Congenital Syphilis – in Theory and in Reality in Estonia, 1991-2005 Liis Toome Tallinn Children’s Hospital 15.09.2006

Incidence of Syphilis in 2001 per 100 000 Population Estonia 2005 – 8,2/100 000 EpiNorth Journal 2002, No 4

Congenital Syphilis in Estonia since 1991 Aim of the study: to describe the epidemiology of congenital syphilis in Estonia, 1991-2001(-2005) Methods: retrospective analysis of the cases of CS in children aged < 2 years T. Rjabova, L. Toome Tallinn Children’s Hospital K. Kink West Tallinn Central Hospital E. Tamm Children’s Clinic, Tartu University Hospitals A. Kangur North Estonia Regional Hospital

Health Protection Inspectorate, 2006 Syphilis in Estonia, 1971 - 2001 Number of cases . Health Protection Inspectorate, 2006

The Incidence of Congenital Syphilis in Estonia, 1982 - 2005 0 - 14 years < 1 year

Microbiology T. Pallidum A tightly coiled motile spirochete Can be detected on dark-field microscopy Has not been cultured in vitro Treponema Pallidum Treponema Pallidum on darkfield

Transmission Maternal infection (N = 428) Transmission rate Stillbirth Live births with congenital syphilis Untreated primary syphilis 29 % 3 % 26 % Untreated secondary syphilis 59 % 20 % 39 % Early latent disease 50 % 17 % 33 % Late latent disease 13 % 5 % 8 % Sheffield JS et al, Am J Obstet Gynecol, 1999

Early Congenital Syphilis - Clinical Manifestations IUGR Nonimmune hydrops fetalis Enlarged placenta Mucocutaneous manifestations Persistent rhinitis (snuffles) Maculopapular eruption Superficial desquamation Pemphigus syphiliticus Condylomata lata

Early Congenital Syphilis - Clinical Manifestations Jaundice, hepatosplenomegaly syphilitic hepatitis Generalized lymphadenopathy Hematologic manifestations hemolytic anemia, thrombocytopenia Bone lesions osteochondritis, -myelitis, periostitis pseudoparalysis of Parrot Pneumonitis, nephrotic syndrome Syphilitic leptomeningitis Ocular manifestations chorioretinitis, glaucoma, cataract Pneumonia alba Metaphyseal dystrophy Wimberger’s sign

Serologic Diagnosis in the Infant “Nontreponemal Antibody Tests” VDRL = Veneral Disease Research Laboratory RPR = Rapid Plasma Reagin Treponemal Antibody Tests TPHA = T.pallidum hemagglutination test FTA-ABS (IgM) = Flourescent Treponemal Antibody IgM Test IgM ELISA = Enzyme-Linked Immunosorbent Assay IgM Immunoblotting

Congenital Syphilis in Estonia, 1991-2005 Tallinn - 12 cases, Harjumaa - 7 cases, Lääne-Virumaa - 5 cases

Children’s Age at the Time of Diagnosis in Estonia, 1991-2005

Clinical Manifestations of Congenital Syphilis in Estonia, 1991-2005

Case 1 Newborn, syphilitic hepatitis GA 36, BW 2529 g jaundice from the birth syphilitic hepatitis hepatosplenomegaly indirect bilirubin 245 mol/l direct bilirubin 187 mol/l elevated serum aminotransferases Anemia, thrombocytopenia Cardiolipin ag 4+ Treponemal ag 4+

Case 2 1 month 2 weeks, pseudoparalysis of Parrot Bone lesions with superimposed fractures BW 2900 g 1 month unexplained rhinitis anemia Hgb 72 g/l, ER 2,5x1012 CRP 187 mg/l pneumonia? Jarisch-Herxheimer reaction Pseudoparalysis of Parrot Serology RPR 1 : 40 TPHA 1 : 2560 Wimberger sign

Case 3 1 month 3 weeks, syphilitic glomerulonephritis maculopapular rash, rhinitis, abdominal distension “snuffles”, syphilitic ileitis rectal bleeding syphilitic glomerulonephritis with nephrotic syndrome generalized edema + ascitis 5166 g  4154 g macrohematuria severe proteinuria hepatosplenomegaly panmetaphysitis RPR 1 : 240, TPHA 1 : 640

Case 4 2 months, “asymptomatic” BW 3250 g Incarcerated inguinal hernia Anemia  Hgb 77 g/l, ER 2,4 x 1012 Maculopapular eruption of the palms and soles, becoming coppery-brown Hepato (+ 3,5 cm) spleno (+ 1,0 cm) megaly Fever 38º Jarisch-Herxheimer reaction, tº 40 º C Serology Cardiolipin ag 4+ Treponemal ag 4+

Case 5 6 months, Jarisch-Herxheimer Reaction Term delivery, BW 2660 g Persistent rhinitis Mucocutaneous manifestations Maculopapular eruption treated as allergic dermatitis and as scabies Deep fissures radial to the angles of the mouth  rhagades Hepatosplenomegaly, osteochondritis SR 70 mm/h, Hgb 83 g/l Jarisch-Herxheimer reaction t° 39° C in 2 hours of treatment RPR 1:640

Case 6 1 year 1 month, manifestations of CNS BW 2731 g, parenteral abuse of alcohol During the first year of life Failure to thrive Maculopapular rash - atopic dermatitis, scabies? Anemia, hepatomegaly 1 year 1 month – 7,1 kg / 71 cm / OFC 44 cm Mental retardation Optic nerve atrophy Brain CT – cortical atrophy Serologic diagnosis RPR 1 : 128 WB IgG positive CSF FTA-Abs 2+

Treatment of the Newborn Maternal Rx Clinical Findings in Newborn Drug (Penicillin G) Route None or inadequate Present Aqueous or Procaine IM/IV IM 10-14 days Absent Benzathine Adequate (during pregnancy) Benzathine (CDC) Follow-up only (AAP) Single dose Adequate (before pregnancy) Follow-up only Or Remington & Klein, 2006

Post-treatment Follow-up Patient Category Follow-up Procedures Infants - diagnosed as having congenital syphilis RPR testing every 2-3 mo until negative or decreased fourfold. If RPR titer is stable or increasing after 6-12 mo after treatment, reevaluate and re-treat. Perform treponemal antibody test after age of 15 mo. If CNS disease, repeat CSF evaluation every 6 mo until normal. With abnormal CSF on re-testing, re-treat. Careful developmental evaluation, vision and hearing testing who received treatment in utero or at birth because of maternal syphilis RPR testing at birth and then every 3 mo until result is negative. Treponemal antibody test after age of 15 mo. Recommendations for follow-up evaluation are summarirized in this table. IT is advisable to monitor the out-come of therapy by repeated RPR testing. Patients responding to therapy should have falling titres and as many as 70-93 % should become seronegative within 1 year. Rathbun KC, Sex Transm Dis 10:102, 1983

Late Congenital Syphilis - after the first two years of the life Dentition Hutchinson’s teeth Eye interstitial keratitis Ear eighth nerve deafness Skin, face rhagades, “saddle nose” CNS mental retardation, HC Bones and joints “saber shins”, “Clutton’s joints” Hutchinson’s teeth “Saber shins” “Clutton’s joints” Remington, 2006

Prevention Congenital syphilis is a preventable disease! At least one serologic test for syphilis during the first trimester For communities with high prevalence of syphilis repeated testing at the beginning of the third trimester at delivery (not in infants) Adequate treatment of infants in utero or at birth with subsequent follow-up

Conclusions from Estonian Experience Political and social changes in the beginning of independent Estonian Republic brought about the increase of incidence of syphilis the cases of congenital syphilis After 15 years congenital syphilis is a disappearing disease thanks to the decreased incidence of syphilis in the population The increased awareness of the importance of adequate prevention of transmission of the disease to the fetus and the newborn