Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings

RESEARCH ARTICLE Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings Ben B. Hui1*, Nathan Ryder2, Jiunn-Yih Su2, James Ward3, Marcus Y. Chen4,5,6, Basil Donovan1,7, Christopher K. Fairley4,5,6, Rebecca J. Guy1, Monica M. Lahra8, Mathew G. Law1, David M. Whiley9,10, David G. Regan1 1 The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia, 2 Sexual Health and Blood Borne Virus Unit, Centre for Disease Control, Department of Health, Darwin, Northern Territory, Australia, 3 South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia, 4 Central Clinical School, Monash University, Melbourne, Victoria, Australia, 5 Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia, 6 School of Population and Global Health, University of Melbourne, Melbourne, Australia, 7 Sydney Sexual Health Centre, Sydney Hospital, Sydney, New South Wales, Australia, 8 WHO Collaborating Centre for STD, Microbiology Department, South Eastern Area Laboratory Services, Prince of Wales Hospital, Sydney, New South Wales, Australia, 9 Queensland Paediatric Infectious Diseases Laboratory, Queensland Children’s Health Services, Queensland, Australia, 10 Queensland Children’s Medical Research Institute, University of Queensland, Queensland, Australia * OPEN ACCESS Citation: Hui BB, Ryder N, Su J-Y, Ward J, Chen MY, Donovan B, et al. (2015) Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings. PLoS ONE 10(7): e0133202. doi:10.1371/journal. pone.0133202 Abstract Editor: William M. Switzer, Centers for Disease Control and Prevention, UNITED STATES Surveillance for gonorrhoea antimicrobial resistance (AMR) is compromised by a move away from culture-based testing in favour of more convenient nucleic acid amplification test (NAAT) tests. We assessed the potential benefit of a molecular resistance test in terms of the timeliness of detection of gonorrhoea AMR. Received: December 11, 2014 Accepted: June 24, 2015 Background Published: July 16, 2015 Copyright: © 2015 Hui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by National Health and Medical Research Council Project Grants (APP1025517). The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, University of New South Wales. The views expressed in this publication do not necessarily represent the position of the Australian Government. Methods and Findings An individual-based mathematical model was developed to describe the transmission of gonorrhoea in a remote Indigenous population in Australia. We estimated the impact of the molecular test on the time delay between first importation and the first confirmation that the prevalence of gonorrhoea AMR (resistance proportion) has breached the WHO-recommended 5% threshold (when a change in antibiotic should occur). In the remote setting evaluated in this study, the model predicts that when culture is the only available means of testing for AMR, the breach will only be detected when the actual prevalence of AMR in the population has already reached 8 – 18%, with an associated delay of ~43 – 69 months between first importation and detection. With the addition of a molecular resistance test, the number of samples for which AMR can be determined increases facilitating earlier detection at a lower resistance proportion. For the best case scenario, where AMR can be determined for all diagnostic samples, the alert would be triggered at least 8 months earlier than using PLOS ONE | DOI:10.1371/journal.pone.0133202 July 16, 2015 1 / 14 Benefits of Molecular Resistance Tests for Gonorrhoea Competing Interests: The authors have declared that no competing interests exist. culture alone and the resistance proportion will have only slightly exceeded the 5% notification threshold. Conclusions Molecular tests have the potential to provide more timely warning of the emergence of gonorrhoea AMR. This in turn will facilitate earlier treatment switching and more targeted treatment, which has the potential to reduce the population impact of gonorrhoea AMR. Introduction The gonorrhoea rate is disproportionately high in some Indigenous populations in remote Australia compared with urban areas, with rates reported to be up to 35 times higher [1, 2]. Prevalence of 7–8% has been reported for 16–34 years old and even higher for 16–19 year olds at more than 10% [3]. Currently, most gonorrhoea infections diagnosed in remote Indigenous communities are sensitive to and treated with penicillin, whereas the predominant gonorrhoea strains circulating in urban Australia and neighbouring countries are resistant to penicillin [4]. It is therefore likely that penicillin-resistant gonorrhoea will eventually be introduced and take hold within remote communities and will compromise the effectiveness of existing control strategies. Strengthening surveillance for antimicrobial resistance (AMR) in settings where gonorrhoea prevalence is high is a key strategy of the World Health Organisation (WHO) [5] and this is necessarily a bacterial culture-based activity. However 50–90% of the gonorrhoea infections from remote regions are diagnosed using nucleic acid amplification tests (NAAT) [6–9] primarily because of distance and transport considerations as well as the convenience and sensitivity of NAAT-based diagnosis. With the increasing trend toward use of NAAT for diagnosis, the number of samples available for culture is expected to reduce even further, possibly to a level that will not be adequate or sufficiently representative for AMR surveillance [10]. Molecular tests specifically designed to identify genetic mutations that confer resistance have the potential to enhance AMR surveillance by improving coverage and representativeness [11]. For example, a molecular test to detect penicillinase-producing Neisseria gonorrhoeae (PPNG) has been recently described [12] and is now in use to enhance the surveillance of penicillin resistance in remote Western Australia where a penicillin-based treatment strategy is in use. Data from the PPNG NAAT-based surveillance is used to inform clinical guidelines for this region [9]. The widespread use of such tests on diagnostic samples could enhance AMR surveillance and enable a more timely response to the emergence of treatment-resistant gonorrhoea. The WHO guidelines for STI management state that a treatment should have a 95% cure rate to be considered effective. [5]. By implication, when the treatment fai (...truncated)