Sutton, Thomas L. MD*; Martinko, Thomas MD*; Hale, Steven PA†; Fairchok, Mary P. MD*
CHLAMYDIA TRACHOMATIS IS the most prevalent bacterial sexually transmitted disease (STD) and the second most commonly reported infection within the United States. 1 Symptoms of chlamydia infection can be absent or nonspecific, making disease identification without screening difficult. Females can experience vaginal discharge or dysuria. In males, penile discharge, dysuria, and pain and swelling of the testes are the most common symptoms. Because most infections in women are asymptomatic, chlamydia is known as a “silent disease.”2 This “silent” reservoir of infection has most likely resulted in significant underreporting of chlamydia incidence rates. Less well known is the percentage of male infections that are symptomatic.
Identifying the prevalence of chlamydia infection in different populations is important to define parameters for routine screening and prevention. Currently, annual screening for chlamydia infection is recommended for all sexually active females under 20 years of age, and for women aged 20 and older with one or more risk factors for chlamydia, 3 but there are not similar recommendations for routine male screening. Definitive risk factors for chlamydia infection that might support routine male screening have not been established. Before the advent of urine-based nucleic acid amplification assays, most of the chlamydia prevalence and risk factor analysis studies were concentrated on females. Ligase chain reaction (LCR), which is performed on first-void urine, has allowed for a sensitive, specific, and less invasive way to screen for chlamydia infection. 4
After the availability of urine-based screening, research in chlamydia infections among males has proliferated. Reported chlamydia prevalence rates in males within the United States range from 2.1% to 11.3%. 5,6 However, the majority of these studies involved high-risk adolescent males. To date, there has been no study investigating the prevalence of chlamydia infection in a population of healthy male Reserved Officer Training Corps (ROTC) college students.
The primary purpose of our study was to define the prevalence of chlamydia infection among healthy ROTC male college students. We also wanted to determine the percentage of asymptomatic chlamydia infection in males and delineate risk factors for infection that could identify male ROTC college students who would benefit most from routine screening.
Male army ROTC cadets aged 18 to 32 from all regions of the United States attending ROTC Advance Camp Training at Fort Lewis, Washington, from June to July 2001 were invited to enroll in the study during the first day of camp. The only location in the United States for cadets to complete Advance Camp is Fort Lewis, and Advance Camp is required training for all cadets. The study was approved by the Madigan Army Medical Center Clinical Investigation Review Board. Each participant provided written informed consent. Of the recruits approached, 1443 volunteered to participate. Based on a maximum of 1990 male cadets available for enrollment, this represented a minimum of 72.5% participation in the study. Cadets who had never had sexual intercourse or had used antimicrobials effective against chlamydia within the prior 4 weeks were excluded from enrollment. Before enrollment, a civilian health educator gave the cadets a briefing on the study and information sheet on C. trachomatis infection written by the Centers for Disease Control and Prevention (CDC). 2 Participants completed a questionnaire on demographics, sexual history, previously diagnosed STDs, partner with previous or active STD, condom use, and symptoms. All STDs were listed by name on the questionnaire. Participants identified themselves by race or ethnicity (recorded as white, black, Hispanic, Asian/Pacific Islander, or other). The frequency of condom use was recorded as always, never, or sometimes. Symptoms elicited were penile discharge or burning on urination. Because the participants were military cadets, we did not include any questions concerning sexual orientation. Confidentiality was maintained by coding the questionnaires.
Participants provided a 20-mL first-void urine specimen. The specimens were promptly placed on ice, and within a few hours were frozen at -80°C until testing. Analysis of specimens by DNA amplification through LCR (Abbott Laboratories, Abbott Park, IL) according to the manufacturer's instructions was performed by the Washington State Department of Health in Shoreline, Washington. If the LCR for chlamydia was confirmed positive, participants were contacted to arrange treatment, further STD evaluation, and contact-tracing interviews. Symptoms were sought during the interview, including dysuria, “tingling” or “burning” with urination, abdominal pain, fever, and penile discharge. All infected participants were treated orally with 1 g Azithromycin.
We calculated the prevalence of infection and the rate of symptomatic infection with C. trachomatis with 95% confidence intervals (CIs). Analyses of categorical variables were performed by chi-square. These associations were summarized with odds ratios (ORs) and 95% confidence intervals. Analyses of continuous variables were assessed using the independent, 2-sample t test. Participants with missing data for risk factor variables were excluded from the analysis for that variable. P <0.05 was considered to be statistically significant. Adjusted odds ratios for various risk factors associated with chlamydial infection were estimated using multivariate logistic regression analysis. All risk factors statistically significant with univariate analysis were included in the model.
From June 12 to July 26, 2001, 1443 college ROTC cadet males consented to participate in the study and completed questionnaires. One hundred ninety-one cadets were dropped from the study because they did not provide urine samples. This was the result of initial logistical difficulties in obtaining the urine samples. When the study was readjusted to allow for urine collection immediately after enrollment, we had 100% compliance with obtaining the samples. A total of 1252 urine samples were collected and analyzed by LCR for the presence of C. trachomatis. Questionnaires correlating to each sample were available to assess for demographic information and independent risk factors predisposing to chlamydial infection.
The mean age of the participants was 23 years of age (standard deviation ± 2.34 years). The racial and ethnic distribution among the 1223 participants with available information was 70.4% white, 13.9% black, 7.4% Hispanic, 6.3% Asian and Pacific Islander, and 2.0% other. Geographic distribution was determined based on the CDC classification of the state of origin. The geographic distribution was uneven, with the majority of participants being from the southern United States (41.4%) and the remainder, including west (16.5%), midwest (17.6%), northeast (22.3%), Pacific Islands (2.1%), and 0.1% uncategorized.
Prevalence of Chlamydia Infection
The overall prevalence of infection was 31 of 1252 (2.48%; 95% CI, 1.6–3.3%). Our sample sizes for each year of age in the study were not large enough to provide statistically valid prevalence rates for each year. Dividing into age groups with large enough sample sizes to achieve narrow confidence intervals revealed the following age-related prevalences: 18 to 20 (4 of 162, 2.5%; 95% CI, 0.1–4.9%), 21 (9 of 505, 1.8%; 95% CI, 0.6–3.0%), 22 to 24 (13 of 384, 3.4%; 95% CI, 1.6–5.2%) and 25+ (5 of 185, 2.7%; 95% CI, 0.4–5.0%). There were no statistically significant age group-related differences in prevalence.
Only 2 of 31 participants with chlamydia reported symptoms by questionnaire or personal interview. This corresponds to an asymptomatic infection rate of 93.6%(95% CI, 84.9–100%). One infected cadet reported burning on urination; the other reported a penile discharge. We found that self-reported symptoms were not specific for chlamydia infection. Only 1 of 8 of participants (12.5%) who reported burning on urination, and 1 of 9 (11%) with penile discharge, were infected with chlamydia.
Table 1 summarizes the relationship using univariate analysis between chlamydia infection and demographic and behavioral characteristics. We identified 3 risk factors for infection: black identity, identification of a partner with a history of an STD, and self-reported symptoms. Prevalence of infection among blacks was 5.9% (95% CI, 3.18–10.2%). This was the only racial or ethnic group identified in this study as being at higher risk for infection. The prevalence rate in the Hispanic population was higher than that in the white group (4.4% vs. 1.6%), but this did not meet statistical significance.
We did not identify any other significant risk factors.
After entering the 3 significant variables into the multiple logistic regression model, all 3 variables continued to be significant: black (P = 0.03; OR, 2.8; 95% CI, 1.3–6); partner with history of an STD (P = 0.04; OR, 3.8; 95% CI, 1.2–11.7); and reported symptoms (P = 0.009; OR, 8.2; 95% CI, .89–76).
We found a prevalence rate of chlamydia infection of 2.48% (95% CI, 1.6–3.3%) in the ROTC cadets. This is a lower prevalence rate than previously reported in most other studies involving United States males, which have noted prevalence rates ranging from 2.1% to 11.3%. 5,6 However, our population differs in several respects from most of the other studies, including patient age, racial diversity, and college education. Additionally, we did not recruit subjects from a high-risk setting such as an STD clinic.
Although prevalence of male chlamydia infection has been shown to peak at 20 to 24 years of age, 7–9 we were unable to identify an age group in our population at highest risk for the infection. Likewise, the prevalence in our population did not reveal differences from region to region within the United States, although participants from the southeast did have the highest prevalence rate.
We found that 93.6% of the infected males in our study did not report any symptoms by questionnaire or personal interview. Interestingly, another large study investigating chlamydia infection in nonhealthcare-seeking male Army recruits found a similar rate of silent infection (86%). 8 Our rate of 93.6% silent infection in males is higher than the rate of approximately 50% cited by the CDC 2 as well as by a prevalence survey of males attending a genitourinary clinic. 10 Asymptomatic chlamydia infection in males could have been underestimated before the availability of noninvasive testing; data are accumulating that males could be asymptomatic as frequently as females. 8,11,12 Thus, the incidence of chlamydia infection in the United States could be higher than the CDC's approximation of 3 million infections per year, which was derived from the lower estimations of asymptomatic male disease. It has also been postulated that infected males would seek treatment for chlamydia more often than females as a result of increased symptoms. 13 However, according to our data, there might not be a significant difference between the proportion of men versus women with symptoms. This finding implies that routine screening of asymptomatic males for chlamydia infection could be an important preventive health measure.
We identified 3 characteristics associated with an increased risk of chlamydia infection. Racial/ethnic identification was a major risk factor in our population. In our study, blacks were 3 times more likely than whites to have chlamydia. This association has also been recognized previously. 7,8,14 The reason for this difference is uncertain. Another risk factor identified by both our study and another study 15 was having a sexual partner with a history of having a previous STD. A possible reason for this association is that a known complication of an STD is the increased likelihood of developing other STDs. Reinfection with the same or a different organism is common in females. Blythe reported that 38% of teenaged females had recurrent chlamydia infection within 9 months after treatment, 16 and Orr found that 17% to 26% of adolescent females were reinfected within 6 months after treatment. 17 A third predictor for infection in our study was self-reporting of related symptoms. However, the majority of infected subjects did not have any symptoms.
Several questions in our study were not significant predictors for infection. The mean number of sexual partners within the past 2 or 12 months revealed no differences between the infected and uninfected subjects. Interestingly, of the 31 participants with chlamydia, 4 reported celibacy for the past 2 months and 3 claimed celibacy for the past 12 months. Nine others reported monogamous relationships for the past 12 months. Using either number of partners or monogamy as a basis for screening would be ineffective according to our results. Marrazzo reported a similar finding in her population of adult males. 18 Unlike a previous study, 8 we did not find that having a new sexual partner in the past 2 months to be a risk factor. Like in previous studies, 12,14,15,18 we did not find lack of condom use to be a risk factor in our study. We did not have enough data to assess whether exposure to an individual with an active STD was a risk factor for chlamydia infection.
Our study had several limitations. We had some incompletely answered questionnaires. Although the majority of subjects answered all of the questions, lack of data from some subjects resulted in different denominators for some risk factors. We were unable to collect data on cadets who declined to participate in the study to determine why they refused. This could have skewed our prevalence rates. Our population consisted of ROTC college cadets, thus our findings might not be applicable to the broader population of male college students. Finally, because we studied military cadets, we were unable to ask about the sexual preferences of the population.
The high rate of asymptomatic infection in our sample suggests that a screening program for asymptomatic male infection in a low-risk population such as ROTC cadets might help overcome the silent reservoir of chlamydia disease. Periodic rescreening and aggressive contact tracing of females infected with STDs could also be useful in detecting infected males based on our risk factor analysis. Potential factors that can identify a higher-risk population for screening of asymptomatic ROTC cadets include racial background, a history of a partner with a previous STD, and self-reported symptoms of burning on urination or penile discharge. Further studies are needed to determine the cost-effectiveness of routine screening of asymptomatic males for chlamydia infection.
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