Test Catalog

Test Id : NSYPH

Syphilis IgG Enzyme Immunoassay, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

An aid in the diagnosis of infection with Treponema pallidum


Routine prenatal screening


This test is not useful for diagnosis of congenital syphilis.


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


This testing should be used to assess for recent or past infection with Treponema pallidum or for routine prenatal screening.


Testing for syphilis is performed using the reverse screening algorithm at Mayo Clinic and Mayo Clinic Laboratories.

Method Name
A short description of the method used to perform the test

Enzyme Immunoassay (EIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Syphilis IgG EIA, S

Lists additional common names for a test, as an aid in searching

Syphilis G, Serum

Treponema pallidum (T. pallidum)

Specimen Type
Describes the specimen type validated for testing


Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.6 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial.


If not ordering electronically, complete, print, and send Infectious Disease Serology Test Request (T916) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Heat-inactivated specimen Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen 14 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

An aid in the diagnosis of infection with Treponema pallidum


Routine prenatal screening


This test is not useful for diagnosis of congenital syphilis.


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

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Syphilis is caused by infection with the spirochete Treponema pallidum subspecies 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 VDRL tests. Because these tests measure the host's immune response to nontreponemal 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-absorption (FTA-ABS) or microhemagglutination (MHA-TP) assay. Although the FTA-ABS and MHA-TP assays 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, many laboratories utilize the reverse syphilis screening algorithm. This algorithm starts with an automated treponemal assay to detect antibodies specific to T pallidum. If this screening assay is positive, the sample is reflexed for testing by RPR, 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 (TP-PA) assay. If the TP-PA is positive, this would indicate previously treated or late-stage syphilis infection. Alternatively, if the TP-PA is negative, the initial positive screen is interpreted as a false-positive result.


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


In some patients, the results of the treponemal screening test and RPR may be discordant (eg, syphilis IgG 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, TP-PA).


In the setting of a positive syphilis IgG screening result and a negative RPR, a positive TP-PA result is consistent with either 1) past, successfully treated syphilis, 2) early syphilis with undetectable RPR, or 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)


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


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

Test and result

Patient history

Syphilis IgG Ab by EIA





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 Centers for Disease Control and Prevention 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


EIA, enzyme immunoassay; NA, not applicable; RPR, rapid plasma reagin; TP-PA, Treponema pallidum particle agglutination

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Reference values apply to all ages

Provides information to assist in interpretation of the test results


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



Recommend follow-up testing in 10 to 14 days if clinically indicated.



Results suggest infection with T pallidum at some point in time. Results do not distinguish between recent or past infection, or between treated and untreated syphilis as treponema-specific IgG may remain elevated despite appropriate therapy. Falsely reactive treponemal results may occur; additional testing by a non-treponemal assay is recommended if not previously performed on this sample.

Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Despite active syphilis, serologic tests may be negative in severely immunosuppressed patients such as those with AIDS.


In very early cases of primary syphilis, serology tests may be negative.


In cases of untreated, late or latent syphilis, the result of rapid plasma reagin may be negative. However, the syphilis screening enzyme immunoassay (EIA) and Treponema pallidum particle agglutination (TP-PA) should be positive. A thorough clinical and historical evaluation should be performed to determine if treatment for latent syphilis is required.


Results should be considered in the context of all available clinical and laboratory data.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Centers for Disease Control and Prevention (CDC): Discordant results from reverse sequence syphilis screening-five laboratories, United States, 2006-2010. Morb Mortal WKLY Rep. 2011 Feb 11;60(5):133-137

2. Radolf JD, Tramont EC, Salazar JC: Syphilis (Treponema pallidum). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:2865-289291

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

Method Description
Describes how the test is performed and provides a method-specific reference

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday, Sunday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

Same day/1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test


Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US 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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NSYPH Syphilis IgG EIA, S 47238-1
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
NSYPH Syphilis IgG EIA, S 47238-1

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
New Test 2022-01-25