URETHRAL DISCHARGE SYNDROME

7URETHRAL DISCHARGE SYNDROME

Urethral discharge among men is commonly caused by N. gonorrhoeae and/or C. trachomatis and/or non-gonococcal and non-chlamydial pathogens, such as M. genitalium and T. vaginalis. The prevalence of each of these pathogens varies geographically and by population group. Countries must conduct studies periodically in their settings to determine the most prevalent and important causes of urethral discharge or urethritis in that setting.

7.1. Clinical presentation – symptoms

Characteristically, men with urethritis (inflammation of the urethra) present with urethral discharge with or without dysuria (pain on urination). Occasionally, dysuria or itching at the tip of the urethra may be the only symptoms.

7.2. Examination findings – signs

Most men with urethritis have urethral discharge, which may range in quantity from being scanty to copious and in character from being clear to purulent. Distinguishing between discharge caused by gonorrhoea, chlamydia or any other cause of urethritis is not clinically possible.

7.3. Laboratory diagnosis

7.3.1. Molecular detection

NAAT is the current gold standard for detecting C. trachomatis and N. gonorrhoeae among men and women. NAAT also performs well for pharyngeal and anorectal samples for C. trachomatis and N. gonorrhoeae. For anorectal samples among men who have sex with men, chlamydia genovar testing for lymphogranuloma venereum should be done to guide the appropriate treatment regimen for lymphogranuloma venereum (48).

7.3.1.1. Specimens for N. gonorrhoeae and C. trachomatis for molecular assays

A first-catch urine or a urethral swab can be used for C. trachomatis and N. gonorrhoeae. NAAT for N. gonorrhoeae from anorectal and pharyngeal samples is also good, but there is potential for cross-reactivity with commensal Neisseria spp., especially in the throat.

7.3.1.2. Specimens for M. genitalium

M. genitalium causes urethritis. NAAT offers the best method for detecting M. genitalium from a first-catch urine in men. M. genitalium testing is not yet widely available.

7.3.1.3. Specimens for T. vaginalis

NAAT has the highest sensitivity of all diagnostic methods for detecting T. vaginalis. Urine can be used for some assays, but residual genital swab samples used for diagnosing chlamydia and gonorrhoea using NAAT are also good enough for detecting T. vaginalis nucleic acids.

7.3.2. Culture methods

Culture of N. gonorrhoeae is still the standard method for performing antimicrobial susceptibility testing. However, this organism is not that easy to grow in the laboratory, requiring special training and a special culture medium. For this reason, culture of N. gonorrhoeae is not routinely performed as part of managing people with gonococcal infection in resource-limited settings.

Culture of T. vaginalis was the cornerstone for detecting T. vaginalis before the advent of point-of-care antigen tests and NAAT. Although a culture medium is commercially available, once inoculated into the medium, cultures from men have to be incubated for a full five days while being examined daily using a microscope before being determined to be negative. Further, multiple sites, including semen, urine and urethral swabs, need to be examined before a definitive negative result can be certain. Routine culture methods for detecting T. vaginalis are no longer widely performed.

7.3.3. Microscopy

N. gonorrhoeae can be identified by light microscopy of Gram-stained samples and a presumptive diagnosis of gonorrhoea made if gram-negative diplococci are observed intracellularly in polymorphonuclear leukocytes, best seen when there is a urethral discharge. If carried out by an experienced person, a negative gram stain for intracellular diplococci, in the context of urethral discharge in a man, can be presumed to suggest non-gonococcal urethritis. Microscopy of methylene blue stain of a male urethral sample is an acceptable method for the presumptive diagnosis of gonorrhoea, but it does not allow for the differentiation of gram-negative cocci.

7.4. Recommendations for the management of urethral discharge

Table

taking a medical and sexual history and assessing the risk of STIs; performing a physical examination of the genital and anal areas; and

Fig. 2

Flow chart for the management of urethral discharge from the penis. NG, N.gonorrhoeae; CT, C. trachomatis. * If molecular assay was performed and results were not available on same day, revise the syndromic treatment initially provided according to the (more...)

Fig. 3

Flow chart for men with persistent or recurrent urethral discharge. This flow chart assumes that the patient has received and taken effective therapy for gonorrhoea and chlamydia before this consultation. NG, N.gonorrhoeae; CT, C. trachomatis; MG, M. (more...)

7.4.1. Evidence summary (Annex 3)

A systematic review of the accuracy of syndromic approaches for urethral discharge was conducted, including history, risk assessment, examination and microscopy (supplementary material: systematic review urethral discharge). Six studies were found for assessing the accuracy of syndromic management to detect N. gonorrhoeae and C. trachomatis, but the pooled sensitivity and specificity of the approaches did not improve as expected when adding microscopy (low-certainty evidence). In addition, studies show that there is variability in the implementation of the syndromic approaches based on symptoms or laboratory testing (49). Instead, the WHO Guideline Development Group considered that, when available, performing molecular assay tests for N. gonorrhoeae, C. trachomatis, T. vaginalis and/or M. genitalium and basing treatment on these results leads to treating the most people correctly. In the systematic review, the median prevalence of N. gonorrhoeae and/or C. trachomatis was 69% in men with urethral discharge. In a population with 60% prevalence of N. gonorrhoeae and C. trachomatis among those with urethral discharge, if molecular assays are not available, treating everyone for N. gonorrhoeae and C. trachomatis would mean 40% of them would be unnecessarily treated. The Guideline Development Group agreed that this proportion is acceptable and even higher proportions in settings with lower prevalence, because treating everyone would ensure that people infected with N. gonorrhoeae and C. trachomatis are treated, thereby reducing the chance of complications and further transmission. The Guideline Development Group also agreed that simple syndromic treatment based on the presence of urethral discharge would likely improve adherence to the approach and costs a minimal amount more than using history and/or risk assessment with or without examination (but with no missed cases).

7.5. Treatment recommendations for urethral discharge

Based on the recommendations in subsection 7.4, syndromic treatment for urethral discharge combines treatment for gonococcal and chlamydial infections. Other modifications can be made based on the availability of molecular diagnostic tests. Table 3 gives first-line and effective substitutes for treating people with urethral discharge syndrome.

Managing people with recurrent or persistent urethral discharge will require excluding reinfection by taking a thorough sexual history. When that has been done, additional treatment for M. genitalium and T. vaginalis may be considered. WHO guidelines on Neisseria gonorrhoeae (24) give guidance on how to approach apparent treatment failures among people with gonococcal infections.

Table 3

Recommended treatment options for urethral discharge syndrome.

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Guidelines for the management of symptomatic sexually transmitted infections [Internet]. Geneva: World Health Organization; 2021 Jun. 7, URETHRAL DISCHARGE SYNDROME.

Table

taking a medical and sexual history and assessing the risk of STIs; performing a physical examination of the genital and anal areas; and

For people with symptom of urethral discharge from the penis, management is recommended to be based on the results of quality-assured molecular assays. However, in settings with limited or no molecular tests or laboratory capacity, WHO recommends syndromic treatment to ensure treatment on the same day of the visit.	(Strong recommendation; moderate-certainty evidence)
Good practice includes: taking a medical and sexual history and assessing the risk of STIs; performing a physical examination of the genital and anal areas; and offering HIV and syphilis testing and other preventive services as recommended in other guidelines.	Good practice statement
Settings with quality-assured molecular testing in a laboratory with a fully operational quality management system and results available on the same day of the visit WHO recommends the following. Perform molecular assays such as nucleic-acid amplification testing (NAAT) to confirm or exclude Neisseria gonorrhoeae and Chlamydia trachomatis. Treat according to the test results on the same day. If urethral discharge is present but tests are negative, treat for non-gonococcal and non-chlamydial urethritis (such as Mycoplasma genitalium or Trichomonas vaginalis). When treatment based on molecular assays is not feasible on the same day of the visit, WHO recommends syndromic treatment of infection with N. gonorrhoeae and C. trachomatis and using the test results to support managing the partner when tests are available. Treat people with recurrent or persistent urethral discharge based on a repeat molecular assay (such as NAAT) after 21 days, testing for N. gonorrhoeae, C. trachomatis as well as M. genitalium and T. vaginalis and testing for antimicrobial-resistant N. gonorrhoeae.	(Strong recommendation; moderate-certainty evidence)
Settings in which same-day treatment is not feasible with molecular testing or with limited or no molecular testing WHO suggests the following. Treat people who have urethral discharge confirmed on examination for N. gonorrhoeae and C. trachomatis to ensure same-day treatment. Treat people with recurrent or persistent urethral discharge for treatment failure based on WHO guidelines and review.	(Conditional recommendation; low-certainty evidence)
Good practice includes: if symptoms persist at review, checking partner notification and treatment history; and for people with recurrent or persistent urethral discharge, referring people to a centre with laboratory capacity to diagnose N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis and to test for antimicrobial-resistant N. gonorrhoeae and M. genitalium.	Good practice statement

Fig. 2Flow chart for the management of urethral discharge from the penis

NG, N.gonorrhoeae; CT, C. trachomatis.

* If molecular assay was performed and results were not available on same day, revise the syndromic treatment initially provided according to the test results when available

# If test is negative but urethral discharge is present, treat for non-gonococcal/non-chlamydial urethritis (such as M. genitalium, T. vaginalis or herpes simplex virus)

Fig. 3Flow chart for men with persistent or recurrent urethral discharge

This flow chart assumes that the patient has received and taken effective therapy for gonorrhoea and chlamydia before this consultation.

NG, N.gonorrhoeae; CT, C. trachomatis; MG, M. genitalium.

Table 3Recommended treatment options for urethral discharge syndrome^a

Infections covered	First-line options	Effective substitutes
Therapy for uncomplicated Neisseria gonorrhoeae (24) Plus Therapy for Chlamydia trachomatis (25)
In settings in which local antimicrobial resistance data are not available, the WHO STI guideline suggests dual therapy for gonorrhoea.
N. gonorrhoeae ^a	Ceftriaxone 250 mg, intramuscularly, single dose Plus Azithromycin 1 gram, orally, single dose	Cefixime 400 mg, orally, single dose Plus Azithromycin 1 gram, orally, single dose
C. trachomatis	Doxycycline 100 mg, orally, twice daily for seven days (to be given only if gonorrhoea therapy did not include azithromycin)	Azithromycin 1 gram, orally, single dose or Erythromycin 500 mg, orally, 4 times a day for 7 days or Ofloxacin 200–400 mg, orally, twice a day for 7 days. (to be given only if gonorrhoea therapy did not include azithromycin)
In settings in which local antimicrobial resistance data reliably confirm the susceptibility of N. gonorrhoeae to the antimicrobial agent, singe therapy may be given.
N. gonorrhoeae	Ceftriaxone 250 mg, intramuscularly, single dose	Cefixime 400 mg, orally, single dose or Spectinomycin 2 grams, intramuscularly, single dose (availability makes this antibiotic impractical)
Additional therapeutic options for recurrent or persistent infections
T. vaginalis	Metronidazole 2 grams, orally, single doses	Metronidazole 400 or 500 mg, twice daily for 7 days
M. genitalium	Azithromycin 500 mg, orally on day 1, 250 mg daily on days 2–5

a: Because of increasing antimicrobial resistance to azithromycin in N. gonorrhoeae and M. genitalium and reduced susceptibility of N. gonorrhoeae to cephalosporins, WHO is in the process of revising current treatment recommendations and dosages.

7URETHRAL DISCHARGE SYNDROME

7.1. Clinical presentation – symptoms

7.2. Examination findings – signs

7.3. Laboratory diagnosis

7.3.1. Molecular detection

7.3.1.1. Specimens for N. gonorrhoeae and C. trachomatis for molecular assays

7.3.1.2. Specimens for M. genitalium

7.3.1.3. Specimens for T. vaginalis

7.3.2. Culture methods

7.3.3. Microscopy

7.4. Recommendations for the management of urethral discharge

Table

Fig. 2

Fig. 3

7.4.1. Evidence summary (Annex 3)

7.5. Treatment recommendations for urethral discharge

Table 3

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Table

Fig. 2Flow chart for the management of urethral discharge from the penis

Fig. 3Flow chart for men with persistent or recurrent urethral discharge

Table 3Recommended treatment options for urethral discharge syndromea

Table 3Recommended treatment options for urethral discharge syndrome^a