Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology - an infrequent but important laboratory phenomenon

Background: Treponema pallidum specific serology generally remains reactive for life. Therefore, the diagnosis of syphilis reinfection relies on clinical assessment and nontreponemal (reagin) serologic testing. The prozone phenomenon can lead to a falsely nonreactive rapid plasma reagin (RPR) assay result. Methods: We report a case of secondary syphilis in a HIV infected patient with a previous history of syphilis infection, where a falsely nonreactive RPR assay was associated with a delayed diagnosis of reinfection and infectious syphilis. The prozone phenomenon was detected in several of the patient's serum samples collected around this time. We subsequently undertook a prospective evaluation for the prozone phenomenon in 3222 consecutive sera, which were assayed using the RPR assay for clinical purposes over a 10-month period. Results: The overall rate of the prozone phenomenon was 2 out of 3222 samples (0.06%; 95% confidence interval (CI): 0.02-0.22%) and the rate per reactive sample was 2 out of 397 (0.5%; 95% CI: 0.14-1.81%). Conclusion: Clinicians should request RPR testing at dilutions of sera when syphilis is suspected clinically and the RPR assay is nonreactive.