Treponema pallidum pallidum
From IDWiki
Background
- Causes syphilis
Microbiology
- Small, slow-growing spirochete
- Not seen on standard microscopy; requires darkfield microscopy
Clinical Manifestations
Overview of Stages
- Primary syphilis (incubation period 3 weeks [range 3 to 90 days])
- Secondary syphilis (incubation period 2 weeks to 3 months [range 2 weeks to 6 months])
- Latent
- Early latent (<1 year)
- Late latent (≥1 year)
- Tertiary syphilis (incubation period years to decades)
- Cardiovascular (incubation period 10 to 30 years)
- Gummatous (incubation period 15 years [range 1 to 46 years])
- Neurosyphilis (incubation period 2 to 20 years)
- Meningovascular
- Parenchymatous
- Tabes dorsalis
- Congenital
- Early (< 2 years)
- Late (≥ 2 years)
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
- Typically begins on trunk
- Start as pinkish-reddish macular lesions that evolve into brownish-reddish papules that may have scaling
- May progress to pustular lesions (pustular syphilids)
- May be itchy
- Can be isolated to palms and soles
- Generalized lymphadenopathy
- Fever, chills, arthralgias
- Less common: condyloma lata, aseptic meningitis, iritis, mucosal white patches, glomerulonephritis, paroxysmal nocturnal hemoglobinuria, hepatitis
Latent Syphilis
- Defined as asymptomatic and untreated but with positive serology
- Can be early latent (<1 year) or late latent (≥1 year)
- If unknown duration, late latent is assumed
- High rate of relapse of secondary syphilis within the first 1-2 years following infection (but especially within the first year)
Tertiary Syphilis
- Eventually occurs in about 30% of untreated cases
Neurosyphilis
- Of the 25-60% of people who have CNS invasion, 95% are asymptomatic during the early stage and 80% of those spontaneously clear it
- Incubation period is 7-15 years
- Three major presentations: meningovascular syphilis, parenchymous syphilis, and tabse dorsalis
Meningovascular
- Possibly the 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"
- Occurs in 2-5% of cases of untreated syphilis
- Commonly found on psychiatric wards
- Causes psychosis and dementia
- Later, coarse tremors, Argyll-Robinson pupil, paresis
Tabes Dorsalis
- Occurs in 2-9% of cases of untreated syphilis
- 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
- Loss of sensation in the Hitzig zones (tip of nose, band including nipple area, medial forearms, and lateral leg)
- 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
- Occurs in 10% of people with untreated 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
- Gummas are necrotizing granulomatous lesions
- Occurs in 15% of people with untreated syphilis
- Incubation period 6-8 years
- Gummas may appear anywhere, in any organ, but most commonly on the skin, on mucosa, and in bones
- CNS lesions look like toxo, so beware in HIV patients
Other Presentations
- Isolated auditory syphilis
- Isolated optic syphilis
Congenital Syphilis
- May be either early (<2 years old) or late (≥2 years old)
- Classic Hutchison triad is interstitial keratitis, cranial nerve VIII deafness, and abnormal teeth
- See Congenital syphilis for more information
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:
- Acute biologic false positive: malaria, brucellosis, and mononucleosis; maybe pregnancy
- Chronic biologic false positive: lupus and other autoimmune disorders, HIV, intravenous drug use, and leprosy
- Only 50% sensitive in primary, 100% sensitive in secondary
- Tests wane over time, and can eventually become nonreactive in late latent or tertiary syphilis
Treponemal Tests
- More specific and sensitive, but more expensive
- False positives: lupus and other autoimmune disorders, Lyme disease, and other treponemal infections
- 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 |
Lumbar Puncture for CSF
- Should be done routinely when:
- Neurological (including optic and auditory) signs or symptoms
- Failure of serologic response
- Tertiary syphilis
- Congenital syphilis
- In patients with HIV: CD4 ≤350 and RPR ≥1:32
- The sample should be sent for cell count and differential, protein, and either VDRL (not RPR) or FTA-Abs
- RPR is specific but less sensitive; it helps to rule in CNS disease when present
- FTA-Abs is sensitive but less specific; it help to rule out CNS disease when absent
Management
- The standard first-line therapy is penicillin
- It is the only antibiotic with proven efficacy in neurosyphilis and pregnancy
- In cases of allergy, desensitization is generally preferred to the second-line therapy of doxycycline
- A distant third-line option is ceftriaxone, only used when the others absolutely cannot given the lack of clinical data
- Azithromycin should not be used, given high rates of resistance
- Treatment may be complicated by a Jarisch-Herxheimer reaction
- Patients should avoid unprotected sexual contact until 1 week after completing treatment
| Syndrome | First-Line | Alternative |
|---|---|---|
| Primary syphilis | benzathine penicillin G 2.4 MU IM once | doxycycline 100 mg PO bid for 14 days ceftriaxone 1 g IV/IM daily for 10 days |
| Secondary syphilis | ||
| Early latent syphilis | ||
| Late latent syphilis | benzathine penicillin G 2.4 MU IM weekly x3 | doxycycline 100 mg PO bid for 30 days ceftriaxone 1 g IV/IM daily for 10 days |
| Tertiary syphilis | ||
| Neurosyphilis | penicillin G 4 MU IV q4h for 10-14 days | desensitization
ceftriaxone 2 g IV/IM q24h for 10-14 days |
Primary, Secondary, and Early Latent
- Benzathine 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
- Monitor serologic response with RPR titres at 3, 6, and 12 months, and until negative or stable low titre
- Primary should decrease 4-fold at 6 months and 8-fold at 12 months
- Secondary should decrease 8-fold at 6 months and 16-fold at 12 months
- Early latent should decrease 4-fold at 12 months
Late Latent and Tertiary (excluding neurosyphilis)
- Benzathine penicillin G 2.4 million units IM q1week for 3 weeks
- Alternative (penicillin allergy): doxycycline for 30 days
- Monitor serologic response with RPR titres at 12 and 24 months, and until negative or stable low titre
Tertiary Neurosyphilis
- Penicillin G 4 million units IV q4h for 10 to 14 days
- Often followed by at least one dose of IM benzathine penicillin, sometimes weekly for 2-3 weeks
- Monitor serologic response with RPR titres at 6, 12, and 24 months, and until negative or stable low titre
- Repeat lumbar puncture every 6 months until parameters normalize
- Pleocytosis normalizes first, within 6 months, followed by protein levels over months to years
- CSF-VDRL should decrease 4-fold in 12 month if it is high, but can persist for years until negative
Pregnancy
- Only penicillin is recommended, including desensitization if needed for allergy
- Some expoerts recommend a second dose of benzathine penicillin G 2.4 MU IM a week after the first dose for primary, secondary, or early latent syphilis
HIV Coinfection
- Treat as above
- Regardless of stage, monitor response with RPR titres at 3, 6, 12, and 24 months, then annually
- CSF parameters normalize more slowly in people with HIV
Congenital Syphilis
- If <1 month of age: crystalline penicillin G 50 kU/kg IV q12h for the first week of life and q8h thereafter, for a total of 10 days
- If ≥1 month of age: crystalline penicillin G 50,000 units/kg IV every 6 hours for 10-14 days
- If there is no neurological involvement, then you can consider benzathine penicillin G 50 kU/kg (max 2.4 MU) IM weekly for 3 weeks
Prevention
Public Health
- Contact tracing should be performed, identifying contacts within the presumed maximum incubation/latency period
- Primary syphilis: 3 months
- Secondary syphilis: 6 months
- Early latent syphilis: 1 year
- Late latent or tertiary syphilis: as appropriate
- Contacts should be tested, and treated if positive
- Reasonable to empirically/epidemiologically treat contacts from the previous 90 days if loss-to-follow-up is likely
