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  1. Update on the Treatment of STI:The Silent Epidemic David E. Soper, MD Department of Obstetrics and GynecologyMedical University of South CarolinaCharleston, South Carolina

  2. Objectives After attending this presentation the practitioner will be able to: • Diagnose and treat chlamydia infection • Treat gonococcal infection • Understand reverse screening for syphilis • Manage mild to moderate PID with IUD in situ • Diagnose genital herpes infection

  3. STI Chlamydia Gonorrhea Syphilis Herpes HPV Hepatitis B Trichomoniasis Bacterial vaginosis Number of Cases per Year 2.86 million 820,000 55,400 776,000 14.1 million 19,000 1.1 million Not available The Silent EpidemicEstimated Annual Rates USA

  4. Sexual Behaviors • 15 million new STIs each year • 25% in teenagers • 900,000 adolescents become pregnant • Adolescent statistics • 47% of high school students had ever had coitus • 15% had >4 lifetime sex partners • 40% did not use a condom with last sex contact

  5. Cervicitis • Two major diagnostic signs • Purulent or mucopurulent endocervical exudate • Sustained endocervical bleeding easily induced by gentle passage of a cotton swab through cervical os

  6. CervicitisEtiology • If pathogen detected, most likely: • Chlamydia trachomatis • Neisseria gonorrhoeae • Can also accompany trichomoniasis and herpes • Most cases = no organism isolated • Other possibilities • BV, Mycoplasma genitalium, frequent douching

  7. Cervicitis Diagnosis • NAAT for chlamydia and gonorrhea • Vaginal, cervical or urine samples • Self collected vaginal swabs most sensitive • CT = 97%[95-98] vs 95% [85-91]

  8. CervicitisTreatment • Recommended regimen • Treat for chlamydia • Azithromycin 1 g orally in a single dose Or • Doxycycline 100 mg orally twice a day for 7 days • Concurrent therapy for GC of prevalence >5% • < 25 years of age • Treat BV and/or trichomonas if detected

  9. CervicitisRecurrent or Persistent • Reinfection? • Consider M. genitalium • Moxifloxicin 400 mg orally once daily for 7 days • Retest CT or GC positive in 3 to 6 months • High rate of reinfection

  10. ChlamydiaScreening Guidelines • Sexually active adolescents • Screen annually, even if asymptomatic • More frequent (q 3-6 mos) if positive • Women aged 20-25 • Annual screening also recommended • Older women with risk factors • New sex partner • Multiple sex partners

  11. Chlamydia ScreeningNew Risk Factors • Screening for older women with risk factors • Sex partner with concurrent sex partners • Resumed sexual activity • Widowed • Divorced • Separated • Bacterial vaginosis

  12. Chlamydia ScreeningOptimal Urogenital Specimen • Vaginal swabs from women • Can be self collected • First catch urine for men • NAATs not FDA cleared for oral or rectal site • Improved sensitivity and specificity over culture • Self collected swabs comparable

  13. Chlamydia Recommended regimens • Azithromycin 1 gram orally single dose OR • Doxycycline 100 mg orally bid for 7 days • Treat partner • NO SEX for 7 days

  14. Chlamydia Alternative regimens • Erythromycin base 500 mg orally qid x 7 days OR • Erythromycin ethylsuccinate 800 mg qid x 7 days OR • Levofloxacin 500 mg orally for 7 days (substituted for ofloxacin 300 mg bid for 7 days) TEST OF CURE >3 weeks after therapy

  15. Uncomplicated Gonococcal Infections of Cervix, Urethra, Rectum DUAL THERAPY !! • Ceftriaxone 250mg in a single IM dose PLUS • Azithromycin 1 gram orally in a single dose

  16. Gonococcal InfectionAlternative Regimens • Cefexime 400 mg in a single oral dose PLUS • Azithromycin 1 gram orally in a single dose • Or doxycycline 100mg orally twice a day for 7 days • High level of tetracycline resistance in GISP • Azithromycin preferrable PLUS • Test of cure in one week

  17. Gonococcal InfectionPenicillin/Cephalosporin Allergy • Azithromycin 2 grams in a single oral dose PLUS • Test-of-cure in one week • Allergy should be severe and an immediate hypersensitivity reaction

  18. Mycoplasma genitalium • Emerging pathogen • Persistent or recurrent urethritis in men • Suggestive as an etiology of cervicitis • Can cause PID • ? Link to preterm birth • Linked to acquisition of HIV

  19. Mycoplasma genitaliumTreatment • Azithromycin 1 gram orally in a single dose • Superior to multidose doxycycline • Multidose azithromycin • 1 gram followed in one week with another 1gram ? Best • Moxifloxicin 400mg daily for 7 days • 91% efficacy • 14 day course 100% • Other quinolones (levo- or ciprofloxacin) ineffective

  20. Pelvic Inflammatory DiseaseMild to Moderate • Outpatient • Ceftriaxone 250mg IM • Doxycycline 100 mg bid for 14 days • With or without metronidazole • Doesn’t cover M. genitalium • If no clinical response rule out abscess then - • Consider Moxifloxin 400mg daily for 14 days

  21. PID and the IUD • “Evidence is insufficient to recommend the removal of IUDs in women diagnosed with PID.” • Risk primarily restricted to the first 3 weeks after insertion • Consider removal only if patient fails to respond to conventional therapy

  22. Genital Ulcer DiseaseDiagnosis • Serologic test for syphilis • Diagnostic evaluation for herpes • H. ducreyi • Syndromic diagnosis • Ulcer plus suppurative adenopathy • Consider HIV testing

  23. Primary and Secondary Syphilis—Rates by Region, United States, 2003–2012 2012-Fig 32. SR Pg 33

  24. Primary and Secondary Syphilis—Rates by Age Among Women Aged 15–44 Years, United States, 2003–2012 2012-Fig 36. SR, Pg 35

  25. Congenital Syphilis—Reported Cases Among Infants by Year of Birth and Rates of Primary and Secondary Syphilis Among Women, United States, 2003—2012 * CS=congenital syphilis; P&S=primary and secondary syphilis. 2012-Fig 43. SR, Pg 39

  26. Syphilis Screening • Non-treponemal testing • Quantitative • VDRL • RPR • Treponemal testing • TP-PA • FTA-abs • EIA

  27. Syphilis SerologyReverse Screening • Start with treponemal test • EIA • Confirm with quantitative, non-treponemal test • RPR

  28. Syphilis SerologyReverse Screening • Why? • Automated (high throughput) • Low cost in high volume settings • Less lab occupational hazard (pipetting) • Objective results • No false negatives due to prozone reaction

  29. Treatment of Syphilis Primary, secondary, Benzathine penicillin and early latent 2.4 mu IM Latent Benzathine penicillin 2.4 mu IM, wkly x 3

  30. SyphilisAlternative Therapies • Limited data to support alternatives to penicillin • Clinical and serologic follow-up mandatory • Ceftriaxone 1-2 gm IM/IV qd x 10-14d • Doxycycline 100 mg bid x 14d • Azithromycin 2 gm once • Emerging macrolide resistance (NEJM,2004)

  31. Herpes Simplex Virus Type 2—Seroprevalence Among Non-Hispanic Whites and Non-Hispanic Blacks by Age Group, National Health and Nutrition Examination Survey, 1976–1980, 1988–1994, 1999–2004, 2005–2008 *Age-adjusted by using the 2000 U.S. Census civilian, non-institutionalized population aged 14-49 years as the standard. NOTE: Error bars indicate 95% confidence intervals. 2012-Fig 49. SR, Pg 46

  32. Genital HerpesDiagnosis • Viral culture • Positive in 80-90% of primary disease • Positive in only 30-50% of recurrent disease • Dependent on stage of lesion • Antigen detection tests • Don’t discriminate between HSV 1 and 2 • PCR • Now established for lesions

  33. HSV Serology • Assays that do not distinguish HSV-1 from HSV-2 remain commercially available • Whole virus lysates of HSV-1 and 2 • Only valuable if seronegative • Type-specific assays • Glycoprotein G2 for HSV-2 • Glycoprotein G1 for HSV-1 • Time frame to conversion 2 weeks to 3 months

  34. HSV Serology • Populations in which testing may be beneficial • Persons seeking STD evaluation • Persons with partners with genital HSV • Patients with atypical lesions or symptoms • Pregnant women • HIV seropositive persons • Persons at risk for HIV

  35. Genital HerpesModern Diagnostic Approach • Clinical diagnosis • PPV = 81% • Sensitivity = 39% • HSV type-specific PCR • When lesions are present • Culture commonly false negative • Type specific HSV antibodies

  36. Genital HerpesTreatment for First Episode • Acyclovir 400 mg tid x 7-10 days OR • Acyclovir 200 mg 5 times daily x 7-10 OR • Famciclovir 250 mg tid x 7-10 days OR • Valacyclovir 1 g orally bid x 7-10 days

  37. Genital HerpesEpisodic Therapy • Acyclovir • 400 mg tid for 5 days • 800 mg bid for 5 days • 800 mg tid for 2 days • Valacyclovir • 500 mg bid for 3 days • 1 gram daily for 5 days

  38. Genital HerpesEpisodic Therapy • Famciclovir • 125 mg bid for 5 days • 1 gram bid for 1 day • 500 mg then 250 mg bid for 2 days

  39. Genital HerpesSuppressive Therapy • Acyclovir 400 mg bid • Famciclovir 250 mg bid • Valacyclovir 500 mg daily* • Valacyclovir 1 gram daily

  40. Covariate Analyses of Factors Influencing the Transmission of Genital Herpes Covariate Acquisition of Symptomatic HSV-2 infection Hazard Ratio (95% CI) P Value Valacyclovir (vs. placebo) 0.25 (0.08-0.75) 0.01 Susceptible partner female 3.30 (1.31-8.28) 0.01 Susceptible partner HSV-1-negative 1.64 (0.64-4.17) 0.30 Less frequent condom use at 1.70 (0.95-3.05) 0.08 time of acquisition More frequent sexual contacts 1.83 (0.97-3.43) 0.06 during study Duration of HSV-2 infection in 2.89 (1.12-7.49) 0.03 source <2 yr (vs. >2 yr) Duration of relationship 3.18 (0.89-11.33) 0.08 <2.5 yr (vs. >2.5 yr)

  41. What have you learned? • Vaginal swabs for chlamydia testing • DUAL THERAPY for gonococcal infection !! • Mycoplasma genitalium is coming • Ok to leave the IUD in while Rx for PID • Reverse screening for syphilis • PCR testing for skin lesions suspicious for HSV