1. Kelley Bemis Use of automated testing in syphilis diagnosis and its impact on surveillance – Connecticut, 2010 CDC/CSTE Applied Epidemiology Fellowship STD Control Program Connecticut Department of Public Health kelley.bemis@ct.gov

2. Background Graph: Together We Can SEE: The National Plan to Eliminate Syphilis, CDC, 2006 National Plan to Eliminate Syphilis implemented

3. Primary and Secondary Syphilis Cases - 2002 - 2010 National elimination plan reframed

4.   Crucial for syphilis elimination Identify infectious patients (laboratory confirmed) for partner notification Identify outbreaks and target interventions   Mainly laboratory reporting Labs must report positive tests in 48 hours Mail reports to DPH Syphilis Surveillance Understanding laboratory testing is necessary for accurate surveillance

5.   Usually two serologic tests   Non-specific test e.g. rapid plasma reagin test (RPR), Venereal Disease Research Laboratory test (VDRL) Detects antibodies against host lipoidal antigens Indicates active infection Inexpensive, simple, manual   Specific test e.g. T. pallidum particle agglutination (TPPA), fluorescent treponemal antibody absorption assay (FTA-ABS) Detects antibodies against treponemal antigens Indicates infection, past or present Syphilis Diagnosis

6. Traditional Screening Algorithm Syphilis unlikely + - Syphilis + - Non-specific test (RPR or VDRL) Specific test (TPPA or FTA- ABS)

7.   One positive doesn’t confirm infection Surveillance must monitor for two positives   Non-specific titers vary with age and stage of infection Surveillance must consider past test results and likelihood of infectiousness Challenge for Surveillance #1 Positive test ≠ Active infection

8. Challenge for Surveillance #2 Photo credit: Reverse Sequence Syphilis Screening Webinar, CDC, 2011  Treponemal EIAs and CIAs gaining popularity  More expensive but less manual labor needed  Still can’t distinguish between active and past infection A shift in testing paradigm: Automated treponemal tests for screening

9. Reverse Sequence Screening Algorithm + Syphilis - Specific test (TPPA) Syphilis (old or new) + EIA or CIA Non-specific test (RPR or VDRL) + Syphilis unlikely - Syphilis unlikely (or do another specific test) - Not identified with traditional algorithm 1.False positive EIA or CIA 2.Previously treated syphilis 3.Early primary syphilis

10. Challenge for Surveillance #2   Increased testing volume   New questions for surveillance How should EIAs and CIAs be reported? Should discordant results be investigated?   Increased DPH workload

11. Objectives  Determine type and volume of syphilis testing performed by Connecticut laboratories  Determine if current surveillance procedures adequately monitors reported tests for infectious cases To conduct a laboratory-focused evaluation of syphilis surveillance in Connecticut

12. Methods, Part 1 Laboratory Survey  Web survey emailed to all hospital and commercial labs in Connecticut (n=30) Number of tests performed in 2010 Testing algorithm Reporting practices  Responses analyzed with descriptive statistics

13. Methods, Part 2 Laboratory Audit  Requested records from two commercial laboratories All patients with a positive test in 2010  Compared against records in state’s surveillance database  Investigated selection of tests missing from state’s database

14. Laboratory Survey Results  30 of 30 (100%) labs completed the survey  28 of 30 (93%) perform syphilis testing  Over 196,700 screening tests performed in 2010

15. Uptake of Automated Tests

16. Referring Samples is Common

17. Reporting Results

18. Laboratory Audit Results Lab B  Screens with an EIA  Confirms all +’s with RPR and TPPA  RPR and TPPA reported  372 (29%) of 1299 positive reportable tests were not in the state’s database Lab A  Screens with a VDRL  Confirms with a FTA- ABS  RPR and FTA-ABS reported  693 (56%) of 1241 positive reportable tests were not in the state’s database

19. Laboratory Audit Results Lab B All patients with both RPR and TPPA missing (n=13) Lab A Random sample (n=35 patients) representing different months, tests, and titers  Small sample of missing tests investigated from both labs  Most patients did not merit field investigation  We concluded that entry into state database is not consistent for these tests

20. Conclusions  Uptake of automated tests is moderate, but increasing  Automated testing algorithms are variable  Referring specimens is common  Labs do not always report both types of tests used for diagnosis  Standard protocols for entering lab tests do not exist or are not enforced

21. Recommendations  Create protocols for entering tests into the surveillance database All non-specific tests are entered Treponemal results may be entered only once Negative tests will be entered if reported

22. Recommendations  Establish provisional procedures for monitoring EIA/CIA’s and discordant results EIA/CIA’s do not need to be reported unless a manual treponemal test was not performed Discordant results will not be investigated

23. Recommendations  Offer training on interpretation of EIA/CIA’s Internal meetings with DPH Disease Intervention Specialists (DIS) Newsletters to local health epidemiologists and clinicians

24. Recommendations  Offer training on reporting requirements to laboratories Newsletter to Laboratory Response Network

25. Acknowledgments  Virginia Kristie, MT ASCP  Mark Lobato, MD  Lynn Sosa, MD  Connecticut laboratories This study was supported in part by an appointment to the Applied Epidemiology Fellowship Program administered by the Council of State and Territorial Epidemiologists (CSTE) and funded by the Centers for Disease Control and Prevention (CDC) Cooperative Agreement Number 5U38HM000414.

26. Extra Slides

27. Reporting of Referral Samples  From the OLC-15 Reporting Form:  From the Public Health Code:

28. Test Sensitivity and Specificity Credit: Seña, A.C., White, B.L. & Sparling, P.F. Novel Treponema pallidum Serologic Tests: A Paradigm Shift in Syphilis Screening for the 21st Century. CID 51, 700-708 (2010).

29. EIA/CIA Algorithms in Connecticut EIA CIA RPR TPPA + & + + + RPR - TPPA RPR & EIA x2 - TPPA

30. Sero-reactivity in Syphilis Tests Credit: Peeling et al. / Bulletin of the World Health Organization / 2004 / Vol. 82 / No. 6 via CDC Reverse Sequence Screening Webinar