congenital syphilis arire

Yves MUTABANDAMA

March 10th 2015

Case presentation

PlanClinical caseIntroductionepidemiologyClinical manifestationsDiagnosisManagementFollow-up

Clinical case Bb M.F, Female, DOB: 25th/12/14 Admitted on 18th/02/2015 CC: 3d history of Bilateral lower limbs swelling, redness and at the

knees. Hb at the referring hospital:4g/dl BW: 3.5kg, cried immediately ROS: at 1mo of age: skin rashes in the back, mandible and abdomen, no

fever, b/feeding well no vomiting, no cough P/E:

W<3rd perc; “nl heigth and HC”; nl vital signs Pallor, no lymphnodes; no HSM; bilateral swelling of the knees with reduced

ROM; R swelling of the elbow and wrist, hypopigmented macules at the level of the mandible, thigh and abdomen

CNS and CVS: NL Any question? DD??:

CONGENITAL SYPHILIS

Introduction Infection of spirochetes: treponema pallidumSignificant morbidity if not treated/inadequately Transmission:

sexual; via placenta; during delivery (maternal genital lesion)

Vertical occurs anytime during gestation decreases as maternal disease progresses:

primary- syphilis 70–100%; secondary 67% ; and 40% for early latent syphilis to 10% for late latent disease

high nontreponemal maternal test titres

Rana Chakraborty, Suzanne Luck Syphilis is on the increase: the implications for child health Arch Dis Child February 2008 Vol 93 No 2

Introduction primary and secondary syphillis

Courtesy of Charles B Hicks, MD. www.visualdx.com

http://www.visualdx.com/

Epidemiology

WHO want to eliminate mother to child transmission of syphilis in 2015, they calculated global and regional estimates of syphilis in pregnancy, as well as antenatal coverage

Clinical manifestationsWHO estimates: 1M of pregnancies are affected worldwide Abortion or stillbirth: 460.000Prematurity; Low birth weight: 270.000

A review of diagnostic tests for congenital syphilis in newborns T. Herremans & L. Kortbeek & D. W. Notermans Eur J Clin Microbiol Infect Dis (2010) 29:495–501

Clinical manifestationsAsymptomatic/symptomatic60% asymptomatic at birthEarly (first 2years) / late (after 2years)vasculitis, with progression to necrosis and

fibrosis

Rana Chakraborty et al. syphilis is on the increase: the implication for child health. Arch Dis Child February 2008 Vol 93 No 2

Objective: investigate clinical features and outcomes of children treated for congenital syphilis in Brazil from 1997-2004

490 pregnancies, 9 sets of twins: syphilis on pregnancy

379 met the criteria of CSSymptoms at birth 21 (5.5%) common in

preterm infants: 21%, vs 3% term 292 (77%) had a conclusive lab/x-ray

evaluation;11deaths with cs

Clinical Features and Follow-up of Congenital Syphilis Eleonor G. Lago et al. Sexually Transmitted Diseases. Volume 40, Number 2, February 2013

Early syphilis

Clinical manifestationsLate after two years of age most often in puberty 40 percent of infants born to women with untreated syphilis Many organs bust most often bones, teeth, CNS 25–33% of infants with untreated congenital syphilis have

asymptomatic neurosyphilis symptomatic, neurosyphilis can result in eighth nerve deafness(8-10y) Hutchinson’s triad: notch incisor, keratitis and deafness saddle nose, palatal erosions, short maxillae, protruding mandible,

frontal bossing, and sabre tibia Others: fissuring around the mouth (rhagades). Rashes can but distinct from those seen in early syphilis: nodules and

gummata


Clinical manifestations of late congenital syphilis

diagnosisBased on clinical and labs findingsSuspected case:

Untreated mothersInadequately treatedPositive maternal serology test within 4weeks

before birth

diagnosisAdequate treatment of syphilis during pregnancyMore than 4weeks before deliveryPrimary/secondary/early latent: Benzathine penicillin G, 2.4

million units IM in a single dose (usually administered as 1.2 million units in each buttock)

Late latent/tertiary/unknown duration: Benzathine penicillin G, 7.2 million units total, administered as three doses of 2.4 million units IM each, at one week intervals

decrease four-fold by six months post therapy and become nonreactive by 12 to 24 months

Errol R norwitz. Syphilis in pregnancy Uptodate.com 2011

diagnosisDifficulties in poorly-resourced settings Antenatal care and documentation LabsAvailable tests: RPR and VDRL; Ig G testcompare infant and maternal titres of the same test. 4fold accepted as significant (sensitivity 4-13%, specificity: 99%) If non reactive at 6months the diagnosis of CS can be excluded if the infant was

not treated Any increase should raise suspicion Falsely negative early primary syphilis, latent acquired syphilis of long duration

and late congenital syphilis False positive: viral: mononucleosis, hepatitis, varicella, measles), lymphoma,

tuberculosis, malaria, endocarditis, connective tissue disease, pregnancy, laboratory error

Harron Saloojee et al. the prevention and management of congenital syphilis: an overview and recommendations. Bulletin of The World Health Organisation June 2004


diagnosisOther tests Rabbit infectivity test: gold standard PCR (sensitivity 78-86%; specificity 100%) Darkfield microscopy: amniotic fluid, snuffles Ig M test

Fluorescent Treponemal Antibody-Absorption (FTA-ABS): false-positive rate of 10% and a false-negative rate of up to 35%

IgM immunoblot: very effective in confirming CS sensitivity of 83–100%, IgM ELISAs sensitivity (88–100%) and specificity (100%) Evidence of an active infection A negative result does not exclude the CS(early infection) More effective in mothers

T. Herremans & L. Kortbeek & D. W. Notermans A review of diagnostic tests for congenital syphilis in newborns Eur J Clin Microbiol Infect Dis (2010) 29:495–501

diagnosisFBC; Xrays; LP; VDRL/RPRif the infant or child has signs of congenital

syphilis if there is no documented maternal treatment in

pregnancy; if the mother was treated within four weeks of

delivery; if the maternal treatment was inadequate

SandraR Arnold et al. Congenital syphilis: A guide to diagnosis and management Paediatr Child Health Vol 5 No 8 November/December 2000

CNS

•July 1989 and July 1999, inTexas

•Objective of the study was the diagnosis of CNS infection among the infant with CS and to assess the standard conventional test including FBC, VDRL/RPR (blood and CSF); Rx; CSF(protein, WBC).

•Rabbit-infectivity test, PCR assay, or IgM immunoblot of serum, blood, or cerebrospinal fluid

Results: N=148; 65had a positive RIT, PCR, IgM OF SERUM, blood or csf The maternal stage of syphilis infection was not associated with the results of the

cerebrospinal fluid RIT any abnormal conventional evaluation has a sensitivity of 94 percent, a specificity

of 61 percent. Only 1 with positive RIT in the csf and neg conventional test Three infants with positive cerebrospinal fluid rabbit-infectivity tests were not

identified by conventional cerebrospinal fluid tests combination of cerebrospinal fluid tests (white cell count, measurement of protein,

and VDRL test) had suboptimal sensitivity (82 percent) and specificity (65 percent) a normal physical examination and normal results on conventional evaluations had

good negative predictive values (96 percent and 97 percent, respectively)

Conclusion Most infants withT. pallidum Infection of the central nervous system can be identified

by physical examination, conventional laboratory tests, and radiographic studies However, the identification of all infants required additional tests

Contribution of long-Bones radiographs to the management of congenital syphilis in the newborn infant Virginia A. Moyer et al. Arch Pediatr Adolesc Med 1998; 152:353-357_

The objective of the study was to determine the contribution of the long-bones radiographs to the diagnosis and management of CS

N=853 in 3large teaching hospitals in Houston26 positive P/E; 17(65%) Abnormal Xray, 166 infants born to adequately treated mothers; all of them

were asymptomatic; only one had an abnormal radiograph (metaphyseal lucencies)

Conclusion: findings on Xray of symptomatic infants are frequently abnormal

and sometimes even on asymptomaticCan stay abnormal in up to 6months in a past infected infantEven, when abnormal, can not differentiate an active/past

infection or other conditions its use in routine evaluation should be reconsidered

BACK TO OUR CASE

investigationsWBC: 11.2; N:31.5%; L:65.1% Hb:5,2G/DL;

plt:405AST:50,9U/L; ALT: 29,5U/LBlood group: B-; malaria:negBrain CT: normalRPR: 1/256; VDRL:positive; TPHA: 1/1280LP: clear csf, RPR negative, 10WBC,

190RBC, gram stain is negative; culture: neg

X-Rays

managementBlood transfusionparacetamolCefotaxime 100mg/kg/day for 2d switched

to Penicillin G IV 50.000IU/kg/dose 6hrly for

10dDischarge and follow-up in 1month

Diagnosis approach and management


TREATMENTDRUGSAqueous penicillin G (50,000 units/kg IV every 12 hours

[for infants ≤7 days of age] and every 8 hours [>7 days of age] for a total of 10 days);

procaine penicillin G 50,000 units/kg IM as a single daily dose for 10 days.

Benzathine penicillin (50,000 units/kg intramuscularly as a single dose)

If >1month of age; aqueous penicillin G (50,000 units/kg intravenously every four to six hours for 10 days)


Treatment None

Adequate maternal treatment, normal physical exam, non reactive RPR/VDRL

Single dose of benzathine penicillin 50.000U/kgInadequate or no treatment but nl P/E; non

reactive RPR/VDRLAdequate maternal treatment, normal physical

exam but <4foldmaternal titer


treatment10 days of parenteral penicillin if:

Examination compatible with congenital syphilis or visualization of spirochete in clinical specimen

≥ Fourfold maternal titer (VDRL/RPR)Abnormal or incomplete of one of these exams: CBC, plt;

LP(protein, cells, VDRL/RPR); quantitative VDRL; X rays


Follow-up at the OPD147 were followed up; 120/398 in CS;

27/120 in the MS group between 8-60moWeight/age lower in CS 8- MS116/120 (13.3%) one or more sequelae- 0/27Only 4/16 had an abnormal physical

examination at birthother 4/16, the onset of symptoms was

within the first 4 weeks of life13 of the 16 neonates had lab/x-ray findings

Clinical Features and Follow-up of Congenital Syphilis Eleonor G. Lago et al. Sexually Transmitted Diseases. Volume 40, Number 2, February 2013

Follow-upRPR or VDRL

Use the sameAt 1, 2,4, 6, 12monthsFourfold decrease at 6months, negative at 12monthsIf not decreasing, or remain positive consider retreating

Csf (if previously abnormal)If positive at 6months, consider retreating

Uninfected babiesserial nontreponemal testsShould be negative at 6months


RWANDAchallengesANTENATAL CARELABS (non treponemal titres)Follow upAvailability of medicationsQuestionsAre we (in the HC, DH,) aware of its mortality and

morbidity?Do we know if the pregnant women are adequately

treated?Do we know if babies from reactive maternal non

treponemal test need evaluation and follow-up?

RWANDA SuggestionManagement in the DH Screening of all pregnancies (1st trimester and

especially when they present for delivery or soon after) and adequate ttt +partner

Treat all “cases at risk” with a 10days regimen and or a dose of benzathine penicilline (if indicate and if possible follow-up). Why?No evidence of a good maternal responseNot all the basics evaluations are available to exclude CS

Counseling of the parents and follow up at OPD at least 3times within one year

Consider retreating

REFERENCES Uptodate.com Rana Chakraborty, Suzanne Luck Syphilis is on the increase: the implications for

child health Arch Dis Child February 2008 Vol 93 No 2 SandraR Arnold et al. Congenital syphilis: A guide to diagnosis and

management Paediatr Child Health Vol 5 No 8 November/December 2000 G. Lago et al. Clinical Features and Follow-up of Congenital Syphilis Eleonor

Sexually Transmitted Diseases. Volume 40, Number 2, February 2013 Virginia A. Moyer et al. Contribution of long-Bones radiographs to the

management of congenital syphilis in the newborn infant Arch Pediatr Adolesc Med 1998; 152:353-357

Harron Saloojee et al. the prevention and management of congenital syphilis: an overview and recommendations. Bulletin of The World Health Organisation June 2004

Eleonor G. Lago et al. Clinical Features and Follow-up of Congenital Syphilis Sexually Transmitted Diseases. Volume 40, Number 2, February 2013

T. Herremans & L. Kortbeek & D. W. Notermans A review of diagnostic tests for congenital syphilis in newborns Eur J Clin Microbiol Infect Dis (2010) 29:495–501

Thank you!

congenital syphilis arire

Health & Medicine