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Lower genital tract infection in men

Urethritis

Non specific urethritis  is the term for a sexually transmitted urethritis not caused by N. gonorrhoeae [gonorrhoea]. In developed countries, Chlamydia trachomatis serovars D to K is the dominant pathogen, being thought to be the cause of around 50% of cases of symptomatic non specific urethritis in men, with various other organisms including Mycoplasma genitalium and Ureaplasma species [Horner et al., 2001; Taylor-Robinson, 2002] and Trichomonas vaginalis [Pepin et al., 2001] and perhaps the anaerobic bacteria of bacterial vaginosis in women [Keane et al., 1997] also involved. In Africa, by contrast, M. genitalium appears to be much more commonly associated with non specific urethritis, particularly in Central Africa [Morency et al., 2001]. Fortunately, M. genitalium is sensitive to similar antibiotics to C. trachomatis.

The incubation period for chlamydial urethritis is approximately 7 - 14 days [Stamm et al., 1984], whereas gonococcal urethritis has a shorter incubation period of the order of 4 days. Patients with symptomatic chlamydial urethritis present with dysuria [lay reader: pain on passing urine] and a whitish, grey or sometimes clear urethral discharge. This discharge is usually most prominent first thing in the morning, but it may be necessary to "milk" the penis for one or two drops of discharge to appear at the urethral opening. Symptomatic gonococcal urethritis classically has a more yellowy-green purulent [pussy] discharge but there is sufficient overlap in the symptoms that neither type of urethritis can reliably be distinguished on clinical grounds alone; laboratory tests are necessary. However, chlamydial urethral infection is much more likely to be asymptomatic than is gonococcal infection  [Burstein & Zenilman, 1999; Stamm et al., 1984]. The presence of 4 or more polymorphonuclear leukocytes in a Gram stained preparation of  discharge examined at x 1000 magnification establishes a diagnosis of urethritis. The absence of gonococci in Gram stain or on culture establishes a diagnosis of non specific [or, better, non gonococcal] urethritis. Additionally, C. trachomatis is often the cause of so-called post gonococcal urethritis, which occurs when gonococcal infection is treated with an antibiotic regime that does not simultaneously eradicate any co-incident chlamydial infection; multiple infection with agents of urethritis is common, particularly in the developing world [Bowden et al., 1998].

The sexually active male with asymptomatic urethritis is a significant reservoir of potential infection for women, in whom the consequences of lower genital tract infection are likely to be  more severe. In one study, infection rates in women exposed to male sex partners with Chlamydia were 65% and with gonorrhoea 73%. Sixty-four percent of chlamydial infected couples were infected with identical serovars while an additional 28% shared at least one serovar. However multiple serovars of C. trachomatis were common in sex partners and exchanged frequently [Lin et al., 1998]. Chlamydial infection in the male also increases by 2 to 3 fold the risk of infecting a partner with HIV. This is because the shedding of co-incident HIV infection is increased if urethritis is present [Winter et al., 1999]. 

Various studies have screened adolescent males for asymptomatic urethritis in an attempt to develop prevention strategies [e.g. Pierpoint et al., 2000]. An important advance first made by Owen Caul and Ian Paul was the observation that urine is a convenient, non-invasive specimen for screening men for chlamydial urethritis without the embarrasment of genital examination or the discomfort of a urethral swab [Caul et al., 1988; Paul & Caul, 1990]. The presence of more than 10 polymorphonuclear leukocytes in the first 15 - 20 ml of "first catch" urine is indicative of asymptomatic urethritis, as is a positive leukocyte esterase test. This latter test is simply a non-specific indicator of the presence of polymorphonuclear leukocytes [lay reader: white cells, part of the bodies defences] due to acute inflammation.  When compared with nucleic acid amplification-based diagnostic tests for C. trachomatis, it has relatively poor positive predictive values, [even for a high prevalence population], but quite good negative predictive values [Bowden et al., 1998]. In resource-poor areas, this may be all that is available. In developed countries a better approach is to use one of the nucleic acid amplification-based tests for C. trachomatis which are able to detect the presence of the organism in the centrifuged pellet from first catch urine with similar or better sensitivity than is obtained by using a urethral swab [Chernesky et al., 1997; Stary et al., 1998]. The use of non-invasive samples for the laboratory diagnosis of chlamydial and other infections [Stary, 1998] is an important advance in the management of these infections. Screening of men for asymptomatic urethritis only becomes a viable proposition when the prevalence of infection is of the order of 5%. In North West London the prevalence of chlamydial infection in asymptomatic males was only 1.9% [Pierpoint et al., 2001] whereas in Papua New Guinea in males it was 26% [Tiwara et al., 1996] [see: prevention of genital tract infections].

Treatment

The CDC STI management guidelines 2002 recommend that patients with urethritis are investigated for possible chlamydial or gonococcal infection. Treatment should be initiated immediately once the diagnosis is in little doubt and patients should be advised to abstain from sexual intercourse for 7 days following the start of treatment. Treatment should commence in the physician's office; observed single dose azithromycin therapy has the advantage that compliance is assured. The CDC 2002 guidelines for antibiotic therapy of urethritis are essentially the same as those for cervicitis: 

Patients should be instructed to return for further evaluation if their symptoms persist. However, symptoms of urethritis often persist for some time after microbiological cure has been achieved. Thus, where laboratory testing is  available, a further course of treatment should not be given unless laboratory tests show continued infection. Patients should also be requested to refer for evaluation any of their sex partners in the previous 60 days. The CDC recommend that patients who have persistent or recurrent urethritis are re-treated with the initial regimen where there is reason to suspect poor compliance or if they were re-exposed to an untreated sex partner. Otherwise, a culture of an intra-urethral swab specimen and a first-void urine specimen for Trichomonas vaginalis should be performed. Some cases of recurrent urethritis following doxycycline treatment may be caused by resistant Ureaplasma urealyticum. Where it seems likely the patient complied with the initial antibiotic therapy and where re-exposure can be excluded, the CDC recommend the following regimen for persistent urethritis: 

See also: chlamydial urethritis in women

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[MEW] Updated November 2002

References

Bowden, F. J. (1998). Reappraising the value of urine leukocyte esterase testing in the age of nucleic acid amplification. Sexually Transmitted Dieases 25, 322 - 326.

Burstein, G. R. & Zenilman, J. M. (1999). Nongonococcal urethritis - a new paradigm. Clinical Infectious Diseases 28, Suppl 1; S66 - S73. 

Caul, E. O., Paul, I. D., Milne, J. D. & Crowley, T. (1988). Non-invasive sampling method for detecting Chlamydia trachomatis. Lancet 2, (8622) 1246 - 1247.

CDC STI Treatment guidelines, May 2002 CDC Atlanta [For clinicians] 

Chernesky, M. A., Chong, S., Jang, D., Luinstra, K., Sellors, J., Mahony, J. B. (1997). Ability of commercial ligase chain reaction and PCR assays to diagnose Chlamydia trachomatis infections in men by testing first-void urine. Journal of Clinical Microbiology 35, 982 - 984.   Full article

Horner, P., Thomas, B., Gilroy, C. B., Egger, M. & Taylor-Robinson, D. (2001). Role of Mycoplasma genitalium and Ureaplasma urealyticum in Acute and Chronic Nongonococcal Urethritis. Clinical Infectious Diseases 32, 995 - 1003.

Keane, F. E., Thomas, B. J., Whitaker, L., Renton, A. & Taylor-Robinson, D. (1997). An association between non-gonococcal urethritis and bacterial vaginosis and the implications for patients and their sexual partners. Genitourinary Medicine 73, 373 - 377.

Lin, J. S., Donegan, S. P., Heeren, T. C., Greenberg, M., Flaherty, E. E., Haivanis, R., Su, X. H, Dean, D., Newhall, W. J., Knapp, J. S., Sarafian, S. K., Rice, R. J., Morse, S. A. & Rice, P. A. (1998). Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among men with urethritis and their female sex partners. Journal of Infectious Diseases 178, 1707 - 1712.

Morency, P., Dubois, M . J., Gresenguet, G., Frost, E., Masse, B., Deslandes, S., Somse, P., Samory, A., Mberyo-Yaah, F.  Pepin, J.  (2001). Aetiology of urethral discharge in Bangui, Central African Republic. Sexually Transmitted Infections 77, 125 - 129.

Paul, I. D. & Caul, E. O. (1990). Evaluation of three Chlamydia trachomatis immunoassays with an unbiased, noninvasive clinical sample. Journal of Clinical Microbiology 28, 220 - 222.

Pepin, J., Sobela, F., Deslandes, S., Alary, M., Wegner, K., Khonde, N., Kintin, F., Kamuragiye, A., Sylla, M., Zerbo, P. J., Baganizi, E., Kone, A., Kane, F., Masse, B., Viens, P. & Frost E. (2001). Etiology of urethral discharge in West Africa: the role of Mycoplasma genitalium and Trichomonas vaginalis. Bulletin of the World Health Organization 79, 118 - 126.

Pierpoint, T., Thomas, B., Judd, A., Brugha, R., Taylor-Robinson, D. & Renton A. (2000). Prevalence of Chlamydia trachomatis in young men in north west London. Sexually Transmitted Infections 76, 273 - 276.

Stamm, W. E., Koutsky, L. A., Bebedetti, J. K., Jourden, J. L., Brunham, R. C., Holmes, K. K. (1984). Chlamydia trachomatis urethral infections in men. Prevalence, risk factors and clinical manifestations. Annals of Internal Medicine 100, 47 - 51. 

Stary, A. (1998). Urethritis. Diagnosis of non gonococcal urethritis. Dermatology Clinics 16, 723 - 726.

Stary, A., Schuh, E., Kerschbaumer, M., Gotz, B. & Lee, H. (1998). Performance of transcription-mediated amplification and ligase chain reaction assays for detection of chlamydial infection in urogenital samples obtained by invasive and noninvasive methods. Journal of  Clinical Microbiology 36, 2666 - 2670.  Full article 

Taylor-Robinson, D. (2002). Mycoplasma genitalium - an up-date. International Journal of STD and AIDS. 13, 145 - 151.

Tiwara, S., Passey, M., Clegg, A., Mgone, C., Lupiwa, S., Suve, N. & Lupiwa, T. (1996). High prevalence of trichomonal vaginitis and chlamydial cervicitis among a rural population in the highlands of Papua New Guinea. Papua New Guinea Medical Journal 39, 234 - 238.

Winter, A. J., Taylor, S., Workman, J., White, D., Ross, J. D., Swan, A. V.  Pillay, D. (1999). Asymptomatic urethritis and detection of HIV-1 RNA in seminal plasma. Sexually Transmitted Infections 75, 261 - 263.

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