STRUCTURE AND PHYSIOLOGYOF TREPONEMES, Pathogenesis, Classification of Syphilis, PRIMARY SYPHILIS, SECONDARY SYPHILIS, TERTIARY SYPHILIS, Late benign syphilis, Cardiovascular syphilis, Neurosyphilis, Lab diagnosis of syphilis

1. SEMINAR PRESENTATION
SYPHILIS
MODERATOR
DR.C.M. KULDEEP

2. 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

3. 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

4. • 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

5. 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

6. Range 9- 90days
2-12 WEEKS

7. Pathogenesis
Mode of transmission
1.
2.
3.
4.
5.
Sexual intercourse
Blood transfusion
Contaminated needles
Vertical transmission
To hospital personnel
indiscriminate handling
infected lesions
by
of
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

8. • 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

9. Classification of Syphilis
1.
2.
Clinical course of acquired
syphilis is divided in to
early &late syphilis.
Early-duration is 1 yrs.
– Includes primary and
secondary stage and
early latent syphilis
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

10. PRIMARY SYPHILIS
•
Starts as painless, erythematous
indurated papule – ulcer
• Lymphadenopathy
•
Usually single , painless, clean, well
defined, Nontender & markedly
indurated
• Inguinal lymph node invariably
involved
•
Site - genital, perineal or anal area;
however, any part of the body may be
affected
• Multiple, non
tender, discrete, rubbery , Usually
Bilateral
•
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
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.

13. 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

14. Fig.Secondary syphilis,macular rashes

15. FIGURE . Secondary syphilitic rash on palm and sole.

16. Syphilitic alopecia
scalp has moth-eaten appearance
eyebrow hair is absent there is rash
on the cheek
Mucus patches involving the
tongue in secondary syphilis.

17. •
•
•
•
•
•
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

18. 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

19. 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

20. 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

21. Clinical manifestations
Skin- Two forms may appear: nodular or noduloulcerative and solitary
lesion.
• 1.Nodular and noduloulcerative
lesions deep indurated nodule
reddish brown in colour that
varies in size
• Multiple nodules - distributed in
arciform pattern
• Site - face,scapular,interscapular
areas and extremities
• May remain for weeks or mths
and may heal without breaking
down but - show scarring
• If nodular lesions break down to
noduloulcerative form, they heal
leaving atrophic noncontractile
scar
2.The solitary gumma
Subcutaneous process that
involves the skin secondarily
• Site thighs, buttocks, shoulders, foreh
ead and scalp.
• As it becomes necrotic it has
characteristics of “cold abscess”
• These lesions resolve promptly
with effective treatment

22. • 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

23. 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.

24. 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.

25. FIGURE . Osteitis of hard palate with perforation

26. 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

27. Aortic aneurysm
• MC manifestations
•
•
Virtually involve ascending thoracic
aorta
Syphilitic aneurysms do not dissect
probably because of the medial
scarring and wall thickening
•
Symptom - develop when aneurysm
encroaches on surrounding
structures or ruptures
•
Radiograph may be N or show a
mediastinal mass with typical
eggshell calcification outlining
aneurysm
Coronary artery disease
• Only the ostia or most proximal
few mm of coronary arteries are
affected
• May lead to IHD including angina
pectoris or sudden death
Aortic regurgitation
• Pure AR without stenosis
formerly was common
cardiovascular manifestation
• Occurring in roughly 30% of pts

28. 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)

29. 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.

30. 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

31. 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

32. • 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

33. 3.DFA-TP
4.DFAT-TP test
• 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.
• 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

34. Non treponemal Tests
1.
2.
3.
4.
VDRL( veneral disease research laboratory test)
USR(unheated serum reagin)
RPR(rapid plasma reagin)
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

35. • 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

36. • 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 falsepositive results

37. • 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

38. 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 FTAABS test results and the diagnosis of systemic, discoid, and druginduced varieties of LE
• Patients with SLE can have false-positive FTA-ABS tests that
exhibit an ‘‘atypical beading’’ fluorescence pattern

39. • 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

40. 1.FTA-ABS test:
•
Indirect fluorescentantibody technique
• Patient’s serum is first
diluted in sorbent (an
extract from cultures of
nonpathogenic Reiter
treponeme)
• To remove group
treponemal antibodies that
are produced in some
persons in response to
nonpathogenic treponemes
2.FTA-ABS test double
staining method:
• Employs
tetramethylrhodamine
isothiocyanate-labeled
anti-human IgG and
counterstain with FITClabeled anti-T. pallidum
conjugate
• Counterstaining organism
ensures that nonreactive
result is due to absence of
antibodies and not to
absence of treponemes on
slide

41. 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

42. Table :Sensitivity and Specificity of Serologic Tests for Syphilis

43. 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

44. 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%)

45. 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

46. •
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

47. 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

48. 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

49. • 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

50. 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

51. 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

52. • 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

53. 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

54. 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

55. HUMAN IMMUNODEFICIENY VIRUS
INFECTl0N
• Treatment same, but follow- up
is closer
• Some experts recommend CSF
examination in patients with CD4
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
F0LLOW-UP
• Patients should be reexamined clinically and
serologically at 6 and 12
months (if HlV- seropositive
then 3, 6,9, 12 and 24 mths)

57. 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

58. 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

59. 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

60. 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

61. 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

62. 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

63. 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

65. 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

67. 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
condyloma latum, other lesionsRenal system: (80%)Nontreponemal tests
glomerulonephritis, nephrotic syndromeLiver:
hepatitisCentral nervous system: headache,
meningismus, cranial neuropathy, iritis and
uveitisConstitutional symptoms: fever,
malaise, generalized lymphadenopathy,
arthralgias, weight loss, others
(100%)Treponemal-specific tests (100%)
Same treatments as for primary syphilis

68. Latent syphilis
None
Nontreponemal tests (95% to
Early latent syphilis: same treatments as for
100%)Treponemal-specific tests (97% to
primary and secondary syphilisLate latent
100%)
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
Tertiary (late) syphilis
Gummatous disease, cardiovascular disease
Nontreponemal tests (71% to
Same treatment as for late latent syphilis
73%)Treponemal-specific tests (94% to 96%)
Neurosyphilis
Seizures, ataxia, aphasia, paresis,
Cerebrospinal fluid examination
Aqueous crystalline penicillin G, 3 to 4 million
hyperreflexia, personality changes, cognitive
units IV every 4 hours for 10 to 14 days; or
disturbance, visual changes, hearing loss,
penicillin G procaine, 2.4 million units IM
neuropathy, loss of bowel or bladder function,
once daily, plus probenecid, 500 mg orally
others
four times daily, with both drugs given for 10
to 14 days

69. 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

70. 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

71. • 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

72. 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

73. 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

74. • 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 fiftysix 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

75. 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

76. 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.

78. THANK YOU