Region I Laboratory UpdateCDC National Infertility Prevention Project

Boston, MassachusettsNovember 15, 2010

Richard Steece, Ph.D., D(ABMM)

Laboratory Consultant

CDC National Infertility Prevention ProjectDrRSteece@aol.com

Laboratory Update

1. CDC Laboratory Guidelines for

CT/GC and Syphilis

Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria

gonorrhoeae Testing

Recommendations from the expert consultation meeting

January 13-15, 2009

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

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

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

CDC Syphilis Testing Guidelines

Recommendations from the expert consultation meeting

January 13-15, 2009

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

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.

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

Treponemal ScreeningPROS• 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

Titer

NonreactiveNot syphilis (or early Not syphilis (or early

syphilis)syphilis)

Reactive

Treponemal TestFTA-ABS, TP-PA

ReactiveSyphilis - Treat

Non-Treponemal TestRPR, VDRL, TRUST

Traditional Testing Algorithm Using Non-Treponemal

Initial Screen

NonreactiveFalse positive

Non-Treponemal Test

Pope Infect Med 2004

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

A1Syphilis EIA or CLIATesting

Algorithm Using EIA or CLIA as Initial Screen

* Laboratory should report the results of all three assays (if applicable) within 7 days

Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

andSyphilis 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– Publish the entire revised laboratory guidelines

document as a Reports and Recommendations supplement in MMWR

• Targeted for late 2010

The End

Questions?