Sexually Transmitted Diseases: Genital Syndromes in Men May 20, 2010 Sexually Transmitted Diseases: Genital Syndromes in Men Julie Dombrowski, MD, MPH With photos and selected slides from H. Hunter Handsfield, MD

I-TECH STD Update Series Genital syndromes in men: Urethritis and related conditions Genital syndromes in women I: Cervicitis, vaginal infections Genital syndromes in women II: PID, STD and pregnancy, HPV and cervical cancer Genital ulcer disease: Herpes, syphilis, and miscellaneous STDs 2

Introduction STDs increase HIV transmission and acquisition Important implications for female partners Two clinical approaches Etiologic diagnosis Target treatment to an identified pathogen Syndromic management Identify syndrome and treat possible causes Guided by algorithm (WHO) Compared to men, women with gonorrhea and chlamydial infection are more often asymptomatic Complications are more severe in women Pelvic inflammatory disease Infertility, ectopic pregnancy Syndromic Management Identify a syndrome (urethritis) Treat for the possible causes of that syndrome WHO algorithms Ideal in resource-limited settings Etiologic Diagnosis Use laboratory tests to diagnose a pathogen Target treatment to the identified pathogen

The STD-Focused Male Exam Palpate inguinal nodes Palpate scrotal contents Testes, spermatic cord, epididymis Exam penis visually, retracting foreskin Rashes, ulcers, inflammation of meatus, urethral discharge If no discharge apparent, milk urethra Real cases, model photos My talk will focus on etiologic diagnsosi

Male Genital Infections Case 1 PRESENTATION 44 year-old man History 3 days of burning with urination Has noticed stains on underwear for 2 days 3 new vaginal sex partners during travel last week Last sex 7 days ago Used condoms most of the time “except when I drank too much”

More typical case with overtly purulent discharge

Diagnosis of Urethritis Symptoms: dysuria, urethral itching/tingling Confirmation requires one of the following: Abnormal urethral discharge Purulent or mucopurulent Preferably examine >4 hr since last urination Documented urethral inflammation Gram stain of discharge with ≥5 WBC per oil immersion field (preferred) Gram stain of urine sediment with ≥10 WBC per oil immersion field +Leukocyte esterase in first-void urine Small amount of completely clear discharge can be normal dysuria

Gonorrhea (Neisseria gonorrhoeae) Males Urethritis (usually symptomatic) Complications Epididymitis Urethral stricture Gonococcal abscess Disseminated gonococcal infection Reactive arthritis (formerly Reiter’s syndrome) Female partners Cervicitis (often asymptomatic) Can lead to PID, ectopic pregnancy, infertility Urethritis Also pharyngitis, proctitis if exposed (males & females) Real cases, model photos

Treatment of Uncomplicated Gonorrhea RECOMMENDED Ceftriaxone 125-250 mg IM Cefixime 400 mg PO x 1 Ciprofloxacin 500 mg PO Ofloxacin 400 mg PO Levofloxacin 250 mg PO PLUS Azithromycin or Doxycycline No longer recommended Alternate regimens include spectinomycin 2g IM x 1 or other single-dose cephalosporine regimens Other single-dose cephalosporin therapies that are considered alternative treatment regimens for uncomplicated urogenital and anorectal gonococcal infections include ceftizoxime 500 mg IM; or cefoxitin 2 g IM, administered with probenecid 1 g orally; or cefotaxime 500 mg IM. Some evidence indicates that cefpodoxime 400 mg and cefuroxime axetil 1 g might be oral alternatives. Chlamydia co-infection Is common. Include if chlamydia has not been ruled out.

Gonococcal Isolate Surveillance Project (CDC) Worldwide, cephalosporins are the drug of choice FQ resistance precludes this as a drug of choice, not recommended for primary therapy Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2007 Supplement, Gonococcal Isolate Surveillance Project (GISP) Annual Report 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, March 2009.

The Next Problem: Cephalosporin Resistance Resistance to 3rd generation cephalosporins Emerged and spread in Asia, Australia Sporadic cases elsewhere Limited data from Africa, Latin America, Caribbean Mechanisms not fully elucidated Reported treatment failures with oral cephalosporins Worldwide, cephalosporins are the drug of choice FQ resistance precludes this as a drug of choice, not recommended for primary therapy

Male Genital Infections Case 2 PRESENTATION 40 year-old man with AIDS on antiretroviral therapy CD4 count 107, HIV RNA undetectable History 2 days of urethral itching and discharge 1 male sex partner in past 2 months, 6 in past 12 months Insertive anal and oral sex, never used condoms

Differential Diagnosis of Urethritis Gonococcal *Also called non-specific urethritis

Gonorrhea versus NGU GC NGU Incubation period 2-5 d 7-14 d Dysuria Prominent Mild or absent Discharge amount Copious Scant to moderate Discharge type Purulent Mucoid, mucopurulent NGU is probably THE MOST COMMON SYNDROME in men or women Lot of overlap

Comparison of Typical Discharge* Gonococcal Non-gonococcal *Cannot reliably distinguish on visual exam alone

Lots of polymorphonuclear leukocytes but no organisms Not uncommon for men to have symptoms but no inflammatory signs ICGND for gonorrhea Sensitivity 90-95% Specificity 90-95%

If positive -> Treat for gonorrhea and chlamydia Examination of gram stained smear for gram-negative intracellular diplococci Sensitivity 90-95% Specificity 90-95% If positive -> Treat for gonorrhea and chlamydia If negative -> Treat for NGU Lots of polymorphonuclear leukocytes but no organisms Not uncommon for men to have symptoms but no inflammatory signs ICGND for gonorrhea Sensitivity 90-95% Specificity 90-95%

Etiologies of NGU Chlamydia trachomatis 15-40% (median 30%)* Mycoplasma genitalium 15-25% (median 19%)* Trichomonas vaginalis 5-15% Ureaplasma urealyticum? Doubtful role HSV (in absence of lesion) 2-3% (HSV-1 > HSV-2 in one study**) Adenovirus 2-4% No identified pathogen ~30-70% This is in initial cases with documented urethritis Bradshaw – case control study of men with and without symptoms of NGU (329 vs. 307) All tested for CT, M genitalium, ureaplasma parvum, U. urrealyticum, HSV-1, HSV2, adenovirus, Garndnerella Fellatio associated with pathogen-negative NGU HSV-1 more common than HSV-2 in one study (Bradshaw et al, JID 2006) Isolation of adenovirus and normal oral flora also suggestive Some portion of cases may be inflammatory reactions to oral flora of partners Role of oral sex? *Median of 16 studies since 1992 (Sexually Transmitted Diseases, 4th Ed, Holmes KK et al) **Bradshaw C et al. JID 2006;193:336-45

Urethritis - Laboratory Testing Gram stained smear of urethral secretions Gram negative intracellular diplococci If available and cost effective N. gonorrhoeae Culture or nucleic acid amplification testing (NAAT) C. trachomatis NAAT Not recommended generally, but may be appropriate in selected cases and settings M. genitalium (not widely available) T. vaginalis HSV Will depend on what the lab capabilities are Most in settings managing syndromically rather than etiologically At least 50% of sexually active people have u. urealyticum in genital secretions

Treatment of NGU Azithromycin 1.0 g, single dose Chlamydia efficacy ~95% Clinical efficacy ~90% Usually effective against M. genitalium, but risk of inducible resistance Doxycycline 100 mg po BID x 7 days Chlamydia efficacy >98% Clinical efficacy ~90% Alternatives: erythromycin, fluoroquinolones Notification and treatment of partners (<60 days) No systematic studies of clinical outcomes in partners Spectinomycin not active against NGU – painful injection Goals:Treat/prevent chlamydia, prevent reinfection Examine for other STDs, if practical

Recurrent and Persistent NGU Symptoms may take 10-14 days to resolve 10-15%: persistent/recurrent symptoms at 4-6wk Documented urethritis? If no  don’t retreat If yes  retreat with different medication Partner re-treatment not recommended

Male Genital Infections Case 3 PRESENTATION 24 year-old man History “Incredibly painful” urination for 2 days 2 lifetime female sex partners 1 new partner in the past 2 mo Last sex 4 days ago Always used condoms with vaginal sex Oral sex (penile-oral & oral-vaginal)

Male Genital Infections Case 3 EXAM Several small ulcers on tongue No groin lymphadenopathy Meatal inflammation Urethral discharge moderate & clear MICROSCOPY >10 PMNs per high-powered field Picture source: O’Mahony, C. International Journal of STD & AIDS 2006; 17: 203-4.

Male Genital Infections Case 3 TREATMENT (prior to lab results) Azithromycin Acyclovir LAB RESULTS NAAT negative for N. gonorrhoeae and C. trachomatis Culture + for HSV-1 and adenovirus Serology negative for HSV-1 & HSV-2

Bacterial versus Viral NGU MG Adeno HSV Mod/severe dysuria 28% 20% 69% 78% Meatal erythema 33% 26% 92% 89% Among those with adeno or herpes – most had prominent dysuria and meatal erythema (meatitis) – consider acyclovir Consider acyclovir in patients with prominent dysuria and meatal inflammation Bradshaw C et al. JID 2006;193:336-45

Male Genital Infections Case (#4) 34 year old HIV-infected man Intermittent ART CD4 100 Weight loss, cough Painful, swollen R testicle 7 days

Male Genital Infections Case #4 – Testicular Enlargement Epididymitis Age <35 Chlamydia, gonorrhea Ceftriaxone x1 and Doxycycline x 10 days Age >35 (Also insertive anal sex, recent urethral instrumentation) Enteric pathogens (E. coli) Levofloxacin x 10 days

Male Genital Infections Case #4 – Testicular Enlargement “The 4 T’s” Trauma Torsion Age <20 Sudden onset, often during sleep Surgical emergency Tuberculosis Local epidemiology Higher risk in HIV Gradual onset Tumor Usually non tender

Prostatitis (National Institutes of Health Classification) Acute bacterial Fever, chills, dysuria, pelvic pain Age <35: GNR > GC, CT Age ≥35: GNR and other UTI pathogens More frequent in HIV infection Chronic bacterial* Dysuria without other acute signs Four week duration of antibiotics Chronic prostatitis/pelvic pain syndrome* Inflammatory Non-inflammatory MOST cases of “prostatitis” May not involve prostate, not infectious, antibiotics ineffective Asymptomatic inflammatory* *Not clearly shown to be caused by sexually transmitted pathogens

Take Home Points Urethritis in men is classified as gonococcal vs. non-gonococcal C. trachomatis is most common identifiable pathogen in NGU Treat for gonorrhea + chlamydia or chlamydia alone based on gram stain Partners within 60 days should be treated Epididymitis treatment based on age, risk factors Think through the “4 T’s” also, especially TB Spectinomycin not active against NGU – painful injection Goals:Treat/prevent chlamydia, prevent reinfection Examine for other STDs, if practical

Contraception and HIV in Women Next session: June 3, 2010 R. Scott McClelland, MD: Contraception and HIV in Women Listserv: itechdistlearning@u.washington.edu Email: DLinfo@u.washington.edu Thank you for attending the session. We will email answers to the questions that we were unable to get to today to the Distance Learning listserv. If you have additional questions, please email them to the listserv. That listserv is: itechdistlearning@u.washington.edu. Please contact DLinfo@u.washington.edu if you would like to get on this listserv.