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

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.

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

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

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

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

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

Natural history of syphilis (Course of untreated syphilis) 9 - 90 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%)

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

TYPES OF GENITAL ULCERS 10

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

Primary syphilis (9 – 90 days) Chancre

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

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

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

Maculo-papular syphilide

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

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

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

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

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

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

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

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.

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

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

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

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

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.

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.

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.

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)

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.

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.

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

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.

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

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

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

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

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.

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

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

Congenital Syphilis 50-80% of exposed neonates.

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

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.

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.

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)

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.

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.

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.

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

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

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

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

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 10 - 14 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.  

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

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

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, 200,000-300,000 units/kg/day administered as 50,000 units/kg/dose 4-6 hourly for 10 to 14 days (B, III)

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