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Treponema pallidum cannot be cultured. Ideally, early syphilis could be diagnosed by direct detection methods, such as darkfield examination, but these methods are often not available and may miss up to 30% of primary cases. Therefore, syphilis is usually diagnosed with serologic tests.
Traditional serologic screening for syphilis uses nontreponemal testing initially with confirmation of reactive results using a treponemal test. New “reverse algorithms” are gaining popularity due to the development of point-of-care CIA/EIA tests. Reverse algorithms use treponemal testing initially (usually EIA or CIA) with confirmation of reactive results using a nontreponemal test.
Traditional versus reverse algorithm syphilis testing pros and cons (see table below)
| Traditional versus Reverse Algorithm Syphilis Testing (Pros and Cons) | ||
Traditional testing Begins with nontreponemal testing (quantitative) | Reverse testing Begins with treponemal testing (qualitative) | |
| Pros |
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| Cons |
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| Source: http://www.cdc.gov/std/syphilis/Syphilis-Webinar-Slides.pdf | ||
Nontreponemal and treponemal tests (see table below)
| Nontreponemal and Treponemal Tests | |
| Nontreponemal Tests (Quantitative) | ARUP Tests Available |
| Rapid Plasma Reagin (RPR) with Reflex to Titer and TP-PA Confirmation 0050478 Rapid Plasma Reagin (RPR) with Reflex to RPR Titer or T. pallidum Antibody by Particle Agglutination 2007443 Rapid Plasma Reagin (RPR) with Reflex to Titer 0050471 Treponema pallidum (VDRL), Serum with Reflex to Titer 0093093 |
| Treponemal Tests (Qualitative/Semi-Quantitative) | ARUP Tests Available |
| Treponema pallidum Antibody by TP-PA 0050777 Treponema pallidum Antibody, IgM by ELISA 0050921 Treponema pallidum Antibody, IgG by Immunoblot 2003095 Treponema pallidum Antibody, IgG by ELISA 0050920 |
Treponema pallidum subspecies pallidum is the causative agent of syphilis, a sexually transmitted infection (STI).
Tests generally appear in the order most useful for common clinical situations
| Test name: Rapid Plasma Reagin (RPR) with Reflex to Titer and TP-PA Confirmation |
| ARUP #: 0050478 |
| Methodology: Semi-Quantitative Charcoal Agglutination/Semi-Quantitative Particle Agglutination |
| Use: CDC recommended test for the screening and diagnosis of syphilis Reactive results reflex to titer and treponemal test (TP-PA) for confirmation |
| Test name: Rapid Plasma Reagin (RPR) with Reflex to Titer |
| ARUP #: 0050471 |
| Methodology: Semi-Quantitative Charcoal Agglutination |
| Use: Order to screen for syphilis; for initial diagnosis, reactive results should be confirmed with a treponemal test (eg, TP-PA) Use to confirm reactive treponemal test (eg, CIA, EIA) if using so-called reverse algorithm testing Preferred test for monitoring treatment response in established syphilis |
| Limitations: False positives may be caused by HIV, herpes simplex virus (HSV), malaria, intravenous drug use (IVDU), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), pregnancy, leprosy, endemic treponematoses |
| Test name: Treponema pallidum (VDRL), Serum with Reflex to Titer |
| ARUP #: 0093093 |
| Methodology: Semi-Quantitative Flocculation |
| Use: Acceptable initial screening test for syphilis May use to confirm reactive treponemal test (eg, EIA, CIA) if using so-called reverse algorithm testing Acceptable test for monitoring treatment response in established syphilis |
| Limitations: Use rapid plasma reagin (RPR) preferentially to decrease false-positive rate False positives may be caused by HIV, HSV, malaria, IVDU, SLE, RA, pregnancy, leprosy, endemic treponematoses |
| Test name: Rapid Plasma Reagin (RPR) with Reflex to RPR Titer or T. pallidum Antibody by Particle Agglutination |
| ARUP #: 2007443 |
| Methodology: Semi-Quantitative Charcoal Agglutination/Semi-Quantitative Particle Agglutination |
| Use: Order to confirm a reactive treponemal screening test (eg, CIA, EIA) when using the reverse testing algorithm to screen for syphilis For traditional CDC recommended algorithm, refer to Rapid Plasma Reagin (RPR) with Reflex to Titer and TP-PA Confirmation |
| Test name: Treponema pallidum Antibody, IgG by ELISA |
| ARUP #: 0050920 |
| Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay |
| Use: Recommended syphilis screening test in so-called reverse screening algorithm Abnormal results require confirmation by a nontreponemal test (ie, RPR or VDRL) The CDC recommends a nontreponemal test (ie, RPR or VDRL) for initial syphilis screening prior to confirmation with a treponemal test (eg, TP-PA) |
| Test name: Treponema pallidum Antibody by TP-PA |
| ARUP #: 0050777 |
| Methodology: Semi-Quantitative Particle Agglutination |
| Use: CDC recommended confirmatory test for syphilis Order to confirm syphilis if initial screening (eg, RPR, VDRL) is reactive |
| Limitations: Cannot differentiate between IgG and IgM antibodies Compares favorably to FTA test but slightly less sensitive in untreated early primary syphilis Cannot be tested with CSF |
| Test name: Treponema pallidum Antibody, IgM by ELISA |
| ARUP #: 0050921 |
| Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay |
| Use: Aids in workup of suspected congenital syphilis Confirm reactive nontreponemal syphilis screening test (ie, RPR or VDRL) Primary screening for syphilis in so-called reverse screening algorithm Monitor serological response to treatment in RPR/VDRL negative primary syphilis |
| Limitations: Congenital syphilis - sensitivity is ~80%; therefore, negative IgM does not rule out congenital syphilis |
| Test name: Treponema pallidum Antibody, IgG by Immunoblot |
| ARUP #: 2003095 |
| Methodology: Qualitative Immunoblot |
| Use: Recommended supplementary confirmatory test for syphilis in so-called reverse screening algorithm Use when a reactive EIA screening test is not confirmed by the TP-PA test or a reactive TP-PA screening test is not confirmed by the EIA test |
| Limitations: Do not use to determine relapse or reinfection of syphilis because of the persistence of reactivity, likely for life |
| Follow-up: Repeat testing in 2-4 weeks is recommended if results are equivocal |
| Test name: Treponema pallidum Antibody (FTA-ABS), Serum, IgG by IFA with Reflex to Treponema pallidum Antibody by TP-PA |
| ARUP #: 0050477 |
| Methodology: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Particle Agglutination |
| Use: Not an optimal reflex test; TP-PA is preferred |
| Limitations: May be falsely positive in some cases of systemic lupus erythematosus, pregnancy, and leprosy Cannot be tested with CSF |
| Test name: Treponema pallidum (VDRL), Cerebrospinal Fluid with Reflex to Titer |
| ARUP #: 0050206 |
| Methodology: Semi-Quantitative Flocculation |
| Comments: Preferred diagnostic assay for CSF specimens in suspected tertiary syphilis |
| Test name: Treponema pallidum Antibody, IgG by IFA (CSF) |
| ARUP #: 0055273 |
| Methodology: Semi-Quantitative Indirect Fluorescent Antibody |
| Comments: May aid in the workup of tertiary syphilis For CSF specimens, VDRL (CSF) with reflex to titer is preferred |
| Test name: Rapid Plasma Reagin (RPR) with Reflex to Titer, FTA-ABS and TP-PA |
| ARUP #: 0050011 |
| Methodology: Semi-Quantitative Charcoal Agglutination/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Particle Agglutination |
| Comments: Not an optimal reflex test Preferred test is RPR with Reflex to TP-PA |
| Test name: Treponema pallidum Antibody Panel (FTA-ABS) IgG and IgM |
| ARUP #: 0093067 |
| Methodology: Qualitative Immunofluorescence Assay |
| Comments: Not recommended If congenital syphilis is suspected, order IgM antibody If syphilis is suspected, preferred test is RPR with reflex to titer and TP-PA confirmation |