Congenital Syphilis –in Theory

and in Reality in Estonia, 1991-2005

Liis ToomeTallinn Children’s Hospital

15.09.2006

Incidence of Syphilis in 2001 per 100 000 Population

EpiNorth Journal 2002, No 4

Estonia 2005 – 8,2/100 000

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

Syphilis in Estonia, 1971 - 2001

0

200

400

600

800

1000

1200

Health Protection Inspectorate, 2006

Number of cases

The Incidence of Congenital Syphilisin Estonia, 1982 - 2005

0

2

4

6

8

10

Health Protection Inspectorate Our cohort (n=28)

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 on darkfield

Treponema Pallidum

TransmissionMaternal infection(N = 428)

Transmission rate

StillbirthLive 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 dystrophyWimberger’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, 1991-2005n = 28

Tallinn - 12 cases, Harjumaa - 7 cases, Lääne-Virumaa - 5 cases

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

1 1 14

21

1. month2. month3. month6. month2. year

(n = 28)

Clinical Manifestations of Congenital Syphilis in Estonia, 1991-2005

4 %

4 %

29 %

33 %

63%

39 %

32 %

0% 20% 40% 60% 80% 100%

CNS

renal manifestations

thrombocytopenia

anemia

hepatosplenomegalia

bone lesions

mucocutaneousmanifestations

(n = 28)

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 21 month 2 weeks, pseudoparalysis of Parrot

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

Bone lesions with superimposed fractures

Case 31 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 42 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 61 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 orinadequate

Present Aqueousor

Procaine

IM/IV

IM

10-14 days

None orinadequate

Absent Aqueousor

Procaineor

Benzathine

IM/IVIMIM

10-14 days

Adequate (during

pregnancy)

Absent Benzathine (CDC)or

Follow-up only (AAP)

IM Single dose

Adequate (before

pregnancy)

Absent Follow-up only Or

Benzathine IMSingle dose

Remington & Klein, 2006

Post-treatment Follow-up

Patient Category Follow-up Procedures

Infants - diagnosed as having congenital syphilis

1. 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.

2. Perform treponemal antibody test after age of 15 mo.3. If CNS disease, repeat CSF evaluation every 6 mo until

normal. With abnormal CSF on re-testing, re-treat.4. Careful developmental evaluation, vision and hearing

testing

Infants - who received treatment in utero or at birth because of maternal syphilis

1. RPR testing at birth and then every 3 mo until result is negative.

2. Treponemal antibody test after age of 15 mo.

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”

“Saber shins” “Clutton’s joints”

Hutchinson’s teeth

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