The Neisseria gonorrhoea (NG) epidemic in England is at the highest level in one hundred years of public health records. The World Health Organisation has listed NG as one of the top five bacterial infections globally because of the ability of the bacteria to develop resistance to antibiotics. Neisseria meningitidis (NM) is a common pharyngeal commensal and it has been shown to be in one in five men who have sex with men (MSM) in London.

In the last year sexual health clinics have had a growing number of MSM presenting with urethritis / proctitis that were treated for NG on the day only to be found later to have been infected with NM from the culture. It appear that virulence factors have been passed from NG to NM enabling these bacteria to infect the urogenital and anal mucosa; consequently, NM in some cases is a new Sexually Transmitted Infection (STI). In 2025, two STI prevention interventions were rolled out in an attempt to address the gonorrhoea & syphilis epidemics and these were the 4CMenB vaccine and doxycycline post exposure prophylaxis (DoxyPEP).

This study will recruit sexual partners of patients who have been diagnosed with NG and the investigators will ask the participant for one additional pharyngeal sample for research that will not impact on their standard of care. The additional sample will be tested using metagenomics, that is where all non-human DNA is analysed, and the initial focus will be on NG or NM infection, co-infection, genes for virulence and antibiotic resistance from whole genome sequencing.

The metagenomic analysis is being undertaken for research purpose only; however, secondary outcomes will look for other STIs in the pharyngeal sample and sample turn around time to inform the management of patients. Any additional STI identified will have validated testing to confirm diagnosis.

The main focus of this study is to develop a metagenomic assay for sexually transmitted infections (STIs) using samples taken from the pharynx of sexual partners of a patient who has been diagnosed with gonorrhoea.

Initial analysis will be on the Neisseria species (N. gonorrhoea [NG] & N.meningitidis [NM]) identified, co-infection, the virulence factors seen and mutations related to antibiotic resistance.

A full clinical history will be taken for each participant and the investigators will ask if they have had the 4CMenB vaccination (against NM with up to 30-40% protection against NG) or taken DoxyPEP (doxycycline 200mg taken after sex) because about 15% of NG is sensitive to tetracyclines.

The secondary research questions will focus on which other STIs are detectable using metagenomics in the pharynx. It is possible that there will be co-infections with Chlamydia trachomatis (serovars D-K and L1-3), Mycoplasma genitalium, Treponema pallidum, Human Papillomavirus and Herpes viruses.

The study will also explore the feasibility, turnaround times, and potential operational considerations associated with metagenomic sequencing within a sexual health research setting.

The metagenomic assay is being used for research purposes only and is not being used as a validated diagnostic test to direct participant management.

Current testing for gonorrhoea (NG) involves a targeted test which uses a primer (a genetic key which is different for each infection) and then the amplification of the Deoxyribonucleic Acid (DNA) or RiboNucleic Acid (RNA).

The clinical team only see what they test for; consequently, if they don't order an NG test then it will be missed. In addition, there is no targeted test for Neisseria meningitidis (NM) in sexual health; therefore, clinical teams only 'see' this infection if the laboratory are able to grow the organism in culture. Culture for NG is only positive in 50% of cases with the standard of care pathway. When an organism does not grow then it is not possible to do antibiotic sensitivity testing.

Metagenomic testing enables the laboratory to identify what organisms are present and then do additional analysis to understand what treatments would be expected to work. The investigators can also use whole genome sequencing to investigate the exchange of genetic material from NG to NM to understand what is driving the change in the clinical presentation.

Testing in London has shown that one in five men who have sex with men (MSM) carry NM in their throat. The current epidemic of NG is unprecedented and the strategy of frequent testing has not helped stem this rise. The recent recommendation to give high risk MSM the 4CMenB vaccine (against NM) has been done with the hope of producing cross protection to NG too. Some studies have shown a 30-40% reduction in NG so it will be interesting to see how that impacts the positivity in partners. Historically 45% of sexual partners of patients diagnosed with NG are found to have the infection.

The roll out of doxycycline as post exposure prophylaxis (DoxyPEP) to reduce the risk of syphilis by 80% will also partially impact on GC too as 15% of these bacteria are still sensitive to this group of antibiotics (tetracyclines).

The identification of gyrA mutation in NG means that it will be resistant to quinolone treatment; however, if it is not present then these patients could be treated with a single ciprofloxacin tablet from pharmacy instead of coming back to clinic for an intramuscular injection with the third generation cephalosporin, Ceftriaxone. In London, half of the NG are still sensitive to quinolones; consequently, identifying that this treatment could be used would speed up access to treatment and release capacity in clinic.

Finally, the identification of other known sexually transmitted infections (STI) will be possible using metagenomics. Oral sex is already known to transmit Chlamydia, Syphilis and Herpes; therefore, this type of testing will enable the identification of infections that would traditionally be missed. During this trial the investigators will determine how metagenomic testing could fit in with the standard of care pathways to support optimal STI control.

In this study the investigators are going to focus on the sexual partners of patients who have been diagnosed with Neisseria gonorrhoea (NG). The rationale for this choice is because data from the UK HSA shows that 45% of these partners will have the infection; consequently, sampling this group will enable us to have nearly a 1:1 ratio of individuals with an NG infected pharynx and a control. One in five will be expected to have Neisseria Meningitidis (NM).

Partners will be alerted of their risk using the anonymous partner notification platform SXT (http://sxt.health) and attracted to the Burrell Street Sexual Health clinic through the provision of targeted appointments. The SXT software shows local appropriate clinics for partners to access testing, treatment and other STI prevention services and those clinics with appointments are prioritised on the clinic search.

When the partner is seen they will receive the normal standard of care which includes chlamydia/gonorrhoea testing from the pharynx, rectum and urine as well as culture testing from the three sites if they are going to be treated with an antibiotic. All eligible partners are offered the opportunity to join the study. If the partner consents to become a participant then add additional swab will be taken from the pharynx in addition to the standard of care. Partners (participants if they consent) who are asymptomatic and not had sex for two weeks will be offered tests only and to await the results.

This observational trial involves taking one additional swab from the pharynx for metagenomic analysis. Initially theses tests will be collected for batch testing and analysis. Later in the trial the investigators will work on the throughput of samples to determine if they can be used to inform the standard of care. If NG is detected then the investigators will determine that there is no quinolone resistance then this may alter treatment options in the future. During this study, metagenomic results will not be used to direct participant treatment or replace standard of care testing pathways.

All treatment decisions will continue to be based on validated standard clinical testing. While identification of quinolone-sensitive NG may inform future clinical investigation into alternative treatment pathways, including use of oral ciprofloxacin, this will not form part of participant management within the current study.

Other aspects of standard of care include blood testing for HIV, Syphilis, Hepatitis (A/B/C) as well as the offer of STI prevention services such as PrEP to reduce their risk of HIV, Vaccinations for Hepatitis A&B, HPV, MPox and 4CMenB (against NM and NG) and DoxyPEP to reduce their risk of syphilis.

Inclusion Criteria:

• Partner alerted of their risk about being a partner of someone diagnosed with Neisseria Gonorrhea using the digital partner notification software SXT and then booking an appointment for standard of care testing.

Exclusion Criteria:

• Under 18 years, unable to speak English

Most of the partners will be men who have sex with men as 80% of the diagnoses of gonorrhea are made in this group

No patient identifiable data will be shared. We plan to do the metagenomic analysis alongside the standard of care and then look at the additional diagnostic information from this approach and determine if it adds value to our patients.

By the end of February 2027

This information will be provided in the publications