Sexually Transmitted Diseases Treatment Update Answers to those burning questions Anne Rompalo, M.D., Sc.M. Professor of Medicine Johns Hopkins School of Medicine Region III STD/HIV Prevention Training Center Conflict of Interest • None Objectives By the end of this lecture, you should be able to: • Identify and elicit risk behaviors for STIs • Choose appropriate tests for common STI screening and diagnosis • Administer recommended therapy for common STIs • Provide guidance and referrals for STI prevention Clinical Prevention Guidance • High intensity behavioral counseling (USPSTF) • Pre-exposure vaccination- HAV, HBV, HPV • Condoms – CDC fact sheet; female nitrile condom • Microbicide trials – Trial updates at www.microbicide.org • Male circumcision may reduce acquisition of some STI (HPV, genital HSV) •Overall HIV incidence= 5.6/100 women-years tenofovir vs. 9.1/100 women years in placebo arm •In high adherers (>80% gel adherence) HIV incidence was 54% lower Clinical Prevention Guidance • Preexposure prophylaxis for HIV/STI – ART has potential to impact HIV transmission – No data PrEP for STD prevention • Postexposure prophylaxis for HIV/STI – genital hygiene methods (douching, washing after sexual exposure) ineffective and may increase risk of BV, some STI, and HIV • CT, GC rescreening Prevention Methods Male Condoms • Correct/consistent latex condom use- highly effective in preventing sexual transmission of HIV; reduced risk- CT, GC, trichomoniasis • May reduce risk of HSV-2 transmission • May reduce risk of genital warts, cervical cancer – Higher rates of CIN regression, HPV clearance, penile lesions – Protective- HPV acquisition (newly sexually active women) Syndromes Urethritis • GC (5-20%), CT (15-40%) • Mycoplasma genitalium – 15-25% of NGU • Trichomonas vaginalis 5-20% of NGU • Ureaplasma urealyticum (UU) – cumulative data insufficient • CT or MG <5 PMNs (10-30% CT or MG) • Diagnostic tools not available Rx CT/GC NGU Pathogens Schwebke JR et al; STI CTG NGU Treatment • Current drug regimens are adequate for majority of bacterial NGU • Azithromycin > doxcycline for M. genitalium (82% vs 39%) • Cost considerations and lack of public health impact data for MG insufficient to demote doxycycline to alternative agent Persistent/Recurrent NGU Management • Recurrence – Re-exposure from untreated partners – T. vaginalis and M. genitalium – U. ureaplasma may account for some failures • Urologic exam usually doesn’t reveal specific etiology • 50% chronic nonbacterial prostatis/chronic pelvic pain syndrome have evidence of urethritis without pathogen Mycoplasma genitalium • Association with acute or persistent NGU – No role in male infertility (limited data) • Conflicting/insufficient evidence for cervicitis, PID, infertility, ectopic pregnancy, adverse birth outcomes • AZM superior to doxy for MG urethritis – Extended duration AZM not superior to single dose – In vitro resistance to AZM and doxycycline • Moxifloxacin for persistent NGU Epididymitis • Chronic infectious epididymitis (M tb) • Ceftriaxone + doxycycline for initial tx – quinolone if GC – (cx or NAAT) or infection likely caused by enteric organism • Ceftriaxone + quinolone – Risk for both sexually transmitted and enteric organisms (MSM-insertive anal intercourse) Cervicitis • CT/GC NAATs-vaginal, cervical, urine • Case reports of treatment of cervical ectopy, but no new antimicrobial treatment trial information • Research is needed on the etiology of persistent cervicitis including the potential role of Mycoplasma genitalium Cervicitis Chlamydia • Primary focus of screening efforts to detect and prevent complications in women • Selective male screening- (adolescent clinics, corrections, national job training program, < 30 yrs, STD, military) • Retest women/men 3 mo post tx – CT testing in third trimester (reinfection) PID • Some association between MG – Insufficient data to support testing/tx MG • Emergence of QRNG – Quinolones not recommended – Parenteral tx not feasible- prevalence/individual risk low; naat+ consider azi 2 gm + quinolone+/- metronidazole • Short term success-ceftriaxone 250 mg IM +azithromycin 1gm qwk x2 • Insufficient evidence to warrant removal of IUD Gonorrhea • Screen sexually active women at increased risk <25 years, previous GC or other STIs, new or multiple partners, inconsistent condoms, CSW, drug use (USPSTF) • No screening in men or women at low risk of infection (USPSTF) • Retest women/men 3 mo after tx Gonorrhea • NAAT sensitivity in genital/non-genital sites superior to culture (variation in NAATs, crossreaction) Historical perspective on antimicrobial resistance in the United States.QRNG = quinoloneresistant Neisseria gonorrhoeae; MSM = men who have sex with men. Workowski K A et al. Ann Intern Med 2008;148:606-613 ©2008 by American College of Physicians The geography of resistance: Global patterns 1990s 2000s 1990s 1980s QRNG 1990s QRNG appears in Rwanda appearsQRNG in appears in SE India Asia 1991 QRNG CDC stops recommending appears on Quinolones West Coast QRNG appears in Hawaii 1984 QRNG appears in Australia Gonorrhea • The gonococcus has evolved a number of different resistance determinants over time and multidrugresistant GC now exist • GC clinical failures after treatment with oral cephalosporins have been reported – these cases are still treatable with high-dose ceftriaxone • There are no new anti-gonococcal drugs on the horizon and singe-dose regimens may need to be replaces with extended regimens or multidrug regimens • Public health approaches to GC control need to be enhanced to reduce global burden Gonorrhea • Ceftriaxone 250 mg IM preferred regimen • Ceftriaxone efficacy (anogenital) – 250 mg = 99.2% ( L95%CI = 98.8%) – Geographic distribution in vitro decreased susceptability, ceftriaxone failures, enhanced pharyngeal efficacy, consistent guidance at all anatomic sites • Cefpodoxime 400 mg alternative regimen – Acceptable efficacy at urogenital; poor at oropharyngeal – Cefpodoxime MIC > cefixime MIC Oropharyngeal GC: a silent cause for concern • Is clinically silent with less than 10% presenting with “sore throat” • Commonly occurs in risk groups without concurrent anogenital infection • Transmission is efficient by both fellatio and insertive oro-anal contact • Diagnosis by culture is insensitive and should be replaced by NAATs; culture remains important for surveillance of antimicrobial resistance • Isolates with multiple antibiotic resistance can emerge • Treatment failure is more likely, and a test of cure is essential Oropharyngeal GC Treatment • Ceftriaxone efficacy for oropharyngeal GC acceptable – 125 mg = 94.1% ( L95%CI = 85.6%) – 250 mg = 98.9% ( L95%CI = 94.0%) • Limited efficacy of oral cephalosporins (poor penetration) – Cefpodoxime 400 mg = 70.3%, 26/37 patients (Hall) – Cefixime 400 mg = 88.9%, 8/9 (McMillan) – Cefixime + azithro 1 g = 100%, 36/36 (McMillan) • Azithromycin 2 gm = 95%, 20/21 (L95%CI=76.2%) (Dan) • + oral exposure- regimen with enhanced pharygneal efficacy GC Treatment Recommendations • Recommended regimens – Ceftriaxone 250 mg IM – Cefixime 400 mg PO • Alternatives – Cefpodoxime 400 mg -Cefuroxime axetil 1 g (marginal) – Azithromycin 2 g (PCN allergy) Co-treat for Chlamydia • Co-treatment might hinder the development of antimicrobial resistance – GC dual treatment (oral cephalo +azi) may enhance oropharyngeal tx response Cephalosporin GC Rx Failures • Treatment failure or in vitro resistance – – – – – infectious disease consultation culture and susceptibility Rx 250 mg of ceftriaxone IM ensure partner tx report to CDC via state or local public health authorities Genital, Perianal, Anal Ulcers Evaluation • History and physical examination often inaccurate • Majority due to HSV or syphilis – Less common chancroid (remove recommendation for testing) – noninfectious (yeast, aphthi, fixed drug eruption, psoriasis) • Serologic test for syphilis • Diagnostic evaluation for HSV (culture, PCR) • Treat for dx most likely based on clinical/epidemiology • Biopsy if uncertain Syphilis • Diagnostic considerations – No commerically available Tp detection tests – Management of treponemal+ RPR – – >20 WBC in CSF (HIV+) may improve specificity of NS diagnosis – CSF FTA negative predictive value for NS Syphilis • No enhanced efficacy of additional BPG or amoxicillin in early syphilis (HIV+/-) • Failure of RPR to decline 4x in 6-12 mo after 1o or 2o may indicate tx failure • Azithromycin used with caution when BPG or doxycycline not feasible – Resistance – No use in MSM or pregnancy Syphilis and HIV • ART may improve clinical outcomes in HIV+ • HIV+ with syphilis of any stage and neurologic sx should undergo CSF exam • Majority of HIV+ respond standard tx – Clinical/CSF abnormalities c/w NS have been shown CD4<350 and/or RPR >1:32; however if asx, no data that CSF exam associated with improved outcomes Syphilis in Pregnancy and Congenital Syphilis • Treponemal screening performed with reflex nontreponemal test • Oral step-wise pcn dose challenge or skin testing may be helpful in identifying women at risk for acute allergy • Erythromycin or azithromycin does not reliably cure maternal infection or infected fetus • Insufficient data on ceftriaxone for treatment of maternal infection and prevention of CS Syphilis Laboratory testing and the EIA dilemma • Two licensed tests for screening and confirmation – Trinity Captia Syphilis G (sonicated treponemes) – Trepchek G (cloned antigens) • Increased use of treponemal EIA for screening; clinical management problems • Quantitative non-treponemal testing to guide patient management; if test is negative, perform a second treponemal test to determine reactivity Recommendations for laboratory syphilis testing algorithm with treponemal EIA (or CIA) as initial test A1 (EIA or CIA) A1 – A1+ Negative for syphilis A2 (quantitative nontreponemal test i.e. RPR) A1+ A2+ Consistent with syphilis A1+ A2 – (past or current) A3 Treponemal test that uses a different Ag platform from A1 (i.e. TPPA, FTA-ABS) A1+ A2 - A3+ A1+ A2 – A3 - Possible syphilis Unconfirmed EIA HSV • IgM testing not useful • Suppressive antivirals does not abrogate increased risk of HIV acquisition • Episodic tx- acyclovir/valacyclovir equally effective; famciclovir less effective • Famciclovir 500 mg x1, 250 mg bid x 2 d episodic • Acyclovir resistance • Stronger recommendation for antiviral tx in late pregnancy with sx HSV Genital Herpes: Serologic Tests • Several licensed type-specific tests (glycoprotein G) • HerpeSelect EIA/immunoblot, and point-of-care tests (BioKit HSV2, SureVue HSV2)-sensitivities 80-98%, specificities > 96% • Non gG-based assays are still on market, less accurate • Potential uses: – culture-negative ulcers with recurrent/atypical lesions – clinical dx without lab confirmation – Partners • Not indicated for general population screening • Some experts suggest use as part of comprehensive STI evaluation – persons with multiple sex partners, HIV, MSM HSV Treatment • Valacyclovir 500 mg qd decreases the rate of HSV-2 transmission in discordant heterosexual couples – Consider treatment as strategy to prevent transmission (avoid sex with lesions, condoms) – Findings likely apply to MSM, multiple partners, asymptomatic HSV2 Lymphogranuloma venereum • Proctitis presentation among HIV+ MSM • Diagnosis – Genital or lymph node aspirates-culture, DFA, nucleic acid detection (CLIA validation) – Genotyping required for determining LGV strains – Serology can support (CF > 1:64), not validated for proctitis • Empiric Rx warranted for appropriate clinical syndrome – Doxycycline 100 mg PO bid x 21 d – ?? Azithromycin 1 g PO q wk x 3 wks Scabies/Pediculosis • Permethrin superior to crotamiton • Combined tx for crusted scabies oral/ topical scabicide – Some specialists recommend combined treatment with a topical scabicide and repeated treatment with oral ivermectin 200 ug/kg on days 1,2,8,9 and 15.Additional treatment on days 22 and 29 may be required for severe cases. Ivermectin should be combined with the application of either 5% topical benzyl benzoate or 5% topical permethrin (full body application to be repeated daily for 7 days then 2x weekly until discharge or cure). • Emerging resistance to all pediculicides except malathion Bacterial Vaginosis • Fastidious/uncultivated anaerobes • BV specific organisms ~antimicrobial resistance – Baseline organisms ?risk of failure • Alternative regimen – Tinidazole 2 g qd x 3 or 1 g qd x 3 • Management of recurrences • USPSTF- insufficient evidence to support screening high risk pregnant women; against screening in low risk Trichomoniasis • Screening- vaginal dc or high risk – Aptima TV analyte specific reagants – Consider rescreen women ( HIV-/HIV+) at 3 mo • NAAT preferred diagnostic in men • Antimicrobial resistance – 5-10% estimated prevalence – No data to guide tx of male partners of tx failure • Metronidazole 500 mg bid x 7 or tinidazole 2 gm • Interaction HIV~Trichomoniasis – Screening at entry into HIV care; rescreen – Tx 500 mg bid x 7 days HPV/Genital Warts • Counseling messages – Oral transmission • Clarification on use of HPV testing • GW treatment – Sinecatechins ointment (15%) as a patientapplied – Vitiligo side effect of imiquimod • HPV vaccine – Emphasis on the difference between bivalent and quadrivalent HPV vaccine for genital wart prevention New treatment for genital warts? • A new therapeutic modality is 15% sinecatechins ointment (Veregen®) – A mixture of 8 catechins which are the major polyphenols found in green tea leaves – It is applies three times daily until complete clearance of all warts or for up to 16 weeks – 3 RCT comparing it to placebo: • Clearance 57% vs 34% placebo; 53% vs 37% placebo; one RCT showed better efficacy in men (61% vs 41% placebo) versus women (58% vs. 34% placebo clearance) – Side effects: erythema, itching, pain, ulceration, edema, induration and vesicular rash Cervical Cancer Screening • Clarify indication for high risk HPV testing • HR HPV testing not indicated – – – – +/- vaccinate; STD screening for HPV Triage of LSIL Age <21 yr Primary cervical cancer screening only • Counseling messages – – – – Purpose of screening Normal pap/+HR HPV test Disclosure to sex partner Prevention measures- condoms, vaccine Anal Cancer Screening • Increased incidence of anal cancer in HIV+ MSM, some specialists recommend screening for anal SIL • Limited data on – – – – the natural history of anal intraepithelial neoplasia, the reliability of screening methods, the response to treatments, programmatic considerations • More data are needed before screening for anal SIL can be recommended Hepatitis A • Hepatitis A - international travelers, household/sex contacts, non-household contacts (e.g., play, daycare), IVDA • Post exposure- hepatitis A vaccine or IG (0.02 mL/kg) based on limited comparative data (no data >40 yr, medical conditions) Hepatitis B • Premastication as source of infection • HBV vaccine should be offered to all unvaccinated persons attending STD clinics and persons seeking STD tx (other settings) • HBV vaccine (hemodialysis dose) recommended in HIV+ OI Guidelines Hepatitis C • Sexual transmission of HCV (syphilis, LGV) • HCV serology at baseline HIV visit – Acute HCV- monitor LFTs • Unprotected sexual contact may facilitate spread of HCV (semen); barrier precautions discussed Sexual Assault in Children • STI screening in children should be independent of symptoms (Giradet et al, Pediatrics 2009) • 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. meningitidis, N. sicca, N. lactamica, N. cinerea, Moraxella catarrhalis) – Data insufficient for extragenital NAAT in girls – 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 • Routine preventive therapy as follow-up poor • HIV, hepatitis B, syphilis testing individualized – – – – Test results likely represent prevalent STIs Some centers have opted to stop STI testing Likely will not impact decision to provide prophylactic Rx Testing costs may be patient’s responsibility