Untreated Chlamydia trachomatis (CT) infections have serious sequelae.1 Early diagnosis and treatment are critical to reduce sequelae. Point-of-care (POC) testing for CT has the potential to improve patient outcomes by providing test results to clinicians during the patient's visit, potentially decreasing the time to treatment and increasing the rate of appropriate antibiotic use.2,3 The Atlas io diagnostic platform (Atlas Genetics, Bath, United Kingdom) is used to detect CT using vaginal samples in Europe, having obtained a CE mark. It is fully automated and does not require sample preparation. The cartridge is processed and analyzed using a reader instrument that provides fluidic and temperature control and electronics and software for user interface. The cartridge contains all reagents needed to test a sample including CT DNA extraction, polymerase chain reaction amplification, and detection using electrochemically labeled DNA probes. Early studies of the Atlas io for CT demonstrated low limits of detection with very low background interference. Testing of stored samples demonstrated a sensitivity and specificity of 98.1% and 98.0%.4
In this study, conducted at 2 clinical sites, we aimed to (1) assess the performance of this rapid, POC polymerase chain reaction assay for CT compared with a laboratory-based nucleic acid amplification assay (NAAT) for CT in clinic populations with high prevalence of CT and (2) evaluate women's attitudes toward sample collection, testing, and partner notification when POC CT testing is available.
MATERIALS AND METHODS
This prospective study was conducted in 2 clinic locations: a sexually transmitted disease (STD) clinic in Baltimore, Maryland and a Teen Health Center (THC) providing primary care to adolescents, located in an academic medical center in Cincinnati, Ohio. In 2016, we recruited consecutive female patients who were getting CT testing as part of their health care visit and were 14 years or older, sexually active with at least 1 male partner within the last 3 months, and had not used antibiotics or any vaginal medications within the previous 2 weeks. Menstruating women were eligible to enroll. The study was approved by the 2 sites' institutional review boards. Women provided written informed consent, parental permission was waived for minors.
Participant Characteristics and Attitudes
Women completed a structured interview to assess sociodemographic characteristics (age, race), risk behaviors (number of sex partners in the past 3 months, condom use at last sex), history of prior CT infection, and clinical symptoms associated with sexually transmitted infections (STIs) or vaginitis (abnormal discharge, vaginal itching, burning during urination, abdominal pain). Women completed a questionnaire to assess ease of self-sample collection and, if a POC test was available, attitudes toward sample collection, time willing to wait for results, preferred location to rescreen after positive CT results, cost willing to pay for POC testing, willingness to tell partner about positive results and preferred method to contact partner. Structured interview items have been previously used in our other studies to examine attitudes toward POC devices.5,6 Questionnaire items were slightly modified from previously validated items evaluating STI testing.7,8
All swabs were self-collected at the same visit. During the health care visit in which women collected a vaginal swab for clinical CT testing, participants self-collected study samples, including a flocked nylon Atlas swab and a Dacron swab. Women were provided written and verbal instructions to insert each swab into their vagina and rotate for 10 seconds. After collection, the Atlas io swab was placed in Atlas io liquid transport media.
Samples used for clinical testing were collected, stored, and transported to each site’s clinical laboratory according to clinical procedures. Testing of samples collected for clinical testing was conducted according to laboratory procedures using Aptima Combo 2 (Hologic/GenProbe, San Diego, CA). Results of clinical testing were obtained by study staff from review of participants' electronic medical records.
Atlas io samples were tested using Atlas io reader instruments located in the THC clinic and in the laboratory near the STD clinic. The THC samples tested within 4 hours of collection. The STD clinic samples were refrigerated until tested within 24 hours (72 hours for samples collected Friday). Operators were laboratorian and nonlaboratorian research personnel trained by Atlas Genetics representatives. Liquid from the sample collection tube was pipetted using a disposable pipette, which delivered a calibrated amount into the disposable io cartridge. Cartridges were stored at 2°C to 8°C up to 4 hours before use. Participant information was entered into the reader using the touch screen on the reader. The cartridge was inserted into the reader. Within 30 minutes of cartridge insertion, result readout was displayed on the reader's screen as words (positive, negative, or indeterminate). Results were saved into a downloadable electronic file stored in the reader.
When the Atlas io and Aptima Combo 2 results from the STD clinic were discordant, the extra specimen collected during the study visit was tested with Cepheid Xpert CT/NG (Sunnyvale, CA). Discrepant results from THC were not retested because specimens were not available at the time of retesting.
Performance characteristics (sensitivity, specificity and positive and negative predictive values) were calculated by standard methods and are presented with the 95% confidence intervals (CI). The 1 specimen with indeterminate results by the Atlas io device was conservatively estimated to be negative. Descriptive statistics were generated for interview and questionnaire items and categorized based on response distribution. Analyses were completed using SAS 9.4.
A total of 296 women were recruited, 284 (192 from the STD clinic, 92 from THC) had both Aptima Combo 2 and Atlas io testing results available. Characteristics of the participants are shown in Table 1. The average age was 27.4 years (SD, 10.8 years). A majority (92%) self-reported their race as black or African American, 55% reported a lifetime history of a previous CT infection, and nearly three quarters reported no new sex partners in the past 3 months. A total of 164 (58%) women reported symptoms associated with STI or vaginitis.
As shown in Table 2, the sensitivity and specificity of the Atlas io test compared with the Aptima Combo 2 test were 83.9% (26/31 specimens; 95% CI, 70.9%–96.8%) and 98.8% (250/253 specimens; 95% CI, 97.5%–100%), respectively. The positive and negative predictive values were 89.7% (26/29 specimens; 95% CI, 78.6%–100%) and 98.0% (250/255 specimens; 95% CI, 96.3%–99.7%), respectively.
Five of 8 specimens with discrepant results between Atlas io test and Aptima Combo 2 test were retested (Table 2). One Atlas-positive/NAAT-negative sample retested negative by both Cepheid Xpert CT/NG and Aptima Combo2. Two Atlas-negative/NAAT-positive samples retested negative by Cepheid Xpert CT/NG, 1 Atlas-negative/NAAT-positive samples retested negative by Aptima Combo2; and 1 Atlas-negative/NAAT-positive retested positive by Cepheid Xpert CT/NG. The adjudicated sensitivity and specificity of the Atlas test were 92.9% (26/28 specimens; 95% CI, 83.3%–100%) and 98.8% (253/256 specimens; 95% CI, 97.5%–100%), respectively. The positive and negative predictive values were 89.7% (26/29 specimens; 95% CI, 78.6%–100%) and 99.2% (253/255 specimens; 95% CI, 98.1%–100%), respectively.
Women's Attitudes Toward POC Testing for CT
A total of 273 (96%) women completed the questionnaire to assess attitudes toward POC testing. As shown in Table 3, a majority of the 273 (70%) women preferred vaginal self-sample specimen collection if a POC test were available and a majority of women (86%) reported that collecting the vaginal self-sample during the study was easy or very easy. Most women (61%) were willing to wait up to 20 minutes for results if they could be treated before leaving clinic. A quarter of women (26%) were willing to wait up to 40 minutes for results if they could be treated before leaving clinic. Most women were willing to pay US $20 or less for CT testing if they could mail a specimen collected at home to a laboratory for testing or get a CT test done at a pharmacy. Women (96%) would tell a partner about a positive CT test result from a POC test and most (97%) prefer to notify their partner in person.
If rescreening after a positive result was necessary, 45% of the women preferred to collect the specimen for rescreening at home. We examined these results by participant characteristics (Table 4) and found that among women 25 years or older, a higher proportion (68%) preferred to rescreen at home compared with an STD clinic or private doctor (P < 0.05). Among women 14 to 18 years of age, a higher proportion (87.5%) preferred to rescreen at an STD clinic or private doctor (P < 0.05). Among women with no STI symptoms, a higher proportion (66%) preferred to rescreen at an STD clinic or private doctor (P < 0.05).
Among 284 women seeking care at an STD clinic and a THC who were tested for CT as part of their medical care, the sensitivity and specificity of a novel, rapid, easy to use, diagnostic test to detect CT had a sensitivity of 84% and specificity of 99%. After discordant testing and sensitivity analysis, sensitivity was 92.9 and specificity was 98.8. Women reported vaginal self-sampling was acceptable and easy and reported a willingness to wait for results if they could receive treatment for a positive infection.
Most current NAAT CT tests have a prolonged turnaround time leading to results reported hours or days after the patient has left the health care visit. These delays can impact clinical outcomes due to treatment delays or missed treatment when patients cannot be located.9 Shorter assays, such as the Atlas io system, which requires 30 minutes, and the GeneXpert assay, which currently requires 90 minutes,10 have the potential to be exceptions to this. Reporting STI test results to patients during the clinical encounter in which testing was initiated may decrease the amount of time spent by clinical staff for following up on STI testing results, assessing for sequelae that may have developed since the clinical encounter, arranging for the patient to get treatment, and discussing and arranging for partner treatment. An additional benefit of patients learning STI test results during the same visit in which testing was ordered is higher understanding among patients of a positive diagnosis.2 Therefore, CT diagnostic tests that provide results quickly at the point of care have the potential to improve patient outcomes,11,12 and improve antibiotic stewardship.3,13–15
Accurate test performance is critical for new STI POC tests, both to gain Food and Drug Administration clearance and because clinicians identify test performance as an important attribute for STI POC tests.16,17 The sensitivity and specificity reported in package inserts for current laboratory-based NAATs for CT using self-collected vaginal specimens range from 96.1% to 98.7% and 95.6% to 99.2%, respectively.18–20 Published evaluations of NAATs report sensitivities ranging from 96.1% to 98.7 and specificities ranging from 96.5% to 99.4%.21–23 A recent report of a multisite study of the Atlas test reported a sensitivity of 96.1% (95% CI, 86.5–99.5) and a specificity of 97.7 (95% CI, 96.3–98.7).24 In our population, the Atlas io test had similar performance. We could not evaluate test performance in symptomatic and asymptomatic patients due to the sample size. The sensitivity and specificity in this study24 compared Atlas with BD ProbeTec Qx on BD Viper (BD Diagnostics, Becton, Dickinson and Company, Franklin Lakes, NJ). The BD ProbeTec Qx Assays can be less sensitive than Aptima Combo 2.
The diagnostic accuracy combined with the rapid turnaround time of the Atlas io test may lead to improved antibiotic stewardship and patient outcomes, but this remains to be studied. Because commonly available platforms for CT testing also include detection of gonococcal infections, future studies of the clinical impact of POC STI tests for CT should consider the impact of POC testing on both CT and gonococcal infections.
Understanding patient attitudes toward POC tests for CT is important to identify potential barriers and facilitators in the acceptance and uptake of new diagnostic tests. The low price point preferred by women in this study could be a barrier to adoption of POC tests by consumers, if and when POC tests become available over-the-counter. It may also be a barrier for adoption of STI POC tests within health care systems; cost of test has been identified as important to clinicians and others offering STI POC tests.25 Patient's preference for vaginal swabs was similar to clinicians and health educators reported preferences during focus groups examining end-user preferences for STI POC tests.17 Additionally, nearly two thirds of participants reported a willingness to wait 20 minutes and a quarter reported a willingness to wait 40 minutes for results, if they received treatment before leaving clinic. These findings are similar to the consensus of clinician and health educator focus group participants that indicated that an acceptable turnaround time for STI POC test results was 20 minutes or less.17 Tests that take longer than 60 minutes may be limited in their clinical impact without careful implementation into the clinical work flow, but this remains to be studied. Optimal strategies for implementing STI POC testing in clinical settings that maximize the benefits of rapidly available results are yet to be demonstrated.26,27
Collection of specimens for rescreening at home may improve rescreening rates. A preference for home collection among older women may reflect greater access to privacy at home among older women compared with younger women. A preference for collection in a medical setting among asymptomatic women with a positive test might suggest a greater trust in specimen collection in the health care setting among women whose only indication of infection was a test result. However, this remains to be studied.
In this preliminary study in 2 clinical populations, the performance of the Atlas io test suggests that it is adequate for adoption as a CT diagnostic test in clinical settings. The potential of this diagnostic test to impact patient outcomes warrants further study.
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