Management of syphilis

This is a education material that was used in one of the medical institute of Nepal. Prepared by Medical student.

1. Syphilis (Management) Jeetendra Bhandari

2. Stages of Syphilis

3. Management Investigation Treatment

4. Investigation Tests to demonstrate the spirochete Serology test

5. Tests to demonstrate the spirochete Dark field microscopy Direct Fluorescent Antibody T. pallidum (DFA-TP) Test Polymerase Chain Reaction

6. Collection of samples The lesion is cleansed with water and dried Grasped firmly between the thumb and index finger Abraded sufficiently to cause clear or faintly blood- stained plasma to exude when squeezed S urface of a clean coverslip is touched to the surface of the lesion so that plasma adheres Then dropped on a slide and pressed down The specimen is quickly examined

7. Dark field microscopy Quickest and most direct method Positive in primary and secondary syphilis Sample can be taken from the primary chancre or papular lesions of secondary syphilis (mostly from condylomata lata ) Unreliable in oral cavity as T. pallidum can not be distinguished from oral saprophytic spirochetes May be negative in patients treated with systemic or local antibiotics Failure to identify do not exclude diagnosis of primary syphilis

8. Motility can be appreciated: A projection in the direction of long axis A rotation on its long axis A bending or twisting from side to side The precise uniformity of the spiral coils is not distorted during this movements

9. Direct Fluorescent Antibody T.pallidum (DFA-TP) test Permit the identification of organism when smares can’t be examined immediately Fluorescent antibodies angainst T.pallidum used for identification Better than dark field microscopy as it is reliable in case of oral lesions as well Air dry specimen of lymph nodes aspirate, genital mucosal lesion, and chancres are used

10. Polymerase Chain Reaction The genetic sequence of T.pallidum has been traced PCR is therefore 100% sensetive and specific for detecting T.pallidum PCR can also diagnose other genital lesions at the same time However, at present, its use is limited to clinical research only

11. Serological tests 2 types Treponemal Non Treponemal

12. Treponemal Detect specific Anti treponemal antibodies Have high specificity and sensitivity exceeding 95% Examples include: Enzyme immunoassay (EIA) for IgG and IgM Fluorescent treponemal antiboy absorption (FTA-ABS) Microhemagglutination assay T.pallidum (MHA-TP) T.pallidum hemagglutination (TPHA) T.pallidum particle agglutination (TPPA) EIA IgM becomes + ve at 2-3 wks after infection (initial time of chancre development) Except EIA IgM, other treponemal test remain positive for life in most of the patients.

13. Non-treponemal test Serum of person with syphilis aggregate cardiolipin -cholesterol-lecithin antigen Can be viewed in slides, tubes or autoanlyser Become positive within 5-6 weeks of infection, shortly before the primary chancre heals N egative in the early stage of primary syphilis N egative or decrease titers with treatment Examples include: Veneral disease research laboratory (VDRL) Rapid plasma reagin (RPR)

14. Important points Due to false-positive result, one positive result must be confirmed by another Usually for screening  a non- treponemal test (VDRL/RPR) If positive, for confirmation  a treponemal test Non- treponemal test is important in monitoring the response to treatment

15. Some important points NTT (+ ve ) TT (+ ve )  syphilis NTT (+ ve ) TT (- ve )  Biological false positive(BFP) NTT NTT (– ve ) TT (+ ve ) previous syphilis, late latent syphilis If two TT do not give same result, than should be confirmed by a third TT

16. Some data:

17. Biological False Positive test(BFP) result Denotes a positive serological test for syphilis in persons with no history or clinical evidence of syphilis Term applied to +vs non trepnemal test and a negative treponemal tests Are of 2 types Acute(revert to negative within 6 months) Chronic(do not revert within 6 months)

18. Causes for acute and chronic BFP Acute BFP Vaccination Infection( infective mononucleosis, hepatitis, measles, typhoid, varicella, influenza, malaria) Pregnancy Chronic BFP Connective tissue disease(SLE) Chronic liver disease Multiple blood transfusion Intravenous drug usage Advancing age

19. False positive result to treponema test are less common Condition for false positive treponema are Lupus erythematous Drug induced Lupus Scheleroderma Rheumatoid arthritis Pregnancy Genital herpes simplex infection

20. CSF analysis in syphilis CSF evaluation are not routinely performed in asymptomatic patients with syphilis CSF analysis is recommended when: Auditory, opthalmic or neurological symptoms HIV +ve with RPR >= 1:32 Patient with latent syphilis and HIV +ve or failure of initial therapy

21. Other tests X-rays of the affected bone in osseous syphilis CT scan of the head for neurosyphilis Chest x-rays for aortic dilatation and syphilitic aortitis . Tests for other sexually transmitted infections like HIV, hepatitis B.

22. Treatment

23. Penicillin Therapy Penicillin G, administered parenterally , is the preferred drug for treating all stages of syphilis The preparation used, dosage, and the length of treatment depend on the stage and clinical manifestations The effectiveness of penicillin was well established through clinical experience even before value of RCT was recognized Parenteral penicillin G is the only therapy with documented high efficacy for syphilis during pregnancy 23

24. Primary, secondary or early latent(less than 1 year) Benzathine Penicillin G ,2.4 MU, Single dose Intramuscular injection If allergic to Penicilline (non pregnant, HIV negative) Tetracycline 500 mg, orally, 4 times a day Or Doxycycline 100 mg, orally, twice daily If intolerable to above Ceftriaxone 1 gm IM or IV for 8-10 days For 2 weeks

25. Azithromycin and Erythromycine no longer used due to resistance Close follow up is recommended in patient treat with non-penicillin based regimens Alternative regimens not recommended for patient with HIV and syphilis

26. For late and late latent syphilis(>1 year) & HIV negative Benzathine Penicillin G - 2.4 MU Intramuscular Once a week for 3 weeks Non-pregnant, penicillin allergic, HIV negative Tetracycline 500 mg, orally, 4 times a day Or Doxycycline 100 mg, orally, 2 times a day 30 days

27. For neurosyphilis Penicillin G Crystalline (3-4 MU) Intravenous Every 4 hour for 10-14 days Or Procaine Penicillin 2.4 MU/day, Intramuscular + Probenecid 500 mg orally, 4 times a day If allergy conformed with penicillin, allergy should be desensitized, and treatment should be continued For 10-14 days

28. For Congenital Syphilis It is complex to treat in neonate For older children with congenital syphilis Aqueous crystalline penicillin G-200000 to 300000 IU/Kg/Day; Intravenous or Intramuscular(50,000 IV every 4-6 hours) for 10-14 days

29. For pregnant women Treated with penicillin in dose appropriate for the stage of syphilis 2 nd dose of Benzathine Penicillin , 2.4 MU, IM, administered 1 week after initial dose USG should be done to identify congenital infection Follow up quantitive serologic test should be performed monthly until delivery Penicillin Allergy should be desensitized

30. HIV positive patient(with primary and secondary syphilis), non allergic, no neurologic or psychiatric problem Benzathine penicillin G 2.4 MU IM For 3 weeks If allergic to penicillin Desensitize to allergy Follow up non treponemal test at 3, 6, 9 and 12 months

31. The Jarisch-Herxheimer Reaction An acute febrile reaction due to a rapid release of treponemal antigen with an associated allergic reaction in the patient Caused by antisyphilitic treatment, especially penicilline A ccompanied by headache, myalgia, fever, exacerbation of inflammatory reaction at sites of localized spirochetal infection Usually occur within 6-8 hours of treatment Occurs most frequently among patients with early syphilis Antipyretics can be used to manage symptoms- not prevent Might induce early labor or cause fetal distress in pregnant women, but this should not prevent or delay therapy 31

32. Treatment of sex partner Partner at risk Exposed within 90 days of diagnosis of primary, secondary or early latent syphilis, Seronegative should also be treated If serologic titer of patient is greater than 1:32 Treatment Benthine penicillin, 2.4 MU, IM, Single dose

33. Serological testing after treatment VDRL or RPR testing performed routinely to ensure appropriate response For primary and secondary syphilis, HIV-negative, non-pregnant patient, testing is repeated every 3 months in the first year, every 6 months in the second year, and yearly thereafter F our-fold decrease in titer is expected at 6 months in primary and secondary (12-24 months in case of latent syphilis) If response is inadequate, HIV testing and CSF analysis is done

34. Aim of treatment

35. References RICHARD WELLER, HAMISH HUNTER AND MARGARET MANN. Clinical Dermatology, FIFTH EDITION. James, William D. (William Daniel), Andrews’ Diseases of the skin : clinical dermatology. — 11th ed. Up to date ver. 21 CDC. Sexually Transmitted Disease Treatment Guidelines, 2010. CDC. 2010 (Available at: http://www.cdc.gov/mmwr/ pdf/ rr /rr5912.pdf NCASC. National Guidelines on Case Management of Sexually Transmitted Infections. NCASC. 2009: 58-61,77-78 (Available at: http://www.ncasc.gov.np/ncasc/Operational%20guidelines/National%20guidelines%20on%20STI%20case%20management.pdf

36. Thank you!!