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Update in Sexually Transmitted Diseases, 2011. William Wong, MD Chicago Department of Public Health City of Chicago. Faculty Disclosure. Commercial, Financial, or Organizational Conflicts of Interest: None Off-label or FDA non-approved use of medications: None. Learning Objectives.
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Update in Sexually Transmitted Diseases, 2011 William Wong, MD Chicago Department of Public Health City of Chicago
Faculty Disclosure • Commercial, Financial, or Organizational Conflicts of Interest: None • Off-label or FDA non-approved use of medications: None
Learning Objectives 1. Describe the impact of HIV and STIs in Chicago and the United States. 2. Discuss trends in antimicrobial resistance in gonorrhea and other STDs 3. Identify recommended treatment regimens for uncomplicated gonococcal infections of the cervix, urethra, and rectum • Describe current HIV and STI screening recommendations for adolescents and adults.
Local Trends in Sexually Transmitted Infections Reported Gonorrhea and Chlamydia – Chicago, 2002-2009 Number of Reported Cases Number of Reported Cases
P&S Syphilis, by Sex and Sexual Behavior - Chicago, 1998-2006 n=295 n=418 n=297 n=267 n=353 n=317 n=292 n=282 n=338
2010 Sexually Transmitted Diseases Treatment Guidelines William Wong, MD Chicago Department of Public Health City of Chicago
Overview of Complications ofSexually Transmitted Diseases • >19 million STDs in the United States annually, most asymptomatic Infertility Ectopic Pregnancy Chronic Pelvic Pain Upper Tract Infection Systemic Infection Low Fetal Birthweight Congenital Infection STDs Cervical and Anogenital Cancer HIV Transmission • Health care cost: $16.4 billion (2009) * Potentially Fatal
Populations at Greatest Risk for STDs • Youth • Nearly 50% of STDs occur in 15-25 year old • Racial and ethnic minorities • STDs among highest of all racial/ethnic disparities • African Americans: 71% GC, 48% CT, 52% syphilis • Over last 5 years, syphilis cases increased more than 150% among African American men • Men who have Sex with Men (MSM) • Account for 62% of syphilis cases in 2009 • High rates of co-infection with HIV
STD Prevention: Clinician’s Role • Pre-exposure vaccination • Provide/refer for risk reduction counseling • Assess risk and test accordingly • Diagnosing and treating • Referring partners • Reporting STD/HIV cases in accordance with state and local laws • Keep STD/HIV reports confidential
December 17, 2010 Sexually Transmitted Diseases Treatment Guidelines, 2010 Division of STD Prevention National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Website: www.cdc.gov/std/treatment/2010or call 1-800-CDC-INFO
2010 STD Treatment GuidelinesMethods • Evidence-based systematic review • Enlistment of Subject Matter Experts • Consultants meeting to evaluate and rate evidence • Guidelines meeting in April 2009 • Identify critical research gaps in knowledge • 2010 Guidelines published and disseminated
Clinical Prevention Guidance • Five major strategies • Education and counseling of persons at-risk towards behavior change • Identification of asymptomatically infected persons, persons unlikely to seek services • Effective diagnosis and treatment of infected persons • Evaluation, treatment, counseling of sex partners of infected persons • Pre-exposure vaccination of persons at-risk
Screening with NAATs • Screen for STDS at anatomic sites • NAATs perform better than culture (rectum and pharynx) • Commercial laboratories have validated NAATS • Most infections asymptomatic • Preferred specimens • Self-collected vaginal swabs in females • Urine specimen in males
Special Populations: Men who have Sex with Men • Recommended Annual Screening Tests • HIV serology, if negative or not tested in last year • Syphilis serology • Chlamydia and Gonorrhea: urethral, rectal, pharyngeal tests depending of site of exposure • More frequent screening (i.e.3-6 month intervals) for MSM with multiple or anonymous partners, illicit drug use, methamphetamines, or partners with high-risk behaviors • HBsAg testing to detect current infection • Hepatitis A & B vaccinations, in nonimmune • Hepatitis C (HCV) screening • HCV serology at initial visit • HCV RNA with unexplained alanine aminotransferase (ALT) rise • Routine HCV testing with high-risk sexual behavior or ulcerative STDs
Clinical Prevention Guidance • High-intensity behavioral counseling for all sexually active adolescents and adults at increased risk of infection (USPSTF) • The Five P’s: Partners, Prevention of Pregnancy, Protection from STDs, and Past History of STDs • Pre-exposure vaccination • Hepatitis A virus (HAV), hepatitis B virus (HBV), human papillomavirus (HPV) (bivalent/quadrivalent) • Condoms • Female nitrile condoms • Microbicides • www.microbicide.org • Pre-exposure prophylaxis for HIV/STD • Male circumcision • Reduced acquisition of HPV/genital HSV
Urethritis • Bacterial STDs: GC (5-20%), CT (15-40%) • Nongonococcal urethritis (NGU) • Mycoplasma genitalium 5-25% • Ureaplasa 0-20%; data inconsistent, biovars vary • Trichomonas vaginalis 5-20% (age, geography) • HSV 15-30%; urethritis in primary infection • Adenovirus, enteric organisms, Candida, anaerobes
Mycoplasma genitalium (MG) • Associated with acute or persistent NGU • No role in male infertility • Conflicting/insufficient evidence in contributions to cervicitis, PID, infertility, ectopic pregnancy, adverse birth outcomes • Azithromycin superior to doxycycline for MG urethritis • Moxifloxicin for persistent NGU
NGU Treatment • Current drug regimens adequate: • Azithromycin 1 gm or Doxycycline 100 mg BID x 7 days • Cost considerations and lack of public health impact data for MG insufficient to demote doxycycline to alternative agent • Recurrence • Reexposure from untreated partners • T. vaginalis, M. genitalium, U. ureaplasma may account for some failures
Cervicitis • CT/GC NAATs on vaginal, cervical, urine recommended • No new antimicrobial treatment trials • Research needed on the etiology of persistent cervicitis including the potential role of Mycoplasma genitalium
Chlamydia • Primary focus of screening efforts to detect and prevent complications in women • Annual screening of all sexually active women aged ≤25 years is recommended • Selective male screening (adolescent clinics, corrections, national job training program, <30 yo, STD clinics, military) • Retest women/men 3 mo post-treatment • CT testing in third trimester (reinfection)
Gonorrhea • Screen sexually active women at increased risk (USPSTF) • <25 years • Previous GC or other STDs • Commercial sex work • No screening in men or women at low risk of infection (USPSTF) • Retest women/men 3 months after treatment • New or multiple partners • Inconsistent condom use • Drug use
Advent of Antimicrobial Resistance in N. gonorrhoeae in the United States • 1936 Sulfanilamide introduced • 1940’s Penicillin and Tetracycline introduced • 1945 1/3 of GC sulfanilamide-resistant; penicillin (50,000 units) becomes therapy of choice • 1972 Recommended therapeutic penicillin dose reaches 4.8 million units • 1985 Widespread tetracycline-resistance, so tetracycline abandoned • 1987 Penicillin abandoned • 1993 Fluoroquinolones (FQ) recommended • 2000 Fluoroquinolone-resistant GC (QRNG) identified; FQ not recommended to treat GC acquired in Hawaii, Pacific Islands, or Asia • 2002 FQs not recommended for GC in MSM in U.S. • 2007 QRNG widespread throughout U.S.; FQs no longer recommended for GC treatment Credit: Adapted from S. Wang, CDC
Gonorrhea Treatment Efficacy • Oropharyngeal • Ceftriaxone • 125 mg = 94.1% • 250 mg = 98.9% • Oral cephalosporins have limited use due to poor tissue penetration • Azithromycin 2 gm = 95% • Anogenital • Ceftriaxone • 125 mg = 98.9% • 250 mg = 99.2% • Geographic distribution in vitro decreased susceptibility, ceftriaxone failures, enhanced pharyngeal efficacy, consistent guidance at all anatomic sites
Neisseria gonorrhoeaeCervix, Urethra, Rectum Recommended Ceftriaxone 250 mg IM single dose (preferred) PLUS Azithromycin 1 gm or Doxycycline 100 mg BID x 7 days OR, IF NOT AN OPTION Cefixime 400 mg single dose PLUS Azithromycin 1 gm or Doxycycline 100 mg BID x 7 days
Neisseria gonorrhoeaeCervix, Urethra, Rectum Alternate Regimens Cefpodoxime 400 mg orally in single dose or Cefuroxime axetil 1 gm orally in single dose or Azithromycin 2 g (penicillin allergy)
Neisseria gonorrhoeaePharynx Recommended Ceftriaxone 250 mg IM in a single dose PLUS Azithromycin 1 gm or Doxycycline 100 mg BID x 7 days Alternatives Azithromycin 2 gm (penicillin allergy)
Cephalosporin GC Treatment Failures • Suspected treatment failure (oral and injectable) • Treatment failure or in vitro resistance • Infectious disease consultation • Culture and susceptibility • Treat with Ceftriaxone 250 mg IM x 1 dose • Ensure partner treatment • Report to CDC via state or local public health
Genital, Perianal, Anal Ulcers • History/physical examination often inaccurate • Majority due to HSV or syphilis • Chancroid is less common • Consider non-infectious eitology (yeast, aphthi, fixed drug eruption, psoriasis) • Serological test for syphilis required • Diagnostic evaluation for HSV (culture, PCR) • Treat for diagnosis most likely based on clinical and epidemiological data • If syphilis is suspected, treat empirically as initial tests may be negative in primary syphilis • Biopsy if uncertain
Syphilis • Definitive diagnosis for early syphilis • Darkfield microscopy, PCR • No commercially available Treponema pallidum detection tests • Nontreponemal/treponemal serological testing (e.g. RPR and FTA) • Reverse serologic screening emerging (Syph EIA and RPR) • Management principles for HIV+ similar • Frequent clinical/serological monitoring • Neurosyphilis can occur at any stage
Evaluation of CNS Involvement • Neurologic, ocular, auditory signs/symptoms = evaluate with lumbar puncture • CNS invasion occurs in early syphilis regardless of HIV or neurologic symptoms (protein, pleocytosis) • Clinical significance unknown (HIV+/-) • Neurosyphilis diagnosis requires combination of tests • CSF evaluation: neuro/ocular symptoms, tertiary, serologic treatment failure • Some studies – clinical and CSF consistent with neurosyphilis are associated with a RPR ≥ 1:32 and/or CD4 ≤350 • Unless neurologic symptoms present, CSF exam has not been associated with improved clinical outcomes
Syphilis Treatment Early Syphilis (Primary, Secondary, Early Latent) • Penicillin is treatment of choice (HIV+/HIV-) • Benzathine Penicillin G 2.4 million units IM x 1 • No benefit of additional therapy • Penicillin alternatives • Doxycycline 100 mg twice daily x 14 days • Ceftriaxone 1 gm IM/IV daily x 8-10 days • Azithromycin 2 gm single dose orally (resistance/treatment failure) • Use only when penicillin or doxycycline not feasible • Do not use in MSM or pregnancy
Azithromycin and Syphilis • Macrolide resistance associated with A2058G mutation in 23S rRNA gene • Present in Canada, Ireland, Czech Republic, China • Prevalence of mutation in US • A2058G found in 9/11 US sites • MSM>MSW; no association with US region, race • Treatment failure • Documented in US, Czech Republic, China
Monitoring Syphilis in HIV+ • Jarisch-Herxheimer reaction in HIV+ • More common in early syphilis, high RPR, prior penicillin treatment • Immune reconstitution inflammatory syndrome uncommon in syphilis and HIV • ART use in HIV+ with syphilis • Reduced risk of serologic treatment failure • Lower risk of neurosyphilis • Normalization of CSF parameters with improvement in serum RPR
Syphilis in Pregnancy and Congenital Syphilis • Treponemal screening performed with reflex nontreponemal test • Oral step-wise penicillin dose challenge or skin testing may be helpful in identifying women at risk for acute allergy • Erythromycin or azithromycin does not reliable cure maternal infection or infected fetus • Insufficient data on ceftriaxone for treatment of maternal infection and prevention of CS
HSV • IgM testing not useful • Antiviral efficacy • Acyclovir, valacyclovir, famciclovir equally effective (episodic) • Acyclovir and valacyclovir effective for suppression • Famciclovir slightly less effective for supression • Famciclovir 500 mg x 1, 250 mg x 2 d episodic • Acyclovir resistance • Topical cidofovir or imiquimod efficacious • Less likely to develop resistance using suppressive therapy (bone marrow transplant)
Lymphogranuloma venereum (LGV) • Proctitis presentation (HIV+MSM) • Diagnosis • Genital or lymph node aspirates – culture, DFA, nucleic acid detection (CLIA validation) • Genotyping required for determining LGV strains • Serology no validated for proctitis presentation • Empiric treatment for appropriate clinical syndrome • Doxycycline 100 mg PO BID x 21 days • Azithromycin 1 gm PO q week x 3 weeks (limited data)
Proctitis • Painful perianal or mucosal ulceration • HSV/LGV presumptive treatment • Consider LGV treatment in MSM with anorectal chlamydia and either proctitis (diagnosed by anoscopy) with >10 wbcs/high-power field or HIV+
Scabies/Pediculosis • Permethrin superior to crotamiton • Combined treatment for crusted scabies oral/topical scabicide • Emerging resistance to al pediculicides except malathion
Bacterial Vaginosis Recommended Metronidazole 500 mg BID x 7 days Metronidazole 0.75% gel QD x 5 days Clindamycin 2% cream qhs x 7 days Alternative regimen Tinidazole 2 g qd x 2 days or 1 g qd x 5 days Clindamycin 300 mg BID x 7 days Clindamycin 100 mg ovules intravaginal QHS x 3 days
Bacterial Vaginosis • Management of recurrences • Metronidazole gel 2 times weekly x 4-6 months • Oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel • USPSTF • Insufficient evidence to support screening high-risk pregnant women • Against screening in low risk
Trichomoniasis • Diagnostic evaluation • APTIMA T. vaginalis analyte specific reagents • Consider rescreen women (HIV-/HIV+) at 3 mos • NAAT preferred diagnostic in men • Antimicrobial resistance (5-10%) • No data to guide treatment of male partners • Metronidazole 500 mg BID x 7 days or Tinidazole 2 mg • HIV and Trichomoniasis • Screening at entry into HIV care • Treatment metronidazole 500 mg BID x 7 days
HPV/Genital Warts • Counseling messages • Clarification on use of HPV testing on certain women • Genital warts treatment • Sinecatecins ointment (15%) • Vitiligo side effect of imiquimod • HPV vaccine • Bi-/Quadrivalent vaccine (70% cervical cancer) • Quadrivalent vaccine (90% genital warts)
Sexual Assault in Children • STD screening should be independent of symptoms • Diagnostic evaluation • CT NAATs (SDA, TMA) on vaginal swabs/urine in girls; specimens retained for additional testing • GC NAATs test dependent; potential cross-reaction between other Neisseria species/commensals (N. meningitis, N. sicca, N. lactamica, N. cinerea, Moraxella catarrhalis) • Data insufficient for extragental NAAT in girsl • Data insufficient for CT/GC NAATS at any site for boys • HPV infection/mode remains controversial
Sexual Assault in Adults • CT/GC NAATs - any site of penetration/attempt • Empirically treat infections, as follow up is poor • HIV, hepatitis B, syphilis testing individualized • Test results likely represent prevalent STDs • Some centers have opted to stop STD testing • Likely will not impact decision to provide prophylactic treatment • Testing costs may be patient’s responsibility
Acknowledgements • Centers for Disease Control and Prevention • Kimberly Workowski, MD • Stuart Berman, MD • Gail Bolan, MD • Edward W. Hook, MD • Charlotte Kent, PhD, MPH • Numerous subject matter experts
Resources • Condoms and STDs: Fact Sheet for Public Health Professional • www.cdc.gov/condomeffectiveness/latex.htm • Expedited Partner Therapy • www.cdc.gov/std/ept • Get Yourself Tested • www.itsyoursexlife.com/gyt