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Test ID SYPHT Syphilis Total Antibody with Reflex, Serum

Specimen Required

Collection Container/Tube: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Instructions: Centrifuge and aliquot serum

Useful For

Aiding in the diagnosis of recent or past Treponema pallidum infection


Routine prenatal screening


This test is not offered as a screening or confirmatory test for blood donor specimens.


This test is not useful for diagnosis of congenital syphilis.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
RPRS RPR Screen w/ Reflex, S No No
RTPPA Syphilis Ab, TP-PA, S Yes, (Order TPPA) No
RRPRQ RPR Titer, S No No
SYPNB Syphilis Total Ab Bill Only 1 No, (Bill Only) No

Testing Algorithm

Total syphilis billing will be captured under SYPNB.


If total syphilis is reactive or equivocal, then rapid plasma reagin (RPR) will be performed at an additional charge.


If RPR screen is reactive, then RPR titer will be performed at an additional charge.


If RPR screen is nonreactive, then syphilis antibody will be performed at an additional charge.


See Syphilis Serology Algorithm in Special Instructions.

Special Instructions

Method Name

SYPHT: Multiplex Flow Immunoassay

RPRS, RRPRQ: Flocculation/Agglutination

RTPPA: Particle Agglutination

Reporting Name

Syphilis Total Ab w/ Reflex, S

Specimen Type


Specimen Minimum Volume

0.4 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
  Frozen  14 days

Clinical Information

Syphilis is a disease caused by infection with the spirochete Treponema pallidum. The infection is systemic and the disease is characterized by periods of latency. These features, together with the fact that T pallidum cannot be isolated in culture, mean that serologic techniques play a major role in the diagnosis and follow-up of treatment for syphilis.


Historically, the serologic testing algorithm for syphilis included an initial non-treponemal screening test, such as the rapid plasma reagin (RPR) or the Venereal Disease Research Laboratory (VDRL) tests. Because these tests measure the host's antibody response to non-treponemal antigens, they lack specificity. Therefore, a positive result by RPR or VDRL requires confirmation by a treponemal-specific test, such as the fluorescent treponemal antibody-absorbed (FTA-ABS) or microhemagglutination assay (MHA-TP). Although the FTA-ABS and MHA-TP are technically simple to perform, they are labor intensive and require subjective interpretation by testing personnel.


As an alternative to the traditional syphilis screening algorithm as described above, many laboratories utilize the reverse syphilis screening algorithm. This algorithm starts with an automated treponemal assay, such as an enzyme immunoassay (EIA) and multiplex flow immunoassay (MFI), to detect antibodies specific to T pallidum. If the screening assay is positive, the sample is reflexed to a RPR assay, which if positive is reported with a titer and is indicative of active or recent syphilis infection. If the RPR is negative, the sample is reflexed to a second treponemal assay, such as the T pallidum particle agglutination (TPPA) assay. If the TPPA is positive, this would indicate previously treated or late stage syphilis infection. Alternatively, if the TPPA is negative, the initial positive screen is interpreted as a false positive result.


Syphilis screening at Mayo Clinic is performed by using the reverse algorithm, which first tests sera for T pallidum specific IgG/IgM antibodies using an automated MFI. A positive treponemal test suggests infection with T pallidum, but does not distinguish between recent or past, or treated and untreated infection. This is because treponemal tests may remain reactive for life, even following adequate therapy. Therefore, the results of a non-treponemal assay, such as RPR, are needed to provide information on a patient's disease state and history of therapy.(Table 1)


In some patients, the results of the treponemal screening test and RPR may be discordant (eg, syphilis IgG/IgM positive and RPR negative). To discriminate between a falsely reactive screening result and past syphilis, a second treponemal-specific antibody test is recommended using a method that is different from the initial screen test (eg, TPPA).


In the setting of a positive syphilis IgG/IgM screening result and a negative RPR, a positive TPPA result is consistent with either:

1. Past, successfully treated syphilis

2. Early syphilis with undetectable RPR titers

3. Late/latent syphilis in patients who do not have a history of treatment for syphilis

Further historical evaluation is necessary to distinguish between these scenarios.(Table 1)


In the setting of a positive syphilis IgG/IgM screening result and a negative RPR, a negative TP-PA result is most consistent with a falsely reactive syphilis IgG/IgM screen.(Table 1) If syphilis remains clinically suspected, a second specimen should be submitted for testing.

Table 1. Interpretation and follow-up of reverse screening results:

Test and result

Patient history

Syphilis total Ab by MFI





Unknown history of syphilis




No serologic evidence of syphilis

None, unless clinically indicated (eg, early/acute/primary syphilis)

Unknown history of syphilis




Untreated or recently treated syphilis

See CDC treatment guidelines 

Unknown history of syphilis




Probable false-positive screening test

No follow-up testing, unless clinically indicated (eg, acute/primary syphilis)

Unknown history of syphilis




Possible syphilis (eg, early or latent) or previously treated syphilis

Historical and clinical evaluation required

Unknown history of syphilis





Unknown history of syphilis

Known history of syphilis



Reactive or NA

Past, successfully treated syphilis


MFI, multiplex flow immunoassay; NA, not applicable; RPR, rapid plasma reagin; TP-PA, Treponema pallidum particle agglutination


Reference Values













Reference values apply to all ages



No serologic evidence of infection to Treponema pallidum (syphilis). Repeat testing may be considered in patients with suspected acute or primary syphilis in 2 to 4 weeks.



Rapid plasma reagin (RPR) has been ordered to help distinguish between infection with T pallidum (syphilis) versus a falsely reactive treponemal antibody result.



RPR has been ordered to help distinguish between infection with T pallidum (syphilis) versus a falsely reactive treponemal antibody result.

Clinical Reference

1. Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening-five laboratories, United States, 2006-2010. MMWR Morb Mortal WKLY Rep 2011;60(5):133-137

2. Tramont EC: Treponema pallidum (Syphilis). In: Mandell GL, Bennet JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Churchill Livingstone; 2000:2474-2491

3. Binnicker MJ, Jespersen DJ, Rollins LO: Direct comparison of the traditional and reverse syphilis screening algorithms in a population with a low prevalence of syphilis. J Clin Microbiol. 2012 Jan;50(1):148-150

Day(s) and Time(s) Performed

Monday through Saturday; 9 a.m.

Analytic Time

Same day/1 day

Test Classification

This test has been cleared, approved or is exempt by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information


86592 (if appropriate)

86780 (if appropriate)

86593 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SYPHT Syphilis Total Ab w/ Reflex, S 47236-5


Result ID Test Result Name Result LOINC Value
SYPHT Syphilis Total Ab w/ Reflex, S 47236-5


If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-General Request (T239)

-Microbiology Test Request (T244)