Chlamydia trachomatis has been described as the "silent epidemic" whose incidence in the United States has continued to climb despite the efforts of the decade-long campaign of the Centers for Disease Control and Prevention (CDC) to increase screening and curb disease. In 2007, 1.1 million diagnoses of chlamydia were reported to the CDC, a 7.5% increase from the previous year. Because more than half of all cases go undiagnosed, it is estimated that there were approximately 2.8 million new cases in 2007 (35). It is the most commonly reported communicable infection in the United States. Ninety percent of infected women and 60% of infected men are asymptomatic, and 74% of all reported cases occur among 15-25 yr olds (9,28).
Untreated C. trachomatis is the major cause of pelvic inflammatory disease (PID), ectopic pregnancy, infertility among women, and perinatal transmission of C. trachomatis to infants, causing neonatal conjunctivitis, blindness, and pneumonia. In addition, chlamydial infections enhance transmission of human immunodeficiency virus infection (4). Of women who test positive on C. trachomatis screening, 96% will be cured with a single dose of azithromycin (1 g po) (21). Thirty percent of women with untreated C. trachomatis infection will remain persistently infected (16), 40% will spontaneously cure (31), and 30% will develop acute PID within 6 months of the initial infection (8). Women younger than 20 yr have a reinfection risk of 12%. That is, women who have had C. trachomatis in the past have a relative risk for reinfection approximately twice that of women with first-time acute infection (17).
Because chlamydia is more likely to be asymptomatic in women than in men and because the burden of disease is greater in women than in men, public health efforts have focused on screening women. The Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force (USPSTF) recommend at a minimum, annual screening for all sexually active women younger than 26 yr (7,26). The 2007 USPSTF guidelines conclude "that the current evidence is insufficient to assess the balance of benefits and harms of screening for chlamydial infection for men (7)." The CDC outlined some considerations for screening men in high-risk settings, such as sexually transmitted disease (STD) clinics and jails, and in prevalence regions greater than 2%-4%. However, in the final consensus statement, because of the lack of empiric evidence for a positive impact of screening for chlamydia in men, screening men is considered a secondary focus to prevent infection and sequelae in women (26).
Testing for C. trachomatis infection has become less invasive with the introduction of nucleic acid amplification tests (NAAT). This urine collection method eliminates the need for painful urethral swabs in men and uncomfortable pelvic examinations in women. This is a particularly pertinent point when discussing testing asymptomatic adolescents and young adults.
Culture testing has been the reference standard for all other C. trachomatis testing. However, culturing C. trachomatis poses problems with maintaining viability during transport, standardization methods, technical issues, and expense. Therefore, nonculture screening tests were developed and have been the standard of use, offering more convenient and more reliable methods than culture. The first generation of nonculture tests includes enzyme immunoassays, which detect specific chlamydial antigens (sensitivity = 81%), and direct fluorescent antibody, which use fluorescein-conjugated monoclonal antibodies. The next generation of test was the nucleic acid hybridization tests, which detect C. trachomatis-specific DNA and RNA sequences (sensitivity 90%). The problem with these tests is that they failed to detect a substantial proportion of infections (6,27). The newest generation of tests, NAAT, is substantially more sensitive (6). NAAT amplify nucleic acid sequences that are specific for the organism being detected. Their increased sensitivity is due to their ability to produce a positive signal from as little as a single copy of the target DNA or RNA. The ligase chain reaction (LCR) when performed on first voided urine specimens has a sensitivity that reaches 96.9% and a specificity of 94.1%-99.9% (1,2,22). Although NAAT are used in endocervical and urethral swabs, their use in urine had been a major advantage because testing can be done without a pelvic examination in women or an intraurethral swab in men.
In light of the young age range of chlamydia prevalence and the ease of testing urine, new approaches to screening adolescents have been attempted. Cohen et al. (9) have offered repeated STD screening to high school students in three Louisiana public schools. Nsuami et al. (29) also explored the use of the high school sports physical examination as an avenue of screening. They found that the prevalence of chlamydia was 2.8% among male and 6.5% among female high school athletes. They also noted that 78% of the athletes used the sports physical examination as their annual health assessment. Other studies have shown that 50% of adolescents use the sports preparticipation examination (PPE) as their only interaction with the medical system (15,20).
In this study, we used a mandatory university sports PPE to examine the prevalence of C. trachomatis in college athletes, taking into account sexual practices, demographics, and symptoms, and to treat those athletes with positive chlamydia urine screening tests. We also determined the student athletes' access to health care and C. trachomatis screening. Metzl (25) addressed the usefulness of the PPE in his article, "The adolescent preparticipation physical examination. Is it helpful?" In it, he quotes a study that found only 1.9% of examined high school athletes were disqualified from competition: a low incidence of disqualification and possibly an unfavorable cost-benefit analysis (36). However, Metzl argues that although there is a low disqualification rate, that same study found 11.9% of the athletes screened required further follow-up. Metzl makes the point that the PPE is not only meant to identify medical and orthopedic conditions that would make sports participation unsafe, it is also meant to screen for underlying illness and facilitate preventive measures.
In Fresno County, CA, 1500 cases of C. trachomatis were reported in 1997. In 2001, the time of this study, 3500 cases were reported, and in 2007 that number increased to 5300 (5,13). In 1999, the STD Control Branch of the California Department of Health Services launched a campaign, "Get Tested," for chlamydia screening in adolescents and young adults in diverse settings. The Fresno County Health Department agreed to collaborate with the study coordinators for education and laboratory testing using the urine LCR method. The Fresno Madera Medical Society, through its Community Health and Relations Committee, offered physician assistance. The California Endowment provided a grant for the study and test completion. The university athletic department allowed use of the sports physical examination as an opportunity to educate and to screen student athletes for C. trachomatis.
Because student athletes are required to attend annual preparticipation sports physical examinations, we used a university setting in Fresno, CA, to capture student athletes (age 18-23 yr) and to educate and screen for C. trachomatis as part of this examination. A total of 439 student athletes participated, 220 men and 219 women.
Approval from the university institutional review board as well as the Saint Agnes Medical Center, Fresno, CA, institutional review board was obtained. Education and screening for C. trachomatis was provided to all athletes. A questionnaire regarding demographic, behavioral, and symptom data was completed by each athlete. Those students with positive tests for chlamydia were treated with single dose azithromycin and encouraged to bring their partners in for screening and treatment. No positively screened students had a history of macrolide allergy.
Students congregated on the assigned days as defined by their sports team. All team sports examinations were completed within a 1-month period. Before the sports examination, the students were given information regarding the chlamydia screening and a consent form. The students received a brief didactic chlamydia education session orchestrated by the primary investigator and the county health department followed by a question and answer period. The students then dispersed to their assigned rotation of examination stations. An additional station was added to the usual sports examination rotation where the student completed a numbered confidential questionnaire. The student was then given a matching numbered specimen container for a first void urine. A physician was available at the station for any questions. The urine specimens were sent to the county public health laboratory for chlamydia testing.
We collected demographic and behavioral data via a questionnaire. Questions included ethnicity, age, sexual activity, STD contact, STD-related symptoms, abdominal pain, contraceptive use, and STD history. Students reported their prior access to the health care system by frequency and location type as well as their use of the sports physical examination as their general medical care. Students also reported if they had ever been offered or ever received a chlamydia screening test.
A station was established at the PPE where the students were instructed on supplying 15-20 mL of a first-catch voided urine specimen. The urine was collected at the PPE site then transported the same day on ice to the Fresno County laboratory. Urine specimens were tested via the Abbott LCX Probe System (North Chicago, IL).
We conducted descriptive statistics and chlamydia prevalence on the basis of positive LCX results from the participating student athletes and by demographics and behavioral variables for all student athletes. Odds ratios and 95% confidence intervals to test for differences in demographic and sexual behavior variables were calculated. Descriptive statistics involving student access and use of the health care system were measured against the availability of chlamydia screening to the students.
Of the 439 student athletes tested, 13 urine LCR tests were positive for C. trachomatis. One positive test in a student who questioned the result because she had not been sexually active was repeated and was negative. C. trachomatis test positivity in the student athlete population was 2.7% overall, 3.2% in men and 2.2% in women (see Table 1).
When only the sexually active athletes were assessed, test positivity rose to 3.8% overall, 4.0% in men and 3.7% in women (see Table 2).
African American student athletes had a higher prevalence of 9.1% overall, 8.9% in men and 9.5% in women. African Americans were six times more likely to have C. trachomatis than Caucasians (odds ratio = 6.43, 95% confidence interval = 1.58-30.55; see Table 3). In the Latino and Asian student athlete population, there were no positive test results (see Table 4).
Number of partners in the past 12 months, contraceptive type, symptoms, and prior history of chlamydia infection did not show a statistical significance between those with disease and those without.
Within the past 12 months, 76.8% of all student athletes (65.5% men and 88% women) and 75% of positively tested athletes (71% men and 80% women) accessed health care.
Of the sexually active students, only 17% were ever offered chlamydia testing, 6.8% men and 31% women. Of the 12 athletes who tested positive for chlamydia, only 1 woman was ever tested. A total of 4 athletes, 3 men and 1 woman, had been offered the test (see Table 5).
When asked where usual medical care was received, many students gave more than one answer. The vast majority of students see their private physicians, 75% of all athletes (62% men and 89% women). Of the athletes who tested positive, 83% see their private physician, 71% men and 100% women.
Chlamydia infection in young adults is prevalent and increasing. The CDC and the USPSTF guidelines recommending annual chlamydia screening for all sexually active women younger than 26 yr are not being met in the community. Responses to the questionnaire demonstrate that all our students had multiple prior interactions with health care, yet only 31% of sexually active women and 7% of sexually active men were ever offered chlamydial screening. Our findings of inadequate screening are supported by the preventive health service study of seven Health Maintenance Organizations in Massachusetts (38). Of the 15- to 19-yr-old women, only 18% received a Pap smear and only 11% received an STD test during the course of a year. Fifty-three percent of those women were sexually active. Health care providers who evaluate this age population for any health-related visit should take every opportunity to offer these patients chlamydial screening. With the prevalence rate eight times higher in African Americans than in Caucasians nationally (26) and six times higher in our study, it is especially important to take advantage of opportunities to screen this population. The benefits of screening for chlamydia have resulted in a significant decline in disease sequelae. Scholes et al. (34) presented data to suggest that chlamydia screening and treatment can reduce the incidence of PID by over 50%.
Although it is difficult to prove that chlamydial infection in men bares a direct relationship to morbidity in women, we know that male infection is directly related to chlamydial transmission to sex partners. Studies have shown that many young women diagnosed with chlamydia become reinfected by male partners who were not treated (33,39). The CDC's 2006 STD treatment guidelines recommend that when an index case of chlamydia is discovered, the partners should also be treated, even if it is necessary for the physician to give the antibiotic to their patient to give to their partner, i.e., expedited partner therapy (6). We found that in our population, the incidence of chlamydial infection in men was similar to that of women, which suggests that treatment of both sexes is needed to decrease disease prevalence.
In 2002, the CDC recommended that NAAT be used to screen for chlamydial infection in men and women (18). In 2005, after performing a systematic review, Cook et al. (11) concluded that urine-based NAAT screening had comparable sensitivity and specificity to cervical and urethral specimens. Although the NAAT is the most effective screening approach, it is relatively expensive, and Ginocchio et al. (14a) concluded that at a prevalence of chlamydial infection of 5% among asymptomatic men, prescreening urine with the leukocyte esterase test followed by confirmatory testing with the urine-based LCR was the most cost-effective strategy. However, after review of all the data, the CDC's 2006 conclusions do not recommend leukocyte esterase test screening but recommend urine-based NAAT as the screening test of choice for men and women.
Dicker et al. (14) found that in STD and family planning clinics in 16 states where chlamydia prevalence ranged from 3.4% to 5.5%, the percentage of positive repeat tests was the same as or higher than the prevalence of C. trachomatis disease, concluding that test positivity can be used as an indicator of chlamydia prevalence in screened women at family planning and STD clinics. The authors did not delineate the testing methods used.
At the time of this testing, California averaged 325.6 cases of chlamydia per 100,000 people (3). In Fresno County, where this study took place, the rate was 512.9 cases per 1,000,000 (12). Using test positivity as a marker for disease prevalence, we found that the chlamydia prevalence rate of 4% in sexually active student athletes mirrored the incidence in the overall community in this age population, supporting the idea that testing student athletes during the preparticipation sports physical is a useful tool.
Looking at the chlamydia results in relation to the cardiac examination in preparticipation sports physicals, it is estimated that 200,000 adolescents (even higher in college athletes who have been screened multiple times in high school) would need to be screened to detect 1000 athletes at risk for a significant cardiac event and one athlete who would actually die (24). Our study estimates that 27,000 sexually active women athletes would need to be screened to detect 1000 athletes with chlamydial trachomatis infection. At a 30% probability of developing PID (33), that would be 300 women who would eventually contract PID. Twenty-five thousand sexually active male athletes would need to be screened to detect 1000 cases of chlamydia. Our study revealed an average of 3.5 partners per positively tested male athlete. At a 60% transmission rate (30), that would be 2100 additional women with chlamydia and 630 additional cases of PID that could be prevented.
Chlamydial screening with a simple, noninvasive urine test has the potential to reduce years of significant morbidity such as PID, infertility, ectopic pregnancies, and chronic pelvic pain in at least 4% of the captured female population screened by the preparticipation sports physical. In addition, it has the potential to prevent transmission of chlamydia from 4% of the male athletes to women beyond the sports physical. Chlamydial screening has one of the highest benefit to effort ratio of any of the medical problems screened for during the sports examination. With the U.S. national incidence of chlamydia climbing nearly 7% each year and approximately 2.8 million new cases each year and 74% of all reported cases occurring in the 15- to 25-yr age group, how can we ignore screening for chlamydia in the PPE (7,18,22)?
Regarding cost-effectiveness, we refer to the computer-based mathematical model of Hu et al. (17). Their model simulates screening, diagnosis, and treatment of chlamydial trachomatis infection in a representative cohort of sexually active American women. They selected model variables and their plausible ranges to estimate direct medical costs and time costs of testing for and treatment of C. trachomatis.
They estimated screening costs to include urine NAAT ($13, range = $4-$40) and 1 g azithromycin ($10). We did not include a clinic visit because the screening is part of the PPE, and the follow-up is with salaried trainers.
Table 6 itemizes the expense incurred by symptomatic C. trachomatis infection. This does not include the additional costs associated with transmitting C. trachomatis to neonates.
With this information, we calculate from our study that testing 310 sexually active student athletes at $13 a test plus retesting 13 positives and treating 12 individuals and their current partners with $10 of azithromycin costs $4439.
Contrast this with the future cost of untreated C. trachomatis infection. We found five C. trachomatis-positive female athletes. According to the probabilities that 30% of untreated women develop PID (33), at least one of these women will suffer from PID. The seven men had a total of 25 partners in the past year. With a 60% transmission rate from men to their partners (30), 15 more women were infected with C. trachomatis, resulting in 4.5 more cases of PID. A conservative estimate would be if we could prevent just two cases of inpatient PID 2($4715 + $1084), three cases of outpatient PID 3($490 + $513), one case of chronic pelvic pain ($1146 + $684), one case of ectopic pregnancy ($4355 + $1445), and one case of tubal infertility ($5000 + $321), we would save $27,558, nearly seven times the cost of the initial screening.
Of our 13 positively tested students, 1 woman contested her result. On repeat testing, with a second urine specimen, her LCR was negative. Zenilman et al. (40) address LCR testing in screenings of low prevalence populations. Because test specificity is not 100%, they believe that confirmatory algorithms are necessary to deal with the decreased positive predictive value (PPV). They calculate that with a prevalence rate of 3.0% and with the specificity of a single LCR test of 99.0%-99.6%, the expected PPV for a single LCR chlamydia test would be 73%-87%. They recommend confirmation testing of positive results with a different, highly specific and sensitive test. For example, if testing with LCR, one could confirm with a polymerase chain reaction repeat assay. Kohl et al. (19) also raise the issue of the possible need for confirmation testing when using NAAT if the prevalence of disease is less than 2%. They calculate that if the NAAT sensitivity is 85%, specificity 99%, and disease prevalence 2%, the PPV would be 63%.
Rather than blanket screening, as we did, more directed screening of the sexually active individuals followed by confirmatory testing would improve the PPV of the test. We did not find that further directed screening on the basis of sexual habits or symptoms would add any further benefit.
We recommend taking every opportunity, where the population of sexually active men and women below the age of 26 yr encounters the health care system, including sport screening examinations, to offer chlamydial screening. Because there have been no trials examining the effects of more than one screening round and no trials examining the harms of chlamydia screening (23), we foresee the use of the college preparticipation sports screening as a mechanism to educate this population, to detect and treat significant, prevalent disease, and lastly to provide the opportunity to rescreen individuals over 4 yr, allowing for the evaluation of education, treatment, benefits, and harm.
We believe that screening athletes for C. trachomatis during the PPE is in alignment with the goals of the American Academy of Family Physicians, the American Academy of Pediatrics, the American College of Sports Medicine, the American Medical Society for Sports Medicine, the American Orthopaedic Society for Sports Medicine, and the American Osteopathic Academy of Sports Medicine. In their consensus PPE monograph, they state that "The overall goal in performing a preparticipation examination (PPE) is to promote the health and safety of the athlete in training and competition. The PPE is a tool to screen athletes for injuries, illness, or factors that might put them or others at risk (32)." They state that two of the primary objectives of the PPE are to screen for conditions that may be life threatening or disabling and to screen for conditions that may predispose to injury or illness. They also state that for a screening tool to be effective, it must identify diseases that will affect the athlete, be sensitive and accurate, and be practical. We believe that C. trachomatis screening meets all these requirements.
This project was supported in part by the California Endowment, the Fresno Madera Medical Society Community Health and Relations Committee, the STD branch of the Fresno County Office of Public Health, and the Fresno STDC branch of the California Centers for Disease Control and Prevention.
Results of the present study do not constitute endorsement by the American College of Sports Medicine.
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