Syphilis

Causative Organism of Syphilis: Syphilis is caused by the spirochete bacterium Treponema pallidum.1

Transmission of Syphilis: Syphilis is primarily transmitted through direct contact with an open lesion, typically during sexual activity.1 It can also be transmitted from mother to fetus during pregnancy.1 Bloodborne transmission is rare.1

Stages of Syphilis:

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Primary Stage: This stage occurs 1-3 weeks after initial exposure.2 It is characterized by the development of a chancre, which is a painless ulcer at the site of entry.2 The chancre typically heals after 4-6 weeks.2 If left untreated, about 25% of primary cases progress to the secondary stage.2

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Secondary Stage: This stage is the most contagious.3 It typically presents with a variety of symptoms, including sore throat, enlarged lymph nodes, fever, weight loss, neck stiffness, headache, and general discomfort.3 Widespread rashes and lesions can occur on the trunk, palms of hands, and soles of feet.3 Wart-like lesions may also appear in the genital region.3

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Latent Stage: The latent stage is characterized by the absence of clinical signs and symptoms of infection.3 It is divided into early and late phases.3 Early latent syphilis refers to cases where the infection has been present for less than 2 years without symptoms.3 Late latent syphilis refers to cases where the infection has persisted for more than 2 years without symptoms.3 Transplacental transmission can still occur during the latent stage.3

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Tertiary Stage: This stage can occur as early as a year after initial exposure but typically develops decades later.4 It manifests in three major forms: Gummas (soft, non-cancerous growths), cardiovascular complications, and neurosyphilis.4 Tertiary syphilis is usually not infectious except to the fetus.4

Congenital Syphilis: Transmission of T. pallidum from mother to fetus typically occurs during the second or third trimester of pregnancy.4 Fetal or perinatal death occurs in 10% of cases.4 Infants often do not show symptoms during the first few weeks of life.4 However, 60-90% of untreated infants will develop symptoms after several months, including rhinitis, skin rashes, lymphadenopathy, hepatosplenomegaly, jaundice, anemia, painful limbs, and bone abnormalities.4 Neurosyphilis occurs in up to 60% of infants with congenital syphilis.5

Advantages of Direct Fluorescent Staining over Darkfield Examination:

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Direct fluorescent staining does not require live organisms, unlike darkfield microscopy.6

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It is more sensitive and specific compared to darkfield microscopy.6

Definitions of Reagin and Cardiolipin:

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Reagin is an antibody that is produced in response to syphilis infection.7 It reacts with cardiolipin.7

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Cardiolipin is a lipid released from the membranes of cells that are damaged as a result of syphilis infection.7

Comparison of Non-Treponemal and Treponemal Tests:

Non-Treponemal Tests:

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Test Principle: Detect antibodies (reagin) against cardiolipin, a lipid released from damaged cells during syphilis infection.7

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Detailed Test Procedure: Examples include the Venereal Disease Research Laboratory (VDRL) test and the Rapid Plasma Reagin (RPR) test.78 These tests involve mixing patient serum with a cardiolipin antigen suspension and observing for flocculation (clumping).89

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Sensitivity: Fairly sensitive, especially in secondary syphilis.9

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Specificity: Low specificity, meaning they can produce false-positive results.10

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Use in Diagnosis: Primarily used as screening tests.9

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Stages Test is Positive/Remains Positive: Positive in primary, secondary, and early latent stages.10 May become negative in late latent and tertiary syphilis.10 Titers decline with successful treatment.11

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Monitor Treatment: Can be used to monitor treatment response by observing changes in antibody titers.10

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Reporting: Results are reported as reactive, weakly reactive, or nonreactive.8

Treponemal Tests:

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Test Principle: Detect antibodies directed specifically against T. pallidum antigens.7

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Detailed Test Procedure: Examples include the Fluorescent Treponemal Antibody Absorption (FTA-ABS) test, T. pallidum Particle Agglutination (TP-PA) test, Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescent Immunoassays (CLIA), and Multiplex Flow Immunoassays (MFI).12

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Sensitivity: Highly sensitive, especially in later stages of syphilis.10

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Specificity: Highly specific, meaning they are less likely to produce false-positive results.10

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Use in Diagnosis: Used as confirmatory tests to verify positive non-treponemal test results.10

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Stages Test is Positive/Remains Positive: Typically remain positive for life, even after treatment.10

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Monitor Treatment: Not typically used to monitor treatment response.10

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Reporting: Results are reported as positive or negative.13

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Causes of False-Positive and False-Negative Reagin Tests:

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False-Positive Reagin Tests: Can be caused by conditions such as mononucleosis, chickenpox, measles, malaria, tuberculosis, pregnancy, systemic lupus erythematosus (SLE), IV drug use, autoimmune arthritis, advanced age, and advanced malignancy.10 Resolution: Confirm with a treponemal test.10

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False-Negative Reagin Tests: Can occur due to the prozone phenomenon, where very high antibody levels interfere with the test reaction.9 Resolution: Diluting the patient's serum may resolve the prozone effect.

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Most Common Test Procedure for Neurosyphilis: The VDRL test or ELISA performed on cerebrospinal fluid is the most common procedure for diagnosing neurosyphilis.11

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RPR and FTA-ABS Results in Congenital Syphilis:

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RPR: A reactive RPR test on infant serum indicates possible congenital syphilis. However, maternal antibodies can cross the placenta and cause a false-positive result.11

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FTA-ABS: A positive FTA-ABS test on infant serum, along with clinical symptoms, is highly suggestive of congenital syphilis.11 To confirm congenital syphilis, an IgM-specific treponemal assay should be performed.11

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CDC-Recommended Laboratory Protocol for Syphilis Diagnosis:

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Traditional Algorithm: Screen with a non-treponemal test (e.g., RPR).10 Confirm positive results with a treponemal test (e.g., FTA-ABS or TP-PA).10

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Reverse Algorithm: Screen with an automated treponemal immunoassay.10 Confirm positive results with an RPR.10 Perform a TP-PA on samples with discrepant results (e.g., positive treponemal test but negative RPR).10