Why is Rapid Plasma Reagin (RPR) screening negative when Treponema pallidum (TP) particle agglutination (TP-EA) and Treponema pallidum particle agglutination (TP-Pa) tests are positive for syphilis?

From the Guidelines

A negative RPR screening with a positive TP-PA antibody test typically indicates a past, successfully treated syphilis infection. This pattern occurs because RPR detects non-treponemal antibodies that typically disappear after successful treatment, while TP-PA detects specific treponemal antibodies that usually remain positive for life regardless of treatment status, as noted in the 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology 1.

Key Points to Consider

• The RPR test detects non-treponemal antibodies that decline and eventually become undetectable after successful treatment.
• The TP-PA test detects specific treponemal antibodies that persist indefinitely, regardless of treatment status.
• This serological pattern is common in patients who have been adequately treated for syphilis in the past.
• In some cases, this pattern may also represent very early syphilis infection or late latent syphilis where RPR sensitivity decreases, as discussed in the context of syphilis diagnosis 1.

Clinical Implications

• If there's no documented history of adequately treated syphilis, clinical evaluation is necessary to determine if this represents a new infection requiring treatment.
• Treatment, if necessary, typically involves benzathine penicillin G 2.4 million units IM as a single dose for early syphilis or weekly for three weeks for late latent syphilis, based on standard treatment guidelines.
• The choice of treatment should be guided by the patient's clinical presentation, medical history, and the results of further diagnostic testing, if needed, considering the limitations of serological tests in certain contexts 1.

From the Research

RPR Screening Negative by Syphilis AB by TP-pa Positive

• The provided studies do not directly address why RPR screening is negative by syphilis AB by TP-pa positive.
• However, the studies discuss the treatment and serological response of syphilis patients to different antibiotics, including benzathine penicillin and doxycycline 2, 3, 4, 5, 6.
• The studies suggest that benzathine penicillin is the treatment of choice for syphilis, but doxycycline is an effective second-line treatment 2, 3, 4, 5, 6.
• The serological treatment response to doxycycline versus benzathine penicillin in syphilis infections is similar, with some studies showing a slightly higher success rate with penicillin 4, 5.
• The time to successful serological response also varies between the two treatments, with some studies showing a faster response with doxycycline 6.
• However, without direct evidence addressing the specific question, it is difficult to provide a clear explanation for why RPR screening is negative by syphilis AB by TP-pa positive.
• Further research is needed to answer this question, as the current studies do not provide sufficient information to draw a conclusion 2, 3, 4, 5, 6.