1. Region I Advisory Board Meeting Wells Beach, ME June 9, 2008 Use and Verification of STD Nucleic Acid Amplification Tests for non-FDA Cleared Clinical Specimens

2. Presenter: Sally Liska, DrPH Director, San Francisco PH Lab sally_liska@sfdph.org “ From Tommy Bahama [Levi Strauss] to LL Bean”

3. Background: San Francisco Public Health Laboratory Local PH Lab – support Communicable Disease programs (STD, HIV, TB, etc.) Methods – microbiology, virology, serology, molecular diagnostics Process > 100,000 specimens/yr from DPH clinics, specialty clinics, jails, NGO clinics, “events”, etc.

4. Hx of CT/GC Lab Testing at the SFDPH Lab A. Culture for N. gonorrhoeae B. Nucleic Acid Amplification (NAAT) Ligase Chain Reaction {LCR} – Abbott; 1995 Strand Displacement Amplification {SDA} – Becton Dickinson; 2001 Transcription Mediated Amplification {TMA} – Gen-Probe; 2004 Polymerase Chain Reaction {PCR}

5. Monthly STD stats – SFDPH Lab STD NAAT Testing by Source; April, 2008 N = 5,000 Cervical/ Vaginal12 % Urethral/ Urine45 % Rectal20 % Oropharyngeal22 %

6. Why Test Rectal & Oropharyngeal Specimens Reduce acquisition and transmission of STD agents (Chlamydia, Gonorrhea, HIV) Rectal infections can cause proctitis and increase risk of HIV infection CDC recommendations for MSM –  GC: annual screening of anatomical sites w/ possible exposure  CT: annual screening for urethral and rectal infection

7. NAAT’s vs. Culture – Pharyngeal Gonorrhea LCR +LCR -TOTAL Culture Positive 819 Culture Negative 14177191 TOTAL22178200

8. Performance Characteristics Pharyngeal Gonorrhea Sensitivity Specificity CULTURE 47.4 % 100 % LCR 94.7 % 97.8 % Page-Shafer et al in CID, 2002; 34:173-6

9. How Prevalent in Non-genital Sites?

10. Symptomatic vs. Asymptomatic Infection

11. What if we didn’t sample these sites? CT (n = 574)GC (n = 785) Identified47 %36 % Non-identified53 %64 % From Kent et al; CID 2005:41

12. What About Women? When to do rectal & pharyngeal screening in women, what are the indicators? 1.HRSA recommends screening HIV + women (by culture) 2.Medical indications – risk of reinfection if not treated for (rectal) infection? 3.PH indications – prevalence for these sites in women largely unknown

13. Use of NAAT’s for R & Ph specimens PRO’s More sensitive than culture More universal than CT culture Faster turn around time Can be automated CON’s May be more expensive NAAT’s not approved for these sites by FDA

14. Performance of NAATs on 1,110 Oropharyngeal Swab Specimens Test Test Sensitivity (%) Specificity (%) CT: Culture Culture44.4100 AC2 AC2 10099.8 SDA SDA 66.7100 GC: Culture Culture 40.4100 AC2 AC284.399.4 SDA SDA71.999.5

15. Performance of NAAT’s on 1,110 Rectal Swab Specimens Test Test Sensitivity (%) Specificity (%) CT: Culture Culture26.5100 AC2 AC2 92.699.6 SDA SDA 63.2100 GC: Culture Culture 43.2100 AC2 AC293.299.7 SDA SDA78.499.9

16. CLIA ’88 Federal regulation w/ oversight on clinical labs – Dx, Rx & prevention of disease Section 493.1213 pertains to requirement for Verification of Method Performance for: –In-house developed method –Modification of a manufacturer’s procedure –Method not cleared by the FDA

17. Verification A 1-time process completed before the test is used for patient testing. Requires determination of the test performance characteristics – ▪ Sensitivity▪ Reportable range ▪ Specificity▪ Reference range ▪ Precision▪ Other characteristics ▪ Accuracy required for test performance From Cumitech 31; ASM press 1997

18. Verification Protocol Purpose of test – e.g. screening for R GC Write an SOP – pre to post-analytical testing Procure specimens – – 20 Positive – 50 Negative Set acceptability criteria Statement of findings w/ regard to implementation – document!

19. Options Do a VERIFICATION of your NAAT Regionalize testing service Send specimens out to commercial lab Reimbursement - –MediCal will reimburse for testing multiple sites

20. Acknowledgements SFDPH Diane Campbell, Leah Rauch & lab staff Charlotte Kent, Dr. Jeff Klausner & City Clinic clinicians UCSF Julius Schachter & Jeanne Moncada CA STD Control Drs. Gail Bolan & Chris Hall CDC – Dr. John Papp Manufacturers