Does a patient with a positive Treponema pallidum hemagglutination assay (TPHA) and a negative Venereal Disease Research Laboratory test (VDRL) with no clinical signs of syphilis require treatment?

From the Guidelines

Treatment is generally not needed for a patient with a positive TPHA and negative VDRL test who has no clinical signs of syphilis. This pattern typically represents either a successfully treated past syphilis infection or a false positive TPHA result. The TPHA is a specific treponemal test that usually remains positive for life after infection, even after successful treatment, while the VDRL is a non-treponemal test that typically becomes negative after effective treatment [ 1 ]. Without clinical signs and with a negative VDRL, there is no evidence of active infection requiring intervention. However, it would be important to confirm the patient's treatment history. If there is documentation of adequate previous treatment for syphilis, no further treatment is needed. If there is uncertainty about previous treatment or high-risk exposures, clinical judgment may warrant treatment with benzathine penicillin G 2.4 million units IM as a single dose. Additionally, consider HIV testing as co-infection is common, and ensure appropriate follow-up to monitor for any changes in clinical status or serological markers [ 1 ].

Some key points to consider in the management of such patients include:

• Confirming the patient's treatment history to determine if they have been adequately treated for syphilis in the past
• Evaluating the patient for any clinical signs or symptoms of syphilis, even if the VDRL is negative
• Considering HIV testing due to the high prevalence of co-infection
• Ensuring appropriate follow-up to monitor for any changes in clinical status or serological markers
• Using clinical judgment to determine the need for treatment in cases where there is uncertainty about previous treatment or high-risk exposures.

It's also important to note that the CDC guidelines [ 1 ] provide recommendations for the treatment of syphilis, but the decision to treat should be individualized based on the patient's specific circumstances.

From the Research

Syphilis Treatment

• The patient has tested positive for TPHA and negative for VDRL with no clinical signs of syphilis, raising questions about the need for treatment.
• According to 2, doxycycline appears to be an effective agent for the treatment of early syphilis, although it is considered a second-line treatment.
• The study in 3 found that doxycycline had a slightly lower success rate compared to penicillin in treating primary syphilis, but appeared to have a reduced success rate in attaining resolution in late and undetermined syphilis infection.
• The treatment of syphilis is based on penicillin or doxycycline in allergic patients, as stated in 4.
• It is recommended to follow up with a serological test in all patients with syphilis to ascertain cure after treatment and to diagnose possible reinfections, as mentioned in 4.

Treatment Options

• Penicillin G is the first-line drug for all stages of syphilis, as stated in 5.
• Doxycycline is a second-line treatment option, particularly for patients who are allergic to penicillin.
• Azithromycin is not recommended due to the emergence of clinically significant resistance in Treponema pallidum subsp. pallidum, as reported in 5.

Diagnostic Tests

• The diagnosis of syphilis is dependent mainly on serological tests, including VDRL, RPR, FTA, and TPHA, as mentioned in 6.
• The nonvenereal treponematoses have the same serological response as in syphilis, making diagnosis and treatment challenging.