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Background: The Centers for Disease Control and Prevention (CDC) recommends syphilis screening with a nontreponemal test followed by a confirmatory, more specific, treponemal test. However, widely available automated enzyme immunoassays (EIAs) have led many laboratories to adopt a “reverse sequence” approach. As treponemal antibodies appear earlier, the “reverse sequence” should have greater sensitivity. We present two case reports highlighting potential problems with the reverse sequence approach.
Methods: n/a
Results: (Case Reports): Case 1 was a 37 year old HIV-infected male seen 24 September 2015 with a rash suspected of being secondary syphilis. His serologic test results were: RPR reactive, VDRL reactive 1:32, and EIA nonreactive. Restest on 1 October demonstrated identical results. Patient was treated 16 October with 2.4 mU benzathine Penicillin G IM. Upon retest, 26 December 2015, EIA remained nonreactive while the VDRL showed a 4-fold titer decrease (1:8). A serum aliquot tested at the CDC revealed: RPR reactive 1:16, TPPA reactive, and EIA nonreactive. Case 2 was a 20 year old HIV-infected male seen 7 November 2015 with a history of recent contact to primary syphilis. His syphilis screening test revealed EIA nonreactive, reactive RPR and reactive VDRL 1:1. He was not treated. On follow-up, 7 January 2016, retesting revealed RPR reactive, VDRL 1:256; EIA was now reactive. Patient reported that within one week of his initial visit, he developed a penile lesion. He was treated with 2.4 mU benzathine penicillin G IM.
Conclusions: Case 1 is a documented false-negative EIA result while Case 2 appears to be a delayed EIA seroconversion. Both cases would be missed with the “reverse sequence” approach. While the EIA is considered more sensitive and specific than nontreponemal tests, one must keep a high index of suspicion for syphilis especially in HIV co-infected case-patients. The TP-PA test is currently considered the most valid confirmatory treponemal test.