Test Id : RRPRS

If the rapid plasma reagin (RPR) screen is positive, then the RPR titer will be performed at an additional charge.

If the RPR screen is negative, then syphilis antibody Treponema pallidum particle agglutination testing will be performed at an additional charge.

Only orderable as a reflex. For more information see SYPH1 / Syphilis IgG with Reflex, Enzyme Immunoassay, Serum

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Information: Centrifuge and aliquot serum into plastic vial.

• Syphilis Serology Algorithm

0.4 mL

Aid for the diagnosis of infection with Treponema pallidum

Rapid plasma reagin testing following a positive treponemal antibody test

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

If the rapid plasma reagin (RPR) screen is positive, then the RPR titer will be performed at an additional charge.

If the RPR screen is negative, then syphilis antibody Treponema pallidum particle agglutination testing will be performed at an additional charge.

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 nontreponemal 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 infections. 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:

Only orderable as a reflex. For more information see SYPH1 / Syphilis IgG with Reflex, Enzyme Immunoassay, Serum.

Negative

Reference values apply to all ages

Negative:

Treponema pallidum-particle agglutination has been ordered to distinguish between infection with T pallidum (syphilis) versus a falsely reactive treponemal antibody result.

Positive:

Specimen reflexed to determine rapid plasma reagin titer value.

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 for syphilis may be negative.

In cases of untreated, late or latent syphilis, the result of rapid plasma reagin may be negative. However, the syphilis screening using a treponemal assay, including the Treponema pallidum particle agglutination test, 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.

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. 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; 2020:2865-2892

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;50(1):148-150. doi:10.1128/JCM.05636-11

If the IgG result is equivocal or reactive, a rapid plasma reagin (RPR) screen is performed manually. If the RPR screen is positive the RPR titer is performed manually. The RPR titer test is a macroscopic screening assay done with unheated serum. Reagin reacts with nontreponemal antigen containing colloidal charcoal particles. This reaction results in a visual flocculation of the black particles against the white card background. The test yields a positive or negative result, and all positive samples are titered to determine the highest positive dilution.(Huber TW, Storms S, Young P, et al. Reactivity of microhemagglutination, fluorescent treponemal antibody absorption, Venereal Disease Research Laboratory, and rapid plasma reagin tests in primary syphilis. J Clin Microbiol. 1983;17[3]:405-409; Kaur G, Kaur P. Syphilis testing in blood donors: an update. Blood Transfus. 2015;13[2]:197-204)

If the RPR screen is negative, the Serodia Treponema pallidum particle agglutination (TP-PA) test is performed. The TP-PA test is based on the agglutination of colored gelatin particle carriers sensitized with T pallidum (Nichols Strain) antigen. Serum samples are serially diluted in microplate wells. Sensitized gelatin particles are added to respective wells and the contents of the plate mixed. The mixture is incubated for 2 hours at ambient temperature. Serum containing specific antibodies will react with the antigen-sensitized colored gelatin particles to form a smooth mat of agglutinated particles in the microplate well. A compact button formed by the settling of the non-agglutinated particles characterizes negative reactions. The agglutination patterns are read visually to determine interpretation.(Package insert: Serodia TP-PA. Fujirebio Diagnostics, Inc; 04/2015)

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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.

86592-Rapid Plasma Reagin Screen

86593-Rapid Plasma Reagin Titer (if appropriate)

86780-Syphilis Antibody by TP-PA (if appropriate)