Factors That Influence Confirmation of Neisseria gonorrhoeae Positivity by Molecular Methods

Abstract

Several Neisseria gonorrhoeae nucleic acid amplification tests (NAATs) with high sensitivity exist. However, the specificity of N. gonorrhoeae NAATs may be suboptimal, particularly for extragenital biospecimens. Consequently, confirmation with a second NAAT is common, although this represents a burden on resources. Furthermore, the rationale for confirmation is contentious. The objective of this work was to assess N. gonorrhoeae confirmation in over 13,000 N. gonorrhoeae screenpositive samples representing various biospecimens and three separate screening assays, the Abbott RealTime CT/NG (Abbott Molecular, Inc., Des Plaines, IL), the Cobas CT/NG test (Roche Molecular Systems Inc., Alameda, CA), and the BD ProbeTec ET CT/GC amplified DNA assay (BD Diagnostics, Sparks, MD). Factors predictive of confirmation were determined via logistic regression involving sex, year, whether the sample was formally validated, and sample site. Level of confirmation varied according to screening assay (96.2%, 86.0%, and 73.9% for the Abbott, Roche, and BD tests, respectively) in sample types formally included according to the manufacturers' instructions (i.e., validated). Sex did not affect confirmation for 2/3 assays, and the likelihood of confirmation of samples not formally included in manufacturer instructions (i.e., nonvalidated) was 89.1%, 82.1%, and 59.2% for the Abbott, Roche, and BD tests, respectively. Rectal swabs, which are nonvalidated samples, confirmed in 91.5%, 90.1%, and 87.4% of samples initially tested with the respective assays. The requirement to confirm N. gonorrhoeae in validated samples is not required for all NAATs, although initial assay-specific evaluation is justified given observed variability. Rectal samples represent robust biospecimens for N. gonorrhoeae NAAT testing and may not require confirmation when screened with the assays described.T he management of Neisseria gonorrhoeae infection represents an increasing and significant clinical burden in various settings, including the United Kingdom. ln Scotland in 2017, there were 2,610 episodes of gonorrhea, in comparison with only 1,073 cases in 2008 (1). Similar observations of an increase over the last decade have also been noted in England (2).Quantification of the magnitude of the increase as a result of changed sexual behaviors and/or shortfalls in management approaches is confounded by variability in indications for testing and the increased use of highly sensitive nucleic acid amplification tests (NAATs). Consistency of recommendations for testing practices and application of robust NAATs can support the more accurate measurement of genuine trends. Certainly, NAAT rather than culture of N. gonorrhoeae is recommended as a first-line test, and an increasing diversity of molecular tests exists. Assay-driven influences in NAAT confirmation of N. gonorrhoeae have been reported, including in a recent UK study, where 27% of samples from females did not confirm with a second-line test (3).

Confirmatory testing ofNeisseria gonorrhoeaein a sexual health clinic: implications for epidemiology and treatment policy

“…Also, BD Viper may have lower Ng-confirmation rates than other platforms. 10 In particular, isolated oropharyngeal NAAT results need to be interpreted with care.…”

Comparison of self-collected meatal swabs with urine specimens for the diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in men

“…Testing algorithms should give a minimum PPV of 90% within the local setting or population group. Even in settings where prevalence exceeds 1% (as in many sexual health clinics), it may be necessary to use a supplementary test to achieve an acceptable PPV, at least for extra-genital specimens (15,16). Where the PPV is greater than 90%, a supplementary test is not required for genital and rectal specimens.…”