CONGENITAL SYPHILIS

1. CONGENITAL SYPHILIS Vanessa Salinas, MD PL-1

2. 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

3. 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%

4. 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 STD’s clinics and outreach activities

5. 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

6. 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.

8. Maternal treatment history among 451 infants with CS in US in 2002

9. PATHOGENESIS/PATHOLOGY

10. 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

11. 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 <= 2 yo -late CS >2 yo

12. 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.

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

14. 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

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

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

18. Clinical manifestations of late onset • Hutchinson’s 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 • Clutton’s joint (bilateral painless swelling of the knees) • Saber chins • Short maxillas • Protruding mandible

21. Laboratory diagnosis • Direct visualization • Serologic testing

22. 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.

23. 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

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

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

26. 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 <30 days before delivery 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.

27. 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 treated>1mo before delivery AND had a documented fourfold decline in titers AND have no evidence of reinfection or relapse, are UNLIKELY to have the infection.”

28. 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.

29. 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

30. 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

31. 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.

32. 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

33. 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

34. 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.

35. 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

36. 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.

37. 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, 3–4 million units intravenously (IV) every 4 hours, or 18–24 million units daily as continuous infusion, for 10–14 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

38. 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].

39. 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.