Male urethritis with and without discharge: relation to microbiological findings and polymorphonuclear counts
S. Vesic, J. Vukicevic, Z. Dakovic, M. Tomovic, D. Dobrosavljevic,
L. Medenica, and M. D. Pavlovic
A B S T R A C T
KEY WORDS
urethritis, discharge, men, polymorphonuclear leukocytes, sexually transmitted infections
Objective We studied the relation between the presence or absence of urethral discharge, urethral pathogens, and polymorhonuclear (PMN) counts on Gram stained urethral smears in men with symptomatic urethritis.
Methods The study population was composed of 630 sexually active heterosexual men (aged 18-45 years) who had urethral symptoms and signs (discharge, dysuria or urethral discomfort). Participants were divided into two groups: the first (n=320) was comprised of men with urethral discharge confirmed on examination, while the other (n=310) was composed of patients with urethral symptoms but without discharge. Urethral swabs for Gram stained smears and microbiological analyses (N. gonorrhoeae, C. trachomatis, T. vaginalis and U. urealyticum) were taken from all study participants. Polymorphonuclear leukocytes (PMN) on Gram-stained urethral smears were counted in 5 oil immersion xloOo PMN per high power fields (phpf). Urethritis was defined as the presence of >5 PMN/hpf.
Results N. gonorrhoeae was isolated only in men with urethritis accompanied by discharge. The prevalence of T. vaginalis, C. trachomatis and U. urealyticum was significantly higher (F=8.854, P<0.01) in urethral swabs of urethritis patients with discharge compared to patients with no discharge. The most common urethral pathogen in both groups of patients was T. vaginalis (31.56% and 26.45%, respectively). One or more microorganisms were isolated in 258 (81%) subjects with urethritis with discharge, and in 166 (53.5%) urethritis patients without discharge. There was a positive correlation between the significant number of PMN in Gram stained urethral smears and positive microbiological findings in men with urethritis both with and without urethral discharge (Spearman's coefficients p=0.986 and p=0.993, respectively; P<0.01).
Conclusions The study found a relatively high prevalence of T. vaginalis among our men with urethritis irrespective of the presence or absence of urethral discharge, and showed that taking into account both discharge found on examination, and relevant PMN counts on Gram stained urethral smears fails to detect only 4.2% of oligosymptomatic urethritis patients who are infected with one of the strict urethral pathogens.
Introduction
Microbial urethritis is one of the most common sexually transmitted infections (STI) in men. Its prevalence and rising incidence worldwide makes it a subject of intense research (1-3). Urethritis is usually classified as gonococcal and non-gonococcal (NGU) depending on the presence or absence of Neisseria gonorrhoeae. Though Chlamydia trachomatis accounts for up to 50% of cases of NGU and Mycoplasma genitalium and Trichomonas vaginalis are known to cause a smaller proportion, the cause of many cases of NGU remains unknown. Ureaplasma urealyticum, Gardnerella vaginalis, Haemophilus species, and Streptococcus spp have been associated with NGU but their causal role is unproved (4,5).
The most remarkable sign of male urethritis is mucopurulent or purulent urethral discharge (6). Sometimes the discharge, and even other signs and symptoms of urethral infection (dysuria, urethral discomfort, etc.) may be absent or very mild (7,8). In these cases, urethral inflammation may be confirmed by Gram stain of urethral secretions demonstrating >5 polymorphonuclear leukocytes (PMN) per oil immersion field. The Gram stain is the preferred rapid diagnostic test for evaluating urethritis (9). Several recent reports suggested that PMN counts on Gram stained urethral smears may not be sensitive enough in cases of C. trachomatis, and even N. gonorrhoeae infections (10,11).
The main objective of the study was to determine the relation between the presence or absence of ure-thral discharge, urethral pathogens, and PMN counts on Gram stained urethral smears in men with symptomatic urethritis.
Patients and methods
The study population was composed of 630 sexually active heterosexual men (aged 18-45 years) attending the Service for Sexually Transmitted Infections at the Institute of Dermatovenereology, Belgrade, from September 2004 to May 2006 who had urethral symp-
toms and signs (discharge, dysuria or urethral discomfort). The study was approved by the Institutional Review Board, and all participants gave an informed oral consent. We excluded men who had male sexual partners, those receiving antibiotics within the preceding month, who had HIV infection, or a current episode of genital herpes.
Urethral swabs for Gram stained urethral smears and microbiological analyses were taken from all study participants. Infection with N. gonorrhoeae was confirmed by finding intracellular Gram-negative diplococci and by culture on the modified chocolate agar under mi-croaerophilic conditions (12). Trichomonas vaginalis was detected in a wet mount of urethral smear by adding 2-3 drops of saline (13). Infection with C. trachomatis was detected by direct immunofluorescence (Chlamydia Direct IF Identification, BioMérieux, Marcey L'étoile, France) (14). Ureaplasma urealyticum was identified by the Mycoplasma IST test (BioMérieux, Marcey L'étoile, France) (15). Polymorphonuclear leukocytes on Gram-stained urethral smear were counted in 5 oil immersion x1000 PMN per high power fields (phpf). Urethritis was defined as the presence of >5 PMN/hpf (11).
For the purpose of analysis, all patients were divided into two groups. The first (n=320) was comprised of men with clinically confirmed urethral discharge, while the other (n=310) was composed of patients with urethral symptoms but without discharge. Data were analysed on SPSS for Windows, Version 9.0 (Chicago, IL, USA). The significance of relationship involving clinical characteristics, urethral PMN count distribution and urethral pathogens was assessed by parametric tests (%2 test and analysis of variance for proportions), whereas the relation between PMN counts and urethral pathogens in patients with and without discharge was assessed by Spearman rank correlation.
Results
Urethral pathogen distribution in men with urethri-tis with and without urethral discharge is given in Table 1. N. gonorrhoeae was isolated only in men with ure-
Table 1. Urethral pathogen distribution across the subject groups
Urethral pathogen	Patients with discharge		Patients without discharge	
		(n =320)		(n=310)
	n	%	n	%
Neisseriae gonorrhoeae	56	17.50	0	0
Trichomonas vaginalis	101	31.56	82	26.45
Chlamydia trachomatis	82	25.62	45	14.51
Ureaplasma urealyticum	77	24.06	58	18.70
F=8.854; /<0.01
Table 2. Correlation between urethral pathogen isolation and PMN counts in urethral smears in urethritis patients with and without discharge, and sensitivity, specificity, negative and positive predictive values for PMN counts.
PMN count phpf	Microbiological results	Microbiological results
(urethritis with discharge)	(urethritis without discharge)
	positive	negative	total	positive	negative	total
>5	254	32	286	119	9	128
<5	4	30	34	47	135	182
total	258	62	320	166	144	310
SN		98%			72%	
SP		48%			94%	
PPV		89%			93%	
NPV		88%			74%	
PMN, polymorphonuclear leukocytes; phpf, per high power field; SN, sensitivity; SP, specificity; PPV, positive predictive value; NPV, negative predictive value; p=0.986, P<0.01; p=0.993; P<0.01; all of the pts had ureaplasma isolated; 29 pts had ureaplasma isolated.
thritis accompanied by discharge (17.5%; n=56). The prevalence of T. vaginalis, C. trachomatis and U. urealyticum was significantly higher (F=8.854, P<0.01) in urethral swabs of urethritis patients with discharge. The most common urethral pathogen in both groups of patients was T. vaginalis (31.56% and 26.45%, respectively).
One or more of microorganisms were isolated in 258 (81%) subjects with urethritis with discharge, and in 166 (53.5%) urethritis patients without discharge. Urethritis caused by a single pathogen is the most common in both groups of patients (n=142; 55%, and n=128; 77%, respectively). Urethritis with simultaneous isolation of two pathogens was the most common occurrence, and more frequently found in patients with discharge. N. gonorrhoeae and C. trachomatis were found together in 11% of urethritis patients with discharge (not shown). Of note, in patients without discharge, there was not a single coinfection with T. vaginalis and C. trachomatis, but only U. urealyticum was found together with either of the former.
We found a positive correlation between the significant number of PMN in Gram stained urethral smears and positive microbiological findings in men with urethritis both with and without urethral discharge (Spearman's coefficients p=0.986 and p=0.993, respectively; P<0.01) (Table 2). In urethritis with discharge, only 1.5% of patients with identified urethral pathogen had <5 PMN phpf in their urethral smears explaining a relatively high sensitivity and positive predictive value (PPV) of the screening method in this group of patients - 98% and 89%, repectively (Table 2). On the other hand, in those patients without urethral discharge and with negative microbiological findings, >5 PMN phpf were found in only 6.2% giving the test in this setting reasonably high specificity and PPV (94 and 93%).
Discussion
The most prevalent urethral pathogen in our patients was T. vaginalis, both in those with (31.56%) and without (26.45%) urethral discharge. According to the World Health Organization (16), in Africa, trichomoniasis affects around 170 million people each year, whereas in Europe and USA the prevalence within high-risk populations ranges from 10-25% (17-19). Since T. vaginalis may be a cause of male infertility (reduces the motility of sperm cells) (13,16), and asymptomatic trichomo-niasis may spread rapidly, it is important to diagnose and treat the infection appropriately (17).
C. trachomatis is the most common cause of nongonococcal urethritis. As a function of different detection methods (culture, direct immunofluorescence test, nucleic acid amplification tests, PCR) (20), its prevalence in symptomatic urethritis ranges from 18 to 31% (19,21), and in asymptomatic forms from 5 to 40.5% (7,22,23). Prevalence of C. trachomatis in our urethritis patients with and without discharge (25.62 and 14.51%) is similar to published prevalence rates. Iser et al. (24) found that the presence of urethral discharge on history or examination, and a history of previous NGU symptoms were statistically associated with the detection of chlamydia. A similar study (11) confirmed, on multi-variate analysis, that the strongest associations with chlamydia infection were age, dysuria, and PMN per hpf. All of our patients were symptomatic but the presence of urethral discharge was associated with a doubled prevalence of C. trachomatis infection.
We isolated N. gonorrhoeae only in urethritis patients with discharge (17.50%). In a recent French survey, N. gonorrhoeae was found to be the second most common cause of male urethritis (13%) just after C. trachomatis (18%) (1). All of our patients had clinical
signs and symptoms of urethritis. In a series of 2626 men attending a STD clinic for routine evaluation, 990 were found positive for C. trachomatis and/or N. gonorrhoeae (11). Of them, 13 and 5%, respectively, were both asymptomatic and without urethral discharge.
U. urealyticum was detected in both groups of patients. It belongs to the normal flora of the genital tract, and the role it plays in nongonococcal male urethritis is not yet known (4,24). In roughly half of our uretritides where U. urealyticum was isolated, it was associated with other pathogens. It is speculated that coinfections trigger genital mycoplasmas to express their pathogenic potential (25).
Coinfection with two urethral pathogens were found in around 20% patients in both groups. The prevalence of C. trachomatis and N. gonorrhoeae coinfection in our patients with two agents detected concurrently was lower (10.81%) than those reported by other authors (25-43%) (26-28), but this may be a consequence of a lower sensitivity of DIF compared to amplification methods used to detect C. trachomatis in these studies. In urethritis patients without discharge, C. trachomatis and T. vaginalis occurred only with U. urealyticum, but never together. It is possible that, as being strict ure-thral pathogens, concommitant infection with chlamy-dia and trichomonas induces a strong inflammatory reaction clinically presenting as urethritis with discharge.
In our series of patients (Table 2), a relevant PMN
R E F E R E N C E S
count (>5 PMN phpf) on Gram stained urethral smears strongly correlated with microbiological findings in both patients groups. Though a number of recent studies (10,11,24) showed that a proportion of men infected with C. trachomatis and even N. gonorrhoeae may have <5 PMN phpf on their uretheral smears, our results support the usefulness of the screening method in areas where more reliable and expensive diagnostic methods are not available. All of our patients with discharge in whom strict urethral pathogens were isolated had >5 PMN phpf in their Gram stained urethral smears (Table 2). Haddow et al. (10) confirmed that discharge was significantly associated with higher PMN count (P<0.001) and was associated with chlamydia infection. Probably those 6 and 11% of urethritis patients without discharge with discordant microbiological and PMN count findings represent recent sexual contacts with infected partners where epidemiologic treatment is justified.
The study disclosed a relatively high prevalence of T. vaginalis among our men with urethritis irrespective of the presence or absence of urethral discharge, and showed that taking into account both discharge found on examination, and relevant PMN counts on Gram stained urethral smears fails to detect only 4.2% of oligosymptomatic urethritis patients who are infected with one of the strict urethral pathogens. Thus in countries with limited diagnostic resources, Gram stained urethral smears are still a useful tool for therapeutic decision making in male urethritis.
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AUTHORS' Sonja Vesic, MD, PhD, professor of dermatology, Institute of ADDRESSES Dermatovenereology, School of Medicine, University of Belgrade,
Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia Jelica Vukicevic, MD, PhD, dermatologist and microbiologist, same address Zorana Dakovic, MD, PhD, dermatologist, same address Maja Tomovic, MD, dermatologist, same address Danijela Dobrosavljevic, MD, dermatologist, same address Ljiljana Medenica, MD, PhD, professor of dermatology, same address Miloš D. Pavlovic, MD, PhD, professor of dermatology, Department of Dermatology and Venereology, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Serbia; e-mail: mdpavlovic2004@yahoo.com, corresponding author