1. Region I Laboratory Update CDC National Infertility Prevention Project Boston, Massachusetts November 15, 2010 Richard Steece, Ph.D., D(ABMM) Laboratory Consultant CDC National Infertility Prevention Project DrRSteece@aol.com

2. Laboratory Update 1.CDC Laboratory Guidelines for CT/GC and Syphilis

3. Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Testing Recommendations from the expert consultation meeting January 13-15, 2009

4. Key Questions (CT/GC) Performance Characteristics – All culture and non-culture tests may generate false-positive and false-negative results – Nucleic acid amplification tests (NAATs) have superior performance to all other tests – Culture is still useful in certain circumstances GC susceptibility testing – Serology Should not be used for the Dx of non-LGV CT infections

5. Key Questions (CT/GC) Screening Applications – Vaginal swabs are the optimal specimen type for use with NAATs Vaginal swab and urine specimens are not intended to replace cervical exams and endocervical specimens for the Dx of female urogenital infections – Urine is the preferred specimen type for testing males with NAATs – NAATs have superior performance to culture for the detection of rectal CT and GC infections and for the detection of pharyngeal GC infections NAATs are not cleared for rectal and pharyngeal specimens by the FDA

6. Key Questions (CT/GC) Laboratory Confirmation – Routine repeat testing of NAAT positive specimens is not recommended for CT – Routine repeat testing of NAAT positive specimens is not recommended for GC unless there are a significant number of false-positive test results, in clinical studies, due to cross- reaction with non-gonococcal Neisseria species – Medico-legal issues (ASM Symposia 05-2010) Data supports the use of NAATs in adult cases of sexual abuse Limited data on the use of NAATs in cases involving children

7. CDC Syphilis Testing Guidelines Recommendations from the expert consultation meeting January 13-15, 2009

8. Key Questions (Syphilis) Direct Detection of T. pallidum (Tp) – Darkfield Microscopy – Immunostaining – Nucleic Acid Amplification Tests Congenital Syphilis – A reactive IgM test may be useful and should be used in conjunction with direct detection – A four-fold or greater ratio of neonatal to maternal titers is rarely useful Neurosyphilis – Neurosyphilis cannot be diagnosed serologically – The use of VDRL in evaluating CSF may still be worthwhile Serology

9. Serology Testing (Syphilis) Non-treponemal tests – RPR, VDRL, TRUST Treponemal tests – FTA-ABS, TP-PA – EIA, CLIA, Microsphere Point of Care tests – None available in U.S.

10. Non-Treponemal Screening PROS High Sensitivity Low cost Does not detect past infections Requires little equipment for testing Usually requires only one reflex test Useful for treatment monitoring CONS Lower specificity Labor-intensive Subjective results Manual data manipulations

11. Treponemal Screening PROS High Sensitivity High Specificity Objective results Automation / high throughput Interface with LIS CONS Cannot distinguish between active and previously treated disease Potential for over diagnosis and over treatment May require more resources for EPI/DIS investigations Specific, potentially costly instrumentation May require multiple reflex tests for resolving discrepants

12. Titer Nonreactive Not syphilis (or early syphilis) Reactive Treponemal Test FTA-ABS, TP-PA Reactive Syphilis - Treat Non-Treponemal Test RPR, VDRL, TRUST Traditional Testing Algorithm Using Non-Treponemal Initial Screen Nonreactive False positive Non-Treponemal Test Pope Infect Med 2004

13. A2 Quantitative Nontreponemal (i.e. RPR) A1- Negative for Syphilis antibodies A1+ A3 Treponemal Test that uses a different antigen or platform from A1 (i.e. TPPA, FTA) A1+ A2+ Consistent with Syphilis (past or current infection) A1+ A2- A1+ A2- A3+ Possible Syphilis infection; Requires further historical and clinical evaluation A1+ A2- A3- Unconfirmed EIA; Unlikely to be Syphilis; If patient is at risk for syphilis, re- test in 1 month A1 Syphilis EIA or CLIA Testing Algorithm Using EIA or CLIA as Initial Screen * Laboratory should report the results of all three assays (if applicable) within 7 days

14. Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria gonorrhoeae and Syphilis Testing Guidelines Next Steps – Proceedings from the Expert Consultation Meetings is available on the APHL website www.aphl.org/aphlprograms/infectious/std/Documents/CTGCL abGuidelinesMeetingReport.pdf www.aphl.org/aphlprograms/infectious/std/Documents/CTGCL abGuidelinesMeetingReport.pdf – Publish the entire revised laboratory guidelines document as a Reports and Recommendations supplement in MMWR Targeted for late 2010

15. The End Questions?