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  • Overall, HSV-2 seroprevalence increases with number of lifetime sex partners for all race/ethnicity groups (p<.001) Seroprevalence high among non-Hispanic blacks even with few lifetime sex partners: with only 2-4 partners, seroprevalence 34%
  • Herpetic lesions are associated with an influx of activated CD4 lymphocytes which may result in an increased expression of HIV on mucosal surfaces. HSV reactivation is more frequent in HIV-infected patients.
  • The burden of infection is highest among sexually active adolescents and young adults. This figure shows chlamydia prevalence by age, based on nationally representative data from the National Health and Nutrition Examination Survey, NHANES. [ CLICK ] Sexually active people aged 14-24 have about 3 times the chlamydia prevalence of sexually active adults aged 25-39.
  • Chlamydia-associated tubal inflammation can result in fibrosis, scarring, and loss of tubal function, which in turn can lead to long-term sequelae, such as tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Tubal factor infertility is the inability to conceive due to structural or functional fallopian tube damage. Chlamydia is the leading preventable cause of tubal factor infertility.
  • To find and treat sex partners of patients with chlamydia, CDC and many medical associations endorse expedited partner therapy, or EPT. EPT involves providing prescriptions or medications to the patient to take to her partner, without examining the partner first. Two randomized controlled trials provide evidence that EPT is useful in assuring partner treatment and reducing repeat infections.
  • Bacterial antibiotic resistance or the inability of an antibiotic to cure an infection, undermines treatment success, heightens the risk of complications, and facilitates disease transmission since it lengthens the duration of the infection. Neisseria gonorrhoeae has demonstrated the ability to progressively develop antibiotic resistance to nearly all of the antibiotics used for treatment. Starting with the sulfa drugs at the dawn of the antibiotic era, gonorrhea subsequently developed resistance to penicillin, tetracycline, and most recently, the fluoroquinolones .
  • before generalizing to the heterosexual population and geographically to the entire US. In 2007, CDC no longer recommended fluoroquinolones for the treatment of gonorrhea. This left us with cephalosporins as the last remaining class of antibiotics that were effective, well-studied and recommended.
  • This is a broad overview of hpv associated diseases and cancers in Men and women. A variety of Genital cancers and precancers are attributed to HPV, of course the most Well described is cervical cancer. In addition, a subset of op cancers are due to HPV, RRP or recurrent respiratory papillomatosis, and anogenital warts. The next few slides I will describe the prevalence Of cervical cancer precursor lesions and anogenital Warts by agegroup. These contribute to a bulk Of the burden of HPV-associated conditions.
  • Australia is one country that has achieved high coverage of HPV vaccine in the target age groups through school based vaccination and national funding of all vaccine in the recommended age groups. They also had a limited 2 year funded catchup through age 26 yrs. Australia is the first country to demonstrate an impact of HPV vaccine – They used Quadrivalent vaccine they were were able to observe an impact on genital warts outcomes, one of the first HPV related out comes expected to be observed since genital warts occur soon after infection. Here is shown proportion of women in the eligible age group with first genital wart diagnoses by half year intervals in two time periods, prevaccine period and the vaccine period. As noted, there have been a significant 73% decrease in GW since introduction of vaccine in resident women compared with 25% decline among those who are non resident.

Am 8.00 workowski Am 8.00 workowski Presentation Transcript

  • STIs:Essentials for the Clinician Kimberly Workowski, M.D, FACP, FIDSA Professor of Medicine, Division of Infectious Diseases, Emory University Division of STD Prevention, CDC
  • Learning Objectives Identify the most common infectious causes of genital ulcers and discuss the diagnostic evaluation Describe the epidemiology, diagnosis, and recommended management of the most common sexually transmitted infections Review various prevention strategies for sexually transmitted infectionsThere are no financial relationships to disclose relevant to this activity.
  • Sexually TransmittedBacteria Infections• Gonorrhea (Neisseria gonorrhoeae)• Chlamydia (Chlamydia trachomatis)• Syphilis (Treponema pallidum)• Chancroid (Haemophilus ducreyi)Viruses• Human papillomavirus• Genital herpes• Hepatitis A, B, CParasites• Trichomoniasis (Trichomonas vaginalis)• Pubic lice (Phthirus pubis)
  • Estimated Annual Burden and Cost of STIs in the U.S. Estimated Annual Estimated Annual Direct Costs Reported Cases, 2009 New Cases** (millions)*** Chlamydia 1,244,180 2.8 million $701 Gonorrhea 301,174 718,000 $138 HIV* 42,959 60,000§ $8,900 Syphilis 13,997 70,000 $25 Hepatitis B* 4,033 80,000 $47 HPV NA 6.2 million $5,800 Genital Herpes NA 1.6 million $1,100 Trichomoniasis NA 7.4 million $198 Total 1,606,343 18.9 million $17 billion* HIV and Hepatitis B estimates include costs of sexually-acquired cases only**US annual estimated new cases (Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalenceestimates, 2000. Perspect Sex Reprod Health. 2004 Jan-Feb;36(1):6-10.)§ Annual new HIV cases, 2008 estimate ; all other annual cases are 2004 estimates (1Hall HI, Ruiguang S, Rhodes P, et al. Estimation of HIV incidence inthe United States. JAMA. 2009;300:520-529.)***Updated to 2010 $US using medical care component of CPI. Total may differ from sum of all diseases due to rounding.Adapted from: Chesson HW, Blandford JM, Gift TL, Tao G, and Irwin KL. The estimated direct medical cost of sexually transmitted diseases amongAmerican youth, 2000. Perspectives on Sexual and Reproductive Health 2004, 36(1): 11-19.
  • STIs Impact on Women• Asymptomatic infection• Symptoms confused with another condition• Reproductive health consequences – Infertility, stillbirth, premature birth• Congenital infection (HSV, syphilis, HIV)• HPV link with cervical cancer
  • USPSTF Screening Recommendations for Women Grade Age/Special ConsiderationsUSPSTFChlamydia Screening in A Sexually active women < 24 and at-risk womennon-pregnant women > 25Chlamydia Screening in B All women < 24 and at-risk women > 25pregnant womenGonorrhea Screening in B All at-risk sexually active women (includingwomen pregnant women) - special considerations also include population risk factorsHIV screening in A All adolescents and adults at increased riskadolescents and adultsSyphilis Screening A All pregnant women and all persons at risk
  • USPSTF & ACIP Screening Recommendations for Women Grade Age/Special ConsiderationsUSPSTFCervical Cancer A Sexually active women with a cervixHepatitis B Screening A At first prenatal visitin pregnant womenHigh-intensity B All adolescents and adults at increased riskbehavioral counselingto prevent STDsACIPHPV Vaccination -- Recommended for women ages 9 – 26
  • Screening• Test all sexually active women at risk regardless of sexual activity• Retest women with chlamydia or gonorrhea 3 months after treatment• Screen women for trichomonasis if HIV+, high risk, or vaginal discharge
  • Clinical Prevention Guidance• High intensity behavioral counseling (USPSTF) – Partners, pregnancy, protection, practices, past STIs• Pre-exposure vaccination- HAV, HBV, HPV• Male latex condom – HIV, GC, CT, Trichomoniasis – May reduce HSV-2, HPV and genital warts• Male circumcision may reduce acquisition of some STI (HPV, genital HSV)2010 CDC STD Treatment Guidelines
  • Clinical Presentation• Genital ulcer: Syphilis, HSV, CT (LGV), H.ducreyi, Granuloma inguinale• Urethritis/Cervicitis: GC, CT• Proctitis: GC, CT(LGV), syphilis, HSV• Vaginal discharge: Trichomonas, BV• Genital warts: Papillomavirus
  • Sexually Transmitted Genital Ulcer Disease Treponema Haemophilus Herpes simplex pallidum ducreyiFeature (Syphilis) (Chancroid)Incubation period 2-7 days 2-4 weeks 1-14 daysestimatesUlcer Small, Superficial, Deep, small toappearance superficial, medium size, large; smooth: well undermined, erythematous demarcated; ragged edge, edge, circular elevated edge, irregular circular/oval shapeInduration None Firm SoftPain Exquisitely Typically painless VariableLymphadenopathy Firm, tender, Firm, Tender, can often bilateral nontender, suppurate; bilateral unilateral: superinfection
  • Sexually Transmitted Genital Ulcer Disease Chlamydia trachomatis CalymmatobacteriumFeature (LGV) granulomatis (Granuloma Inguinale)Incubation period 3-42 days 8-80 daysestimatesUlcer appearance Variable depth, small Small to large lesions; to medium size; with elevated edge and elevated edge, round/ beefy base, irregular oval shapeInduration Occasionally firm FirmPain Variable Not typicalLymphadenopathy Large, tender, Pseudobuboes; regionalcharacteristic unilateral; suppurate lymphadenopathy with superinfection
  • Genital Ulcer Evaluation• Clinical diagnosis often inaccurate• Multiple agents• Immunocompromised• Prevalence of disease; travel history• Evaluation – syphilis serology, darkfield microscopy, HSV culture or PCR, biopsy• Treat for dx most likely- clinical presentation/epi
  • Herpes Simplex Virus Type 2 (HSV-2)Highly prevalent, most common cause of genital ulcer disease worldwide (Corey, JAIDS 2004) HSV-2 Population Seroprevalence 14-49 year-olds in US 17% US STD clinic patients 40% African-American women, 14-49 years 50% HIV-negative women, southern Africa 70% HIV-positive persons globally ~80%
  • HSV-2 Seroprevalence by Number of Lifetime Sex Partners and Race/Ethnicity (Xu, JAMA 2006) 60 1 partner 50 2-4 partners 40 5-9 partners 30 10+ partners 20 10HSV-2 seroprevalence (%) 0 Non-Hispanic White Non-Hispanic Black Mexican American
  • Herpes Simplex Virus (HSV)• HSV-1 & HSV-2 cause genital infections – HSV-2 more likely to reactivate – HSV-2 associated with risk of HIV acquisition• Primary infection: fever, HA, myalgias, itching, vaginal/urethral dc, tender LN• Majority of infections unrecognized
  • HSV2 Genital Shedding• Sexual transmission through subclinical shedding• 498 men and women with HSV2+ self collected genital swabs x 30 d (Tronstein, JAMA 2011;305(14):1441-9) Symptomatic Asymptomatic HSV2 (% of days) 20% 10% <.001 Subclinical 13% 8.8% <.001 shedding HSV DNA 4.3 log 4.2 log .27
  • HSV Diagnosis• Cell culture or PCR• IgM test unreliable• Type–specific HSV serology (IgG) – Recurrent/atypical lesions cx neg ulcers – clinical dx without lab confirmation – partners – not indicated for general population screening 2010 CDC STD Treatment Guidelines
  • HSV• Antiviral efficacy – Acyclovir, valacyclovir, famciclovir effective – Acyclovir/valacyclovir effective (suppression) – Famciclovir slightly less effective (suppression)• Acyclovir resistance – Rare in immunocompetent – Topical cidofovir or imiquimod – Suppression- less resistance (bone marrow trans) 2010 CDC STD Treatment Guidelines
  • Efficacy of Oral Valacyclovir in Prevention of HSV-2 Transmission (Corey. NEJM 2004) 4.5 4.0 3.8% P=0.039Percentage with Infection 3.5 (28/741) RR: 0.50 (95% CI: 0.26, 0.94) 3.0 50% Reduction 2.5 2.0 1.9% 1.5 (14/743) 1.0 0.5 0.0 Placebo Valaciclovir 500 mg once daily
  • Primary and Secondary Syphilis—Rates by Sex and Male-to-Female Rate Ratios, United States, 1990–2010Rate (per 100,000 population) Rate Ratio (log scale)25 16:1 Male Rate Female Rate20 Total Rate 8:1 Male-to-Female Rate Ratio15 4:110 2:150 1:1 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year
  • Primary and Secondary Syphilis—Reported Cases* by Stage, Sex, and Sexual Behavior, United States, 2010 Cases 6,000 Primary 5,000 Secondary 4,000 3,000 2,000 1,000 0 MSW† Women MSM†* Of the reported male cases of primary and secondary syphilis, 18.3% were missing sex of sex partner information.† MSW = men who have sex with women only; MSM = men who have sex with men.
  • Syphilis• Definitive diagnosis for early syphilis – darkfield microscopy; PCR – No commercially available Tp detection tests• Nontreponemal/treponemal serologic testing – Reverse serologic screening (trep/nontreponemal)• CNS involvement can occur at any stage• Management principles for HIV+ similar
  • Treatment Recommendations Primary, Secondary, Early Latent• Penicillin treatment of choice +/-HIV – Benzathine penicillin 2.4 mu IM x 1• No benefit of additional therapy – Enhanced treatment (IM + oral)• Penicillin alternatives – Doxycycline, ceftriaxone – Azithromycin 2 gm (resistance/treatment failure) • Use only if penicillin or doxycycline not feasible • Do not use in MSM or pregnancy
  • Cervicitis• Frequently asymptomatic - purulent or mucopurulent endocervical exudate - easily induced endocervical bleeding• Etiology: CT, GC, Trichomonas, HSV, BV• Dx: CT/GC NAAT, Trichomonas, BV• Presumptive therapy: - azithromycin 1gm PO once OR - doxycycline 100 mg PO bid for 7d
  • Urethritis• Bacterial STDs: GC (5-20%), CT (15-40%)• Nongonoccocal urethritis (NGU) – Mycoplasma genitalium 5-25% • Association with NGU, data conflicting in women – Ureaplasma 0-20%; data inconsistent,biovars differ – Trichomonas vaginalis 5-20% (age, geography) – HSV 15-30%; urethritis in primary infection – Adenovirus, enterics, Candida, anaerobes
  • Chlamydia Infection in Sexually Active Adolescents/Young Adults Sexually active people aged 14-24 have about 3x the chlamydia prevalence of sexually active adults aged 25-39Prevalence, % Age group (years) NHANES, National Health and Nutrition Examination Survey, 1999-2008 Sexual activity =“yes” response to “Have you ever had sex?” Sex = vaginal, anal, or oral sex
  • Chlamydia• Primary focus of screening – Sexually active women < 25 (USPSTF, Ann Int Med 2007)• Selective male screening (adolescent clinics, corrections, national job training program, < 30 yrs, STD, military)• Treatment: azithromycin vs doxy – retest women/men 3 mo post treatment – CT testing in third trimester (reinfection)2010 CDC STD Treatment Guidelines
  • Long-term Reproductive Complications• Tubal inflammation can result in scarring, loss of function• Long-term sequelae – Tubal factor infertility – Ectopic pregnancy – Chronic pelvic pain• Tubal factor infertility: Normal tubal tissue, 1200x Post-PID, 1200x Inability to conceive leading preventable cause of Chlamydia is the due to fallopian tubal factor infertility tube damage Scanning electron microscopy photos courtesy of Dorothy L. Patton, University of Washington, Seattle, WA
  • Expedited Partner Therapy (EPT) • Providing prescriptions /medications to take to partner • Endorsed by CDC, professional organizations  Two Randomized trials: EPT useful in assuring partner treatment and reducing repeat infections in heterosexuals with CT or GC (Golden NEJM 2006, Schillinger Sex Trans Dis 2003) “partner pack”39
  • Gonorrhea—Rates by Age Among Women Aged 15–44 Years, United States, 2001–2010 Rate (per 100,000 population) Age Group 1,000 15–19 30–34 20–24 35–39 800 25–29 40–44 600 400 200 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year
  • Testing for GC• Screening is important component of GC control• USPSTF (Ann Fam Med 2007) – sexually active women at risk:< 25, prior GC, other STI, new/many partners, +/- condom use, CSW, drugs• Nucleic acid amplification tests (NAATs) – superior sensitivity/specificity – vaginal swabs (women), urine (men) – asymptomatic infection
  • Neisseria gonorrhoeae Antibiotic Resistance Antibiotic resistance  Undermines treatment success  Heightens risk of complications  Facilitates transmission Neisseria gonorrhoeae (NG) has demonstrated ability to progressively develop antibiotic resistance Resistance
  • Emergence of Fluoroquinolone-resistant N. gonorrhoeae (QRNG), United States FQ not recommended in US‡Percentage of GISP isolates resistant to ciprofloxacin Hawaii* MSM† California** US * CDC, MMWR 2000; ** CDC, MMWR, 2002; † CDC, MMWR, 2004.; ‡ CDC, MMWR, 2007.
  • Anogenital GC Treatment• Decreasing options for treatment – Cephalosporins MIC increases (SE Asia, Europe,US), treatment failure, pattern similar to QRNG• Dual therapy – Ceftriaxone 250 mg IM (preferred) • PLUS azithromycin 1 gm or doxy 100 mg bid x 7 d• Alternatives – Cefixime 400 mg PO (draft recommendation) • PLUS azithromycin 1 gm or doxy100 mg bid x 7
  • Trichomoniasis• Diagnostic evaluation – T. vaginalis nucleic acid test – Consider rescreen women at 3 mo• Tx metronidazole or tinidazole 2 gm – Resistance 5-10%• HIV and Trichomoniasis – Screening at entry into care – Rx metronidazole 500 mg bid x 7 days (Kissinger, AIDS 2010)2010 CDC STD Treatment Guidelines, Bachman, CID 2011
  • Tests for Trichomonas Test Assay Sensitivity (%) Specificity (%) Wet Preparation* 50-72 100 Culture* 70-78 100 OSOM** 83-99 100 XenoStrip** 77-90 93-99 Affirm VPIII** 80 98 PCR*** 97 98 TMA**** 96.7-98.2 98*compared to NAATs; ** compared to culture; ***Compared to culture and other primersets for trichomonas;-Madico JCM 1998;36:3205-3210; ****Compared to research PCR—Huppert CID 2007 & Hardick JCM 2006Gaydos, C. Rapid Tests for STDs Current Infect Dis Reports 2006;8:115-124
  • Bacterial Vaginosis• Recommended regimen – Metronidazole 500 mg bid x 7 – Clindamycin cream 2% x 7 – Metrogel 0.75% qday x 5• New alternative regimen – Tinidazole 2 g qd x 2 or 1 g qd x 5• Management of recurrences – Metronidazole gel 2x weekly x 4-6 mo (Sobel, 2006) – Oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel (Reichman 2009)
  • Recurrence• Persistence of BV-associated organisms and failure of lactobacillus flora to recolonize (Marrazzo , Ann Int Med 2008)• Risk factors: black, older age, higher Nugent score, BV hx, regular sex partner, female sex partner, hormones (Bradshaw, Sobel)• No evidence of benefit with yogurt or exogenous oral lactobacillus treatment (CDC Treatment Guidelines)• Biofilm may increase risk of treatment failure to G. vaginalis, A.vaginae (Swidsinski 2008)
  • HPV-Associated Disease in Males and FemalesHPV-associated Disease Males Females Genital precancers and penile, anal cervical, vaginal, cancers vulvar, anal Oropharyngeal cancers X X Recurrent respiratory X X papillomatosis Anogenital warts X X
  • Association of no. of lifetime sex partners with prevalent oral HPV – U.S. pop. aged 14-59 Overall study prevalence of oral HPV infection was 6.9%Source: Figure 4. Gillison ML, 2010. JAMA. 2012 Jan 26
  • Projected annual number of patients (ages 30 to 84 years) of oropharyngeal cancers and cervical cancersSource: Figure 4B. Chaturvedi AK, Engels EA, Pfeiffer RM et. al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011Oct 3. [Epub ahead of print]
  • HPV/Genital Warts• Counseling messages (Dunne, CID 2011) – Oral transmission• HPV testing (ASCUS, >30 + PAP) – Not indicated- +/-vaccinate, STI screen, <21• GW treatment – Sinecatechins ointment (15%) – Imiquimod induced vitiligo• HPV vaccine2010 STD Treatment Guidelines
  • HPV Vaccine• Quadrivalent vaccine licensed in females June 2006; bivalent vaccine October 2009 – Routine rec in girls 11-12; catch up to age 26 – Quadrivalent vaccine licensed for males 9-26 (2009) • Routine use December 2011• HPV uptake relatively low in US – National immunization survey 2010 • 49% of girls 13-17 received 1+ dose/32% all three doses • 1.4% boys 13-17 received 1+ doses
  • Proportion of eligible age women* with genital warts, by resident status, Australia, 2004-2010 p-trend=0.96 p-trend=0.84 p-trend=0.06 -25% p-trend<0.001 -73% Pre-vaccine period Vaccine period* Eligible age - <26 years old in July 2007 Donovan B et al. ISSTDR Quebec City, July 2011 54
  • Prevention Guidance• Education/counseling to reduce risk of STI acquisition• Detection of asymptomatic infection• Effective diagnosis and treatment• Evaluation, treatment, counseling of sexual partners• Pre-exposure vaccination-hepatitis A, B, HPV
  • Resources for Women• (HIV/STI testing sites)• 1-800-CDC-INFO• for consumer fact sheets and brochures• Condoms and STIs –• Get Yourself Tested –
  • Peer Reviewed References• Workowski KA, Berman S. 2010 CDC Sexually Transmitted Diseases Treatment Guidelines. MMWR 2010;59(RR-12):1-116.• Lin JS, Whitlock E, O’Connor E, et al. Behavioral Counseling to prevent sexually transmitted infections: recommendation statement. Ann Int Med 2008:149:491-6.• Meyers D, Wolff T, Gregory K, et al. USPSTF recommendations for STI screening. Am Fam Physician 2008;77:819-24.• Peterman T, Tian LH, Metcalf CA, et al. High incidence of new sexually transmitted infections in the year following a sexually transmitted infection: a case for rescreening. Ann Intern Med 2006;145:564-72.• CDC. Quadrivalent human papillomavirus vaccine: MMWR 2007;56(No RR-2); bivalent vaccine and updated recommendations MMWR 2010;59:626-9; licensure of quadrivalent vaccine in males MMWR 2010;59;630-2..• Workowski KA, Berman SM, Douglas JM. Emerging Antimicrobial Resistance in Neisseria gonorrhoeae: Urgent Need to Strengthen Prevention Strategies. Ann Intern Med 2008;148:606-13.