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; C M Lowndes; S T Sadiq

doi:10.1016/j.cmi.2018.06.003

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

Clin Microbiol Infect. 2019 Mar;25(3):380.e1-380.e7. doi: 10.1016/j.cmi.2018.06.003. Epub 2018 Jun 12.

Authors

E M Harding-Esch¹, S S Fuller¹, S-L C Chow², A V Nori³, M A Harrison², M Parker⁴, O Piepenburg⁴, M S Forrest⁴, D G Brooks⁴, R Patel⁵, P E Hay⁶, N Fearnley⁷, M J Pond², J K Dunbar⁸, P D Butcher², T Planche⁹, C M Lowndes¹, S T Sadiq¹⁰

Affiliations

¹ Applied Diagnostic Research & Evaluation Unit (ADREU), Institute for Infection & Immunity, St George's University of London, London, UK; HIV/STI Department, National Infection Service, Public Health England, London, UK.
² Applied Diagnostic Research & Evaluation Unit (ADREU), Institute for Infection & Immunity, St George's University of London, London, UK.
³ Applied Diagnostic Research & Evaluation Unit (ADREU), Institute for Infection & Immunity, St George's University of London, London, UK; HIV/STI Department, National Infection Service, Public Health England, London, UK; St George's University Hospitals NHS Foundation Trust, London, UK.
⁴ TwistDx Limited, Cambridge, UK.
⁵ Department of Sexual Health, University of Southampton, Southampton, UK.
⁶ St George's University Hospitals NHS Foundation Trust, London, UK.
⁷ Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
⁸ HIV/STI Department, National Infection Service, Public Health England, London, UK.
⁹ Applied Diagnostic Research & Evaluation Unit (ADREU), Institute for Infection & Immunity, St George's University of London, London, UK; St George's University Hospitals NHS Foundation Trust, London, UK.
¹⁰ Applied Diagnostic Research & Evaluation Unit (ADREU), Institute for Infection & Immunity, St George's University of London, London, UK; HIV/STI Department, National Infection Service, Public Health England, London, UK; St George's University Hospitals NHS Foundation Trust, London, UK. Electronic address: ssadiq@sgul.ac.uk.

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.

Keywords: Chlamydia trachomatis; Diagnostic accuracy; Neisseria gonorrhoeae; Nucleic acid amplification tests; Performance evaluation; Point of care.

Publication types

Evaluation Study
Multicenter Study

MeSH terms

Adolescent
Adult
Aged
Ambulatory Care Facilities
Chlamydia trachomatis / isolation & purification*
Cross-Sectional Studies
Female
Humans
Male
Middle Aged
Neisseria gonorrhoeae / isolation & purification*
Nucleic Acid Amplification Techniques / standards*
Point-of-Care Testing*
Prospective Studies
Sensitivity and Specificity
Sexually Transmitted Diseases / diagnosis*
Specimen Handling
Young Adult

Grants and funding

G0901608/MRC_/Medical Research Council/United Kingdom