1. PENGENDALIAN IBU HAMIL SIFILIS POSITIF
Dr. Nor Azah bt Mohamad Nawi
Pakar Perubatan Keluarga UD54
Klinik Kesihatan Bakar Arang

2. KANDUNGAN Apakah VDRL, RPR, TPHA dan TPPA?
Syphilis – klasifikasi dan rawatan
Pengurusan kontak
MSA untuk ulser genital

3. 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.

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

5. TPHA/TPPA? TPHA: Treponema pallidum hamagglutination assay
Bound to erthrocytes
TPPA: Treponema pallidum particle agglutination
Bound to gelatin
Baru dan lebih mudah dari TPHA
Kedua-2 mengesan antibodi,
Dilakukan bila RPR/VDRL reactive

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

7. 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

8. 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 8

9. 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%)

10. 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 , mucocutaneous 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

11. TYPES OF GENITAL ULCERS11

12. 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

13. Primary syphilis (9 – 90 days)
Chancre

14. 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
condylomata lata

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

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

17. Maculo-papular syphilide

18. 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

19. 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

20. 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

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

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

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

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

25. 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.

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

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

28. 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

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

30. 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.

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

32. 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.

33. 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)

34. 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.

35. 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.

36. 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

37. 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.

38. Treatment 2. Late Latent Syphilis
Inj. Benzathine Penicillin 2.4 million 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

39. 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

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

41. Congenital Syphilis Rx if sero-positive mother is Untreated
Rx < 1/12 before delivery
Rx with non penicillin regime
Titre of VDRL not decreased as expected
Treated but insufficient serologic f/up

42. 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

43. 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.

44. STI – USING THE SYNDROMIC APPROACH
Syndrome
Treat for
Men
Urethral Discharge
# Gonorrhoea
# Chlamydia
Women
Lower Abd. Pain
Vaginal Discharge
Gonorrhoea, Chlamydia & other bacteria
Cervicitis – Gonorrhoea, Chlamydia
Vaginitis – Trichomoniasis and Candidiasis
Both
Genital Ulcers
# Syphilis
# Chancroid
# Genital Herpes

45. Patient c/o GENITAL ULCER or SORE
FLOW CHART FOR GENITAL ULCER SYNDROME
Patient c/o GENITAL ULCER or SORE
Take History and Examine
Investigations
Tzank smear
Gram stain for H. ducreyi
Dark ground microscopy
RPR/TPPA, HIV Ab, anti-HCV, HBsAg
Consider Urine Pregnancy Test
ULCER present ?

46. FLOW CHART FOR GENITAL ULCER SYNDROME (cont’d)
ULCER present ? NO
Educate behav change
TCA 2/52 – review result
Single painless/
multiple painful ulcers
YES
Painful grouped vesicles, erosions, ulcers
Treat for Syphilis and Chancroid
Educate for behavior change
Advise sex abstinence for 2 weeks
Provide condom or promote usage
Partner management
Follow-up after 7 days for results
Repeat swabs if positive
Repeat VDRL/RPR, HIV Ab, HBsAg after 3/12
Genital herpes Mx
Educate for behaviour change
Review after 7 days for results

47. FLOW CHART FOR GENITAL ULCER SYNDROME (cont’d)
ULCER present ? NO
Educate behav change
TCA 2/52 – review result
Single painless/
multiple painful ulcers
YES
Painful grouped vesicles, erosions, ulcers
Treat for Syphilis and Chancroid
Educate for behavior change
Advise sex abstinence for 2 weeks
Provide condom or promote usage
Partner management
Follow-up after 7 days for results
Repeat swabs if positive
Repeat VDRL/RPR, HIV Ab, HBsAg after 3/12
Genital herpes Mx
Educate for behaviour change
Review after 7 days for results

48. Treatment For Genital Ulcer Syndrome
FIRST CHOICE
IM Benzathine Penicillin 2.4 million units single dose
Plus
Azithromycin 1.0 gm single oral dose
Treatment For Syphilis and Chancroid
SECOND CHOICE
IM Benzathine Penicilline 2.4 million units single dose
Plus
IM Ceftriaxone 250 mg single dose
If patient develops allergic reaction to 1st dose of IM B. Penicillin, do not give the 2nd dose.
If allergic to B. Pen: Doxycline 100 mg bd x 14 days or
EES 800 mg qid x 14/7
Doxycycline: should not be used during pregnancy, lactation or children.
Babies of mothers who are treated with Erythromycin must be treated for syphilis.

49. 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

50. THANK YOU