Congenital Syphilis

1. Congenital Syphilis N.Frewan, PL2 Neonatology Division July 2008

3. Background • Between 1905 -1910, Schaudinn & Hoffman identified T pallidum as the cause of syphilis • The name "syphilis" was coined by Italian physician and poet Girolamo Fracastoro in his Latin written poem “Syphilis sive morbus gallicus” ("Syphilis or The French Disease") in1530

4. Introduction • Curable STD caused by the Treponema pallidum organism • 1998: Complete genetic sequence of T. pallidum was published which helped understanding the pathogenesis of syphilis • Belongs to “Spirochaetaceae family” • The genus name, Treponema, is derived from the Greek term for "turning thread“

5. Treponema Pallidum • Thin • Motile • Extremely fastidious • Survive only briefly outside host • Not cultivated successfully on artificial media

6. Transmission • Direct sexual contact with ulcerative lesions of skin or mucous membranes • Trans placental: • Typically during second half of pregnancy • As early as 6 weeks of gestation • Pregnant with primary or secondary syphilis are more likely to transmit the disease than those with latent (not clinically apparent) disease Cannot be spread through contact with toilet seats, doorknobs, swimming pools, hot tubs, bathtubs, shared clothing, or eating utensils

7. Congenital syphilis • Severe, disabling, and often life-threatening infection seen in infants • About half of all infected fetuses die shortly before or after birth

8. IncidenceUS • Despite the fact of being curable if caught early, rising rates among pregnant ♀ in the US have recently ↑ the number of infants born with congenital syphilis • 1985-1990: overall incidence ↑ 75% ( Sex-Drug traffic)

9. IncidenceUS • 1998: 81.3% of reported cases of CS occurred because the mother received no/inadequate penicillin tx before or during pregnancy • According to the CDC: • 40% of births are stillborn • 40-70% of the survivors will be infected • & 12% of these will subsequently die

11. Reported cases for infants < 1 year of age and rates of 1ry & 2ry syphilis among women: United States, 1997–2006

12. Rates for infants < 1 year of age: US, 1997–2006 and the Healthy People 2010 target as per STD surveillance

13. Incidence International • Worldwide, predominantly in large cities • Certain European countries have seen ↑in congenital syphilis cases • Major public health problem in sub-Saharan Africa and developing world • Main focus in control: Antenatal screening & treatment of infected mothers

14. Jul-2006

15. PathophysiologyCS • Trans placental transmission • Transmission rate:~ 60 - 100% • With early onset disease, manifestations result from trans placental spirochetemia and are analogous to secondary stage of acquired syphilis • CS does not have a primary stage

16. Clinical Manifestations • Intra-uterine: -Placenta -Fetus • Post-natal: - Early - Late

17. Intra-uterine: Placenta • The placenta is typically large and edematous • Characteristic placental findings include: - Hydrops placentalis • Chronic villitis • Perivillous fibrous proliferation • Normoblastemia • Necrotizing funisitis • Acute chorioamnionitis • Plasma cell deciduitis

18. Intra-uterine: Fetus • Depends on stage of development at time of infection & duration of untreated infection • Initially characterized by placental involvement and hepatic dysfunction (e.g., abnormal LFT), followed by amniotic fluid infection, hematologic abnormalities, ascites, and hydrops • Stillbirth / Neonatal death

19. Intra-uterine: Fetus • >24 weeks gestation: 66 % of fetuses have either congenital syphilis or T.Pallidum detected in amniotic fluid • Intrauterine death: 25 % of affected • Perinatal mortality: 25-30 %, if untreated

20. Post-Natal • Among survivors, manifestations been divided into: Early stage = First 2 years Late stage = After 2 years • Inflammatory changes do not occur in the fetus until after first trimester → organogenesis is unaffected • Nevertheless, all organ systems may be involved

21. Early CS- Asymptomatic • Occurs between 0 - 2 years • If asymptomatic : - Identified on routine prenatal screening - If not identified and treated, these newborns develop poor feeding and rhinorrhea ➨ Earliest signs of CS may be poor feeding and snuffles (i.e., syphilitic rhinitis)

22. Symptomatic Early CS If Symptomatic: • Variable • Appear within 1st 5 weeks of life • Stillborn/ Premature • Failure to gain weight or FTT • Fever / Irritability • Severe congenital pneumonia

23. Symptomatic Early CS • Most striking lesions affect the mucocutaneous tissues and bones: - Mucous patches - Rhinitis =snuffle - Condylomatous lesions ➨ ➨ highly characteristic features of mucous membrane involvement in CS

24. Symptomatic Early CS • Snuffles → Followed quickly by diffuse maculopapular desquamative rash that involves extensive sloughing of the epithelium, on the palms & soles and around the mouth & anus • When chronic → “Saddle Nose” • Lesions & nasal fluid: highly infectious

25. Symptomatic Early CS • Bullous skin disease known as “pemphigus syphiliticus” ➲ Early rash -- small blisters on the palms and soles → Ulcerated ➲ Later rash -- copper-colored, flat or bumpy rash on the face, palms, and soles

26. Symptomatic Early CS • Other early manifestations include hepatosplenomegaly (100%), jaundice, anemia • Metaphyseal dystrophy and periostitis often are noted on radiographs at birth +/_ Pseudoparalysis

27. Congenital syphilis - early evidence of infection - bullae and vesicular rash

28. Multiple, punched out, pale, blistered lesions, with associated desquamation of palms & plantars

29. Intraoral mucous patches & facial skin lesions

30. Secondary lesions on feetLesions first appeared during 4th week

31. Late-onset CS •  Develop from scarring related to early infection • Can be prevented by treatment within first 3 months • Can appear as late as 40 years after

32. Late-onset CS • Manifestations include neurosyphilis and involvement of teeth, bones, eyes, and 8th cranial nerve • E.g.: Frontal bossing, short maxilla, high palatal arch, Hutchinson triad, saddle nose, and perioral fissure (Rhagades = bacterial infection of skin lesions )

33. Hutchinson triad • Deafness (10 – 40 years) • Hutchinson’s teeth = centrally notched, widely-spaced peg-shaped upper central incisors • Interstitial Keratitis → blindness (5-20 years)

34. Notched incisors known as Hutchinson’s teeth

35. Moribund newborn with CSOral / skin lesions and saddle nose

36. Metaphyseal osteomyelitis Radiolucent distal radius & ulna with cupping distal ulna

37. Osteochondritis of femur & tibia

38. 1-m-old . Classical Wimberger's sign of destructive metaphysitis involving medial aspects of distal femora and proximal tibae

39. “Saber shins” = Osteoperiostitis Tibia

40. Interstitial keratitis

41. Possible Complications • Blindness • Deafness • Facial deformity • Neurological problems

42. Labs Definitive diagnosis: • By direct visualization of spirochetes using darkfield microscopy • Or direct fluorescent antibody tests of lesion exudate or tissue (Placenta/UC) -Helpful early in the disease, prior to development of seroreactivity

43. Serologic tests - Presumptive diagnosis can be made using • Nontreponemal ( False + in medical conditions) • Treponemal (False+ in other spirochetal Diseases) → So use of only one type is insufficient - If nontreponemal test is +→ confirmatory testing is performed with a specific treponemal test

44. Nontreponemal test • VDRL (Venereal Disease Research Laboratory) • RPR (Rapid plasma reagin) • ART (Automated reagin test)

45. Nontreponemal test - Used for screening (sensitive but not specific) - Inexpensive, performed rapidly, and provide quantitative results → helpful indicators of disease activity & monitor treatment response • Measures Ab directed against lipoidal Ag from T. Pallidum, Ab interaction with host tissues or both - Nonspecific Ab develop 4-8 weeks following infection

46. False negative Early primary S Latent acquired S Late CS Prozone phenomenon False Positive Viral infection ( EBV, Hepatitis, Varicela, Measles) Lymphoma TB Malaria Endocarditis CT diseases Pregnancy IV drugs Wharton Jelly contamination in cord samples Nontreponemal test

47. Nontreponemal test • Any reactive NT test must be confirmed by Treponemal test to exclude false positive • Treatment should not be delayed if symptomatic or at high risk of infection • Monitor: • Sustained 4 fold ↓NT test titer after treatment → Adequate treatment - Sustained ↑: Re-infection or relapse

48. Nontreponemal testNewborn Dilemma • Testing of newborn often is problematic because IgG antibody may be a reflection of maternal rather than infant infection • Unless NT titer is much higher in baby than in mother → f/u serology over 1st 6 months of life, when maternal IgG is lost, would be required to make a diagnosis i.e.Loosing precious time in treatment initiation

49. Treponemal Specific Test • T pallidum immobilization (TPI) • Fluorescent treponemal antibody absorption (FTA-ABS) • Microhemagglutination assay for antibodies to T pallidum (MHA-TP)

50. Treponemal Specific Test • Confirm + nontreponemal reaginic test • Remain positive for life i.e. Result do not correlate with disease activity and tests are not quantified • False + reactions: → Other spirochetal diseases (e.g., yaws, pinta, leptospirosis, rat-bite fever, relapsing fever, Lyme disease