No conflicts of interest to disclose No FDA non approved use of medications STD Update GC/CT NAATs are not FDA approved for use as test of cure Carolyn Gardella, MD, MPH Associate Professor UW Dept OB/GYN Women s Health Update CME 2015 Objectives Transgender Care Upcoming changes to CDC STD Treatment Guidelines.. Due any day now Management of Transgender Populations NAATs for Trichomonas Alternative treatments for N.G. Treatment options for genital warts HPV counseling messages Role of Myocoplasma genitalium in cervicitis Transgenders are individuals whose gender identity differs from that which they were assigned at birth Transgender Men (FTM): female sex at birth based on appearance of genitalia Transgender Women (MTF): male sex at birth Transgenders are diverse Sex with men, women, both 1
35 yo MTF patient accessing health care for the first time. What is the most important testing for her? Pap smear HIV test Lipid panel Mammogram Transgender Women Highest HIV Prevalence in the US! 27.7% for all 56.3% for AA transgender women Majority have not had genital affirmation surgery so retain a functional penis Insertiveoral, vaginal or anal sex with men and women Herbst JH et al. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: a systematic review. AIDS and behavior. Jan 2008;12(1):1 17. Nuttbrock L et al. Lifetime risk factors for HIV/sexually transmitted infections among male to female transgender persons. J Acquir Immune Defic Syndr. Nov 1 2009;52(3):417 421. 24 year old FTM patient accessing care for the first time. What do you recommend? Lipid panel Pap smear HPV vaccine Mammogram Chlamydia screening Transgender Men Many still have vagina and cervix putting them at risk for bacterial STDs as well as cervical HPV and cancer. Some risky behavior but lower prevalence of HIV than transgender women. Sevelius J. "There's no pamphlet for the kind of sex I have": HIV related risk factors and protective behaviors among transgender men who have sex with nontransgender men. The Journal of the Association of Nurses in AIDS Care : JANAC. Sep Oct 2009;20(5):398 410. Reisner SL et al. A mixed methods study of the sexual health needs of New England transmen who have sex with nontransgender men. AIDS patient care and STDs. Aug 2010;24(8):501 513. 2
Trichomonas: Who would you test? 30 year old presents with vaginal discharge and itching 45 year old for well woman exam; asymptomatic; recently incarcerated 26 year old whose boyfriend was recently treated for trichomonas 50 year old with trichomonads noted on liquid based pap Risk Factors in Women Incarceration: 9 32% prevalence >40 years old: 11% Symptoms 70 85% of infected persons are asymptomatic Recent sexual contact Ginocchio CC et al. Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay. J Clin Microbiol. Aug 2012;50(8):2601 2608. Trichomonas: How would you test? Source? Wet Mount Pap smear Culture Trichomonas NAAT FDA +Test Point of Care Method Sensitivity Specificity APTIMA TV No RNA by transcription medicated amplification 95 100% 98 99% OSOM Trich Rapid Test Yes 10 min Antigen detection 71 99% 99 100% NAAT Point of care; Lab based Affirm VP III Yes 45 min Nucleic acid probe hybridization 63 93% 99.9 100% Schwebke JR, Hobbs MM, Taylor SN, et al. Molecular testing for Trichomonas vaginalis in women: results from a prospective U.S. clinical trial. J Clin Microbiol. Dec 2011;49(12):4106 4111. 3
Trichomonas Diagnosis Culture was gold standard Vaginal Secretions more sensitive than Urine Wet mount is most common Sensitivity: 44 80% Drops to 20% if delayed by 10 min Pap smear not accurate Nye MB, Schwebke JR, Body BA. Comparison of APTIMA Trichomonas vaginalis transcriptionmediated amplification to wet mount microscopy, culture, and polymerase chain reaction for diagnosis of trichomoniasis in men and women. Am J Obstet Gynecol. Feb 2009;200(2):188 e181 187. Trich Treatment Recommended Regimens Metronidazole 2 g orally in a single dose 84 98% cure rate OR Tinidazole 2 g orally in a single dose 92 100% cure rate Alternative Regimen Metronidazole 500 mg orally twice a day for 7 days *All sex partners should be treated at the same time to reduce reinfections. If needed, these regimens may be administered parenterally instead of orally. All persons with a known exposure to T. vaginalis infection should be treated routinely, with or without symptoms or a positive diagnostic test. Follow Up Important Refractory Trich Why? 17% rate of reinfection Consider re infection When? Re test within 3 months Can re test with NAAT as early as 2 weeks but why would you? Peterman TA et al. High incidence of new sexually transmitted infections in the year following a sexually transmitted infection: a case for rescreening. Annals of internal medicine. Oct 17 2006;145(8):564 572. Van Der Pol Bet al. Prevalence, incidence, natural history, and response to treatment of Trichomonas vaginalis infection among adolescent women. J Infect Dis. Dec 15 2005;192(12):2039 2044. Williams JA et al. Time from treatment to negative PCR results for C. trachomatis, N. gonorrhoeae and T. vaginalis National STD Prevention Conference; March 10 13, 2008, 2008; Chicago, IL. Resistance MTZ: 4 10% Tinidazole: 1% Try MTZ or T 500mg po bid x 7d Try MTZ or T 2 gm x 7 d Get help: CDC 404 718 4141; www.cdc.gov/std 4
21 yo requests STD testing at the end of unrelated visit CT Rates in King County What are your options for GC/CT testing? Skip it, she is likely low risk Do a pelvic and collect endocervical swab for culture Do a pelvic and collect vaginal swab for NAAT Have her collect a vaginal swab for NAAT Collect a first stream urine for NAAT http://www.doh.wa.gov/portals/1/documents/pubs/347 634 KingProfile12.pdf, accessed 3/13/2014 Age Specific CT Rates in King County GC Rates King County http://www.doh.wa.gov/portals/1/documents/pubs/347 634 KingProfile12.pdf, accessed March 13, 2014 http://www.doh.wa.gov/portals/1/documents/pubs/347 634 KingProfile12.pdf, accessedmarch 13, 2014 5
Age Specific GC Rates GC & CT Testing Nucleic acid amplification tests (NAATs) are the recommended test method. A self or clinician collected vaginal swab is the recommended sample type. Self collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. An endocervical swab is acceptable when a pelvic examination is indicated. A first catch urine specimen is acceptable but might detect up to 10% fewer infections when compared with vaginal and endocervical swab samples. An endocervical swab specimen for N. gonorrhoeae culture should be obtained and evaluated for antibiotic susceptibility in patients that have received CDCrecommended antimicrobial regimen as treatment, and subsequently had a positive N. gonorrhoeae test result (positive NAAT 7 days after treatment), and did not engage in sexual activity after treatment. CDC. Recommendations for the laboratory based detection of Chlamydia trachomatis and Neisseria gonorrhoeae 2014. MMWR, March 14, 2014, vol 63, No2 http://www.doh.wa.gov/portals/1/documents/pubs/347 634 KingProfile12.pdf, accessed 3/15/2014 CT Treatment GC DualTherapy Recommended Regimens Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days Alternative Regimens Erythromycin base 500 mg orally four times a day for 7 days OR Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days OR Levofloxacin 500 mg orally once daily for 7 days OR Ofloxacin300 mg orally twice a day for 7 days Recommended Regimen Ceftriaxone 250 mg in a single intramuscular dose (99.2%, 98.9% Pharynx) PLUS Azithromycin 1g orally in a single dose If ceftriaxone is not available: Cefixime 400 mg in a single oral dose Azithromycin 1 g orally in a single dose* PLUS *If azithromycin is not available or if the patient is allergic to azithromycin, doxycycline 100 mg by mouth twice daily may be substituted for azithromycin as the second antimicrobial. 6
Why Dual Therapy? Prevention of antibiotic resistance.. In 2007, emergence of fluoroquinolone resistant N. gonorrhoeae in the US prompted CDC to no longer recommend fluoroquinolones for treatment of gonorrhea, leaving cephalosporins as the only remaining class of antimicrobials recommended for treatment of gonorrhea Suspected Cephalosporin Failure Perform culture and susceptibility testing Consult a specialist for guidance in clinical management, and Report the case to CDC through state and local public health authorities. Cephalosporin resistance emerging in Asia and Europe; cefixime failures CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR. 4/13/2007 2007;56(14):332 336. 27 yo Noted Bumps on her Perineum HPV 6, 11 What is most likely diagnosis? Normal Variant Skin Tag Genital Warts Genital Herpes Do you need to biopsy? What are the treatment options? Do nothing Cryotherapy Surgical excision Imiquimod 3.75% qhs 7
Treatment Options HPV Counseling Podofilox 0.5% solution or gel BID x 3 d; may repeat q 4d x 4 Wart area <10cm2; no more than 0.5mL/d Imiquimod 3.75% or 5% cream 3.75% q hs x up to 16 wks 5% q hs three times/wk Sinecatechins 15% ointment Tidup to 16 wks Baker DA, Ferris DG, Martens MG, et al. Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results from women in two randomized, placebo controlled studies. Infect Dis Obstet Gynecol. 2011;2011:806105. Very common almost all sexually active people get it and partners share it. Usually body s natural defenses fight HPV before it can cause health problems. HPV warts do not cause cancer No way to test partner Condom use can decrease but not eliminate transmission risk Warts may regress on their own. Treatment is for symptoms. Treatment does not prevent transmission. Myoplasma genitalium Mycoplasma genitalium Smallest free living bacteria Genome only 521 genes Second complete bacterial sequence ever sequenced First isolated in 1980 from 2/13 men with NGU Difficult to culture Fastitious with slow growth (>50 days) 20% of NGU in men but role in women less clear Vagina, cervix, endometrium Detected in 2 22% (10%)PID cases Detected in 10 30% of cervicitis cases May be related in infertility Mobley VL et al. Mycoplasma genitalium infection in women attending a sexually transmitted infection clinic: diagnostic specimen type, coinfections, and predictors. Sex Transm Dis. Sep 2012;39(9):706 709. Gaydos C et al. Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis in women attending sexually transmitted disease clinics. Sex Transm Dis. Oct 2009;36(10):598 606. 8
Cervicitis Endometritis/PID Does MG cause Cervicitis and PID? Odds Ratio (95% CI) 0.3 (0.1-1.8) (2.1- ) 0.8 (0.3-1.9) 3.3 (1.7-6.4) 1.6 (1.0-2.7) 5.7 (1.1-25.5) 2.3 (1.0-5.5) 0.7 (0.2-2.9) 2.0 (1.1-3.7) 1.4 (0.8-2.8) 0.8 (0.4-1.5) 2.8 (1.6-4.9) 1.3 (1.0-1.6) 1.6 (0.4-7.7) 1.2 (1.0-1.5) 2.1 (1.0-4.3) 1.3 (0.8-1.9) 3.8 (2.1-7.0) Odds Ratio (95% CI) (2.0 - ) (1.4- ) 1.0 (0.6-1.7)* 4.6 (1.1-20.1) 2.4 (1.3-4.6) 6.3 (1.6-25.2) 2.4 (0.7-7.5) 9.0 (1.6-49.9) 2.1 (0.3-11.0) MG Guidelines Meeting 33 Cervicitis 17 studies (5 new) 9 (53%) significant assoc. 5 (29%) elevated OR, but NS 3 (18%) no association OR range 1.2 5.7 Suggests an association Endometritis/PID 14 studies (7 new) 3 sero studies conflicting 10 PCR based studies 6 (60%) significant assoc. 3 (30%) elevated OR but NS OR range 2.1 6.3 Suggests a causal association 3/16/2015 Infertility Preterm Birth Does MG cause Female Infertility, Adverse Birth Outcomes? Odds Ratio (95% CI) 0.7 (0.2-1.8) 4.2 (1.9-9.4) 4.5 (1.0-17.7) 5.4 (0.7-243.3) 2.8 (0.8-9.8) Odds Ratio (95% CI) 1.4 (0.7-2.6) 3.5 (1.4-8.6) 2.5 (1.2-5.0) 0.9 (0.2-3.8) MG Guidelines Meeting 34 Infertility 6 studies (2 new) All but one with elevated ORs (range 2.8 5.4) 2 strongest studies show significant association Suggests an association Preterm birth 7 studies (1 new) Adverse birth outcomes rare in studies (1 4%) Limited evidence conflicting Insufficient evidence Ectopic Pregnancy Single study no assoc. Insufficient evidence 3/16/2015 What Diagnostic Tests are Available for MG? No commercially available diagnostic tests currently approved in US Some large medical centers have in house PCR assays available to general patients, but this is rare. In house PCR assays used in research settings, but not generally available to patients not participating in research studies. APTIMA RUO TMA assay often used in research studies, but results cannot be used for treatment decisions. Not currently pursuing FDA approval. At least 2 multiplex MG assays are commercially available in Europe Bio Rad (GC/CT/MG) Sacace Biotechnologies, CT/MG/UU M. hominis) for Sacace. Cepheid may develop MG test for GeneXpert platform, but not on current agenda. What is the Efficacy of Moxifloxacin (400mg x 7d) against MG? Study Syndrome Moxifloxacin dose Micro Cure Bradshaw 2006 AZM 1g treatment failures 400mg x 10 days 9/9 (100%) Ross 2006 PID 400mg x 14 days 3/3 (100%) Jernberg 2008 STD sx, or partner sx or MG+ or CT+ 400mg x 7 days 3/3 (100%) Bradshaw 2008 AZM 1g treatment failures 400mg x 14 days 8/8 (100%) Terada 2012 Cervicitis 400mg x 7 days 38/42 (91%) 400mg x 14 days 42/42 (100%) Twin 2012 AZM 1g treatment failures 400mg x 10 days 77/77 (100%) Walker 2013 AZM 1g treatment failures 400mg x 10 days 3/3 (100%) Anagrius 2013 AZM 1g treatment failures 400mg x 7 days 9/9 (100%) Manhart 2013 Treatment failures (AZM1g, DOX, both) 400mg x 7 days 17/20 (85%) CONCLUSION: Moxifloxacin appears to be superior to other treatments for MG, but the drug has not been tested in clinical trials, and resistance may be emerging. MG Guidelines BD may Meeting be pursuing FDA approval 35 3/16/2015 MG Guidelines Meeting 36 3/16/2015 9
Should the recommended therapies for MPC, and/or PID be altered? MPC Existing evidence does not support a recommendation to alter the currently recommended therapies for cervicitis. MG should be considered in cases of persistent cervicitis and treatment with moxifloxacin 400mg po qd x 7 days should be considered. PID Current PID treatment regimens are not effective against MG. Given the relatively low prevalence of MG in women with PID, the existing evidence does not support a recommendation to change the current therapies for PID in the absence of diagnostic testing for MG. However, clinicians should consider MG in cases that fail to respond to MG within 2 3 days and treat with moxifloxacin 400mg/day x 14 days. Where MG testing is available, clinicians should test women diagnosed with PID for MG, and when MG is detected moxifloxacin 400mg/day x MG Guidelines Meeting 37 3/16/2015 14 days should be prescribed. Summary Transgender care: anatomy & history; HIV Trich: Vaginal swab NAAT CT/GC: Vaginal swab NAAT; Dual therapy for GC Genital Warts: Imiquimod 3.75% qhs; HPV counseling Emerging pathogens: M. Genitalium Resources HMC STD Clinic HMC Virology Research Clinic HSV CDC website http://www.cdc.gov/mobile/mobileapp.html http://www.doh.wa.gov/youandyourfamily/illnessanddisease/se xuallytransmitteddisease/expeditedpartnertherapy.aspx http://www.doh.wa.gov/portals/1/documents/pubs/347 634 KingProfile12.pdf cgardel@uw.edu with questions 10