Treponema pallidum

Treponema pallidum is the spirochete bacterium responsible for syphilis, a sexually transmitted infection that can also be transmitted from mother to child during pregnancy. 

Known as "the great imitator" due to its diverse clinical presentations across primary, secondary, latent, and tertiary stages, this pathogen can lead to severe complications including neurosyphilis, cardiovascular syphilis, and congenital syphilis if left untreated.

What is Treponema pallidum?

Syphilis is a sexually transmitted infection (STI) caused by Treponema pallidum, a spirochete that spreads through sexual contact or vertical transmission during pregnancy. 

Known as "the great imitator," it presents in distinct stages with relapsing and remitting symptoms—primary, secondary, latent, and tertiary—each with varying systemic manifestations. 

If untreated, syphilis can lead to severe complications, including neurosyphilis, cardiovascular syphilis, and congenital syphilis.

Clinical Stages of Syphilis

Syphilis progresses through discrete clinical stages that must be identified and treated promptly.

Primary Syphilis

Primary syphilis develops 10–90 days after exposure. It presents with a painless, indurated chancre at the infection site (genital, anal, oral).

Primary syphilis resolves in 3–6 weeks even without treatment, but systemic spread occurs.

Secondary Syphilis

Secondary syphilis appears 2–24 weeks after the primary lesion resolves. It is characterized by a maculopapular rash (palms/soles), mucous patches, condylomata lata, fever, and lymphadenopathy in up to 85% of cases.

Secondary syphilis is highly contagious and may relapse if untreated.

Latent Syphilis

Latent syphilis is an asymptomatic phase detected only via serology.

• Early latent (<1 year): High transmission risk, possible symptom recurrence.
• Late latent (>1 year): Lower transmission risk but disease progression risk remains.

Tertiary Syphilis (Rare but severe complications in untreated cases)

If untreated, syphilis can progress to tertiary syphilis, which includes:

• Neurosyphilis: Stroke, dementia, sensory loss (tabes dorsalis).
• Cardiovascular syphilis: Aortitis, aneurysm formation.
• Gummas: Soft, destructive granulomas affecting skin, bones, or organs.

Congenital Syphilis

Congenital syphilis results from maternal-fetal transmission, leading to stillbirth, neonatal death, or severe complications.

Early signs include hepatosplenomegaly, rash, skeletal abnormalities.

Late signs include Hutchinson’s triad (interstitial keratitis, notched incisors, deafness).

Prevention includes routine prenatal screening and penicillin treatment.

Syphilis Diagnosis and Serology

Serologic Testing is the gold standard. Because T. pallidum cannot be cultured, serologic tests are essential for screening, diagnosis, and monitoring.

Testing Procedure

Syphilis serologic testing typically follows a two-step approach, beginning with a nontreponemal test (RPR or VDRL) for screening. If reactive, a treponemal test (TPPA, FTA-ABS, or EIA/CIA) is used for confirmation. 

Blood samples are taken via venipuncture and analyzed for antibodies, with titers measured in serial dilutions for disease staging and treatment monitoring. 

In cases of suspected neurosyphilis, cerebrospinal fluid (CSF) is tested using CSF-VDRL or CSF FTA-ABS to detect central nervous system involvement.

Nontreponemal Tests (Screening & Monitoring)

Nontreponemal tests detect anti-cardiolipin antibodies, which are in response to cellular damage, not T. pallidum directly.

This testing is used for screening, staging, and treatment monitoring.

Examples include:

• Venereal Disease Research Laboratory (VDRL)  
• Rapid Plasma Reagin (RPR)

Limitations of Nontreponemal Tests:

False positives occur in pregnancy, autoimmune diseases (e.g., lupus), and certain infections.

Titers correlate with disease activity—a fourfold decline in RPR/VDRL (e.g., from 1:32 to 1:8) within 6–12 months suggests successful treatment.

Persistent low-positive titers (≤1:8) may indicate a serofast state, where antibodies remain despite effective treatment.

Rising titers after treatment suggest reinfection or treatment failure, warranting further evaluation.

Treponemal Tests (Confirmatory)

Treponemal tests detect antibodies against T. pallidum; results remain positive for life. Rapid tests are available and allow for same-visit treatment initiation.

Examples include:

• Fluorescent Treponemal Antibody Absorption (FTA-ABS)
• Treponema Pallidum Particle Agglutination (TPPA)
• Enzyme Immunoassays (EIA/CIA)

Treponemal testing is not useful for monitoring treatment response.

Testing Algorithms

The CDC and other medical authorities recommend the following algorithms: 

• Traditional Algorithm: Start with RPR/VDRL → Confirm with TPPA/FTA-ABS.
• Reverse Algorithm: Start with TPPA/EIA → Confirm with RPR/VDRL (used in high-volume labs).
• Neurosyphilis Testing: Requires CSF analysis:
  
  • CSF-VDRL (most specific, but low sensitivity).
  • CSF FTA-ABS (more sensitive but less specific).

Special Populations

Pregnant Women: Universal screening is recommended at first prenatal visit; this should be repeated for high-risk cases. A woman delivering a stillborn infant after 20 weeks should be tested for syphilis.

HIV Patients: These individuals are at higher risk for neurosyphilis; test interpretation is similar to HIV-negative individuals.

Congenital Syphilis: Neonatal RPR/VDRL (not treponemal tests) used for diagnosis.

Treatment Guidelines

Penicillin is the gold standard for syphilis treatment.

Primary, Secondary, or Early Latent Syphilis 

General recommendations for penicillin doses include:

• Benzathine Penicillin G 2.4 million units IM (single dose).
  
  • Benzathine Penicillin G (BPG) is the only WHO-recommended treatment for syphilis in pregnancy.
• Late Latent or Tertiary (excluding neurosyphilis):
  
  • Benzathine Penicillin G 2.4 million units IM weekly ×3 weeks.

Neurosyphilis, Ocular, or Otosyphilis

Treatment for neurosyphilis, ocular, or otosyphilis includes aqueous Penicillin G 18-24 million units/day IV for 10–14 days.

Congenital Syphilis

Treatment for congenital syphilis includes aqueous Penicillin G IV for 10 days. Babies with congenital syphilis require immediate treatment.

Penicillin Allergy Alternatives

Patients who cannot use penicillin may instead be given: 

• Doxycycline 100 mg BID ×14 days (primary/secondary).
• Ceftriaxone 1–2 g IV/IM daily ×10–14 days (for neurosyphilis).
• Pregnant patients require desensitization—no alternatives exist.

Follow-Up and Monitoring

Repeat RPR/VDRL titers at 6, 12, and 24 months to confirm treatment success. A fourfold decline in titers confirms treatment success.

Rising titers suggest reinfection or treatment failure.

Public Health and Prevention

Public health and prevention measures include:

• Routine STI screening for high-risk groups (MSM, sex workers, multiple partners).
• Prenatal screening to prevent congenital syphilis.
• Condom use reduces but does not eliminate transmission.
• Contact tracing and partner treatment are critical.

Key Takeaways for Clinicians

• Syphilis can be asymptomatic—screen high-risk individuals.
• Always confirm reactive nontreponemal tests with a treponemal test.
• Penicillin is the only recommended treatment for pregnant women.
• Monitor treatment success with serial RPR/VDRL titers.
• Encourage partner notification and STI screening.

Early detection and treatment prevent severe complications and reduce transmission.

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