Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation

E. M. Harding-Esch, S. S. Fuller, S. L.C. Chow, A. V. Nori, M. A. Harrison, M. Parker, O. Piepenburg, M. S. Forrest, D. G. Brooks, R. Patel, P. E. Hay, N. Fearnley, M. J. Pond, J. K. Dunbar, P. D. Butcher, T. Planche, Catherine Lowndes, S. T. Sadiq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Objectives: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification–based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Methods: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. Results: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4–100.0; 356/357), 97.1% positive predictive value (95% CI 84.7–99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1–100; 29/29) than for SCVS (96.4%; 95% CI, 81.7–99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). Conclusions: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

Original languageEnglish
Pages (from-to)380.e1-380.e7
JournalClinical Microbiology and Infection
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2019

Bibliographical note

Funding Information:
Funded by TwistDx, St George's, University of London; and by a UK Clinical Research Collaboration , Translational Infection Research Initiative Consortium Grant (grant G0901608 ). STS reports on behalf of himself and colleagues of the SGUL ADREU grants from UKCRC, other from TwistDx; and RP, PH and NF declare CLRN support to conduct portfolio research during the conduct of the study. STS declares the following relevant financial activities outside the submitted work: other from Atlas Genetics Ltd, other from Alere, other from Cepheid, other from SpeeDx, other from Sekisui, grants from Innovate UK, grants from National Institute for Health Research. MP, OP, MSF and DGB are employees of TwistDx. Advisory board membership is declared by EHE, SF, RP and PH for Becton Dickinson; by RP for Roche, Novartis, GSK, Genoccea and CLJC; and by PH for Hologic and Bayer Consumer Healthcare, outside the submitted work. In addition, MP has a patent EP2029782 issued, a patent EP2426221 issued; and OP has a patent 7 666 598 issued (not owned by the author) and a patent 9 663 820 issued (not owned by the author). The other authors report no conflicts of interest relevant to this article.

Funding Information:
We thank all the participants for taking part and the staff who recruited them to the study, including J. Turpitt (Solent NHS Trust) and P. Sharratt (Bradford Teaching Hospitals NHS Foundation Trust). We would also like to thank A. Nardone and R. Howell-Jones, Public Health England, their input within the ?Electronic self-testing instrumentation for sexually transmitted infections? (eSTI2) consortium. We thank H. Mohammed, Public Health England, for providing national GUMCAD 2014 prevalence data and S. Clifton, University College London, for providing The National Survey of Sexual Attitudes and Lifestyles 3 (Natsal-3) ? weighted prevalence data. ADREU also acknowledges the support of the UK National Institute of Health Research Clinical Research Network (UKCRN). This study was included in the UKCRN ID 15136 ?Patient-consented samples for STI diagnostic & biomarker evaluation? database.Funded by TwistDx, St George's, University of London; and by a UK Clinical Research Collaboration, Translational Infection Research Initiative Consortium Grant (grant G0901608). STS reports on behalf of himself and colleagues of the SGUL ADREU grants from UKCRC, other from TwistDx; and RP, PH and NF declare CLRN support to conduct portfolio research during the conduct of the study. STS declares the following relevant financial activities outside the submitted work: other from Atlas Genetics Ltd, other from Alere, other from Cepheid, other from SpeeDx, other from Sekisui, grants from Innovate UK, grants from National Institute for Health Research. MP, OP, MSF and DGB are employees of TwistDx. Advisory board membership is declared by EHE, SF, RP and PH for Becton Dickinson; by RP for Roche, Novartis, GSK, Genoccea and CLJC; and by PH for Hologic and Bayer Consumer Healthcare, outside the submitted work. In addition, MP has a patent EP2029782 issued, a patent EP2426221 issued; and OP has a patent 7 666 598 issued (not owned by the author) and a patent 9 663 820 issued (not owned by the author). The other authors report no conflicts of interest relevant to this article.

Funding Information:
We thank all the participants for taking part and the staff who recruited them to the study, including J. Turpitt (Solent NHS Trust) and P. Sharratt (Bradford Teaching Hospitals NHS Foundation Trust). We would also like to thank A. Nardone and R. Howell-Jones, Public Health England, their input within the “Electronic self-testing instrumentation for sexually transmitted infections” (eSTI 2 ) consortium. We thank H. Mohammed, Public Health England, for providing national GUMCAD 2014 prevalence data and S. Clifton, University College London, for providing The National Survey of Sexual Attitudes and Lifestyles 3 (Natsal-3) – weighted prevalence data. ADREU also acknowledges the support of the UK National Institute of Health Research Clinical Research Network (UKCRN). This study was included in the UKCRN ID 15136 ‘Patient-consented samples for STI diagnostic & biomarker evaluation’ database.

Publisher Copyright:
© 2018 The Authors

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Chlamydia trachomatis
  • Diagnostic accuracy
  • Neisseria gonorrhoeae
  • Nucleic acid amplification tests
  • Performance evaluation
  • Point of care

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