This document discusses the diagnosis and treatment of syphilis infection in pregnant women. It begins by classifying syphilis according to WHO stages and describing the typical progression and symptoms of the disease. It then discusses strategies for diagnosing congenital syphilis in infants based on physical exam findings, serology, and other tests. Treatment guidelines are provided for pregnant women and infants depending on the stage of maternal syphilis and evaluation results. The natural course of untreated maternal syphilis is described, highlighting the risk of adverse pregnancy outcomes like stillbirth and preterm birth. Screening approaches and the sensitivity and specificity of various serology tests for syphilis are also reviewed.

1. PERAN SpOG DALAM TATALAKSANA IBU HAMIL
DENGAN INFEKSI HIV, SIFILIS DAN HEPATITIS B GUNA
MENDUKUNG TRIPLE ELIMINASI
POKJA INFEKSI SALURAN REPRODUKSI POGI
2019

2. PMTCT SYPHILIS INFECTION

3. Klasifikasi SIFILIS (WHO)

4. Perjalanan penyakit SIFILIS

5. Skin lesions of secondary syphilis
Red to violet raised papules on the palms (A) and
soles (B) are characteristic of secondary syphilis.
([A and B] Courtesy Dr. Stanton Wesson,
Department of Dermatology, University of Florida
College of Medicine, Gainesville, FL.)
Duff. P
. Maternal and Fetal Infections. In: Resnik R, editor. Creasy and resnik's maternal-fetal medicine : principles and
practice. 8th edition. ed. Philadelphia, MO: Elsevier; 2018. p. 862-919.e8,.

6. Congenital Syphilis Case Definition
Confirmed Case
Infant in whom Treponema
palladium is identified by darkfield
microscopy, fluorescent antibody,
or other specific stains in
specimens from lesions, placenta,
umbilical cord, or autopsy material
Presumptive Case
Any infant whose mother had untreateda
or inadequately treated syphilis at
delivery, regardless of signs or
symptomsb
or
Any infant who has a reactive
treponemal test for syphilis and any one
of the following:
• Evidence of congenital syphilis on
physical examination
• Evidence of congenital syphilis on long-
bone radiography
• Reactive CSF VDRL test
• Elevated CSF white blood cell count
(>5/mm3) or protein concentration (>5
mg/dL)
Duff. P
. Maternal and Fetal Infections. In: Resnik R, editor. Creasy and resnik's maternal-fetal medicine : principles and
practice. 8th edition. ed. Philadelphia, MO: Elsevier; 2018. p. 862-919.e8,.

7. Infants should be treated for presumed congenital syphilis if they were born to mothers in
the following categories:
• Mothers who have untreated syphilis at delivery
• Mothers who have serologic evidence of relapse or reinfection after treatment (i.e., a
fourfold rise in titer)
• Mothers who were treated for syphilis during pregnancy with nonpenicillin regimens
• Mothers who were treated for syphilis less than 1 month before delivery
• Mothers who do not have a well-documented history of treatment of syphilis
• Mothers who do not demonstrate an adequate response (fourfold decrease of
nontreponemal antibody titers) despite appropriate penicillin treatment
• Mothers who were treated for syphilis appropriately before pregnancy but had
insufficient serologic follow-up to ensure response to treatment.
Any child with symptomatic congenital syphilis should undergo a lumbar puncture, complete
blood count, and long-bone radiography before treatment. If these results are normal, a
single intramuscular dose of benzathine penicillin G (50,000 units/kg) should be given. With
abnormal results or if compliance is not ensured, the infant should be given a 10-day course
of either aqueous crystalline penicillin G (50,000 units/kg IV every 12 hours for the first 7
days of life, and then every 8 hours for the next 3 days) or procaine penicillin (50,000
units/kg/d IM).
Duff. P
. Maternal and Fetal Infections. In: Resnik R, editor. Creasy and resnik's maternal-fetal medicine : principles and
practice. 8th edition. ed. Philadelphia, MO: Elsevier; 2018. p. 862-919.e8,.
Congenital Syphilis

8. The natural history of untreated syphilis
in pregnancy
Blencowe H, Cousens S, Kamb M, Berman S, Lawn JE. Lives Saved Tool supplement detection and treatment of syphilis
in pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health. 2011;11 Suppl 3:S9.

9. The course of untreated syphilis.
Dobson SR. Syphilis. In: Cherry JD, Harrison GJ, Kaplan SL, Hotez PJ, Steinbach WJ, editors. Feigin and Cherry's Textbook
of Pediatric Infectious Diseases 8th edition. ed. Philadelphia, PA: Elsevier/Saunders; 2019. p. 1268-84.e3.

10. Algorithm for evaluation and treatment of infants born to
mothers with reactive serologic tests for syphilis
TREATMENT:
(1)Aqueous penicillin G 50,000 U/kg IV q 12
hr ( 1 wk of age), q 8 hr (>1 wk), or procaine
penicillin G 50,000 U/kg IM single daily
dose, x 10 days
(2)Benzathine penicillin G 50,000 U/kg IM x 1
dose
Dobson SR. Syphilis. In: Cherry JD, Harrison GJ, Kaplan SL, Hotez PJ, Steinbach WJ, editors. Feigin and Cherry's Textbook
of Pediatric Infectious Diseases 8th edition. ed. Philadelphia, PA: Elsevier/Saunders; 2019. p. 1268-84.e3.

11. Treatment Guidelines for Congenital Syphilis
Dobson SR. Syphilis. In: Cherry JD, Harrison GJ, Kaplan SL, Hotez PJ, Steinbach WJ, editors. Feigin and Cherry's Textbook
of Pediatric Infectious Diseases 8th edition. ed. Philadelphia, PA: Elsevier/Saunders; 2019. p. 1268-84.e3.
Scenario Maternal Stage/Treatment Evaluation Antimicrobial Regimen
Infant age ≤28 d with proven or highly
probable disease:
(a) Abnormal physicalexamination
a
(b) Abnormal evaluation
(c) Serum nontreponemal titer ≥4 times
maternal titer
(d)Visualization of spirochetes in clinical
specimen
Any or none CSF analysis: VDRL, cell count, and
protein; CBC and platelet count; other
tests as clinically indicated (e.g., long
bone radiographs, liver function tests,
ophthalmologic examination, hearing
evaluation, neuroimaging)
Aqueous penicillin G 50,000 U/kg IV q12h
(≤1 wk old), q8h (>1 wk old, ≤4 wk old),
q6h (>4 wk old) × 10 d, or
Procaine penicillin G 50,000 U/kg IM × 10
d (≤4 wk old)
Infant age ≤28 d with possible congenital
syphilis: normal physical examination and
serum quantitative nontreponemal titer
the same or less than fourfold the
b
maternal titer
Any stage of infection and: mother
(a) was not treated, inadequately
treated, or has no documented
treatment; (b) was treated with
erythromycin or other nonpenicillin
regimen; or (c) received appropriate
treatment but ≤4 wk before delivery
CSF analysis for VDRL, cell count, and
protein; CBC and platelet count; long
b
bone radiographs
If complete evaluation normal:
(a)benzathine penicillin G 50,000 U/kg
IMc
× 1 or
(b)aqueous penicillin G 50,000 U/kg IV
q12h (≤1 wk old), q8h (>1 wk old, ≤4 wk
old), q6h (>4 wk old) × 10 days, or
(c) procaine penicillin G 50,000 U/kg IM ×
10 d (≤4 wk old)
Infant age ≤28 d with congenital syphilis
less likely: normal physical examination
and serum quantitative nontreponemal
titer the same or less than fourfold the
maternal titer
Mother with:
(a)adequate therapy >4 wk before
delivery, and appropriate for stage of
infection; or
(b)nontreponemal titers remained stable
and low for late syphilis and no evidence
of reinfection or relapse
No evaluation Benzathine penicillin G 50,000 U/kg IM ×
1 (preferred), or
Clinical, serologic follow-up
Infant age ≤28 d old with congenital
syphilis unlikely: normal physical
examination and serum quantitative
nontreponemal titer the same or less
than fourfold the maternal titer
Mother with adequate therapy before
pregnancy and nontreponemal serologic titer
remained low and stable during pregnancy
and at delivery
None None
Congenital syphilis in infant age >28 d Any or none CSF analysis: VDRL, cell count, protein;
CBC and differential; platelet count.
As clinically indicated: radiographs of
long bones, liver function tests,
neuroimaging (cranial ultrasonography),
eye examination, hearing evaluation
Aqueous penicillin G, 50,000 units/kg q4–
d
6h × 10 d

12. Natural course of untreated syphilis
Radolf JD. Syphilis (Treponema pallidum). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases.
8th Ed, Updated Edition ed2015. p. 2684-709.e5.

13. Stage of syphilis
POKJA Infeksi Saluran Reproduksi PB POGI

14. Stages of syphilis
Cohen SE, Engelman J, Klausner JD. Syphilis (Treponema pallidum). Netter’s Infectious Diseases2012. p.
351-61.

15. Study-specific and summary estimates of the proportion (%) of all
adverse pregnancy outcomes (APOs) among women with untreated
syphilis and women without syphilis
Gomez GB, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ. Untreated maternal syphilis and adverse outcomes of
pregnancy: a systematic review and meta-analysis. Bull World Health Organ. 2013;91(3):217-26.

16. Study-specific and summary estimates
of the proportion (%) of selected
adverse outcomes among women
WITHOUT syphilis
Study-specific and summary estimates of
the proportion (%) of selected adverse
outcomes among women with
UNTREATED SYPHILIS
Gomez GB, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ. Untreated maternal syphilis and adverse outcomes of
pregnancy: a systematic review and meta-analysis. Bull World Health Organ. 2013;91(3):217-26.

17. Stillbirth
Neonatal
death
Premature birth/
low birth weight
n n % 95% CI n % 95% CI n % 95% CI
2013 233 5 2.15 [0.70– 4.94] 3 1.29 [0.27– 3.72] 22 9.82 [6.01– 13.95]
2014 350 4 1.14 [0.31– 2.90] 1 0.29 [0.72– 1.58] 25 7.25 [4.68– 10.36]
2015 2330 5 2.15 [0.70– 4.94] 0 0 [0–1.57] 26 11.40 [7.42– 15.92]
Total 8160 14 1.72 [0.94– 2.86] 4 0.49 [0.13– 1.25] 73 9.16 [7.08– 11.12]
Neonatal
asphyxia
Congenital
syphilis
APO (excluding
premature or low
birth weight)
n n % 95% CI n % 95% CI n % 95% CI
2013 233 2 0.89 [0.10– 3.07] 3 1.34 [0.27– 3.72] 13 5.63 [3.00– 9.35]
2014 350 3 0.87 [0.18– 2.48] 3 0.87 [0.18– 2.48] 11 3.17 [1.58– 5.55]
2015 2330 0 0 [0–1.57] 1 0.44 [0.01– 2.37] 6 2.62 [0.95– 5.52]
Total 8160 5 0.63 [0.20– 1.42] 7 0.88 [0.35– 1.76] 30 3.72 [2.49– 5.21]

18. Quality assessment of evidence for treatment with at least 2.4MU
penicillin for women with active syphilis in pregnancy to prevent
adverse pregnancy and neonatal outcomes
Blencowe H, Cousens S, Kamb M, Berman S, Lawn JE. Lives Saved Tool supplement detection and treatment of syphilis in
pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health. 2011;11 Suppl 3:S9.

19. Sensitivity and Specificity of Serologic Tests for Syphilis
Sensitivity during stage of infection, % (range) Specificity, %
(range)
Primary Secondary Latent Late
Nontreponemal tests
VDRL 78 (74–87) 100 96 (88–100) 71 (37–94) 98 (96–99)
TRUST 85 (77–86) 100 98 (95–100) NA 99 (98–99)
RPR 86 (77–99) 100 98 (95–100) 73 98 (93–99)
Early treponemal tests
MHA-TP 76 (69–90) 100 97 (97–100) 94 99 (98–100)
TPPA 88 (86–100) 100 100 NA 96 (95–100)
TPHA 86 100 100 99 96
FTA-ABS 84 (70–100) 100 100 96 97 (94–100)
Enzyme immunoassays
IgG-ELISA 100 100 100 NA 100
IgM-EIA 93 85 64 NA NA
ICE 77 100 100 100 99
Immunochemiluminescence
assays
CLIA 98 100 100 100 100
Sena AC, White BL, Sparling PF. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the
21st century. Clin Infect Dis. 2010;51(6):700-8.

20. Screening Syphilis Infections in Pregnancy
When to screen All women should be screened at their
first prenatal visit.
Repeat screening should be performed in
all pregnancies early in the third trimester.
Patients should be screened at delivery if
not screened previously or if at high risk.
How to screen* Treponemal and nontreponemal test
Diagnostic criteria Positive treponemal and nontreponemal
test
Nyholm JL. Maternal and Perinatal Infection: Chlamydia, Gonorrhea, and Syphilis in Pregnancy. In:
Gabbe SG, Niebyl JR, Simpson JL, Landon MB, Galan HL, Jauniaux ERM, et al., editors. Obstetrics :
normal and problem pregnancies. Seventh edition. ed. Philadelphia, PA: Elsevier; 2017. p. 1089-98.

21. Sena AC, White BL, Sparling PF. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the
21st century. Clin Infect Dis. 2010;51(6):700-8.
Composite results of syphilis
testing algorithms using
treponemal tests for initial
screening and recommendations
from the Centers for Disease
Control and Prevention, 2008

22. DIAGNOSA IBU HAMIL DENGAN SIFILIS
POKJA Infeksi Saluran Reproduksi PB POGI
1. Tes serologi : tes non-treponema & treponema
Tes non- treponema
RPR (rapid plasma reagin/rapidtest)
VDLR (venereal diseases research labotory).
Tes spesifik treponoma
tes TPHA (Treponema Pallidum HaemagglutinatioAssay)
TP Rapid (Treponema Pallidum Rapid),
TP-PA(Treponema Pallidum Particle AgglutinationAssay),
FTA-ABS (FluorescentTreponemal AntibodyAbsorption).
2. Tes Cepat Sifilis (Rapid test Syphilis)

23. Test
Primary
Stage
Secondary
Stage
Latent
Stage
Tertiary
Stage
VDRL or RPR 80-85 95-98 75 <66
FTA-ABS, TP-PA 75-85 100 100 100
Seroreactivity of Common Tests
for Untreated Syphilis
Kollmann TR. Syphilis. Remington and Klein's Infectious Diseases of the Fetus and Newborn
Infant. 8th Ed ed2016. p. 512-43.

24. SKRINING
POKJA Infeksi Saluran Reproduksi PB POGI
• Semua ibu hamil  skrining sebelum usia
kehamilan 16 minggu dan diulang pada awal
kehamilan trimester 3 (3 bulan kemudian).
• Skrining dengan VDRL / RPR atau TP rapid jika
fasilitas ini ada pada kunjungan pertama
pelayanan antenatal di semua Fasyankes.
• Jika selama kehamilan belum dikerjakan
skrining, maka dilakukan pada masa nifas.

25. Alur Tes Serologis Sifilis Pada
Ibu Hamil
Bila Hanya Tersedia TP Rapid

26. Alur Tes Serologis Sifilis
Bila TERSEDIA Tes Non
Treponema dan Treponema

27. Interpretasi
Tes Serologi Sifilis
RPR atau
VDRL
TPHA atau
TP Rapid INTERPRETASI
Reaktif Non reaktif Tes skrining nontreponema
positif palsu
Reaktif Reaktif  Sifilis yang belum diobati;
 Sifilis lanjut yang pernah
diobati
 Frambusia

28. RPR atau
VDRL
TPHA atau
TP Rapid
INTERPRETASI
Non reaktif Reaktif  Sifilis sangat dini yang belum
diobati;
 Sifilis dini yang pernah diobati
 Frambusia
Non reaktif Non reaktif  Bukan sifilis;
 Sifilis masa inkubasi;
 Sifilis sangat lanjut;
 Sifilis bersamaan dengan infeksi
HIV dan imunosupresi
Interpretasi
Tes Serologi Sifilis

29. Tatalaksana
SIFILIS pada ibu hamil
• Sifilis DINI (S-1 dan S-2):
– Benzathin penicillin G 2,4 juta unit dosis tunggal
injeksi intramuskular ATAU
– Procaine penicillin G 1,2 juta unit injeksi
intramuskular sekali sehari selama 10 hari
– Bila alergi penisilin dan tidak memungkinkan untuk
desensitisasi, atau tidak tersedia:
• Eritromisin 4X500 mg per oral selama 14 hari ATAU
• Seftriakson injeksi intramuscular 1 g sekali sehari, selama 14 hari, ATAU
• Azitromisin 2g per oral dosis tunggal
• Catatan: ketiga obat dapat mengobati ibu hamil, namun tidak dapat
melewati sawar plasenta, sehingga tidak dapat mengobati janinnya
WHO guidelines for the treatmentof Treponema pallidum (syphilis).2016

30. • Sifilis LANJUT (termasuk S laten):
– Benzathin penicillin G 2,4 juta unit injeksi
intramuskular sekali seminggu selama 3 minggu
berturut-turut (interval jangan melebihi 14 hari)
ATAU
– Procaine penicillin 1,2 juta unit injeksi intramuskular
sekali sehari selama 20 hari
– Bila alergi penisilin dan tidak memungkinkan untuk
desensitisasi, atau tidak tersedia:
• Eritromisin 4X500 mg per oral selama 30 hari
• Catatan: obat dapat mengobati ibu hamil, namun tidak dapat
melewati sawar plasenta, sehingga tidak dapat mengobati janinnya
WHO guidelines for the treatmentof Treponema pallidum (syphilis).2016
Tatalaksana
SIFILIS pada ibu hamil

31. Reaksi Jarisch-Herxheimer
• Reaksi demam akut, seringkali disertai nyeri
kepala, mialgia, dan keluhan lain
• Biasanya terjadi dalam 24 jam pertama setelah
pemberian terapi awal apapun untuk sifilis dan
seringkali terjadi pada pasien sifilis dini,
kemungkinan karena bakteri masih sangat
banyak dalam stadium dini

32. • Pasien harus diberi tahu mengenai kemungkinan
ini
• Dapat diberikan antipiretik untuk mengurangi
simtom, namun tetap tidak dapat mencegah
reaksi ini
• Reaksi Jarisch-Herxheimer dapat menginduksi
partus atau menyebabkan fetal distress pada
perempuan hamil, namun keadaan ini jangan
menjadi alasan untuk tidak mengobati atau
menunda pengobatan
Reaksi Jarisch-Herxheimer

33. Jarisch-Herxheimer Reactions
• Up to 60% of patients with early syphilis and a significant proportion of patients with later
stages of syphilis experience a transient febrile reaction after therapy for syphilis.
• The pathogenesis is unclear, but it may be caused by the liberation of antigens from
spirochetes.
• This reaction usually occurs in the first few hours after therapy, peaks at 6 to 8 hours, and
disappears within 12 to 24 hours of therapy.
• On occasion, Jarisch-Herxheimer reactions are mistaken for allergic reactions to syphilis
therapy.
• Temperature elevation is usually low grade, and there is often associated myalgia,
headache, and malaise.
• The skin lesions of secondary syphilis are frequently exacerbated during the Jarisch-
Herxheimer reaction, and cutaneous lesions that were not visible may become visible.
• The reaction is generally of no clinical significance and in most cases can be treated with
salicylates.
• Corticosteroids have been used to prevent adverse effects of the Jarisch-Herxheimer
reaction, but there is no evidence that they are clinically beneficial (other than reducing
fever) or necessary. Institution of treatment with small doses of penicillin does not
prevent the reaction.
Hook EW. Syphilis. In: Goldman L, Schafer AI, editors. Goldman-Cecil medicine. Philadelphia, PA:
Elsevier/Saunders; 2016. p. 2013-20.e2.

34. MONITOR
• Pemeriksaan serologi VDRL dan RPR pada bulan ke – 3
dan bulan ke – 6 (VDRL dan RPR menurun 4x)
• Selama kehamilan titer serologi diperiksa setiap bulan
(wanita risiko tinggi reinfeksi).
• Evaluasi USG pada usia kehamilan > 20 minggu untuk
melihat sifilis kongenital yaitu:
• hepatomegali,
• penebalan plasenta,
• hidramnion,
• ascites,
• hidrops fetalis dan
• peningkatan arteri serebri media.

35. SIFILIS KONGENITAL
W_Indriatmi 44
Organ tubuh janin yang terkena sifilis:
• Plasenta
• Hepar
• Paru-paru
• Tr. Gastrointestinal
• Ginjal
• Pankreas
• Susunan syaraf pusat
• Sistem tulang

36. TERIMA KASIH