Urethritis

Epidemiology

  • Peak Group: young, sexually active males
  • Relative Incidence: CDC estimates that there are 3x as many Chlamydia cases as gonococcal cases in the US

Risk Factors for Sexually Transmitted Infections (STI)

  • Contact with Sex Workers
  • History of Sexually Transmitted Infection Within the Last 24 Months
  • Illicit Drug Use
  • Imprisonment
  • Meeting Partners on the Internet of Other Potentially Risky Partner Behaviors
  • Multiple Sex Partners
  • New Sex Partner in Last 3 Months
  • Residence in Urban Area
  • Unmarried Status
  • Young Age

Recommended Screening for Sexually Transmitted Infections (STI) (2010: CDC, IDSA, USPTF)

  • Sexually Active Females <25 y/o
    • Screen annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis
  • Females 13-25 y/o
    • Screen at least once for HIV
    • Screen annually for HIV, if high risk
    • Screen for other sexually transmitted infections based on risk profile
  • Females 26-64 y/o
    • Screen at least once for HIV
    • Screen annually for HIV, if high risk
    • Screen for other sexually transmitted infections based on risk profile
  • Pregnant Females
    • Screen for Chlamydia Trachomatis/HIV/Hepatitis B/Syphilis in first trimester
  • HIV-Positive Female
    • Screen annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Trichomoniasis
    • Screen for Hepatitis B/Hepatitis C/Syphilis/HSV2 at first visit and then per risk profile
  • Heterosexual Men 13-64 y/o
    • Screen for HIV at least once
    • Screen annually for HIV, if high risk
    • Screen for other sexually transmitted infections based on risk profile
  • Males Who Have Sex with Males
    • Screen annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Syphilis/HIV, and more frequently according to risk
    • Screen for Hepatitis B at least once
  • HIV Positive Males
    • Screen annually for Neisseria Gonorrhoeae/Chlamydia Trachomatis/Syphilis
    • Screen for HSV-2/Hepatitis B at first visit
  • Injectable Drug Users
    • Screen for Hepatitis A/Hepatitis B -> if not immune, vaccination should be offered
  • Persons with History of Multiple Sexual Partners
    • Screen for Hepatitis A/Hepatitis B -> if not immune, vaccination should be offered
    • Screening for Hepatitis C is of uncertain need in this population (and in those with other sexually transmitted infections)
  • Adults Born Between 1945-1965: this age group accounts for approximately 27% of the population, but accounts for approximately 75% of all chronic Hepatitis C infections
    • Screen for Hepatitis C (CDC recommendation in 1/14)

(Note: there is no current recommendation to screen for HSV in HIV-negative patients with risk factors for sexually transmitted infections)

Screening Interval

  • Patients with Prior Negative Screening: interval for repeat testing is based on risk factor profile
  • Previously Infected Females: rescreening at 3-4 months is recommended (due to high rates of reinfection)
    • Previously Infected with Neisseria Gonorrhoeae/Chlamydia Trachomatis: California Department of Public Health recommends rescreening at 3 months
  • Previously Infected Males: rescreening interval is unclear
    • Previously Infected with Neisseria Gonorrhoeae/Chlamydia Trachomatis: California Department of Public Health recommends rescreening at 3 months

Etiology

Infection

  • Adenovirus (see Adenovirus, [[Adenovirus]])
    • Risk Factor: insertive oral sex in males who have sex with males
  • Chlamydia Trachomatis (see Chlamydia Trachomatis, [[Chlamydia Trachomatis]])
    • Epidemiology: accounts for most cases of non-gonococcal urethritis
    • Incubation Period (Variable): 2-35 days
  • Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
  • Herpes Simplex Virus (HSV1 or HSV2) (see Herpes Simplex Virus, [[Herpes Simplex Virus]]): more commonly in primary than secondary infection
    • Risk Factor: insertive oral sex in males who have sex with males
  • Mycoplasma Genitalium (see Mycoplasma Genitalium, [[Mycoplasma Genitalium]])
  • Neisseria Gonorrhoeae (Gonococci) (see Neisseria Gonorrhoeae, [[Neisseria Gonorrhoeae]]): Gram-negative coffee bean-shaped diplococci
    • Incubation Period: <2 wks
  • Trichomonas Vaginalis (see Trichomonas Vaginalis, [[Trichomonas Vaginalis]])
  • Ureaplasma Urealyticum (see Ureaplasma Urealyticum, [[Ureaplasma Urealyticum]])
  • Uropathogenic Escherichia Coli (UPEC) (see Escherichia Coli, [[Escherichia Coli]])
    • Risk Factor: insertive anal sex

Other


Diagnosis

Nucleic Acid Amplification Test (NAAT)

  • Indications: second generation tests are indicated to detect both Neisseria Gonorrhoeae and Chlamydia Trachomatis in males/females with or without symptoms
  • Availability: commercially available from multiple manufacturers (Roche, etc)
  • Technique: PCR amplification, strand displacement amplification (SDA), or transcription-mediated amplification (TMA) of organism DNA/RNA in sample
    • Technique can theoretically detect as little as one organism per samples (the detection threshold of culture is approximately 1000 organisms per sample)
    • Sensitivity of various amplification methods varies
  • Optimal Specimen Type
    • Male: first void urine sample
      • Perform as well or better than urethral swabs
    • Female: vaginal swab
      • Vaginal swabs perform as well as cervical swabs (although cervical swabs may be substituted in cases when pelvic exam is performed)
      • Self-collected vaginal swabs are equivalent in sensitivity/specificity to clinician-collected vaginal swabs
      • Female urine specimens are 10% less effective than vaginal swabs for detection of Neisseria Gonorrhoeae (possibly related to the presence of urine inhibitory substances which may interfere with NAAT)
      • Female “clean catch” urine (if being performed at the same time) requires external cleansing of the urethra, which will impede optimal NAAT testing of urine -> therefore, NAAT of female urine should be performed using first void urine without external cleansing prior to collection
  • Cost-Effectiveness: cost effective in preventing sequelae of Neisseria Gonorrhoeae and Chlamydia Trachomatis infections
  • Cross-Reactivity with Non-Gonococcal Neisseria Species: none
  • Advantages of NAAT Over Urethral Swab Culture
    • Faster Test Turnaround Time Than Urethral Swab Culture
    • Higher Sensitivity (100%) and Equal Specificity (99%) Than Urethral Swab Culture
    • Non-Invasive Collection Method: requires only urine to perform, rather than a urethral swab
    • Single Test Can Be Employed for Both Organisms
  • Advantages of NAAT Over Other Molecular Testing Methods: NAAT is preferred over direct fluorescence antibody testing/ELISA/nucleic acid hybridization tests, due to their superior sensitivity/specificity
  • Disadvantages of NAAT
    • Expensive
    • Does not Enable Determination of Antibiotic Sensitivity for the Organism: therefore, cultures are still required in cases where antibiotic resistance is suspected
    • Requires Processing in the Lab (Not Available at the Point of Care)
  • Use of NAAT with Non-Genital Body Specimens: NAAT has higher sensitivity than culture to detect Chlamydia Trachomatis in oropharyngeal or rectal samples in males who have intercourse with other males: however, this use is not FDA-approved and needs to be validated in terms of performance at the local lab/clinical site

Urinalysis with Urine Culture

  • Specimen: first void urine specimen is required
    • Urination within 2 hrs of exam should be avoided, as it may impair the ability to detect organisms
  • Criteria: >10 WBC per hpf on first void urine is consistent with urethritis
  • Criteria: positive leukocyte esterase (on dipstick) on first void urine is consistent with urethritis

Urethral Swab with Culture

  • Used historically to diagnose Neisseria Gonorrhoeae and Chlamydia Trachomatis infections: however, NAAT above is now the preferred diagnostic method to detect these organisms
  • Culture is currently the only means of detecting Mycoplasma Genitalium and Ureaplasma Urealyticum infections
    • DNA-based testing methods (with 97% sensitivity) for these organisms have been developed, but are not commercially available yet
  • Criteria: >5 neutrophils per hpf indicates presence of urethritis
  • Disadvantages
    • Urethral Swab Procedure is Uncomfortable

Other Testing

  • Herpes Simplex Virus (HSV) Culture and PCR: indicated in patients who have genital ulcer(s)
  • Affirm PCR Assay: indicated only in female cases to detect the 3 major causes of bacterial vaginosis (Candida, Gardnerella, and Trichomonas)
    • Utilizes vaginal/cervical swab
  • HIV Test: usually indicated in cases of suspected sexually-transmitted infection, due to possibility of co-infection with HIV
  • RPR: usually indicated in cases of suspected sexually-transmitted infection or genital ulcer(s), due to possibility of co-infection with syphilis

Clinical Manifestations

  • General Comments
    • Presence of Symptoms
      • Males: historically, only 5-10% of gonoccocal urethritis were believed to be asymptomatic (however, some studies suggest that this rate may be much higher)
      • Males: anywhere between 40-90% of Chlamydia Trachomatis cases are asymptomatic
      • Males: Mycoplasma Genitalium may be more likely to be symptomatic than Chlamydia Trachomatis infection
    • Usefulness of Clinical Features to Distinguish Microbiologic Etiologies: clinical features alone are not usually adequate to distinguish gonococcal from non-gonococcal/chlamydial urethritis
    • Prevalence of Co-Infection: 25-30% of male gonococcal urethritis cases are co-infected with Chlamydia
  • Dysuria (see Dysuria, [[Dysuria]]): most common symptom
    • May consist of urethral pain or pruritus
  • Urethral Discharge (“Drip”) (see Urethral Discharge, [[Urethral Discharge]]): may be present only prior to first morning void or throughout the day
    • Presence of urethral discharge is more commonly seen in gonococcal urethritis than Chlamydial urethritis
    • Trichomonas may produce purulent urethral discharge
  • Painful, Genital Ulcers (see Mucocutaneous Ulcers, [[Mucocutaneous Ulcers]]): seen in cases due to Herpes Simplex Virus (HSV)
    • Commonly Associated Features
      • Fever (see Fever, [[Fever]])
      • Headache (see Headache, [[Headache]])
      • Tender inguinal Lymphadenopathy (see Lymphadenopathy, [[Lymphadenopathy]])

Complications

  • Epididymitis (see Epididymitis, [[Epididymitis]]): 4x-increased risk following Chlamydia Trachomatis urethritis
  • Prostatitis (see Prostatitis, [[Prostatitis]]): slightly increased risk following Chlamydia Trachomatis urethritis
  • Impact on Male Fertility: Chlmydia Trachomatis infection is not believed to impact male fertility
  • Note: it is currently unclear as to whether Mycoplasma Genitalium and Ureaplasma Urealyticum infections cause long-term complications

Treatment

Antibiotics

  • Azithromycin PO (1000 mg x 1) or Doxycycline PO (100 mg BID x 7 days) + Ceftriaxone IM (250 mg x1): without culture data (and without certain patient follow-up with the provider), patient should be treated for both Neisseria Gonorrhoeae and Chlamydia Trachomatis infections
    • For Chlamydia Trachomatis Infection: Azithromycin is preferred over Doxycycline, due to increased compliance with a single dose medication
    • Patient and partner(s) should abstain from sexual acivity until course of therapy is completed

Expedited Partner Therapy (EPT)

  • Legal Statute: allowed in 27 states (including California)
  • Procedure
    • Health care provider is allowed to give treatment medications to patient to pass along to their sexual partner(s), as well as information recommending that the partner seek medical care
    • While provider can assist with notification of the patient’s sexual partners (at patient’s request), they are not legally obligated to do so
    • Provider or laboratory where testing was done are required to notify the public health department of the infection, as described below
  • Per CDC Guidelines
    • EPT is beneficial in heterosexual males/females for the treatment of Neisseria Gonorrhoeae and Chlamydia Trachomatis urethritis
    • EPT has a limited role in partner management for trichomoniasis
    • No data support its use in the routine management of syphilis

Sexually Transmitted Infections Required to Be Reported to California Public Health Department

  • Report Required Immediately
    • Outbreak of Any Sexually Transmitted Disease
  • Report Required Within One Day (Fax/Telephone/Email)
  • Report Required Within 7 Days (Fax/Telephone/Email)

References

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