What is the frequency of false negative Neisseria gonorrhoeae (N. gonorrhoeae) and Chlamydia trachomatis (C. trachomatis) nucleic acid amplification tests (NAATs) in patients with symptoms of urethritis?

From the Guidelines

Frequency of False Negative N. gonorrhoeae and C. trachomatis NAATs

False negative N. gonorrhoeae and C. trachomatis nucleic acid amplification tests (NAATs) can occur in patients experiencing symptoms of urethritis, with reported false negative rates ranging from 10-30% for gonorrhea and 10-20% for chlamydia 1.

• The sensitivity of NAAT specimens collected from genitourinary sites for detecting chlamydia ranged from 86% to 100% in studies without major limitations 1.
• In men, testing of urine specimens was slightly more sensitive than testing of urethral specimens, with sensitivity of NAATs for gonorrhea ranging from 90% to 100% in studies without major limitations 1. Given the potential for false negatives, it is recommended to consider empirical treatment with antibiotics such as ceftriaxone 500mg IM as a single dose for gonorrhea and azithromycin 1g PO as a single dose for chlamydia, in addition to repeating the NAAT test if symptoms persist 1.

Key Considerations

• Patients should also be advised to return for follow-up evaluation if symptoms do not resolve with treatment.
• The USPSTF found convincing evidence that available screening tests can accurately diagnose chlamydial and gonococcal infections, with high sensitivity and specificity across all specimens and tests for both chlamydia and gonorrhea 1.
• NAATs have high sensitivity and specificity and are cleared by the U.S. Food and Drug Administration for use on urogenital sites, including male and female urine, as well as clinician-collected endocervical, vaginal, and male urethral specimens 1.

From the Research

Frequency of False Negative N. gonorrhoeae and C. trachomatis NAATs

• The frequency of false negative N. gonorrhoeae and C. trachomatis NAATs in patients with symptoms of urethritis is not directly stated in the provided studies.
• However, study 2 reports a case of a potential false-negative diagnosis of N. gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample.
• Study 3 evaluates the performance of non-NAAT point-of-care (POC) tests and rapid NAAT tests for chlamydia and gonorrhoea infections, and reports that the best chlamydia rapid NAAT (GeneXpert) has a sensitivity of 97.5%-98.7% and specificity of 99.4%-99.9%, while the best rapid NAAT for gonorrhoea (GeneXpert) has a sensitivity of 96%-100% and specificity of 99.9%-100%.
• Study 4 examines epidemiological risk-factors for discordant cases (NAAT positive but culture negative) and finds that women are 4-times more likely than men to have discordant cultures, and individuals tested for gonorrhoea without symptoms are 2.3 times more likely than those with symptoms to be discordant.
• Study 5 evaluates the performance of culture and NAATs for rectal chlamydial and gonococcal diagnosis, and reports that test sensitivities for N. gonorrhoeae ranged from 66.7% to 71.9% for culture to 100% for TMA, and test sensitivities for C. trachomatis ranged from 36.1% to 45.7% for culture and among NAATS from 91.4% to 95.8% for PCR to 100% for TMA.

Factors Affecting False Negative Results

• Mutations of DNA sequence in the probe region of opa-MGB assay can lead to false-negative results for N. gonorrhoeae 2.
• The NAAT method and having one week or more between NAAT and culture testing can also increase the likelihood of discordance 4.
• The use of NAATs in low-prevalence settings can lead to high numbers of false positive results 6.

Performance of NAATs

• The performance of NAATs can vary depending on the type of test and the population being tested 3, 5.
• Rapid NAATs can reduce the time to treatment by 4 days for initially untreated patients 3.
• NAATs are more sensitive for the detection of chlamydial and gonococcal infection at the rectal site than is culture 5.