1. Advances in Trichomonas vaginalis Diagnostics and Research Barbara Van Der Pol, PhD, MPH University of Alabama at Birmingham School of Medicine

2. Disclosures  Honorarium, Speaking Fees or Research Support  Atlas Genetics  BD Diagnostics  Beckman Coulter  Cepheid  Great Basin Scientific  Hologic  Rheonix  Roche Molecular Diagnostics

3. Topics  Why test for Trich?  How should we test?  What’s on the way?

4. Background  2012 WHO estimates of incident STI in 2008  Chlamydia105.7 million4.1% ↑  Gonorrhea106.1 million21.0% ↑  Trichomonas276.4 million11.2% ↑

5. Regional variation in Trichomonas prevalence Newman L, et al. PLoS One, 2015

6. STI rates in the US

7. AWARE Study findings  Women attending 9 STD clinics in the US  Baseline and 6 month f/u  Of 245 (14.6%) positive at baseline, only 177 would have been tested by wet prep  109 were positive at 6 mo  Previous TV positive was the largest single risk factor RR 3.37 (2.35-4.83), p<.001 Alcaide ML, et al. STI 2016

8. Meta-Analyses of Pre-term Birth Outcomes Silver, BJ et. al. STD 2014

9. Effect of TV infection on risk of HIV acquisition By 30 mo, risk increases from 4%  17% P=.036 Mavedzenge SN, et al. STD, 2010

10. Effect of HIV infection on risk of acquiring TV infection By 30 mo, risk increases from 11%  24% P=.001 Mavedzenge SN, et al. STD, 2010

11.  Clinical manifestations  Wet prep microscopy  Rapid tests  Laboratory tests  Culture  Nucleic acid probe  Nucleic acid amplification What are the options?

12.  Discharge may be confused with other vaginal disturbances  Co-infections are common  pH is not reliable  Strawberry cervix is clear, but not common  Sensitivity - unknown Clinical Manifestations

13. Microscopy  Sensitivity – 50-60%

14.  Immunochromatographic  OSOM ® sensitivity – 80-90% Rapid tests

15. Culture  Sensitivity:60-75%  Time to results: 3-7 days

16.  Hologic Aptima TV assay detects rRNA  High throughput  BD TV Q x DNA-based assay  High throughput  BD MAX CT/GC/TV  Low-medium throughput  Cepheid Xpert TV DNA-based assay  Throughput depends on size of system purchased Nucleic Acid Amplification Tests

17.  Can be performed with sample used for CT/GC  Urine, vaginal and endocervical  Can detect nucleic acid in asymptomatic women  40-50% of infections may be asymptomatic! Advantages of NAAT

18. Comparison of diagnostic assays AssayEquipmentSample TypesNotes MicroscopyMicroscopeVag swabRequires motility and a clean microscope OSOMNoneVag swabCLIA waived so true POC Affirm VPIIIAffirm VPIII instrument Vag swabSymptomatic patients only; lab- based AmpliVueAmpliVue instrument Vag swabLab-based CultureIncubator; microscope Vag swab, urine sediment Lab-based XpertXpert instrument Vag or cervical swab; urine Lab-based TVQ x MAX BD Viper BD MAX Vag or cervical swab; urine High-complexity Aptima TVTigris or Panther Vag or cervical swab; urine High-complexity Adapted from Van Der Pol. J Clin Microbiol, 2016

19. Comparison (continued) AssayTime to resultCo-testingSensitivityCost Microscopy<5 minBV+$ OSOM15 minnone+++$$ Affirm VPIII<1 hBV++$$ AmpliVue<1 hnone++$$ Culture1-7 daysnone++$$ Xpert90 minCT/GC++++$$$$ TVQ x MAX <6 hCT/GC++++$$$ Aptima TV<6 hCT/GC++++$$$ Adapted from Van Der Pol. J Clin Microbiol, 2016

20. Assays on the near horizon  Instrument-dependent triplex NAATs  ~30 min to results  Instrument-free POC assays (mostly TV only)  Antigen capture LFA  NAATs  Disposable test materials  reduces costs  increases accessibility

21. Resistance?  Treatment failure that suggests resistance occurs  Reduced in vitro metronidazole susceptibility  Occurs in ~5-10% of isolates tested in the US  Does not correlate well with clinical outcomes  May be a function of the presence/absence of the TV virus and/or Mycoplasma hominis  Data from da Luz Becker (Infection, Genetics & Evolution, 2015) do not support this hypothesis  However, strain type may play a role in this association

22. Other aspects to think about  Infertility  Associations with tubal factor infertility  Associations with atypical spermatozoa and seminal fluid properties supported by in vitro studies  Cervical Neoplasia?  Pathogenesis mechanisms exist  Association with HPV persistence has been shown  Prostate disorders?  BPH  Prostate cancer

23. Rethinking the TV Diagnostics  Prevalence & long-term sequelae suggest TV control is warranted in some settings  Screening, regardless of symptoms makes sense in some settings  Wet prep is great as a primary screening tool  Some POC are useful if affordable  Treating partners is likely important

24. Thank You! Questions?