Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multi-centre cross-sectional pre-clinical evaluation

12 Jun 2018
Harding-Esch EM, Fuller SS, Christine Chow SL, Nori AV, Harrison MA, Parker M, Piepenburg O, Forrest M, Brooks DG, Patel R, Hay P, Fearnley N, Pond MJ, Kevin Dunbar J, Butcher PD, Planche T, Lowndes CM, Tariq Sadiq S

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 (RPA)-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).

METHODS: Prospective, multi-centre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were: additional self-collected vulvo-vaginal swab (SCVS) (females); first-catch urine (FCU) aliquot (females and males). 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 RPA and routine clinic NAAT results were available for 392 males and 395 females. 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 (PPVs) 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% PPV (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 WHO ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialised, this test could positively impact clinical practice and public health.

Chlamydia trachomatis; Neisseria gonorrhoeae; Nucleic Acid Amplification Tests; Performance evaluation; Point-of-care; diagnostic accuracy