SYPHILIS

Morphology of Treponema
pallidum
subsp. pallidum
 Causative agent of SYPHILIS
 Fine spiral organism with 3 periplasmic
flagella
 10-13 coils
 Appears white against a dark
background
 Microaerophilic; survives longer in the
presence of 3-5% oxygen
 Composed of phospholoipids bilayer
and protein antigens – outer membrane
Scanning Electron Micrograph of
T. pallidum
 Mode of Transmission
 Organism is very fragile, destroyed
rapidly by heat, cold and drying;
susceptible to disinfectants
 Sexual transmission most common,
occurs when abraded skin or mucous
membranes come in contact with open
lesion.
 Can be transmitted to fetus.
 Rare transmission from needle stick and
blood transfusion.
 Has a remarkable tropism to arterioles
(endarteritis)
 2 types of antibodies produced: treponemal
and nontreponemal (reagin)
1. Non Treponemal Abs
REAGIN – an anti-cardiolipin Ab, reacts with
lipid Ags
2. Treponemal Abs – directed against
pathogenic T. Pallidum and closely related
strains
a. Group antibodies – directed against
group antigens
b. Specific Treponemal Antibodies – specific
for each treponemal antigen
 Antigen
1.Wassermann Antigen
 Cardiolipin
- a normal constituents of host tissue
- is a hapten and is bound to the microbial
cell in order to be antigenic
-a phospholipid
 Pathogenic treponemes growing in vivo
INCORPORATES this plentiful supply of
phospholipid
 Microbial cell/ treponemes- is the foreign
carrier
 Bound phospholipid(cardiolipin)- is the
antigenic determinant
2.TREPONEMAL ANTIGEN
Reiter CHON (group antigens)
- a protein found in most treponemes
(both in saprophytic and pathogenic
treponemes)

Specific Treponemal Antigens

- specific for each treponeme species
 Clinical Infection
 Syphilis
- French disease/Italian disease/ The
Great Pox
- also known as the “great imitator”
- a disease of blood vessels and of
the perivascular areas; can cross the
placenta
- it is characterized by chancre,
fever, sore throat, headache and
rash[palms and soles], gummas in
skin, neurosyphilis
-if untreated, T. Pallidum can
Stages of Disease

 Primary
 Secondary
 Latent
 Tertiary
 Congenital Syphilis
Primary Syphilis

 Organism enters directly through skin

or through mucosal tissue.
 Carried by blood throughout the
body.
 Organisms remaining at the site
begin to multiply.
Primary Syphilis -
Chancre
 Variable incubation period of 10 days to
several months, a primary lesion,
chancre, forms at the entrance site.
 Chancre begins as a small, usually
singular nodule; as it enlarges, the
overlying epithelial tissues begins to
necrose, resulting in a relatively
painless ulcer.
 Unlike other bacterial infections, there is
no formation of pus unless a secondary
bacterial infection sets in.
Primary - Chancre
 Chancre is most frequently seen on the
external genitalia
 In women the lesions may form in the vagina
or on the cervix.
 In men it may be inside the urethra, resulting
in a serous discharge.
 The lesion heals spontaneously after 1-5
weeks.
 Swab of chancre smeared on slide,
examined under dark-field microscope,
spirochetes will be present.
 Thirty percent become serologically
positive one week after appearance of
chancre, 90% positive after three weeks.
Penis: The most common
sites of infection in men
are on the penis. Within 90
days of infection (three
week average), a painless
sore or ulcer called a
chancre appears.  This
chancre contains a clear
fluid that is full of syphilis-
causing bacteria making
you highly contagious. The
chancre will heal even
without treatment within a
few weeks.
Primary Syphilis - Chancre
Primary Syphilis - Chancre
Fluid From Chancre
Spirochetes in Blood
Secondary Syphilis

 Occurs 6-8 weeks after initial chancre,

becomes systemic, patient highly
infectious.
 Characterized by localized or diffuse
mucocutaneous lesions, often with
generalized lymphadenopathy.
 Primary chancre may still be present.
 Secondary lesions subside in about 2-6
weeks.
 Serology tests nearly 100% positive.
Secondary Syphilis

 A widespread eruption resembling

psoriasis or pityriasis rosea which
prominently involves the hands should
always include the differential diagnosis of
secondary syphilis.
Secondary Syphilis

 Secondary syphilis lesions on back

Around the Mouth: Secondary symptoms can include
multiple sores on the penis, anus or around the
mouth.  They can also be found in the throat,
which cannot be readily seen.
Wart Like Growths: hair loss, white
patches on your tongue or multiple wart-
like growths called condylomata lata.ike
Growths: hair loss, white patches on your
tongue or multiple wart-like growths
called condylomata lata
Latent Syphilis

 Stage of infection in which organisms

persist in the body of the infected
person without causing symptoms or
signs (asymptomatic).
 This stage may last for years.
 One-third of untreated latent stage
individuals develop signs of tertiary
syphilis.
 After four years it is rarely
communicable sexually but can be
passed from mother to fetus.
Tertiary Syphilis

 Divided into three manifestations:

 Gummatous syphilis
 Cardiovascular syphilis
 Neurosyphilis
Tertiary Syphilis -
Gummatous
 Gummas are localized areas of
granulomatous inflammation found on
bones, skin and subcutaneous tissue.
 Cutaneous gummas may be single or
multiple, generally asymmetric and
grouped together.
 Visceral lesions often cause local
destruction of the affected organ.
 Contain lymphocytes, plasma cells and
perivascular inflammation.
Tertiary Syphilis Buboe
of Neck
Tertiary Syphilis
Tertiary Syphilis -
Gumma
Tertiary -
Cardiovascular
 This condition appears 20 or more years
post-infection.
 Usually involves the aorta.
 Invading treponemes cause scarring of
the tunica media.
 Over many years, the inflammatory
scarring weakens the aortic wall,
leading to aneurysm formation, which
causes incompetence of the aortic valve
and narrowing of the coronary ostia.
Tertiary -
Cardiovascular
 Antibiotic treatment cures the
syphilis infection and stops the
progress of cardiovascular syphilis.
 The damage that has already
occurred may not be reversed.
Neurosyphilis
 Caused by invasion of organisms into
the CNS.
 Manifests as an insidious but
progressive loss of mental and physical
functions and is accompanied by mood
alterations.
 General paresis of the insane:
 forgetful,
 personality change,
 psychiatric symptoms.
 Onset usually 10-20 years after primary
infection.
 Treatment may not improve symptoms.
Neurosyphilis

 Neurological complications at this stage

include generalized paresis of the
insane which results in personality
changes, changes in emotional affect,
hyperactive reflexes.
 Tabes dorsalis, degeneration of lower
spinal cord, general paresis and chronic
progressive dementia often results in a
characteristic shuffling gait.
 Can only be diagnosed serologically by
VDRL.
Neurosyphilis

 Cerebral atrophy, most prominent in

frontal lobes seen in general paresis.
Congenital Syphilis

 Transmitted from mother to fetus.

 Fetus affected during second or third
trimester.
 Forty percent result in syphilitic
stillbirth-fetal death that occurs after
a 20 week gestation and the mother
had untreated or inadequately
treated syphilis at delivery.
Congenital Syphilis

 According to the CDC, 40% of births

to syphilitic mothers are stillborn.
 40-70% of the survivors will be
infected, and 12% of these will
subsequently die prematurely
 Death from congenital syphilis is
usually through pulmonary
hemorrhage.
Congenital Syphilis

 Bone deformities
 Blindness
 Deafness
 Deformed faces
 Dental deformities
 Skin rashes
 Neonatal death
Congenital Syphilis

 Live-born infants show no signs

during first few weeks.
 Sixty to 90 % develop clear or
hemorrhagic rhinitis.
 skin eruptions (rash) especially around
mouth, palms of hands and soles of feet.
 Other signs: general
lymphadenopathy,
hepatosplenomegaly, jaundice,
anemia, painful limbs, and bone
abnormalities.
Congenital Syphilis

 Early onset syphilis manifests at birth or

months after, exhibiting a diffuse
infiltration, scabs and fissuring along the
periphery of the mouth, which leave sulci
in a radiated pattern or rhagades
Congenital Syphilis

 clear or hemorrhagic rhinitis

Congenital Syphilis

 Skin eruptions (rash) especially around

mouth, palms of hands and soles of feet
Congenital Syphilis

 Hutchinson’s incisors.
SEROLOGIC TESTS FOR
SYPHILIS
1.NonTreponemal methods/ Reagin
Tests for Syphilis
A. VDRL (Venereal Disease Research
Laboratory Test)
-uses heated serum (@56ºC for 30min.) as
specimen and result is read microscopically
PRINCIPLE: FLOCCULATION (agglutination of
colloidal particles)
Colloidal suspensions
of lipoids + REAGIN (+)
flocculation
- Rgt Ag: colorless alcoholic solution
containing cardiolipin, lecithin, cholesterol
- Rotator: 180rpm for 4 minutes
- False (+) VDRL result: SLE, rheumatic fever,
IM, malaria, pregnancy
Results:
no clumping (or slight roughness): nonreactive
small clumps: weakly reactive
medium or large clumps: reactive
Rapid plasma reagin

 -uses unheated serum as specimen

and the result is read microscopically
 - uses the incorporation choline-
chloride to modify the basic VDRL
antigen and allows testing of plasma
without preliminary heating
 -Principle: FLOCCULATION
 -Rgt Ag: colorless alcoholic sol’n
containing cardiolifin lecithin
cholesterol with charcoal
 -Rotator: 100 rpm for 8 mins
2. Treponemal
Mtds/Specific Mtds
 TPI (T. Pallidum Immobilization Test)
-test of choice for CSF specimen when
regain give NR results
-Principle: The antibody produced against
T. Pallidum plus complement can
immobilize the live treponemes.
-Rgt ag: live actively motileT.pallidum
organisms (extracted from lessions of
infected rabbits)
-Ab:Patient syphilitic serum
-Complement: guinea pig complement
-(+) result: immobilization of treponemes
(>50% immobile)
(Fluorescent Treponemal
Antibody Absorpion Test)
 Principle: Indirect Fluorescent
immunoassay
 Rgt ag: Dead T.pallidum (Nichols strain)
dried and fixed on slide
 Ab: patient syphilitic serum
 Absorbent: Reiter treponemes
 *patient serum is prediluted in a heated
culture filtrate of Reiter Treponemes so
that grouped antibodies are blocked and
the specific antibody will be then free to
bind with the Treponemal antigen.
 Conjugate: Fluorescent-labeled AHG
FTA-ABS Step 1

 Teponema pallidum, the known

antigen, is fixed to a microscope
slide.
FTA-ABS – Step 2
 If there are antibodies against Treponema
pallidum in the patient's serum, they will
bind to the spirochete.
 All other antibodies are washed from the
slide.
FTA-ABS- Step 3
 Fluorescent anti-human gamma globulin (anti-
HGG) is added to the well.
 The anti-HGG will bind with human IgG antibodies
bound to the Treponema pallidum on the slide.
 All unbound anti-HGG is washed from the slide.
 Viewed with a fluorescent microscope, the
spirochetes will fluoresce
Positive FTA Test for Syphilis
Viewed with a Flourescent
Microscope
T.Pallidum
Hemeagglutination Test
 Principle: Hemeagglutination
 Uses RBC coated with treponemal
antigen to detect patients
treponemal antibodies
 Rgt ag: glutaraldehyde stabilized
turkey RBC coated with treponemal
antigen
 Antibody: patients syphilitic serum
 (+) result: hemeagglutination
MHA-TP (Microhemeaggutination
T. Pallidum Test)
 PRINCIPLE: HEMEAGGLUTINATION
 Uses RBC coated wih Treponemal
antigen to detects patients
treponemal antibodies
 Rgt Ag: tanned formalin sheep RBC
coated with treponemal antigen
 Ab: Patient’s syphilic serum
 Positive result : hemagglutination