Review of the Performance of Laboratory-Based Molecular Diagnostics for Chlamydia trachomatis and Neisseria...

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most commonly reported sexually transmitted infections (STIs) in the United States, and their accurate diagnosis is critical for preventing serious health outcomes. Nucleic acid amplification tests (NAATs) are still considered the gold standard for the laboratory diagnosis of chlamydia and gonorrhea due to their high sensitivity and specificity. Since the 2014 CDC laboratory recommendations, several key improvements to FDA-cleared NAATs have been made including expanded specimen types, technology, and process improvements.

We conducted a systematic literature search and a narrative review focused on the performance of laboratory-based molecular diagnostics for CT and NG. This systematic review evaluated 145 studies to assess current diagnostic performance, focusing on six key areas: FDA-cleared diagnostic NAATs, self-collected specimens, pooling strategies, time to negativity, confirmatory/repeat testing, and LGV diagnostics.

Many assays now include claims for clinician-collected extragenital specimens and self-collected vaginal swabs with high sensitivity (>90%) and specificity (>98%), and the recent FDA authorization of the first self-collection kit for nonclinical settings represents a major milestone in STI care access. However, no NAATs currently have claims for patient-collected extragenital specimens, despite strong evidence of comparable performance and high patient acceptability. Newer versions of assays incorporate dual targets for both CT and NG to enhance positive predictive value and reduce diagnostic escape. While no FDA-cleared assays exist for LGV differentiation, several laboratory-developed tests show promise.

Future directions include expanding FDA clearance for self-collected extragenital specimens and developing viability assays to better distinguish active infection from residual nucleic acids. Together, these advances underscore the progress in CT/NG testing and highlight opportunities to further improve diagnostic reach and clinical relevance.