Treponema pallidum pallidum
From IDWiki
Etiology
- Infection by Treponema pallidum subspecies pallidum
Stages
graph LR Syphilis --2 to 6 weeks--> Primary[Primary syphilis] Syphilis --3 weeks to<br/>3 months--> Secondary[Secondary syphilis] Syphilis --years to<br/>decades--> Tertiary[Tertiary syphilis] Tertiary --> Cardiovascular Tertiary --> Gummatous Tertiary --> Neurosyphilis subgraph Neurosyphilis Neurosyphilis --> Meningovascular Neurosyphilis --> Parenchymatous Neurosyphilis --> Tabes[Tabes dorsalis] end
Primary syphilis
- Incubation period is about 3 weeks
- Chancre
- Ulcerative lesion
- Clean borders
- Indurated
- Not painful unless secondarily infected
- Lasts 2 to 6 weeks
- May present with regional lymphadenopathy
- Diagnosis with darkfield microscopy, fluorescent antibody smear, or (most commonly) serology
- Serology often negative in early syphilis
Secondary syphilis
- Incubation period 3 weeks to 3 months
- Often no history of chancre
- Diffuse maculopapular rash that involves palms and soles
- Can have extremely variable presentation
- Generalized lymphadenopathy
- Fever, chills, arthralgias
- Less common: condyloma lata, aseptic meningitis, iritis, mucosal white patches, glomerulonephritis, paroxysmal nocturnal hemoglobinuria, hepatitis
Tertiary syphilis
Neurosyphilis
- Most common tertiary syphilis (75%)
- Incubation period is 7-15 years
- Three major presentations: meningovascular syphilis, parenchymous syphilis, and tabse dorsalis
Meningovascular
- Most common neurosyphilis
- Subdivided into cerebromeningeal (diffuse or focal) and cerebrovascular
- Stroke-like symptoms, especially MCA or basilar territory
- Can present as a sudden change, as syphilitic apoplexy
- Can present following a prodrome of weeks to months of non-specific headaches, vertigo, irritability, insomnia, and personality changes
Parenchymatous
- Previously known as "generalized paresis of the insane"
- Commonly found on psychiatric wards
- Causes psychosis and dementia
- Later, coarse tremors, Argyll-Robinson pupil, paresis
Tabes dorsalis
- Least common neurosyphilis
- Isolated posterior cord degeneration leading to a loss of proprioception in the lower extremities
- Stomp the ground when walking to use intact pain/pressure sensation
- Can present with Charcot foot and, rarely, recurrent abdominal pain
- Diagnosed by serum CMIA, but RPR may be negative
Others
- Isolated ocular neurosyphilis
- Meningitis: can present at any time during the course of disease
- Others
Cardiovascular syphilis
- Incubation period is 20-25 years
- Aortic root involvement leading to aortitis and dilatation
- May result in aneurysm, aortic insufficiency, or angina secondary to stenosis at the aortic root
- Diagnosed by RPR +/- CMIA
Gummatous syphilis
- Least common (10-15%) tertiary syphilis
- Incubation period 6-8 years
- Gummas may appear anywhere, in any organ
- CNS lesions look like toxo, so beware in HIV patients
Other presentations
- Isolated auditory syphilis
- Isolated optic syphilis
Latent syphilis
- Most common form of syphilis is latent, at any stage
Diagnosis
- Often done as non-treponemal test to screen, followed by treponemal test to confirm
- In Ontario, we do a treponemal test to screen (CMIA), then repeat it with a more specific treponemal test (TPPA) alongside RPR
Direct visualization
- Darkfield microscopy
- Chancre cleaned and smear obtained
- Smear must be visualized immediately
- Sensitivity decreases with duration
- Smear for fluorescent monoclonal antibody
- Best to use in primary syphilis
Non-treponemal tests (VDRL/RPR)
- Veneral Diseases Research Laboratory (VDRL) has been replaced by the rapid plasma reagin (RPR) test
- Quantitative tests for a non-specific anti-cardiolipin antibody that is produced in syphilitic (and other) infections
- False positives in pregnancy, autoimmune disorders (lupus, APLA), and chronic infections (leishmaniasis, leprosy, ...)
- 50% sensitive in primary, 100% sensitive in secondary
- Tests will eventually become nonreactive
Treponemal tests
- More specific and sensitive, but more expensive
- False positive in lupus and Lyme disease
- Remain positive for life
- Four main tests:
- Fluorescent treponemal antibody absorption (FTA-Abs): Essentially the gold standard
- Chemoluminescnence microparticle immunoassay (CMIA or CLIA): the screening test used in Ontario. Often used as a screening test as it is an easily-automated immunoassay and is more sensitive and specific than RPR.
- Treponema pallidum Particulate Agglutination assay (TPPA): a modification of the TPHA. Used as the confirmatory test (alongside RPR) used in Ontario.
- T. pallidum hemagglutination assay (TPHA): very old test.
- T. pallidum enzyme immunassay (TP-EIA)
Interpretation of serology
CMIA screen | RPR | TPPA | Interpretation |
---|---|---|---|
Non-reactive | — | — | Negative result; or early syphilis (consider repeat in 4 weeks) |
Reactive | Reactive | Reactive | Recent or prior syphilis infection |
Reactive | Non-reactive | Reactive | Recent or prior syphilis infection |
Reactive | Non-reactive | Non-reactive | False positive; or early syphilis, previously treated, or late latent (repeat in 4 weeks) |
Reactive | Non-reactive | Indeterminate | Inconclusive result; false positive, early syphilis, old treated syphilis, or old untreated syphilis (repeat in 4 weeks) |
Reactive | Reactive | Non-reactive | Inconclusive result; false positive, early syphilis, old treated syphilis, or untreated syphilis (repeat in 4 weeks) |
Reactive | Reactive | Indeterminate | Recent or prior syphilis infection |
Treatment
Primary and secondary
- Benzethine penicillin G 2.4 million units IM once, divided between two buttocks
- Alternative (penicillin allergy): doxycycline 100mg BID for 2 weeks
- Alternative (penicillin allergy and pregnancy): penicillin desensitization or azithromycin
Tertiary
- Benzethine penicillin G 2.4 million units IM q1week for 3 weeks
- Alternative (penicillin allergy): doxycycline for 30 days
- Monitor response with RPR titres, which should drop 4-fold within 6 months
Tertiary (Neurosyphilis)
- Penicillin G 4 million units IV q4h for 10 to 14 days
- Often followed by at least one dose of IM benzethine penicillin, sometimes weekly for 2-3 weeks