Treponema pallidum is member of family Spirochaetaceae. They are Gram negative bacteria, but some regard them too thin to be Gram stained. It is a delicate, tightly spiraled, motile spirochete having tapered ends. It is microaerophilic bacteria that cannot be grown on standard culture media. These microbes are poorly stained, so not detected by conventional light microscopy.
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Image : “2ndsyphil2” by
Herbert L. Fred, MD, Hendrik A. van Dijk. License: CC BY-SA 2.0

Treponema Pallidum

It can be detected in clinical samples through dark-field or phase contrast microscopy or direct immunofluorescent staining. It cannot be even cultured in standard culture media.

At least four subspecies are known:

  1. Treponema pallidium pallidum, which causes syphilis
  2. T. p. endemicum, which causes bejel or endemic syphilis
  3. T. p. carateum, which causes pinta
  4. T. p. pertenue, which causes yaws

Treponema causes a disease called syphilis. It is a chronic systemic disease transmitted sexually from person to person. Infection can be treated if detected early but manifests late and has significant morbidity if left untreated.

Epidemiology of Syphilis

This disease can be acquired or congenital. It can occur in children and adolescents as well. It is prevalent in the whole world most common in many underdeveloped countries, the main group of people affected by the disease is sexually active age groups.

The highest incidence in U.S. Men who have sex with men among poor, minority communities in southern states. Rates in Europe are 4.4-10.4/100,000 population. Increased rates in eatern Europe and Russia.


Acquired syphilis is transmitted exclusively by sexual contact, i.e. vaginal, anal, and oral. Other modes of transmission are through blood transfusion or direct contact with infected tissues.

Primary and secondary syphilis peaked in 1989 in the US; later, the annual rate declined by 90% until 2000. After 2000, due to sexual contact of men with men, the total number of cases of primary and secondary syphilis has increased significantly.

Congenital syphilis also became common after 2004 but has now fallen after 2008. Congenital syphilis is transmitted through the placenta during pregnancy or during childbirth through direct contact of the child with the infectious lesions.

Women with active disease have more chances of transmission to the child, compared to ones with latent infection. Early transmission can even lead to fetal loss, preterm or low birth-weight infants, stillbirths, neonatal deaths, or infants born with a congenital disease.

The risk of transmission is highest during the first four years. Risk factors for the congenital disease include limited access to healthcare, late or no prenatal care, maternal drug use, multiple sex partners, unprotected sexual contact, work in the sex trade, and inadequate treatment of syphilis during pregnancy.

Clinical Manifestations and Laboratory Findings

Infected individuals often do not exhibit symptoms for years without evident early signs of the disease. The Centers for Disease Control and Prevention (CDC) recommend screening of even young adults if they have lesions or positive risk factors.

treponema pallidum Dieterle stain

Image: “Micrograph showing Treponema pallidum, the spirochete that causes syphilis. Dieterle stain.” by Nephron – Own work. License: CC BY-SA 3.0

Primary syphilis

Primary disease occurs alone in the absence of any other disease and it is characterized by a chancre and regional enlarged lymph nodes (lymphadenitis).

Initially, a small painless papule is formed at the site of infection, mostly genitals roughly 2-6 weeks after contact or transmission. Later it becomes a clean, painless and highly contagious ulcer having raised borders called the chancre.

Chancre is full of T. pallidum, the organism causing the disease. Chancres can be found on extra-genital areas as well making it difficult for diagnosis. Lesions in the oral cavity can be misdiagnosed for aphthous ulcers or herpes. Lesions on the nipple can be mistaken for cellulitis or eczema.

Painless lymphadenopathy is a typical feature of this disease. The chancre heals after 4-6 weeks into thin scar tissue. Those who are not treated develop the symptoms of secondary syphilis after 2-10 weeks of healing.

Secondary syphilis

Untreated primary syphilis complicates later on into secondary syphilis. Patient presents with generalized nonpruritic maculo-papular rash more on the palms and soles along with pustular lesions. Various skin lesions in this disease include Condylomata lata and white plaques.

Condylomata lata are grayish white or sometimes reddish erythematous wart-like lesions mostly around the anus and vagina, and white plaques (mucous patches) may be found in mucous membranes.

Other clinical features include flu-like symptoms with low-grade fever, headache, malaise, anorexia, weight loss, sore throat, , arthralgias, and generalized lymphadenopathy.

Systemic involvement

Renal, hepatic, and ophthalmologic involvement can occur. Approximately 30% of patients can have meningitis proven on CSF examination which shows pleocytosis and raised protein level. Without treatment, if the patient survives, secondary infection subsides after a month and later relapses after one year almost with tertiary syphilis.

Tertiary syphilis

Tertiary disease occurs in one-third of the untreated cases. Patients usually come with neurologic, cardiovascular, and gummatous skin lesions.

Diagnosis of Syphilis

It is difficult to diagnose this disease through usual investigations, but specific labs along with correlation with the history and examination results can lead to the diagnosis. Syphilis should be treated if suspected clinically and on the basis of epidemiology.

For primary disease

Presence of T. pallidum can be confirmed by dark-field microscopy or direct fluorescent antibody testing on samples from skin lesions, placenta, or umbilical cord. Polymerase chain reaction (PCR) can be done but not usually done. Serologic testing for antibodies is the principal diagnostic test. Suspected patients with T. pallidum infection should be screened using non-treponemal test followed by a confirmatory treponemal test.

Non-treponemal test

These include:

  1. Venereal Disease Research Laboratory (VDRL) tests and
  2. Rapid plasma reagin (RPR) tests

“Rapid Plasma Reagin” Image created by Lecturio

Antibodies against phospholipid antigens on the surface of the organism that cross-react with cardiolipin-lecithin-cholesterol antigens of damaged host cells are detected in these tests. Both qualitative and quantitative tests can be done for both screening and monitoring the therapy. Antibody titers increase with active disease, treatment failure or in reinfection. Titers decrease with proper treatment.

Biologic false:

Transient Chronic
  • Malaria
  • Brucellosis
  • Mononucleosis
  • Autoimmune diseases (esp. SLE)
  • HIV infection
  • IV drug use
  • Leprosy
  • Hepatitis C

Treponemal tests

Treponemal tests are done to confirm the diagnosis and measure specific T. pallidum antibodies (immunoglobulin IgG, IgM, and IgA). These antibodies appear even before non-treponemal antibodies appear in the body. These include:

  1. T. pallidum particle agglutination test
  2. T. pallidum hemagglutination assay
  3. Fluorescent treponemal antibody absorption test.

Treponemal antibody titers are positive even after initial infection. It remains positive for life.

Therapy of Syphilis

Early syphilis (primary, secondary, or early latent syphilis):

  • Benzathine penicillin G, 2.4 MU IM (single dose)
  • Alternative regimens: Doxycycline 100 mg PO bid x 14 d and Ceftriaxone 1 g IM or IV daily x 10–14 d and Tetracycline 500 mg orally four times daily x 14 d and Amoxicillin 3 g plus probenecid 500 mg, both given orally twice daily x 14 d

Neurosyphilis (including otic & ocular):

  • Penicillin G 18–24 MU IV daily (3–4 MU IV q 4 h) x 10–14 d
  • Procaine penicillin G 2.4 MU IM daily, plus probenecid 0.5 g PO qid x 10–14 d
  • Alternative: ceftriaxone 2 g IM or IV daily x 14 d

Late latent syphilis, tertiary syphilis, or syphilis of unknown duration:

  • Benzathine penicillin G 2.4 MU IM weekly x 3
  • Alternative regimen: Doxycycline 100 mg PO bid x 28 d


  • As for non-pregnant patients
  • Penicillin-allergic patients should be desensitized & treated with penicillin
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