More than 3 to 4 million Chlamydia trachomatis urogenital infections occur in the United States every year 1,2 among young sexually active persons from all socioeconomic groups. 3,4 Although highly prevalent in both sexes, women are disproportionately affected. C trachomatis is a major underlying cause of pelvic inflammatory disease, ectopic pregnancy, and infertility. 1,5 Healthcare costs from these sequelae pose a large economic burden on society. 6,7 Programs to screen and treat women for chlamydia infections are cost effective. 8,9 Because infections are mostly asymptomatic in females, routine screening of young sexually active women, who may not be attending sexually transmitted disease (STD) or family planning clinics, has been recommended. 1,10 In the past, screening for C trachomatis infections in females has been limited by access to a medical clinic and by the need for a pelvic examination. However, C trachomatis infections can now be detected with high sensitivity and specificity using nucleic acid amplification assays on urine specimens. 11–17 Use of easily obtainable and noninvasive specimens is efficient and even cost effective for screening large numbers of asymptomatic women. 18
Previously, we reported that screening 13,204 Army female recruits for C trachomatis infections using nucleic acid amplification testing of urine at Fort Jackson, SC, yielded a prevalence of infection of 9.2%. 19 Despite this high prevalence, no policy change to begin chlamydia screening in the Army for new recruits has resulted. A follow-up study of 7,053 of these women who remained on active duty indicated a possible reduction in morbidity associated with screening and treatment of those infected. 20 Our objectives in this study were to assess whether prevalence and risk factors for chlamydia infection in US Army female recruits changed over time and to examine variables that may have contributed to any observed differences. We have now completed a 42-month prevalence study of 23,010 female Army recruits and report here on increasing trends in chlamydial prevalence in the yearly cohorts, changing risk factors, and geographic variability in prevalence of infection. Because these women were screened within 3 days of joining the Army, monitoring of the sample should be representative of women at risk for chlamydia acquisition in the source (home) states and should reflect, to some extent, the impact of chlamydia control in the source states. These analyses should assist military and civilian policy makers in assessing nationwide trends of C trachomatis infection in young females, in choosing epidemiologic correlates that would be useful for screening, and in developing or further refining chlamydia control programs.
Between January 1996 and June 1999, all female Army recruits who were present on Sundays at the Physical Examination Section, Reception Battalion, Fort Jackson, SC, were invited to participate in a study to assess the prevalence of, and risk factors for, C trachomatis infections. The study was approved by the Institutional Review Boards of The Johns Hopkins University, The US Army Medical Research and Materiel Command, Fort Detrick, MD, and Fort Jackson (supported by the Eisenhower Army Medical Center, Fort Gordon, GA). Those female recruits who were just entering basic training and undergoing basic training in-processing (approximately the first 3 days at Fort Jackson) were eligible. There were no exclusion criteria. A total of 23,010 women volunteered (approximately 80% of more than 29,000 that were offered screening). The women were given a study and educational briefing about chlamydia infections by a civilian research nurse or health educator. Annually, approximately 50% to 70% of all women entering the Army underwent recruit training at Fort Jackson during the study period (personal communication, Timothy Powers, Preventive Medicine, Walter Reed Army Institute of Research and Dr. John Brundage, US Army Center for Health Promotion and Preventive Medicine).
Each subject signed a consent form and completed a survey questionnaire requesting demographic information, sexual risk history, and the presence or absence of any genital symptoms, as explained by the nurse to be consistent with sexually transmitted infections. The survey also included questions about whether the woman ever had vaginal sex or a prior history of chlamydia, gonorrhea, syphilis, or trichomonas infection. Questions about a prior history of a STD were later combined into one variable (history of any of these infections) for the multivariate model. The home-of-record state was also recorded. The data instrument was a one page, two-sided scannable form (Scantron Corporation, Tustin, CA).
Each volunteer was instructed to collect 20 ml of first-voided urine. All urine specimens, consent forms, and questionnaires were shipped to The Johns Hopkins University International Chlamydia Laboratory. Urine specimens were kept at 4°C at Fort Jackson during shipping and in the laboratory until processing within 48 to 72 hours per the manufacturer's instructions.
Laboratory Procedures and Treatment
Urine specimens were processed upon receipt in the laboratory and tested by ligase chain reaction (Abbott Laboratories, Abbott Park, IL) for chlamydia DNA according to the manufacturer's directions. 19 Each week, a list of the infected individuals was sent to the research nurse. The infected women were promptly contacted, treated using directly observed therapy with a single 1 g dose of azithromycin, and received a comprehensive evaluation for other STDs, including a pelvic examination. Infected women were also referred to the Preventive Medicine Clinic for counseling and encouragement to notify their sexual partners. No active partner notification was possible. The women had to have contracted chlamydia in their home state before coming to Fort Jackson because they were tested within 3 days of their arrival and new recruits are cohorted by sex upon arrival.
Questionnaire forms were scanned into a database (d-base III plus, AshtonTate, Borland International, Spring Valley, CA). Ligase chain reaction results, demographics, and risk-factor information were analyzed as dichotomous variables using the chi-square test. Prevalence for each year of the study was assessed as a separate variable to determine trend (chi-square for trend). Univariate and multivariate logistic regression analyses for factors associated with chlamydia infection were performed (Intercooled Stata 4.0, Stata Corporation, College Station, TX). All independent variables that were significant at P < 0.05 in univariate analyses were included in multivariate analyses, and variables that remained significant at the P < 0.05 level were included in the final models. Interactions among independent variables were considered in the analysis. Three progressively simplistic models (models I, II, and III) were used to analyze the variables possibly associated with influencing C trachomatis infection and to determine whether changes in prevalence might be attributed to one or more factors. Successive models were simplified in an effort to identify readily measurable and practical variables predictive of C trachomatis infection that could be used in future screening and treatment programs.
To assess the representativeness of the volunteers to the recruit population as a whole, individuals available who did not volunteer for the study were offered the opportunity to complete the demographic and sexual risk behavior questionnaire anonymously. The responses of these individuals were compared with those of the volunteers. P < 0.05 was considered significant.
Patient Characteristics, Prevalence, and Risk Factors
Of 23,010 volunteers, 85.8% were 25 years of age or younger; median age was 20.6 (range 17–39) years. Half of the women were white, 35.2% were black, 13.7% were other races, and 1.1% did not report race (Table 1). The prevalence for C trachomatis for the entire population was 9.5% (2,189/23,010). The prevalence was 16.0% in blacks, 5.4% in whites, and 7.9% in those reporting other races (P = 0.000). Prevalence was 10.4% for those 25 years or younger(variable termed “young age”) and 4.1% for women older than 25 years of age (P = 0.000).
By questionnaire, 91.1% reported ever having had vaginal sex, 25.7% had more than one sex partner in the 90 days before being studied, 29.1% had a new sex partner in the previous 90 days, and only 16.4% always used condoms in the previous 90 days. A prior history of chlamydia infection was reported in 8.3% (Table 1). A total of 56 women were chlamydia positive (2.6% of the positives) who answered no to “ever had vaginal sex?” Thus, those reporting “no” to vaginal sex were not removed from the denominator in estimates of prevalence, and vaginal sex was not used in the models as a covariate.
Six hundred ten recruits who did not volunteer for the urine screening completed the demographic and sexual risk behavior questionnaire anonymously. Very few of these nonvolunteers supplied data on age; 49.2% were white and 33.4% were black, which was not significantly different from the volunteers. Only 69.5% reported having vaginal sex compared with 91.5% of the volunteers (P < 0.001). Three other variables were significantly different in volunteers, even after controlling for vaginal sex: only 3.0% reported prior chlamydia infections (P < 0.001), only 17.9% had a new sex partner (P = 0.001), and 21.5% consistently used condoms (P < 0.001). Volunteers were not significantly more likely than nonvolunteers to have more than one partner in the prior 90 days or previous diagnoses of gonorrhea, trichomonas, and syphilis after controlling for vaginal sex.
Trends and Risk Factors Associated with Chlamydia Infection
The prevalence of C trachomatis infections for each of the four years of observation were 1996, 8.5% (441/5185); 1997, 9.7% (779/8046); 1998, 9.9% (510/5159); and 1999, 9.9% 459/4628, P = 0.018, using 1996 as referent) (Table 2). The proportions of whites screened over the study period did not differ significantly and varied from a high of 52.3% for year 1 to a low of 48.6% for year 4 (Table 2). The proportions of blacks did not change significantly, varying from a low of 33.8% to a high of 36.7%. However, the mean age was significantly different, varying from 21.0 years of age (SD ±3.6 years) in year 1, 20.4 years (SD ± 3.6 years) in year 2, 20.6 years (SD ± 3.7 years) in year 3, to 20.3 years (SD ± 3.7 years) in year 4 (P = 0.000). Furthermore, the proportion of individuals 25 years old or younger was different between years of the study (P = 0.000) (Table 2).
Using the recruits’ stated homes-of-record, individuals were assigned a geographic variable according to one of the Centers for Disease Control and Prevention reporting regions: West, Midwest, Northeast, South, or Territories. Overall prevalence of chlamydia infection for these regions varied significantly: West, 5.8%; Midwest, 7.3%; Northeast, 7.5%; Territories, 9.5%; and South, 12.3% (Figure 1). The proportion of all individuals screened who came from each region did not vary significantly over time (Table 2). No one geographic region contributed substantially to a changing prevalence, nor did the overall trend mimic the prevalence pattern for any one region (Table 2).
The prevalence of high-risk sexual behavior (e.g., condom use and more than 1 or a new sexual partner, all within the previous 90 days) reported by questionnaire did not increase but generally decreased over successive years of the study. Women having more than one sex partner ranged from a high of 27.3% for year 2 to a low of 24.0% for year 4 (P = 0.00); those with a new sex partner ranged from a high of 32.5% in year 2 to a low of 26.9% in year 4 (P = 0.00), and condom use ranged from 15.3% for year 1 to 16.5% for year 3 (P = 0.244), (Figure 2). Although, overall, more than 91% reported vaginal sex, fewer reported vaginal sex in years 1997 to 1999 (92–82%) than in 1996 (94%) (P = 0.010, 0.001, 0.000, respectively, versus 1996), (Figure 3). The proportion reporting the presence of any genital symptoms and history of any STD did not change significantly over time (Figure 3).
Multivariate Logistic Regression Models
Model I contained region of home-of-record in addition to all variables found to be significant in univariate analysis, and included the variables age 25 years or younger, race, year of the study, more than one or a new sex partner in the 90 days preceding being studied, condom use, and history of any STD (Table 3). Black race (odds ratio [OR] 2.9, 95% CI 2.6, 3.2) and young age (OR 2.7, 95% CI 2.3, 3.2) were the strongest predictors of increased risk for chlamydia infection (Table 3). Using the South as the referent, homes-of-record in the West, Midwest, Northeast, and Northeast were significantly protective. When analyzing the model by year of the study, being screened in years 3 or 4 of the study and having a new or more than one sex partner in the last 90 days were associated with chlamydia infection (Table 3). Reported condom use was protective (Table 3).
Model II (region, young age, and year of study) (Table 4) contained the variables with the highest predictive values as determined by ORs and those which represented easily measurable and significant variables that could be used in directing future screening programs: southern region and young age (≤25 years). Year of the study was kept in the model to assess the impact of time. Race was removed from the model as not representing a valid screening characteristic. Being screened in years 2, 3, and 4 was significantly associated with chlamydia infection. Being from the South or age 25 years or younger remained independent predictors of chlamydia infection (Table 4).
Model III removed the variable year of the study. Both being from the South and being of young age remained significantly associated with risk of chlamydia infection: OR 1.9 (95% CI 1.8, 2.1) and 2.8 (95% CI 2.4, 3.4), respectively.
We conducted a C trachomatis screening program over 4 consecutive years in young female military recruits from across the United States and its territories using nucleic acid amplification assays on urine samples. Our survey confirmed earlier observations that, with a prevalence of 9.5%, women just joining the US Army are at high risk for having a chlamydia infection. 19 More disturbing, however, was our finding that the prevalence was sustained over time and even appeared to increase independently of other measured risk factors, including “young age,” rising from 8.5% in 1996 to 9.9% in 1999. These data confirm the need to screen women 25 years of age and younger who are entering the Army from the civilian sector for chlamydia. The US Army's current policy is to not screen recruits upon entry into basic training, despite the fact that both the Centers for Disease Control and Prevention and the US Preventive Services Task Force strongly recommend routinely screening of all sexually active women aged 25 years and younger. 21,22 Our data agree with other regional and national trends reported from the Centers for Disease Control and Prevention Infertility Prevention Project, which has monitored chlamydia prevalence in family planning clinics, STD clinics, and those entering the Job Corps, and which has reported sustained or increasing chlamydia prevalences. 23
Although our study demonstrated a sustained (and slightly increasing) prevalence of chlamydia infection in female recruits over the years of observation independent of other measured risk factors, it is difficult to conclude that our findings alone are indicative of a growing epidemic of chlamydia in young women in this country. A readily identifiable limitation of this study is that it may not be generalizable to other young women who do not join the military. However, we studied approximately 80% of women beginning basic training at Fort Jackson and can conclude that the prevalence was sustained and may have increased among a majority of women entering the Army.
The year of the study was found in our model to be a significant predictor of chlamydia infection, independent of other risk factors including “young age.” However, the increasing proportion of recruits of “young age” screened over successive years of the study may have partially influenced the observed increase in prevalence in concert with another risk factor or factors that we were not able to identify or quantify. Even if the increases in prevalences of chlamydia infection in this study are caused by unidentified biases or variables for which we were not able control, the fact remains that depending on age, race, and home-of-record, about 10 to 16% of women in any one of these groups who just joined the Army are at risk for having acquired a silent, easily treatable infection capable of causing painful, serious, and costly sequelae. Because chlamydia infections have also been associated with ectopic pregnancy, stillbirths, and perinatal complications, infected and untreated recruits may also be at increased risk during later pregnancy. 24–26 The recently reported association of chlamydia infections with cervical cancer deserves further study but if confirmed may identify an additional risk for infected and untreated female recruits. 27,28
Screening of young women for C trachomatis and rescreening of cases within 3 to 4 months have been shown to be effective strategies for chlamydia control and to limit the reservoir of infection. 21,29–32 Moreover, screening could provide a cost savings for the military. 33,34 Because approximately 50% of women do not remain in the active Army for very long beyond their initial entry training, the civilian health care sector would derive significant economic benefit as well were the Army to screen its female recruits for this infection. 34
Young age has previously been shown to be an effective variable upon which to base screening and has been recommended. 19,21,22,33,34 Other studies have demonstrated the value of age-based screening programs as well. 35,36 In the current study, home-of-record in the South region of the United States as well as being 25 years old or younger (“young age”) were found to be highly associated with increased risk of chlamydia infection among women entering military service. Sexual risk factors and black race were also associated with increased risk. However, identification of sexual risk factors requires a questionnaire or interview and race/ethnicity is, for a variety of reasons, not appropriate for use as a screening criterion. On the basis of our observations from this study, home-of-record in the South was a significant, independent risk factor for C trachomatis in female Army recruits, and although it may never become a screening criterion, this variable could be evaluated for its cost effectiveness in screening women who join the military. The markedly higher prevalence of chlamydia in the South may reflect the fact that historically there have been less extensive screening programs in the South compared with the relatively longer implementation of such programs in, for example, the Northwest.
Cecil et al. 37 demonstrated a C trachomatis prevalence of 5.3% in new male recruits who were screened at Fort Jackson during the same time period as this study. Although men have not been identified to be at risk for such serious sequelae as described for women, epididymitis and, in at least one study, male infertility have been associated with prior chlamydia infection. 38 Screening male military recruits may have the added benefit of reducing the sustainability of the epidemic and female reinfection rates through reduction of reservoirs of infection in the military community.
Reproductive and sexual health are an important part of military medicine. As a point-of-entry into military service, recruit training provides a unique opportunity to efficiently screen, treat, and inform women and men at high risk of chlamydia infection. A chlamydia control program for new recruits based on young age would benefit individuals and healthcare systems both inside and outside the military. 34 Education programs at recruit training centers coupled with noninvasive screening and treatment of infections would necessarily need to be followed by continued, periodic rescreening at later medical encounters to manage reinfections. 21,31 Implementing such programs, however, would clearly be of benefit to both the military and civilian communities.
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