Communicable Disease Management Protocol

Syphilis
Communicable Disease Control Unit

Etiology presence of one or more typical lesions (chancres),

and reactive treponemal serology, regardless of
Syphilis is primarily a sexually transmitted infection nontreponemal test reactivity, in individuals with
(STI). Syphilis can also be acquired through no previous history of syphilis;
congenital transmission to the newborn and blood
transfusion, but these are much less common. It is a OR
systemic disease caused by the spirochete presence of one or more typical lesions (chancres)
Treponema pallidum subspecies pallidum (1). This is and at least a four-fold (e.g., 1:8 to 1:32) increase
one of the clinically important spirochetes and is in titre over the last known nontreponemal test in
related to such agents as Borellia burgdorferi (the individuals with a past history of syphilis treatment.
cause of Lyme Disease) and Leptospira (the cause of
leptospirosis). Syphilis occurs exclusively in Secondary Syphilis:
humans; there is no animal reservoir (2).
Identification of T. pallidum by darkfield
Non-venereal treponemal infections cause pinta, microscopy, fluorescent antibody, or equivalent
yaws, and bejel. These diseases are endemic to some examination of mucocutaneous lesions and
developing nations and are seen in developed condyloma lata;
nations primarily as a result of immigration.
OR
Serologic testing cannot distinguish syphilis from
these endemic treponematoses (3). presence of one or more typical mucocutaneous
lesions, alopecia, loss of eyelashes and lateral third
Case Definitions (4) of eyebrows, iritis, generalized lymphadenopathy,
fever, malaise, or splenomegaly;
Incubating Syphilis: PLUS
An asymptomatic person with a history of sexual
either a reactive serology (nontreponemal and
exposure within the past 10-90 days to a partner
treponemal);
with a confirmed diagnosis of infectious syphilis;
OR
PLUS
at least a four-fold (e.g.,1:8 to 1:32) increase in titre
either a reactive serology (nontreponemal and
over the last known nontreponemal test.
treponemal);
OR Early Latent Syphilis:
at least a four-fold (e.g., 1:8 to 1:32) increase in An asymptomatic person with reactive serology
titre over the last known nontreponemal test. (nontreponemal and treponemal) who within the
past one year had ONE of the following:
Incubating syphilis is a subset of Early Latent
Syphilis. 1) non-reactive serology;
2) symptoms suggestive of primary or secondary
Primary Syphilis: syphilis; or
Identification of T. pallidum by darkfield 3) exposure to a sexual partner with primary,
microscopy, fluorescent antibody, or equivalent secondary or early latent syphilis.
examination of material from a chancre or regional
lymph node;
OR

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Late Latent Syphilis: radiographic evidence of congenital syphilis, whose

An asymptomatic person with persistently reactive mother is seropositive for syphilis without
treponemal serology (regardless of nontreponemal documented evidence of adequate treatment.
serology reactivity) who does not meet the criteria NOTE: The national case definitions for syphilis
for early latent disease and who has not been are currently in the process of being revised. This
previously treated for syphilis. protocol will be updated accordingly.
Neurosyphilis:
Reporting Requirements
Reactive treponemal serology (regardless of
nontreponemal serology reactivity) and ONE of the • All positive syphilis tests (both nontreponemal
following: and treponemal) are reportable by laboratory
operators to the Communicable Disease Control
1) reactive CSF-VDRL in non-bloody Unit, Manitoba Health.
cerebrospinal fluid (CSF);
• Operators of Manitoba clinical laboratories
2) clinical evidence of neurosyphilis and CSF detecting nontreponemal or treponemal
pleocytosis (particularly lymphocytes) in the antibodies must forward sera or cerebrospinal
absence of other known causes; or fluid positive for these antibodies to Cadham
3) clinical evidence of neurosyphilis and elevated CSF Provincial Laboratory.
protein in the absence of other known causes. • All cases and contacts are reportable by attending
Neurosyphilis may be seen during primary or health care professionals to the Communicable
secondary syphilis stages and can occur at any time Disease Control Unit, Manitoba Health.
after initial infection.
Epidemiology
Tertiary Syphilis other than Neurosyphilis:
Reservoir: Humans
Presence of reactive treponemal serology (regardless
of nontreponemal test reactivity) together with Transmission: Approximately 90% of all syphilis is
characteristic abnormalities of the cardiovascular sexually transmitted. Exposure mainly occurs
system, bone, skin or other structures, in the during oral, anal, or vaginal intercourse.
absence of other known causes of these Transmission occurs through direct contact with
abnormalities (T. pallidum is rarely seen in these infectious exudates from moist skin lesions or
lesions, although when present is diagnostic); mucus membranes of infected persons during
sexual contact (1, 5). Primary, secondary, and early
AND latent stages are considered infectious, with an
no clinical or laboratory evidence of neurosyphilis. estimated risk of transmission per partner of 60%.
Early latent syphilis is considered infectious because
Congenital Syphilis: of the 25% chance of relapse to secondary stage (6).
Identification of T. pallidum by darkfield Transmission from touching children with
microscopy, fluorescent antibody, or equivalent congenital syphilis, kissing, blood transfusion,
examination of material from nasal discharges, skin sharing of needles and drug equipment, and
lesions, placenta or umbilical cord, or autopsy accidental direct inoculation are extremely rare.
material of a neonate (up to four weeks of age); Ulcerative STIs like syphilis promote HIV
OR transmission and/or acquisition by augmenting
HIV infectiousness and susceptibility. Syphilis
reactive serology (treponemal and nontreponemal) increases the rate of HIV acquisition between two
from venous blood (not cord blood) in an and four-fold and the risk of transmission of HIV
infant/child with clinical, laboratory, or between two and nine-fold (7).

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Pregnant women can transmit the infection Clinical Presentation and Natural
transplacentally to the fetus at all stages during the History
course of untreated disease or during passage
through the birth canal (8). The rate of vertical Incubating Syphilis:
transmission is approximately 70-100% in
Persons with incubating syphilis are asymptomatic.
untreated early syphilis. Transmission is more likely
They are identified through self-reporting or
with primary and secondary infections and less
contact tracing after having been exposed to a
likely during latent infections (9, 10, 11).
confirmed syphilis case within the last 90 days. An
Breastfeeding does not result in syphilis
early spirochetemia develops during this phase,
transmission unless an infectious lesion is present
which results in secondary invasion of virtually
on the breast (12).
every bodily organ (3).
Occurrence: The incidence of infectious syphilis in
Canada and Manitoba was very low in the 1990s Primary Syphilis:
with most cases being imported rather than locally Primary syphilis most often presents as a single
acquired. After achieving rates of 0.4-0.6/100,000 painless lesion (chancre) that develops at the site of
in Canada from 1994 to 2000, rates of infectious inoculation. The chancre is most commonly found
syphilis rose to 1.5/100,000 in 2002 and on the external genitalia. These lesions frequently go
3.5/100,000 in 2004 (6, 13). unnoticed, particularly among women and MSM,
In the last few years, several provinces (British who cannot see vaginal or anal lesions. The ulcer is
Columbia, Alberta, Ontario, Quebec, and clean-based with a raised, indurated border. In men,
Manitoba) have experienced local syphilis outbreaks the most common site affected is the penis, more
(12). Since January of 2003, Manitoba has specifically the coronal sulcus and glans. Anorectal
experienced an outbreak of locally acquired chancres are common in MSM. In women, the most
infectious syphilis. Most cases reside in the common locations for lesions are the labia majora,
Winnipeg region affecting men in the 40-44 year labia minora, fourchette, and perineum. Ulcers may
old age group and females in the 30-34 year old age also be found on the lip, in the mouth, and on
group (14). Risk factors identified in Winnipeg fingers. The chancre usually resolves spontaneously in
include heavy and frequent alcohol use; casual one to four months. Painless, firm regional
unprotected sex among heterosexuals; and lymphadenopathy, often associated with genital
unprotected sex in anonymous partnering venues lesions, is common and occurs in up to 80% of
(bathhouses, bars and internet chat lines) among patients. These clinical findings usually occur about
men who have sex with men (MSM) (14, 15). three weeks after infection with T. pallidum.
Incubation Period: For a primary chancre, the Variations in clinical presentation have been
incubation period is three days to three months, reported in HIV infected patients. These variations
usually about three weeks (1). Refer to Table 1: include multiple single chancres and chancres that
Clinical Manifestations and Incubation Period for may be slower to resolve (16).
further details.
Secondary Syphilis:
Period of Communicability: Variable. Syphilis is The most common feature is a skin rash, which is
infectious during primary, secondary, and early present in about 90% of cases. This rash may be
latent stages, and also in mucocutaneous macular, papular, papulosquamous, pustular, or
recurrences. Congenital transmission is most likely non-specific. The rash of secondary syphilis is
during primary and secondary maternal syphilis, somewhat unique in that it involves the palms of
but can occur in the latent period. the hands and soles of the feet. The rash usually
resolves without scarring over several weeks. Hair
loss can also be an important clue to the diagnosis.

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Condylomata lata are characteristic of secondary Tertiary Syphilis:

syphilis. They are large fleshy lesions that may form Tertiary syphilis is a slowly progressive,
in warm moist areas such as the perineum and inflammatory disease that can affect any organ in
perianal skin, axillae, and beneath the breasts. the body to produce clinical illness 10-30 years
These lesions are painless but highly infectious. after the initial infection. Tertiary syphilis refers to
The original genital chancre is still present in up to gummatous and cardiovascular syphilis, but not to
30% of patients with secondary syphilis. all neurosyphilis. These forms of syphilis are now
uncommon.
Constitutional symptoms such as fevers, muscle
aches, and weight loss are also common. There may • Gummatous syphilis (late benign syphilis)
be evidence of central nervous system involvement Gumma or granulomatous-like lesions are
in a number of cases. Headache is present in about indolent and most commonly found in the
30% of patients. Symptomatic meningitis may skeletal system, skin, and mucous membranes,
occur in up to 1-2% of cases; however but can develop in any organ. Lesions rarely
asymptomatic meningitis is more common and can cause incapacity or death, but when lesions
occur in up to 40%. occur in organs like the brain or heart, serious
complications occur.
Latent Syphilis:
• Cardiovascular syphilis
Left untreated, secondary syphilis may progress to a
period of subclinical infection. During the latent Cardiovascular syphilis results from destruction of
stage of syphilis, skin lesions resolve and patients the elastic tissue of the aorta which leads to
are asymptomatic. The only clue for the diagnosis ascending aortitis and the formation of
of latent infection is a positive serologic test for aneurysms that, rarely, rupture. The ascending
syphilis. aorta is most often affected, with the potential
complications of valve insufficiency and coronary
Latent syphilis is divided into early latent and late artery stenosis. Approximately 11% of untreated
latent syphilis. Patients are classified as having early patients progress to cardiovascular syphilis.
latent disease if they are asymptomatic and have
acquired the infection within the past year. Neurosyphilis:
This stage can be established only in patients who Central nervous system (CNS) disease can occur
have seroconverted within the past year, who have during any stage of syphilis. A patient who has
had symptoms of primary or secondary syphilis clinical evidence of neurologic involvement with
within the past year or who have had a sexual syphilis (e.g., cognitive dysfunction, motor or
partner with primary, secondary or early latent sensory deficits, ophthalmic or auditory symptoms,
syphilis within the past year. Patients who do not cranial nerve palsies, and symptoms or signs of
meet these criteria should be presumed to have late meningitis) should have a CSF examination (16).
latent syphilis or latent syphilis of unknown Neurosyphilis is divided into early (acute)
duration. A patient with early latent syphilis is neurosyphilis and late (chronic) neurosyphilis (3).
considered to be infectious due to the 25% risk of Both early and late neurosyphilis can be divided
relapse to secondary syphilis. Early latent syphilis is into asymptomatic and symptomatic phases. The
infectious by sexual contact whereas late latent symptomatic phase of late neurosyphilis is further
syphilis is not. However, a pregnant woman with distinguished as meningovascular or
late latent syphilis can infect her fetus in utero, and parenchymatous neurosyphilis. Clinical overlap
an infection can be transmitted via transfusion of with combinations of meningovascular and
contaminated blood. parenchymatous features are common as this form
of chronic meningitis involves every portion of the
CNS (3).

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Asymptomatic neurosyphilis occurs in up to 40% Clinical manifestations of congenital syphilis are

of patients (3). Asymptomatic neurosyphilis is divided into early (appear within the first two years
defined as patients who have no clinical of life) and late (after first two years of life) stages.
manifestations of neurologic involvement but who Late congenital syphilis usually manifests near
have one or more of the following CSF puberty. Most clinical signs of early congenital
abnormalities: elevated WBC count, elevated syphilis develop within the first three months of
protein concentration, a decreased glucose life. Snuffles or persistent rhinitis is one of the
concentration, or a positive nontreponemal test earliest clinical manifestations occurring in 4-22%
(e.g., VDRL). RPR is not recommended for CSF of infants. The nasal discharge may be profuse,
testing. purulent, or blood tinged and is highly infectious.
Hepatomegaly with or without splenomegaly
Syphilis in Pregnancy and Congenital occurs in 33-100% of patients. Asymptomatic
Syphilis: central nervous system involvement manifesting in
Syphilis can be transmitted transplacentally to the CSF abnormalities of lymphocytosis, elevated
fetus at all stages during the course of untreated protein levels, and positive serologic tests occur in
maternal disease from incubating syphilis to up to 80% of infected infants. Symptomatic
primary, secondary, tertiary, and latent disease (16). neurosyphilis develops rarely. Bone lesions develop
Syphilis can also be transmitted during passage within eight months of birth in early congenital
through the birth canal when the newborn infant syphilis. Late manifestations of congenital syphilis
contacts a genital lesion (8). Breastfeeding does not include Hutchinson’s triad of interstitial keratitis,
result in transmission of syphilis unless an peg shaped upper incisors, and eighth cranial nerve
infectious lesion is present on the breast. Pregnancy deafness. The hearing loss can be sudden and
has no known effect on the clinical course of usually occurs at eight to 10 years of age.
syphilis. The rate of vertical transmission in The optimal treatment of an infant born with
untreated women is 70-100% in primary syphilis, congenital syphilis is not known.
40% for early latent syphilis, and 10% for latent
disease. The longer the interval between infection HIV and Syphilis:
and pregnancy, the more benign is the outcome in Coinfection is common as both syphilis and HIV
the infant. are sexually transmitted infections. The two diseases
All pregnant women should be screened for syphilis can affect each other in several ways. As with other
(with a nontreponemal test) and other STIs ulcer-causing infections, syphilis can enhance the
(including HIV) on their first prenatal visit. High acquisition of HIV. Syphilis in the HIV-infected
seroconversion rates for both syphilis and HIV in individual can be highly aggressive. Patients can
high risk populations during pregnancy has led progress from primary to tertiary syphilis over
some experts to suggest repeat screening of women several years, as opposed to several decades in
during late pregnancy and delivery (17). individuals not infected with HIV. Despite this
progression, the conventional staging of syphilis is
Syphilis in pregnancy can cause widespread similar with HIV coinfection.
complications for both the infected mother and
fetus. At least two-thirds of all babies born to Although patients with syphilis and HIV
untreated women with syphilis are infected (10). If coinfection have shown no distinctive or unique
evidence of syphilis is present, treatment should be features from those without concurrent HIV
initiated immediately according to the stage of the infection, they are at increased risk to manifest a
disease. Efficacy of syphilis treatment in pregnancy more protracted and malignant course. This
considers resolution of maternal infection and includes greater constitutional symptoms, greater
prevention of congenital syphilis. organ involvement, atypical and florid skin rashes,
multiple genital ulcers, concomitant chancre during

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the second stage, and a significant predisposition to two types of serologic tests for syphilis; nonspecific
develop symptomatic neurosyphilis, especially nontreponemal antibody tests (VDRL and RPR)
uveitis (3). and specific treponemal antibody tests (FTA-ABS
and TP-PA). To establish a diagnosis of syphilis,
Coinfected patients should be managed in
both types of serologic tests are usually necessary. It
consultation with an infectious disease specialist or
should be emphasized that serologic test results for
physician knowledgeable in HIV/AIDS.
syphilis on rare occasions may be negative in active
cases, especially in older patients, or very early in
Diagnosis of Syphilis primary infections.
Diagnosis of syphilis is based on history, physical All clinical serology testing and screening for
examination, and laboratory investigation. It is syphilis are performed at the Cadham Provincial
essential that the stage of syphilis be accurately Laboratory. Samples are routinely tested Monday-
assessed and documented in order to ensure Friday within 24 hours of being received. Contact
appropriate management of cases and contacts. the Serology section at CPL at (204) 945-6123 for
questions about testing and (204) 945-6805 to
Darkfield Microscopy & Direct or Indirect order CPL requisitions forms. After hours testing is
Fluorescent Antibody Test (DFA/IFA): conducted for transplant and other emergent
Darkfield microscopy and DFA/IFA testing of purposes. An appropriate sample is 5-10 ml of
lesion exudates or tissues are the definitive methods blood collected in a red-stoppered tube which
for diagnosing early syphilis when an active should be sent to CPL with a request for “serum
chancre, mucous patch, or condyloma latum is for VDRL”. The CPL lab requisition should also
present. It is also useful for testing nasal discharge provide information on the reason for testing
in a neonate with snuffles. (sexual contact to case, genital ulcer, clinical
findings, etc). It is extremely important to include
Darkfield microscopy is often not practical (it is
the relevant history on the lab requisition.
not available in most labs including CPL) as it
requires a skilled technician on-site. In addition, Routine screening of umbilical cord blood is NOT
specimens must be appropriately collected and recommended for serological testing where a
quickly examined within 5-20 minutes of diagnosis of congenital syphilis is considered.
collection. Positive tests on these materials for Testing of maternal serum is preferred to testing
immunofluorescent (DFA) testing are diagnostic. infant serum because infant serum can be
Samples collected from serous exudates from a nonreactive if maternal serology is low titre or if the
chancre or secondary skin or mucous membrane infection was late in pregnancy. Cord blood that is
lesions for DFA testing should be submitted on a contaminated with maternal blood may lead to a
slide and sent to CPL. CPL requests an additional false positive test result. Contact CPL at 945-7582
dry Dacron swab be collected for nucleic acid or 945-7545 if further diagnostic strategies are
amplification testing (NAAT), and transported in a sought.
dry sterile urine container. NAAT is used for See Table 2: Interpretation of Serologic Tests for
syphilis subtyping and not for diagnosis. Prior Syphilis.
arrangements are generally not required.
Nontreponemal Tests (VDRL and RPR):
Serology:
Syphilitic infection leads to the production of
Serologic tests for syphilis are essential for diagnosis nonspecific antibodies (IgM and IgG) directed
of individuals, for following the efficacy of therapy, against a lipoidal antigen resulting from the
and for screening purposes. They detect antibodies interaction of host tissues with T. pallidum or from
formed during the course of syphilitic infection. A T. pallidum itself. This antibody-antigen reaction is
presumptive diagnosis is possible with the use of the basis of nontreponemal tests such as the

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Venereal Disease Research Laboratory slide test lower with time, but serum frequently remains
(VDRL) and the rapid plasma reagin test (RPR). reactive, usually in low titre. As with all quantitative
The RPR test is more sensitive than the VDRL. serologic tests, only a four-fold or greater change in
CPL uses the rapid plasma reagin card test (RPR). titre is meaningful.
After adequate treatment of syphilis, Specific Treponemal Tests:
nontreponemal tests (NTT) eventually become
nonreactive. However, even with sufficient These tests measure antibodies against specific
treatment, patients sometimes have a persistent T. pallidum antigens and are used primarily to
low-level positive nontreponemal test referred to as confirm the diagnosis of syphilis in patients with a
a serofast conversion. Nontreponemal test titres of reactive nontreponemal test. The principal specific
persons who have been treated for latent or late treponemal antibody tests performed in most
stages of syphilis or who have become reinfected do laboratories are the T. pallidum particle
not decrease as rapidly as do those of persons in the agglutination tests (TP-PA) and fluorescent
early stages of their first infection. In fact these treponemal antibody-absorption test (FTA-ABS).
persons may remain serofast for life. Most patients who have reactive treponemal tests
VDRL and RPR become positive one to four weeks will have reactive tests for the remainder of their
after the appearance of the primary chancre or six lives, regardless of treatment or disease activity.
weeks after exposure. Biologic false positive However, reversion to a nonreactive status may
reactions occur at a rate of 1-2% in the general occur in up to 10% of patients, especially in those
population. Acute false positive tests lasting less who are treated early (3). Treponemal test antibody
than six months can occur following a febrile illness titres correlate poorly with disease activity and
or immunization. As a rule, 90% of false positive should not be used to assess treatment response.
titres are less than 1:8, but low titres are also seen in False positive results can occur especially when the
latent infection. False positive rates in pregnancy are FTA-ABS test is used in patients with Lyme disease,
similar to the general population. More than 10% HIV, pregnancy, drug addiction, toxoplasmosis,
of IDU may have false positive results (18). HIV H. pylori, autoimmune disorders like lupus and
infection has not been associated with increased rheumatoid arthritis, and in persons with other
false positive NTT in individuals at low risk of treponemal diseases such as yaws, pinta or bejel.
IDU. Causes of acute and chronic biologic false
positive reactions in NTT are listed in Table 3 of Confirmatory Test:
the appendix. The TP-PA test is a specific treponemal test for
Serial nontreponemal tests are useful to determine the serologic detection of antibodies to various
the stage of the disease; a four-fold rise in titre may species and subspecies of treponemes. Reports
indicate recent infection, reinfection in an from CPL refer to the TP-PA as a confirmatory
adequately treated person, or relapse in an test result.
inadequately treated person. Adequate treatment of Reference Test:
infectious syphilis is indicated by a four-fold or
greater decline in titre within one year. Titres The FTA-ABS test is an indirect
should generally become non-reactive or weakly immunofluorescent antibody test using T.
reactive within one year following treatment of pallidum from rabbit testis as the antigen. Its
primary syphilis and within two years after interpretation is subjective and requires great
treatment for secondary syphilis. Treatment of late attention to detail. Its principal use is to verify
latent or late syphilis usually has little or no effect the diagnosis of syphilis. Reports from CPL
on the titre and should not be used to gauge the refer to this as the reference test.
adequacy of the treatment. Titres tend to become

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Tests for Neurosyphilis: 5. HIV coinfection with late latent or syphilis of

No single test is diagnostic for neurosyphilis; the unknown duration;
CSF-VDRL is highly specific but it is insensitive; as 6. Where HIV coinfection exists, a lumbar puncture
low as 30%. Most other tests are both insensitive (LP) is strongly recommended when neurological
and nonspecific and must be interpreted in relation signs or symptoms are present, VDRL/RPR
to other test results and the clinical assessment. ≥1:32 dilutions, CD4+ counts <350 cells/µL or
Diagnosis of neurosyphilis usually depends on the treated syphilis with suboptimal decline in
combination of patient history, physical VDRL/RPR titre. Some experts recommend a LP
examination, reactive serologic test results, and for all syphilis cases with HIV coinfection.
abnormalities of CSF (cell count, protein, or a A LP may be considered in other patients on a case
reactive CSF-VDRL). The CSF leukocyte count is by case basis.
usually elevated (>5 WBC/mm3) in patients with
neurosyphilis. The CSF leukocyte count can also be Tests for congenital syphilis:
used as a sensitive measure of the effectiveness of Venous samples should be obtained from both
therapy. A positive CSF-VDRL result in the mother and baby for serology (treponemal and
appropriate clinical setting establishes the diagnosis nontreponemal tests). Cord blood is not suitable
of neurosyphilis although serum antibody for testing. The interpretation of reactive antibodies
contamination is possible. A negative CSF-VDRL in the neonate must take into consideration the
does not rule out the possibility of neurosyphilis. maternal history, including stage of syphilis, history
Normalization of CSF markers is affected by the of treatment, and syphilis serology results.
stage of syphilis at which treatment is initiated and Placenta, neonatal nasal discharge, or skin lesions
pretreatment levels of particular CSF markers. In may be examined by darkfield microscopy or
patients without HIV infection treated with DFA/IFA for T. pallidum. CSF examination should
penicillin regimens, the CSF pleocytosis and VDRL be performed on all infants with suspected
titre normalize within one year. Reversion of congenital syphilis. Long bone x-rays should also be
pleocytosis is more likely when pretreatment CSF performed.
WBC counts are high. CSF-VDRL normalization
is less likely when pretreatment CSF-VDRL titres
are high. In HIV-infected patients, CSF WBC Key Investigations
count, protein, and VDRL may be slow to • Interview case for history of exposure, risk
normalize. CSF-VDRL titres are less likely to behaviours, sexual contacts, adequacy of
normalize after treatment when CD4+ counts are treatment, and promotion of safer sex practices.
<200 cells/µL compared to CD4+ counts >200
• Interview sexual contacts and provide
cells/µL. Therefore in HIV-infected patients, it is
epidemiological treatment if indicated (see
not possible to exclude treatment failure and more
Management of Sexual Contacts section), with
intensive regimens may be required.
risk assessment and promotion of safer sex
Examination of CSF should be considered in the practices.
following circumstances:
1. Congenital syphilis; Control
2. Neurologic, ophthalmic, or otologic signs and Management of Cases:
symptoms;
• Close collaboration between Public Health and
3. Tertiary syphilis; Primary Care in addition to timely completion
4. Previously treated patients who fail to achieve an and return of NSTD forms are crucial to ensure
adequate serologic response; there is sufficient information to identify and
locate sexual contacts in a timely manner.

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• Seroreactive persons should be expeditiously provincial and federal requirement. Bicillin L-A®
evaluated. This evaluation should include a is provided to Manitoba Health through the
history and physical examination, laboratory Special Access Programme (SAP) of the
testing, risk assessment, and promotion of safer Therapeutic Products Directorate (TPD) at
sex practices. Public Health Agency of Canada.
• All persons with syphilis should be counseled – The product monograph will be provided
concerning the risks of HIV infection and other with the Bicillin L-A® medication in 2 ml
STIs and testing for these infections should be TUBEX sterile cartridge-needle units
offered. containing 1.2 mU of benzathine
• Cases with infectious syphilis (primary, penicillin G. The dosage, administration,
secondary, and early latent) should be contraindications, and precautions
interviewed for sexual contacts (see sections should be reviewed thoroughly
Management of Sexual Contacts section). prior to use.
• The following principles of case management – Refer to Table 4: Diagnosis and Treatment
apply: of Syphilis by Stage for the specific
management of syphilis by stage.
– Treat all cases of infectious syphilis
Additional resources include Public
immediately;
Health Agency of Canada’s Canadian
– Interview cases within one working day Guidelines on Sexually Transmitted
whenever possible; Infections, 2006 Edition (see Additional
– Evaluate cases within one week after Resources and References section).
treatment to document clinical response. • Crystalline penicillin G is recommended for the
• Manitoba Health provides free drugs for STI treatment of neurosyphilis as treponemicidal
treatment to practitioners in the provincial levels of benzathine penicillin G are not reliably
jurisdiction. achieved in the CSF.
• Expert opinion suggests the alternative use of
Treatment: doxycycline for the treatment of early syphilis and
• Penicillin G, administered parenterally is the late latent syphilis for nonpregnant adults who
preferred drug for treatment of all stages of are penicillin allergic (6). However, treatment
syphilis. failures have been documented with the use of
• Injectable benzathine penicillin G (Bicillin L-A®) doxycycline. Because penicillin G is the most
is available for the treatment of incubating, reliable treatment for all stages of syphilis,
primary, secondary, latent, and tertiary syphilis. desensitization of patients should be considered.
Orders can be made by contacting the CDC This can be done orally or intravenously and in
Unit of Manitoba Health at 788-6737. The consultation with an infectious disease specialist
CDC Unit will fax or mail out the STI and/or allergy specialist. Protocols for oral
Medication Order form which must be desensitization are found in the Canadian
completed and faxed back to the Unit (CDC Guidelines on Sexually Transmitted Infections,
Unit confidential fax 948-3044). After 2006 Edition (see Additional Resources and
administration of the medication, the STI References section) (6).
Medication Administration form and Adverse • Azithromycin monotherapy should not be used
Drug Reactions form (as appropriate) must also as a treatment option for early or incubating
be completed and faxed back to Manitoba syphilis as azithromycin resistance has been
Health. Appropriate documentation of reported and is increasing.
administration and adverse reactions is both a

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– In exceptional circumstances, • Persons who require retreatment should be

azithromycin may be considered for retreated according to the schedules
suspect syphilis cases (at the time that recommended for syphilis of more than one
serology is performed) only if benzathine year’s duration. In general, a person should be
penicillin G is not readily available, with retreated only once, since they may maintain
the understanding that the patient will stable, low titres when nontreponemal tests are
require benzathine penicillin G if their used.
serology confirms that they have syphilis. • All cases of infectious syphilis should abstain
– This may include the epidemiologic from sexual activity until they and their sex
treatment of incubating syphilis of sexual partners are appropriately treated and clinical
contacts in the preceding 90 days to signs are no longer present.
primary, secondary, or early latent syphilis • Cases in hospital should be managed with
pending the results of serologic tests appropriate infection control precautions.
where follow-up is assured. A single 2
gram oral dose is indicated in this Syphilis in HIV-infected persons:
circumstance (6). • Because of the concurrent immune dysfunction
• Ceftriaxone can be used as an alternative for the and the propensity for developing more severe
treatment of neurosyphilis in penicillin allergic disease, some experts feel that coinfected persons
patients and under exceptional circumstances in should be treated with a course of antibiotics
early syphilis (19, 20, 21, 22). similar to those used for late latent syphilis (6).
However, limited data suggest that there is no
• Therapeutic regimens other than penicillin have difference between standard and prolonged
not been well studied, especially in patients with regimens (23).
syphilis of longer than one year’s duration;
therefore, careful follow-up is mandatory. • Treatment failures with ceftriaxone, doxycycline,
Consultation with an infectious disease specialist and azithromycin have been reported so use of
is advised if regimens other than penicillin are these agents is discouraged in HIV-infected
considered. persons.
• Persons for whom there is documentation of • Desensitization for penicillin allergic patients is
recommended treatment for syphilis in the past strongly recommended.
need not be treated again unless there is clinical • Consultation with an infectious disease specialist
or serologic evidence of reinfection such as or physician knowledgeable in HIV/AIDS is
lesions positive for syphilis as detected by direct strongly recommended.
fluorescence antigen (DFA) or a four-fold rise in
titre when a nontreponemal test is used. Syphilis in Pregnancy:
• Retreatment should be considered when: • Pregnant patients should receive penicillin,
following dosage schedules appropriate for the
– clinical signs or symptoms of syphilis stage of syphilis as recommended for
persist or recur; nonpregnant patients.
– there is a four-fold increase in titre with a • Despite the administration of the recommended
nontreponemal test; or penicillin regimen, as many as 14% will have
– a nontreponemal test showing a high titre fetal deaths or deliver infants with clinical
initially fails to show a four-fold decrease evidence of congenital syphilis. The Canadian
within a year following treatment. Guidelines on Sexually Transmitted Infections,
2006 Edition suggests that women with
secondary syphilis in late pregnancy receive two

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doses of benzathine penicillin G 2.4 mU IM one Management of Sexual Contacts

week apart. The effect of this regimen in (Partner Notification)
preventing fetal syphilis is not known.
• Rapid identification and investigation of sexual
• If there is a documented penicillin allergy,
partners/contacts is essential to locate persons
consultation with an infectious disease specialist
with early (primary, secondary, early latent) or
and an allergy specialist for testing and
incubating syphilis and provide them with
desensitization is recommended.
treatment to prevent further transmission.
• The mother should be monitored closely during
• Approximately 46%-60% of contactable sex
and after the pregnancy, and if an increase in a
partners of patients and pregnant women with
nontreponemal test titre occurs, she and her
infectious syphilis also have the infection (24,
infant must be retreated (3).
25).
• If the mother is >20 weeks gestation, an
• Transmission probability per partner is around
ultrasound should be performed and she should
60% (26).
be managed with an obstetrician/fetal-maternal
medicine specialist; if fetal abnormalities are • All sexual and perinatal contacts identified
identified, the mother should be hospitalized for within the following time periods should be
treatment and fetal monitoring (6). located, tested, and treated if serologically
reactive:
• All babies should be assessed at delivery by a
pediatrician, and if a maternal non-penicillin
regimen was used, consideration should be given Patient’s Stage Examine All Sexual and
to treating the baby empirically for congenital Perinatal Contacts Exposed
syphilis. Consultation with an infectious disease Primary Syphilis during the three months prior
specialist is advised. to the onset of chancre
and
Jarisch-Herxheimer reaction: up to and including the
interview date
• Patients should be made aware of this possible
reaction to penicillin therapy (6). Secondary Syphilis during the six months prior to
onset of clinical symptoms
• An acute febrile illness with headache, myalgia, and
and chills/rigors can occur within 8-12 hours of up to and including the
penicillin therapy, with resolution within 24 interview date
hours (6).
Early Latent Syphilis one year prior to diagnosis
• More common in early syphilis and not usually
clinically significant unless there is neurologic or Late Latent Syphilis Marital and long term sex
partners of patients with latent
ophthalmologic involvement or in pregnancy
syphilis should be evaluated
where it may cause fetal distress and premature clinically and serologically for
labour (6). syphilis and treated on the basis
• This kind of reaction is not an allergic reaction, of the evaluation findings.
and should not be treated with antihistamines. Children of persons with late
latent syphilis should be assessed
• Patients demonstrating a reaction can be treated as appropriate.
with antipyretics. More severe reactions can be
treated with corticosteroids (in consultation with Congenital Syphilis Assess mother and her sexual
partner(s).
a medical specialist).

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Presumptive or epidemiologic treatment of sex Follow-up and Serologic Response to

partners should be considered under the following Treatment
circumstances:
The adequacy of therapy can be determined with
• Persons who were exposed within three months serial RPR (or VDRL) tests; the same test in the
preceding the diagnosis of primary, secondary or same laboratory should be followed sequentially.
early latent syphilis in a sex partner might be Table 5: Monitoring of NTT of the appendix
infected, even if testing indicates seronegative reflects the minimum follow-up required for
status; therefore such persons should be treated serological testing.
presumptively.
Once treatment has been completed, serological
• Persons who were exposed more than three response can be used to evaluate adequacy of
months preceding the diagnosis of primary, treatment. The guidelines for determining adequate
secondary or early latent syphilis in a sex partner serologic response are found in Table 6: Adequate
should be treated presumptively if serologic test Serologic Response of the appendix.
results are not available immediately and the
opportunity for follow-up is uncertain.
Otherwise management should be dependent on
serologic results.
Syphilis of Unknown Duration:
For purposes of partner notification and
presumptive treatment of exposed sex partners,
patients with syphilis of unknown duration who
have high nontreponemal titres (i.e., RPR or
VDRL ≥1:32) should be assumed to have early
latent syphilis and be managed accordingly.

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Appendix
Table 1: Clinical Manifestations and Incubation Period (6)
Stage Clinical manifestations Incubation period
Primary Chancre, regional lymphadenopathy 3 weeks (3-90 days)
Secondary Rash, fever, malaise, generalized lymphadenopathy, 2-12 weeks (2 weeks-6 months)
mucous lesions, condylomata lata, alopecia,
meningitis, headaches, uveitis, retinitis
Latent Asymptomatic Early: <1 year
Late: ≥1 year
Tertiary
Cardiovascular syphilis Aortic aneurysm, aortic regurgitation, coronary 10-30 years
artery ostial stenosis
Neurosyphilis Ranges from asymptomatic to symptomatic with <2 years-20 years
headaches, vertigo, personality changes, dementia,
ataxia, presence of Argyll Robertson pupil
Gumma Tissue destruction of any organ; manifestations 1-46 years (most cases 15 years)
depend on site involved
Congenital
Early Fulminant disseminated infection, Onset <2 years
mucocutaneous lesions, osteochondritis, anemia,
hepatosplenomegaly, neurosyphilis
Late Interstitial keratitis, lymphadenopathy, Persistence >2 years after birth
hepatosplenomegaly, bone and joint involvement,
anemia, Hutchinson’s teeth, neurosyphilis

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Table 2: Interpretation of Serologic Tests for Syphilis (6)

Screening test Confirmatory test Reference test Most likely condition
(RPR/VDRL) TP-PA FTA-ABS
NR NR R Early primary syphilis with compatible history and
clinical findings
R R R Infectious syphilis (primary, secondary, or early latent)
(dilutions (test not indicated especially if titre >1:8
can vary) if screening and OR
confirmatory tests Old treated syphilis (especially if titre <1:8)
are positive) OR
Follow-up of treated syphilis
OR
In persons from endemic countries, yaws (e.g.
Caribbean), pinta (e.g. Central America), or bejel
NR R R Usually treated syphilis
OR
Late latent of unknown duration if no history of
confirmed treatment
OR
In persons from endemic countries, yaws (e.g.
Caribbean), pinta (e.g. Central America), or bejel
OR
Early infection (primary syphilis)
R NR NR Biological false positive (see Table 3 for possible causes
of a biologic false positive result)
Repeat testing in 3-4 weeks
R NR R Possible incubating or primary syphilis. Suspect
incubating or primary syphilis based on client history
and/or clinical findings
NR = non-reactive; R = reactive

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Table 3: Causes of Biologic False Positive Syphilis Nontreponemal Test Serology (RPR/VDRL)
Acute Chronic
Hepatitis Connective tissue/autoimmune diseases
Viral pneumonia Immunoglobulin abnormalities
Measles Narcotic addiction
Malaria Aging
Pregnancy Leprosy
Infectious mononucleosis Malignancy
Chicken pox
Other viral infections
Immunizations
Drug use
Lab/technical error

Table 4: Diagnosis and Treatment of Syphilis by Stage (6, 27)

Stage Diagnosis(sensitivity) Preferred Treatment Alternative treatment for penicillin
allergic patients
Primary Syphilis† • Darkfield microscopy Benzathine penicillin G • Doxycycline 100 mg po BID for 14
of skin lesion (80%) 2.4 million units IM, days
• Nontreponemal tests as a single dose (1.2 • Ceftriaxone 1g IM or IV once daily
(78-86%) million units into each for 10 days (to be used in
• Treponemal specific buttock) exceptional circumstances)
tests (76-84%)
Secondary • Darkfield microscopy Benzathine penicillin G Same as for Primary Syphilis
Syphilis† of skin lesions (80%) 2.4 million units IM,
• Nontreponemal tests as a single dose (1.2
(100%) million units into each
• Treponemal specific buttock)
tests (100%)
Latent Syphilis†
Early latent • Nontreponemal tests Early latent: Benzathine Early latent: Same as for Primary
(95-100%) penicillin G 2.4 million Syphilis
• Treponemal specific units IM, as a single
tests (97-100%) dose (1.2 million units
into each buttock)
Late latent or Late latent: Benzathine Late latent:
unknown penicillin G 2.4 million • Strongly consider penicillin
duration units IM once weekly desensitization
for 3 weeks • Doxycycline 100 mg po BID for 28
days
• Ceftriaxone 1g IM or IV once daily for
10 days (to be used in exceptional
circumstances)

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Stage Diagnosis(sensitivity) Preferred Treatment Alternative treatment for penicillin

allergic patients
Tertiary Syphilis • Nontreponemal tests Benzathine penicillin • Strongly consider penicillin
(71-73%) G 2.4 million units IM desensitization
• Treponemal specific once weekly for 3 weeks • Doxycycline 100 mg po BID for 28
tests (94-96%) days
• Ceftriaxone 1g IM or IV once daily
for 10 days (to be used in
exceptional circumstances)
Neurosyphilis Crystalline penicillin G • Strongly consider penicillin
3-4 million units IV every desensitization followed by
4 hrs (18-24 million units/ treatment with penicillin
day) for 10-14 days • Ceftriaxone 2 g IV/IM daily for 10-
Alternative regimen: 14 days
IM procaine penicillin
G, 2.4 million units once
daily with oral probenecid,
500 mg QID both for
10-14 days
Pregnant Women Benzathine penicillin G • There is no satisfactory alternative
Primary 2.4 million units IM as to penicillin for the treatment of
Secondary†† a single dose (1.2 million syphilis in pregnancy; insufficient
Early latent units into each buttock) data exists to recommend
ceftriaxone in pregnancy
• Strongly consider penicillin
desensitization
Pregnant Women Benzathine penicillin G • There is no satisfactory alternative to
Late latent 2.4 million units IM penicillin for the treatment of syphilis
syphilis once weekly for 3 weeks in pregnancy; insufficient data exists
Latent syphilis to recommend ceftriaxone in
of unknown pregnancy
duration • Strongly consider penicillin
Cardiovascular desensitization
syphilis and
other tertiary
syphilis not
involving
the central
nervous system
Congenital Early (<1 month of age): • No data are available to recommend
Syphilis Crystalline penicillin G penicillin alternatives in the case
50,000 units/kg IV every of penicillin allergy
12 hours for the first week
of life and every 8 hours
thereafter for a total of
10 days of therapy

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Stage Diagnosis(sensitivity) Preferred Treatment Alternative treatment for penicillin

allergic patients
Late (≥1 month of age): • If no neurologic involvement and
Crystalline penicillin G normal CSF: benzathine penicillin
50,000 units/kg IV every G 50,000 units/kg IM (max 2.4
6 hours for 10-14 days million units) weekly for 3 successive
weeks
• No data are available to recommend
penicillin alternatives in the case of
penicillin allergy
Epidemiologic Benzathine penicillin G Azithromycin alone should not be
treatment of 2.4 million units IM, as a used as a treatment option for early or
sexual contacts single dose (1.2 million incubating syphilis as azithromycin
in the preceding units into each buttock) resistance has been reported and is
90 days to increasing. Under exceptional
primary, circumstances, the use of azithromycin
secondary, and 2g stat dose may be considered for
early latent suspect syphilis cases (at the time that
syphilis serology is performed) only if
benzathine penicillin G is not readily
available, with the understanding that
the patient will require benzathine
penicillin G if their serology confirms
that they have syphilis.

† Some experts recommend three weekly doses (total of 7.2 million units) of benzathine penicillin G in HIV-infected
individuals however limited data suggest that there is no difference between standard and prolonged regimens (6, 23).
†† Some experts recommend a second dose (2.4 million units) benzathine penicillin G one week after initial dose especially in
third trimester or with secondary syphilis (6).

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Table 5: Monitoring of NTT (6)

Stage of Syphilis NTT Monitoring intervals
Primary, secondary, and early latent syphilis 1, 3, 6, and 12 months following treatment
Late latent and tertiary syphilis 12 and 24 months following treatment
Neurosyphilis 6, 12, and 24 months following treatment. A lumbar puncture
and CSF analysis should be repeated every 6 months until the
cell count has normalized
HIV-infected
Early syphilis Re-examine 1-2 weeks after treatment and follow serologically
and clinically at 1, 3, 6, 9, 12, 24 months after treatment and
annually thereafter
Late syphilis 1, 3, 6, 12, 18, and 24 months after treatment and annually
thereafter
Babies born to mothers with reactive 3 and 6 months after birth; repeat nontreponemal and
syphilis serology* treponemal tests at 12 and 18 months if test is reactive at
6 months
Congenital syphilis* 0, 3, 6, 12, and 18 months after birth

*NTT titres should decline by 3 months of age and be non-reactive by 6 months if the infant was not
infected. If the titres are stable or increase after 6-12 months of age, the child should be evaluated (including
CSF examination) and treated for congenital syphilis. Passively transferred treponemal antibodies can be
present in an infant up to 15 months; a reactive treponemal test after 18 months is diagnostic of congenital
syphilis.
Table 6: Adequate Serologic Response (6)
Following treatment of One would expect to see
Primary syphilis 4-fold decrease at 6 months*
8-fold decrease at 12 months
16-fold decrease at 24 months
Secondary syphilis 8-fold and 16-fold decrease at 6 and 12 months respectively
Early latent syphilis 4-fold decrease by 12 months
HIV-infected
Early syphilis 4-fold decrease 6-12 months following treatment
Late latent syphilis or syphilis of unknown duration 4-fold decrease 12-24 months following treatment

*e.g., a change from 1:32 dilutions (32 DL) to 1:8 dilutions (8 DL)

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Additional Resources 6. Public Health Agency of Canada. Canadian

Guidelines on Sexually Transmitted Infections
Public Health Agency of Canada’s Sexual Health 2006 Edition. Available at: www.phac-aspc.
and Sexually Transmitted Infections Website gc.ca/std-mts/sti_2006/pdf/sti2006_e.pdf.
available at: www.phac-aspc.gc.ca/std-mts/ Accessed July 4, 2007.
syphilis_e.html.
7. Fleming DT, Wasserheit JN. From
Public Health Agency of Canada. Canadian Epidemiologic Synergy to Public Health
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Edition. Available at: www.phac-aspc.gc.ca/std-mts/ Sexual Transmission of HIV Infection. Sexually
sti_2006/pdf/sti2006_e.pdf. Transmitted Infections 1999;75(2):3-17.
Centers for Disease Control and Prevention (CDC) 8. Tsui AO et al. (eds.). Reproductive Health in
Sexually Transmitted Disease (Syphilis) Website Developing Countries. Expanding Dimensions,
available at: www.cdc.gov/std/syphilis/default.htm. Building Solutions, National Academy Press,
Centers for Disease Control and Prevention (CDC) Washingtom, 1997.
2002 Sexually Transmitted Disease Treatment 9. Schulz KF et al. Congenital syphilis. In:
Guidelines available at: www.cdc.gov/STD/ Sexually Transmistted Diseases 2nd ed. McGraw-
treatment/. Hill Inc New York,1990; 821-42.
Department of Reproductive Health and Research 10.Zenker PN, Rolfs RT. Treatment of Syphilis
(RHR), World Health Organization. Guidelines for 1989. Reviews of Infectious Disease
the management of sexually transmitted infections 1990;12(6):S590-S605.
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