Syphilis
Organism causing syphilis
- Treponema pallidum is the causative agent of syphilis.
- T. pallidum is a thin, elongated (0.10 to 0.18 um) bacterium that
cannot be readily visualized by light microscopy, instead requiring
visualization by darkfield microscopy, which uses obliquely applied light.
-
The organism displays 6 to 14 regularly wound coils, has a characteristic
corkscrew motility, and flexes centrally at 90-degree angles.
- Sustained in
vitro cultivation of T. pallidum is not currently possible for
diagnostic purposes. Investigators have propagated T. pallidum in
rabbits or guinea pigs to provide organisms for scientific study, to
evaluate new antimicrobial agents or candidate vaccines, or to demonstrate
the presence of treponemes in clinical specimens.
Method of transmission
- In most cases, T. pallidum infection is acquired from direct
sexual contact with an individual who has an active primary or secondary
syphilitic lesion.
- Transmission occurs in approximately one third of such
contacts.
- Less commonly the disease may be spread by: a) sharing of needles by IV drug
users b) by non-genital contact with a mucosal lesion (e.g. infant contact
with a maternal chancre) c) occasional cases result from accidental
inoculation of infected material. Modern precautions have essentially
eliminated blood transfusions as a source of disease d) transplacental
transmission.
The pathogenesis of Congenital syphilis
- Is contracted from an infected mother via transplacental transmission of
T. pallidum at any time during pregnancy or at birth.
- In women with
untreated early syphilis, 40% of pregnancies result in spontaneous abortion,
stillbirths, or perinatal deaths.
- Untreated syphilis, at any stage of the
disease, can be transmitted to the fetus; the rate of transmission is almost
100% during the secondary stage and slowly decreases with increasing
duration of disease.
- Infection can be asymptomatic, especially in the first
weeks of life; or it may have multi-system manifestation, including osteitis,
hepatitis, lymphadenopathy, pneumonitis, mucocutaneous lesions, anemia, and
hemorrhage.
- Late manifestations of congenital syphilis can involve the
central nervous system, bones, teeth, eyes, skin and/or cartilage.
The pathogenesis of Primary syphilis
- The spirochete reaches the subepithelial tissues through inapparent
breaks in the skin or possibly by passage between the epithelial cells of a
mucous membrane.
- It multiplies locally with a generation time of about 30
hours; although the primary lesion is local, the organism also disseminates
rapidly to local lymph nodes and then to other organs by way of the
bloodstream.
- The primary lesion develops 2 to 10 weeks after infection as an indurated
swelling at the site of infection.
- The surface necroses to yield a
hard-based ulcerated lesion, termed the chancre, which is teeming with
spirochetes and is highly infectious.
- The basic pathologic lesion is an
endarteritis.
- The small arterioles show swelling and proliferation of their
endothelial cells.
- This reduces or obstructs local blood supply and probably
accounts for the necrotic ulceration.
- Dense, granulomatous cuffs of
lymphocytes, monocytes, and plasma cells surround the vessels. Untreated,
the lesion heals within 3 to 8 weeks. The primary lesion is not always
apparent.
The pathogenesis of Secondary syphilis:
- Occurs 2 to 10 weeks after the primary hematoenous dissemination stage
and results in a secondary stage with varying degrees of severity.
- Lesions
are heavily infected with T. pallidum. In moist areas around the
vulva or anus, hypertrophic papular lesions (condyloma lata) can occur.
-
Generalized lymphadenopathy, fever, malaise, spienomegaly, sore throat,
headache, and arthralgia can be present.
Immune complexes of antibody, spirochetal components and complement are
present in arteriolar walls and account for some of he clinical
manifestations.
- This stage may last several weeks and may relapse. It may be
mild, however, and go unnoticed by the patient. The factors that control the
secondary stage are unclear.
The pathogenesis of Tertiary syphilis:
- After the secondary state, nontreponemal antibody test results of one
fourth of patients revert to negative, possibly the result of spontaneous
cure.
- In another 45%, serologic tests remain positive, but no further
clinical manifestations appear.
- The remaining untreated cases develop
tertiary manifestations.
- The manifestations may appear as early as 5 years
after infection, but characteristically occur after 15 to 20 years.
- Meningovascular syphilis involves vascular changes of the meninges
associated with increased cells and protein in
the cerebrospinal fluid and focal neurologic changes.
- In general paresis,
there is extensive cortical degeneration of the brain, with mental changes
ranging from decreased memory to hallucinations or frank psychosis.
- Tabbes
dorsalis involves demyelination of the posterior columns and dorsal roots and
damage to dorsal root ganglia.
- The latter produces ataxia, wide-based gait,
foot slap, and loss of the sensations of position, pain, and temperature.
- Not
all patients with central nervous system involvement have symptomatic disease.
- The most characteristic lesion of late cardiovascular syphilis is the
development of an aneurysm of the ascending and
transverse segments of the aortic arch as a result of gummatous
changes in the middle coat of the aorta and loss of elasticity.
- This aneurysm
can lead to aortic valve incompetence, pressure necrosis of structures
adjacent to the aorta, or rupture of the aorta.
- The isolated gumma is a granulomatous reaction to T. pallidum
infection. .
- It occurs most often in skin, bones, or joints, but may involve
any organ.
- Clinical manifestations of gumma are similar to those of other mass-producing
lesions in the tissues, such as tumors.
- Too few spirochetes are in the lesions
to be demonstrated by microscopic techniques, except in general paresis, when
large numbers are found in the cerebral cortex.
- Late disease is not infectious
to others.
Immunity to infection
-
In the early stages of syphilis, the patient rapidly becomes immune to
reinfection, but immunity is short-lived if the
patient is successfully treated.
- In the later stages, immunity to reinfection
is more solid and continues after treatment.
- Syphilis in immunocompromised
patients such as those suffering from the- acquired immunodeficiency syndrome
may present with unusually aggressive or atypical manifestations.
Method of diagnosis of syphilis
a) Definitive diagnosis is achieved by identifying spirochetes by
-
microscopic darkfield examination or
- direct fluorescent antibody tests of
lesion exudate or tissue.
b) Most cases of syphilis are diagnosed serologically.
- Presumptive
diagnosis is possible using two types of serologic tests, i.e., (1)
nontreponemal tests and (2) treponemal tests.
- Neither type of test alone is
sufficient for diagnosis.
-
nontreponemal tests
- The nontreponernal tests for syphilis include:
- the
VDRL slide test
- the rapid plasma reagin (RPR) test
- the automated reagin
test (ART)
- These tests measure antibody directed against lipoidal antigen
from T. pallidum and/or its interaction with host tissues.
- They become
positive in the early stages of the primary lesion and, with the possible
exception of some patients with advanced HIV infection, are uniformly positive
during the secondary stage.
- They slowly wane in
the later stage of the disease. In neurosyphilis, VDRL tests on cerebrospinal
fluid may be positive while the serum VDRL has
reverted to negative.
- Cardiolipin tests are nonspecific: they may become
false-positive in a variety of autoirnmune diseases or in those involving
substance tissue destruction or liver involvement,
such as lupus erythernatosus, viral hepatitis, infectious
mononucleosis, and malaria.
- False-positive results can also occur occasionally
in pregnancy and in patients with HIV infection. Non-treponemal tests are thus used as screening procedures for diagnosis and are
confirmed by one of the treponemal tests.
- Treponemal tests: involve direct detection of antibody to T. pallidum.
-
The spirochetes used in the tests are derived from rabbit testicular lesions.
-
Two procedures are now used most frequently,
- the
fluorescent treponemal antibody absorption tests (FTA-ABS)
- and increasingly the
microhemagglutination test for T. pallidum antibody (MHA-TP).
- The FTA-ABS procedure is an indirect immunofluorescence serodiagnostic test
involving treatment of the patient’s serum with extracts of a cultivated
treponeme that is T. pallidum.
- The MHA-TP is simpler than FTA-ABS and
only slightly less sensitive.
- It is a hemagglutination test employing T.
pallidum antigens adsorbed to erythrocytes that have been stabilized by
tannic acid and formaldehyde.
- Appropriate blocking antigens are added to avoid
nonspecific reactions.
- Treponemal tests are considerably more specific than those using cardiolipin,
but titers of positive tests do not decrease rapidly with cure.
- Thus, they are
valuable confirmatory tests, but they are not helpful in monitoring therapy.
Effectiveantimicrobial agents against this organism
- Penicillin remains the best-studied and the preferred therapy for
syphilis.
- For early (primary, secondary or latent less than one
year)
syphilis use penicillin G benzathine 2.4 million units IM once.
- For late
(more than one year’s duration) cardiovascular or gumma syphilis use
penicillin G benzathine 2.4 million units IM weekly for 2 weeks.
- For neurosyphilis
use pencillin G 2-4 million units IV daily for 10-14 days.
- For congenital
syphilis use penicillin G procaine 50,000 units/kg IM daily for 10-14 days.
Preventive neasures
The following control measures will aid in prevention of this disease.
-
Congenital Syphilis can be prevented by adequate treatment of an infected
mother before the last month of pregnancy.
- Routine serologic testing is
performed in early pregnancy and should be repeated in the last trimester in
women at high risk of acquiring syphilis.
- Drainage/secretion precautions in addition to the routinely recommended
universal precautions are indicated for all infants with suspected or proven
congenital syphilis until therapy has been administered for at least 24 hours.
-
Because moist open lesions and possibly blood are contagious in all forms of
syphilis, these precautions are also required for primary and secondary
syphilis with skin and mucous membrane lesions.
- Education about sexually transmitted diseases, treatment of sexual contacts,
reporting of each case to local public health authorities for contact
investigation and appropriate follow-up, and serologic screening of high-risk
populations are indicated.
- All recent sexual contacts of a person with acquired syphilis should be
identified, examined, serologIcally tested, and treated appropriately.
- Sexual
contacts within the last 3 months who are seronegative are at high risk for
early syphilis and should be treated for early acquired syphilis.
Long term sequelae
Untreated syphilis can lead to tertiary syphilis attacking
- CNS
- CVS
- skin
- bones
- joints
- oral and nasal cavities.