| Pathogen | Reported frequency in cases of urethritis |
|---|---|
| Neisseria gonorrhoeae | 12%–34% |
| Chlamydia trachomatis | 15%–55% of NGU |
| Mycoplasma genitalium | 3%–38% of NGU |
| Ureaplasma urealyticum | 6%–60% of NGU |
| Trichomonas vaginalis | <5% of NGU |
| Gardnerella vaginalis | 12% of NGU in a single study |
| Mycoplasma hominis | Rare, frequency vaguely defined |
| Herpes simplex virus | Rare |
| Gram-negative bacteria | Rare |
| Adenoviruses | Rare |
| Other: mycobacteria, syphilis, lymphogranuloma venereum, streptococci, Neisseria meningitidis, anaerobes, fungi | Very rare/isolated reports |
Abbreviation: NGU = nongonococcal urethritis.
Epidemiology
The global annual incidence of urethritis is enormous: An estimated 62 million cases of GU and 89 million cases of NGU occur annually. In the United States alone, approximately five million annual cases are reported, the great majority of which is NGU. The incidence of GU has been declining in the United States since 2000, while inverse trends have been observed for NGU. The latter are accompanied though by a declining incidence of chlamydial NGU and may actually reflect the increasing recognition of other etiologies of NGU or the effect of chlamydial control programs. A steady increase of the total urethritis cases reported in males has been observed in France in recent years. The increasing availability of sophisticated diagnostic techniques in developing countries has also helped underline the magnitude of the problem.
There seems to be no racial predilection for the incidence of the syndrome but certain socioeconomic factors may apply, urethritis being more common in low-income populations. Gender predilection seems also not to exist, although the difference in the syndrome’s clinical presentation between males and females may account for a larger percentage of female cases that are asymptomatic and thus not reported; on the other hand, while male urethritis is a distinct syndrome, female disease is often misdiagnosed in the context of, or coexists undiagnosed with, inflammation of other sites of the female urogenital tract, most importantly cervicitis. Due to urethritis being a sexually transmitted disease, the age group of 20 to 24 years predominates in reported cases. The use of condoms has been inversely related to the incidence of urethritis. Other risk factors include the use of spermicides (which, however, may predispose to chemical urethritis only), the number of sexual partners, homosexuality in males, unprotected anal sex for heterosexual males, and history of other sexually transmitted diseases.
Clinical manifestations
The disease is often asymptomatic, particularly so in female patients and in cases of chlamydial etiology. Up to 75% of women with chlamydial urethritis experience no symptoms. Gonococcal urethritis exhibits a shorter incubation period than NGU and a more abrupt onset, and is usually symptomatic. Incubation period lies between a few days, for gonococcal disease, and up to 2 weeks for the nongonococcal one. Urethral discharge, dysuria, and urethral pruritus are the cardinal symptoms: Discharge is a product of the polymorphonuclear cell influx in the region as part of the immune response and epithelial cell apoptosis, is usually mucopurulent, most often observed at the morning, may be blood-tinged, and is a result of the inflammatory interplay following entry of the pathogen: this inflammatory response is more pronounced in cases of gonococcal compared to chlamydial urethritis and in males compared to females. Occasionally, in women with gonococcal infection symptoms can result from endocervical infection, such as altered vaginal discharge or intermenstrual bleeding and menorrhagia. Other causes of NGU such as M. genitalium tend also to cause symptomatic disease whereas Trichomonas infection in males can range from asymptomatic to more severe clinically than GU.
Diagnosis
The diagnosis of urethritis is based on the presence of relevant clinical symptoms accompanied by laboratory findings: Gram stain microscopy of urethral secretions that exhibits five or more white blood cells (WBCs) per oil-immersion field, or a positive WBC esterase test of first-void urine, or a first-void urine sample exhibiting 10 or more WBCs per high-power field. The latter though has been considered inadequate by various studies reporting that 12% of chlamydial infections and 5% of gonococcal ones may be undiagnosed by this criterion.
Gram stain microscopy allows for initial etiologic workup, since the observation of gram-negative intracellular diplococci may allow for a rapid diagnosis of gonococcal urethritis, with a sensitivity and specificity of >95% and >99% respectively in symptomatic men. However, microscopy has poor sensitivity (around 50%) in urethral samples of asymptomatic men and urethral and cervical samples of females. Thus, absence of pathologic findings on a Gram smear does not rule out gonococcal infection, especially in the later situations. Cultures may allow for isolation of the specific pathogen and evaluation of its antimicrobial susceptibility. Due to the increase in worldwide prevalence of cephalosporin-resistant strains of N. gonorrhoeae, cultures and susceptibility testing have become useful for new cases of urethritis and essential for cases with recurrence after treatment for GU.
Molecular diagnostic methods have been increasingly applied to urethritis diagnosis, nucleic acid amplification tests (NAAT) being the most popular choices, since they can be performed with urine specimens as well as urethral samples. These assays have shown exquisite sensitivity and specificity both for gonococci and Chlamydia, but lack the ability to identify resistant strains of gonococcus. Other NAAT exist for less common pathogens, such as M. genitalium, but their standard application in clinical practice has been under dispute. Other diagnostic tests for NGU include a wet preparation for Trichomonas diagnosis and a potassium hydroxide (KOH) preparation for fungal infections. Table 59.2 summarizes current diagnostic facilities for each pathogen and specific data about each assay’s sensitivity and specificity. After confirmation of GU or NGU diagnosis, especially in cases of high-risk populations or GU recurrence, it is advisable to test for other sexually transmitted diseases, including human immunodeficiency virus (HIV) and syphilis, and, in female patients, pregnancy should be ruled out before specific antibiotic recommendations.
| Pathogen | Diagnostic tools | Comments |
|---|---|---|
| Neisseria gonorrhoeae | Gram stain Culture NAHT NAAT | Culture and NAHT require urethral swab specimens, whereas NAAT can be performed on urine specimens. Culture allows identification of resistant strains |
| Chlamydia trachomatis | Culture Direct immunofluorescence Enzyme immunoassays NAHT NAAT | NAHT require urethral swab specimens, whereas NAAT can be performed on urine samples/in females addition of cervical samples increases sensitivity NAAT more sensitive and 100% specific |
| Mycoplasma genitalium | NAAT | NAAT can be performed on urine samples/in females addition of cervical samples increases sensitivity |
| Ureaplasma urealyticum, Mycoplasma hominis | Culture | Cultures need specialized media, not performed in everyday practice Urethral swabs preferred to urine samples |
| Trichomonas vaginalis | Wet preparation Culture NAAT | Wet preparation is 60% sensitive, often negative in males Anaerobic culture of urethral swab or first-void urine, 95% sensitive NAAT is considered superior to cultures (97% sensitivity and 98% specificity), but needs multiple samples in males |
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