CONGENITAL SYPHILIS

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CONGENITAL SYPHILIS

• Vanessa Salinas, MD
• PL-1

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• Syphilis is a chronic infection caused by the
  spirochete T. pallidum, which is of particular
  concern during pregnancy because of the risk of
  transplacental infection of the fetus
• Congenital infection is associated with severe
  adverse outcomes
• -perinatal death
• -premature delivery
• -Low birth weigth
• -congenital anomalies

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Modes of transmission

• Sexual contact
• Transplacental, from the mother to the fetus
• By contact with a lesion at the time of delivery
• The risk of developing syphilis after contact is
  40

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Risk factors for CS

• Lack or inadequate PNC
• Maternal substance abuse
• Failure to repeat a serologic test for syphilis
  during the third trimester
• Treatment failure
• Inadequate access to STDs clinics and outreach
  activities

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Epidemiology
The CS rate peaked in 1991 at 107.3 cases per
100,000 live births, and declined by 90.5 to
10.2 cases/per 100,000 live births in 2002. The
HP2010 objective for CS is 1.0 case per 100,000
live births. In 2002, 27 states, the District of
Columbia, and one outlying area had rates higher
than this objective. Adapted from CDC
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CDC surveillance

• Before 1989 reported cases of CS were defined and
  classified on the basis of clinical and
  serological features known as the Kaufman
  criteria. The Kaufman criteria were not designed
  for use as a surveillance case definition.
• In 1988 CDC developed a surveillance case
  definition for CS. This surveillance case
  definition differs from the clinical diagnosis of
  CS in several ways. All infants born to mothers
  who have untreated or inadequately treated for
  syphilis are considered potentially infected.
  Asymptomatic infants and stillbirths are included
  in the case definition.

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Maternal treatment history among 451 infants with
CS in US in 2002
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PATHOGENESIS/PATHOLOGY
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Syphilis in newborns

• Congenital syphilis
• - Transplacental
• beginning 9 - 10 weeks
• analogous to secondary adquired syphilis
• affects bone, brain, liver, lung
• placenta large and thickened, hypercellular
  villi, UC abscess-like necrotic foci
• - Vertical transmission
• more freq. primary and secondary dz.
• Risk diminishes with after 4 years of infection

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Syphilis in newborns

• 2/3 of NB with CS are asymptomatic at birth
• Overt infection can manifest in the fetus, the
  newborn or late childhood
• The infant may have many or even no signs until
  6-8 wks of life (delayed form)
• Clinical manifestations after birth are divided
  in
• -early CS
• -late CS 2 yo

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Clinical manifestations of early CS

• The earliest sign of CS is nasal discharge
  (snuffles) that occurs 1-2 weeks before the onset
  of the rash. Treponemes abound in the discharge,
  providing a definitive means of diagnosis.

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• Secondary lesions on face they first appeared
  during the fourth postnatal week.

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• The vesiculobullous eruption, known as pemphigus
  syphiliticus, is highly distinctive when present.
  When the bullae rupture, they leave a macerated,
  dusky red surface that readily dries and crusts

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• Other stigmata seen before the age of 2 years
  include maculopapular rash, hepatosplenomegaly
  and jaundice.

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Congenital syphilis. Diaphysitis with abundant
callus formation secondary to pathologic
fractures through the metaphyseal lesions. The
lesions healed, and there were no sequelae
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Clinical manifestations of late onset

• Hutchinsons triad (63)
• Hutchinson teeth (blunted upper incisors)
• Interstitial keratitis
• VII nerve deafness
• Frontal bossae (bony prominence of the forehead)
  83
• Saddle nose 74
• Defect of hard pallate
• Cluttons joint (bilateral painless swelling of
  the knees)
• Saber chins
• Short maxillas
• Protruding mandible

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Laboratory diagnosis

• Direct visualization
• Serologic testing

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Serologic Testing

• The non-treponemal screening tests include the
  VDRL (Venereal Disease Research Laboratory), RPR
  (rapid plasma reagin), or ART (automated reagin
  test).
• - usually correlate with dz activity, in titers
• - On the other hand, other disease states or
  physiologic states, such as pregnancy, can yield
  false-positive results.

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Serologic Testing

• 2. Treponemal-specific tests including
  fluorescent treponemal antibody absorption test
  (FTA-ABS) or Treponema pallidum particle
  agglutination (TP-PA) are necessary to confirm
  the diagnosis of syphilis after a positive
  nontreponemal test.
• Nontreponemal screening during pregnancy is
  recommended at the first prenatal visit, and
  again in the third trimester, particularly in
  high-risk populations

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• Adapted from Sexually Transmitted Diseases, by
  Holmes, Sparling, Mardh, et al.

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Case definitions for CS

• CONFIRMED OR DEFINITE CS
• a. infant lesions
• b. placenta
• c. ummbilical cord
• d. amniotic fluid
• e. autopsy material

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Case definitions for CS

• 2. PRESUMPTIVE OR PROBABLE,
• if mother had
• a. untreated syphilis
• b. no documentation of treatment
• c. non penicillin therapy
• d. penicillin
• if baby has a reactive treponemal test and any
  of
• a. any evidence of CS on clinical exam
• b. any evidence of CS on long bone radiograph
• c. positive VDRL in CSF
• d. abnormal CSF without any other cause
• e. quantitative nontreponemal test titer 4 fold
  higher than maternal titer
• f. reactive treponemal antibody test beyond 15
  months.

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Case definitions for CS

• 3. POSSIBLE in asymptomatic infants when
• a. reactive treponemal or nontreponemal test
• b. maternal tx during pregnancy s/
  post-treatment fall in titers
• c. maternal tx before pregnancy s/ adequate
  follow up
• infants whose mothers were treated1mo before
  delivery AND had a documented fourfold decline in
  titers AND have no evidence of reinfection or
  relapse, are UNLIKELY to have the infection.

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Evaluation of neonates with Suspected or
Confirmed CS

• Detailed physical examination
• Quantitative nontrep. Test on infant
• Specimens for testing for the presence of
  spirochetes form mucocutaneous lesions
• CBC to assess for anemia or thrombocytopenia
• CSF analysis
• Long bone radiographs unless the diagnosis has
  been confirmed otherwise
• Pathologic examination of the placenta or UC.

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Treatment

• Definitive or probable CS
• IV aqueous crystalline penicillin G x 10-14 days
  50 000UI/kg q 12hr (1-7 dol) and q 8hr (8-30dol)
• IM procaine penicillin G 50 000U/kg/dose q day
  for 10 to 14 days

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Treatment

• 2. Infants with probable syphilis, BUT who are
  asymptomatic and c/ normal evaluation
• If f/u is certain a single dose IM benzathine
  penicillin G may be adequate
• Some experts will prefer a 10-14 day full course
  if any part of the evaluation is abnormal or
  uninterpretable.
• 3. Asymp. Infants with possible CS.
• a) single dose of benzathine penicillin

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Follow up

• Re-evaluation after treatment at 1, 2, 3, 6 and
  12 months of age.
• Nontreponemal tests should be repeated every 2 to
  3 months until they have become nonreactive or
  diminished four-fold.
• Maternal origin Ab (nontreponemal) titers become
  negative within 3 mo, and should become negative
  at 6 mo.
• Treponemal-specific Ab of maternal origin persist
  for 12 to 15 mo IN 15 of uninfected infants from
  seropositive mothers.
• Congenital neurosyphilis should be evaluated
  (clinical and CSF) every 6 months until CSF
  clears.

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Follow up evaluation

• Non treponemal antibody serologic testing should
  be checked at 1,3,6, 12 and 24 months following
  the treatmetn
• Titers should decrease by four fold by 6 months
  of therapy and became non reactive by 12 or 24
  months
• Titers that show a four fold rise or do not
  decrease suggest either failure of treatment or
  reinfection

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• Sexually transmitted infections remain a major
  public health concern in the
• United States. An estimated 19 million infections
  occur each year
• Sexually transmitted infections are relatively
  common during pregnancy, especially
• in indigent, urban populations effected by drug
  abuse and prostitution.
• Education, screening, treatment, and prevention
  are important components of
• prenatal care for women at increased risk for
  these infections. Treatment of these
• sexually transmitted infections is clearly
  associated with improved pregnancy
• outcome and reductions in perinatal mortality

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• Syphilis is caused by the spiroquete Treponema
  pallidum.
• Syphilis is primarily acquired through sexual
  contact,though approximately 1000 cases of
  vertically acquired congenital infections occur
  each year in the United States.
• Antepartum syphilis can profoundly affect
  pregnancy outcome by causing
• preterm labor, fetal death, and neonatal
  infection by transplacental or perinatal
• infection 8,9. Fortunately, of the many
  congenital infections, syphilis is not
• only the most readily prevented but also the most
  susceptible to therapy.

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DIAGNOSIS

• Diagnostic testing involves a two-step process,
  beginning with a nonspecific test and concluding
  with a treponeme-specific test for patients
  screening positive.
• The non-treponemal screening tests include the
  VDRL (Venereal Disease Research Laboratory), RPR
  (rapid plasma reagin), or ART (automated reagin
  test). Nontreponemal test antibody titers usually
  correlate with disease activity and should be
  reported with a quantitative titer.
• On the other hand, other disease states or
  physiologic states, such as pregnancy, can yield
  false-positive results.
• Because the current incidence of syphilis is so
  low, the majority of positive screening tests are
  not due to treponemal infection.
• Treponemal-specific tests including fluorescent
  treponemal antibody absorption test (FTA-ABS) or
  Treponema pallidum particle agglutination (TP-PA)
  are necessary to confirm the diagnosis of
  syphilis after a positive nontreponemal test.
  These tests are specific for T pallidum antigens
  and are reported as positive or negative.
• Nontreponemal screening during pregnancy is
  recommended at the first prenatal visit, and
  again in the third trimester, particularly in
  high-risk populations

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TREATMENT

• Penicillin G, in benzathine, aqueous procaine, or
  aqueous crystalline form, is the drug of choice
  for treatment of all stages of syphilis, and is
  the only effective treatment for the prevention
  of congenital syphilis in pregnancy.
• Erythromycin may be curative in the mother, but
  may not prevent congenital syphilis because of
  the variability of transplacental passage of the
  antibiotic.
• Ceftriaxone may prove useful in adults as an
  alternative regimen for patients who have
  penicillin allergy however, there is
  insufficient information on its use in pregnancy
• The efficacy of azithromycin in the
  penicillin-allergic pregnant woman has not been
  adequately evaluated.

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• A recommended dosage regimen for pregnant women
  is as follows
• Primary, secondary, or early latent stage
  benzathine penicillin G, 2.4 million units
  intramuscularly (IM) in a single dose
• Late latent stage or syphilis of unknown
  duration benzathine penicillin G, 2.4 million
  units IM once a week for 3 consecutive weeks
• Neurosyphilis aqueous crystalline penicillin G,
  34 million units intravenously (IV) every 4
  hours, or 1824 million units daily as continuous
  infusion, for 1014 days
• The rate of treatment failure may be increased in
  pregnant patients who have secondary syphilis,
  therefore some experts recommend the use of a
  second injection of benzathine penicillin G 2.4
  million units IM 1 week after the first to treat
  early syphilis in pregnancy

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• Within hours after treatment, patients can
  develop an acute complication called the
  Jarisch-Herxheimer reaction. Symptoms include
  fever, chills, myalgias, headache, tachycardia,
  hyperventilation, vasodilation, and mild
  hypotension. Uterine contractions and fetal heart
  rate decelerations may occur.
• Although the reaction occurs in 10 to 25 of
  patients overall, it is most common in the
  treatment of early syphilis. A recent report 20
  noted an incidence of 40 among treated pregnant
  women. Symptoms last for 12 to 24 hours and are
  usually self-limiting. Patients can be treated
  symptomatically with antipyretics. Routine
  hospitalization is not recommended for treatment
  during pregnancy, though this has not been
  systematically evaluated 16.

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Evaluation of treatment

• Consideration should be given to ultrasound
  evaluation of the fetus before
• therapy when syphilis is diagnosed after 24
  weeks. Ultrasound abnormalities
• associated with syphilis include polyhydramnios,
  hepatosplenomegaly, ascites,
• and hydrops 21. Fetuses that have physical
  evidence of severe disease discovered
• on ultrasound have also been shown to have
  biochemical evidence
• of severe disease. Treatment failure and other
  complications are more common
• among these fetuses 22. When the fetal
  ultrasound is abnormal, consultation
• with specialists in maternal-fetal medicine and
  neonatology should occur. Complications
• such as preterm labor, preterm premature rupture
  of the membranes,
• fetal heart rate decelerations, and stillbirth
  may be precipitated by treatment.
• In the severely affected fetus, particularly with
  preexisting fetal heart rate
• abnormalities, consideration may be given to an
  untreated preterm or term
• delivery followed by neonatal treatment 16,23.
  Despite the advantages of
• ultrasound assessment, maternal treatment should
  not be delayed unduly to obtain
• imaging.