Syphilis

Definition and Causative Organism

• T. pallidum is a delicate, spiral, actively motile organism (5-20 μm long, 4-14 spiral coils)
• It can be seen in fresh lesion preparations by darkfield microscopy or fluorescent antibody techniques
• It lacks the ability to be cultured in vitro due to limited metabolic capacity
• It disseminates widely and rapidly after infection - reaching the bloodstream within hours and the brain within 18 hours of inoculation
• It evades the immune system by expressing very few surface antigens and rapidly mutating its outer membrane proteins

Transmission

• Sexual contact with an infected partner carries a 16-30% risk of acquisition
• Transplacental transmission causes congenital syphilis
• Risk is highest during primary and secondary stages when active lesions are present

Stages of Disease

1. Primary Syphilis

• Appears 2-6 weeks after exposure
• Presents as a painless, indurated ulcer (chancre) with well-defined borders and a clean base
• Usually on the genital mucosa, but can occur on oral or anorectal mucosa
• Heals spontaneously even without treatment

2. Secondary Syphilis

• Develops in 60-90% of persons with untreated primary syphilis
• Results from systemic dissemination of treponemes
• Features: fever, generalized lymphadenopathy, headache, sore throat, arthralgias, and rash (characteristically involves the palms and soles)
• Can also involve the CNS, eyes, liver, and kidneys (immune-complex glomerulonephritis)

3. Latent Syphilis

• Defined by reactive serologic tests without clinical evidence of disease
• Early latent: acquired within the past year
• Late latent: all other cases
• Patients are not infectious (except pregnant women, who can still transmit congenitally)

4. Tertiary (Late) Syphilis

• Cardiovascular syphilis: aortic aneurysm, aortic regurgitation, coronary stenosis
• Neurosyphilis: general paresis, tabes dorsalis, CNS gumma (inflammatory mass with necrotic center)
• Gummatous disease: granulomatous lesions in skin, bones, or viscera

Diagnosis

• In secondary syphilis, RPR is 99% sensitive and MHA-TP is 100% sensitive
• Tertiary syphilis is diagnosed by a reactive RPR + confirmatory treponemal test + consistent clinical findings
• Indications for CSF evaluation include: neurologic/auditory/ophthalmic/cardiovascular signs, treatment failure, or latent syphilis with HIV co-infection

Treatment

• Treatment failure is defined as failure of non-treponemal titers to decrease fourfold (e.g., from 1:32 to 1:8) within 6 months
• Penicillin G remains the only proven treatment in pregnancy

Congenital Syphilis

• Results from transplacental transmission, most common when the mother has untreated primary or secondary syphilis
• Can cause stillbirth, prematurity, or multi-organ disease in newborns
• A recent 2025 meta-analysis (PMID: 41671009) confirmed that treating gestational syphilis even in the last trimester significantly reduces congenital syphilis incidence

Epidemiology

Key Takeaways

• Caused by T. pallidum, transmitted sexually or congenitally
• Four stages: primary (painless chancre) → secondary (systemic rash/symptoms) → latent (no symptoms) → tertiary (heart, brain, gummas)
• Diagnosis by darkfield microscopy (primary) or serology (other stages)
• Fully curable with penicillin G at all stages; early treatment prevents serious complications
• Syphilis co-infection significantly worsens HIV outcomes and vice versa