A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.
ABSTRACT: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min.Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection.CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT.The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.
Project description:Background Most studies evaluating extragenital testing performance for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection by the Xpert® CT/NG show high per cent agreement with comparison assays; however, the precision around positive per cent agreement is low and thus the values that have been reported are not highly informative. Therefore, a systematic review was conducted and data from five studies were combined to better assess positive per cent agreement. METHODS:The literature indexed on PubMed.gov was searched. Included studies were those that were an evaluation of the Xpert CT/NG assay with rectal and/or pharyngeal specimen types compared with another nucleic acid amplification test (NAAT), the Aptima transcription mediated amplification assay. A full Bayesian method was used for bivariate fixed-effect meta-analysis of positive and negative per cent agreement and pooled estimates (and 95% confidence intervals (CI)) were presented for each. RESULTS:The pooled positive and negative per cent agreement for detection of CT in rectal specimens was 89.72% (95% CI: 84.97%, 93.64%) and 99.23% (95% CI: 98.74%, 99.60%), and in pharyngeal specimens, they were 89.96% (95% CI: 66.38%, 99.72%) and 99.62% (95% CI: 98.95%, 99.95%) respectively. For NG detection in rectal specimens, the pooled positive and negative per cent agreement was 92.75% (95% CI: 87.91%, 96.46%) and 99.75% (95% CI: 99.46%, 99.93%), and in pharyngeal specimens, they were 92.51% (95% CI: 85.84%, 97.18%) and 98.56% (95% CI: 97.69%, 99.23%) respectively. CONCLUSIONS:It was found that the Xpert CT/NG assay performed similarly to the Aptima transcription mediated amplification assay for the detection of CT and NG in extragenital specimens. The Xpert assay has the benefit of providing faster results at the point-of-care, thus reducing the turnaround time for results, potentially enabling same-day treatment.
Project description:OBJECTIVES:To determine the proportion of patients who received a treatment for Clostridioides difficile infection (CDI) among those presenting a discordant C. difficile diagnostic assay and to identify patient characteristics associated with the decision to treat CDI. DESIGN:Cross-sectional study. SETTING:Monocentric study in a tertiary care hospital, Geneva, Switzerland. PARTICIPANTS:Among 4562 adult patients tested for C. difficile between March 2017 and March 2019, 208 patients with discordant tests' results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA-)) were included. MAIN OUTCOME MEASURES:Treatment for CDI. RESULTS:CDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95%?CI 1.96 to 110.8) was the only factor associated with CDI treatment. CONCLUSIONS:The proportion of NAAT+/EIA- patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.
Project description:This study aimed to estimate the prevalence of chlamydial trachomatis (CT) infection and explore its risk factors among patients attending sexual and reproductive health clinics in Shenzhen, China. We collected demographic and clinical information from attendees (aged 18-49). CT and Neisseria gonorrhoeae (NG) infection was determined by nucleic acid amplification test (NAAT) on self-collected urine specimens. Of 1,938 participants recruited, 10.3% (95% confidence interval [CI]: 9.6%-11.0%) tested positive for CT. Prevalence was similar between men (10.6% [85/804]; 95% CI, 9.5%-11.7%) and women (10.1% [115/1134]; 95% CI: 9.2%-11.0%). Being 18-25 years old (adjusted odds ratio [aOR] = 2.52; 95%CI:1.35-4.71), never tested for CT before (aOR = 2.42; 95%CI: 1.05-5.61) and infected with NG(aOR = 3.87; 95%CI: 2.10-7.10) were independently associated with CT infection. We found that CT infection is prevalent among patients attending sexual and reproductive health clinics in Shenzhen, China. A comprehensive program including CT screening, surveillance and treatment is urgently needed.
Project description:OBJECTIVES:Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS:Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS:Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS:This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.
Project description:This study was aimed to estimate the prevalences of chlamydia (CT) and gonococcal (NG) infections and explore risk factors associated with the CT infection among women in Shenzhen, China. We collected socio-demographic and clinical data from women (aged 20-60) and determined positivity of CT or NG by nucleic acid amplification test (NAAT) with self-collected urine specimens. We estimated prevalence of CT and NG and determined risk factors associated with CT infection. Among 9,207 participants, 4.12% (95% confidence interval [CI], 3.71%-4.53%) tested positive for CT and 0.17% (95% CIs, 0.09%-0.25%) for NG. Factors significantly associated with CT infection included being an ethnic minority (ethnicity other than Han China) (Adjusted odds ratio [AOR], 1.9; 95% CI, 1.2-3.0), using methods other than condom for contraception (AOR, 1.5; 95% CI, 1.2-1.8), having a history of adverse pregnancy outcomes (AOR, 1.4; 95% CI, 1.1-1.8), and experiencing reproductive tract symptoms in the past three months (AOR, 1.3; 95% CI, 1.0-1.7). we found that CT infection is prevalent among women in Shenzhen, China and associated with both demographic and behavioral factors. A comprehensive CT screening, surveillance and treatment programme targeting this population is warranted.
Project description:Nucleic acid amplification testing (NAAT) is the preferred method to detect Chlamydia trachomatis and Neisseria gonorrhoeae, but no commercial tests are cleared by the U.S. Food and Drug Administration for use with extragenital swab samples. This study evaluated the performance of the Gen-Probe Aptima Combo2 assay (Aptima) and the Cepheid Xpert CT/NG assay (Xpert) to detect C. trachomatis and N. gonorrhoeae in rectal and pharyngeal samples from 224 men and 175 women reporting a history of anal receptive sexual intercourse. Discordant results between the NAATs were repeated using the assays APTIMA CT or APTIMA GC, which target alternate primers, as the confirmatory tests. C. trachomatis was detected from 59 rectal swabs and 8 pharyngeal samples, with 97.7% and 99.5% agreement between the two test systems, respectively. For C. trachomatis, Xpert was 95% sensitive (95% CI, 86 to 99%) and Aptima was 92% sensitive (95% CI, 81 to 97%) from rectal swabs, while both systems were 100% sensitive from pharyngeal samples. N. gonorrhoeae was detected from 30 rectal and 40 pharyngeal samples, with 99.5% and 97.5% agreement between the two test systems. The sensitivity of Xpert for N. gonorrhoeae from rectal swabs was 100% (95% CI, 88 to 100%) versus 93% (95% CI, 78 to 99%) for Aptima. From pharyngeal swab samples, Xpert was 98% sensitive (95% CI, 87 to 99.9%) versus 93% (95% CI, 80 to 98%) for Aptima. For C. trachomatis, neither system was >95% sensitive from the rectum, though both were >99.5% specific. For N. gonorrhoeae, Xpert had higher sensitivity than Aptima, but with more false positives from pharyngeal samples.
Project description:Microscopic examination of acid-fast-stained sputum smears is the current standard of care in the United States to determine airborne infection isolation (AII) of inpatients with presumptive pulmonary tuberculosis (PTB). However, nucleic acid amplification testing (NAAT) with the Xpert MTB/RIF assay (Xpert) may be more efficient and less costly.This prospective observational cohort study enrolled a consecutive sample of 318 AII-eligible inpatients from a public hospital in Seattle, Washington, from March 2012 to October 2013. Sputum samples were collected from each inpatient and analyzed using smear microscopy, culture, drug susceptibility testing, and NAAT. The performance, clinical utility (AII duration and survival), and cost-effectiveness from an institutional perspective were compared for 5 testing strategies.Among the 318 admissions with presumptive PTB, 20 (6.3%) were culture-positive for Mycobacterium tuberculosis. The sensitivity of 1 Xpert, 2 Xperts, 2 smears, or 3 smears compared to culture was 0.85 (95% confidence interval [CI], .61–.96), 0.95 (95% CI, .73–1.0), 0.70 (95% CI, .46–.88), and 0.80 (95% CI, .56–.93), respectively. A cost-effectiveness analysis of the study results demonstrated that an Xpert test on 1 unconcentrated sputum sample (assuming equivalent results for unconcentrated and concentrated sputum samples) is the most cost-effective strategy (99.9% preferred at willingness-to-pay of US$50000) and on average would save 51.5 patient-hours in AII and up to $11466 relative to microscopy without a compromise in sensitivity.In hospitalized patients with presumptive PTB in a low-burden setting, NAAT can reduce AII and is comparably sensitive, more specific, and more cost-effective than smear microscopy.
Project description:Background:We used an ultrasensitive, quantitative single molecule array (Simoa) immunoassay to test whether concentrations of Clostridioides (formerly Clostridium) difficile toxins A and/or B in the stool of adult inpatients with C. difficile infection (CDI) were higher than in asymptomatic carriers of toxinogenic C. difficile. Methods:Patients enrolled as CDI-NAAT had clinically significant diarrhea and a positive nucleic acid amplification test (NAAT), per US guidelines, and received CDI treatment. Potential carriers had recently received antibiotics and did not have diarrhea; positive NAAT confirmed carriage. Baseline stool samples were tested by Simoa for toxin A and B. Results:Stool toxin concentrations in both CDI-NAAT (n = 122) and carrier-NAAT (n = 44) cohorts spanned 5 logs (0 pg/mL to >100000 pg/mL). Seventy-nine of 122 (65%) CDI-NAAT and 34 of 44 (77%) carrier-NAAT had toxin A + B concentration ≥20 pg/mL (clinical cutoff). Median toxin A, toxin B, toxin A + B, and NAAT cycle threshold (Ct) values in CDI-NAAT and carrier-NAAT cohorts were similar (toxin A, 50.6 vs 60.0 pg/mL, P = .958; toxin B, 89.5 vs 42.3 pg/mL, P = .788; toxin A + B, 197.2 vs 137.3 pg/mL, P = .766; Ct, 28.1 vs 28.6, P = .354). However, when CDI/carrier cohorts were limited to those with detectable toxin, respective medians were significantly different (A: 874.0 vs 129.7, P = .021; B: 1317.0 vs 81.7, P = .003, A + B, 4180.7 vs 349.6, P = .004; Ct, 25.8 vs 27.7, P = .015). Conclusions:Toxin concentration did not differentiate an individual with CDI from one with asymptomatic carriage. Median stool toxin concentrations in groups with CDI vs carriage differed, but only when groups were defined by detectable stool toxin (vs positive NAAT).
Project description:We evaluated saliva (SAL) specimens for SARS-CoV-2 RT-PCR testing by comparison of 459 prospectively paired nasopharyngeal (NP) or mid-turbinate (MT) swabs from 449 individuals with the aim of using saliva for asymptomatic screening. Samples were collected in a drive-through car line for symptomatic individuals (N=380) and in the emergency department (ED) (N=69). The percent positive and negative agreement of saliva compared to nasopharyngeal swab were 81.1% (95% CI: 65.8% - 90.5%) and 99.8% (95% CI: 98.7% - 100%), respectively. The sensitivity increased to 90.0% (95% CI: 74.4% - 96.5%) when considering only samples with moderate to high viral load (Cycle threshold (Ct) for the NP <=34). Pools of five saliva specimens were also evaluated on three platforms: bioMérieux NucliSENS easyMAG with ABI 7500Fast (CDC assay), Hologic Panther Fusion, and Roche COBAS 6800. The median loss of signal upon pooling was 2-4 Ct values across the platforms. The sensitivity of detecting a positive specimen in a pool compared with testing individually was 100%, 93%, and 95% for CDC 2019-nCoV Real-Time RT-PCR, Panther Fusion® SARS-CoV-2 assay, and cobas® SARS-CoV-2 test respectively, with decreased sample detection trending with lower viral load. We conclude that although pooled saliva testing, as collected in this study, is not quite as sensitive as NP/MT testing, saliva testing is adequate to detect individuals with higher viral loads in an asymptomatic screening program, does not require swabs or viral transport media for collection, and may help to improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
Project description:BACKGROUND:Sexual transmission rates of Chlamydia trachomatis (Ct) cannot be measured directly; however, the study of concordance of Ct infection in sexual partnerships (dyads) can help to illuminate factors influencing Ct transmission. METHODS:Heterosexual men and women with Ct infection and their sex partners were enrolled and partner-specific coital and behavioral data collected for the prior 30 days. Microbiological data included Ct culture, and nucleic acid amplification testing (NAAT), quantitative Ct polymerase chain reaction, and ompA genotyping. We measured Ct concordance in dyads and factors (correlates) associated with concordance. RESULTS:One hundred twenty-one women and 125 men formed 128 dyads. Overall, 72.9% of male partners of NAAT-positive women and 68.6% of female partners of NAAT-positive men were Ct-infected. Concordance was more common in dyads with culture-positive members (78.6% of male partners, 77% of female partners). Partners of women and men who were NAAT-positive only had lower concordance (33.3%, 46.4%, respectively). Women in concordant dyads had significantly higher median endocervical quantitative Ct polymerase chain reaction values (3,032) compared with CT-infected women in discordant dyads (1013 inclusion forming units DNA equivalents per mL; P < 0.01). Among 54 Ct-concordant dyads with ompA genotype data for both members, 96.2% had identical genotypes. CONCLUSIONS:Higher organism load appears associated with concordance among women. Same-genotype chlamydial concordance was high in sexual partnerships. No behavioral factors were sufficiently discriminating to guide partner services activities. Findings may help model coitus-specific transmission probabilities.