1. Laboratory Issues in STD Testing From the Perspective of The Bureau of STD Control Jennifer Baumgartner, MSPH Preeti Pathela, DrPH Julia Schillinger, MD, MSc

2. Today’s talk Fluoroquinolone Resistance (QRNG) Anorectal NAATs for GC and Ct detection Selected results from the Bureau’s 2004 annual lab survey will be used as a context for discussion of the above key issues.

3. STDs Reportable to NYC DOHMH Syphilis (Treponema pallidum) Gonorrhea (Neisseria gonorrhoeae) Chlamydia (Chlamydia trachomatis) Chancroid (Haemophilus ducreyi) Lymphogranuloma venereum (Chlamydia trachomatis L1, L2, L3) Granuloma inguinale (Calymmatobacterium granulomatis) Non-gonoccocal urethritis Neonatal Herpes (any HSV positive test for an infant =<60 days old)

4. Annual Clinical Laboratory Survey Objectives –To determine current STD diagnostic testing methods provided to NYC residents –To monitor trends in STD testing –To monitor current laboratory compliance with citywide reporting mandates

5. Annual Clinical Laboratory Survey Methods –The NYC DOHMH Bureau of Sexually Transmitted Disease Control (BSTDC) surveyed clinical laboratories that were licensed to perform sexually transmitted disease (STD) testing by NYS –Survey instrument was a self-administered mail-in questionnaire to collect information for calendar year 2004.

6. Laboratories Sampled in 2004 Lab Survey 330 Laboratories did not perform STD Testing on NYC residents † 528 Laboratories Licensed by NYS DOH To perform STD testing* 132 (72%) Laboratories Located In New York State 6 Laboratories not on NYS DOH licensed list, but performed Testing on NYC residents in 2002 178 Laboratories licensed to Perform STD testing on NYS ‡ 102 (77%) Laboratories Located In New York City 30 (23%) Laboratories Located Outside New York City *Clinical laboratories currently holding a New York State (NYS) Department of Health (DOH) permit in at least one of the following categories: Bacteriology-General, Bacteriology-Gram Stains, Bacteriology-Other, Bacteriology-Restricted, Diagnostic Immunology- Services Serology, Diagnostic Immunology Donor Services Serology, Virology-Direct Detection, Virology General, Virology Herpes Group Viruses Only, Wet Mounts †Based on findings from 2002 Lab Survey. Includes one laboratory that had closed. ‡Includes NYS licensed laboratories that performed testing on NYC residents based on findings from 2002 lab survey or were not surveyed in 2002. 54% (96/178) Labs were surveyed in 2002, 46% (82/178) Labs were not surveyed in 2002. 184 Laboratories sent 2004 Lab Survey 52 (28%) Laboratories Located Outside New York State

7. Description of Respondents (n=172) Location: –All five New York City Boroughs 56% (96/172) Respondents located in NYC –Other states 57% (98/172) of 2004 respondents had responded to the 2002 survey 89% (80/90) of the 2002 respondents who perform testing STD testing on NYC residents responded to the 2004 survey.

8. Reporting Methods 2002 and 2004 Method of Reporting Percent of Labs Reporting 20022004 Electronically * 26%43% Mail † 50%23% Fax ‡ 2%3% Other Reporting10%12% * Labs reporting at least 1 STD electronically † Labs reporting at least 1 STD by mail and do not report electronically ‡ Labs reporting at least 1 STD by fax and do not report electronically or by mail

9. Gonorrhea Testing Results 58% (81/139) of laboratories indicated that they performed at least one type of gonorrhea testing in 2004: –NAATs – 17% (23/139) reported performing Nucleic Acid Amplification Tests (NAATs) –Dual gonorrhea/chlamydia probe was the most frequently performed test –Culture - 44% (61/139) of laboratories perform gonorrhea cultures –Urethral gram stain – 38% (53/139) indicated that they performed urethral gram stains (UGS)

10. Gonorrhea Testing Types * Labs reporting performance of test, may not have provided information for each of the above categories † Laboratories could report more than 1 test type Test Type*†No. of labs performing test Urethral gram stain38% (53/139) GC culture44% (61/139) DNA GC-only amplification 7% (10/139) DNA dual test (GC&Ct) amplification16% (22/139) DNA GC-only hybridization 7% (10/139) DNA Dual test (GC&Ct) hybridization19% (26/139) EIA 0% (0/139) Other 1% (2/139) - 49% (30/61) of laboratories performing GC culture tests also perform antimicrobial susceptibility testing.

11. Gonorrhea Antimicrobial Testing *Survey permitted labs to specify more than one class of antibiotic **Survey permitted labs to specify more than one method of antibiotic susceptibility testing Type of Antibiotic*No. of labs performing test Cephalosporins77% (23/30) Penicillins77% (23/30) Fluoroquinolones77% (23/30) Spectinomycin23% (7/30) Tetracyclines50% (15/30) Macrolides13% (4/30) Type of Testing**No. of labs performing test Disk Diffusion77% (24/30) Broth Microdilution 0% (0/30) E-test13% (4/30) Agar Dilution 3% (1/30) Other (Beta-lactamase)17% (5/30)

12. Anorectal and Oropharangeal Gonorrhea NAATs Testing Gonorrhea NAATs testing on anorectal specimens and oropharangeal specimens: –1% (1/139) of laboratories performed NAATs testing on anorectal specimens –1% (1/139) of laboratories performed NAATs testing on oropharangeal specimens

13. Fluoroquinolone-Resistant GC, NYC BSTDC Clinics, 1999-2005 YearNo. Specimens cultured GC No. GC (%) QRNG No. QRNG (%) 1999n/a*n/a0 2000n/a 4 200188,4003162(4)3(0.1) 200258,0472668(5)8(0.3) 200330,0941026(3)30(2.9) 2004n/a*608n/a48(7.9) 2005479 † n/a44(9.2) † *Data not available † There were 9 additional positive GC isolates that could not be AST’d.

14. Prevalence of NYC BSTDC Clinic QRNG, by Sex, 2005 Anatomic Site of Infection No. QRNGTotal GC(%) QRNG Males42402(10.4) Anal1967(23.9) Oral759(11.9) Urethral19276(6.9) Females277(2.6) Anal08(0.0) Oral015(0.0) Endocervical254(3.7) Total44479(9.2)

15. Gonorrhea Performing gonorrhea culture is an important surveillance tool, since it can aid the BSTDC in monitoring antibiotic resistance. Recently the CDC has recommended that fluoroquinolones not be used to treat gonorrhea infections in MSM. NYC DOHMH BSTDC has adopted these treatment guidelines and further recommends that providers who treat gonorrhea in non MSM men avoid fluoroquinolones, or if using fluoroquinolones, either perform culture or conduct follow-up testing to insure that the treatment given was effective 1. The BSTDC also recommends caution in using fluoroquinolones in women diagnosed with gonorrhea. 1 Centers for Disease Control & Prevention. Increases in Fluoroquinolone-Resistant Neisseria gonorrhoeae Among Men Who Have Sex with Men – United States, 2003 and Revised Recommendations for Gonorrhea Treatment, 2004. MMWR 2004:53:335-338.

16. Chlamydia Testing Results 37% (51/139) of labs perform at least one type of chlamydia testing: –NAATs – 19% (26/139) reported performing Nucleic Acid Amplification Tests (NAATs) –Dual chlamydia/gonorrhea probe was the most frequently performed test –34% (47/139) labs accept male urethral/urine specimens

17. Chlamydia Test Types * Labs reporting performance of test, may not have provided information for each of the above categories † Laboratories could report more than 1 test type Test Type*†No. of labs performing test Ct culture 8% (11/139) DNA Ct-only amplification10% (14/139) DNA dual test (Ct&GC) amplification16% (22/139) DNA Ct-only hybridization10% (14/139) DNA Dual test (Ct&GC) hybridization19% (26/139) DFA 6% (8/139) Serology 3% (4/139) EIA 5% (7/139) Other 1% (1/139)

18. Chlamydia NAATs Testing at Alternative Sites Chlamydia NAATs testing on: –anorectal specimens: 1% (1/139) –oropharangeal specimens: 1% (1/139) –neonatal eye specimens: 2% (3/139) –pulmonary specimens: 1% (2/139)

19. Lymphogranuloma Venereum 3% (4/139) of laboratories performed Lymphogranuloma Venerum (LGV) testing in 2004: –The 4 labs reported performing tests by: Amplification Culture IFA

20. Discussion Chlamydia anorectal NAAT Currently, NAAT not approved for use on anorectal or oropharyngeal specimens, however Laboratories that have performed local validation studies may conduct testing (e.g. San Francisco PHL) SF study using anorectal NAAT (Ct and GC) among men who have sex with men (MSM)* - 7.9% Ct NAAT- positive NYC Public Health Laboratory to validate commercial NAAT for Ct detection from anorectal specimens –Will be used routinely for STD evaluation in NYC STD clinics (~4,000 MSM/year reporting anorectal sex) –Detection and treatment reduces HIV transmission * Kent CK, et al., Clinical Infectious Diseases 2005;41:67-74

21. Discussion LGV in NYC LGV recognized among MSM in NYC in early 2004 –Proctitis (hemorrhagic and non-hemorrhagic) most common clinical presentation –MSM, most HIV co-infected Need to differentiate L-serovars of chlamydia from other serovars –Treatment regimen for LGV longer than for non-L serovars of Ct –Partner follow-up more intensive –Need for timely and sensitive LGV diagnostics lent urgency to developing anorectal NAAT capability Wadsworth Laboratory validated an in-house NAAT for anorectal testing, and developed a nested PCR to detect the L-2 serovar of C. trachomatis –>250 specimens submitted –~1/3 of anorectal specimens tested are Ct-positive, of genotyped specimens, 80% were L-2 (n=33) –Clinical syndrome does not differ between L-2 and non-L serovar * Kent CK, et al., Clinical Infectious Diseases 2005;41:67-74

22. Discussion Monitoring antimicrobial susceptibility in GC, NYC Currently, NYC gonococcal AST results reported nationally come only from STD clinic patients –‘GISP’ (Gonococcal Isolates Surveillance Project) Substantial number of NYC laboratories have culture and AST capacity Interest in collaborating to monitor resistance from broader sample?