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Acceptability of Urine-Based Screening for Chlamydia trachomatis in Asymptomatic Young Men: A Systematic Review

Marrazzo, Jeanne M. MD, MPH*; Scholes, Delia PhD

doi: 10.1097/OLQ.0b013e31816938ca

We performed a structured literature review of published studies from 2000–2007 that measured the acceptability and acceptance (uptake) of urine testing for C. trachomatis among asymptomatic men. Studies were categorized as three types: (a) non-STD clinic venues where men were approached in person and offered testing on site (urgent care clinics, freestanding clinics or health screening settings, corrections, community centers); (b) delivery of testing kits to men at their homes; and (c) qualitative measurement related to men's experience of screening. When offered in established nonhome-based settings (clinics, schools, corrections), acceptability and consequent uptake of testing by men is generally good (mid-60% range). However, acceptance rates even in these settings vary widely and are influenced by venue, provider, and a diversity of other factors. Acceptance of home-based testing invitations, including direct mailing of test kits, is considerably lower. Attitudinal characteristics of men who decline testing primarily include low self-perception of risk for asymptomatic infection and perceived inconvenience of providing test specimens. Given these findings, testing strategies targeting asymptomatic men in established community and clinic settings are most likely to yield relatively high acceptance rates. However, barriers to both implementation and uptake remain, even when such testing is free. Interventions to enhance uptake of testing in asymptomatic men should be developed and selected with underlying C. trachomatis population prevalence in mind.

The acceptability and uptake of urine-based screening for Chlamydia trachomatis among asymptomatic men is influenced by the context in which screening is offered. Barriers to testing exist, even when testing is free.

From the *Department of Medicine, University of Washington; and †Center for Health Studies, Group Health Cooperative, Seattle, Washington.

Correspondence: Jeanne M. Marrazzo, MD, MPH, Harborview Medical Center, Division of Infectious Diseases, 325 9th Avenue, Mailbox #359931, Seattle, WA 98104. E-mail:

Received for publication December 3, 2007, and accepted January 15, 2008.

AT LEAST 60% AND PROBABLY closer to 90% of all men with genital chlamydial infection do not report urethral discharge or dysuria.1–6 The widespread availability of nucleic acid amplification testing (NAAT) of urine for Chlamydia trachomatis infection has dramatically increased the capability to screen asymptomatic men. However, relatively little work has evaluated the readiness of asymptomatic men to accept such testing or the factors that might impact willingness to undergo testing. Data that address these issues are important for several reasons. First, screening asymptomatic men in venues with moderately high chlamydia prevalence could be an important component of comprehensive chlamydia control programs.7–9 Although selective screening for chlamydial infection in women has been associated with a reduction in symptomatic pelvic inflammatory disease, and with marked declines in C. trachomatis prevalence,10,11 these declines have not been sustained, especially among adolescents, with prevalence at stable or increasing levels in some areas.12–15 Increasing use of NAAT, which are more sensitive than previously used tests, only partly explains these trends,13,16 and the additional impact of control efforts directed at primary detection in men may be important. Second, empirical treatment of male sex partners of women infected with C. trachomatis is recommended and, at a population level, likely to have a favorable impact on population prevalence of C. trachomatis.17 However, it is performed infrequently, presumably resulting in high rates of reinfection among women.18,19 Third, understanding acceptability of screening to asymptomatic men is necessary to optimally allocate scarce C. trachomatis control resources to strategies that meaningfully involve men and their health care providers. Finally, a randomized controlled trial performed in a managed care setting demonstrated that an intervention to increase screening of adolescent males during preventive care visits markedly increased testing, with an associated detection of moderate disease prevalence.20

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We performed a search of the MEDLINE computerized database of the US National Library of Medicine English language literature for the years 2000 to 2007, using the MeSH Terms “Chlamydia trachomatis,” “males,” and “screening.” We then confined these results to studies that offered urine-based testing. In constructing the review, we generally followed CONSORT guidelines for reporting on observational studies, with the exception that we did not perform a formal meta-analysis, given the marked diversity of methodology across studies.21 The search of the published literature yielded 21 articles that contributed relevant data.

We divide our discussion of these data into 3 main areas: studies performed in non-STD clinic venues where asymptomatic men were approached in person and typically offered testing on-site (usually sites where medical interventions are either standard or have an established track record, such as urgent care clinics, freestanding clinics or health screening settings, corrections, or community centers); studies that assessed delivery of testing kits to men at their homes; and studies that focused on qualitative measurement related to men's experience of screening.

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Although a variety of studies reporting on the uptake of testing among men offered urine-based chlamydia testing, fewer queried men as to their reasons for accepting or declining testing. Table 1 provides an overview of the major studies, which are discussed in detail below.



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Studies in Established Settings

A single large, national study has evaluated the feasibility of offering urine-based NAAT for C. trachomatis to young asymptomatic men outside of sexually transmitted disease (STD) clinics in the United States. Testing was made available at no cost to the sites or to the men who participated. Across 4 cities, nearly 23,000 asymptomatic men (median age, 21 years) were tested for C. trachomatis at over 50 different venues, using several approved NAAT.22 The numbers of asymptomatic men tested for C. trachomatis and percentage positive were: Baltimore, 2838 (10%); Denver, 3323 (9%); Seattle, 765 (1%); and San Francisco, 15,706 (5%). Venue types included adult and juvenile detention, school clinics, street outreach, adult primary care. Acceptability logs administered for discrete periods at all centers revealed that the majority of men in most settings were approached and accepted (median acceptance across all sites was 64%); however, testing uptake ranged widely depending on the city, the venue and the approach used.23 Acceptance varied within venue type (for example, median acceptance in school-based clinics ranged from 17% to 66% across cities). Both the highest and lowest uptake occurred in adult detention settings: 90% in San Francisco, where 10,515 men were approached for testing, and <10% in Baltimore.

More detailed evaluation of men accepting and declining testing was conducted in Seattle, where most testing was conducted in juvenile detention and university-based health clinics. Of 1080 men offered testing, 859 (79%) accepted; 765 (88%) were asymptomatic. In a multivariable analysis that included subject characteristics and whether an incentive was offered, accepters of testing were significantly more likely to be younger than 20 years, and to report a higher number of sex partners in the previous 2 months, not knowing whether they previously had any STD, and less recent use of any health care. Receipt of incentive was also independently associated with accepting testing. In multivariable analysis, men who accepted chlamydia testing did not differ from those who declined by race or reported condom use at last sex (with main or casual sex partner), new sex partner (2 months), or ever having been tested for C. trachomatis. Of 221 men who refused testing, only 39 (18%) provided a reason for doing so. The most commonly cited reasons were not feeling at risk for any STD (28%) and lack of symptoms (21%). Other reasons reported were lack of time (5%), not being sexually active (5%), and having been tested recently for STD (5%). Interestingly, health care providers who were surveyed as part of this study also indicated a belief that most asymptomatic men did not perceive themselves to be at risk for STD, and that the majority of men they saw with chlamydial infection were asymptomatic. In summary, this study demonstrated wide variation in testing uptake across participating settings, an observation that was linked to the manner in which testing was offered to asymptomatic men. Men in key target groups—including adolescents, those who had not sought any recent health care, and those with higher number of recent sex partners—were significantly more likely to accept than to decline testing.

Settings that provide pediatric care comprise another setting for which acceptability of testing has been assessed. In the one other study that compared persons who accepted urine-based chlamydia testing to those who refused, overall acceptance among 521 male adolescents seeking care at an urban pediatric emergency department was 42%.24 In multivariable analysis of the male and female participants combined (N = 1231), those who accepted testing were more likely to be older (16 vs. 15 years), black, and uninsured or insured by Medicaid; however, acceptance rates also differed significantly by which of the 3 study interviewers invited subjects to participate. Unfortunately, gender-specific data on this outcome was not reported. In their report on a study that randomized managed care pediatric clinics to a system-level intervention to increase screening of adolescent men making health maintenance visits or to usual clinical care, Tebb and colleagues noted that “fewer than 5%” of men who were invited to be tested declined; however, detailed data were not provided.20 In a cross-sectional survey of 365 adolescents (of whom 42%, or 153, were male) interviewed after urgent pediatric care visits in a health maintenance organization,25 Miller and colleagues assessed participants' ratings of acceptability of both discussing sexual health and of potentially providing a urine sample for testing. Eight percent of all surveyed felt that testing would be acceptable. Acceptability of testing was associated with adolescents' perception that the clinician knew “how to talk with teens like me” (adjusted OR 14.3; 95% CI 4.3–54.9) and “listened carefully as I explained my concerns” (adjusted OR, 14.3; 95% CI 1.1–11.5). Given the relatively small number of men who participated, detailed subset analysis was not performed, but rates of acceptability were comparable between sexes.

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Home-Based Approaches to Testing

Several studies have now used the approach of mailing test kits to men at their place of residence. This has shown promise in reaching asymptomatic individuals, who may be unlikely to present to clinic-based settings for routine care.26–32 However, the majority of reports to date have evaluated outreach in countries with some form of national health care coverage. A recent study, discussed below, indicates the yield of these strategies may be lower when targeting men in the United States.33

Andersen and colleagues, in Denmark, were among the first groups to perform population-based, randomized trials of this approach.27 They randomized all 30,439 persons 21 to 23 years old in a single county to receive 1) a home sampling kit for urine testing, 2) a card to mail back to request a kit, or 3) access to usual care. The approach yielded significantly more testing and detection of infections in men relative to usual care: 25.3% of those receiving direct mailed kits and 15.1% of men in the test-request arm provided specimens, even with no reminders, whereas only 1.4% of the usual care group sought clinic testing. The relative risks of being tested during 3 months of follow-up were 19.1 (95% CI 16.0–22.8) and 11.8 (95% CI 9.8–14.2), for arms 1 and 2, respectively; C. trachomatis prevalence in these groups was 5.9% and 5.7%, respectively. Approximately 75% of men who returned mailed specimens were asymptomatic. In this study, direct mailing of a test kit to men was deemed feasible and likely to be effective at the population level as part of a general chlamydia control program. These investigators also mailed questionnaires to a random sample of 400 men and women who did not participate in the study, with 76% of 200 men responding. Nonparticipating men were significantly more likely than nonparticipating women to state that they did not feel at risk for chlamydial infection. Eighty-four percent of male nonparticipants also felt that invitation by mail was a “good approach,” and only 15% stated that they would prefer to have the test done by a physician.

The only population-based, randomized trial in the United States to assess rates of testing using this approach in men was performed in a managed care setting, evaluating strategies very similar to those of Andersen et al.27 Male enrollees aged 21 to 25 years (N = 8820) were selected from the automated files of Group Health Cooperative and randomized to 1 of 3 arms (n = 2940 in each): (a) a letter explaining the opportunity for screening and a card to mail back to request a urine home sampling kit; (b) a letter explaining the opportunity for screening and a urine home sampling kit; or (c) a usual care control, where testing occur only if men presented to a group health cooperative (GHC) clinic during the study period.33 One reminder was sent to the intervention groups. The outcome was testing rates in the 4 months postrandomization. Rates of specimen return were 3.6% (105 men) in the test request group and 7.8% (230 men) in the direct mailing group. All 335 respondents were sexually experienced, 43% had >2 sex partners in the past year, and 80% reported no genitourinary symptoms. Compared with arm 3 (usual clinic care), the relative risk of being tested was 5.6 (95% CI 3.6–8.7) for arm 1 and 11.1 (95% CI 7.3–16.9) for arm 2. Prevalence of C. trachomatis for mailed-back specimens was 1.0% for arm 1 and 2.6% for arm 2; 70% of all positive intervention tests were from mailed samples. These investigators concluded that, although both intervention strategies resulted in significantly higher testing rates relative to usual care and directly mailing the kit performed best, the intervention response rate was low (5.7% overall), as was the prevalence; thus, the value of mailed outreach strategies to US men should be considered in the context of other chlamydia screening priorities.

Interventions outside the randomized trial setting have also been recently reported. Domeika and colleagues in Sweden invited both community-based and university-based groups of men aged 19 to 24 years old to be screened with a letter; kits were mailed to men who mailed back a positive response.34 Participants were then asked to mail the urine sample to a central laboratory. Of the 1936 men thus invited, 462 (24%) responded; of these, 182 (40%) declined testing, with the reasons most commonly cited (87%) reflecting a perception of low risk for STD (“steady” partner, condom use). Among 280 men (60% of invited) who accepted testing, urine was tested for 247, among whom only 5 had C. trachomatis. All received their test results with a web-based system specifically designed to give confidential, secure information. These investigators concluded that although their approach was feasible, both the response rate and consequent detection of disease were too low to recommend it. In the United Kingdom, Rogstad reached a similar conclusion; they invited 2607 male undergraduates to be screened by a mailed letter and kit, with a response rate of 29.1% overall and prevalence of 1.2% among the 758 students consequently tested.32

Other similar nonrandomized “invitational” studies have reported higher response rates than those noted above. For example, Stephenson and colleagues invited 223 men aged 18 to 35 years already established as patients of UK general practitioners to provide urine by mail to be screened; 46% provided samples.35 Using a stratified national probability survey directed by area address density in the Netherlands, van Bergen and colleagues randomly selected 21,000 men and women age 15 to 29 years to receive a home sampling test kit. The overall response rate was 41% among the eligible population, which included 8768 men; overall, 2930 men provided a urine sample (33.4% of those eligible). Prevalence adjusted for age, sex, and area address density was 1.5% (95% CI 1.1–1.8).30 In a detailed analysis of acceptability, this group assessed the experience of screening in a subset of 156 chlamydia-positive and 600 chlamydia-negative participants (total N = 756) who were invited to complete a questionnaire 6 to 12 weeks after receiving the results of their test. The response rate to the mailing overall was 50% (N = 374), and among men, 38%. Overall, most respondents had a favorable reaction to the invitation (84% positive and 9% neutral), and there was a significant difference among infected participants in that men generally viewed the experience somewhat less favorably (P = 0.01) on a 5-point scale. Men were less likely than women to report feeling “dirty” as a result of testing positive, or feeling anxious about the possibility of infertility related to infection. Half of the participants expressed a willingness to be tested in the future; this was not related to participants' sex.31 Despite the relatively high response rates in this study, the prevalence of chlamydial infection among those tested was still low [1.5% (95% CI 1.1–1.8)].

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Qualitative Studies Assessing Attitudes Towards or Experience With Testing

Although provision of testing in alternative venues may remove the potential stigma associated with seeking care and testing at STD clinics, significant concerns and barriers associated with STD testing are likely to remain.36–38 A number of studies that have not provided testing have examined these attitudinal characteristics. In focus groups centered on obstacles to and motivators for obtaining young men obtaining chlamydia screening, participants expressed a wide variety of concerns about testing, including privacy and confidentiality, and considerable lack of knowledge about chlamydial infection itself and the meaning of a positive test.39 For example, some participants thought they could potentially die from a chlamydial infection or that a positive test might mean they were at risk of also having AIDS. The authors concluded that home-based chlamydia testing could potentially avoid many of the barriers to testing cited by participants, and were prompted to explore offering testing with an Internet-based approach.40,41 Although uptake by men has not yet been reported, uptake by women was relatively brisk and yielded a high detection rate for C. trachomatis (10.3% of 400 women tested by NAAT of self-collected vaginal swab).40 Attempts to more fully characterize participants' experience of being screened for C. trachomatis were also described by the UK-based Chlamydia Screening Studies investigators, who conducted in-depth interviews with 45 randomly sampled participants aged 16 to 39 years who had been previously tested in general practice settings; 19 of the participants were men.42 Four main themes were identified: initial discomfort with screening arising from unease with sexual health issues in general; anxiety (most associated with receipt of a positive result) due to fear of informing partners, risk of infertility, and possibility of other STD; concern about stigmatization, notably absent among the males; and recognition of need to balance harms of screening with potential benefits. The investigators concluded that public education and more open discussion of STD, especially C. trachomatis, could greatly address these issues.

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Research to date suggests that simply making urine NAAT available and affordable outside of STD clinics will not ensure widespread uptake of testing by men who are appropriate screening targets. Because this topic is a relatively new one, the literature is young, and as such, the available studies are diverse in both methods and study populations. In selecting the studies to include, we were faced with the challenge of reconciling the paucity of the available data with the inconsistent methods used to date. Despite this, one can discern some consistent trends across these diverse studies. Rates of testing uptake vary widely, but indicate that most men are likely to accept testing offered in person, depending on the venue and how they are approached. Some of the highest reported rates have been in corrections settings, where C. trachomatis prevalence is generally high. The yield, and prevalences, of mailed (at-home) approaches have been considerably lower.

Uptake of testing by asymptomatic men may be limited for several key reasons. First, while provision of testing in alternative venues may remove the potential stigma associated with seeking care and testing at STD clinics, significant concerns associated with STD testing are likely to remain, as indicated by several studies discussed earlier.36–38 Eliciting these concerns, and related attitudes towards testing (particularly reasons for refusal and related beliefs), may require an approach other than the traditional self-administered questionnaire. Among the more consistent findings that men report for declining testing are lack of perception of being at risk for STD, indicating that young men at risk for chlamydial infection require education about the rationale for and value of chlamydia testing, including the implications that infection has for their sex partners. However, men also were more likely to express a favorable attitude toward receiving a test, including a home-based test, and less likely to report concerns regarding stigma related to a positive test than were women.

Uptake of testing by asymptomatic men is likely to be strongly affected by the structural context in which the test is offered. For example, available studies suggest that incarcerated youth or adults asked to submit a urine sample for STD testing at registration may be more likely to comply, given the circumstances, than might youth approached in the context of a street-based outreach project. In less structured settings, the approach used by individual providers or outreach staff might impact men's decision to be tested more substantially. Finally, mailed outreach to men is a strategy that deserves further consideration—with caveats—despite disappointing data on test uptake. In the randomized trials summarized earlier, these real-world approaches resulted in notably higher testing than occurred in usual care and were relatively inexpensive to implement. However, the low response rates mean that at a minimum, further targeting would be needed to favorably affect chlamydia disease burden. Potential subgroups to target with this approach could include men with recent infection (repeat testing) or men in at-risk age brackets residing in local high prevalence areas. Small incentives, strategies to increase recognition of risk, and more aggressive follow-up also may increase participation, but would increase costs, as well. Because lack of knowledge about the largely asymptomatic nature of infection was evident in many studies, strategies that address this deficit should be considered. Education can be provided through peers, in media or educational venues, or at health care encounters not originally intended to provide STD care. Finally, the studies we reviewed were highly diverse, and the available data were too sparse to provide a sense of how the underlying C. trachomatis prevalence might impact acceptability of testing to men. None of the studies targeted the intriguing issue of prevalence-specific measures to increase testing among populations one would really like to undergo screening. Interventions to enhance uptake of testing might need to be developed and selected with this important parameter in mind.

Most of the studies we reviewed had limitations. Some used several methods to estimate the acceptability of testing in the context of existing or recently initiated screening programs. Even those that used a consistent method to specifically assess self-reported measures of acceptability relied on self-selection of respondents, a challenge that intrinsically presents a bias favoring a subset of the eligible target population. Some evaluations also had less than optimal response. Among men specifically queried about reasons for declining testing in the Seattle-based study, relatively few provided a reason for doing so,23 suggesting the need for alternative formats to elicit men's knowledge, beliefs, and attitudes about chlamydia screening, especially in the United States.39

For asymptomatic men, the decision to be tested for chlamydial infection probably involves numerous complex factors. These include stimuli that might motivate men to seek testing because of increased self-perceived risk for STD, notification that a partner has an STD, and education about the reason for screening. Other factors might involve opportunistic encounters at which men are presented with screening options, including screening in schools, sports teams, detention settings, or in outreach projects. A successful approach to a cogent policy for screening asymptomatic men will need to emphasize a variety of these factors, and should certainly include education of men and their providers about the largely asymptomatic nature of genital chlamydial infections, the value of screening in preventing adverse health outcomes (particularly in women), and continued availability of screening in critical venues outside of STD clinic settings—particularly detention settings and clinics for teens in areas with high chlamydia prevalence. As the evidence base to inform policy for screening men for chlamydial infection accrues, more systematic assessment of health care providers' attitudes and practices and system barriers to implementation will be necessary. Most of the research on acceptability and feasibility of screening in men has been pursued without cross-connection to similar research in women. Given limited prevention resources, future research could contribute to a cogent screening policy by considering how to optimally balance efforts to increase testing uptake in appropriate populations of women and men to achieve the greatest impact on the public health burden of disease.

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