Detection and Treatment of Sexually Transmitted Infections

1. Detection and Treatment of Sexually Transmitted Infections 27 March 2014 Maj Jeremy King, M.D.

2. Objectives Understand the causes, signs, and symptoms of sexually transmitted infections (STIs) that cause: • Genital ulcers • Vaginitis • Cervicitis • Pelvic inflammatory disease Understand the rational for screening and the current recommended screening strategies Understand recommended screening in special conditions such as pregnancy and sexual assault

3. STIs in the US 20 million new infections per year. 110 million current infections. $16 billion in direct medical costs per year. Complications of untreated STIs: - upper genital tract infections - infertility, cervical cancer - enhanced transmission of HIV Satterwhite CL, et al. Sexually transmitted infections among U.S. women and men: Prevalence and incidence estimates, 2008. Sex TransmDis 2013

4. Screening Screening tests detect early disease or risk factors for disease in large numbers of apparently healthy individuals Diagnostictestsconfirm the presence (or absence) of disease in symptomatic or screen positive individuals

5. When should we screen? Tests are available Risk factors are present • relatively inexpensive, reliable, prevent morbidity • age, current sexual practices, past infections eg: Chlamydia

6. Chlamydia Reported Chlamydia Cases in Texas, 1992-2012 2012 Sexually Transmitted Diseases Surveillance http://www.cdc.gov/std/stats12/figures/5.htm

7. Chlamydia Reported Chlamydia Cases in Texas, 1992-2012 2012 Texas STD and HIV Epidemiologic Profile February 2014

8. Chlamydia • 85% of cases are asymptomatic • Potential complications: • PID • Chronic pelvic pain • tubal infertility • Ectopic pregnancy • Screeningrecommendations: • All sexually active women up to 25 y/o • All women > 25 y/o with risk factors • Men with risk factors

9. Cervicitis Symptoms • Abnormal vaginal discharge • Intermenstrual vaginal bleeding Signs • Mucopurulentendocervicalexudate • Sustained endocervical bleeding easily induced by cotton swab • Leukorrhea (>10 WBC per HPF) is specific, but not sensitive Diagnosis • Microscopy • NAAT • Culture

10. Cervicitis GC and Chlamydia most common organisms isolated • NAAT is preferred diagnostic test • Saline prep to assess for PID, BV, Trich In majority of cases no organism isolated • Presumptive treatment (azithromycin 1g PO) should be provided for women at increased risk for STIs (≤25 y/o, new or multiple sex partners, and those who engage in unprotected sex)

11. Chlamydia Chlamydial genital infection is the most frequently reported infectious disease in the US Intracellular bacterium May be asymptomatic, or sx may occur weeks to months after exposure

12. Chlamydia Screening Recommendations Annually for all sexually active women ≤ 25 y/o Annually for women > 25 w/ risk factors Screen + patients for other STDs

13. Chlamydia Treatment Recommended regimens (97-98% cure rate): • Azithromycin 1 g PO single dose or • Doxycyline 100 mg PO bid for 7d Alternative regimens: • Erythromycin base 500 mg PO qid for 7d • Erythromycin ethylsuccinate800 mg PO qid for 7d • Ofloxacin 300 mg PO bid for 7d • Levofloxacin 500 mg PO qd for 7d

14. Chlamydia Treatment Patient counseling Take first dose immediately (observed, on site, if possible) TOC is not advised routinely (except in pregnancy) Retest in 3 months to screen for re-infection Advise most recent partner and any other sex partners w/i 60 days preceding symptoms to seek evaluation/tx Abstain from IC until pt and partner(s) complete tx (7d after single dose regimen)

15. Gonorrhea N. gonorrhoeae infections are the 2nd most common reportable communicable disease in the US Tend to cause a stronger inflammatory response than C. trachomatis but are typically asymptomatic in women until complications such as PID develop In men, usually causes urethritis with painful urination. May cause epididymitis or disseminated gonococcal infection

16. Gonorrhea Screening based on population, at risk pts Patients w/ + GC should be tested for chlamydia, syphilis, and HIV Culture and sensitivities for persistent infection Tx: cephalosprin + azithomycin No TOC needed, but consider retesting after 3 months to screen for reinfection Refer partners for testing/tx (most recent partner and all partners w/i 60d before onset of symptoms or + test)

17. Vaginitis • Vaginal discharge, odor, vulvar itching and irritation • Most common causes are • bacterial vaginosis (40%- 45%) • vulvovaginalcandidiasis (20%-25%) • trichomoniasis (15%- 20%)

18. Bacterial Vaginosis (BV) • Polymicrobial clinical syndrome resulting from replacement of normal hydrogen peroxide-producing Lactobacillus species with anaerobic bacteria • Prevotella, Mobiluncus, G. Vaginalis, M. Hominis • Malodorous vaginal discharge reported more commonly after intercourse and after menses; +/- pruritus • Sx may remit spontaneously • Can be diagnosed by clinical criteria or gram stain

19. BV Recommended Rx: • Metronidazole 500 mg PO bid for 7d • Metrogel 0.75% 5 g vaginally qd for 5d • Clindamycin cream 2% 5 g vaginally qd for 7d • Do not use in second half of pregnancy Alternative Rx: • Clindamycin 300 mg PO bid for 7d • Clindamycin ovules 100mg vaginally qhs x3d • Tinidazole 2 g poqd x2d • Tinidazole 1 g poqd x5d

20. Trichomoniasis T. Vaginalis(a protozoan) 3% of US women currently infected • 70%-85% asymptomatic • Sx include "frothy" gray or yellow-green vaginal discharge and itching Almost always sexually transmitted Without treatment, trichomoniasis can increase a person’s chances of getting or spreading other STIs

21. Trichomoniasis Diagnosis • Motile trichomonads on wet prep • Only 60-70% sensitive • Various point of care tests 80+% sensitive • Can culture if negative wet prep and high suspicion Screening recommended in women: • with new or multiple partners • with a history of STIs • who trade sex for drugs or money • who use IV drugs

22. Trichomoniasis Recommended treatment options • Metronidazole 2 g PO x1 (or 500 mg BID x 7d) • Tinidazole 2 g PO x1 Counseling • Abstain from alcohol until 24h after last metronidazole (3d for tinidazole) • Advise partners to seek eval and tx • Avoid intercourse until all tx completed and both partners are asymptomatic • Breastfeeding: withhold feeding for 12-24h after last dose of metronidazole (3d for tinidazole)

23. VulvovaginalCandidiasis (VVC) “yeast infection” Caused by Candida albicans (85%-90%), C. glabrata and C. parapsilosis are responsible for ~10% of cases Symptoms: vulvar itching; thick, white, clumpy Vaginal discharge Diagnosis: wet prep, gram stain, or culture

24. Treatment of uncomplicated VVC • Multiple topical azoles, applied 1-7d • OTC: butaconazole, clotrimazole, miconazole, tioconazole • Rx: butoconazole, nystatin, terconazole • nb: If symptoms persist after using OTC preparation or recur w/i 2 months should be evaluated with office-based testing • Oral agent (Rx): Fluconazole 150 mg x1 • Treat partners only if symptomatic (balanitis)

25. Complicated VVC • Recurrent • Severe • Non-albicanscandidiasis • Women with uncontrolled diabetes, debilitation, or immunosuppression

26. PID Minimum diagnostic criteria • Women at risk for STDs experiencing pelvic or lower abdominal pain, if no cause for the illness can be identified, andone or more of the following are present on pelvic examination: • CMT • Uterine tenderness • Adnexal tenderness Treat empirically Screen all PID pts for N. gonorrhoeae, C. trachomatis, HIV

27. PID RecommendedParenteralTreatment: Regimen A Cefotetan 2 g IV q12h ORCefoxitin 2 g IV q6h PLUSDoxycycline 100 mg PO or IV q12h Regimen B Clindamycin 900 mg IV q8h PLUSGentamycin 2 mg/kg IV/IM load, then 1.5 mg/kg q8h (Can substitute single daily dosing) Alternative Parenteral Regimen: Ampicillin/Sulbactam 3 g IV q6h PLUS Doxy 100 mg IV or PO q12h

28. PID May discontinue parenteral therapy 24 hrs after a clinical improvement • Continue doxycycline 100 mg PO bid ORclindamycin 450 mg PO qid to complete total of 14d of RX (Clindamycin preferred with TOA)

29. PID Recommended Oral Regimen Starts with single IM injection of • Ceftriaxone 250 mg • OrCefoxitin 2g PLUS Probenicid 1g PO x1 • Orother 3rd gen cephalosporin (ceftizoxime, cefotaxime) PLUS 14 d PO • Doxycycline 100 mg bid • +/- Metronidazole 500 mg PO bid

30. PID Parental and oral therapy have similar efficacy in mild/moderate cases Suggested criteria for hospitalization: • Cannot exclude appendicitis or other surgical emergency • Pregnancy • Inadequate response to PO Rx • Unable to follow or tolerate PO Rx • Severely ill, N/V, high fever, etc. • TOA

31. Genital Ulcers In the U.S. most likely to be genital herpes or syphilis Other possiblities: • Chancroid, syphilis • GranulomaInguinale • LymphogranulomaVenereum

32. Genital HSV U.S. statistics >50 million persons in the U.S. have genital HSV infection >1 million new cases occur each year 17% of adults aged 14-49 affected Transmission HSV-2 is transmitted sexually(genital to genital, oral to genital, or genital to oral) and perinatally(mother to child) HSV-1 transmission is usually non-sexual; but sexual transmission is increasing

33. Genital HSV Primary (initial) infection • numerous bilateral painful lesions • more severe, last longer, and have higher titers of virus than recurrent infections. • papules  vesicles  pustules  ulcers  crusts  healed • systemic symptoms

34. Genital HSV Recurrent infection • Prodromal symptoms (localized tingling, irritation) 12-24 hrs before lesions

35. Genital HSV Culture is confirmatory test • Low sensitivity, esp. in recurrent lesions • PCR more sensitive, not FDA-cleared Type-specific serologic tests • Sensitivity 80-98%, Specificity ≥ 96% • Routine screening not indicated • Useful in the following scenarios: • Recurrent genital symptoms or atypical symptoms with negative HSV cultures • Clinical diagnosis of genital herpes without laboratory confirmation • Partner with genital herpes • Consider for persons requesting STD evaluation, and for HIV+ pts

36. Genital HSV Treatment of initial episode • Systemic antivirals for 7-10 days • Acyclovir, Famciclovir or Valacyclovir • Use of topical antivirals discouraged Recurrent Infection Start tx within 1 day of lesion onset or during prodrome Suppressive Therapy • Reduces frequency by 70-80% • Decreases transmission

37. Genital HSV Patient counseling • Potential for recurrent episodes, asymptomatic viral shedding, risks of sexual transmission • Inform current and future partners • Abstain from sexual activity with uninfected partners when lesions or prodromal symptoms present • Type-specific serologic testing recommended for asymptomatic partners • HSV-2 seropositive persons are at increased risk for HIV acquisition if exposed to HIV • Suppressive antiviral therapy does not reduce this risk

38. Genital HSV Pregnancy • Women w/o genital herpes should abstain from intercourse during 3rd trimester w/ partners having known or suspected genital HSV • Serologic testing is recommended for these women • Daily suppression for patients w/ genital HSV begining at 36 weeks (ACOG recommendations) • Acyclovir400 mg PO TID (more data in pregnancy) or • Valacyclovir 500 mg PO BID • C-section for women with active lesions at onset of labor

39. Syphilis Primary • Ulcer Secondary • Rash, mucocutaneous, lymphadenopathy Tertiary • Cardiac, ophthalmic, auditory, gummas

40. Syphilis –Diagnosis Definativedx requires darkfield exam of lesion exudate or tissue Serologic tests can be used to make presumptive Dx • Nontreponemal – VDRL, RPR • Correlate with disease activity; should be reported quantitatively • Low levels may persist Treponemapallidum • Treponemal – FTA-ABS, TP-PA, EAIs • Test will remain + in > 75% of pts treated for primary syphilis • Must be + on both types of serologic tests to make dx

41. Syphilis - Rx Penicillin G • Primary, Secondary, Early Latent: Benzathine penicillin G 2.4 million units IM X1 • Late latent, treatment failures, tertiary not neurosyphilis: Benzathine penicillin G 2.4 million units IM weekly X3 • Neurosyphilis • Aqueous crystalline PCN G 18-24 million units per day for 10-14 days • Alternative: Procaine PCN 2.4 million units IM qdPLUS Probenecid 500mg poqid for 10-14 days

42. Syphilis - Rx Special considerations • Partners exposed w/i 90 days of primary/secondary/ early latent syphilis should be treated presumptively • Pregnant patients allergic to PCN should be skin tested and desensitized and treated w/ PCN

43. Human Papillomavirus (HPV) > 100 types • > 40 can infect the genital area • Oncogenic, or high-risk types (e.g.16,18), cause cervical cancer • Nononcogenic, or low-risk types (e.g. 6,11), cause genital warts and recurrent respiratory papillomatosis 14.1 millioninfections/year in the U.S. > 50% of sexually active persons are infected at least once • Dx is usually clinical; can be confirmed by bx

44. HPV Clinical manifestations of infection: • Genital warts • Cervical cellular abnormalities detected by Pap tests • Some anogenitalsquamous cell cancers • Some oropharyngeal cancers • Recurrent respiratory papillomatosis

45. HPV Prevention • Two HPV vaccines are licensed in the US: • Cervarix® – types 16, 18 • Gardasil® – types 6, 11, 16, 18 • Indicated in 9 – 26 y/o • CDC recommends first dose at age 11-12 years • Only Gardasil® has male indication • Condoms may reduce risk but not fully protective

46. HPV Treatment • Goal is alleviation of symptoms; tx does not lower risk of transmission or development of malignancy • Treatment method is guided by preference of the patient, available resources, and experience of the provider • In general, warts located on moist surfaces or in intertriginous areas respond best to topical treatment • Most genital warts respond within 3 months of therapy • Recurrence common after tx, especially in first 3 mos

47. HPV Patient-applied • Podofilox 0.5% solution/gel applied w/ cotton swab bid x 3d followed by 4d of no tx; repeat up to 4 cycles • Imiquimod 5% cream QHS 3x per week for up to 16 weeks. • Wash w/ soap & water 6-10 hrs after application • Sinecatechins 15% ointment • Safety in pregnancy not established (all 3) Provider-applied • Cryotherapy every 1-2 weeks • Podophyllin resin 10-25% in a compound tincture of benzoin • TCA (or BCA) 80-90% solution weekly • Surgical removal (sharp, currette, or laser) • Intralesional interferon

48. HPV Recommended Regimens for Vaginal or Anal Warts • Cryotherapywith liquid nitrogen or • TCA AvoidImiquimod, sinecatechins, podophyllin, and podofilox in pregnancy

49. Hepatitis B Half symptomatic • Sx include jaundice, fatigue, mild fever, nausea, vomiting, abdominal pain, and dark urine • 1% acute liver failure 2-6% result in chronic hepatitis (up to 25% mortality) Transmission • percutaneous or mucous membrane exposure to body fluids that contain blood • Vertical (birth), horizontal (premastication) • risk factors: unprotected sex, multiple partners, MSM, history of other STDs, illegal injection-drug use

50. Hepatitis B No specific therapy for acute hepatitis B Focus is on prevention • hepatitis B immune globulin (HBIG) • provides temporary (3–6 mo) protection from HBV infection • hepatitis B vaccine