Syphilis:

Return of
the king
Aung Zayar Paing

syphistory.ca
Outline
• Brain teaser
• Introduction
• History of syphilis
• Bacteriology
• Pathophysiology
• Diagnosis
• Treatment
• Syphilis + HIV
Brain teaser

Causal organism of Syphilis ?

Introduction
• Syphilis is one of the earlies STIs in history.
• It was called as ‘the great mimicker’ because its so many signs and
symptoms were difficult to differentiate with other diseases.
• Its origins are still debated and only human can harbor the disease.
• According to WHO, it was estimated that 5.6 million new cases and 18
million prevalent cases of syphilis occurred worldwide in 2012.
• Some reports reflected increased incidence of syphilis (especially in
PLHIV) in recent years.
Trends of syphilis prevalence among
key populations, 2007-2014 (Myanmar)

% 15

12

0
2007 2008 2009 2010 2011 2012 2013 2014
6
Sources: Prepared by www.aidsdatahub.org based on HIV Sentinel Sero‐surveillance Survey Reports.
History of syphilis
• The name ‘Syphilis’ comes from the poem Syphilis sive morbus gallicus (Latin for
"Syphilis or The French Disease") written by Italian physician and poet, Girolamo
Fracastoro in 1530.
• It was called several names depending on the regions and political frictions
among the countries.
• French disease in Italy, Malta, Poland and Germany
• Italian disease in France
• Spanish disease by Dutch
• Polish disease in Russia
• Christian/Frank disease by Turks

• Sometimes called as Great pox to distinguish from smallpox.

History of syphilis (2)
• Early 1800s ‐ Philippe Ricord differentiated syphilis from gonorrhea
• 1837 ‐ he published Traite des maladies veneriennes mentioning the 3 stages of syphilis.

• Late 1800s ‐ Jonathan Hutchinson described about classical ‘Hutchinson’s triad’

of congenital syphilis.
• 1905 ‐ German scientists Fritz Schaudin and Erich Homan identified the gram
negative causal organism for syphilis.
• 1906 ‐ August von Wassermann developed first serologic test (Wassermann
test).
• Early treatments contain arsenic, mercurial compounds with limited efficacy and
high toxicities.
• Fleming’s discovery of penicillin in 1928 and its mass production in 1940s
marked the turning point for syphilis treatment.
montolieu.org
History of syphilis (2)
• 1932 ‐ the notorious Tuskegee study started.
• 1940s ‐ not all the participants did not received the standard
treatment.
• 1972 ‐ the study was discontinued.
• 1997 ‐ President Bill Clinton made a public apology at the White
House attended by the survivors of the study.
 CDC

President Bill Clinton with a study survivor

Origins of Syphilis
• Two theories for the origins of syphilis
• Columbian hypothesis
• Outbreak in 1495 after the return of Columbus from America
• Pre‐Columbian hypothesis
• Skeletal remains showed possible evidence of congenital and tertiary syphilis.
Bacteriology
• Treponema pallidum is the causal organism of syphilis.
• Belongs to a family of spiral‐ shaped bacteria, the Spirochaetaceae
(spirochetes).
• T. pallidum measures 6 to 15 �m in length and is 0.2 �m in diameter.
• Pathogenic only to human.
• Mode of transmission:
• Sexual contact
• Vertical
• Transfusion
Pathophysiology
• Stages of syphilis

Primary Secondary Latent Tertiary

• Condylomata lata • Persistence of organisms • Gumma

Chancres • Clinical latency
• Constitutional Symptoms
• Lymphadenopathy
• Alopecia

6‐8 weeks

1‐20 years
Primary Syphilis
• Incubation period ‐ 3 weeks (range 10‐90 days)
• Genital lesion starts with a papule and then progress to an ulcer
which is
• Painless
• Indurated
• Well circumscribed
• Healed spontaneously within 1‐6 weeks
• Inguinal lymphadenopathy for genital lesions and cervical
lymphadenopathy for oral ones can be present.
• Syphilitic chancres are highly infectious.
 Chancres!

Source: Public Health—Seattle & King County STD Clinic Centers for Disease Control and Prevention
Public Health Image Library (Robert E. Sumpter,
Secondary Syphilis
• This stage indicates haematogenous dissemination of the organism (Bacteremia)
and high infectiousness.
• Secondary stage starts 4 to 8 weeks after the onset of the primary chancre.
• Victims may present with constitutional symptoms such as fever, malaise, arthralgia
• Rash is present in 75‐100% of cases.
• Lymphadenopathy ‐ 50‐86% of cases
• Mucous patches ‐ 6‐30% of cases (oral cavity, pharynx, larynx or genitalia
• Condylomata lata ‐ 10‐20% of patients (wart‐like papules)
• Alopecia ‐ 5% of patients
• Visceral organs involvement
• Neurologic symptoms ‐ can present with neurosyphilis.
Latent Syphilis
• This stage represent the latency of the disease when few signs and symptoms
appear in spite of the persistent of the organisms.
• This stage can occur between primary and secondary and between secondary
relapses.
• The latent syphilis should be considered in the following situations:
• Seropositivity for T. Pallidum
• No past diagnosis of syphilis
• No evidence of active primary, secondary or tertiary syphilis
• It can be subclassified into:
• Early latent syphilis
• Late latent syphilis
• Latent syphilis of unknown duration
Early Latent Syphilis
• It represent the period of infection of < 1 year. (WHO: <2
years)
• No clinical/serological diagnosis of primary/secondary syphilis
with at least one of the following:
• No past signs and symptoms of primary or secondary syphilis
• A documented seroconversion or a sustained (>2 weeks) fourfold or
greater increase in titre in non‐treponemal test in 1 year
• A history of sexual exposure with a partner with documented
primary/secondary/early latent syphilis
• No other source of transmission in 1 year
Late Latent Syphilis
• It represents the infection with > 1 year in duration (WHO: > 2 years)
• No clinical/serological diagnosis of primary/secondary syphilis with at
least one of the following:
• Reactive nontreponemal tests and no past diagnosis of syphilis
• A past history of syphilis treatment and currently reactive nontreponemal test
with fourfold or greater increase from the previous one
Latent syphilis of unknown duration
• It’s the condition when the duration of infection cannot be known.
• It’s practically to manage this condition as late latent syphilis.
Tertiary syphilis
• Also called as late syphilis.
• It’s rare in antibiotic era.
• Without appropriate treatment, about 30% of patients progress to
tertiary stage within 1‐20 years.
• Gummatous lesions can appear in skeletal, spinal and mucosal areas,
eyes and viscera.
• the lesions can be confused with CA.
• About 20‐30 years after infection, it can present as ascending aortic
aneurysm, aortic insufficiency or coronary ostial stenosis.
Neurosyphilis
• The patient can present with neurological signs and symptoms when T. pallidum
invades CNS.
• It can occur in ANY stage of syphilis.
• Early neurosyphilis
• A few years after infection
• Can manifest as acute syphilitic meningitis, a basilar meningitis with cranial nerves III, VI, VII
and VIII involvement, meningovascular syphilis, an endarteritis with stroke‐like syndrome and
seizures.
• Late neurosyphilis
• Decades after infection
• Can manifest as general paresis and tabes dorsalis
• Can also present with wide variety of neurologic symptoms
• Ocular involvement can occur in both early and late.
Ocular syphilis
• T. pallidum can infect any part of eye.
• Signs and symptoms can vary and be broad.
• Anterior/posterior/pan‐ uveitis
• Lid involvement
• Episcleritis
• Vitritis
• Retinitis
• Papillitis
• Interstitial keratitis
• Acute retinal necrosis
• Retinal detachment
• Can present with acute or chronic.
• Ocular syphilis can be seen solely without other neurological manifestations.
 Don’t Forget the Eyes!

CDC. http://www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm. Slide credit: clinicaloptions.com

Laboratory diagnosis of syphilis
• Direct detection of T. pallidum
• Dark‐field microscopy
• Direct Fluorescent antibody test (DFA)
• Nucleic acid amplification tests (NAATs) (PCR)
• Serologic testing for syphilis
• Nontreponemal Serologic Tests: RPR, VDRL, TRUST, USR
• Treponemal Serologic Tests: TPHA, TPPA, FTA‐ABS, EIAs
Direct detection of T. pallidum
• Dark field microscopy of exudate or tissue is the definite method for
diagnosing early syphilis.
• Rarely used in clinical practice
• Oral specimens can produce false positive results due to
nonpathogenic spirochetes from oral cavity.
• Direct Fluorescent antibody test need fluorescent microscope.
• Commercial PCR for T. pallidum is not available
Nontreponemal Serologic testings for
syphilis
• These tests detect anti‐lipid immunoglobin M or G (IgM or IgG)
antibodies.
• False positive results are common because antibodies against T.
pallidum can cross react with those against other spirochetes.
• Changes in titres can help in disease progress monitoring.
• 4 fold or greater changes in titres are considered as significant. (e.g.,
1:8 to 1:32)
• Even after clearance of the organisms with treatment, ‘serological
scar’ may persist with low titre.
Treponemal Serologic Tests for syphilis
• These tests measure antibody directed against T. pallidum antigens by
particle agglutination, immunofluorescence, or enzyme immunoassay
• Some detect IgG only whereas others detect both IgM and IgG.
• The antibody titres of these tests correlate poorly with disease
activity.
• These cannot be used to monitor treatment response.
Clinical Infectious Diseases 2010;51(6):700–708
DOI: 10.1086/655832
from keynote of Simon J. Tsiouris
Prozome Phenomenon

from Dr. T.V. Rao’s slides from slideshare

Testing algorithms

Clin Vaccine Immunol 22:137–147. doi:10.1128/CVI.00681‐14.

 Treatment
Stage Treatment
Early syphilis (primary, secondary IM Benzathine Penicillin G
and early latent syphilis) 2.4 million units x 1
Late syphilis (Syphilis with unknown IM Benzathine Penicillin G
duration) 2.4 million units weekly x 3
Aqueous crystalline
penicillin G, 18 ‐ 24 million
units daily, administered as
Neurosyphilis 3 ‐ 4 million units IV every 4
hours, for 10 ‐ 14 days
(? Followed by IM Benzathine
Penicillin G 2.4 million units)
Alternative treatment (including for
Penicillin allergic patients)
Doxycycline 100 mg bd x 14 days
(Pregnancy: Desensitize?
Erythromycin 500 mg qid x 30 days
IM/IV Ceftriazone 1‐2 G x 10‐14days
Azithromycin 2 G )
Doxycycline 100 mg bd x 30 days
Pregnancy: Desensitize?
Erythromycin 500 mg qid x 30 days
Procaine penicillin G 2.4 million units, IM,
daily
PLUS
Probenecid 500 mg, orally, 4 times a day,
both for 10 ‐ 14 days
HIV + Syphilis
HIV on Syphilis
• HIV infected patients have increased risk of developing neurologic
complications.
• Chancres can be more than one.
• More treatment failures.
• More chance to have higher titres or false negative results of serologic
tests.
Syphilis on HIV

Syphilitic ulcers increase HIV transmission risk. Syphilis can cause transient increase in HIV RNA and
decrease in CD4 count
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References
• National STD Curriculum https://www.std.uw.edu
• Sexually Transmitted Diseases Treatment Guidelines, 2015, CDC
• WHO guidelines for the treatment of Treponema pallidum (syphilis)
2016
• STI management guidelines, 2017 (Myanmar)
Thank you for your attention.