, leaving the reinfection source largely untreated.
Kizito 2008 · Parkes-Ratanshi 2020700,000 annual congenital syphilis cases — representing preventable neonatal morbidity and mortality — persist because maternal infection recurs while male reservoirs remain untreated.
Korenromp 2019 · WHO 2022Uncircumcised men — BASIC consortium, CST 4–7
Parvimonas · Dialister · Sneathia sanguinegens
CST 4–7 in female partner
Impaired epithelial barrier → enhanced pathogen entry
Male circumcision produces a reproducible, sustained shift from anaerobic-dominant to aerobic-dominant microbiota at the subpreputial site — mirroring the CST shift ADJUNCT-SYPH proposes to achieve non-surgically.
The anaerobe-rich subpreputial and coronal-sulcus community — including taxa such as Parvimonas, Dialister and Sneathia — was quantified in uncircumcised Ugandan men, with anaerobe abundance falling sharply after circumcision, at the Rakai Health Sciences Program — the same site as ADJUNCT-SYPH.
A prospective study in HIV-serodiscordant African couples found male circumcision associated with a 59% reduction in incident syphilis among female partners (aHR 0.41, 95% CI 0.25–0.69); a subsequent systematic review rated the evidence that male circumcision protects women against syphilis as highly consistent — establishing that modifying the male genital environment confers measurable downstream female protection.
The StepUp trial (NEJM 2025) demonstrated that male partner treatment to modify genital microbiota reduces female BV recurrence from 63% to 35% at 12 weeks — validating the dyadic transmission hypothesis that ADJUNCT-SYPH will extend to syphilis.
The ring is worn continuously and everts the foreskin, eliminating the closed subpreputial space and increasing local aeration. This removes the warm, moist, oxygen-depleted microenvironment that supports the BASIC consortium of anaerobic taxa.
Increased local O₂ tension over 8 weeks is hypothesised to progressively suppress anaerobic taxa (BASIC consortium) and shift the subpreputial community state type (CST) toward the aerobic, diverse profile observed after surgical circumcision. This shift is the primary measurable endpoint of the pilot.
Currently placed on the EU market as a hygiene product under the General Product Safety Regulation (GPSR) by Circunaro SL.
Previously CE-marked as a Class I medical device under Directive 93/42/EEC.
Regulatory classification for use in this pilot study will be confirmed with the Ugandan National Drug Authority (NDA) and the Ethics Committee prior to first participant in.
Participant recruitment has not yet commenced. We are currently building the investigator consortium. The study will open to recruitment only after funding confirmation and ethics committee approval.
Δ log₁₀ BASIC consortium abundance (qPCR copies/swab), W0→W8, between-arm difference
≥1.5 log₁₀ reduction in BASIC consortium in Arm A vs. Arm B at W8, with ≥70% retention and acceptable safety profile → proceed to full dyadic RCT design and Wellcome programme grant application.
0.5–1.5 log₁₀ reduction, or retention 50–70% → protocol review with DMC and funder; potential protocol amendment before escalation.
<0.5 log₁₀ reduction, or retention <50%, or unacceptable safety events → halt programme, publish null results, reassess device modification.
The following Ugandan investigators have co-developed this proposal. All are researchers at RHSP and/or AMBSO with deep expertise in Rakai-based male-circumcision and STI research. Roles shown are as agreed in the current draft and will be formally confirmed upon funding and ethics approval.
Senior research scientist who has led medical male-circumcision trials and outcome studies in Rakai, Uganda (e.g. Kigozi et al., PLoS ONE 2014; BJU Int 2013).
Researcher at the Rakai Health Sciences Program whose work characterised the penile coronal-sulcus microbiome and anaerobe abundance before and after circumcision in Ugandan men (Galiwango et al., Microbiome 2022).
Research scientist at the Rakai Health Sciences Program, Uganda.
Epidemiologist at the Rakai Health Sciences Program, Uganda, with extensive experience in population-based cohort research.
Researcher at AMBSO and the Rakai Health Sciences Program, Uganda.
We welcome enquiries from potential collaborators, funders, and scientific reviewers. A full protocol summary is available for institutional review on request.