STIs. Sexually Transmitted Infections. Kimberly A. Workowski, MD, FACP, FIDSA Professor of Medicine Emory University Atlanta, Georgia

Transcription

1 Sexually Transmitted Infections Kimberly A. Workowski, MD, FACP, FIDSA Professor of Medicine Emory University Atlanta, Georgia FORMATTED: 11/17/15 Learning Objectives After attending this presentation, participants will be able to: Discuss the current epidemiology of the most common bacterial sexually transmitted pathogens Describe the updated management and treatment recommendations per guidelines Identify prevention strategies on the individual and population level Slide 3 of 57 STIs and their Consequences Slide 4 of 57 Impaired fertility 19 million estimated annual new cases HIV transmission STIs Reproductive tract cancer Adverse pregnancy outcomes $17 billion estimated annual direct costs CDC. STD Surveillance Atlanta: U.S.DHHS; 2012 Chesson HW, et al. Perspect Sex Reprod Health 36(1):

2 STI Testing during HIV care Initial care visit Syphilis serology, NAAT at sites of exposure (gonorrhea, chlamydia) Hepatitis A, B, C Women Trichomonas testing (NAAT, culture) Cervical pap test per existing guidance (HIV OI guidelines) More frequent screening dependent on risk New sex partner, partner with concurrent partners or more than one partner, or partner with an STI High risk behavior Partner services, prevention counseling Slide 5 of Treatment Guidelines, HIVMA 2014 Proportion of MSM* Attending STD Clinics with Primary and Secondary Syphilis, Gonorrhea or Chlamydia by HIV Status, STD Surveillance Network (SSuN), 2014* Slide 6 of data are preliminary Slide 7 of adults in HIV primary care clinics in 4 cities GC,CT, syphilis,tv (women) screening (0,6 mo) 13% with STD at enrollment 94% of incident STDs in MSM (excluding trich) Most common in men: rectal chlamydia, oral GC Risks: polysubstance use, > 4 partners in 6 months 20% of MSM diagnosed with an STD by 6 months Mayer et al. Sex Transm Dis

3 Slide 8 of 57 SYPHILIS Slide 9 of 57 Slide 10 of 57 Cases of Syphilis, by Sex and Sexual Behavior United States, Cases Men who only have sex with men Men who only have sex with women Women Men who have sex * with men & women Primary and Secondary Syphilis Includes 30 states and Washington, DC which reported sex of partner data for 70% of reported cases of P&S syphilis for each year during *2014 data preliminary as of Mar 26,

4 Slide 11 of 57 Congenital Syphilis (CS) Rate and Rate of Syphilis Among Females CS rate (per 100,000 live births) CS rate United States, syphilis rate among females * Year syphilis rate (per 100,000 females) Primary and Secondary *2014 data preliminary as of Mar 26, 2015 Sensitivity of Serological Tests Slide 13 of 57 Stage of Disease (Percent Positive [Range]) Test Primary Secondary Latent Tertiary VDRL 78 (74 87) (88 100) 71 (37 94) RPR 86 (77 99) (95 100) 73 FTA-ABS* 84 (70 100) Treponemal Agglutination* 76 (69 90) (97 100) 94 EIA *FTA-ABS and TP-PA are generally considered equally sensitive in the primary stage of disease. Syphilis serologic screening algorithms Traditional Reverse sequence Slide 14 of 57 Quantitative RPR EIA or CIA RPR+ RPR- EIA/CIA+ EIA/CIA- TP-PA or other trep. test Quantitative RPR Early primary, requires RPR (active), false + TP-PA+ TP-PA- Syphilis Syphilis (past or unlikely present) Active infection, F+, miss early RPR+ Syphilis (past or present) TP-PA+ Syphilis (past or present) TP-PA RPR- TP-PA- Syphilis unlikely MMWR 60(5);2011 4

5 Slide 15 of 57 Slide 16 of 57 Seronegative Syphilis Slide 18 of 57 Syphilis Treatment Primary, Secondary, Early Latent Penicillin treatment of choice +/- HIV Benz Pcn 2.4 mu IM x 1 No benefit of additional therapy (Rolfs 1997) Enhanced (IM+oral) PCN alternatives Doxycycline, ceftriaxone Azithromycin 2 gm (Reidner 2005, Hook 2010) A2058G mutation/tx failure MSM>MSW (Su, CID 2013) Do not use in MSM or pregnancy CDC STD Treatment Guidelines

6 Monitoring Slide 19 of 57 Jarisch-Herxheimer reaction (Yang CID 2010) early syphilis, high RPR, prior pcn tx IRIS uncommon ARVs reduced risk of serologic tx failure lower risk of neurosyphilis CSF normalization with serum RPR decline Marra 2008, Ghanem 2008 Syphilis Management Issues in HIV+ Neurologic complaints should prompt consideration of neurosyphilis Symptoms: visual changes, hearing loss, facial weakness, stuttering stroke symptoms Early forms of neurosyphilis are most common Acute syphilitic meningitis (CN VI, VII, VIII) Meningovascular (stuttering stroke) Ocular syphilis Treat for neurosyphilis regardless of CSF evaluation Slide 20 of 57 CDC Clinical Advisory: Ocular Syphilis Outbreak April 3, 2015 Slide 21 of 57 CA and WA reported 15 cases from 12/ / Other states with cases under investigation (> 150 cases) - Most men over 40 yrs, 45% secondary or early latent, CSF 55% (70%+CSF VDRL) Most cases among MSM with HIV (>50%); new HIV diagnosis 30% - A few among HIV-negative persons, including heterosexual men and women Several have resulted in significant sequelae including visual loss, retinal detachment, and blindness For more information: 6

7 Evaluation of CNS Involvement Neurologic, ocular, auditory signs/sxs CNS invasion in early syphilis +/- HIV or neuro Clinical significance unknown (protein, pleocytosis) Neurosyphilis - combination of tests + clinical Higher cut off for CSF >20 WBCs may improve specificity of NS diagnosis LP: neuro/ocular sx, serologic treatment failure, tertiary Some studies - clinical and CSF consistent with NS RPR 1:32 and/or CD4 350 Unless neurologic sx, CSF exam has not been associated with improved clinical outcomes Slide 22 of STD Treatment Guidelines; Marra 2004; Libois A, STD 2007 ; Ghanem CID;Marra CID 2008 Slide 23 of 57 Slide 24 of 57 CHLAMYDIA 7

8 Chlamydia Treatment Effectiveness of azithromycin < doxycycline Data from one NGU trial and several rectal infection studies Doxycycline delayed release 200 mg tablets Amoxicillin moved to alternative regimen in pregnancy In vitro studies demonstrate PCN induces persistent viable noninfectious Chlamydia forms that revert to infectious forms after PCN removal (Wyrick) Earlier amoxicillin Rx studies in CT in pregnancy had major limitations RCT by Kacmar et al. showed higher TOC by LCR w/ azithro vs. amox (95% vs. 80%), Slide 25 of 57 Slide 26 of 57 LGV Proctitis Slide 27 of 57 Chlamydia serovars L1,L2,L3 Proctocolitis among HIV+ MSM (NAAT) Genotyping LGV vs non LGV Presumptive tx (doxy 100 mg bid x 21 d) Painful perianal ulcers or mucosal ulcers (HSV) 8

9 Urethritis Which agent is most likely associated with NGU treatment failure? Slide 28 of 57 1.Chlamydia trachomatis 2. Trichomonas vaginalis 3. Ureaplasma urealyticum 4. Mycoplasma genitalium 5. Herpes simplex M. genitalium Slide 29 of 57 Syndrome Summary risk estimate NGU 5.5 ( ) Cervicitis 1.7 ( ) PID/Endometritis 2.1 ( ) Infertility 2.4 ( ) 3.5 ( )* ~2.0 Preterm Delivery 1.9 ( ) Taylor-Robinson & Jensen, Clin Microbiol Rev, 2011; Sena et al, JID 2012, Lis, CID 2015 *Excluding one outlying study Recurrent NGU MSW > MSM (T. vaginalis) Urethral meatus (HSV); insertive rectal IC (E coli) Mycoplasma genitalium 15-25% of NGU, no FDA cleared test Azithromycin>doxycycline (3 RCTs) Azithromycin efficacy declining (Manhart, CID 2013) Moxifloxacin for recurrence (resistance reported) Slide 30 of 57 9

10 Slide 31 of 57 GONORRHEA Slide 32 of 57 Gonorrhea Rates of Reported Cases by Sex, United States, data are preliminary Criteria for GC Treatment Recommendations Antimicrobial resistance surveillance (GISP) Change in antimicrobial if resistance prevalence >5% (MMWR 1987) GC treatment efficacy >95% and 95% CI lower bound 90% (Handsfield,1992) >95% and 95% CI lower bound 95% (Moran, 1995) PK/PD factors Serum concentration at least 4x MIC90 x 10 hr after peak (Jaffe1987) At least twice the minimum efficacious dose Slide 33 of 57 10

11 GISP sites and regional laboratories United States University of Washington Portland Seattle Slide 34 of 57 San Francisco Las Vegas Orange Co. San Diego Los Angeles Phoenix Denver Albuquerque Tripler AMC Honolulu Dallas Minneapolis Oklahoma City Austin Pontiac City Chicago ClevelandPhiladelphia Baltimore Indianapolis Kansas Columbus Richmond City Greensboro Miami New York City Cleveland Clinic Birmingham Atlanta Emory University New Orleans University of Alabama at Birmingham Texas Dept. of State Health Services CDC surveillance report 2013 Slide 35 of 57 Prevalence of Penicillin, Tetracycline and Fluoroquinolone Resistance and Cefixime Reduced Susceptibility in Neisseria gonorrhoeae isolates, United States, Percent Tetracycline Resistance Penicillin Resistance 10 Reduced cefixime 5 Fluoroquinolone Resistance susceptibility Source: Gonococcal Isolate Surveillance Project (GISP), Centers for Disease Control and Prevention Percentage 2 Percentage of Neisseria gonorrhoeae isolates with reduced cefixime susceptibility Gonococcal Isolate Surveillance Project (GISP), Slide 36 of / 2008 Minimum inhibitory concentration (MICs) 0.25 µg/ml *2014 data are preliminary as of Mar 30, 2015 Cefixime susceptibility not tested in 2007 and * Revised Tx Recommendations 12/2010 Revised Tx Recommendations 8/

12 Slide 37 of 57 Uncomplicated Gonococcal Infections of Cervix, Urethra & Rectum Ceftriaxone 250 mg as a single intramuscular dose PLUS Azithromycin 1 g orally Alternative: If Ceftriaxone is not available: Cefixime 400 mg PLUS azithromycin 1 gram Test of cure not needed after treatment for urogenital/ rectal infection, but for pharynx (alternative) 2015 CDC STD Treatment Guidelines New Treatment Option NIH sponsored RCT (Kirkcaldy, CID 2014) Gentamicin 240 mg IM + azithromycin 2 g PO, OR Gemifloxacin 320 mg PO + azithromycin 2 g PO Rationale Additive effect, gentamicin and azithromycin in vitro Gemifloxacin more active against ciprofloxacin resistance or GyrA and ParC mutations Slide 38 of 57 New Clinical Data on Other Regimens Cefixime PK extended duration high dose (NCT ) Solithromycin 1200 mg (n=22; 22/22 ur/cx, 2/2 rectal, 5/5 pharynx (Hook, CID 2015) 1000 mg vs Ceftriaxone 500 mg (NCT ) Delafloxacin 900 mg vs ceftriaxone 250 mg IM (terminated) GSK mg vs 3000 mg (NCT ) AZD or 3000 mg vs ceftriaxone 500 mg IM Slide 39 of 57 12

13 Suspect Treatment Failures Most treatment failure likely due to reinfection If tx failure suspect, obtain culture/susceptibility test Treatment Slide 40 of 57 If reinfection likely (ceftriaxone/azi ); Rx ceftriaxone 250 mg +azithromycin 1 gram If reinfection likely (cefixime/azi), Rx ceftriaxone 250 mg + azithromycin 2 gram If tx failure suspected, Rx gemifloxacin 320 mg +azithromycin 2 g or gentamicin 240 IM + azithromycin 2g Report (local/state health department) Test of cure 7-14 days after retreatment (culture/ast preferred with NAAT) Ensure partner treatment 2015 CDC STD Treatment Guidelines Genital Herpes Increasing proportion of anogenital infections HSV-1 (young females, MSM) IgM testing not useful Type specific serologic tests HerpeSelect HSV-2 ELISA may be false + at low index values ( )- confirmed with Biokit or WB HerpeSelect HSV-1 ELISA insensitive for HSV-1 (80%) Head to head comparison of type specific assays vs WB No change in recommended therapy Antiviral resistance (Foscarnet, topical therapy) Slide 41 of CDC Treatment Guidelines Sexually Transmitted GI Syndromes Proctitis GC, CT, HSV, syphilis Proctocolitis Campylobacter, shigella, salmonella, Entamoeba histolytica, LGV Enteritis Giardia Hepatitis A, B, C Slide 42 of 57 13

14 Slide 43 of 57 Antimicrobial Resistant Shigella in MSM HCV Infection in MSM Increased awareness of sexually acquired HCV Unprotected receptive anal intercourse Rough or poorly lubricated anal penetration(fisting) Ulcerative STIs (syphilis, LGV) Rapid progression after acute hcv Risk based annual screening per guidelines Acute infection may have negative HCV antibody (CD4 <200) HCV RNA in patients with new, unexplained transaminase elevation Slide 44 of 57 STD Treatment Guidelines, HIV OI Guidelines T vaginalis and HIV infection Slide 45 of 57 Screening at entry to care and annually if active APTIMA T vaginalis; BD Probe Tec TV Qx amplified DNA Assay A molecular test-resolved algorithm (negative wet prep followed by NAAT - Aptima TV - sensitivity %, specificity of % (Nye) Longer treatment course better in women metronidazole 500mg BID x7d (vs. 2g )-less TV at TOC/3 mo RR 0.46, CI: (Kissinger, 2010) Potential factors- BV infection, arv, changes in vaginal ecology Treatment reduces genital HIV shedding (Kissinger 2009, Anderson 2012) Retesting 3 mo after treatment CDC Treatment Guidelines 14

15 Slide 46 of 57 HPV Estimated number of HPV attributable cancer cases per year, United States Slide 47 of 57 Anal Cancer Screening Primary Prevention HPV vaccination of MSM 4v or 9v (MMWR 2015;64:300 4) 3 dose schedule (ongoing studies of 2 dose schedule) Secondary Prevention Some centers perform anal cytology in high risk populations High risk HPV tests not clinically useful for anal cancer screening (high prevalence of anal HPV infection) No studies document treatment of anal HSIL reduces anal ca No routine standard treatment for HSIL Anchor study-? tx of anal HSIL reduces incident anal cancer vs digital rectal exam; safety (infrared coagulation, electrocautery, imiquimod, laser, 5FU) Biomarkers for anal precancer Slide 48 of 57 15

16 Slide 49 of 57 Progression model of human papillomavirus (HPV)- related cancers Source: Wentzensen N. Screening for anal cancer: endpoints needed. Lancet Oncol May;13(5): Slide 50 of 57 Slide 51 of 57 ACIP HPV vaccine recommendations Routine vaccination at age 11 or 12 years* Vaccination recommended through age 26 for females and through age 21 for males not previously vaccinated Vaccination recommended for men who have sex with men and immunocompromised men (including persons HIV infected) through age 26 Vaccination of females is recommended with 2vHPV, 4vHPV, or 9vHPV Vaccination of males is recommended with 4vHPV or 9vHPV *vaccination series can be started at 9 years of age MMWR 2015;64:

17 number of cases per year Slide 52 of 57 Estimated numbers of HPV associated cancers attributable to HPV 16/18 and 5 additional types in 9 valent vaccine, U.S. females males * HPV 16/18 5 additional types Proportion of Australian born females and males diagnosed as having genital warts at first visit, by age group, Females Impact of HPV vaccination in Australia Males Slide 53 of 57 Ali, et al. BMJ 2013 Prevention Strategies High-intensity behavioral counseling Partners, pregnancy, protection, practices, past STIs Pre-exposure vaccination (hepatitis A, B, HPV) Screening per guidelines (syphilis, CT, GC, trichomonas) Male latex condoms Mucosal fluids (HIV, GC, CT, trichomoniasis) Avoid agents that disrupt anal/vaginal epithelium N9 spermicide, hyperosmolar lubricants Male circumcision reduces risk of HPV, genital herpes (African heterosexuals) Slide 54 of 57 17

18 Slide 55 of 57 Patel et al. Sex Transm Dis STD Treatment Guidelines Slide 56 of 57 Diagnostic, treatment, and prevention recommendations Evidence based systematic review (IOM report on Clinical Guidelines) MMWR, Evidence Tables, Screening Recommendations, and wall chart MMWR, pocket guide, and wall chart available for order STD Treatment Guide app for Apple and Android Devices National Network of STD Clinical Prevention Training Centers National STD training calendar Free STD clinical consultation for Course registration healthcare providers 1-5 business days depending on In-person and virtual urgency STD resources/links Requests linked to local expert faculty Slide 57 of 57 18