An oropharyngeal gonorrhoea controlled human infection model: a provisional protocol using a novel Neisseria gonorrhoeae challenge strain
- Author(s)
- Williams, E; Pollock, GL; Price, DJ; Crocker-Buque, T; de Kretser, D; Jamrozik, E; Osowicki, J; Pasricha, S; Azzato, F; Steer, A; Groom, JR; Hill, DL; Roberts, JA; Huston, WM; Seib, KL; Fairley, CK; Chow, EP; Chen, MY; Hocking, JS; Williamson, DA; McCarthy, JS;
- Journal Title
- Wellcome Open Research
- Abstract
- INTRODUCTION: Gonorrhoea is a sexually transmissable infection caused by Neisseria gonorrhoeae that causes a significant global burden of disease. Urogenital infection can result in long-term impacts on reproductive, perinatal, and neonatal health. Little progress has been made in the public health control of gonorrhoea, and novel preventative strategies are urgently needed. Furthermore, future gonorrhoea management is threatened by increasing antimicrobial resistance (AMR). Oropharyngeal gonorrhoea is usually asymptomatic; likely plays an important role in development of AMR; and is a high-risk site for treatment failure. Here, we describe a protocol for an oropharyngeal gonorrhoea controlled human infection model (CHIM) that has been designed to maximize participant safety, with the aim of developing this as a platform to accelerate prevention and treatment strategies. METHODS AND ANALYSIS: This dose-escalation CHIM study will enrol 20-35 healthy adult volunteers aged 18 to 50 years who were assigned male at birth and only have sex with people assigned male at birth. The primary objectives are to determine i) the safety and tolerability of an oropharyngeal gonorrhoea CHIM; and, ii) the minimum infectious dose of isolate AUSMDU00053933 required for 60-80% of participants to develop oropharyngeal N. gonorrhoeae infection. Secondary and exploratory endpoints include description of clinical, immunological, microbiological and pharmacometric responses. Participants will be monitored daily as outpatients during the five-day experimental infection phase. All participants will be treated with antibiotics, and followed up for three months. Statistical analysis and dose escalation/de-escalation decisions will follow a model-based continual reassessment method in a Bayesian statistical framework. ETHICS AND DISSEMINATION: After scientific peer review of this provisional protocol, a detailed protocol will be submitted for human research ethics committee assessment. Protocol development was informed by feedback from community engagement. Study findings will be disseminated in peer-reviewed journals and at scientific meetings, with summaries provided to relevant stakeholders.; This report outlines a research study protocol using a controlled human infection model, where participants are inoculated in the throat with Neisseria gonorrhoeae, the bacteria that causes gonorrhoea. Throat infections usually have no symptoms but can still lead to unintentional spread to others. Genital gonorrhoea can cause painful symptoms. In rare cases, the infection can spread through the bloodstream to affect joints, tendons, and skin. It can also cause serious long-term health problems in women, including infertility. Although gonorrhoea can be treated with antibiotics, the only effective treatment is ceftriaxone and ceftriaxone-resistant gonorrhoea is increasingly reported. This increasing resistance makes it vital to develop new treatments. This initial study aims to confirm that the research approach is safe and to find the dose of bacteria that reliably causes throat infection within five days. All participants will be treated with antibiotics within five days of being exposed to the bacteria. As gonorrhoea can cause long-term reproductive impacts in people with a female reproductive system, only adults aged 18 to 50 who were assigned male at birth and have sex exclusively with others assigned male at birth will be eligible. Participants will attend the clinic as outpatients and must agree not to have any form of sexual contact, including oral sex and kissing, until they are cured. The study will explore clinical symptoms, immune responses, and how the bacteria behave in the throat. This will improve understanding of throat gonorrhoea. If this early research is successful, the model will be used to test new antibiotics, vaccines, and prevention strategies, with the ultimate goal of reducing the global burden of disease due to gonorrhoea.; eng
- Publisher
- F1000
- Keywords
- Controlled human infection model; antimicrobial resistance; gonorrhoea; sexually transmitted infection; study protocol; vaccine
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 41695297
- Publisher's Version
- https://doi.org/10.12688/wellcomeopenres.25103.1
- Open Access at Publisher's Site
https://doi.org/10.12688/wellcomeopenres.25103.1- Terms of Use/Rights Notice
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Creation Date: 2026-03-16 01:38:20
Last Modified: 2026-03-16 01:52:35