Chapter 10 - Syphilis

Publication Details

Syphilis is a systemic infection that has been known since the 15th century. It is caused by the spirochete Treponema pallidum and is almost always spread by contact with infectious lesions during sexual intercourse.


If left untreated, syphilis goes through several phases.

Symptoms of primary syphilis usually occur within 3 weeks of the initial infection. Secondary syphilis occurs within 4 to 10 weeks following exposure. Tertiary syphilis typically appears 2 to 20 years after the initial infection. Latent syphilis is the term applied to the interval between stages - primary, secondary, or tertiary - that have disease manifestations. Having sexual contact with a person with early (primary or secondary phase) syphilis, particularly contact with a primary chancre, carries the greatest risk of infection. About one third of those having sexual contact with persons with early syphilis will be infected.

Transmission of infection may occur after sharing needles with injection drug users who are infected with syphilis, although this would be unusual. Donated blood and blood products, however, are routinely screened for syphilis, and the risk of infection by transfusion is essentially nil.

Congenital syphilis is of increasing concern, given the rise in the incidence of syphilis in women of childbearing age. The fetus may be infected if the mother has untreated syphilis. The risk to the unborn fetus is greatest when the infection of the mother is recent.


With the introduction of penicillin and improved public health measures, the number of reported cases of syphilis in the United States declined steadily from the 1940s to the 1970s. In the late 1970s and early 1980s, the incidence of syphilis increased, with a disproportionate rise among men who have sex with other men. At the beginning of the AIDS epidemic, the number of cases of syphilis declined. In 1985, however, the incidence of syphilis in heterosexual men and women began to rise. From 1985 to 1990, the incidence of primary and secondary syphilis increased 75 percent, with over 50,000 reported cases. Today the Centers for Disease Control and Prevention estimates that there are 120,000 cases of syphilis detected each year, of which 40,000 to 50,000 are infectious.

The greatest rise in syphilis has been among young African-American men and women in the inner cities and is related to the use of illegal drugs, especially crack cocaine. The use of crack cocaine has been shown to be associated with increased sexual activity with multiple sexual partners, and the concomitant spread of syphilis.

Course of the Disease

The natural course of untreated syphilis goes through several well-described phases. After the initial infection, usually by sexual contact with a syphilitic lesion, there is an incubation period of about 3 weeks before the symptoms of primary syphilis develop. The primary lesion of syphilis is a chancre that occurs at the site of inoculation, most often the genitals. This chancre is usually painless and may be inconsequential. Chancres heal in a matter of weeks even without treatment.

The disseminated or secondary stage of syphilis occurs 4 to 10 weeks after the initial exposure. Secondary syphilis may have multiple manifestations, including skin rash; constitutional symptoms; central nervous system involvement with headache, meningismus, meningitis, and other complications; and, more rarely, hepatitis and renal abnormalities.

Latent syphilis is that stage of the disease in which the serologic tests for syphilis are positive, but there are no clinical manifestations of infection. Tertiary syphilis may affect any organ system and occurs 2 years to many years after infection. The major manifestations of tertiary syphilis are benign latent syphilis with gummata, syphilitic aortitis, or neurosyphilis.

A pregnant woman infected with syphilis may have a stillbirth or spontaneous abortion. An infant born with congenital syphilis may have multiple complications, including characteristic congenital defects. In the HIV-infected person, syphilis infection may be more virulent and more likely to invade the central nervous system.

Program Issues for Drug Treatment Settings

The high correlation between drug use and syphilis makes it especially important to identify and treat the disease among persons enrolled in drug treatment programs. Syphilis, fortunately, is responsive to treatment with antibiotics. Screening and treatment should be accompanied by appropriate counseling and medical followup.

In setting up a screening and treatment or referral program, the following components need to be included:

  • Screening should be provided for all persons entering drug treatment programs.
  • Screening should be repeated every year if at-risk behavior continues, or earlier if signs and symptoms suggestive of syphilis infection occur.

Special Considerations With Infected Patients

Drug treatment programs need to be aware of the following issues with regard to patients infected with syphilis:

  • Infected mothers should be advised to have their young children screened for undetected congenital syphilis if they were not screened at birth.
  • Persons known to be infected with syphilis should be counseled regarding safer sex practices. The correct use of condoms will decrease the likelihood of exposure to a genital/rectal syphilis lesion. For further information on condom use, see the chapter "Counseling Issues."
  • Testing for HIV infection should be encouraged. Syphilis may increase the risk for infection with and transmission of HIV.

Other Program Considerations

Clients Who Refuse Testing

A person has the right to refuse screening and treatment for syphilis. Clients who refuse testing should not be excluded from treatment programs because of presumed or actual infection. They should be counseled and treated as if they were potentially infectious to others.

Universal Precautions

Staff should employ universal precautions when coming in contact with body fluids, regardless of the documented status of a person. Precautions are appropriate for patients with primary and secondary syphilis, and for infants with early congenital syphilis. Precautions are unnecessary for latent and tertiary disease.

Mandatory Reporting Procedures

All States mandate that cases of syphilis be reported. Reporting should be done promptly in accordance with local/State health department regulations to facilitate contact tracing. Contact tracing and subsequent interviewing by health authorities are fundamental for control of the disease.


Indicators for Screening

Drug treatment facilities need to screen all patients for syphilis. In particular, persons should be screened who have a current diagnosis or past history of gonorrhea, genital herpes, HIV infection, or any other sexually transmitted disease. Also, screening is indicated for any person with a genital chancre, skin rash characteristic of secondary syphilis, or lymphadenopathy.

Table 1 presents behavioral risk factors for syphilis.

Box Icon


Table 1. Behavioral risk factors. Syphilis is primarily transmitted through contact with an infectious lesion, usually during sexual intercourse. Syphilis can be acquired by kissing or touching a person who has (more...)

Screening Techniques

Preliminary Screening Tests

Serologic tests for screening include the following quantitative nontreponemal or reaginic tests:

  • Venereal Disease Research Laboratory (VDRL)
  • Rapid-plasma-reagin (RPR)
  • Automated reagin test (ART)

If the preliminary screening test is positive, a confirmatory test is done.

Confirmatory Tests

Specific antitreponemal antibody tests:

  • Fluorescent treponemal antibody absorption (FTA-ABS)
  • T. pallidum microhemagglutination (MHA-TP)

Darkfield Examination for Syphilis

If examined by darkfield microscopy, treponemes may be seen in fluid obtained from a chancre, the lesion of primary syphilis or condyloma lata, lesions occurring during secondary syphilis. If the treponemes are seen, this is diagnostic of syphilis.

This technique will not be available, however, in most drug treatment programs and is not a screening test to determine prior infection with syphilis.

Special Considerations in Screening Tests

Test results are dependent on the stage of the infection (see table 2).

Table 2. Percentage of patients with positive serologic test results in untreated syphilis.


Table 2. Percentage of patients with positive serologic test results in untreated syphilis.

Interpretation of Test Results

  • The serologic tests may be negative in the incubation period, in primary syphilis, and in untreated syphilis of many years' duration.
  • A false-positive screening test for syphilis (VDRL or RPR) may be associated with many conditions and is usually reactive at low titers of less than 1:8.
  • False-positive tests may occur with tuberculosis, injection drug use, pregnancy, viral hepatitis, chronic liver disease, and bacterial endocarditis. When the VDRL or RPR is a false positive, the FTA-ABS or MHA-TP will be nonreactive in most cases.
  • Any person with positive serologic tests for syphilis should be advised to have an HIV test and asked about signs and symptoms of other sexually transmitted diseases, such as gonorrhea and genital herpes.

Frequency of Screening

Serologic screening should be repeated every year if at-risk behavior continues, or sooner if a person has signs or symptoms suggestive of syphilis infection.

Medical Management Issues

The clinical stage of the syphilis infection dictates the medical management, treatment, and followup. The different clinical categories of syphilis infection are

  • Early syphilis: primary and secondary syphilis and early latent syphilis of less than 1-year duration
  • Late latent syphilis: syphilis of more than 1-year duration or of unknown duration
  • Neurosyphilis
  • Congenital syphilis
  • Syphilis in pregnancy
  • Syphilis and HIV infection

Early Syphilis

Primary Syphilis

The main symptom of primary syphilis is a painless ulcer, a chancre, that appears at the site of exposure 14 to 21 days after that exposure. A primary chancre usually occurs in the genital, perirectal, or oral cavity. If untreated, the lesion heals on its own in 3 to 8 weeks.

Secondary Syphilis

Secondary syphilis occurs 4 to 10 weeks after the primary chancre. The classical presentation is that of a disseminated, symmetric, papular rash that involves the trunk, palms, and soles. The infection is systemic with generalized lymphadenopathy and, less commonly, headaches, malaise, fever, hepatitis, and arthritis, as well as kidney, eye, and central nervous system involvement. Even without treatment, the patient's symptoms will improve.

Early Latent Syphilis of Less Than 1-Year Duration

Many patients will not remember their initial infection and the length of time since exposure may not be known.

Clinical Management and Followup for Early Syphilis

Table 3 presents the recommended treatment regimen for early syphilis.

Box Icon


Table 3. Recommended treatment regimen for early syphilis. Recommended regimen: Benzathine penicillin G, 2.4 million units (mu) intramuscularly (IM) (1.2 mu in each buttock) - one treatment (more...)

Followup for Early Syphilis

  • Patients should be examined and serologic tests should be repeated at 3 months and 6 months.
  • For primary and secondary syphilis, the VDRL or RPR should decline by fourfold 3 months after treatment (e.g., VDRL of 1:64 to 1:16; 1:8 to 1:2).
  • For early latent syphilis, the titer should decrease by fourfold 6 months after treatment.
  • If the titer has not dropped appropriately or if signs and symptoms persist, the patient should be referred to a physician for a spinal tap and possible retreatment.

Late Latent Syphilis of More Than 1-Year Duration or of Unknown Duration

If a patient has a positive syphilis serology and the length of infection is unknown, the patient should be treated for late latent syphilis.

Clinical Management and Followup for Late Latent Syphilis

The patient with late latent syphilis should have a lumbar puncture to examine the cerebrospinal fluid in the following circumstances: if neurological signs or symptoms are present; the initial treatment was unsuccessful; or the VDRL is greater than or equal to 1:32.

Table 4 presents the recommended treatment for late latent syphilis.

Box Icon


Table 4. Recommended treatment regimen for late latent syphilis. Recommended regimen: Benzathine penicillin G: 2.4 million units IM (1.2 mu in each buttock) given weekly for 3 weeks (more...)

In addition, HIV-infected persons and penicillin-allergic patients may require a lumbar puncture to examine the cerebrospinal fluid (CSF). CSF findings in a patient with neurosyphilis include an elevated white count, primarily lymphocytes, and an elevated CSF protein. The VDRL may or may not be reactive. If the findings on examination of the CSF are consistent with neurosyphilis, the patient should be treated with high-dose intravenous penicillin. A person with a penicillin allergy and central nervous system syphilis should be hospitalized and desensitized to penicillin.

Followup of Late Latent Syphilis. The VDRL or RPR should be repeated after treatment at 6 months and 12 months. The treatment was adequate if the titer declines by fourfold and the patient has no signs or symptoms of syphilis. If not, the patient may have been reinfected or the patient will need to be evaluated for possible neurosyphilis.


Any patient, with or without concurrent HIV infection, should be evaluated for possible neurosyphilis. The cerebrospinal fluid should be examined if the patient has cranial nerve abnormalities such as an ocular palsy, deafness, nystagmus, vertigo, or stroke symptoms; headaches; meningitis; or personality change.

Clinical Management and Followup of Neurosyphilis

Table 5 presents the recommended treatment regimen for neurosyphilis.

Box Icon


Table 5. Recommended treatment regimen for neurosyphilis. Aqueous penicillin G, 24 million units per day intravenously for 10 days; followed by benzathine penicillin G, 2.4 million units intramuscularly (more...)

Followup of Neurosyphilis. After treatment for neurosyphilis, the patient should have a repeat lumbar puncture every 6 months or until the cell count is normal. Retreatment is indicated if the cell count fails to decline after 2 years.

Congenital Syphilis

The fetus or infant of a woman with untreated or inadequately treated syphilis is at risk for congenital syphilis. Approximately a third of the mothers whose infants or children have syphilis received no prenatal care. No infant should be released from a hospital until the syphilis serology of the mother is known. Likewise, older infants and children of a woman with syphilis, especially latent syphilis, should be examined by a pediatrician.

The clinical signs of congenital syphilis are diverse. Infants and children who have congenital syphilis should receive appropriate medical care and followup. Without treatment, a child may at some time in the future develop neurosyphilis.

Medical Management With Special Groups

With HIV Co-Infection

There is a considerable amount of controversy surrounding the appropriate management of syphilis in the HIV-infected person. In the HIV-infected person, the development of neurosyphilis is more frequent. Neurosyphilis may present as meningitis, optic neuritis, or deafness, as well as cranial nerve palsies with meningitis in some cases.


The serologic test results for syphilis may be different in the HIV-infected person, with a higher than expected RPR in early HIV and an undetectable or lower RPR in late HIV infection. While serologic tests are reliable, the interpretation of test results in HIV-infected persons should include these considerations:

  • The presence of a primary syphilitic chancre increases the risk for infection with and transmission of HIV.
  • In most HIV-infected persons, the serologic tests for syphilis are reliable and accurate.
  • Most HIV-infected persons will respond to appropriate treatment for syphilis, and the serologic responses after treatment will be similar to those of non-HIV-infected persons.
  • Mean syphilis titers may be higher in HIV-infected than in noninfected persons.


For most HIV-infected persons, the course of syphilis is the same as for those who are HIV-negative. Penicillin is the preferred drug to treat syphilis in HIV-infected persons. If an HIV-infected person has a known penicillin allergy, desensitization may be appropriate, because of concerns about the efficacy of doxycycline or other drugs in treating syphilis in HIV-infected persons.

In an HIV-infected person with no neurologic deficits, it is not always necessary to do a lumbar puncture. At this time, some physicians recommend that an HIV-infected person with a reactive serum VDRL undergo a lumbar puncture and subsequent treatment for neurosyphilis with high-dose penicillin if there are abnormalities in the cerebrospinal fluid (CSF), even if the CSF-VDRL is nonreactive. The presence of an elevated white blood cell count or protein in the CSF, with no other explanation, may be caused by CSF syphilis; therefore, treatment is considered appropriate. There is controversy concerning these recommendations, and expert medical consultation would be appropriate if there are questions concerning the diagnosis of neurosyphilis in an HIV-infected person.

Table 6 presents alternative treatment regimens for syphilis in persons co-infected with HIV.

Box Icon


Table 6. Recommended treatment regimens for HIV-infected persons. Penicillin is the recommended treatment for all stages of syphilis For the penicillin allergic patient, densensitization to pencillin is (more...)


After appropriate treatment, patients should be followed clinically and serologically with a VDRL/RPR at 1, 2, 3, 6, 9, and 12 months after treatment. After 6 months, the VDRL/RPR should decrease by fourfold. If the titer rises or does not decrease, the patient should have a lumbar puncture for examination of the cerebrospinal fluid and retreatment if appropriate.

With Pregnancy


All pregnant women should be screened for syphilis during their initial prenatal care. If no prenatal care is provided, the woman should have serologic screening for syphilis at the time of delivery. In populations at high risk for syphilis, the screening should be done at the initial prenatal visit, at the end of the second trimester, and at the time of delivery.


A pregnant woman with untreated syphilis should be treated with penicillin at the dosage appropriate for the stage of infection as outlined above (early, early latent, or late latent). Tetracycline and doxycycline are contraindicated during pregnancy. Erythromycin is associated with treatment failures in pregnancy.

For a pregnant woman with a true penicillin allergy, the appropriate treatment of syphilis is to hospitalize and desensitize her to penicillin prior to treatment.

Any woman treated for syphilis in the second half of pregnancy is at risk for a Jarisch-Herxheimer reaction, with possible premature labor or fetal distress.

The HIV-infected pregnant woman should be treated according to the guidelines for any HIV-infected person. Doxycycline and tetracycline, however, are contraindicated.


Monthly followup is mandatory for a pregnant woman after being treated for syphilis. The followup should include a clinical examination. Retreatment may be necessary for some pregnant women.

Note: Treatment recommendations for pregnant women are especially subject to change.


  1. Centers for Disease Control. Sexually transmitted diseases: Treatment guidelines. Morbidity and Mortality Weekly Report. 1989;38(S-8):1-43 [PubMed: 2770678]
  2. Gourevitch, M.N.; Selwyn, P.A.; Davenny, K.; Buono, D.; Schoenbaum, E.E.; Klein, R.S.; and Friedland, G.H. Effects of HIV infection on the serologic manifestations and responses to treatment of syphilis in intravenous drug users. Annals of Internal Medicine. 1993; 118:350-355 [PubMed: 8094280]
  3. Hook, E.W. III, and Marra, C.M. Acquired syphilis in adults. New England Journal of Medicine. 1992;326:1060-1069 [PubMed: 1549153]
  4. Jaffe, H.W., and Musher, D.M. Management of the reactive syphilis serology. In: Holmes, K.; Mardh, P.; Sparling, P.; Wiesner, P.; Cates, Jr., W.; Lemon, S.; and Stamm, W. Sexually Transmitted Diseases. 2d ed. New York: McGraw-Hill, 1990, p. 935.
  5. Musher, D.M. Syphilis, neurosyphilis, penicillin, and AIDS. Journal of Infectious Diseases. 1991; 163:1201-1206 [PubMed: 2037785]
  6. Tramont, E.C. Treponema pallidum. In: Mandell, G.L.; Douglas, R.G.; and Bennett, J.E., eds. Principles and Practice of Infectious Diseases. New York: Churchill Livingstone, 1990.