URBAN, MARGUERITE A. MD*; COURY‐DONIGER, PATRICIA FNPC*; REICHMAN, RICHARD C. MD*†
The most common sexually transmitted bacterial pathogen in the United States is Chlamydia trachomatis. The Centers for Disease Control and Prevention (CDC) estimate there to be 4 million new infections each year with a total cost exceeding 50 million dollars.1 Infection in men has been associated with urethritis, epididymitis, proctitis, and Reiter's syndrome.1,2 In women, infection has been associated with urethritis, and cervicitis, and the complications of pelvic inflammatory disease(PID), chronic pelvic pain, increased risk of ectopic pregnancy, tubal infertility, and perinatal transmission.1,2 The major public health impact of sexually transmitted chlamydial infections results from these complications in women.1 This coupled with the high rates of asymptomatic infection in women has led to the development of public health policies recommending diagnostic screening programs for women at high risk of chlamydial infection.1 Such programs now exist in a number of locations in the United States including many public sexually transmitted diseases (STD) clinics, family planning clinics, and adolescent health centers.3–6
There have been fewer studies evaluating chlamydial infection in men, and large‐scale screening is uncommon in the United States. This is most likely because of the lower rate of complications of chlamydial infection in men as well as the high cost of screening programs. Nonetheless, men are an important source of infection and subsequent morbidity in women. Genital chlamydial infection in men may be asymptomatic or only mildly symptomatic; thus, it seems reasonable to expect that a screening program could enhance accurate diagnosis and treatment of infected men and potentially decrease transmission to susceptible women.
Men attending STD clinics have been shown to be a population at high risk for infection with C. trachomatis with reported prevalence rates ranging from 15% to 20%.7 The CDC STD Treatment Guidelines recommend presumptive treatment for C. trachomatis in men at highest risk for infection, who are defined as men who are sexual partners of women diagnosed with gonorrhea, chlamydia, cervicitis, or PID as well as heterosexual men diagnosed with gonorrhea, nongonoccocal urethritis (NGU), or epididymitis.8
In 1994, the New York State Department of Health began supplying the Monroe County Sexually Transmitted Diseases (MC STD) Clinic with Syva MicroTrak DFA tests (Palo Alto, CA) for C. trachomatis. The results of the subsequent screening program forC. trachomatis infection in men attending the MC STD Clinic are reported.
Monroe County is located in western New York State and includes the city of Rochester. The county population is approximately 750,000, 250,000 of whom reside in Rochester. The MC STD Clinic is located in an urban neighborhood in Rochester, and the overwhelming majority of patients treated at the clinic are city residents. The study was conducted from July 1, 1994 to June 30, 1996.
All men attending the MC STD Clinic are evaluated with a standard history and physical examination that complies with the CDC Clinical Practice Guidelines for STD Clinics.9 As part of the history, men are asked specifically about symptoms of dysuria and urethral discharge. Specimens are obtained for urethral smear, urethral culture of Neisseria gonorrhoeae (N. gonorrhoeae), and syphilis serology unless these specimens had been obtained at the clinic within the preceding 30 days and the patient was currently asymptomatic (e.g., men returning for human immunodeficiency virus [HIV] test results). Pharyngeal or rectal specimens are also obtained for culture of N. gonorrhoeae in men reporting a history of oral or rectal sex. During the study period, an additional urethral specimen was obtained for chlamydia testing.
Specimen Collection and Laboratory Methods
Urethral specimens were obtained by inserting Dacron swabs (Spectrum Laboratories, Dallas, TX) 2 to 3 cm into the urethra. The first swab was used to prepare a urethral smear and was then streaked onto enriched chocolate agar plates. The second swab was applied to the Syva MicroTrak DFA slide per the manufacturer's directions. Cotton swabs were used to obtain pharyngeal and rectal specimens, which were inoculated directly onto enriched chocolate agar.
Enriched chocolate agar plates were incubated at 37°C and transported daily to the University of Rochester Clinical Microbiology Laboratory where they were evaluated for the presence of N. gonorrhoeae by standard techniques.
Urethral smears were stained and interpreted by a laboratory technician on site. The number of white blood cells/high‐powered field was reported as ≥ 4 or less than four, and the presence/absence of gram‐negative intracellular diplococci was noted.
Specimens for DFA testing were shipped to Cytology Screening, Albany, NY, and were analyzed according to the manufacturer's specifications.
Gonorrhea was diagnosed if any culture grew N. gonorrhoeae or if the urethral Gram's stain was suggestive of gonorrhea (contained ≥ 4 white blood cells/high‐powered field plus gram‐negative intracellular diplococci).
NGU was diagnosed if the patient did not have gonorrhea and the urethral Gram's stain had ≥ 4 white blood cells/high‐powered field.
C. trachomatis infection was diagnosed if the DFA test was positive. DFA results were reported as positive (≥ 10 elementary bodies), negative(no elementary bodies), suspicious (1 to 9 elementary bodies), or unsatisfactory(inadequate sample).
These following data were collected from the clinic chart: race/ethnicity, diagnosis (gonorrhea, NGU, epididymitis, sexual contact with a person diagnosed with gonorrhea, chlamydia, cervicitis, or PID), and DFA results.
Patients diagnosed with NGU were also characterized as symptomatic if they reported dysuria or a history of discharge or had a discharge after urethral stripping on physical examination. All other men diagnosed with NGU were characterized as asymptomatic.
Sexual contacts were either self‐reported with a signed medical release allowing for epidemiologic treatment, physician‐reported, or reported through the local public health service system (gonorrhea only).
Comparisons among groups were made using chi‐square test for linear trend (Epi Info 6, Version 6.02, October, 1994; USD, Inc., Stone Mountain, GA).
During the study period, 8,510 men were evaluated at the MC STD Clinic for a total of 15,739 male visits. Of these visits, 9,662 were either new patient visits or visits for a new complaint. At each of these 9,662 visits a history and physical examination were performed and specimens were obtained for laboratory testing. The remainder of the 15,739 visits were follow‐up visits primarily for HIV post‐test counseling and are not included in the analysis. No DFA specimen was obtained for 110 of the eligible 9,662 visits; thus, data from 9,552 were available for analysis. Of the 9,552 DFA tests performed, 409 (5.2%) were unsatisfactory (data not shown).
The general characteristics of men seen at the MC STD Clinic during the study period are presented in Table 1. Race/ethnicity was reported as African‐American, white, or other (Asian, Native‐ American, Hispanic, or undefined). Fifty‐two percent of the men attending the clinic were African‐American; 41% were white; and 8% were classified as other. Ten percent (10%) of men attending the clinic were younger than 20 years of age; 45% were between the ages of 20 and 30; and 45% were greater than 30 years of age.
There were 474 positive DFA tests in 398 patients. The prevalence of chlamydial infection in men attending the clinic during the study period was 4.7%. Men with positive DFA tests were more likely to be African‐American (77.6%) (p < 10−7) and less than 24 years of age. (p < 10−7) (Figure 1).
C. trachomatis was identified in 4.96% of DFA tests performed for men who were new patients or returned for a new problem. Chlamydial infection was diagnosed in 10.7% of cases of gonorrhea and 10.0% of cases of NGU.C. trachomatis was identified in 12.6% of all men who were sexual contacts to cases of gonorrhea, chlamydia, cervicitis, or PID and in 20.0% of men diagnosed with NGU or gonorrhea who were also identified as sexual contacts to cases of gonorrhea, chlamydia, cervicitis, or PID. The lowest prevalence (0.6%) was in men not diagnosed with gonorrhea, or NGU, and who were not identified as contacts to cases of gonorrhea, chlamydia, cervicitis, or PID (Table 2).
C. trachomatis Infection In Men With NGU
There were 3,185 men diagnosed with NGU during the study period (Table 3). Fifty‐two percent(1,643) were asymptomatic, and 48% (1,542) were symptomatic. C. trachomatis was detected in 10.0% of all men with NGU, 7.6% of the asymptomatic men and 12.5% of the symptomatic men. There were 385 men with NGU who were also sexual contacts at risk for chlamydial infection. Chlamydial infection was identified in 19.5% of this group.
DFA Results for Men Treated Presumptively at Clinic Visit
According to clinic protocol, all men diagnosed with gonorrhea or NGU (regardless of symptoms) or as a sexual contact to cases of gonorrhea, chlamydia, cervicitis, or PID are treated with a therapy effective againstC. trachomatis. Of the 474 men with positive chlamydia tests, 444 were treated at the time of the visit: 105 were treated because of a diagnosis of gonorrhea, 317 because of a diagnosis of NGU, and 22 as sexual contacts to cases of gonorrhea, chlamydia, cervicitis, or PID. The remaining 30 (6.3%) men with untreated chlamydial infections were contacted to return to the clinic for treatment.
This report presents results from a large diagnostic screening program for C. trachomatis in men. We are able to comment both on the impact of the screening program compared with usual clinic protocols as well as on the disease prevalence in our clinic population.
The characteristics of the men diagnosed with chlamydial infection were similar to those reported in the literature. The men were more likely to be less than 24 years of age and to be African‐American. African‐American men under the age of 24 made up 18% of the clinic population but accounted for 49% of the cases of chlamydial infection diagnosed during the study period. The literature has often drawn attention to differences in rates of chlamydial infection between heterosexual and homosexual men. We did not screen our data for sexual preference; however, the clinic population is overwhelmingly heterosexual.
Of the 474 cases of chlamydial infection detected by DFA, 297 (62.6%) had symptoms of infection. Another 125 chlamydia cases (26.4%) were asymptomatic but had an abnormal urethral Gram's stain, and an additional 22 (4.6%) cases without signs or symptoms were identified as sexual contacts to cases of gonorrhea, chlamydia, cervicitis, or PID. All of the above were treated at their clinic visit for possible chlamydial infection. Thus, the combination of presumptive treatment for C. trachomatis infection of men with gonorrhea, men with abnormal urethral Gram's stains (NGU), and sexual partners of cases of gonorrhea, chlamydia, cervicitis, and PID resulted in same‐day treatment of 93.7% of the chlamydia cases. The remaining 30 cases (6.3%) of chlamydial infection were unsuspected and untreated on the day of the visit. These patients were notified to return to the clinic for treatment. These observations suggest that specific diagnostic screening with Syva MicroTrak DFA for C. trachomatis infection does not greatly increase case finding in this population. The case finding benefits of this screening program may have been minimized owing to the policies already in place in our STD clinic. For example, if clinic policy had been to diagnose and treat NGU only in men with signs and/or symptoms of infection, the use of the DFA test would have identified 110 chlamydia cases (23% of all chlamydia cases) not treated during their visit. There are other potential benefits to a specific diagnosis that are more difficult to measure. A specific diagnosis of C. trachomatis infection may enhance compliance with therapy. Specific diagnosis also allows patients to inform their sexual partners of exposure to chlamydia. Such notification may increase the likelihood of the partners seeking evaluation and treatment.1 Accurate reporting of disease statistics is possible with the use of a specific diagnostic test. This would be of particular importance in areas of the United States with mandatory reporting and where partner notification services are available.
The same policies that allow for same‐day therapy of the majority of patients with chlamydial infection resulted in 4,578 men being treated presumptively for possible chlamydial infection who ultimately were not documented to have C. trachomatis infection. There are several possible reasons why this seemingly unnecessary treatment may be exaggerated. Some patients (particularly known contacts) were incubating chlamydial infection at the time of testing and would require therapy despite a negative test. Also, it is likely that at least some of the suspicious DFA results represent true infections. If all suspicious results were actually true positives, the overall prevalence would have increased to 6.6%. Most importantly, DFA is not the most sensitive diagnostic test for chlamydial infection currently available. In our clinic, DFA had a sensitivity of 73% in asymptomatic women as compared with chlamydia culture as the gold standard(unpublished data). Most authorities would now agree that additional cases (perhaps as many as 30% to 40%) would be identified if DNA‐based testing such as ligase chain reaction or polymerase chain reaction were used.10–13 Infections missed by DFA testing but detected by other means such as nucleic acid amplification may represent infections with a lower organism burden and therefore may be more likely to be asymptomatic. Without direct data, it is impossible to say whether the presumptive treatment protocols would still have allowed for treatment of such an overwhelming majority of chlamydial infections detected by a more sensitive test. Finally, there are benefits to treating men with chlamydia‐negative NGU such as improvement in symptoms. At least some of the cases who were presumptively treated but not diagnosed with chlamydial infection were infected with other agents responsible for NGU. The benefit of therapy to chlamydia‐negative, asymptomatic men with abnormal urethral smears is unknown. We continue to treat men in this category because of the possibility of a false‐ negative DFA test for chlamydia. As more sensitive tests for chlamydial infection become available, this policy may not be warranted.
The relative value of same‐day treatment as part of “syndromal management” is hard to quantify. Potential benefits include improvement of symptoms, improved compliance, and decreased transmission of infection. In contrast, syndromal management may lead to overtreatment with unnecessary exposure of patients to side effects of medications and the potential social stigma of a diagnosis of an STD. Unnecessary antibiotic use may also produce antibiotic resistance. The CDC has recommended that the benefits of syndromal management and same‐day treatment in high‐risk settings such as STD clinics likely outweigh the risks.1 This is particularly true when the diagnostic test may not be 100% sensitive. Our results suggest that with our current protocols as outlined above, syndromal management does effectively ensure same‐day treatment of the overwhelming majority of cases of chlamydia that would be detected by DFA testing.
Forty percent of all of the cases of chlamydia were asymptomatic (no dysuria or discharge by history or physical examination), and 10.9% had a normal urethral Gram's stain. Asymptomatic chlamydial infection in men has been described previously.14–18 In 1984, Stamm reported that 27% of men diagnosed with chlamydial urethritis (diagnosed by culture) were asymptomatic and that 34% had a normal urethral Gram's stain.14 Van Duynhoven et al. reported that 41% of chlamydia cases diagnosed by chlamydia culture were asymptomatic and that 38% did not have urethral discharge. Urethral smear was only performed on those patients with discharge in their study.15 Reitmeijer et al. reported that 40.9% of men with positive chlamydia cultures at the Denver STD Clinic were asymptomatic. However, in that study, 78% of cases of chlamydia were not identified by an abnormal urethral Gram's stain (≥ 4 white blood cells/high‐powered field).16 In our clinic, the rate of asymptomatic infection was very consistent with these previous studies. However, the urethral smear was abnormal in 94% of the patients with positive DFA tests. It is possible that chlamydia culture is significantly more sensitive than the DFA test, leading to the apparent difference in utility of routine urethral smear in identifying men at high risk for chlamydial infection.
The prevalence of chlamydial infection in men attending our clinic was lower than has generally been reported in STD clinics. Previous reports have ranged from 15% to 20%, although more recent studies in some areas have shown lower rates.18 Jaschek et al. screened consecutive asymptomatic and symptomatic men attending two Baltimore STD clinics with urethral culture and found rates of 9.8% and 10.6%, respectively.17 The proportion of cases of NGU attributable to chlamydia was also lower than the expected 30% to 50%.2 Other recent studies have shown this trend as well. A multicenter treatment trial for NGU documented NGU from C. trachomatis ranging from 4% to 35%, depending on geographic location. In our population, chlamydia accounted for 10% of the cases of NGU. Comparing rates of NGU caused by chlamydia can be problematic because of varying definitions of NGU in the literature (e.g., presence or absence of discharge), and this may account for some of the variation between studies. However, our data show that even those patients with symptoms, an abnormal urethral Gram's stain, and a history of sexual contact with a partner who may have chlamydia were diagnosed with C. trachomatis infection only 20% of the time. It has been postulated that the wide use of diagnostic screening for chlamydia in women has led to this change in prevalence in men.12 Another possible explanation that could account for some of the geographic variability in rates of chlamydia causing NGU would be the effect of dual therapy for gonorrhea. The city of Rochester has high case rates for gonorrhea (909/100,000).19 The lower rates of chlamydia may reflect the recommended practice of treating all gonorrhea cases with a regimen effective against chlamydia.
The results of one of the largest reported universal screening programs for chlamydial infection in men are presented and confirm that chlamydial infection is common and often asymptomatic in men attending public STD clinics. Routine screening for chlamydia with a chlamydia DFA test will detect unsuspected cases in men. The number of unsuspected and untreated cases that would be detected by more widespread use of this approach in other clinics would depend on existing clinic protocols for presumptive treatment of chlamydial infection.
1. Centers for Disease Control and Prevention. Recommendations for the prevention and management of Chlamydia trachomatis
infections. MMWR 1993; 42:1-39.
2. Stamm WE, Holmes KK. Chlamydia trachomatis
infections of the adult. In: Holmes KK, Mardh P-A, Sparling PF, Wiesner PJ, eds. Sexually Transmitted Diseases. New York: McGraw-Hill, 1990:181-194.
3. Addiss DG, Vaughn ML, Luka D, Pfister J, Davis JP. Decreased prevalence of Chlamydia trachomatis
infection associated with a selective screening program in family planning clinics in Wisconsin. Sex Transm Dis 1990; 20:28-35.
4. Mertz KJ, Levine WC, Mosure DJ, Berman SM, Dorian KJ. Trends in the prevalence of chlamydial infections: the impact of community-wide testing. Sex Transm Dis 1997; 24:169-175.
5. van Duynhoven YTHP, van de Laar MJW, Fennema JSA, van Doornum GJJ, den Hoek JAR. Development and evaluation of screening strategies for Chlamydia trachomatis
infections in an STD clinic. Genitourin Med 1995; 71:375-381.
6. Marrazzo JM, Celum CL, Hillis SD, Fine D, DeLisle S, Handsfield HH. Performance and cost-effectiveness of selective screening criteria for Chlamydia trachomatis
infection in women: implications for a national chlamydia control strategy. Sex Transm Dis 1997; 24:131-141.
7. Weinstock H, Dean D, Bolan G. Chlamydia trachomatis
infections. Infect Dis Clin North Am 1994; 8:797-819.
8. Centers for Disease Control and Prevention. 1993 Sexually transmitted disease treatment guidelines. MMWR 1993; 42:1-102.
9. Centers for Disease Control. Sexually Transmitted Diseases: Clinical Practice Guidelines. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; 1991:II 3-8.
10. Rumpianesi F, Donati M, Negosanti M, D'Antuono A, LaPlaca M, Cevenini R. Detection of Chlamydia trachomatis
by a ligase chain reaction amplification method. Sex Transm Dis 1996; 23:177-180.
11. Chernesky MA, Lee H, Schachter J, Burczak JD, et al. Diagnosis of Chlamydia trachomatis
urethral infection in symptomatic and asymptomatic men by testing first-void urine in a ligase chain reaction assay. J Infect Dis 1994; 170:1308-1311.
12. Schmid GP, Fontanarosa PB. Evolving strategies for management of the nongonococcal urethritis syndrome. JAMA 1995; 274:577-579.
13. Catry MA, Borrego MJ, Cardoso J, Azevedo, Santo I. Comparison of the Amplicor Chlamydia trachomatis
test and cell culture for the detection of urogenital chlamydial infections. Genitourin Med 1995; 71:247-250.
14. Stamm WE, Koutsky LA, Benedetti JK, Jourden JL. Chlamydia trachomatis
urethral infections in men. Ann Intern Med 1984; 100:47-51.
15. Stamm WE, Cole B. AsymptomaticChlamydia trachomatis
urethritis in men. Sex Transm Dis 1986; 13:163-165.
16. Reitmeijer CA, Judson FN, Van Hensbroek MB, et al. UnsuspectedChlamydia trachomatis
infection in heterosexual men attending a sexually transmitted diseases cinic: Evaluation of risk factors and screening methods. Sex Transm Dis 1990; 18:28-35.
17. Jaschek G, Gaydos CA, Welsh LE, Quinn TC. Direct detection of Chlamydia trachomatis
in urine specimens from symptomatic and asymptomatic men by using a rapid polymerase chain reaction assay. J Clin Microbiol 1993; 31:1209-1212.
18. Stamm WE, Hick CB, Martin DH, et al. Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men: a randomized double-blind study. JAMA 1995; 274:545-579.
19. Centers for Disease Control and Prevention. STD Surveillance Report. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; 1995: 72.