1. The Changing Paradigms of Who, Where, and How to Screen for Chlamydia Charlotte A. Gaydos, MS, MPH, DrPH Professor, Division of Infectious Diseases Johns Hopkins University Baltimore, Maryland Chlamydia Symposium Chlamydia: The Good, the Bad, and The Promising Marrakesh IUSTI May 9-12, 2016

2. Disclosures I have received funding for research grants and/or have been a lecturer for Becton Dickinson, Gen-Probe Hologic, Abbott Molecular, Siemens Health Care Diagnostics, Cepheid, and Quidel

3. Chlamydia trachomatis is a highly prevalent STI worldwide and screening is needed in order to control the epidemic of undiagnosed and untreated infections A paradigm shift is needed as new recommendations, places to test, and new diagnostic tests become available Background Estimated Prevalence of Sexually Transmitted Infections in the World (Total 2,993,200,000)

4. Discuss new recommendations for whom to screen based on age and sexual preference WHO Review use of NAATs and non-genital specimens, such as rectal and oral-pharyngeal samples HOW Examine use of non-invasive specimen types available and screening outside a clinic WHERE Assess how of point-of-care (POC) tests for chlamydia allow opportunities to enable patients to be immediately treated according to an exact diagnosisHOW Objectives

5. Who Shall We Screen? European Guidelines: Indications for laboratory testing (Level of evidence IV; Grade C recommendation). Risk factor(s) for C. trachomatis infection and/or other STI (age<25 years, new sexual contact in the last year, more than one partner in the last year. Symptoms or signs of urethritis in men. Cervical or vaginal discharge with risk factor for STI. Acute epididymo-orchitis in males aged <40 years or w/ risk factors for STI. Acute pelvic pain and/or symptoms or signs of PID. Proctitis/proctocolitis according to risk

6. Purulent conjunctivitis in a neonate or adult. Atypical neonatal pneumonia. Persons diagnosed with other STI. Sexual contact of persons with an STI or PID. Termination of pregnancy. Any intrauterine interventions or manipulations Who Shall We Screen?

7. September 2014** Chlamydia Gonorrhea screening: women The USPSTF recommends screening for chlamydia in sexually active women age 24 years or younger and in older women who are at increased risk for infection. B September 2014** Sexually transmitted infections counseling The USPSTF recommends intensive behavioral counseling for all sexually active adolescents and for adults who are at increased risk for sexually transmitted infections. B LeFevre ML. Screening for Chlamydia and Gonorrhea: Annals of internal medicine. Sep 23 2014.

8. Who Shall We Screen? Women: Sexually active women < 25 years of age Sexually active women aged 25 years & older at increased risk Retest approximately 3 months after treatment Pregnant Women: All pregnant women under 25 years of age Pregnant women, aged 25 and older if at increased risk Retest in 3rd trimester for women < 25 years of age or at risk Pregnant women with chlamydial infection should have a test- of-cure 3-4 weeks after treatment and be retested within 3 months Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015.

9. Who Shall We Screen? Men: Consider screening young men in high prevalence clinical settings or in populations with high burden of infection (e.g. MSM) Men Who have Sex With Men (MSM): At least annually for sexually active MSM at sites of contact (urethra, rectum) regardless of condom use Every 3 to 6 months if at increased risk Persons with HIV: For sexually active individuals, screen at first HIV evaluation, and at least annually thereafter More frequent screening for might be appropriate depending on individual risk behaviors and the local epidemiology

10. Discuss new recommendations for whom to screen based on age and sexual preference WHO Review use of NAATs and non-genital specimens, such as rectal and oral-pharyngeal samples HOW Examine use of non-invasive specimen types available and screening outside a clinic WHERE Assess how of point-of-care (POC) tests for chlamydia allow opportunities to enable patients to be immediately treated according to an exact diagnosisHOW Objectives

11. CDC Recommendations for the Laboratory- Based Detection of Chlamydia trachomatis and Neisseria gonorrhoeae — 2014 NAATS are recommended for genital infections  Vaginal swabs for women  Urine for men  Endocervical/female urine OK  Self-collected approved NAATs recommended for rectal and oropharyngeal infections (not FDA cleared) Papp JR, Schachter J, Gaydos CA, Van Der Pol B. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae- 2014. MMWR 2014;63(RR-02):1-19.

12. How Shall We Screen? All 5 commercial companies who sell NAATs have approval for self- collection of vaginal swabs and urines as well as clinician-collection of cervical swabs. How does the clinician decide which sample type to submit for testing? Let’s look at some data

13. Clinician Collected vs. Self- Collected Vaginal Swabs: Aptima

14. Patient-Collected Vaginal Swab ACT (pkg. insert) Asymptomatic: Sens 98.4%; Spec 95.6% Clinician Collected Vaginal Swab ACT (pkg. insert) Symptomatic: Sens 96.5% Spec 95.3% Asymptomatic: Sens 98.4% Spec 94.5% Clinician Collected vs. Self- Collected Vaginal Swabs: Aptima Vaginal swab specimens allowed sensitive and specific detection of CT and GC in the APTIMA assays Vaginal swabs identified as many infected patients as endocervical swabs and more than FCUs Schachter JCM 2005

15. Clinician Collected vs. Self- Collected Vaginal Swabs CT: m2000 Performance of the Abbott RealTime CT/NG for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Gaydos et al. JCM, 48:3236–3243, 2010 No statistical difference Clinician collected Sym92.5% Asym87.2% Self-collected Sym94.7% Asym84.8%

16. Vaginal Swabs CT Comparison: ProbeTec Taylor et al. JCM 38:603-609, 2011 Clinical Evaluation of the BD ProbeTec™ Chlamydia trachomatis Qx Amplified DNA Assay on the BD Viper™ System With XTR™ Technology

17. Van Der Pol STD 40:247-250, 2013 Cobas 4800

18. Distribution of positive results by sample type. Chlamydia resultsVan Der Pol STD 40: 247-250 2013 CT 248 detected Vag 232 + Vag 16 - Cobas 4800

19. Results CT/NG 1,722 female & 1,387 males Xpert CT/NG vs. Patient Infected Status SpecimenSensitivitySpecificity CT Cervical97.4%99.6% CT Vaginal98.7%99.4% CT Female Urine97.6%99.8% NG Cervical100% NG Vaginal100%99.9% NG Female Urine95.6%99.9% CT Male Urine97.5%99.9% NG Male Urine98.9%99.9% Gaydos et al. J Clin Microbiol. 51:1666-1672, 2013

20. STD Clinic Collection Aptima Percent Positivity according to infected patient status for chlamydia 11.1% (36/324) N= 319 cervical swabs; 322 self-administered vaginal swabs (SAS); 324 urines Sensitivity (%) Specificity (%) Gaydos et al STD 2009

21. NAATs recommended for rectal and oropharyngeal infections (not FDA cleared) Labs must perform own verification/verification studies Rectal and Oropharyngeal Swabs

22. Proportion of Infections Detected by Rectal or Genital Sampling Van Der Pol, BASHH 2012

23. Discuss new recommendations for whom to screen based on age and sexual preference WHO Review use of NAATs and non-genital specimens, such as rectal and oral-pharyngeal samples HOW Examine use of non-invasive specimen types available and screening outside a clinic WHERE Assess how of point-of-care (POC) tests for chlamydia allow opportunities to enable patients to be immediately treated according to an exact diagnosisHOW Objectives

24. Where Shall We Screen? Standard: STD/STI Clinics GUM Clinics Hospital Clinics Emergency Departments Primary Care Doctors Adolescent Clinics High School Clinics College Clinics New venues to recruit and screen: Internet Home Health Fairs Vans and Privacy Shelters Pharmacies

25. Internet: www.iwantthekit.org June 2004- April 2016www.iwantthekit.org FEMALE Vaginal (N =6900) (2004) CT: prevalence 7.05% GC prevalence 0.86% TV prevalence 6.5% FEMALE Rectal (N = 1198) (2009) CT: prevalence 7.10% GC prevalence 0.92% TV prevalence 5.85% MALE Penile (N = 3700) (2006) CT: prevalence 7.82% GC prevalence 0.74% TV prevalence 2.38% MALE Rectal (N = 769) (2009) CT: prevalence 7.28% GC prevalence 4.16% TV prevalence 0.65%

26. Am J Public Health. 2014;104:2313– 2320. Results. During a 3-month period, 217 women aged 18 to 30 years enrolled; 67% returned the kit. Of these, 92% viewed their results online. STI prevalence was 5.6% (chlamydia and trichomoniasis). All participants with STIs received treatment either the same day at a pharmacy (62%) or within 7 days at a clinic (38%). Among participants completing follow-up surveys, 99% would recommend the online eSTI system to a friend, and 95% preferred it over clinic-based testing within a study.

27. STD 42:13-19, 2015 STD 38:815-820 2011

28. Where: Vans, Health Fairs, & Privacy Shelters Pittman et al. Patient acceptability and feasibility of self-collecting genital samples for Chlamydia and gonorrhea testing in community settings using privacy shelters SAHM 2016 Among 27 men and 58 women 8 other gender, a majority reported self-sampling in a privacy shelter as “very acceptable” Hess EA, et al. Feasibility and acceptability of point-of-care testing for sexually transmissible infections among men and women in mobile van settings. Sexual Health. 12:71-72, 2015. Providing mobile point-of-care and near-patient STI testing to the general population is feasible and acceptable. 42 tested Cincinnati Children's Hospital Medical Center

29. Where Shall We Screen? Pharmacies? Retail Clinics, Academic Thought Leaders & Diagnostic Technology Teams to Share Opportunities for POC Testing According to a recent report by Accenture, nearly 3,000 retail health clinics are expected by 2017. Meanwhile, 95% of the nation's 60,000 pharmacies are providing immunizations Consumers see their local pharmacy, a place traditionally reserved for medications and greeting cards, as a stop for acute care and chronic disease management. Currently, about 18% of pharmacies hold a CLIA waiver allowing them to perform diagnostic and screening tests. Given the convenient locations and hours as well as the trust consumers already have in their pharmacists, there remains huge opportunity for growth.

30. Discuss new recommendations for whom to screen based on age and sexual preference WHO Review use of NAATs and non-genital specimens, such as rectal and oral-pharyngeal samples HOW Examine use of non-invasive specimen types available and screening outside a clinic WHERE Assess how of point-of-care (POC) tests for chlamydia allow opportunities to enable patients to be immediately treated according to an exact diagnosisHOW Objectives

31. A ffordable by those at risk of infection S ensitive few false negatives S pecificfew false positives U ser-friendlysimple to perform: 3-4 steps, minimal training R apid and Robust rapid: enable treatment at first visit robust: no refrigerated storage E quipment-free easily collected non-invasive specimens D elivereddelivered to end-users http://www.who.int/std_diagnostics/about_SDI/priorities.htm ASSURED Criteria for POC

32. POC Tests for STIs POC tests are desired by clinicians and patients Many are not yet accurate enough or able to be performed in a short period of time Promising NAAT POC tests are in the pipeline GeneXpert (FDA: near patient now; faster coming) Atlas Genetics(promising reports; CE marked) Many Others Coming

33. Needs Assessment of Clinicians: Build Your Own Test Hsieh Y-H et al. Plos One vol 6, issue 4, e19263, 2011. Hsieh Y-H et al. Point of Care 11:126-129, 2012 For which organisms do Clinicians want a POC test? (Most say chlamydia) How sensitive?; (most important -90-99%) How specific? (99%) How fast does it have to be? (-20 min) Forced Choice Questions used in a survey with multivariate analysis What about cost? (second most important- $20) What about equipment? (no or little equipment)

34. Willingness to wait is important Willingness to self-collect specimens is important Willingness to pay is important What about Patients Needs?

35. Patient Focus Group and Clinic Questionnaire about POC Tests (N =371) Specimen Type Preference Percent Cervical15.4% Vaginal50.9% Urine33.7% Willingness to Wait Percent 20 min59.0% 40 min20.8% 60 min10.8% 90 min9.4% Willingness to PayPercent $1046.6% $2031.0% $3010.8% $40 2.7% $50 8.9% Barnes et al. 2014 CDC STD Conf, Atlanta GA

36. POC tests for STIs: What do “end users” want? (N=58, 5 focus groups) ) Favorable POCTs (Rapid, Easy to read, Simple to use) Home testing acceptable – better privacy Clinic-based- definitive results & immediate treatment Barriers- cost and ability to read and perform tests Hispanic patients questioned home test reliability, wanted bi-lingual instructions Rompalo et al. Sexual Health 2013;10:541-545

37. STI: 2013; 89:88-89 Netherlands compared three CE-marked POC tests (one enzymatic and other two antigen tests) for diagnostic performance in a high CT-prevalence population (11%), compared with NAATs over 8-months The sensitivity of the tests was disappointing, and ranged from 12% to 27% in 772 women tested van Dommelen et al. Alarmingly poor performance in Chlamydia trachomatis point-of-care testing. Sex Transm Infect 2010;86:355–9. An ‘ASSURED’ POC test for chlamydia is yet to become available Currently available POC tests are limited by their performance and cost. Further studies are required to assess the ‘rapid test paradox’; patient and staff acceptability.

38. A New Near-Patient Model of Care Dean Street Express, London England Asymptomatic STI screening Walk in: 30 min on site Nurse-led service Better resource management Results within hours Immediate treatment

39. The Patient Experience Private self-check inProgrammed test request Sample transportFast sample processingAutomated results via textOnline booking for follow up Self collected sample Walk In No stigma Self-directed care Reducing human error Sample confidence No logistics Asympto. screening Quality of service Patient satisfaction

40. Potential to Impact Outcome Faster Results: From 183 hours to 4 hours Quicker Treatment: 80% reduction in time to treatment Reduced Waiting Time: From 2 hours to 32 minutes Less Patients Lost to Follow-Up: From 15.6% to 3% High Uptake: Monthly increase in testing ~600% Rated “Excellent” by 94% of users

41. Barriers to implementation of POCTs Financial viability Money for instruments and consumables Obtaining CLIA certificate Verifying/validating the new test Policies and procedures (training manuals) Operator training (recertification, proficiency) Getting results into the EMR (interface- $7K?) Space Work Flow Disruption Billing and Reimbursement

42. New guidelines for screening and treating individuals are available from professional organizations; NAATs are recommended Non-invasive sample types are approved by all 5 commercially- available NAATs; Approval for collection outside of clinic is needed Possible: health fair, pharmacy, recruitment via the Internet, and on mobile vans and in privacy shelters POC tests allow rapid diagnosis/treatment POC tests could potentially allow self-testing to reduce the incidence of chlamydial infections globally Conclusions: Who, Where, and How