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      Public health impact and cost-effectiveness of gonorrhoea vaccination: an integrated transmission-dynamic health-economic modelling analysis

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      , PhD a , b , c , , Prof, DPhil d , e , f , , Prof, PhD a , b , c , g , *
      The Lancet. Infectious Diseases
      Elsevier Science ;, The Lancet Pub. Group

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          Summary

          Background

          Gonorrhoea is a rapidly growing public health threat, with rising incidence and increasing drug resistance. Evidence that the MeNZB and four-component serogroup B meningococcal (4CMenB) vaccines, designed against Neisseria meningitidis, can also offer protection against gonorrhoea has created interest in using 4CMenB for this purpose and for developing gonorrhoea-specific vaccines. However, cost-effectiveness, and how the efficacy and duration of protection affect a gonorrhoea vaccine's value, have not been assessed.

          Methods

          We developed an integrated transmission-dynamic health-economic model, calibrated using Bayesian methods to surveillance data (from the Genitourinary Medicine Clinic Activity Dataset and the Gonococcal Resistance to Antimicrobials Surveillance Programme) on men who have sex with men (MSM) in England. We considered vaccination of MSM from the perspective of sexual health clinics, with and without vaccination offered to all adolescents in schools (vaccination before entry [VbE]), comparing three realistic approaches to targeting: vaccination on attendance (VoA) for testing; vaccination on diagnosis (VoD) with gonorrhoea; or vaccination according to risk (VaR), offered to patients diagnosed with gonorrhoea plus individuals who test negative but report having more than five sexual partners per year. For the primary analysis, vaccine impact was assessed relative to no vaccination in a conservative baseline scenario wherein time-varying behavioural parameters (sexual risk behaviour and screening rates) stabilise. To calculate the value of vaccination per dose administered, the value of vaccination was calculated by summing the averted costs of testing and treatment, and the monetary value of quality-adjusted life-year (QALY) gains with a QALY valued at £20 000. Costs were in 2018–19 GB£, and both costs and QALYs were discounted at 3·5% per year. We analysed the effects of varying vaccine uptake (0·5, 1, or 2 times HPV vaccine uptake by MSM in sexual health clinics in England), vaccine efficacy (1–100%) and duration of protection (1–20 years), and the time-horizon considered (10 years and 20 years). In addition, we calculated incremental cost-effectiveness ratios for the use of 4CMenB using assumed vaccine prices.

          Findings

          VbE has little impact on gonorrhoea diagnoses, with only 1·7% of MSM vaccinated per year. VoA has the largest impact but requires more vaccine doses than any other strategy, whereas VoD has a moderate impact but requires many fewer doses than VoA. VaR has almost the same impact as VoA but with fewer doses administered than VoA. VaR is the most cost-effective strategy for vaccines of moderate efficacy or duration of protection (or both), although VoD is more cost-effective for very protective and long-lasting vaccines. Even under conservative assumptions (efficacy equivalent to that of MeNZB and protection lasting for 18 months after two-dose primary vaccination and 36 months after single-dose booster vaccination), 4CMenB administered under VaR would likely be cost-saving at its current National Health Service price, averting an estimated mean 110 200 cases (95% credible interval 36 500–223 600), gaining a mean 100·3 QALYs (31·0–215·8), and saving a mean £7·9 million (0·0–20·5) over 10 years. A hypothetical gonorrhoea vaccine's value is increased more by improving its efficacy than its duration of protection—eg, 30% protection lasting 2 years has a median value of £48 (22–85) per dose over 10 years; doubling efficacy increases the value to £102 (53–144) whereas doubling the duration of protection increases it to £72 (34–120).

          Interpretation

          We recommend that vaccination of MSM against gonorrhoea according to risk in sexual health clinics in England with the 4CMenB vaccine be considered. Development of gonorrhoea-specific vaccines should prioritise maximising efficacy over duration of protection.

          Funding

          Medical Research Council (UK), National Institute for Health Research (UK).

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          Most cited references25

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          Sexually transmitted infections: challenges ahead.

          WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.
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            Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action

            In a Policy Forum, Teodora Wi and colleagues discuss the challenges of antimicrobial resistance in gonococci.
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              Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018

              We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.
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                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Science ;, The Lancet Pub. Group
                1473-3099
                1474-4457
                1 July 2022
                July 2022
                : 22
                : 7
                : 1030-1041
                Affiliations
                [a ]Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK
                [b ]MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
                [c ]NIHR Health Protection Research Unit in Modelling and Health Economics, School of Public Health, Imperial College London, London, UK
                [d ]School of Life Sciences, University of Warwick, Coventry, UK
                [e ]Department of Statistics, University of Warwick, Coventry, UK
                [f ]NIHR Health Protection Research Unit in Genomics and Enabling Data, University of Warwick, Coventry, UK
                [g ]Modelling and Economics Unit, National Infection Service, Public Health England, London, UK
                Author notes
                [* ]Correspondence to: Prof Peter J White, Department of Infectious Disease Epidemiology, Imperial College School of Public Health, London W2 1PG, UK p.white@ 123456imperial.ac.uk
                Article
                S1473-3099(21)00744-1
                10.1016/S1473-3099(21)00744-1
                9217755
                35427491
                d244ab8d-3619-4ed2-8ab5-4571058de3da
                © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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