Missed Gonorrhea Infections by Anatomic Site among Asymptomatic Men who have Sex with Men (MSM) Attending U.S. STD Clinics, KC Mahle 1, DJ Helms 1, MR Golden 2, LE Asbel 3, T Cherneskie 4, B Gratzer 5, CK Kent 1,6, JD Klausner 6, CA Rietmeijer 7, A Shahkolahi 8, E Weckerly 9, HS Weinstock 1 1 Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA 2 Public Health, Seattle and King County, Seattle, WA 3 Philadelphia City Dept. of Public Health, Philadelphia, PA 4 New York City Dept. of Public Health, New York, NY 5 Howard Brown Health Center, Chicago, IL 6 San Francisco Dept. of Public Health, San Francisco, CA 7 Denver Public Health, Denver, CO 8 Whitman Walker Clinic, Washington DC 9 Legacy Clinic, Houston, TX

CDC Gonorrhea (GC) Screening and Diagnostic Testing Guidelines for MSM Annual GC screening for MSM: –Urethral test: insertive sex –Rectal test: receptive anal sex –Pharyngeal test: receptive oral sex Perform screening regardless of reported condom use Screen every 3-6 months for higher risk MSM Use culture or a test cleared by the FDA or locally verified Workowski K, Berman S. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines MMWR Morb Mortal Wkly Rep. 2006; 55:1-94.

Objectives 1) Determine the proportion of GC infections that were asymptomatic at each anatomic site 2) Estimate the proportion of GC infections at each anatomic site that remain undiagnosed

Methods (1) Data from a sentinel surveillance project (MSM Prevalence Monitoring Project) – Purpose: assess prevalence and trends in STDs, HIV, and risk behaviors among MSM and inform prevention and control efforts – Demographic, clinical, and behavior data are collected as part of routine care 89,488 visits from 10 STD clinics/Gay Men’s Health clinics in 8 cities – Chicago, Denver, Houston, New York City, Philadelphia, San Francisco, Seattle, and Washington D.C.

Methods (2) January 2002 – December 2006 and MSM aged years GC tests used: culture, NAATs, and nucleic acid hybridization probes Unit of analysis: clinic visit City-specific medians and ranges were calculated

Proportion* of visits where gonorrhea tests were performed and positivity, * City-specific median

MSM Population Flowchart Unexposed Undiagnosed Infections MSM Visits (n = 89,488) Asymptomatic visits (48.3%) Not Tested Exposed Tested Symptomatic visits (51.7%)

Proportion* of asymptomatic and symptomatic gonococcal infections by anatomic site, Urethral 93% 7% 74% Rectal Pharyngeal 26% 89% 11% * City-specific median

Proportion* of asymptomatic MSM visits tested where an exposure was reported, Large variations across clinics * City-specific median

Positivity* of GC by anatomic site among asymptomatic MSM, No. of Visits Among Not Tested Exposed Positivity Among Tested Undiagnosed Infections * City-specific median

Estimated proportion* of GC infections undiagnosed among asymptomatic MSM, Large variations across clinics * City-specific median

Limitations Assumed infections were equally common in tested and untested groups Results reflect MSM in STD clinics/Gay Men’s Health Clinics Medical records and testing practices not standardized across all clinics Evaluated MSM visits, not individual MSM

Conclusions Positivity among asymptomatic MSM: –Rectal Infection > Pharyngeal Infection > Urethral Infection Majority of gonorrhea infections at non-genital sites are asymptomatic Substantial proportion of asymptomatic rectal and pharyngeal GC infections remain undiagnosed

Lack of knowledge of asymptomatic nature of non-genital infections Failure to perform risk assessments Limitations of laboratory testing –Culture Technique is labor intensive Availability of culture inadequate –Nucleic Acid Amplifications Tests (NAATs) Not FDA-approved for use on non-genital specimens Local verification studies of non-genital NAATS necessary Barriers to GC screening

Conduct routine GC screening for sexually active MSM visiting STD clinics –Screen based on behavior, not symptoms alone Perform STD/HIV risk assessments –Gender and number of partners –Types of sex: oral receptive, anal receptive, or insertive (anal, vaginal, or oral) Encourage provider-focused education –CDC STD Treatment Guidelines –Prevalence of asymptomatic infection Increase availability of diagnostic tests Implications for Programs, Policy, and Research

Acknowledgements Seattle (Public Health – Seattle King County): Matthew Golden Fred Koch Chicago (Howard Brown Health Center): Beau Gratzer DC (Whitman Walker Clinic): Akbar Shahkolahi Bruce Furness Mike Smoot Celestin Hakiruwizera Philadelphia (City Dept. of Public Health): Lenore Asbel Melinda Salmon New York City (Dept. of Health): Tom Cherneski San Francisco (Dept. of Public Health): Kyle Bernstein Jeff Klausner Bob Kohn Denver (Denver Public Health): Kees Rietmeijer Dean McEwen Theresa Mickiewicz Houston (Legacy Clinic): Ed Weckerly Thomas Taylor Dennis Watson CDC: Donna Helms Charlotte Kent Jim Braxton Hillard Weinstock The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention

Additional Slides

Next Steps…. Adjust estimates to reflect risk of co- infection at other anatomic sites –Assumed rectal GC occurs in an equal proportion of ASX persons tested and not tested As a result, adjust distribution of undiagnosed infections in a manner that is proportional to the risk of co-infection observed in the fully tested Determine predictors of not being tested (i.e., age, race, facility type, year, type of test) using logistic regression

Derivation of the estimate Calculated # of visits in Not Tested Group by anatomic site Multiplied # of visits in Not Tested Group by positivity in Tested Group for each anatomic site, Subtracted infections would have been identified as missed, if an infection was diagnosed at another anatomic site for that visit Divided # of estimated missed infections in Not Tested Group by # of missed infections in Tested and Not Tested Groups for each anatomic site in ASX MSM not tested at all reported sites of exposure

Factors Potentially Affecting the Estimate Under-estimation: –Majority of GC tests are culture & not as sensitive –A proportion of exposures are not reported or documented, causing underestimation of results Over-estimation: –Majority of visits limited to new problem visits, however this could not be done for all sites and repeat visits in a short time period could have caused a slight over-estimation

Distribution of Reported Exposures among Asymptomatic MSM Urethral only7.4% Rectal only0.6% Pharyngeal only1.0% Urethral and rectal2.8% Urethral and pharyngeal25.2% Rectal and pharyngeal0.6% All 3 sites62.5%

Distribution of gonorrhea by anatomic site, among MSM, STD clinics, * Overall infection where gonorrhea testing was done at all 3 anatomic sites (n = 28,901 visits) Type(s) of infectionOverall GC infection (n = 4,940)* No. CitiesnMedian % of visitsRange Urethral only ( ) Rectal only ( ) Pharyngeal only ( ) Rectal and urethral ( ) Rectal and pharyngeal ( ) Urethral and pharyngeal ( ) All 3 sites ( )

Distribution of gonorrhea by anatomic site, among asymptomatic MSM, STD clinics, Type(s) of infectionOverall GC infection (n = 1,572)* No. CitiesnMedian % of visitsRange Urethral only6826.2( ) Rectal only ( ) Pharyngeal only ( ) Rectal and urethral4191.1( ) Rectal and pharyngeal ( ) Urethral and pharyngeal4191.4( ) All 3 sites2171.2( ) * Overall infection where gonorrhea testing was done at all 3 anatomic sites (n = 15,111 visits)

NAATs Advantages NAATs have essentially replaced bacterial culture for the diagnosis of gonococcal and chlamydial urogenital infections in both men and women. –High sensitivity and specificity –Use of non-invasively obtained specimens (e.g., urine), ease of provider collection of specimens for testing, and feasibility of patient self-collected specimens (e.g., vaginal swabs). Recent research demonstrated the reliability of NAATs using self-collected rectal specimens for screening in non-clinical settings.

Number of gonorrhea tests and number of positive tests in men who have sex with men, STD clinics, Note: The bars represent the number of GC tests at all anatomic sites (pharyngeal, rectal, and urethral) each year. The scales on the left and right axis differ. The bar graphs use the scale on the left. The line graphs use the scale on the right.

Syphilis serologic reactivity among men who have sex with men, STD clinics, 1999–2006 *Data not reported in Titer data not reported in 2004 or Note: Seroreactivity was based on nontreponemal tests results. All sites used the Rapid Plasma Reagin (RPR) test, with the exception of San Francisco where the Venereal Disease Research Laboratory (VDRL) test was used and Seattle where the type of test was changed from VDRL to RPR in *

City-specific median number of HIV tests and positivity among men who have sex with men, STD clinics, 1999–2006 *Excludes persons previously known to be HIV-positive. Note: The bar graph uses the scale on the left. The line graph uses the scale on the right.

Status of Tests Rectal & pharyngeal CT & GC – previously verified nucleic acid amplification test (NAAT) (LCx, Abbott Laboratories; ProbeTec, BD Diagnostics; or Aptima, Gen-Probe). NAATs approved for use for Labcorp specimens Tests for gonorrhea included culture, NAATs, and nucleic acid hybridization tests (DNA probes). Tests for chlamydia included culture, NAATs, DNA probes, or direct fluorescent antibody tests (DFAs).

Summary Rectal infections are more common than urethral infections. About 85% of rectal infections are asymptomatic & would be missed without screening. More than 75% of rectal infections have no concomitant urethral infection. About 80% of rectal CT infections have no concomitant rectal GC infection. Pharynx is most common site of GC infection.

HIV and Rectal Infections Majority of incident HIV infections among MSM. Most HIV infections acquired through receptive anal sex. While HIV positive men are at greater risk for rectal infections, the majority of rectal infections are in HIV negative men. Rectal infections might contribute to 10% of recent HIV infections Rectal screening & treatment might be an effective bio-medical HIV prevention strategy & needs further study.

Impact of Rectal Screening Rectal screening & treatment is likely the most efficient way to control the role STDs play in HIV acquisition in United States.