False‐Positive Gonorrhea Test Results with a Nucleic Acid Amplification Test: The Impact of Low Prevalence on Positive Predictive Value

Abstract

Five false-positive gonorrhea test results from a private laboratory using a nucleic acid amplification test led to an investigation by the Hawaii State Department of Health. No unexplained increase or variation in the laboratory's positive gonorrhea test results was detected. The proportion of positive gonorrhea test results among tests performed in the population was 1.06%. The calculated positive predictive value (PPV) of the test in this setting was 60%. Documentation of sexual histories was lacking for all cases. It is imperative to obtain a sexual history for both assessing sexually transmitted disease (STD) risk and interpreting STD test results. The possibility that positive test results may be false should be considered when patients have unanticipated positive test results. Clinicians who perform STD screening tests should know the approximate prevalence of STDs in the population being screened and have a conceptual understanding of PPV and the impact of low prevalence on screening tests with imperfect specificity.

Specific andSensitive Detection of Neisseria gonorrhoeae in ClinicalSpecimens by Real-Time PCR

“…This confirms that the COBAS AMPLICOR test produces false-positive results and needs a subsequent confirmation assay(s) (12,15,30,38). In addition to the 36 16S rRNA-positive (and opa assay-positive) samples, the opa assay showed three more samples as positive.…”

“…In addition, their application is often restricted to specific specimen types due to limited validation of the assays. The COBAS AMPLICOR test for N. gonorrhoeae (COBAS AMPLICOR CT/NG; Roche Diagnostics Nederland BV, Almere, The Netherlands), for instance, produces false-positive results with certain nonpathogenic Neisseria species (Neisseria subflava and Neisseria cinerea) and lactobacilli, and a subsequent confirmation test is necessary (5,12,15,30,38). CppB-and 16S rRNA gene-based assays are used for confirmation (35); however, about 5% of N. gonorrhoeae strains do not carry the CppB plasmid (5, 7), and not all 16S rRNA-based tests are sensitive and specific enough (12,39).…”

Nucleic Acid Amplification Testing for Neisseria gonorrhoeae

“…In particular, positive predictive values can be unacceptably low in populations in which the prevalence of N. gonorrhoeae is low. 10,70 A simplified explanation for this is provided by Klausner 71 : if the specificity of a N. gonorrhoeae NAAT is 99.5%, then 0.5% of positive results will be false-positive results. Therefore, if the rate of test positivity in the population is 1.0%, then one-half of the observed positive results may be false-positive results, providing a positive predictive value of only 50%.…”

Evaluation of CDC-Recommended Approaches for Confirmatory Testing of Positive Neisseria gonorrhoeae Nucleic Acid Amplification Test Results

“…The majority of laboratories use either the ProbeTec (strand displacement amplification [SDA]) (Becton Dickinson Co., Sparks, MD) or the Aptima Combo 2 (AC2) (Gen-Probe Inc., San Diego, CA) assay, and fewer use the Amplicor (PCR) (Roche Diagnostics Corp., Branchburg, NJ) test. Although NAATs are commonly used, there have been some concerns about test specificity, particularly in low-prevalence populations, where the positive predictive values (PPVs) would be negatively impacted (5,10,13). False-positive (FP) results can occur with SDA and PCR, as their target may cross-react with several different species of Neisseria (N. cinerea, N. flavescens, N. lactamica, N. subflava, and N. sicca) (6,19).…”