Dataset Information

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

ABSTRACT:

Background

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.

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 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.

SUBMITTER: Hui BB

PROVIDER: S-EPMC4504484 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

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

Hui Ben B BB Ryder Nathan N Su Jiunn-Yih JY Ward James J Chen Marcus Y MY Donovan Basil B Fairley Christopher K CK Guy Rebecca J RJ Lahra Monica M MM Law Mathew G MG Whiley David M DM Regan David G DG

PloS one 20150716 7

<h4>Background</h4>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.<h4>Methods and findings</h4>An individual-based mathematical model was developed to describe the transmission of gonorrhoea in a remote Indigenous population in Austr ...[more]

PMID: 26181042

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Project description:BackgroundHelicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment.Methods and findingsH. pylori was isolated from 102 patients diagnosed with gastrointestinal diseases, who underwent endoscopy at University Malaya Medical Centre (UMMC). The isolates were tested for their susceptibility on eleven antibiotics using Etest. Based on susceptibility test, 32.3% of the isolates were found to have primary metronidazole resistance; followed by clarithromycin (6.8%) and fluoroquinolones (6.8%). To further investigate the resistant strains, mutational patterns of gene rdxA, frxA, gyrA, gyrB, and 23S rRNA were studied. Consistent with the previous reports, metronidazole resistance was prevalent in the local population. However, clarithromycin, fluoroquinolone and multi-drug resistance were shown to be emerging. Molecular patterns correlated well with phenotypic data. Interestingly, multi-drug resistant (MDR) strains were found to be associated with higher minimum inhibitory concentration (MIC) than their single-drug resistant (SDR) counterparts. Most importantly, clarithromycin-resistant strains were suggested to have a higher incidence for developing multi-drug resistance.ConclusionData from this study highlighted the urgency to monitor closely the prevalence of antibiotic resistance in the Malaysian population; especially that of clarithromycin and multi-drug resistance. Further study is needed to understand the molecular association between clarithromycin resistance and multi-drug resistance in H. pylori. The report serves a reminder that a strict antibiotic usage policy is needed in Malaysia and other developing countries (especially those where H. pylori prevalence remained high).

Project description:BackgroundGonorrhoea is a highly prevalent sexually transmitted infection and an urgent public health concern because of increasing antibiotic resistance in Neisseria gonorrhoeae. Only ceftriaxone remains as the recommended treatment in the USA. With the prospect of new anti-gonococcal antibiotics being approved, we aimed to evaluate how to deploy a new drug to maximise its clinically useful lifespan.MethodsWe used a compartmental model of gonorrhoea transmission in a US population of men who have sex with men (MSM) to compare strategies for introducing a new antibiotic for gonorrhoea treatment. The MSM population was stratified into three sexual activity groups (low, intermediate, and high) characterised by annual rates of partner change. The four introduction strategies tested were: (1) random 50-50 allocation, where each treatment-seeking infected individual had a 50% probability of receiving either drug A (current drug; a ceftriaxone-like antibiotic) or drug B (a new antibiotic), effective at time 0; (2) combination therapy of both the current drug and the new antibiotic; (3) reserve strategy, by which the new antibiotic was held in reserve until the current therapy reached a 5% threshold prevalence of resistance; and (4) gradual switch, or the gradual introduction of the new drug until random 50-50 allocation was reached. The primary outcome of interest was the time until 5% prevalence of resistance to each of the drugs (the new drug and the current ceftriaxone-like antibiotic); sensitivity of the primary outcome to the properties of the new antibiotic, specifically the probability of resistance emergence after treatment and the fitness costs of resistance, was explored. Secondary outcomes included the time to a 1% resistance threshold for each drug, as well as population-level prevalence, mean and range annual incidence, and the cumulative number of incident gonococcal infections.FindingsUnder baseline model conditions, a 5% prevalence of resistance to each of drugs A and B was reached within 13·9 years with the reserve strategy, 18·2 years with the gradual switch strategy, 19·2 years with the random 50-50 allocation strategy, and 19·9 years with the combination therapy strategy. The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored and was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimise the number of annual gonococcal infections (under baseline model conditions, mean number of incident infections per year 178 641 [range 177 998-181 731] with combination therapy, 180 084 [178 011-184 405] with the reserve strategy).InterpretationOur study argues for rapid introduction of new anti-gonococcal antibiotics, recognising that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters-ie, the likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic-are available.FundingUS Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

Project description:IntroductionGonorrhoea is a disease associated with humans and caused by Neisseria gonorrhoea. N. gonorrhoea's ability to evolve and evade various treatment regimens can lead to untreatable gonorrhoea. In the absence of a viable vaccine and a national database on the antimicrobial resistance (AMR) and molecular characteristics of N. gonorrhoea, and with reliance on a syndromic management regime, continuous national antimicrobial resistance surveillance and molecular characterization of N. gonorrhoea remain imperative. Only two gonococcal studies have described N. gonorrhoea's molecular characteristics linked to AMR in Ghana.MethodsSecondary N. gonorrhoea isolates (n=4) were collected from two metropolises in Ghana: Tamale in the northern sector (n=1) and Accra in the southern sector (n=3). The isolates were confirmed and characterized using polymerase chain reaction (PCR) targeting the porB and tbpB genes, and the disc diffusion method was used to evaluate AMR. N. gonorrhoea multi-antigen sequence typing (NG-MAST) and porin B (porB) gene sequence analyses were employed to reveal the molecular epidemiology and evolutionary trajectory, respectively.ResultsAll four isolates showed resistance to at least four of the tested antibiotics. One isolate showed resistance to all seven antibiotics, i.e. ceftriaxone, azithromycin, ciprofloxacin, tetracycline, erythromycin, togamycin and penicillin. NG-MAST typing revealed isolate S3 (MZ313864) as ST211. The locus of S2 (MZ313863) (transferrin-binding protein B; tbpB) was identified as tbpB1844, and its porB locus, as porB6412, with only 4 closely related variants but with 15 nucleotide differences. However, its sequence type does not exist. The porB analysis identified isolate S3 (MZ313864) to be found globally, while S2 (MZ313863) is unique to this study.DiscussionDespite the small number of isolates tested, this study recorded multidrug resistance and previously unknown gonococcal variants based on porB gene. Additionally, the molecular typing schemes revealed a disparity between NG-MAST and the National Center for Biotechnology Information (NCBI) platforms. There is a need for continuous gonococcal AMR and molecular surveillance in Ghana to contribute to the global efforts to describe circulating strains and support proper application of the syndromic management regime to gonorrhoea.

Dataset Information

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

Background

Methods and findings

Conclusions

Publications

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

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