Optimising benzathine penicillin G for dyadic syphilis control when the male partner does not reach the clinic: a pilot randomised study of a reversible biophysical adjunct delivered as part of an integrated partner-engagement package, in Rakai, Uganda
A mechanistic pilot to determine whether the subpreputial silicone ring shifts the male genital microbiome toward a post-circumcision-like state — enabling a definitive dyadic trial for syphilis control in high-burden settings.
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 · Nakku-Joloba 2019700,000 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 BASIC consortium (Parvimonas, Dialister, Sneathia sanguinegens) was defined and characterised in uncircumcised Ugandan men at the Rakai Health Sciences Program — the same site as ADJUNCT-SYPH.
Data from the Rakai circumcision trials, and a later systematic review, suggest a lower acquisition of some STIs among female partners of circumcised men. These are secondary analyses; the size of the effect depends on the infection and the study.
In the StepUp trial (NEJM 2025), treating the male partner with antibiotics reduced female BV recurrence at 12 weeks from 63% to 35%. This supports the idea that male partners matter for female reproductive tract infections. It does not show that a non-antibiotic approach works, and it did not study syphilis; ADJUNCT-SYPH tests a different intervention for a different infection.
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.
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.
Senior research scientist at the Africa Medical and Behavioural Sciences Organization (AMBSO), Rakai. Lead investigator for the ADJUNCT-SYPH pilot.
Medical Officer / Laboratory Director, Rakai Health Sciences Program, Uganda. Characterised the BASIC consortium in the study population (Galiwango 2019).
We welcome enquiries from potential collaborators, funders, and scientific reviewers. A full protocol summary is available for institutional review on request.