What is the interpretation of a negative Rapid Plasma Reagin (RPR) test and a detected Enzyme Immunoassay (EIA) for syphilis serology?

From the Guidelines

The patient with a negative Rapid Plasma Reagin (RPR) test but a detected Enzyme Immunoassay (EIA) result should undergo further evaluation with a treponemal confirmatory test, such as TP-PA or FTA-ABS, to determine the presence of a syphilis infection. This approach is based on the understanding that EIA detects specific treponemal antibodies that remain positive for life after infection, while RPR measures non-specific antibodies that can fluctuate with disease activity and treatment 1.

Interpretation of Test Results

The discrepancy between the RPR and EIA results can indicate early syphilis infection, previously treated syphilis, or a false positive EIA result. It is essential to consider these possibilities when interpreting the test results. The sensitivity of RPR in primary lesions ranges from 62.5–76.1%, although one high-quality paper reported a sensitivity of 92.7% based on 109 patients with darkfield-confirmed primary syphilis 1.

Recommended Next Steps

If the confirmatory test is positive, treatment with Benzathine Penicillin G 2.4 million units intramuscularly as a single dose is indicated for early syphilis (primary, secondary, or early latent syphilis of less than one year's duration) 1. For late latent syphilis or syphilis of unknown duration, three weekly doses of Benzathine Penicillin G 2.4 million units intramuscularly are recommended.

Considerations for Treatment and Follow-Up

Sexual partners should be notified, tested, and treated if necessary, and follow-up testing is essential to ensure treatment success. The Centers for Disease Control and Prevention (CDC) guidelines for the treatment of syphilis in pregnancy recommend parenteral benzathine penicillin G, and evidence on the efficacy or safety of alternative antibiotics in pregnancy is limited 1.

Key Points for Clinical Practice

• Perform a treponemal confirmatory test (TP-PA or FTA-ABS) for patients with a negative RPR but a detected EIA result.
• Treat with Benzathine Penicillin G based on the stage and duration of syphilis.
• Notify, test, and treat sexual partners as necessary.
• Conduct follow-up testing to ensure treatment success, using the same nontreponemal test for comparable results 1.

From the Research

Syphilis Serology

• RPR (Rapid Plasma Reagin) test is used to diagnose syphilis, with a negative result indicating no infection or successful treatment 2, 3, 4
• EIA (Enzyme Immunoassay) is another test used to detect syphilis, which can detect the presence of antibodies against the bacteria that cause syphilis 5, 6
• A negative RPR result with a detected EIA result may indicate:
  • Early stages of syphilis, where the RPR test has not yet turned positive 2, 4
  • Successful treatment of syphilis, where the RPR test has turned negative but the EIA test still detects antibodies 3, 6
  • False negative RPR result, which can occur in some cases 5, 4

Treatment of Syphilis

• Penicillin is the recommended treatment for syphilis, with a single dose of 2.4 million units of benzathine penicillin G being the most effective treatment 2, 3, 4
• Azithromycin is an alternative treatment for syphilis, but its effectiveness is still being studied and it is not recommended as a first-line treatment 2, 6
• Ceftriaxone is another alternative treatment for syphilis, which has shown promising results in some studies 5

Serological Response to Treatment

• Serological response to treatment is evaluated by monitoring the RPR test results, with a decrease in titer indicating successful treatment 2, 3, 4
• The "serofast state" refers to a condition where the RPR test remains positive despite successful treatment, which can occur in some cases 3, 4
• The serological response to treatment can take several months to occur, with the RPR test turning negative in most cases within 6-12 months after treatment 2, 3, 4