Syphilis:
Diagnosis and Treatment
Veronica T. Soler MD
Infectious Diseases
Medical Director& Principal Investigator
South Dakota AIDS Education and Training Center
Clinical Challenges: Syphilis
 Most providers have little experience in diagnosing syphilis
 Even in cities with syphilis outbreaks, most providers see few
cases and under-diagnose
 Syphilis manifestations are protean, and easily misdiagnosed,
particularly rashes, spots, lesions, CNS problems, eye disorders
 A high degree of clinical suspicion is necessary; routinely
perform RPR serology's in high risk persons even if they are
asymptomatic
Clinical Presentation: Clinical Stages of Syphilis
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Primary Stage- chancre- ulcerative lesion
Secondary Stage- rash
Tertiary- cardiovascular or gummatous
Congenital Syphilis- oral defects, teeth and bone
deformities; saber shins, Hutchinson's incisors
• Neuro-syphilis-eye symptoms and central
nervous system problems
• Latent Syphilis
– Early latent < 1 year
– Late latent > 1 year
Latent Syphilis
• A period of time in which there may be no
outward signs of infection
• Between primary and secondary stage,
between secondary relapses, or after secondary
stage
• Categories:
– Early latent: < one year duration
– Late latent: > one year duration
Diagnosis of Syphilis
• Treponema pallidum; has never been cultured.
• The organism can be viewed; indirectly via Dark
Field Microscopy or directly via Fluorescent
Microscopy.
• Serological testing is necessary for diagnosis.
• Multiple tests are often necessary in sequence.
• Services of reference laboratories and clinical
experts are often needed.
• Both non-treponemal and treponemal serologies
are involved and will be discussed.
MICROSCOPY
• Obtain a specimen by scraping the base of the
ulcer/lesion and smearing the material on a
microscope slide
• Place the slide and view directly under the
dark field microscope- not readily available
• Apply antibody tagged fluorescent dye to the
slide and observe under a fluorescent
microscope- also not readily available
80% sensitive; varies with experience/skill of examiner ;
decreased sensitivity as the lesion ages
Fluorescent Microscope:
Demonstration of T. pallidum by using fluorescein-conjugated monoclonal
antibodies
 It is the most specific test for the diagnosis of syphilis when lesions are
present.
Special microscope, and some specialized laboratory handling is required.
Syphilis Serology
• Non-treponemal tests:
– RPR
– VDRL
• Treponemal tests:
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–
–
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FTA-ABS
TP-PA
ELISA/Western Blot
Syphilis PCR- able to detect as low as one to 10
organisms per specimen with high specificity ; limited
availability and not FDA approved
RPR/VDRL
• All non-treponemal tests measure both immunoglobulin IgG
and IgM anti-phospholipid antibodies formed by the host in
response to lipoidal material released by damaged host cells
early in infection and lipids from the cell surface of the
treponeme itself.
• Tests are reported as a qualitative result (RPR) and then as a
quantitative titer (VDRL) which falls back to normal with
successful cure.
• The RPR is reported as a positive or negative result.
• The VDRL is quantified and is followed serially from high titer
to low or undetectable titer as the infection responds to
treatment and resolves (cure).
RPR/VDRL
Non-treponemal serology
• A negative RPR does not exclude the diagnosis of syphilis; only
~75-85% sensitive in primary syphilis but 100% sensitive in
secondary disease.
• The VDRL is quantified (example 1:32) and used to assess
treatment response with four fold drop in titer indicative of
treatment success
• These tests lack specificity (biologic false positives occur) all
reactive tests need to be confirmed by a treponemal test for a
definitive syphilis diagnosis
Potential Pitfalls of Non-treponemal tests
• False positives- the test is measuring
something else that reacts with the reagin but
is not syphilis..
• False negatives- the test is not always positive
in the very earliest phase of infection and
sometimes reverts to negative in tertiary
disease.
Benefits of Non-treponemal Tests
• Easy, inexpensive, fast (RPR).
• Can be quantified (titer) and degree of
antibody levels can be measured (VDRL)
• The antibody titer drops with successful
treatment and reverts to undetectable with
successful treatment.
• The titer becomes positive again with reinfection or relapse of the infection.
Treponemal Tests
Measure specific antibodies to T. pallidum
• TP-PA test; The Treponema pallidum particle
agglutination (TP-PA)- sensitive in primary
syphilis, easy to perform
• FTA-ABS: sensitive in primary syphilis,
complicated and expensive
• Treponemal EIA tests- detect serum
antibodies to T. pallidum
Treponemal Serology
FTA-ABS and others…
• Treponemal tests are used mainly as confirmatory tests to
verify the reactivity in non-treponemal tests.
• However, in populations of low disease prevalence,
treponemal tests can be used for screening.
• All positive patients would either be treated presumptively
because the serious consequences of untreated infection far
outweigh the effect of overtreatment, or have a follow-up
RPR or VDRL to determine if they have active infection before
treatment.
• Usually remain positive for life and are not useful to
determine re-infection.
Diagnostic Flow Chart
DO NOT CONFUSE
Three IM PNC Preparations
• Penicillin G procaine: 600,000 units/mL (1 mL,
2 mL)
• Bicillin® C-R; Bicillin® C-R 900/300: Penicillin G
benzathine and penicillin G procaine; 1.2
million units/mL (1mL, 2mL)
• Bicillin L-A: PNC G Benzathine: 600,000
units/mL (1 mL); 1,200,000 units/2 mL (2 mL);
2,400,000 units/4 mL (4 mL)
Prevention
“ an once is worth a pound”
• Detection of cases; consider it when you have skin sores, oral
lesions, rash or any unusual situation:
– Syphilis is the greatest mimic of all infectious diseases- “when you do
not have a snowballs chance in hell send an RPR/VDRL”.
• Low threshold of testing; RPR/VDRL should be part of your STD/HIV
bundle especially for pregnant, or at risk individuals.
– HIV patients best practice is yearly RPR!
– Treat presumptively for primary syphilis when in doubt.
• Risk reduction- condoms- remember this important prevention
message to all sexually active persons.
• Partner notification and empiric treatment of all sexual contacts
within 90 days.
• Syphilis is a reportable disease in all states.
• Syphilis is curable- treatment as prevention!
Contact Information: www.aidsetc.org
Veronica Soler, MD
PI and SD Medical Director DAETC
vtsolermd@gmail.com
Char Lowman
Program Coordinator
clowman@usd.edu
Rita Shewmake
SD Special Projects Coordinator
ritashewmake@gmail.com