Download Congenital Syphilis

Syphilis
Dr. Mohammad Shakeeb, MD
Specialist in clinical
pathology/Microbiology and
immunology
TREPONEMA PALLIDUM AND
SYPHILIS
• Morphology and identification
• T pallidum are slender spirals measuring
about 0.2 μm in width and 5–15 μm in
length.
• The spiral coils are regularly spaced at a
distance of 1 μm from one another
• The organisms are actively motile, rotating
steadily around their endoflagella even after
attaching to cells by their tapered ends.
• Culture
• Pathogenic T pallidum has never been
cultured continuously on artificial media, in
fertile eggs, or in tissue culture.
• Antigenic Structure
• The outer
membrane
surrounds
the
periplasmic space and the peptidoglycan–
cytoplasmic membrane complex.
• The endoflagella are in the periplasmic
space
• T pallidum subspecies pallidum has
hyaluronidase that breaks down the
hyaluronic acid in the ground substance of
tissue and presumably enhances the
invasiveness of the organism.
• Cardiolipin is an important component of the
treponemal antigens.
• Humans with syphilis develop antibodies
capable of staining T pallidum by indirect
immunofluorescence,
immobilizing
and
killing live motile T pallidum and fixing
complement in the presence of a
suspension of T pallidum or related
spirochetes.
• The spirochetes also cause the development
of a distinct antibody-like substance, reagin,
which gives positive complement fixation (CF)
and flocculation test results with aqueous
suspensions of cardiolipin extracted from
normal mammalian tissues
• Both reagin and antitreponemal antibody can
be used for the serologic diagnosis of syphilis.
Pathogenesis, Pathology, and Clinical
Findings
Acquired Syphilis.
Congenital Syphilis.
Acquired Syphilis
• Natural infection with T pallidum is limited
to the human host.
• Human infection is usually transmitted by
sexual contact.
• The infectious lesion is on the skin or
mucous membranes of genitalia.
• In 10–20% of cases, however, the primary
lesion is intrarectal, perianal, or oral.
• T pallidum can probably penetrate intact
mucous membranes, or the organisms may
enter through a break in the epidermis.
• Spirochetes multiply locally at the site of
entry, and some spread to nearby lymph
nodes and then reach the bloodstream.
• Within 2–10 weeks after infection, a papule
develops at the site of infection
• breaks down to form an ulcer with a clean,
hard base (“hard chancre”)
• The inflammation is characterized by a
predominance of lymphocytes and plasma
cells.
• This
“primary
lesion”
always
heals
spontaneously, but 2–10 weeks later, the
“secondary” lesions appear.
• These consist of a red maculopapular rash
anywhere on the body, including the hands
and feet, and moist, pale papules
(condylomas) in the anogenital region,
axillae, and mouth.
• The patient may also have syphilitic
meningitis,
chorioretinitis,
hepatitis,
nephritis (immune complex type), or
periostitis.
• The secondary lesions also subside
spontaneously.
• Both primary and secondary lesions are rich
in spirochetes and are highly infectious.
• Contagious lesions may recur within 3–5
years after infection, but thereafter the
individual is not infectious.
• In about 30% of cases, early syphilitic
infection progresses spontaneously to
complete cure without treatment.
• In another 30%, the untreated infection
remains latent (principally evident by
positive serologic test results).
• In the remainder, the disease progresses to
the “tertiary stage”.
• characterized by :
development of granulomatous lesions
(gummas) in the skin, bones, and liver
 degenerative changes in the central
nervous system (meningovascular syphilis,
paresis, tabes); or cardiovascular lesions
(aortitis, aortic aneurysm, aortic valve
insufficiency).
• In all tertiary lesions, treponemes are very
rare.
• exaggerated tissue response must be
attributed to
hypersensitivity
to
the
organisms.
Congenital Syphilis
• A pregnant woman with syphilis can
transmit T pallidum to the fetus through
the placenta beginning in the 10th–15th
weeks of gestation.
• Some of the infected fetuses die, and
miscarriages result; others are stillborn at
term.
• Others are born live but develop the signs
of congenital syphilis in childhood
interstitial keratitis.
Hutchinson’s teeth.
Saddlenose.
Periostitis.
variety
of
central
nervous
system
anomalies.
• Adequate treatment of the mother during
pregnancy prevents congenital syphilis.
• In congenital infection, the child makes
immunoglobulin M (IgM) antitreponemal
antibody.
Diagnostic Laboratory Tests
• Specimens
• tissue fluid expressed from early surface
lesions for demonstration of spirochetes by
either
dark-field
microscopy
or
immunofluorescence and nucleic
acid
amplification.
• Blood can be obtained for serologic tests.
• cerebrospinal fluid (CSF) is useful for Venereal
Disease Research Laboratory (VDRL) testing.
• Dark-Field examination
• A drop of tissue fluid or exudate is placed
on a slide, and a coverslip is pressed over
it to make a thin layer.
• The preparation is then examined under oil
immersion within 20 minutes of collection
with dark-field illumination for typical
motile spirochetes.
• Immunofluorescence
• Tissue fluid or exudate is spread on a
glass slide, air dried, and sent to the
laboratory. It is fixed, stained with a
fluoresceinlabeled antitreponeme antibody,
and
examined
by
means
of
immunofluorescence microscopy for typical
fluorescent spirochetes.
• Nucleic Acid Amplification Tests
• Molecular assays are most useful when
testing is performed on genital ulcers.
• Serologic Tests for Syphilis
• Nontreponemal tests
• Treponemal antibody tests
•
•
•
•
Nontreponemal tests
used as screening tests for syphilis
used to follow the efficacy of therapy.
they are not very sensitive in early syphilis,
and the results may not turn positive until a
few weeks after initial infection
• false-positive results can occur with many
other diseases;
• and there may be a prozone phenomenon,
particularly in secondary syphilis.
• The antigens in these tests contain measured
amounts of cardiolipin, cholesterol, and
purified lecithin
• the cardiolipin was extracted from beef heart
or liver with added lecithin and cholesterol to
enhance reaction with syphilitic “reagin”
antibodies.
• Reagin is a mixture of IgM and IgG antibodies
reactive with the cardiolipin–cholesterol–
lecithin complex.
• The VDRL and tests require microscopic
examination to detect flocculation.
• rapid plasma reagin (RPR) test has colored
particles that become caught in the mesh
of the antigen–antibody complex, allowing
the tests to be read without microscopic
magnification.
• The
nontreponemal
tests
can
give
quantitative results using serial twofold
dilutions.
• An estimate of the amount of reagin
present in serum can be expressed as the
titer.
• Quantitative
results are
valuable
in
establishing a diagnosis and in evaluating
the effect of treatment.
• Positive nontreponemal test results develop
after 2–3 weeks of untreated syphilis and are
positive in high titer in secondary syphilis.
• Positive nontreponemal test results typically
revert to negative, often in 6–18 months and
generally by 3 years after effective treatment
of syphilis.
• A positive nontreponemal test result late after
treatment for syphilis suggests ineffective
treatment or reinfection.
• The VDRL test is standardized for use on
CSF, and the result becomes positive in
patients with neurosyphilis.
• Treponemal antibody tests
• The treponemal tests measure antibodies
against T pallidum antigens.
• The tests are used to determine if a
positive result from a nontreponemal test is
truly positive or falsely positive.
microhemagglutination T pallidum (MHATP)
fluorescent treponemal antibody absorbed
(FTA-ABS) test.
• These tests are not useful for screening or
after therapy because, once positive, they
usually remain so for life except for the
immunocompromised.
TREATMENT
• Treponema pallidum remains exquisitely
sensitive to penicillin, which is the preferred
treatment in all stages.
• In primary, secondary, or latent syphilis,
persons hypersensitive to penicillin may be
treated with doxycycline.