1. PENCEGAHAN SIFILIS DARI IBU KE ANAK
Dr. Nor Azah bt Mohamad Nawi
Pakar Perubatan Keluarga UD54
Klinik Kesihatan Bakar Arang

2. VDRL dan RPR Venereal Diseases Research Laboratory
Juga dikenali sebagai non-treponemal test.
RPR: Rapid Plasma Reagin
Ujian saringan untuk sifilis.
False positive: kehamilan, yaws, malaria, Connective tissue disease, HIV, leprosy etc.
Untuk diagnos sebagai sifilis, perlu sahkan dgn ujian pengesahan:
TPHA, TPPA, dark-ground microscopy, FTA-Abs, ELISA, EIA, atau PCR.

3. Diagnosis
Dark ground field microscopy: Treponema pallidum sphirochaette
2. Serum VDRL
3. Serum TPHA
4. FTA abs

4. TPHA/TPPA? TPHA: Treponema pallidum haemagglutination assay
Bound to erthrocytes
TPPA: Treponema pallidum particle agglutination
Bound to gelatin
Baru dan lebih mudah dari TPHA
Kedua-duanya mengesan antibodi
Dilakukan bila RPR/VDRL reactive

5. SENSITIVITY OF SEROLOGICAL TESTS FOR SYPHILIS
Latent
FTA-Abs
85%
100%
97%
TPHA
60-70%
VDRL
75%
70%

6. Interpretasi Ujian Darah
Category
VDRL
TPPA
Comment
Negative NR
Tiada bukti sifilis. Ulang ujian 1 & 3 bln
Reactive
Cross reaction? Rpt test
Weakly positive WR
Positive
Current or past infection
SEJARAH PENDEDAHAN PENYAKIT PENTING

7. Syphilis Cause: Treponema pallidum A sphirochaette
50% pesakit ada tanda-2 klasikal
Screening : at booking and 28/52 POA.
Cara Jangkitan:
Diperolehi/Acquired
Early
Late
Kongenital
Early, < 2 years
Late, > 2 years 7

8. Natural history of syphilis (Course of untreated syphilis)
days
6 wks - 6mths
First 2 years
2 years to a lifetime
Spontaneous
cure (30%)
Exposure
Primary
syphilis
Secondary
syphilis
Early
latent
Late latent syphilis(30%)
Neuro-
syphilis
(12%)
Cardio
vascular
(14%)
Gumma
(14%)

9. Acquired Syphilis Late Syphilis: Early Syphilis: After 2 years
1st 2 years
Primary
IP 9 – 90 days
Chancre (ulcer) and lympadenopathy
2. Secondary: stage bacteraemia
IP: 6 wk – 6/12
Generalised non-irritating skin lesion, condylomata lata , mucucutaneous lesion and patchy alopecia
3. Early latent: Positive serology without Sn n Sx
Late Latent
- Tiada gejala
Tertiary Benign
1 – 45 (15) years later
Benign gumma of skin, bones
3. Cardiovascular
15 – 30 years later
Aortic aneurysm
4. Neurosyphilis
- Bila-bila masa
Berlaku lebih awal di kalangan RVD positive

10. TYPES OF GENITAL ULCERS10

11. Early : Primary syphilis
IP: 1-3 weeks
Usually Painless single papule then became ulcer, round/oval
Well circumscribed, clean floor, no exudate
Usually no vesicle
Regional lymphadenopathy
Any anogenital ulcer should be considered to be due to syphilis unless proven otherwise.
90% genital ulcer, 10% extragenital

12. Primary syphilis (9 – 90 days)
Chancre

13. Early: Secondary syphilis
6 weeks to 6 months
Stage of bacteremia
May cause uveitis, cranial nerve palsies, hepatitis and splenomegaly
The most common features
fever,
lymphadenopathy,
diffuse non irritating
rash
condyloma lata

14. Patchy alopecia of secondary syphilis
Patchy alopecia of secondary syphilis.  Hair loss also occurs commonly from the lateral third of the eyebrows.

15. Early: Secondary syphilis
Malignant syphilis – widespread necrotic papulopustules and ulcers with severe systemic symptoms

16. Maculo-papular syphilide

17. Diagnosis of Secondary Syphilis
All serological tests for syphilis are expected to be positive in secondary syphilis
RPR/ VDRL titres in untreated cases are often > 1:8 (VDRL) and > 1: 16 (RPR)
If a specific treponemal test is used for diagnosis and is found to be positive, use the VDRL/ RPR test to determine disease activity, and to monitor response to therapy

18. Early Latent Syphilis
Diagnosed by a POSITIVE SEROLOGY without symptoms and signs in a person known to be sero-negative in the previous 2 years

19. LATE SYPHILIS: > 2 years
Late latent: Asx
Benign Tertiary Syphilis (Gumma)
1 – 45 (average 15) years after infection,
destructive granulomatous lesions on skin, bones
Cardiovascular Syphilis
15 – 30 yrs
Neurosyphilis: at any stage of syphilis, earlier in HIV patient

20. Tertiary syphilis (3 – 12 years later)
Necrotic nodules
or plaques
Gummas on lower limb

21. Late: Benign Tertiary syphilis
Gummatous Syphilis
Nodules on skin, bones,
Can also involve the kidney, heart, brain and respiratory

22. Late: 3. Cardiovascular Syphilis
Aortitis (Proximal aorta)
Aortic incompetence causing Heart failure
Coronary ostial stenosis
Aortic medial necrosis causing aortic aneurysm

23. Late: 4. Neurosyphilis Involves Central Nervous System
Meningovascular (MV) or parenchymatous syphilis
Sx of MV syphilis: Headache, vertigo and CN palsy
Parenchymatous: General paresis of insane

24. Parenchymatous syphilis
GPI: gradual personality change, ataxia, stroke, opthalmic involvement and tabes dorsalis (lightning pain, sensory impairment and mobility problem)
Rx: Admit for Ix (LP) and IM/IV antibiotic.

25. Serology interpretation
34 years old female G3P2 at 12 weeks came for booking. Below the serology finding
Interpretasi?
VDRL
Reactive
1:2 titre
TPHA
negative
FTABs

26. Serology interpretation
42 years old Malay male, asymptomatic came for VDRL screening as his pregnant partner was treated for syphilis. Below his serology result.
VDRL NR
TPHA
positive
FTAabs

27. Serology Interpretation
23 years old Male history of painless penis ulcer for 5 days. History of visit to Thai border recently
Below the serology result
Next step?
VDRL
negative
TPHA
FTA abs

28. Treatment Early Syphilis
- IM Benzathine Penicillin 2.4 mega units single dose or
- IM Procaine Penicillin G 600,000 daily x 10/7

29. Early Syphilis: For patients allergic to penicillin:
T. Doxycycline 100 mg bd x 14/7: (contraindicated in pregnancy)
T. Erythromycin 500 mg qid x 14/7
T. Erythromycin ES 800 mg qid x 14/7
IM Ceftriaxone 250 mg daily x 10/7
T. Azithromycin 2 G single dose
Erythromycin should not be used because of the high risk of failure to cure the foetus.
If erythromycin is used, paediatricians must be alerted and babies have to be treated prophylactically with penicillin and monitored.

30. Penicillin allergy in Pregnant Women
Should be meticulously interviewed regarding the validity of the history.
Currently, no proven alternative therapies to penicillin are available for treating neurosyphilis, congenital syphilis or syphilis in pregnancy.
Therefore, skin testing, with desensitisation, if indicated, should be done for these patients.

31. MANAGEMENT OF PATIENTS WITH HISTORY OF PENICILLIN ALLERGY
Desensitisation should be done in a hospital setting because serious IgE-mediated allergic reactions may occur.
A protocol is recommended (refer STI guideline).
Oral penicillin in increasing concentration is administered every 15 minutes. Sensitisation is completed within 4 hours with a cumulative dose of 1.3 million units of penicillin V.

32. Jarisch-Herxheimer reaction
An acute febrile illness with headache, myalgia, chills and rigors and resolving within 24 hours.
This is common in early syphilis but is usually not important unless
neurological or ophthalmic involvement or
in pregnancy when it may cause fetal distress and premature labour (second half of pregnancy)

33. Jarisch-Herxheimer reaction
It is uncommon in late syphilis but can potentially be life threatening if there is involvement of strategic sites (coronary ostia, larynx, nervous system).
Prednisolone can reduce the reaction.
Recommendation
In early syphilis : Treat with Paracetamol
In Neurosyphilis, Cardiovascular, certain cases of benign tertiary and late latent syphilis:
Treat with Prednisolone 40-60mg daily for 3 days: begin 24 hours before treatment and for 2 days after starting treatment.

34. ADVICE
Abstain from sex until 1 week after they and their partner(s) have completed treatment.
CONTACT TRACING 
Examine and investigate all sex partners and treat epidemiologically.
Primary syphilis, notify sexual partners within the past 3/12.
Secondary syphilis with clinical relapse or in early latent syphilis: 2 years  
All patients should be offered patient and provider referral as a method of contacting any sexual partner. The method agreed upon with the patient should be clearly documented.
Epidemiological treatment for asymptomatic contacts of early syphilis is recommended.

35. Incubating/ Epidemiological Rx: Partner
IM B. Penicillin 2.4 mega units single dose or
T. Doxycycline 100 mg bd x 14/7 or
T. Azithromycin 1 G single dose

36. F/UP for TPHA Positive in Pregnancy
Repeat VDRL/RPR titre
1/12 after last dose
then monthly until delivered and then
3/12ly – 6/12ly as non-pregnant women until seronegative or at low titre.

37. Treatment 2. Late Latent Syphilis
Inj. Benzathine Penicillin 2.4 millionunit i.m once a week for 3/52
i.e. 3 doses
Gap between doses: < 14/7.
If missed< repeat whole cycle of Rx.
Or IM Procaine penicillin G 600,000 units for 17 days

38. For patients allergic to penicillin:
T. Doxycycline 100 mg oral bd x 28/7 (c/i in pregnancy) or
Erythromycin 500mg q.i.d P.O for 28 days
Erythromycin ES 800mg q.i.d P.O for 28 days

39. Follow-up of Late Syphilis
Examine and 6 monthly VDRL x 2 years then yearly until seronegative or low titre (1:4 or less)

40. Syphilis: Rx Failure and Re-Rx
Clinical Sx persist
Initial High titre VDRL failed to decreased fourfold by 1 year
Sustained four fold increase of VDRL titre

41. Syphilis: Persistent Reactor
Titre VDRL persistently > 1:4 despite retreatment with B. Penicillin and trial of treatment with Doxycycline for 28 days when she was not pregnant.

42. REMINDER
For all pregnant lady and partner with TPHA positive, don’t forget to screen for other STIs i.e:
HIV Ab, HCV, HBsAg
GC smear
TV wet smear

43. Pengendalian Bayi dari Ibu TPPA Positif
Dr Nor Azah Mohamad Nawi
Pakar Perubatan Keluarga UD54
Klinik Kesihatan Bakar Arang

44. Congenital Syphilis
50-80% of exposed neonates.

45. Congenital Syphilis
Caused by transplacental transmission of spirochetes; the transmission rate approaches 90% if the mother has untreated primary or secondary syphilis.
The child is at greatest risk of contracting syphilis when the mother is in the early stages of infection
A woman in the secondary stage of syphilis decreases her child's risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy

46. Untreated Syphilis in Pregnancy
Fetal infection can develop at any time during gestation.
Because inflammatory changes do not occur in the fetus until after the first trimester of pregnancy, organogenesis is unaffected.
All organ systems may be involved.
Can cause:
Miscarriages,
Premature birth
Stillbirths
Death of newborn babies: pulmonary haemorrhage.

47. Congenital Syphilis Manifestations are defined as Early-onset disease,
Early if they appear in the first 2 years of life
Late: develop after age 2 years.
Early-onset disease,
result from transplacental spirochetemia and are analogous to the secondary stage of acquired syphilis. (Congenital syphilis does not have a primary stage)
Late-onset disease (>2 years) is considered contagious.

48. Early-onset congenital syphilis (before or at age 2 y)
60% are asymptomatic at birth.
Sx develop within the first 2/12 of life. Almost 100% has hepatomegaly; biochemical evidence of liver dysfunction is usually observed.
Common Sn: skeletal abnormalities, rash, and generalized lymphadenopathy.
Radiographic abnormalities, periostitis or osteitis, involve multiple bones. Sometimes, the lesion is painful and an infant will favor an extremity (pseudopalsy)

49. Early-onset congenital syphilis (before or at age 2 y)
Maculopapular rash, may involve palms and soles.
In contrast to acquired syphilis, a vesicular rash and bullae (pemphigus syphiliticus) may develop - highly contagious.
Mucosal involvement may present as rhinitis ("snuffles") – poor feeding.
Nasal secretions are highly contagious.

50. Early-onset congenital syphilis (before or at age 2 y)
Hematological abnormalities include anemia and thrombocytopenia. Some have leukocytosis.
Abnormal CSF examination
Seen in a half of symptomatic infants,
10% of asymptomatic baby.

51. Late Onset Manifestations
Neurosyphilis and involvement of the teeth, bones, eyes, and the eighth cranial nerve, as follows:
Bone involvement - Saber shins, saddle nose, short maxillae, protruding mandible, swollen knees
Higoumenakis sign, enlargement of the sternal end of clavicle in late congenital syphilis.
Teeth involvement - Notched, peg-shaped incisors (Hutchinson teeth)
Pigmentary involvement - Linear scars (rhagades) at the corners of the mouth and nose result from bacterial infection of skin lesions.
Interstitial keratitis - Presents in the 1st or 2nd decade of life
Sensory-neural hearing loss (eighth cranial nerve deafness) - Presents between age 10 and 40 years.

52. Classic Hutchinson triad
Defective incisors,
interstitial keratitis,
eighth cranial nerve deafness

53. Infants should be evaluated if they were born to sero +ve women who:
Have untreated syphilis
Were treated for syphilis less than 1 month before delivery
Were treated for syphilis during pregnancy with a non - penicillin regimen
Did not have the expected decrease in RPR titre after treatment
Were treated but had insufficient serologic follow-up during pregnancy to assess disease activity

54. EVALUATION OF INFANT A thorough physical examination
RPR (compare with mother’s titre) / EIA
FTA-Abs
CSF analysis for cells, protein and CSF-VDRL test
Long bones X-ray
Chest X-ray

55. Treat if they have: Any evidence of active disease
A reactive CSF-VDRL / FTA-Abs
An abnormal CSF finding ( WBC > 5/ mm3 or protein > 50 mg / dl ) regardless of CSF serology
Serum RPR titre that are at least 4 times higher than their mother's.
Positive EIA-IgM antibody
* Treatment (with penicillin) before the development of late symptoms is essential

56. Rx
Aqueous Cystalline Penicillin G: 50,000 units/kg/dose 12 hourly for first 7 days then 8 hourly for the following 3-7 days OR
Procaine Penicillin, 50,000 units/kg daily IM for days OR
*IV/IM Ceftriaxone 75 mg/kg (< 30 days old) or 100 mg/kg (>30 days old)
*If more than a day of treatment is missed, the whole course should be restarted
Infants who should be evaluated but whose follow-up cannot be assured should be treated with a single dose of Benzathine Penicillin, 50,000 units/kg IM.

57. F/up and Monitoring
Sero-positive untreated infants must be closely monitored at 1, 2, 3, 6, and 12 months of age.
RPR should decrease by 3/12 of age and usually disappear by 6/12 of age. 
Treat (with the same regimen as above) if:
Symptoms and signs persist or recur
RPR titre increase fourfold or more by 3/12 of age
RPR still positive by 6/12 of age
TPHA still positive by 1 year of age

58. Treated Infants
Monitored clinically and serologically at 1, 3, 6, 12, 18, and 24 months. Lumbar puncture should be repeated 6 monthly till normal.

59. THERAPY OF OLDER INFANTS AND CHILDREN
After the newborn period, children discovered to have syphilis should have a CSF analysis to rule out congenital syphilis.
Any child with congenital syphilis or with neurologic involvement should be treated with
Aqueous Cystalline Penicillin, 200, ,000 units/kg/day administered as 50,000 units/kg/dose 4-6 hourly for 10 to 14 days (B, III)

60. THANK YOU