Agent-based modelling study of antimicrobial-resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment
Adam K. Zienkiewicz A B * , Nicolás Verschueren van Rees A B * , Martin Homer A , Jason J. Ong C D E , Hannah Christensen E , Darryl Hill F , Katharine J. Looker E , Paddy Horner E , Gwenda Hughes
G H and Katy M. E. Turner B E I
A Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK.
B School of Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK.
C Clinical Research and Development, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
D Central Clinical School, Monash University, Clayton, Vic. 3800, Australia.
E Population Health Sciences, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
F School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
G Instituto de Medicina Tropical, Universidade de São Paulo, Avenuenida Dr Enéas Carvalho de Aguiar, 470, CEP 05403-000, São Paulo, Brasil.
H Blood Safety, Hepatitis, STI & HIV Division, National Infection Service, Public Health England, NW9 5EQ, UK.
I Corresponding author. Email: katy.turner@bristol.ac.uk
Sexual Health 16(5) 514-522 https://doi.org/10.1071/SH18235
Submitted: 15 December 2018 Accepted: 29 July 2019 Published: 3 September 2019
Journal Compilation © CSIRO 2019 Open Access CC BY-NC-ND
Abstract
Background: Antimicrobial-resistant (AMR) gonorrhoea is a global public health threat. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised resistance-guided therapy. Methods: An individual-based dynamic transmission model of gonorrhoea infection in MSM living in London has been developed, incorporating ciprofloxacin-sensitive and resistant strains. The time-dependent sexual contact network is captured by periodically restructuring active connections to reflect the transience of contacts. Different strategies to improve treatment selection were explored, including discriminatory POCT and selecting partner treatment based on either the index case or partner susceptibility. Outcomes included population prevalence of gonorrhoea and drug dose counts. Results: It is shown that using POCT to detect ciprofloxacin-sensitive infections could result in a large decrease in ceftriaxone doses (by 70% compared with the reference case in the simulations of this study). It also suggests that ceftriaxone use can be reduced with existing technologies, albeit to a lesser degree; either using index case sensitivity profiles to direct treatment of partners, or testing notified partners with strain discriminatory laboratory tests before treatment, reduced ceftriaxone use in our model (by 27% and 47% respectively). Conclusions: POCT to detect ciprofloxacin-sensitive gonorrhoea are likely to dramatically reduce reliance on ceftriaxone, but requires the implementation of new technology. In the meantime, the proportion of unnecessary ceftriaxone treatment by testing partners before treatment could be reduced significantly. Alternatively, index case sensitivity profiles could be used to select effective treatments for partners.
Additional keywords: antimicrobial resistance, diagnostics, gonorrhoea, point-of-care test, resistance-guided therapy.
References
[1] Holmes KK. Sexually transmitted diseases, 4th edn. New York: McGraw-Hill Education; 2008.[2] Bignell C, Fitzgerald M, Guideline Development Group British Association for Sexual Health and HIV UK UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS 2011; 22 541–7.
| UK national guideline for the management of gonorrhoea in adults, 2011.Crossref | GoogleScholarGoogle Scholar | 21998172PubMed |
[3] Public Health England. Sexually transmitted infections: annual data tables 2008–2017. London: Public Health England; 2018. Available online at: https://www.gov.uk/government/statistics/sexually-transmitted-infections-stis-annual-data-tables [verified 13 August 2019].
[4] Town K, Obi C, Quaye N, Chisholm S, Hughes G, Group GC. Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales. Sex Transm Infect 2017; 93 39–45.
| Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales.Crossref | GoogleScholarGoogle Scholar | 27382010PubMed |
[5] World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Geneva: WHO; 2016.
[6] Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 2014; 27 587–613.
| Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future.Crossref | GoogleScholarGoogle Scholar | 24982323PubMed |
[7] Kampmeier RH. Introduction of sulfonamide therapy for gonorrhea. Sex Transm Dis 1983; 10 81–4.
| Introduction of sulfonamide therapy for gonorrhea.Crossref | GoogleScholarGoogle Scholar | 6362039PubMed |
[8] Rosenblatt-Farrell N. The landscape of antibiotic resistance. Environ Health Perspect 2009; 117 A244–50.
| The landscape of antibiotic resistance.Crossref | GoogleScholarGoogle Scholar | 19590668PubMed |
[9] Fenton KA, Ison C, Johnson AP, Rudd E, Soltani M, Martin I, et al Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002. Lancet 2003; 361 1867–9.
| Ciprofloxacin resistance in Neisseria gonorrhoeae in England and Wales in 2002.Crossref | GoogleScholarGoogle Scholar | 12788575PubMed |
[10] Bignell CJ. BASHH guideline for gonorrhoea. Sex Transm Infect 2004; 80 330–1.
| BASHH guideline for gonorrhoea.Crossref | GoogleScholarGoogle Scholar | 15459396PubMed |
[11] Public Health England. Surveillance of antimicrobial resistance in Neisseria gonorrhoeae in England and Wales: key findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) – data to May 2018. London: Public Health England; 2018. Available online at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/746261/GRASP_2017_report.pdf [verified 13 August 2019].
[12] Whittles LK, White PJ, Didelot X. Estimating the fitness cost and benefit of cefixime resistance in Neisseria gonorrhoeae to inform prescription policy: a modelling study. PLoS Med 2017; 14 e1002416
| Estimating the fitness cost and benefit of cefixime resistance in Neisseria gonorrhoeae to inform prescription policy: a modelling study.Crossref | GoogleScholarGoogle Scholar | 29088226PubMed |
[13] Fifer H, Natarajan U, Jones L, Alexander S, Hughes G, Golparian D, et al Failure of dual antimicrobial therapy in treatment of gonorrhea. N Engl J Med 2016; 374 2504–6.
| Failure of dual antimicrobial therapy in treatment of gonorrhea.Crossref | GoogleScholarGoogle Scholar | 27332921PubMed |
[14] Eyre DW, Sanderson ND, Lord E, Regisford-Reimmer N, Chau K, Barker L, et al Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Euro Surveill 2018; 23 pii=1800323
| Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018.Crossref | GoogleScholarGoogle Scholar | 29991383PubMed |
[15] Whiley DM, Jennison A, Pearson J, Lahra MM. Genetic characterisation of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin. Lancet Infect Dis 2018; 18 717–8.
| Genetic characterisation of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin.Crossref | GoogleScholarGoogle Scholar | 29976521PubMed |
[16] Katz AR. Ceftriaxone-resistant Neisseria gonorrhoeae, Canada, 2017. Emerg Infect Dis 2018; 24 608
| Ceftriaxone-resistant Neisseria gonorrhoeae, Canada, 2017.Crossref | GoogleScholarGoogle Scholar |
[17] O’Neill LJ. Tackling drug-resistant infections globally: final report and recommendations – the Review on Antimicrobial Resistance chaired by Jim O’Neill. 2016. Available online at: https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf [verified 13 August 2019].
[18] Turner KM, Christensen H, Adams EJ, McAdams D, Fifer H, McDonnell A, et al Analysis of the potential for point-of-care test to enable individualised treatment of infections caused by antimicrobial-resistant and susceptible strains of Neisseria gonorrhoeae: a modelling study. BMJ Open 2017; 7 e015447
| Analysis of the potential for point-of-care test to enable individualised treatment of infections caused by antimicrobial-resistant and susceptible strains of Neisseria gonorrhoeae: a modelling study.Crossref | GoogleScholarGoogle Scholar | 28864707PubMed |
[19] Vickerman P, Watts C, Alary M, Mabey D, Peeling RW. Sensitivity requirements for the point of care diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in women. Sex Transm Infect 2003; 79 363–7.
| Sensitivity requirements for the point of care diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in women.Crossref | GoogleScholarGoogle Scholar | 14573829PubMed |
[20] Herbst de Cortina S, Bristow CC, Joseph Davey D, Klausner JD. A systematic review of point of care testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Infect Dis Obstet Gynecol 2016; 2016 4386127
| A systematic review of point of care testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.Crossref | GoogleScholarGoogle Scholar | 27313440PubMed |
[21] Keeling MJ, Danon L. Mathematical modelling of infectious diseases. Br Med Bull 2009; 92 33–42.
| Mathematical modelling of infectious diseases.Crossref | GoogleScholarGoogle Scholar | 19855103PubMed |
[22] Adams EJ, Ehrlich A, Turner KM, Shah K, Macleod J, Goldenberg S, et al Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK. BMJ Open 2014; 4 e005322
| Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK.Crossref | GoogleScholarGoogle Scholar | 25056977PubMed |
[23] Turner KM, Round J, Horner P, Macleod J, Goldenberg S, Deol A, et al An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England. Sex Transm Infect 2014; 90 104–11.
| An early evaluation of clinical and economic costs and benefits of implementing point of care NAAT tests for Chlamydia trachomatis and Neisseria gonorrhoea in genitourinary medicine clinics in England.Crossref | GoogleScholarGoogle Scholar | 24273127PubMed |
[24] Yorke JA, Hethcote HW, Nold A. Dynamics and control of the transmission of gonorrhea. Sex Transm Dis 1978; 5 51–6.
| Dynamics and control of the transmission of gonorrhea.Crossref | GoogleScholarGoogle Scholar | 10328031PubMed |
[25] Turner KM, Garnett GP. The impact of the phase of an epidemic of sexually transmitted infection on the evolution of the organism. Sex Transm Infect 2002; 78 i20–30.
| The impact of the phase of an epidemic of sexually transmitted infection on the evolution of the organism.Crossref | GoogleScholarGoogle Scholar | 12083443PubMed |
[26] Ghani AC, Ison CA, Ward H, Garnett GP, Bell G, Kinghorn GR, et al Sexual partner networks in the transmission of sexually transmitted diseases: an analysis of gonorrhea cases in Sheffield, UK. Sex Transm Dis 1996; 23 498–503.
| Sexual partner networks in the transmission of sexually transmitted diseases: an analysis of gonorrhea cases in Sheffield, UK.Crossref | GoogleScholarGoogle Scholar | 8946636PubMed |
[27] Chen MI, Ghani AC, Edmunds WJ. A metapopulation modelling framework for gonorrhoea and other sexually transmitted infections in heterosexual populations. J R Soc Interface 2009; 6 775–91.
| A metapopulation modelling framework for gonorrhoea and other sexually transmitted infections in heterosexual populations.Crossref | GoogleScholarGoogle Scholar | 18986961PubMed |
[28] Chen MI, Ghani AC. Republished paper: populations and partnerships: insights from metapopulation and pair models into the epidemiology of gonorrhoea and other sexually transmitted infections. Sex Transm Infect 2010; 86 iii63–9.
| 21098058PubMed |
[29] Whittles LK, White PJ, Didelot X. A dynamic power-law sexual network model of gonorrhoea outbreaks. PLOS Comput Biol 2019; 15 e1006748
| A dynamic power-law sexual network model of gonorrhoea outbreaks.Crossref | GoogleScholarGoogle Scholar | 30849080PubMed |
[30] Hui BB, Ryder N, Su JY, Ward J, Chen MY, Donovan B, et al Exploring the benefits of molecular testing for gonorrhoea antibiotic resistance surveillance in remote settings. PLoS One 2015; 10 e0133202
| Exploring the benefits of molecular testing for gonorrhoea antibiotic resistance surveillance in remote settings.Crossref | GoogleScholarGoogle Scholar | 26181042PubMed |
[31] Craig AP, Gray RT, Edwards JL, Apicella MA, Jennings MP, Wilson DP, et al The potential impact of vaccination on the prevalence of gonorrhea. Vaccine 2015; 33 4520–5.
| The potential impact of vaccination on the prevalence of gonorrhea.Crossref | GoogleScholarGoogle Scholar | 26192351PubMed |
[32] Kenyon CR, Schwartz IS. Effects of sexual network connectivity and antimicrobial drug use on antimicrobial resistance in Neisseria gonorrhoeae. Emerg Infect Dis 2018; 24 1195–203.
| Effects of sexual network connectivity and antimicrobial drug use on antimicrobial resistance in Neisseria gonorrhoeae.Crossref | GoogleScholarGoogle Scholar | 29912682PubMed |
[33] Ruf M, Delpech V, Osuagwu U, Brown AE, Robinson E, Chadborn T. Men who have sex with men: estimating the size of at-risk populations in London primary care trusts. Int J STD AIDS 2011; 22 25–9.
| Men who have sex with men: estimating the size of at-risk populations in London primary care trusts.Crossref | GoogleScholarGoogle Scholar | 21364063PubMed |
[34] Prah P, Hickson F, Bonell C, McDaid LM, Johnson AM, Wayal S, et al Men who have sex with men in Great Britain: comparing methods and estimates from probability and convenience sample surveys. Sex Transm Infect 2016; 92 455–63.
| Men who have sex with men in Great Britain: comparing methods and estimates from probability and convenience sample surveys.Crossref | GoogleScholarGoogle Scholar | 26965869PubMed |
