1. 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

2. 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

3. 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

4. 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

5. 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”

6. More typical case with overtly purulent discharge

7. 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

9. 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

10. Treatment of Uncomplicated Gonorrhea
RECOMMENDED
Ceftriaxone 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.

11. 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 Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, March 2009.

12. 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

13. 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

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

16. 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

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

18. 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%

19. 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%

20. 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

21. 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

22. 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

23. Recurrent and Persistent NGU
Symptoms may take 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

24. 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)

25. 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:

26. 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

27. Bacterial versus Viral NGUMG
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

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

29. 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

30. 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

31. 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

32. 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

33. Contraception and HIV in Women
Next session: June 3, 2010
R. Scott McClelland, MD:
Contraception and HIV in Women
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