Postgraduate Education Course
Infectious Diseases of Pregnant Women, Fetuses and Newborns
3 – 7 October 2010
Syphilis and pregnancy
Alberto Matteelli
Unità di Infezioni Comunitarie
Dipartimento di Malattie Infettive e Tropicali
Spedali Civili di Brescia
The burden of syphilis
12 million new
syphilis cases
every year
worldwide
2 million
pregnant
women
715,000-1,575,000 events:
Impact on pregnancy outcome:
Spontaneous aborption, stillbirth, perinatal death,
intrauterine growth retardation congenital syphilis
Simms I,Broutet N:Congenital Syphilis reemerging. JDDG (2008) 6:269-272
Aetiology and classification
Agent:Treponema pallidum, spp pallidum
• Acquired syphilis: via sexual route (STI)
• Congenital / prenatal syphilis: via
transplacental route (ToRCH)
• Perinatal syphilis: acquired at passage through
the birth channel
1/4 Acquired syphilis
Primary syphilis: genital ulcer syndrome with painless,
usually single lesion at the site of bacterial entry:
indurated margins; inguinal adenopathy.
In males:
1/4 Acquired syphilis
Primary syphilis: genital ulcer syndrome with painless,
usually single lesion at the site of bacterial entry:
indurated margins; inguinal adenopathy.
In females:
2/4 Acquired syphilis
Secondary syphilis: muco-cutaneous manifestations
(skin rash, maculo-papular rameic lesion at palms
and plants) visceral manifestations
(lymphadenopathy, hepatitis, polyarthritis, iridocyclitis, meningitis)
3/4 Acquired syphilis
Tertiary syphilis:
cardiovascular system
(aortitis and artheritis) CNS
(progressive paralysis, tabes
dorsalis), gummas
(skin/mucosae, bones,
joints, liver, muscles, etc.
4/4 Acquired syphilis
Latent syphilis : no signs or symptoms, positive
serology.
• early: 2 years or lss since infection
• late: more than 2 years since infection
• Undetermined duration: time of infection unknown
Syphilis scar: positive treponemal (EIA/TPHA) tests with
negative non treponemal (RPR) tests and
documented penicillin treatment
1/2 Congenital syphilis
Transmission rate depends on syphilis stage
• Primary syphilis: 70-100%
• Secondary syphilis: 67%
• Early latent syphilis: 40-83%
• Late latent syphilis: 2,5-10%
2/2 Congenital syphilis
Transmission rate
Increases directly with gestational timing
Treatment virtually abolish the risk of transmission
Provided that treatment is given 4 weeks ormore
before delivery
Role of timely diagnosis in the mother !!!
Clinical consequences of
congenital infection
• Spontaneous aborption
• Foetal loss and perinatal death
• Hydrops fetalis
• LBW
• Pre-term delivery
• Congenital syphilis:
early
late
Diagnosis of syphilis
Direct diagnosis
1. Dark field microscopy
2. Direct immunofluorescence
3. Molecular biology
Non treponemal tests as well as most treponemal
tests detect a combination of IgG and IgM
antibodies.
These antibodies cross the placental filter; their
detection in the newborn circulation does not
indicate that syphilis infection occurred in the
newborn.
Tests which detect IgM class antibodies are
specifically important for the diagnosis of
congenital syphilis.
Screening for syphilis in pregnancy in
Italy
• During pre conceptional period
• During the first trimester of pregnancy
• During the third trimester of pregnancy (only
at risk categories)
• Payed by the Italian National Health System
for both women and partners
(Decreto Ministeriale, September 1998)
Antental care examination
1. B.C., 24 yrs old, 23-week pregnant, attends
with:
• TPHA: positive
Indication to treat ?
Antental care examination
1. E.Y., 19 yrs old, 8-week pregnant, attends
with:
• TPHA: positive
• RPR: positive 1:2
Indication to treat ?
Antental care examination
1. S.H., 29 yrs old, 18-week pregnant, attends
with:
• TPHA: positive
• RPR: negative
Indication to treat ?
Antental care examination
1. C.M., 25 yrs old, 15-week pregnant, attends
with:
• RPR: positive
Indication to treat ?
Antental care examination
1. A.C., 17 yrs old, 9-week pregnant, attends
with:
• Genital ulceration – suspect for primary syphilis
Indication to treat ?
Serologic screening
1. Treponemal tests (TPHA, TPPA, EIA)
2. If positive → confirm with a second
treponemal test
3. If positive → a non treponemal test (RPR,
VDRL) to determine the stage of syphilis and
steer treatment decision
TREPONEMAL TEST
‒
+
SECOND TREPONEMAL TEST
‒
+
NON TREPONEMAL TEST
‒
WESTERN BLOT
+
+
IS THERE A DOCUMENTED
HISTORY OF TREATMENT?
NO
YES
NO TREATMENT
TREAT ACCORDING TO
THECLINICAL STAGE
‒
Treatment of syphilis during
pregnancy
• Primary, secondary and early latent syphilis: Benzathinpenicillin G 2.4 million units IM as a single dose
• Unknown duration latent syphilis : Benzathin-penicillin G
2.4 million units IM once a week administred as 3 doses
at 1-week intervals (total of 7.2 million units)
The effectiveness of alternative regimens during pregnancy is
not documented. Pregnant women with an history of
penicillin allergy should be desensitized and treated with
penicillin
FOLLOW-UP: RPR titers at 3, 6 months and at delivery
Follow-up of the treated mother
1. S.H., 29 yrs old, 18-week pregnant, serology
at the time of treatment:
• TPHA: positive
• RPR: negative
Does she need to repeat serology
before delivery ?
Follow-up of the treated mother
1. E.Y., 19 yrs old, 8-week pregnant, serology at
the time of treatment:
• TPHA: positive
• RPR: positive 1:2
Does she need to repeat serology
before delivery ?
How to wellcome the newborn
1. S.H., 29 yrs old, 18-week pregnant, treated
for syphilis, serology immediately prior to
delivery:
• TPHA: positive
• RPR: negative
Does the newborn require any
investigation ?
Does the newborn need to be treated ?
How to wellcome the newborn
1. E.Y., 19 yrs old, 8-week pregnant, treated for
syphilis, serology immediately prior to
delivery :
• TPHA: positive
• RPR: positive 1:2
Does the newborn require any
investigation ?
Does the newborn need to be treated ?
How to wellcomethe newborn
1. C.E., 23 yrs old, delivering with no prior
serological investigation for syphilis. Serology
at the time of delivery :
• TPHA: positive
• RPR: positive 1:2
Does the newborn require any
investigation ?
Does the newborn need to be treated ?
How to wellcome the newborn
The newborn of a mother with syphilis (even if
treated) must undertake a screening:
• Mother’s RPR - at delivery: clinical and
serological screening
• Mother’s RPR+ at delivery: clinical, serological
and instrumental screening
1/3 Newborn screening
•Serologic screening: quantitative RPR, quantitative
TPHA, IgM detection test
!! there is regular transplacentar passage of antibodies
through the placental filter. IgM antibodies are
specific for congenital infection as they cannot cross
the placenta
IgM positive→ infection confirmed
2/3 Newborn screening
•Clinical screening: look for signs of congenital syphilis
Absence of signs does not rule out infection: more than
a half of infected children are asymptomatic at birth
Signs and symptoms may be aspecific and can vary
dramatically!!!!!
3/3 Newborn screening
•Instrumental screening:
Blood count, kidney and liver function
Abdominal ultrasonography
Femoral X-ray
Brain ultrasonography
Ophthalmologist visit
1/2 Algorithm if mother RPR‒
‒ at
delivery
T.PALLIDUM
IDENTIFIED IN
LESIONS
SIEROLOGIC
INFECTED
IgM +
TPHA/RPR TITER
> 4MT
< 4MT
PROBABLY
INFECTED
SIGNS AND SYMTOMS
CLINICAL
ASYNTOMATIC
MT= maternal titers
LOW
PROBABILITY
OF INFECTION
2/2 Algorithm if mother RPR+ at
delivery
T.PALLIDUM
IDENTIFIED IN LESION
INFECTED
SEROLOGIC
IgM +
TPHA/RPR TITER
CLINICAL/INSTRU
MENTAL
SIGNS AND
SYMPTOMS/DIAGNOSTIC
INSTRUMENTAL TEST
ASYNTOMATIC
MT= maternal titers
> 4MT
< 4MT
PROBABLY
INFECTED
LOW
PROBABILITY
OF INFECTION
1/3 Newborn classification in
relation to syphilis infection
1.Infected newborn: IgM positivity or
T. pallidum identified from
mucocutaneous lesions or other
body fluids
2/3 Newborn classification in
relation to syphilis infection
2. Probably infected: clinical signs AND
positive serologic tests or RPR/TPHA
titer fourfold the mother’s one
3/3 Newborn classification in
relation to syphilis infection
3. Low probability of infection: no
signs or symtoms AND serologic
titer less than fourfold the mother’s
one
Syphilis is conclusively ruled out when the
child’s treponemic tests turn to negative
1/6 Clinical manifestations of
early congenital syphilis
• Bony lesions (most frequent presentation)
- Multiple and simmetrical
- Osteomyelitis, periostitis
- Metaphyses and diaphyses most often involved
- Especially of long bones, upper limbs
- Poor correlation between clinical and radiological
findings
Important periosteal
reaction of the median tract
of the diaphysis
2/6 Clinical manifestations of
early congenital syphilis
• Osteochondritis (Parrot’s pseudoparalysis):
presenting as flaccid paralysis of the upper
limbs. Knees may also be involved
Initial diaphyseal
osteochondritis
and periostitis
3/6 Clinical manifestations of
early congenital syphilis
• Mucocutaneous manifestations (15-60%)
- Rhinitis
- Maculopapular rash (oval, pink or red, evolving
into coppery brown) with desquamation and
scaling
- Pemphigus (widely disseminated vesicular
bullous eruption)
- Condylomata lata (perianal,perioral)
- Hydrops fetalis
- Jaundice, petechial lesions
4/6 Clinical manifestations of
early congenital syphilis
• CNS manifestations
- Acute leptomeningitis (cells > 25, proteins >
150 mg/dl)
- Chronic meningovascular syphilis (resulting in
progressive hydrocephalus, cranial nerve
palsies, vascular lesions of the brain, gradual
intellectual deterioration)
- Optic nerve atrophy
- Deafness
5/6 Clinical manifestations of
early congenital syphilis
• Eye disorders
Chorioretinitis
Uveitis
Glaucoma
6/6 Clinical manifestations of
early congenital syphilis
• Other manifestations:
Liver and spleed enlargement (90%)
Generalized lymphadenopathy (50%)
Nefrotic syndrome - Ascitis
Trombocytopenia
Anaemia
Clinical manifestations of late
congenital syphilis:
•
•
•
•
•
•
•
•
•
Frontal bossing
Palatal deformation
Dental dystrophies
Interstitial keratitis
Abnormal bone x-ray
Nasal deformity
Eight nerve deafness
Neurosyphilis
Joint disorders
30-87%
76%
55%
20-50%
30-46%
10-30%
3-4%
1-5%
1-3%
Genc M, Sex Transm Inf, 2000
Lumbar puncture in the newborn
Lumbar puncture is recommended in
all infected and probably infected
newborns.
Neurosyphilis diagnosis:
• Non treponemic test positive on CSF
• Pleyocitosis on CSF
Treatment in the newborn
Infected or probably infected
Aqueous penicillin G 100.000 UI/Kg /day EV
for 10 days
Low probability of infection
Benzathin-penicillin G 50.000 UI/Kg IM in a single
dose (efficacy not demonstrated). The rational is to
control damage in case of default from follow-up
1/2 Newborn follow up
Quantitative TPHA and RPR every three
months
• Both RPR and TPHA titer expected to decrease and disappear
in 6-12 months
• The RPR titer of an infected and treated child decreases after
treatment. The TPHA titer will remain positive for life
If RPR titer persistently positive after 18 months or increasing:
CONGENITAL SYPHILIS
2/2 Newborn follow up
In case of any neurological signs or
abnormal CSF:
Repeat lumbar puncture every six
months
Evaluate growth, mental development,
sight and hearing capacities up to three
years of age
Serologic tests in the newborn
• Both RPR and TPHA titer must decrease
and disappear in 6-12 months if they
come from the mother
• The RPR titer of an infected and treted
child decreases after treatment. The
TPHA titer will remain positive virtually
all life long
Summary
• Prompt diagnosis and treatment of
syphilis in pregnant women can eliminate
congenital syphilis
• Every case of congenital syphilis must be
considered as a failure of the health
system:
– Failure in accessing screening
– Failure in interpreting serologic tests
Thanks!