SEMINAR PRESENTATION

SYPHILIS

MODERATOR
DR.C.M. KULDEEP
 INTRODUCTION
• Syphilis - infectious treponematoses caused by Treponema
pallidum transmitted usually by sexual intercourse

• Discovered by Schaudinn and Hoffmann(1905)

• Affects most of the organs

– Marked by florid manifestations on the one hand
– And years of asymptomatic latency on the other hand

• Affects both man & women in age group of 20-40 years

 STRUCTURE AND PHYSIOLOGY
OF TREPONEMES
• motile spiral-shaped gram –ve
bacteria
• Size – approx 10–14 μm in length
and 0.1–0.2 μm in diameter,10
regular spirals at interval of about
1 μm.
• Outer membrane of T. pallidum
differs from most gram-negative
bacteria in major respects:
 lacks lipopolysaccharide
 has a dearth of integral
membrane proteins
 has less cytoplasm
 And has 9 cytoplasmic fibrils
• T. pallidum - stealth pathogen(antigenic inertness)

MOTILITY
• T. pallidum is actively motile, moving with a corkscrew motion, with bending
and flexing, but with little translational movement

CHEMOTAXIS
• Chemotaxis machinery is thought to assist T. pallidum as it navigates
throughout the body during dissemination
• Recent microarray studies indicate that a number of chemotaxis genes are
upregulated during early active syphilis infection

Two strains – Nichol’s and Reiter strains

 METABOLISM AND SURVIVAL IN
VITRO
• Lacks genes for –
Krebs cycle
Haem proteins involved in electron transport
To synthesize most amino acids purines, pyrimidines and lipids
• This suggests that T. pallidum is able to generate only two molecules of
ATP per glucose molecule through glycolysis
• Accounting for its significantly lower growth rate (generation time of
~30–33 hours).
• Survives better in microaerophilic rather than anaerobic conditions
• So far it had not been cultured in artificial media
 Range 9- 90days

2-12 WEEKS
 Pathogenesis
Mode of transmission
1. Sexual intercourse
2. Blood transfusion
3. Contaminated needles
4. Vertical transmission
5. To hospital personnel by
indiscriminate handling of
infected lesions
1.ATTACHMENT, INVASION AND
DISSEMINATION
2. INNATE HOST RESPONSE – TLR2
3. ACQUIRED IMMUNITY - clinical
manifestations caused by
inflammatory and immune
responses rather than by any direct
cytotoxic effect of T. pallidum
4. BACTERIAL CLEARANCE- phagocytosis
of treponemes by macrophages
• Predominant cytokine –Th1
• Predominant mediator- IFN-γ
5. ANTIBODIES IN SYPHILIS
6. INVASION OF HOST IMMUNITY AND
ESTABLISHMENT OF LATENT
INFECTION
7. PROTECTIVE AND LONG-LASTING
IMMUNITY
• Of these, only relative lack of surface proteins is currently considered to
be major factor in persistence.
• One of most intriguing discoveries in syphilis pathogenesis is recent
description of antigenic variation
• The gene encoding TprK, a putative target of opsonic antibody, was
demonstrated to have seven sequence variable regions (V regions)
• Thus, changing the amino acid sequence of antibody epitope even
slightly permits bacterium to escape activities of anti-TprK antibodies that
are induced during infection.
• This antigenic variation mechanism likely permits some treponemes to
escape local bacterial clearance during resolution of early lesions
• And contributes to the long-term survival of T. pallidum during latent
syphilis and chronic infection
• Study demonstrate that immunity to syphilis is very slow to develop, is
often incomplete except in untreated syphilis, and may be strain specific
 Classification of Syphilis
Clinical course of acquired
syphilis is divided in to
early &late syphilis.
1. Early-duration is 1 yrs.
– Includes primary and
secondary stage and
early latent syphilis
2. Late-after 1 yrs.
– Include late latent &
tertiary syphilis
Congenital Syphilis
• COLLES’S LAW(1837)
Syphilitic infants could transmit the
disease to previously healthy wet
nurses but never to their own
mother
• KASSOWITZ’S LAW(1876)
Untreated syphilitic mother tends to
improve on her past performance
 PRIMARY SYPHILIS
• Starts as painless, erythematous
indurated papule – ulcer
• Usually single , painless, clean, well
defined, Nontender & markedly
indurated
• Site - genital, perineal or anal area;
however, any part of the body may be
affected
• Syphilis d emblee- when primary
chancre may be overlooked or
concealed
• Phagedena – invasion of ulcer with
Vincent organisms may result in
gangrenous changes
• Heal spontaneously leaving behind
tissue paper scar
• Lymphadenopathy
• Inguinal lymph node invariably
involved
• Multiple, non
tender, discrete, rubbery , Usually
Bilateral
Regardless of stage of disease and
location of lesions, histopathologic
hallmarks of syphilis include
endarteritis (which in some instances
may be obliterative in nature) and a
plasma cell–rich infiltrate.
 SECONDARY SYPHILIS
• 2-12 weeks of development of primary syphilis – pt manifests
with symptoms of secondary syphilis
• Characterized by low-grade fever, malaise, sore
throat, headache, adenopathy and cutaneous or mucosal
rash.
• Manifest as- Evanesent copper-colored macular rash
• A few days later, symmetric papular eruption
appears, involving entire trunk and the extremities, palm and
soles
• Papules - reddish brown,scaly,discrete,0.5–2 cm in diameter.
• Variats - pustular,combination of these , lichenoid , acneiform
nodular ,circinate,corymbose,annular
• 25% of pts have abnormal CSF
Fig.Secondary syphilis,macular rashes
FIGURE . Secondary syphilitic rash on palm and sole.
Syphilitic alopecia Mucus patches involving the
scalp has moth-eaten appearance tongue in secondary syphilis.
eyebrow hair is absent there is rash
on the cheek
• Mucosal lesions -
small, superficial, ulcerated areas
with grayish borders that resemble
painless aphthous ulcers or larger
gray plaques
• Condyloma lata is a term used to
describe large, raised, whitish or gray
lesions found in warm, moist
areas,intertriginous area
• Generalised LN enlargement present
in majority of pts
• Periosteal inflammation – 25% cases
• Subclinical hepatitis - 20%
• Iritis , glomerulonephritis or
nephrotic syndrome - Deposition of
immune complexes
 LATENCY
• Definition-persons with historical or serological evidence for
syphilis who have never received treatment for this disease and
who have no clinical manifestations (Symptoms/Sign)

• Requires exam of CSF to rule out asymptomatic neurosyphilis

• In Oslo study of untreated syphilis ,secondary relapses occurred in

25% of patients whose infection had become latent, with most
relapses occurring in the first year.

• U.S. Public Health Service therefore defines early (potentially

infectious) latency 1 year from onset of infection
 TERTIARY SYPHILIS
• Morbidity and mortality of syphilis in adults in past years were
due to late manifestations of illness

• There may be an interval of 1 - 20 yrs from acute infection to

clinical onset of late or tertiary stages of disease

• Tertiary syphilis conveniently divided into three main groups

 Late benign syphilis
 Cardiovascular syphilis
 Neurosyphilis
 BENIGN TERTIARY SYPHILIS
- Characterized by gumma & appear 3-10 yrs after infection

- proliferative granulomatous inflammatory process causing

destructive of affected tissues

- Most lesions occur in skin and bones, with lesser frequency in

mucosa and of viscera muscles and ocular structures

Theory:
1. Best evidence in support of hypersensitivity was
provided by Magnuson et al. who inoculated volunteers in Sing
Sing Prison with the Nichols strain of T. Pallidum
2. Gummas developed only in persons with a history of
previous syphilis .They concluded that superinfection in sensitized
patient may explain gumma formation
 Clinical manifestations
Skin- Two forms may appear: nodular or noduloulcerative and solitary
lesion.
• 1.Nodular and noduloulcerative 2.The solitary gumma
lesions deep indurated nodule Subcutaneous process that
reddish brown in colour that involves the skin secondarily
varies in size • Site -
• Multiple nodules - distributed in thighs, buttocks, shoulders, foreh
arciform pattern ead and scalp.
• Site - face,scapular,interscapular • As it becomes necrotic it has
areas and extremities characteristics of “cold abscess”
• May remain for weeks or mths • These lesions resolve promptly
and may heal without breaking with effective treatment
down but - show scarring
• If nodular lesions break down to
noduloulcerative form, they heal
leaving atrophic noncontractile
scar
• Skeleton- periostitis, gummatous osteitis and sclerosing osteitis.
• C/Fs- pain (especially nocturnal), tenderness, swelling, bony tumor, stiffness
and limited motion

• Upper respiratory tract, mouth, and tongue- Gummatous osteitis of the nasal
bones, hard palate and nasal septum(perichondritis)

• Digestive system-can involve any part

• Gumma of the liver was the most common

• Myocardium-gummas especially of the left ventricle and commonly

asymptomatic have been reported
A. Nodular syphilid on inferior side of the penis. B. Nodular syphilid of the pubic
area and solitary gumma on dorsum of the penis. C. Nodular
syphilid of the knee. There were signs of aortic incompetency.
FIGURE Ulcerating solitary gumma of skin of 12 months’ duration.
Note scarring from spontaneous healing. Accompanying solitary ulcers on
each shoulder and on the leg, 4–8 cm in diameter, began as pimples
7 months previously.
FIGURE . Osteitis of hard palate with perforation
 CARDIOVASCULAR SYPHILIS
• Clinically manifest after latent period of 15–30 years

Pathology
• Spirochetes appear to have predilection for vasa vasorum of
aorta particularly the proximal aorta
• Produce transmural inflammatory lesions - endarteritis of
these vessels
• Obliteration of lumen of vasa vasorum the aortic media
develops patchy necrosis with subsequent focal scarring
Aortic aneurysm Coronary artery disease
• MC manifestations • Only the ostia or most proximal
few mm of coronary arteries are
• Virtually involve ascending thoracic affected
aorta

• May lead to IHD including angina

• Syphilitic aneurysms do not dissect
probably because of the medial
scarring and wall thickening
• Symptom - develop when aneurysm
encroaches on surrounding
structures or ruptures
pectoris or sudden death
Aortic regurgitation
• Pure AR without stenosis
formerly was common
cardiovascular manifestation

• Radiograph may be N or show a

• Occurring in roughly 30% of pts
mediastinal mass with typical
eggshell calcification outlining
aneurysm
 NEUROSYPHILIS
• Abnormalities in CSF have been noted in
 13% of pts with untreated primary syphilis
 25–40% of pts with untreated secondary syphilis

• After initial invasion of CNS during early syphilis, untreated

infection
 may resolve spontaneously
 persist as asymptomatic syphilitic meningitis
 progress to symptomatic acute syphilitic meningitis
 progression of early asymptomatic or symptomatic meningeal infection
may lead to meningovascular syphilis (usually 5–12 yrs after primary
infection) or parenchymatous forms of neurosyphilis such as tabes or
paresis (usually 18–25 yrs)
Table. Classification of Neurosyphilis
Asymptomatic 31a
Early
Late
Meningeal 20
Acute syphilitic meningitis 6
Meningovascular 11b
Cerebral
Spinal form 3
Parenchymatous 48
General paresis 12
Tabes dorsalis 30
Taboparesis (mixed) 3
Optic atrophy 3c
Gummatous 1
Cerebral form
Spinal form
Total 100
aDistinction between early and late asymptomatic syphilis could not be
made.
b”Deafness,” comprising 1% of cases in Merritt et al.26, was included in this
category.
c“Optic neuritis,” comprising 3% of cases in HH Merritt et al.26, was included
in this category.
 Lab diagnosis of syphilis
Tests are divided in four categories -

– (i) direct microscopic exam - used when lesions are present

– (ii) non treponemal tests - used for screening
– (iii) treponemal tests - are confirmatory
– (iv) direct antigen detection tests - used in research
settings and as gold standards for test evaluation
 Direct detection methods
1.Animal inoculation
• Oldest method
• Most sensitive method
• Used as gold standard for measuring sensitivity of methods such as
PCR

2.Dark-field microscopy
• When lesions are present, most specific and easiest means of
diagnosing syphilis is by direct detection of organism
• Since treponeme are viabile organisms examination must be
accomplished immediately after specimen is obtained
• Most productive during primary, secondary, infectious relapsing and
early congenital syphilis
• Enlarged regional lymph nodes can also serve as a specimen source
• Lesion should be cleansed only if encrusted or obviously
contaminated
• Normal saline (without antibacterial additives) should be used
• After cleansing lesion, gently abrade it and apply gentle pressure
until only clear serum exudes
• Place a drop of serum on surface of cover slip or slide
• Positive findings on dark-field examination permit specific and
immediate diagnosis of syphilis
• Sensitivity of this test is not more than 50% hence it should be done
on 3 consecutive days
3.DFA-TP
• Detects and differentiates
pathogenic treponemes from
nonpathogenic treponemes
• Hence Organism is not required
to be motile in DFA-TP
• Drawback-cannot distinguish
between the pathogenic strains
of Treponema spp.
4.DFAT-TP test
• Use of DFA-TP test has been
extended to include staining of
tissue sections
• Used to diagnose late-stage or
congenital syphilis or to
distinguish skin lesions of
secondary or late syphilis from
those of Lyme disease
 Non treponemal Tests
1. VDRL( veneral disease research laboratory test)
2. USR(unheated serum reagin)
3. RPR(rapid plasma reagin)
4. TRUST(toludine red unheated serum test)

• USR test antigen is VDRL antigen stabilized by the addition of

EDTA
• So Need for daily preparation of an antigen suspension is
eliminated
• TRUST and RPR card test antigens differ only in the
visualization agent added to antigen
For RPR card test - sized charcoal particles are added to antigen
For TRUST - paint pigment particles are added
• Particles of both tests become entrapped in antigen-antibody lattice
formed with a reactive serum

• Based on an antigen composed of : alcoholic solution containing

measured amts of cardiolipin , cholesterol and sufficient purified lecithin
to produce standard reactivity

• Serum - specimen of choice for both non treponemal and treponemal

tests

• VDRL only test that can be used for testing CSF (NEUROSYPHILIS)

• In screening for congenital syphilis, CDC recommends the testing of

mother’s serum followed by neonatal serum - with cord blood being least
reactive
• Done in two ways : qualitative
and quantative
• Quantitative tests - establish
baseline of reactivity from which
change can be measured
• Recent infection can be
demonstrated by fourfold rise in
titer
• Reinfection / relapse can be
detected among persons with a
persistently reactive (serofast)
test for syphilis
• All non treponemal tests have
approx same sensitivity and
specificity
• Advantage :
- widely available
- inexpensive
- convenient to perform on large
numbers of specimens
- necessary for determining
efficacy of treatment
• Limitations
- lack of sensitivity in early dark
field- positive primary cases and
in late syphilis
- possibility of prozone
reaction(false-negative) or false-
positive results
• Non treponemal (reagin) tests measure IgM and IgG
antibodies to lipoidal & lipoprotein-like material released
from damaged host cells as well as to cardiolipin released
from treponemes

• Without some other evidence for the diagnosis of syphilis, a

reactive non treponemal test does not confirm T. pallidum
infection

• Causes of False-positive reactions

 Acute: < 6 month duration
 Chronic :>6 month duration
 Treponemal Tests
• FTA-ABS, FTA-ABS double staining, MHA-TP and TPI
• Use - T. pallidum as antigen
• Confirmatory test - Used when non treponemal test is NR but
there is evidence of syphilis, such as might occur in late syphilis
• Technically more difficult and costly to perform and cannot be
used to monitor treatment
• 1% of the general population will have false-positive results(cause is
unknown)
• A definite association has been made between false-positive FTA-
ABS test results and the diagnosis of systemic, discoid, and drug-
induced varieties of LE
• Patients with SLE can have false-positive FTA-ABS tests that
exhibit an ‘‘atypical beading’’ fluorescence pattern
• To resolve these types of false positive reactions, absorption with
calf thymus DNA can be used to remove the anti-DNA antibodies in
the serum

• Some false-positive reactions may be due to failure of sorbent

used in the tests to remove all cross-reacting group, genus, or
family antibodies, e.g. in Lyme disease

• In these instances, absorption with Reiter treponeme or the use of

hemagglutination test may be only means of differentiating
between syphilis and a falsepositive reaction

• MHA-TP is more sensitive and specific than FTA-ABS except In 3rd

to 4th wk of infection
1.FTA-ABS test:
• Indirect fluorescent-
antibody technique • Employs
• Patient’s serum is first
diluted in sorbent (an
extract from cultures of
nonpathogenic Reiter
treponeme)
2.FTA-ABS test double
staining method:
tetramethylrhodamine
isothiocyanate-labeled
anti-human IgG and
counterstain with FITC-
labeled anti-T. pallidum
conjugate

• To remove group • Counterstaining organism

treponemal antibodies that
are produced in some
persons in response to
nonpathogenic treponemes
ensures that nonreactive
result is due to absence of
antibodies and not to
absence of treponemes on
slide
3.T. pallidum immobilization (TPI) test:
• In 1949, Nelson and Mayer proved that serum from syphilitic patients
contains an antibody which in presence of complement inhibits normal
movements of virulent T. pallidum
• Reaction of treponemes in presence of patient’s serum is observed by
dark-field microscopy
• Positive - 50% or more are immobilized test
• Negative - if less than 20%
• In 99% of cases, result is very clear-cut and certainly very
specific, probably nearly 100%
• Test is time consuming and expensive
Table :Sensitivity and Specificity of Serologic Tests for Syphilis
MOLECULAR BIOLOGY-BASED METHODS FOR THE
DIAGNOSIS OF SYPHILIS
• Shortcomings of standard tests for syphilis for diagnosis of
early primary, congenital and neuro syphilis have made
techniques based on detection of treponemal DNA or
antigens

1. DNA Probes
• Assay gave a positive result when approx - 2,500 treponemes
were present in sample
• LIMITATION: Only rarely that many numbers of treponemes
seen in clinical samples
2.PCR:
• Extremely valuable in diag-
– congenital syphilis
– neurosyphilis (serologic
test available presently is
only 50% sensitive)
– early primary syphilis
– distinguishing new
infections from old
infections
3.RT PCR:
• Targeting the polA gene of
treponeme
• Assay is fast and has high
sensitivity(94%) &
specificity(100%)
 ENZYME IMMUNOASSAY
• A number of treponemal EIA tests are commercially available , including
Captia Syphilis G , Captia Syphilis M and Captia select Syph-G (Trinity
Biotech, Ireland), SpiroTek syphilis test (Organon Teknika, USA), Enzygnost
Syphilis (Dade Behring, Germany) and Bio-Rad Syphilis G (Bio-Rad
Laboratories, USA)

• Captia Syphilis G test detects IgG antibodies

• May be used both as screening test and confirmatory test and is an

appropriate substitute for the MHA-TP test

• Captia Syphilis M test - designed to detect IgM antibodies in congenital

syphilis - may be more sensitive than FTA-ABS 19S IgM

• Considered to be suitable for detection of early syphilis

• SpiroTek syphilis test has highest sensitivity of all treponemal tests

(especially in untreated primary syphilis) and is recommended as
confirmatory test by CDC
• EIA tests have been shown to be equal to or better than FTA-ABS and
TPHA tests in overall sensitivity and specificity and are more useful in HIV
coinfected individuals

• While a number of laboratories have switched over to treponemal EIAs for

screening

• Drawback is that treponemal tests generally remain reactive for life in

most patients

• CDC is currently recommending that, if EIA is used for screening, then an

RPR test should be performed on all EIA reactives, and a second
treponemal test such as TPHA or FTA-ABS should be used for
confirmation if the RPR test is reactive
 Laboratory diagnosis for different stages for
syphilis
Primary syphilis

• Serous fluids from lesion contain numerous treponemes, detectable by

either dark-field microscopy or the DFA-TP
• Humoral antibodies appear 2 to 3 weeks after chancre
• App. 30% of those with early primary syphilis will have NR nontreponemal
test results on First visit
• Definitive diagnosis of primary syphilis requires direct microscopic
identification of T. pallidum in lesion material, lymph node aspirate, or
biopsy section
• For persons with a h/o syphilis fourfold increase in titer on quantitative
non treponemal test when results of past tests are compared with most
recent test results
• MHA-TP is less sensitive than FTA-ABS test and non treponemal tests
• Suggestive diagnosis based on presence of lesion and sexual contact
within preceding 90 days with person in whom syphilis has been
diagnosed
Secondary syphilis

• In secondary stage, with few if any exceptions, all serologic tests for
syphilis are reactive
• And treponemes may be found in lesions by direct microscopic
examination
• As with primary syphilis Definitive diagnosis based on observation
of T. pallidum by direct microscopic examination
• Presumptive diagnosis is based on presence of typical lesions and
a reactive non treponemal test titer of 8 or more and no previous
history of syphilis or,
• For persons with history of syphilis fourfold increase in most
recent titer compared with past test results
• For patients with atypical lesions and/or non treponemal test
titers of <8, non treponemal tests should be repeated and a
confirmatory treponemal test should be performed before a
presumptive diagnosis is made.

• Sensitivity of MHA-TP is equal to sensitivity of FTA-ABS tests

• Suggestive diagnosis is made only when serologic tests are

not available and is based on both presence of clinical
manifestations and sexual exposure within past 6 months to a
person with syphilis
Latent syphilis

• Since lesions are not present, a definitive diagnosis is not

possible
• Presumptive diagnosis of latent syphilis is based on
combination of serologic results and a history of a nonreactive
non treponemal test the prior year
• Or fourfold increase in titer compared with the most recent
test for persons with a history of syphilis, or a history of
symptoms compatible with those of earlier stages of syphilis
Tertiary syphilis.
• Because results for approx 30% of pts with late syphilis will be
nonreactive in the non treponemal tests

• Treponemal test results should be obtained if syphilis in these

stages is suspected and non treponemal tests are non reactive

• Treponemal tests are almost always reactive and may be

only basis for diagnosis
• For neurosyphilis CSF examinations should be done

• Diagnosis of neuro syphilis requires

– a reactive treponemal test result with a serum sample
– a CSF cell count of >5 mononuclear cells per cubic centimeter
– CSF total protein >40 mg/dl

• A definitive diagnosis is made on the basis of

– a reactive serum treponemal test
– a reactive VDRL-CSF on a spinal fluid sample
– identification of T. pallidum in tissue by microscopic
examination of tissue stained with silver stain or fluorescent
antibody
 Management of Syphilis
• Parenteral penicillin is DOC for all stages of syphilis
• Parenteral penicillin is only treatment with documented
efficacy in neurosyphilis, HIV infection and pregnancy
• Tetracyclines, erythromycin, and third-generation
cephalosporins have strong anti treponemal activity in
experimental and clinicai trials but are less effective than
penicillin
• HIV serology is recommended for all patients with syphilis and
should be repeated in 3 months in patients living in areas with
high HIV prevalence
 Treatment of primary, secondary and
early latent syphilis
First line
• Inj Benzathine penicillin G 2.4 MU i.m. single dose
Penicillin allergy
• Cap Doxycycline 100 mg twice daily orally for 14 days
• Tab Erythromycin 500 mg four times daily orally for 14 days
• Inj Ceftriaxone 1g daily i.m. for 10 days (if no anaphylaxis to
penicillin)

CHILDRENS
• A single intramuscular injection of benzathine penicillin 50,000
units/kg up to 2.4 million units
 HUMAN IMMUNODEFICIENY VIRUS F0LLOW-UP
INFECTl0N
• Patients should be re-
• Treatment same, but follow- up examined clinically and
is closer serologically at 6 and 12
• Some experts recommend CSF months (if HlV- seropositive
examination in patients with CD4 then 3, 6,9, 12 and 24 mths)
counts <350 cells/mm3 and
nontreponemal titers equal or
above 1:32
• No evidence to support
administration of three weekly
injections of benzathine
penicillin G
• Or enhanced therapy with
ampicillin and probenecid after a
course of benzathine penicillin
injections
 Late Latent Syphilis

• Inj Benzathine penicillin G, 2.4 million units intramuscularly

week apart for three doses
• If patient misses a dose, treatment may be resumed as long as
the interval between injections has not exceeded 2 weeks
with exception of pregnant women

CHILDREN
• Three weekly intramuscular injection of Inj benzathine
penicillin G 50,000 units/kg up to 2.4 million units
CSF examination:
• Asymptomatic individuals ,yield of positive findings in lumbar
puncture is low, but CSF examination is clearly indicated in
certain cases:
– Cardiovascular, neurologic, eye, or auditory symptoms or
in late benign syphilis
– HIV infection
– RPR titer> 1:32
– Treatment failure
– Treatment other than penicillin
• If the CSF examination demonstrates abnormalities patient
should be treated for neurosyphilis
 Tertiary syphilis ( Cardiovascular,
Late Benign syphilis)
• Inj Benzathine penicillin G 2.4 million units 1 week apart for
three doses is recommended treatment

Penicillin allergy
• Cap Doxycycline 100 mg twice daily orally for 30 days
• If the patient is not HIV infected and CSF is negative
 Neurosyphilis

• Inj Aqueous crystalline penicillin G 18 to 24 mu administered

daily as 3 to 4.0 million units iv every 4 hours for 10 to 14 days

• Alternatively, treatment with procaine penicillin G, 2.4 mu i.m.

daily, and probenecid 500 mg orally every 6 hours for 10 to 14
days

• Treatment with ceftriaxone ( 1 g i.v. daily for 14 days)is not as

effective as penicillin
PENICILLIN ALLERGY
• Desensitize and treat with penicillin
F0LL0W-UP
• Re -examination CSF every 6 months until normal
• Cell counts should decrease by 6 months and CSF VDRL and
protein levels by 2 year
• If not, retreat with i.v. penicillin
 Treatment in pregnancy
• Penicillin regimen appropriate for stage of infection should be
used
PENICILLIN ALLERGY
• Desensitize and treat with penicillin
• Erythromycin's ability to cross placenta is fair to poor
• Infants born to mothers who received erythromycin for
syphilis during pregnancy should be thoroughly evaluated for
active disease
 Syphilis in HIV infected patients
• A penicillin regimen should be instituted according to the stage of
disease
PENICILLIN ALLERGY
• Desensitize and treat with penicillin
CSF EXAMINATION:
• Some experts recommend CSF examination before treatment of early
syphilis as well as 6 months after treatment
• but there is no evidence of improved outcomes
FOLL0W-UP
• Closer follow-up with clinical and serological tests required at 3
month interval
• CSF examination is indicated if there is serologic evidence of
treatment failure at any time, or if the serofast response continues
after 12 months
 Recommended treatment and follow-up for syphilis in HIV-infected patients.

Zetola N M , and Klausner J D Clin Infect Dis.

2007;44:1222-1228

© 2007 by the Infectious Diseases Society of America

TABLE
Stages of Syphilitic Infection
Stage Clinical manifestations Diagnosis (sensitivity) Treatment
Primary syphilis Chancre Dark-field microscopy of skin lesion Penicillin G benzathine, 2.4 million units IM
(80%)Nontreponemal tests (78% to (single dose)Alternatives in nonpregnant
86%)Treponemal-specific tests (76% to 84%) patients with penicillin allergy: doxycycline
(Vibramycin), 100 mg orally twice daily for 2
weeks; tetracycline, 500 mg orally four times
daily for 2 weeks; ceftriaxone (Rocephin), 1 g
once daily IM or IV for 8 to 10 days; or
azithromycin (Zithromax), 2 g orally (single
dose)

Secondary syphilis Skin and mucous membranes: diffuse rash, Dark-field microscopy of skin lesion Same treatments as for primary syphilis
condyloma latum, other lesionsRenal system: (80%)Nontreponemal tests
glomerulonephritis, nephrotic syndromeLiver: (100%)Treponemal-specific tests (100%)
hepatitisCentral nervous system: headache,
meningismus, cranial neuropathy, iritis and
uveitisConstitutional symptoms: fever,
malaise, generalized lymphadenopathy,
arthralgias, weight loss, others
Latent syphilis None
Tertiary (late) syphilis Gummatous disease, cardiovascular disease
Neurosyphilis Seizures, ataxia, aphasia, paresis,
hyperreflexia, personality changes, cognitive
disturbance, visual changes, hearing loss,
neuropathy, loss of bowel or bladder function,
others
Nontreponemal tests (95% to
100%)Treponemal-specific tests (97% to
100%)
Nontreponemal tests (71% to
73%)Treponemal-specific tests (94% to 96%)
Cerebrospinal fluid examination
Early latent syphilis: same treatments as for
primary and secondary syphilisLate latent
syphilis: penicillin G benzathine, 2.4 million
units IM once weekly for 3 weeksAlternatives
in nonpregnant patients with penicillin allergy:
doxycycline, 100 mg orally twice daily for 4
weeks; or tetracycline, 500 mg orally four
times daily for 4 weeks
Same treatment as for late latent syphilis
Aqueous crystalline penicillin G, 3 to 4 million
units IV every 4 hours for 10 to 14 days; or
penicillin G procaine, 2.4 million units IM
once daily, plus probenecid, 500 mg orally
four times daily, with both drugs given for 10
to 14 days
 Penicillin reactions

• Accidental deaths following treatment are very rare and

mainly due to anaphylactic shock reactions to penicillin
• If penicillin is used in patients with a history of allergy, it is
advisable to keep the patient under observation for 15–20
min after injection
• An emergency kit should always be available
• In addition to early and late allergic reactions and the Jarisch–
Herxheimer reaction
• Hoigne reactions (acute psychotic symptoms due to
inadvertent iv injection of procaine in procaine penicillin) are
recognized
Jarisch–Herxheimer reaction
• An acute febrile reaction that occurs in many patients within
24 hr of commencing treatment
• Mediated by cytokines
• Headache, myalgia, bone pains and an exacerbation of skin
lesions may accompany the fever
• Must be differentiated from penicillin allergy
• Patients should be advised that it might occur
• Symptoms may be controlled by antipyretics
• Fever (38–40°C) rarely persists more than 8 h
• In pregnant women reaction may induce early labour or cause
fetal distress
• In late neurosyphilis and cardiovascular syphilis, reaction can
be more serious and may be associated with life-threatening
sequelae
• Many clinicians advocate a short course of corticosteroids to
lessen its effects in these patients
• One such regimen is to prescribe oral prednisolone 30–60 mg
daily for 3 days, beginning syphilis treatment 24 h after first
dose
 Management of sexual contacts

• It is recommended that attempts be made to identify, trace and

offer further investigation to at-risk sexual contacts
• In early syphilis, these are those contacts occurring within 3
months plus the duration of symptoms for primary syphilis
• Within 6 months plus the duration of symptoms for secondary
syphilis and within 1 year for early latent disease
• All long-term partners of patients with late syphilis should be
offered investigation
• Many clinicians recommend presumptive treatment of all sexual
contacts within 90-day period preceding patient presentation of
early syphilis
• if serological test results are not immediately available and if
follow-up cannot be assured
 Efficacy of azithromycin on the
treatment of syphilis
• Penicillin therapy is associated with low cost and also
inexistence of problems with adherence to treatment
• Although, the injection is painful and nearly 10% of the
population has allergic reactions to penicillin
Results
• We selected three clinical trials comparing azithromycin
with benzathine penicillin, totaling 499 patients in the
study group and 471 patients in the control group
• One study examined two dosages of azithromycin (2g and
4g) whereas the other two used the dosage of 2g
• Penicillin G benzathine was administered at its
conventional dose (2.4 million units) in all studies
• Healing in three months: Three studies have compared azithromycin with
benzathine penicillin in the period of three months. One hundred and
ninety-five patients in the study group and 190 patients in the control
group didn't heal in this period. There was no statistically significant
difference between groups (p=0.88, I2=0%).
• Healing in six months: Three studies have compared azithromycin with
benzathine penicillin in a follow-up of six months. One hundred and fifty-
six patients in the study group and 165 patients in the control group didn't
heal in this period. There was no statistically significant difference
between groups (p=0.39, I2=44%).
• Healing in nine months: Two studies have compared azithromycin with
benzathine penicillin in a follow-up of nine months. Thirty two patients in
the study group and 44 in the control group had no cure in this period.
Azithromycin has increased the chance of cure in 8% (95%CI 0,01 to 0,15;
p=0.02 and I2=21%) when compared with benzathine penicillin, needing
to treat 13 patients to obtain this benefit
Conclusion
• This review showed clearly that a single dose of
azithromycin, orally, is as effective as the 2.4 million units of
benzathine penicillin for treating syphilis
Antibiotic Desensitization Therapy in Secondary Syphilis
and Listeria Infection: Case Reports and Review of
Desensitization Therapy
• A 45-year-old male presented with a two month history of an
erythematous, pruritic, maculo-papular rash initially involving the truncal area and
then spreading to the genital area and extremities, including both palmar and
plantar surfaces. The lesions varied in size from 0.5 to 2.5 cm and gradually
became hyperpigmented with superficial desquamation. Secondary syphilis was
suspected and confirmed with Rapid Plasma Reagin (RPR) positivity (1:64) and
Fluorescent Treponemal Antibody (FTA) reactivity. The patient admitted to having
two recent sexual contacts, one casual contact and another with a commercial sex
worker.
• Past medical history was significant for reaction to penicillin with
hives, dyspnea, loss of consciousness, and hypotension requiring hospitalization at
age fourteen. He also had a remote history of treated gonococcal and chlamydial
genital infections.
• Due to his previous severe reaction to penicillin, the patient was initially started on
alternative therapy with a fourteen day course of doxycycline with no resolution of
his disseminated rash. The infectious disease consultant recommended that the
patient undergo penicillin desensitization for optimal therapy.
• He was admitted to the hospital for antibiotic desensitization followed by penicillin
therapy under unit-level observation He tolerated the procedure well with no
hypersensitivity reaction and was discharged the following day. The patient
subsequently had complete resolution of his rash and negative RPR testing at
follow-up.
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