1. Syphilis in VOICE MTN 003 Site Training

2. Scenario #1  A 26 year old woman presents for screening and is found to have a 1.5 cm painless ulcer. You suspect syphilis on clinical grounds, but she has no known history of syphilis and is otherwise well. She is married and has 2 children

3. Assuming normal labs, can she be enrolled now? 1. Yes 2. No

4. When can she be enrolled? 1. Never 2. After she receives treatment with one dose of benzyl benzathine penicillin and the ulcer has resolved 3. After she receives treatment with three doses of benzyl benzathine penicillin and the ulcer has resolved 4. 42 days after she receives treatment with three doses of benzyl benzathine penicillin regardless of whether the ulcer is still present

5. Protocol 5.3.6- Exclusion Criteria  Diagnosed with pelvic inflammatory disease, an STU or reproductive tract infection (RTI) requiring treatment per WHO guidelines  Note: Otherwise eligible participants may be enrolled after completing treatment and when all symptoms have resolved assuming this occurs with 56 days of screen

6. The participant’s RPR is negative. Does this exclude the possibility of syphilis? 1. Yes 2. No

7. RPR  In primary syphilis evidenced by painless genital ulcer the RPR is negative up to 30% of the time.  It can take 2-3 weeks to convert to positive RPR

8. Scenario #2  A 26 year old woman presents for screening and is found to have a positive RPR with a titer of 1:4. On questioning, she reports that she was diagnosed with syphilis several years ago and was treated but does not have records. She has no symptoms or signs on examination.

9. Assuming she is otherwise eligible, can she be enrolled right now? 1. Yes. Her pelvic exam is normal 2. Yes. She says she was treated. 3. No. You don’t have proof that she was treated.

10. How will you proceed? 1. Exclude from the study completely. 2. Treat with one dose of benzyl benzathine penicillin and enroll immediately 3. Treat with three doses of benzyl benzathine penicillin and enroll immediately 4. Treat with three doses of benzyl benzathine penicillinand wait for the titer to decreasebefore enrolling

11.  She is treated at the Screening Part 2 visit and enrolled.

12. When will you check titers again? 1. Within 1 week 2. 1 month 3. 3 months 4. 6 months 5. Never. She’s been treated

13. Checking titers: RPR  Used to quantify antibodies Not antibodies to T. pallidum but a proxy antibody (to cardiolipin-cholesterol-lecithin antigen)  Serially dilute sample

15. 1:2

16. 1:4

17. 1:2 1:4 1:8

18. 1:2 1:4 1:8 1:16

19. Why do we check titers?  Document adequate treatment Expect a four fold decrease within 1 year  1:16 to 1:4  1:8 to 1:2  Persistently high titer after treatment Inadequate treatment New infection