Overview of Reverse Sequence Syphilis Testing

Presented May 2012 at Oregon Epidemiologist Conference by Doug Harger, Manager, STD Prevention and Control Program, HIV/STD/TB Program, Center for Public Health Practice, Oregon Health Division– 971-673-0181; douglas.r.harger@state.or.us

Modifed July 23, 2012

Syphilis Testing: Something New?

There are 2 classes of blood test for syphilis

Syphilis Testing: Something New?

(1) non-treponemal, cardiolipin antibody tests—used for screening asymptomatic people and assessing response to treatment– Rapid Plasma Reagin (RPR) – Venereal Disease Research Laboratory test

(VDRL)

Syphilis Testing: Something New? (2) Treponemal tests—in US generally used as

confirmatory tests but EIA and CIA sometimes used for screening.– Fluorescent treponemal antibody absorbtion test (FTA-

ABS) – Treponema Pallidum-Particle Agglutination Test (TP-

PA)– Microhemaglutination Treponema Pallidum (MHA-

TP)– Enzyme Immunoassay (EIA)– Chemiluminescent Immunoassay (CIA) ,

Syphilis Testing Points If an individual has newly acquired

syphilis, a treponemal test generally is positive before the non-treponemal test.

Example: a person has a primary syphilitic lesion for 5 days – the FTA may be reactive and the RPR non reactive.

Traditional Sequence Testing non-treponemal test first, e.g., RPR, if

non-reactive, generally no further testing;

If RPR is reactive, the specimen is reflexed for a treponemal test, e.g., FTA, TP-PA.

Reverse Sequence Syphilis Testing

Testing serum for syphilis first with a confirmatory test, generally a treponemal EIA (enzyme immunoassay), or chemiluminescence immunoassay (CIA).

If the treponemal EIA result is non-reactive the result is reported as negative – no further testing generally recommended.

Reverse Sequence Syphilis Testing

If the treponemal EIA or CIA is reactive, the specimen is reflexed for an RPR.

If the RPR is reactive, the interpretation is past or present syphilis infection. If no treatment history—treat

Reverse Sequence Syphilis Testing

If the RPR is non-reactive after a positive EIA or CIA, the specimen should be tested reflexively with another treponeme specific test, ideally TP-PA. If the TP-PA is non-reactive, the EIA is likely a false positive.

If the TP-PA is reactive, likely represents and old infection, or possibly a very new infection.

Why Switch to EIA/CIA? Automated Lower costs No false negatives due to prozone reaction Objective results May be useful for dx of early primary

syphilis—positive earlier in infection than non-treponemal tests

Limitations of EIA/CIA Cannot distinguish between new/active

disease & old disease - treated or untreated.

Confusion about management of patients with discrepant serology – positive EIA/CIA and a negative RPR

Recent Examples Patient presents with a rash, EIA is highly

reactive > 8.0, reflexed RPR is 1:128; patient is treated as secondary syphilis.

Routine draw on a patient, EIA is reactive, reflexed RPR is non-reactive, TP-PA is non-reactive, the EIA result is considered false positive, patient not infected.

CDC Recommendations “CDC continues to recommend the

traditional syphilis screening algorithm …, however, if reverse sequence screening is used, reactive sera by a treponemal test should be tested reflexively with a quantitative non-treponemal test.” For example, a RPR.