Syphilis
Historical facts:
1. "Pre-columbian theory" -
present in Europe.
2. "Columbian Theory" - Haiti,
Cristopher Columbus
3. Syphilis in medical literature -
1495
4. Heavy metal treatment-
Arsenic, mercury, 1497
5. Spirochaeta pallida- T.pallidum-
1905
6. Wasserman test- first test to
identify T. pallidum, 1906
7. Penicillin as miraculous cure.
Morphology of T.pallidum
 Order: Spirachaetale
 Family: Treponemataceae
 Genus: Treponema
 The genus treponema contains
four principal species of
pathogenic organisms, T
pallidum, T pertenue, T
carateum and T cuniculi.
 T. pallidum subsp. pallidum the
etiologic agent at venereal
syphilis is a thin (0.2 um)
spirochete, 6-20 um in length
with 10-13 coils.
 Multiplies by transverse
fission.
 The spirochete has corkscrew
motility with an undulating
central flexion.
Metabolism of T. pallidum
 Outside the host, the pallidum
is susceptible to a variety of
physical and chemical agents
that rapidly bring about its
destruction. It is readily killed
by heat, cold, desiccation,
disinfectants, and osmotic
changes.
 The treponemes have a complex
nutritional requirements.
 They require glucose, amino
acids, purines and pyrimidines
for metabolism. Some stains
also need bicarbonates, co
enzyme and fatty acids.
 T. pallidum has not been
recovered in the blood, serum
or plasma stored at 4 degrees
celsius for more than 48 hours.
 Treponemes can be kept viable
when frozen at 70 degrees
celsius for years.
 Both humoral and cell-mediated
immune responses are involved
in the interaction between T.
pallidum and the human host.
Antibodies are produced, there
is an inflammatory response,
immune complexes are formed,
and the lesions is walled off.
The disease enters the latency
stage.
Antigens
 The Wasserman antigen
- Antigen used in Wasserman
test
 The treponemal antigens
Reiter strain- nonpathogenic
Nichols strain- pathogenic
 Non treponemal test:
-RPR, VDRL
 Treponemal test
-MHA-TP
-FTA-Abs
-TPI
Modes of transmission
 Sexual contact with infected
person
 Pregnancy
4 clinical stages of Syphilis
Primary/ Early Syphilis
 Inflammatory lesions
(chancres)
-appears 2-8 weeks
-Lasts for 1-5 weeks
  Serum test for syphilis are
positive in 90% of patients
after 3 weeks.
 Antibodies are IgM.
 May develop inguinal
adenopathy.
Secondary Syphilis
 Generalized rash
 Secondary lesions in the eyes,
joints, or CNS.
-Highly contagious lesions but
heal within 2-6 weeks.
 Serologic test are positive.
 Antibodies are IgG
 May develop general
adenopathy.
 Muscular lesions in the palms
and the soles of the feet.
 Candylamata lata- Flat lesions
warts in the moist areas of the
body.
Latent stage
 No clinical symptoms but
serologically positive.
 Still considered infection.
 After 4 years, syphilis is not
usually contagious but still
communicable through
pregnancy.
Tertiary/Late syphilis
 Granulomatous lesions (
gummata)
 CNS involvement (80%)
-Neurosyphilis
-Dementia
 Cardiovascular syphilis (10%)
Congenital syphilis
 Caused by maternal
spirochetemia and
transplacental transmission of
microorganisms
 Typing of congenital syphilis is
based on age at diagnosis.
Early stage:
 Under 2 years old
 Rash
 Condyloma latum
 Bone changes
 Hepatosplenomegaly
 Jaundice
 Anemia
Late stage:
 Over 2 years old
 Eighth nerve deafness
 Hutchinson's teeth
 Arthropathy
 Collapse of nasal bones.
Neurosyphilis
Meningeal syphilis
 Usually less than 1 year after
infection.
 Involves brain or spinal cord,
suffers headaches and stiff
neck.
Meningovascular syphilis
 Usually 5-10 years after
infection.
 Inflammation of the pia mater
and arachnoid spaces.
Parenchymatous syphilis
 Manifests as general paresis,
joint degeneration, tabes
dorsalis ( demyelination of
posterior columns, dorsal roots
and dorsal root ganglia)
Nontreponemal tests ( Screening
tests)
 VDRL- Venereal Disease
Research Laboratory
 RPR- Rapid Plasma Reagin
VDRL Principle:
 Patients with syphilis develop
REAGIN to a tissue derived
substance known as
CARDIOLIPIN.
Equipments:
Antigen needles:
 Qualitative test- deliver 1/60
ml ( 60 drops /ml) of antigen
  Quantitative test- deliver 1/75
ml ( 75 drops /ml) of antigen.
Reagent
 Antigen (alcoholic solution of
cardiolipin-cholesterol-lecithin)
 Cardiolipin
 Cholesterol
 Lecithin
Sample preparation
 Serum complement should be
inactivated by heating at 56
degrees celsius for 30 minutes.
 If interval between inactivation
and testing is 4 hrs or greater,
reinactivate by heating at 56
degrees celsius for 10 minutes.
Qualitative test
 Serum + 1 drop (1/60 ml)
antigen (serum antigen ratio
3:1)
 Rotate on mechanical rotator
for 4 minutes at 180 rpm.
 Observe microscopically for
flocculation.
Interpretations:
 Reactive
 Weakly reactive
 Nonreactive
Note:
 Test must be performed at
room temperature within 23to
29 degrees celsius (7.8-7.5
degrees Fahrenheit)
 All sera with reactive ar weakly
reactive results must be tested
using the quantitative slide
test.
VDRL on CSF
 Antigen for serum VDRL test is
sensitized with 10% reactive
results virtually diagnostic of
neurosyphilis.
Qualitative test
 Serum + 1 drop ( 1/60 ml)
antigen without mixing.
 Rotate for 8 minutes at 100
rpm.
 Read macroscopically for
clumping ( black particles on
white card).
 Interpret the results.
Quantitative test:
 Test is done on minimally
reactive and reactive sera.
 Prepare 2 fold dilution of serum
in 0.9 saline.
 Report the highest dilution.
Both VDRL AND RPR are considered
screening test. Why?
Reagent composition of RPR Ag
 Cardiolipin-antigen
 Cholesterol- Makes Ag increase
number size.
 Lecithin-standardization
 Choline chloride- replaces heat,
no need for maturation.
Treponemal test:
 TPI
 FTA-ABS
 MHA-TP
Antigens used:
 Nichols strain of T.pallidum-
pathogenic
 Reiter strain of T.pallidum-
Nonpathogenic
TPI test
 First test developed for
detection of specific anti-
treponemeantibody.
Principle:
 Antibody against T.pallidum are
capable of immobilizing live
treponemes.
 Antigen( suspension of motile
T.pallidum)
 Examined under darkfield
illumination.
  Immobilizing antibody titer
most reliable and standard test
against other treponemal test.
 Too cumbersome for routine
use.
FTA-ABS
 Used killed suspension of T
pallidum spirochetes as the
antigen.
 Overlying whole treponemes
fixed into the slide with serum
from patients suspected of
having syphilis.
Procedure:
 Patient's serum should be
absorbed with non T pallidum
treponemal antigen.
 Fluorescein- conjugated anti-
human antibody reagents is
added as a marker.
Microhemagglutination:
 Agglutination of specific
antibodies in the pxn serum
with specific sheep
erythrocytes sensitized to
T.pallidum antigen.
Other reagin test:
 Plasmacrit (PCT)
 Unheated serum reagin
 automated reagin test
Other treponemal test:
 Treponemal pallidum
complement fixation ( TPCF)
 Reiter protein complement
fixation ( RPCF)
 Treponema pallidum
hemagglutination test (TPHA)
 Direct fluorescent antibody
test (DFA)
Properties of C reactive protein
 Homogeneous molecule (
molecular weight 120,000)
 Sedimentation coefficient of
6.5
 Electrophoretic mobility is the
gamma region.
 Consists of 5 probably identical
non covalently bound subunits
of approximately 21,500 to
23,500 d each linked in the
form of a cyclic pentamer.
 Made up of 100% peptide.
 it inhibits the aggregation of
platelets induced to aggregated
human gamma globulin and
thrombin.
 Shares immunoglobulin the
ability to initiate precipitation,
agglutination, opsonization,
capsular swelling and
complement activation.
 Differs from immunoglobulins in
antigenicity, tertiary structure,
homogeneity, required stimuli
for formation and release and
binding specificities and that is
produced entirely by
hepatocytes on liver/
parenchymal cells.
 Thermolabile-it is by heating to
70 degress celsius for 30 min.
CRP does not cross the human
placenta.
 Used clinically for monitoring
infection, tissue necrosis, and
healing after myocardial
infection.
 Values are parallel with
inflammatory response.
 Demonstrates a large
incremental change with as
much as a too fold increase in
concentration.
 Fastest responding and most
sensitive indicator of acute
infection.
 Method of choice for screening
for inflammatory and malignant
organic diseases and monitoring
 therapy in inflammatory
diseases.
CRP in bacterial infection
 Could differentiate between
bacterial and viral infection.
 Extremely elevated in possible
bacterial infection.
 Advocated as an indicator of
bacterial infection in at risk
patients in whom the clinical
assessment of infection is
difficult to make but lack of
specificity rules out CRP as a
definitive diagnostic tool.

 Septicemia
 Meningitis in neonates
 infections in immunosuppressed
patients.
 Burns complicated by infection.

 Rheumatic disease
 Serious post proliferative
_________
 MI
 Malignant tumors
CRP rises after tissue injury or
surgery
 Peaks about 2 days after
surgery and gradually returns
to normal levels within 7 days
and 10 days.
 If still elevated, it may suggest
underlying sepsis and could
indicate postoperative
complications.