How Is Syphilis Diagnosed?

Two tests-known as dark-field microscopy and direct fluorescent antibody tests-can definitively diagnose syphilis. However, neither of these tests is widely available since they are used to analyze samples from oral lesions and, when viewed under a microscope, some of the bacteria normally found in the mouth and throat look very similar to Treponema pallidum, the bacteria that causes syphilis. As a result, examining material obtained from oral lesions can lead to false-positive results (in which the person is mistakenly found to be infected). Therefore, doctors use blood testing (serology) to diagnose syphilis. These tests aim to detect antibodies to an infectious agent. (Your immune system produces antibodies specific to an organism that has invaded your body; the antibodies’ job is to kill that organism). If you have syphilis, your blood will contain antibodies to T. pallidum.

Treponemal and Nontreponemal Tests

There are two types of serologic tests for syphilis, treponemal and nontreponemal. Treponemal tests specifically identify antibodies targeted against T. pallidum. Interestingly, although this antibody is evidence that your body is mobilizing in self-defense, it does not inhibit the progression of the disease or provide immunity against reinfection. In any case, findings from different types of treponemal tests reflect how much antibody is present in the blood, which determines the extent of disease activity.

Nontreponemal tests go about detecting infection in a more indirect way. They use cardiolipin, a substance found in heart tissue. Patients with syphilis invariably form antibodies to cardiolipin. But, false-positive nontreponemal tests may occur in patients who are pregnant, are intravenous drug users, have autoimmune diseases such as systemic lupus erythematosus, or have recently had a viral infection. When this kind of test leads to positive findings, it must be confirmed with a treponemal test.

Analysis of Cerebrospinal Fluid

Any patient with syphilis who has signs that suggest the infection is causing neurologic effects should have a cerebrospinal fluid exam. Signs or symptoms suggesting neurologic involvement include visual or hearing changes, inability to move the muscles of the face or eyes, loss of feeling in the face, headache, stiff neck, or fever. The cerebrospinal fluid is produced in the brain and bathes the brain and spinal cord. A sample of this fluid for analysis is obtained through a needle placed in the lower back (lumbar puncture). This needle punctures the protective covering of the spinal cord, but does not enter the cord itself.

Comprehensive Evaluation

All female patients with syphilis should undergo a complete evaluation, including a pelvic examination, to determine the stage of the disease. In addition, if you are diagnosed with this infection, you should be tested for other sexually transmitted diseases, including HIV.

How Should Syphilis Be Treated?

Antibiotic Treatment

Penicillin G (Bicillin) is the most common drug used to treat syphilis. It is the only treatment proven effective for neurosyphilis or syphilitic infection during pregnancy; that is, it treats both the mother and her baby.

If you are pregnant and have a history of penicillin allergy, you should undergo skin testing. If skin tests are positive, you will be ? desensitized? and then treated with penicillin.

The most recent treatment recommendations of the Centers for Disease Control and Prevention (CDC) are presented in the table below.

Table 1. CDC Recommendations for Syphilis Treatment
Stage of DiseasePreferred TreatmentAlternative Regimes*
Primary, Secondary or Early-LatentBenzathine penicillin G 2.4 million units intramuscularly as a single doseDoxycycline (Vibramycin) 100 mg orally twice daily or tetracycline (Sumycin) 500 mg orally four times daily, each for two weeks
Late-Latent, Latent of Unknown Duration, or TertiaryBenzathine penicillin G 2.4 million units intramuscularly once a week for three dosesDoxycycline (Vibramycin) 100 mg orally twice daily or tetracycline (Sumycin) 500 mg orally four times daily, each for four weeks
Neurologic or OphthalmicPenicillin G 3-4 million units intravenously every 4 hours for 10-14 days OR procaine penicillin 2.4 million units intramuscularly once daily and probenecid 500 mg orally four times daily, each for 10-14 daysnone acceptable

Source: Centers for Disease Control and Prevention (MMWR 1998; 47(RR-1):28-49) *Doxcycline and tetracycline are contraindicated in pregnancy.

Source: Centers for Disease Control and Prevention (MMWR 1998; 47(RR-1):28-49) *Doxcycline and tetracycline are contraindicated in pregnancy.

Erythromycin, once used as an alternative treatment, is less effective than other agents and is no longer recommended.

Possible Side Effects

Within a few hours of treatment for syphilis, there is a small chance you will develop what’s known as the Jarisch-Herxheimer reaction, which causes fever, chills, rapid heart beats, rash, muscle aches, and headaches. This is an allergic reaction to the breakdown of the spirochetes. In pregnant women, this reaction may include preterm labor or abnormal fetal heart rate. However, concern over this possibility should not prevent or delay treatment.

Management of Sexual Partners

Anyone you have had sexual contact with during the 90 days before you were diagnosed with primary, secondary, or early-latent syphilis should be treated with the same regimen recommended for primary syphilis. If you have been diagnosed with late-latent or tertiary syphilis, anyone with whom you have had long-term sexual contact should undergo serologic evaluation and receive treatment based on the results.

Follow-up Treatment

Follow-up treatment depends on the stage of disease for which you are treated.

  • If you are treated for primary or secondary syphilis, you will undergo a physical examination and repeat serologic testing at six months and again at 12 months after treatment. If testing does not indicate a marked decrease in antibodies to T. pallidum or if you have persistent or recurrent signs of infection, either your treatment has failed or you have been reinfected. You will probably be re-treated following the regimen for late-latent syphilis.
  • If treatment has failed (not reinfection), you will be evaluated for subclinical neurosyphilis, using the lumbar puncture procedure described earlier. You will also be tested for HIV infection.
  • If you are treated for latent disease, you will have a repeat physical examination and serologic testing at six, 12, and 24 months after treatment. Re-treatment and lumbar puncture are recommended if you have signs or symptoms of recurring infection or if testing indicates continued high levels of antibodies.
  • If you are treated for neurosyphilis, you will undergo repeat evaluation of the cerebrospinal fluid every six months until the findings are normal. Your doctor will suggest re-treating you if the cell count in the cerebrospinal fluid does not normalize within six months.

HIV Infected Patients

Syphilis affects between 14 and 36% of individuals with HIV. Although HIV infection adversely affects the immune system, serologic tests are still useful for diagnosis of syphilis in these patients. Patients infected with HIV are more likely to fail treatment for syphilis, and the rate of neurosyphilis is higher in this population. Nevertheless, the recommended treatment of syphilis does not change if you are co-infected with HIV.

HIV-infected patients treated for syphilis should undergo physical examination and serologic testing every three months for the first year following treatment and again 24 months after treatment. Because co-infected patients are at a higher risk of complications, doctors will perform a lumbar puncture earlier than they would with other patients.

What Is New and Emerging?

As mentioned previously, erythromycin (Ery-Tab) is an antibiotic previously used as an alternative treatment for syphilis, but is no longer recommended. A related but newer antibiotic, azithromycin (Zithromax), might be recommended as an alternative agent when the CDC publishes its next set of treatment guidelines. Because azithromycin is only administered once daily, it may offer a dosing advantage over the currently recommended alternative agents, doxycycline and tetracycline.

It is important to remember that in certain situations, such as pregnancy or neurosyphilis, penicillin (PenVK) is the only treatment proven to be effective, and this agent should be used even for those with a history of penicillin allergy.

Can Syphilis Be Prevented?

There is no vaccine for syphilis. Prevention, therefore, centers on two issues:

  • education regarding safer sexual practices (abstinence, monogamy, and using condoms and spermicides); and
  • identification and treatment of infected individuals to prevent transmission to others.