Can a patient with a negative Rapid Plasma Reagin (RPR) test and a positive Treponema Pallidum Hemagglutination Assay (TPHA) be contagious?

Contagiousness of Syphilis with Negative RPR and Positive TPHA

A patient with negative RPR and positive TPHA is generally not contagious, as this pattern typically represents successfully treated or late latent syphilis where the organism is no longer transmissible. This serological pattern indicates past infection with Treponema pallidum where the nontreponemal antibodies (detected by RPR) have declined while the treponemal antibodies (detected by TPHA) persist, often for life.

Understanding Syphilis Serology

Interpretation of Test Results

• RPR (Rapid Plasma Reagin): A nontreponemal test that detects antibodies to cardiolipin, which correlate with active infection
• TPHA (Treponema pallidum Hemagglutination Assay): A treponemal test that detects specific antibodies against T. pallidum

The combination of negative RPR and positive TPHA typically indicates one of the following scenarios:

1. Successfully treated syphilis - After effective treatment, nontreponemal tests (RPR) typically decline and may become negative, while treponemal tests (TPHA) usually remain positive for life 1
2. Late latent syphilis - In late stages, RPR sensitivity decreases to 61-75%, potentially yielding negative results while TPHA remains positive 1
3. Very early primary syphilis - Rarely, this pattern can occur in early infection before RPR becomes positive 2

Clinical Implications for Contagiousness

Non-Contagious Scenarios (Most Common)

• Successfully treated syphilis: After appropriate treatment, patients are no longer contagious, even though treponemal tests remain positive 1
• Late latent syphilis: After >1 year of untreated infection, syphilis enters a latent phase where it's generally not transmissible sexually (though vertical transmission can still occur in pregnant women)

Potentially Contagious Scenarios (Rare)

• Very early primary syphilis: In rare cases, TPHA may become positive before RPR in early infection, when the patient could still be contagious 2
• False negative RPR: Prozone phenomenon or technical errors can cause false-negative RPR results in active infection 3

Clinical Assessment Algorithm

To determine if a patient with negative RPR and positive TPHA is contagious:

1. Review treatment history:

   • Previous documented treatment with appropriate regimen → Not contagious
   • No previous treatment → Proceed to next step

2. Clinical examination:

   • Presence of primary chancre, secondary rash (especially on palms/soles), or mucous patches → Potentially contagious despite negative RPR
   • No clinical signs of primary or secondary syphilis → Likely not contagious

3. Consider testing limitations:

   • If high clinical suspicion of active infection despite negative RPR:
     • Repeat testing with diluted serum to rule out prozone phenomenon 3
     • Consider additional treponemal test (TPPA or FTA-ABS) as a third confirmatory test 1

Important Caveats

• HIV co-infection: HIV-positive patients may have atypical serological responses, including false-negative results, requiring closer clinical correlation 1
• Recent treatment: RPR titers decline at variable rates after treatment, with 29% becoming negative within 6 months and 86% returning to normal within 24 months 2
• Prozone phenomenon: In some cases of secondary syphilis with high antibody levels, undiluted serum may yield false-negative RPR results due to antibody excess 3

Management Recommendations

For patients with negative RPR and positive TPHA:

• If previously treated adequately: No further treatment needed; patient is not contagious
• If no documented treatment history: Consider treatment with benzathine penicillin G 2.4 million units IM as a single dose (for presumed late latent syphilis) 1
• If clinical signs of active infection present: Treat as active syphilis regardless of serology results 1

Remember that clinical correlation is essential in interpreting syphilis serology, and treatment decisions should be based on the complete clinical picture rather than serological results alone.