Overview. Disclosures. Sexually Transmitted Diseases: Key Clinical Information for 2017
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1 Sexually Transmitted Diseases: Key Clinical Information for 2017 Susan S. Philip, MD, MPH Director, Disease Prevention and Control Branch Population Health Division San Francisco Department of Public Health Assistant Clinical Professor of Medicine Division of Infectious Diseases University of California, San Francisco Disclosures The views expressed herein do not necessarily reflect the official policies of the City and County of San Francisco; nor does mention of the San Francisco Department of Public Health imply its endorsement. S. Philip has received research support from Roche Diagnostics, SeraCare Life Sciences, Melinta Therapeutics, GlaxoSmithKline and Cepheid Inc. Overview (Very!) Brief US STD Epidemiology Sexual History Select STDs: Updates in screening, prevention or treatment CDC Treatment Guidelines App for ios and Android THE guide for STD treatment Available now, FREE! (accept no competitors) 4 1
2 Why Diagnose and Treat STDs? > 19 million STDs in US annually Increases across syphilis, CT, GC for first time in 2015 Cost: 16.4 billion (2009) Health consequences Pelvic Inflammatory Disease Ectopic pregnancy Infertility Blindness (Ocular syphilis) Neonatal HIV, herpes simplex virus (HSV) and congenital syphilis Increased risk of HIV acquisition Screening as a quality indicator HEDIS (CT screening in young women) HIV Primary Care Health Disparities Nationally there are populations who bear a disproportionate share of STDs Men who have sex with men (MSM) Adolescents African Americans Transgender persons Studies demonstrate that individual behaviors alone do not account for the increased rates Ellen STD Laumann STD Oster AIDS 2011 High rates of syphilis and HIV in US MSM Rates per 100, Syphilis HIV MSM MSW Women CDC % 50% 40% 30% 20% 10% 0% As HIV Pre Exposure Prophylaxis (PrEP) Expands, STD screening is important STI Incidence After 12 Months of PrEP Use In Kaiser SF PrEP Cohort 50% 33% 33% 28% 5.5% Any STI Rectal STI Chlamydia Gonorrhea Syphilis HIV 0% Volk et al. CID 2015; slide courtesy Dr. Jonathan Volk 2
3 Brief(!) Sexual History is Key Neutral language: Do you have sex with men, women, or both? (highest value) What are you doing to prevent unwanted pregnancies or STDs rather than You use condoms 100%, right? Consider adding questions to selfregistration materials Find referral resources for complex trauma or sexual dysfunction Practical Provider Tools for Sexual History Fenway Institute and National Association of Community Health Centers Scripts Downloadable presentation Coding Guides EMR implementation CDC STD Treatment Guidelines Case 1 At a new patient s initial visit, you learn he is a gay man who has had 3 sex partners in the last year. He feels fine and says all STD tests were negative a year ago. In addition to an HIV test, what else would you order? 1. No additional tests he is asymptomatic 2. Urine gonorrhea and chlamydia 3. Syphilis serology 4. pharyngeal GC, rectal GC and CT, syphilis serology 5. I need to know more before deciding Strongest recs: Men who have sex with men HIV positive persons Syphilis screening Recommendations for Non-Pregnant Adults Others informed by national and local epi: hx incarceration, sex work, geography (highest proportion in South, highest rates in West) Screening for Syphilis Infection in Non-pregnant Adults and Adolescents. US Preventive Services Task Force Recommendation Statement JAMA
4 STD Asymptomatic Screening for Women Sexually Active women up to age 25 Routine annual chlamydia and gonorrhea screening Other STDs and HIV based on risk Women over 25 years of age STD/HIV testing based on risk Pregnant women Chlamydia Gonorrhea (<25 years of age or risk) HIV Syphilis serology HepB sag Hep C (if high risk) STD Asymptomatic Screening for MSM Screen at least annually, or every 3 6 mos if high risk* HIV Syphilis Urethral GC and CT Rectal GC and CT (if anal sex) Pharyngeal GC (if oral sex) Also screen for: Hepatitis B surface Ag (frequency not specified) Hepatitis C if IDU, born or transfusion before 1992 * High risk: multiple and/or anonymous partners, drug use, or these risks in patient s partners STD Asymptomatic Screening for HIV+ MSM : Same as HIV uninfected MSM plus: Anal Cancer in HIV+ MSM: Annual digital rectal exam may be useful, some centers perform anal Pap and HRA for ASC US or worse. HCV : HCV antibody tests should be serially monitored, at least yearly and more frequently depending on local circumstances (HCV prevalence, incidence, resources, and other factors), to detect conversion from HCVantibody negative to positive. Summary: Use Nucleic Acid Amplification Tests (NAATs) for symptomatic AND asymptomatic patients Optimal Specimens: Women vaginal swabs (may be self collected) Men first catch urine Extragenital (oropharyngeal, rectal) NAAT not FDA-cleared, but recommended need lab validation 4
5 Proportion of asymptomatic rectal and urethral chlamydial and gonococcal infection among MSM San Francisco City Clinic, 2011 Rectal Infections 5% 9% 70-90% of GC and CT infections in MSM would be missed if only urine based screening were done 95% 91% Urethral Infections Chlamydia n=308 42% Gonorrhea N=237 11% Asymptomatic Symptomatic 58% Chlamydia n=234 89% Gonorrhea n=244 Adapted from Kent, CK et al, Clin Infect Dis July 2005 Patton CID 2014 Case 1, continued Patient reports receptive anal sex (intermittent condom use) and oral sex. The GC/CT NAATs come back first positive for rectal gonorrhea. All others neg. Treatment? He adamantly refuses to consider any injectable regimen. Gonorrhea Treatment is one of CDC s key strategies to reducing risk of resistant Neisseria gonorrhoeae 1. Azithromycin 2 g PO x 1 2. Ciprofloxacin 400 mg PO x 1 3. Cefixime 400 mg PO x1 PLUS azithromycin 1 PO x1 4. Gemifloxacin 320 mg PO + azithromycin 2 g PO Antibiotic Resistance Threats in the United States, CDC
6 Current Recommended Gonorrhea Treatment any anatomic site Kirkcaldy CID 2014 Ceftriaxone 250mg IM x 1 Azithromycin 1g PO x 1 This is Dual treatment for GC add the azithromycin or doxycycline regardless of CT result Alternative: Cefixime 400mg PO x 1 Azithromycin 1g PO x 1 Primary Outcome Gentamicin/Azithro Gemifloxacin/Azithro Urethral/cervical (n/n=202/202) (n/n=198/199) 100% (95%CI 98.5% 100%) 99.5% (95% CI 97.6% - 100%) Secondary Outcomes Gentamicin/Azithro Gemifloxacin/Azithro pharyngeal n/n= 10/10 (100%) n/n=15/15 (100%) rectal N=1/1 (100%) N=5/5 (100%) Mild-mod GI side effects were common in both arms (47-55%) Resistant Gonorrhea : More to Come? Question If a male patient who presents with urethritis is treated empirically with azithromycin 1g PO, and NAAT returns 2 days later as gonorrhea positive, does patient need to get CTX 250mg IM x 1 AND repeat dose of Azithro 1g? Routine gonorrhea surveillance: Seven isolates from Honolulu with high level Azithromycin resistance. Remember: Monotherapy with macrolides or fluoroquinolones not recommended Very Concerning: Five of seven also with reduced susceptibility to ceftriaxone (first cases documented in US) No treatment failures yet in U.S. with CDC recommended dual treatment 1. Definitely Yes 2. Definitely No 3. Maybe? 6
7 When do you have to re dose? May not always need to re dose if azithro taken first Most experts state due to long half life of azithromycin, probably OK to administer ceftriaxone within 5 days California Department of Public Health Guidance: redose azithro if greater than 24h delay until ceftriaxone administered But, if Ceftriaxone administered first and delay in taking azithro (e.g. delay in picking up azithro at pharmacy) MUST re administer both simultaneously Disseminated Gonococcal Infection (DGI) Arthritis (monoarticular) in 30% Dermatitis arthritis syndrome Characterized by fever, chills, skin lesions (70%), arthralgias, tenosynovitis Less commonly, hepatitis, myocarditis, endocarditis, meningitis Rash characterized as macular or papular, pustular, hemorrhagic or necrotic, mostly on distal extremities DGI Skin Lesions DGI Management May require hospitalization Clinical evaluation for endocarditis and meningitis Labs Synovial fluid culture and cell count Blood cultures x 2 (ask lab eval for GC) positive in 50% of patients presenting with dermatitis arthritis syndrome Genital, rectal, skin lesion GC testing (culture and NAAT) Tx: Ceftriaxone 1g IM or IV q 24 hours + azithromycin 1g PO x 1 Alternative: Cefotaxime OR Ceftizoxime 1g IV q8 hours + azithromycin 1g PO x 1 Continue IV/IM hours after clinical improvement, then may switch to oral GC agent per sensitivities Evaluate and empirically treat asymptomatic sex partners for uncomplicated GC Suzaki et al. Internal Medicine
8 Case 2 A 27 year old sexually active HIV+ gay man presents with complaints of severe rectal pain and bleeding. These symptoms began acutely 3 days ago. He is unable to tolerate anoscopy due to pain but there is evidence of purulent mucus and blood on external exam. If you were to pick an empiric treatment regimen today, while awaiting laboratory results, would it be: Treatment of uncomplicated Chlamydia Adolescents and Adults Recommended regimens (non pregnant): Azithromycin 1 g orally in a single dose Doxycycline 100 mg orally twice daily for 7 days Recommended regimens (pregnant): Azithromycin 1 g orally in a single dose 1. Ceftriaxone 250mg IM x 1 + Azithromycin 1g PO x 1 2. Doxycycline 100mg PO bid x 21 days 3. Azithromycin 1 g PO x 1 4. Azithromycin 1g PO qweek x 3 weeks Treatment of uncomplicated Chlamydia Changes in the 2015 Guidelines Additional Alternative Regimen (non pregnant): Doxycycline (delayed release) 200 mg po QD x 7 d Equally efficacious to BID doxy, less GI side effects More $$$$ Move to Alternative Regimen (PREGNANCY): Amoxicillin 500 mg po TID x 7 days CT persistence documented in vitro after treatment prompted removal from recommended to alternate Lymphogranuloma venereum (LGV) Caused by specific serovars of Chlamydia trachomatis Serovars L1, L2, L3 Compared to other serovars of CT, more invasive and virulent, tending to result in systemic disease Organism travels through lymphatics to multiply within macrophages in regional lymph nodes Transmission primarily sexual Rate of transmission unknown Reservoir not defined Endemic in many tropical regions, sporadic in N. America and Europe 8
9 Classic LGV Infection Three stages Similar to syphilis local, early systemic, late localized areas Primary Secondary generally 2-6 weeks after painless genital primary papule Lymphadenititis 3-42 days after Classic exposure presentation of Resolves in days groove sign Stage often Constitutional missed symptoms Relationship to Buboes 1/3 urethritis and rupture cervicitis unclear Tertiary Year to years after initial infection Genital elephantiasis Rectal strictures, lymphorrhoids, perirectal abscesses, anal fistula Frozen pelvis, infertility LGV: Recent shift? In N. America and Western Europe clinical presentation since 2000 s shifting to anorectal syndromes in MSM, particularly HIV infected Proctitis Anal pruritus (itching) Mucous rectal discharge Proctocolitis & hyperplasia of intestinal and peri rectal lymphatic tissue Symptoms of fever, rectal pain, tenesmus (straining) Anoscopy shows diffuse friability and discrete ulcerations May be mistaken for inflammatory bowel disease LGV Primary lesions LGV Bilateral Inguinal Adenopathy groove sign papule generally painless DOIA
10 LGV Bubo, ruptured LGV Proctitis: Sigmoidoscopy findings diffuse friability discrete ulceration Diagnosing LGV Proctocolitis: Primarily by clinical findings/history severe proctocolitis in MSM is concerning for LGV May be mistaken for inflammatory bowel disease Serologic tests can support diagnosis Rectal CT NAAT will be positive but does not further specify whether LGV serovars are the cause Swabs of rectal lesions visualized by anoscopy is better than blind rectal swab Local or state public health may be able to facilitate molecular confirmation, but likely with time delay. Treatment of LGV Recommended: Doxycycline 100 mg PO BID x 21 days Alternative: Erythromycin base 500 mg PO QID x 21 days Azithromycin 1 g PO weekly for 3 weeks also may be effective based on expected anti chlamydial activity but not routinely recommended Partners within past 30 days of onset of symptoms need evaluation. If w/o symptoms treat: Doxycycline 100 mg BID x 7 days or azithromycin 1g PO x 1 10
11 Case 3 38 year old woman, new to your practice, previously injected drugs but none in the past 10 years. HIV and HCV screen negative and she is asymptomatic. The lab reports the patient s syphilis test results are: RPR 1:4 and TPPA+ Your next step? 1. Treat with benzathine PCN 2.4 mu IM x 1 2. Treat with benzathine PCN 2.4 mu IM x 3 3. Do nothing as this is unlikely to be syphilis 4. Perform an LP to rule out neurosyphilis 5. Perform a pregnancy test Syphilis No Change in 2015 Guidelines Stage determines Treatment Primary, Secondary & Early Latent (infection in past 1 year): Benzathine penicillin G 2.4 million units IM in a single dose Late Latent and Unknown Duration (infection earlier than 1 year ago): Benzathine Penicillin G 7.2 million units total, given as 3 doses of 2.4 million units each at 1 week intervals Neurosyphilis (can occur anytime in the course of infection): Aqueous Crystalline Penicillin G million units IV daily administered as 3 4 million IV q 4 hr for d No enhanced efficacy of additional doses of penicillin, amoxicillin or other antibiotics even if HIV infected! Syphilis No Change in 2015 Guidelines Stage determines Treatment Primary, Secondary & Early Latent: Alternatives (non pregnant penicillin allergic adults): Doxycycline 100 mg po bid x 2 weeks Tetracycline 500 mg po qid x 2 weeks Ceftriaxone 1 g IV (or IM) qd x d Azithromycin 2 g po in a single dose* * Should be used with caution and not in MSM or pregnant women In pregnancy, benzathine penicillin is the only recommended therapy. No alternatives Syphilis When to LP? Clinical signs of neurosyphilis Cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, auditory or ophthalmic abnormalities Serologic treatment failure Evidence of active tertiary syphilis (e.g. aortitis and gumma) HIV positive and late latent syphilis or syphilis of unknown duration 11
12 Consider Ocular Syphilis! Additional Screening after an STD infection Cluster of four cases Washington State Dec 2014 Jan 2015 All MSM, 75% HIV-infected Two patients with permanent visual loss Subsequently eight cases identified in San Francisco Dec 2014-March 2015 (75% MSM, 88% HIV-infected) Providers should have a high suspicion for syphilis in patients with visual complaints, especially HIV-infected MSM Treatment for ocular syphilis is IV PCN as for neurosyphilis even if the CSF lab tests are unremarkable Women with CT, GC or trichomonas should be rescreened at 3 months after treatment. Men with CT or GC should be rescreened at 3 months after treatment. Patients diagnosed with syphilis should undergo follow up serologic serology per current recommendations as well as be screened for other STDs including HIV. HIV testing should also be considered in all patients with a prior STD history Should also perform pregnancy testing in women diagnosed with an STD Slide Courtesy I. Park MD, MS Rates of Congenital Syphilis continue to rise Additional Points on Preventing Congenital Syphilis Congenital cases are sentinel events for clinical delivery systems AND public health Public health prioritizes female partners of male syphilis cases please prepare patients and encourage them to work with us to ensure partners are treated Remember that penicillin is the only acceptable treatment for pregnant women with syphilis must desensitize if serious true allergy Must adhere to strict 7 day interval for weekly benzathine penicillin in pregnant patients with late latent syphilis (likely OK to extend interval up to 14 days in non pregnant adults). If longer than 7 day interval in pregnancy, must restart series. Bowen MMWR Morb Mortal Wkly Rep Nov 13;64(44): accessed March 1,
13 Fantastic new STD Clinical and CME resource: Thank You! Ina Park California STD/HIV Prevention Training Center Stephanie Cohen 2015 CDC STD Treatment Guidelines: Contact information:
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