S exually Transmitted Infections ( STIs ) Update: 2014

1. Sexually Transmitted Infections (STIs) Update: 2014 Joseph M. Gastaldo, MD OhioHealth, Riverside Methodist Hospital April 23, 2014

2. Evolution of words ... Venereal Disease (VD): venereus (Venus; Roman goddess of love); relating to sexual intercourse or desire; term lost favor in late 20th century Sexually Transmitted Disease (STD) symptomatic Sexually Transmitted Infection (STI) term introduced by public health officials; more inclusive; may be symptomatic or asymptomatic

3. What are STIs & How are They Transmitted ? Caused by more than 30 different bacteria, viruses, & parasites & are spread predominantly by sexual contact (vaginal, oral, anal) Pathogens with greatest incidence of illness: syphilis, gonorrhea, chlamydia, trichomoniasis HBV, herpes, HIV, HPV Variable presentation: vaginal discharge, urethral discharge in men, oral or anogenital ulcers, abdominal pain, asymptomatic

4. Objectives / Outline Recognize the public health burden & spectrum of pathology associated with STIs Understand the association of STIs and risk of HIV transmission; STI prevention is part of HIV prevention Appreciate the common presentation and disease spectrum associated with various STIs; recognize treatment regimens Have an appreciation to the complexity of a practicing venereologist

5. CDC Statistics April is STD Awareness Month STIs are a significant health challenge; costing the nation an estimated $16 billion annually 20 million new STIs annually; half among persons ages 15-24 years Reported data is only a fraction of the true burden; many cases of chlamydia, gonorrhea, & syphilis go undiagnosed & underreported; HPV, HSV, trichomoniasis are not routinely reported CDC.Gov Fact Sheet; 2012

6. WHO Statistics who.int More than 1 million people acquire an STI every day Each year, an estimated 500 million people become ill with one of 4 STIs: chlamydia, gonorrhea, syphilis, and trichomoniasis More than 530 million people have the virus mostly associated with genital HSV (HSV2) More than 290 million women have HPV infection The majority of STIs are present without symptoms

7. Estimated new cases of curable STIs (gonorrhea, chlamydia, syphilis, trichomoniasis), 2008 who.int

8. STIs: Widespread Health Implications Infertility/reproductive health: pregnancy complications, infertility, PID Int J Gyn Ob. 2013 Dec; 123(3): 183-4 Neonatal health: in utero & perinatal transmission; stillbirth, pneumonia, congenital deformities J FamPract 1990 Apr; 30(4):448-56 Malignancy: worldwide, HPV infection causes 530K cases of cervical cancer (275K deaths) WHO fact sheet; updated 2013; who.int Antibiotic resistance: gonorrhea with evolving resistance to ceftriaxoneExpert Rev Anti In Ther 2014 Apr 4 Transmission of HIV; STD prevention is part of HIV prevention

9. Strong association between STIs & Increased risk of HIV infection CurrOpin HIV AIDS Jul 2010; 5(4):305-10 Infections that disrupt the the epithelial surface of the genital tract  facilitate the the access of HIV to target cells under the epithelial surface Ulcerative diseases: herpes, syphilis BMJ 1989; 298(6674):623-4 inflammatory conditions: trichomoniasis Observed striking increase in the prevalence of concordant HIV infection & syphilis CID (2007) 44(9):1222-8 HIV patient: conditions that recruits PMNs to the genital tract are associated with increase in HIV shedding STDs 2008; 35(11):946-59

10. STIs & HIV Infected Persons In HIV infected persons, new STIs are events that signal HIV exposure to others Baltimore City HD; 796 men/354 women diagnosed with HIV from 1993-8; 13.9% of men & 11.9% of women were diagnosed with an STI after there HIV diagnosis JAIDS 33:247-52 Higher risk for HIV/STI coinfections: MSM, minorities, lower socioeconomic class AIDS Behav 2011 15(sup 1)

11. Dr. Gastaldo’s Suggestions for Intervention; slide 1 Assume that all HIV infected/STI patients are sexually active ! (Duh) Sexual inquiries; lack of HCWs “comfort level”, lack of sensitivity, lack of training to sensitive questioning. Risk behavior counseling: mental health screening, substance abuse/PNP, “hook up” smart phone apps Routine STI screening: syphilis antibody,NAAT for gonorrhea & chlamydia

12. Dr. Gastaldo’s Suggestions for Intervention; slide 2 Safe sexual practice discussion Discussion & consideration for PrEP in appropriate HIV (-) person Immunizations: HAV, HBV, HPV: ACIP recommends vaccination with HPV4 through age 26 in: MSM, immunocompromised males, HIV infected males

13. Pathogens / Presentation / Treatment Bacterial: syphilis, gonorrhea, chlamydia Protozoa: Trichomonasvaginalis Viruses: HSV, HPV

14. NeisseriagonorrhoeaeCDC.gov, practice guidelines Gram (-) diplococcus; infects surfaces lined with columnar epithelial cells (endocervix, urethra, anogenital, oropharyngeal, conjuctiva); always considered a pathogen Men: usually causes symptomatic urethritis, up to 25% may be asymtomatic, epididymitis: most frequent complication MSM, screening: urethral, rectal, & pharyngeal infection (NAAT)

15. NeisseriagonorrhoeaeCDC.gov, practice guidelines Women: up to 50% asymptomatic; cervicitis, perihepatitis, PID, perinatal morbidity Both sexes: anorectal infection, pharyngitis, conjuctivitis, disseminated infection (tenosynovitis, severe: meningitis, IE) Incubation period: 3-7 days in men, unclear in women (10 days?) Diagnosis: culture & gram stain: only test that determines antibiotic sensitivity; gram stain alone is diagnostic for urethral (SYMPTOMATIC men) testing; preferred method when dx unclear; used to confirm positive NAAT result in low prevalence areas, culture all sites will increase yield NAAT: routinely used for urine, vaginal, penile/urethral (FDA approved) more rapid turnaround time than culture; use culture for dx from extra-genital sites (rectal & pharyngeal) unless the lab has conducted internal validation of non-cultured based method (Quest Diagnostics & Laboratory Corporation of America have validated)

16. Neisseriagonorrhoeae: RxCDC.gov, practice guidelines Resistance rates (>25%) to fluoroquinolones: No Oral cephalosporins are not preferred Uncomplicated infections of cervix, urethra, rectum, & pharynx: 250 mg IM plus azithromycin 1 gram single dose or PO doxycycline for 7 days (for specific circumstances, other regimens exist, but TOC needed) Disseminated infections: IV ceftriaxone; consideration to PO antibiotic transition 24-48 hours after improvement; meningitis/IE: IV ceftriaxone Evaluate & treat partners

17. Chlamydia trachomatisCDC.gov, guidelines Does not gram stain; intracellular; D-K biovars: GU infection;L serovars: lymphogranulomavenereum (LGV); systemic infection; genital ulcer-adenopathy syndrome Only 10% of men & 5-30% of women develop symptoms Spectrum of disease: urethritis, cervicitis, PID, epididymitis, prostatitis (rare), protitis, colitis, pharyngitis, sexually associated reactive arthritis, SARA, formerly known as Reiter’s syndrome MSM: 3-10% test positive on rectal screening; 1-2% on pharyngeal screening J Am Coll Health 60:481, 2012 Testing: NAATsmore sensitive than non amplification tests Endocervical, vaginal (self collected), urethral, oropharyngeal**, urine, rectal swabs** (not FDA approved, some labs have met CLIA requirements & validated NAAT testing on rectal swabs) Check with your lab.

18. Chlamydia trachomatis: RxCDC.gov, practice guidelines Azithromycin 1 gram orally in a single dose or doxycycline 100 mg orally BID for 7 days. Treat sexual partners To minimize disease transmission, persons treated should obstain from from sexual intercourse for 7 days after a single dose Rx or until 7 day Rx is complete Test of cure: pregnant women Infected persons should be retested 3 months after Rx; post treatment infection: re-infection

19. Syphilis; TreponemapallidumCDC.gov, practice guidelines Systemic infection; protean signs & symptoms Primary: chancre (painless, clean based ulcer with indurated edges) occurs at point of introduction/contact 10-90 days after exposure; chancre can occur in many places Regional adenopathy; patient is contagious Untreated lesions spontaneously heal in 3-6 weeks Diagnosis: examination, darkfield microscopy or DFA, RPR often (-)

20. Secondary syphilis; highly variable CDC.gov, practice guidelines “Copper penny” macular lesions on palms & soles, generalized or focal, non-puritic/painless Fever, malaise, anorexia, occasionally meningismus Onset up to 6 months after exposure Highly infectious; lesions will heal without Rx Diagnosis: RPR, high titers can be seen, examination

21. Early latent & late latent syphilisCDC.gov, practice guidelines Early: asymptomatic period from spontaneous resolution of primary or secondary  first year 25% will have relapse of secondary; patients considered infectious; unrecognized relapse Diagnosis: both non-trepomenal & treponemal tests (+) Late: asymptomatic infection; non-infectious evaluate for clinical evidence of teriary or ocular disease Diagnosis: serology, non-treponemal test may revert to normal Consider CSF exam if neurologic symptoms; HIV patient with neurologic symptoms

22. Neurosyphilis: can occur at any stageCDC.gov, practice guidelines Meningitis & eye disease may occur during primary or secondary stages & during the first 5-10 years of untreated infection Syphilitic eye disease eye disease: uveitis, iritis, optic neuritis, neuroretinitis “Classic manifestations” after 15-20 years of untreated infection: tabesdorsalis & general paresis (can be with psychotoc or dementia features) Diagnosis: CSF examination; serology (pleocytosis, elevated protein, VDRL)

23. Syphilis: Rx: penicillinCDC. Gov, guidelines Primary & secondary: benzathine PCN (BPG) 2.4 mu IM as a single dose; allergy: 14 days doxycycline, 2 grams PO azithromycin: need CLOSE f/u; Jarisch-Herxheimer reaction Early latent: BPG IM times 1 dose Late latent or unknown: BPG IM q 7 days time 3 doses; being late >2 days not recommended Neurosyphilis/ocular: IV PCN-G for 10-14 days consider desensitization with PCN allergy Pregnant women: use PCN; desensitize HIV: PCN is drug of choice

24. Syphilis: follow upCDC.gov, practice guidelines NTAT (RPR): 4 fold change in titer (2 dilutions) considered a significant change; use same test & lab NTAT usual revert to NR status over time; persistent low levels: serofast Treponemal EIA: identifies previously treated & untreated persons Neurosyphilis: if pleocytosis initially seen, repeat CSF every 6 months until cell count is normal; if cell count is not decreased at 6 months or normal at 2 years, consider re-treatment. HIV: RPR at 3,6,9,12, & 24 months; failure: persistant or recurrent symptoms, sustained rise in RPR. If failure: consider CSF exam & retreatment; consider Rx for late latent

25. TrichomonasvaginalisCDC.gov, practice guidelines Most common non-viral STI in US; 7.3 million estimated annual new cases Pear shaped, motile, flagellated protozoan parasite Parasites invade superficial epithelium; inflammation; enhances acquisition of HIV infection; can survive up to 45 minutes on clothing & bathwater Women: 50% asymptomatic; vaginal discharge; profuse, sometimes frothyvulvovaginal irritation, “strawberry” cervix, consider PID with abdominal pain Men: up to 75% asymptomatic, urethritis, epididymitis, prostatitis, balantitis

26. TrichomonasvaginalisCDC.gov, practice guidelines Diagnosis women: microscopy of vaginal secretions (60-70% sensitive), “whiff test”, pH >4.5, POC testing; nucleic acid probe tests (Affirm VP III), culture Diagnosis men: wet prep with poor sensitivity, no approved point-of-care tests; culture of urethral swab, urine, or semen APTIMA T. vaginalisAnalyte Specific Reagents (ASR); detects RNA using same methodology for GC & Chlamydia; CLIA verification studies T. vaginalishas not been found to infect oral sites Rectal prevalence appears low in MSM

27. Trichomonasvaginalis: RxCDC.gov, practice guidelines Uncomplicated: metronidazole 2 gr PO x 1 dose Cystitis, prostatitis, epididymitis: longer duration PO metronidazole with 95% cure rate Metronidazole gel: 50% efficacy; not recommended Low level metronidazole resistance: 2-5% high level resistance is rare; retreat patients with 7 day course if Rx failure Metronidazole: Antabuse reaction; avoid EtOH Treat partners

28. Herpes Simplex virus (HSV)“Most people infected with genital herpes do not know they have it” CDC.gov, practice guidelines HSV-1 & HSV-2, Herpes DNA virus family (HHV-1 & HHV-2) After primary infection, establishes latency in neurons, potential for reactivation, usually near site of primary infection Most infections are asymptomatic: HSV-1: 50-80% of adults seropositive, HSV-2: 20-40% of adults are seropositive(US data) HSV-1: herpes labialis most common form of recurrent HSV-1, 30% of genital HSV is HSV-1 Diagnosis for GU/mucocutaneousinfx: clinical presentation; viral culture of ulcer/vesicle Primary infection: Asymptomatic in two-thirds of both HSV-1 & HSV-2; clinical presentation: vesicular infection; primary gingivostomatitis; mononucleosis syndrome; genital infection: small painful, clustered vesicles; shallow ulcerations; can be “systemically ill”

29. HSV: FYICDC.gov, practice guidelines HSV-2 more likely to have clinical recurrences Genital ulcer disease (HSV, chancre) increases the risk of acquisition & transmission of HIV Psychological impact of HSV cannot be overestimated Both condom use & daily valacyclovir use: reduce the transmission course in discordant couples NEJM 350:11, 2004 HIV infection: 60-70% infected with HVS-2; disseminated/severe infections can occur with CD4<200 Acute immunosuppression may reactivate

30. HSV: RxCDC.gov, practice guidelines Acyclovir, valacyclovir*, famciclovir* Generally well tolerated; nausea, vomiting, HA Dose adjustment need for GFR < 50 mL/min Dosing based on indication: use reference Valacyclovir: first episode of genital HSV: 1 gr BID for 7-10 days Recurrent genital HSV: 500 mg BID (1 gr BID if severe) Suppressive therapy: 500 mg BID Herpes labialis: 1 grq 12 hours for 2 doses

31. Salutida Roma !