Comparison of an automated rapid plasma reagin (RPR) test with the conventional RPR card test in syphilis testing.
ABSTRACT: OBJECTIVE:We compared the automated non-treponemal reagin (rapid plasma reagin (RPR)) test with the conventional RPR card test for usefulness in clinical applications. SETTING:A comparative study of laboratory methods using clinical specimens in a single institute. PARTICIPANTS:A total of 112 serum samples including 59 Treponema pallidum particle agglutination (TPPA)-positive and 53 TPPA-negative specimens were evaluated. OUTCOME MEASURES:HiSens Auto RPR LTIA (HBI, Anyang, Korea) was compared with Macro-Vue RPR Card Tests (Becton Dickinson BD Microbiology Systems, Sparks, Maryland, USA). Treponemal-specific tests were performed by Serodia TPPA assay (Fujirebio, Tokyo, Japan). The percentage agreement, ? value and overall sensitivity and specificity of the two RPR tests were compared. Seroconversion rates after treatment were also compared for each RPR test. RESULTS:The percentage agreement between the two RPR tests was 78.6% (? 0.565; 95% CI 0.422 to 0.709). Sensitivity and specificity of the automated RPR test relative to the TPPA test was 52.5% (95% CI 39.1% to 65.7%) and 94.3% (95% CI 84.3% to 98.8%), respectively, while the same values for the conventional RPR card test were 86.4% (95% CI 75% to 93.9%) and 94.3% (95% CI 84.3% to 98.8%), respectively. The conventional RPR card test showed overall higher positivity than the automated RPR test, whereas the automated RPR test showed higher seroconversion (43.5%, 10/23) than the conventional RPR card test (4.3%, 1/23) in treated patients. CONCLUSIONS:The automated RPR test showed overall lower sensitivity than the conventional RPR test based on the treponemal test, but higher seroconversion after treatment. The automated RPR test could be used to monitor treatment response, especially in the reverse screening algorithm in syphilis testing.
Project description:New rapid point-of-care (POC) tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP) Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA), rapid plasma reagin (RPR), HCV enzyme immunoassay (EIA), and HIV-1/2 EIA.A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8.The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.
Project description:WHO has targeted yaws for global eradication by 2020. The program goals are to interrupt the transmission in countries where yaws is endemic and to certify countries as yaws free where yaws was endemic in the past. No new rapid plasmin reagin (RPR) seroreactivity in young children is required for certification of elimination at a country level. We sought to evaluate whether antibody responses to specific treponemal antigens measured in a high-throughput multiplex bead array (MBA) assay differentiate past versus current infection and whether a nontreponemal lipoidal antigen test can be incorporated into the MBA. Serum and dried blood spot specimens collected for yaws surveillance projects in Ghana, Vanuatu, and Papua New Guinea (PNG) were run on MBA to measure antibodies against recombinant p17 (rp17) and treponemal membrane protein A (TmpA) treponemal antigens. Results were compared to standard treponemal laboratory (TPPA or TPHA [TPP(H)A]) and quantitative RPR test data. Of 589 specimens, 241 were TPP(H)A(+)/RPR(+), 88 were TPP(H)A(+)/RPR(-), 6 were TPP(H)A(-)/RPR(+), and 254 were negative for both tests. Compared to TPP(H)A, reactive concordance of rp17 was 93.7%, while reactive concordance of TmpA was only 81.9%. TmpA-specific reactivity showed good correlation with RPR titers (R(2) = 0.41; P < 0.0001). IgG responses to the lipoidal antigen used in RPR testing (cardiolipin) were not detected in the MBA. Our results suggest that TmpA can be used as a treponemal antigen marker for recent or active infection and potentially replace RPR in a high-throughput multiplex tool for large-scale yaws surveillance.
Project description:Manual treponemal and nontreponemal serologic testing has historically been used for the diagnosis of syphilis. This approach is simple and reproducible but labor intensive. Recently, the FDA cleared the fully automated BioPlex 2200 Syphilis Total & RPR assay for the detection of treponemal and nontreponemal antibodies. We evaluated the clinical performance of this assay at a tertiary medical center with a high syphilis prevalence. Prospective consecutively collected (n = 400) and known RPR-positive (n = 100) specimens were compared using predicate manual rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA) methods and the BioPlex 2200 Syphilis Total & RPR assay. Positive and negative percent agreements (PPA and NPA, respectively) between the assays were calculated. The PPA and NPA between the manual and BioPlex 2200 RPR results for the prospective population were 85% (17/20; 95% confidence interval [CI], 69% to 100%) and 98% (373/380; 95% CI, 97% to 99%), respectively. The PPA for the manual RPR-positive population was 88% (88/100; 95% CI, 82% to 94%). Overall, the manual and BioPlex 2200 RPR titers demonstrated 78% (99/127) concordance within ±1 dilution and 94% (120/127) within ±2 dilutions. An interpretation of the syphilis serologic profile using the traditional algorithm showed a concordance of 99.5% in the prospective population and 85% in the manual RPR-positive cohort. The performance of the BioPlex 2200 Syphilis Total & RPR assay is comparable to those of manual methods. The high NPA of this assay combined with the ability to automate a historically labor-intensive assay is an appealing attribute for syphilis screening in a high-volume laboratory.
Project description:Repeated nontreponemal serologic test for syphilis titers is recommended to evaluate treatment response. However, it is unknown whether serum rapid plasma reagin (RPR) titer can serve as a surrogate for determining the efficacy of treatment in general paresis (GP) remains unknown.We retrospectively reviewed data from 105 GP patients, who were divided into two groups (62 CSF RPR+ patients and 43 CSF RPR- patients) according to reactive RPR test status in CSF. Clinical assessment included the Mini-Mental State Examination (MMSE) scores, CSF examinations (WBC count, protein concentration and RPR titer), and serum tests (RPR titer and TPPA). Among the 105 GP patients, 13 CSF RPR+ patients and 6 CSF RPR- patients had a 12 months follow-up of CSF, serum measures and MMSE.The median serum RPR titer was significantly higher in CSF RPR+ patients than that in CSF RPR- GP patients, 1:8 [IQR 1:4-1:32] vs. 1:4 [IQR 1:4-1:8] (P?<?0.001). The number of CSF RPR+ patients with serum RPR titer?1:32 was significantly higher when compared with CSF RPR- patients (P?=?0.001). For CSF RPR+ patients, the MMSE scores improved or remained constantly after penicillin treatment. For CSF RPR+ patients, the CSF RPR titer declined four-fold in 85% (11/13) of the patients, whereas the serum RPR titer declined four-fold in only 46% (6/13) of the patients, the odds ratio is 6.4 (95% confidence interval 1.0-41.2).A four-fold decline in CSF RPR titer is a good predictor for treatment efficacy in CSF RPR+ GP patients within 12 months after the completion of therapy.
Project description:Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp. pertenue. The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020. The development of a rapid diagnostic test (RDT) for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy. We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands. 415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR) and the Chembio DPP Syphilis Screen and Confirm RDT. We calculated the sensitivity and specificity of the RDT as compared to gold standard serology. The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%. The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%. The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16. Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA) setting.
Project description:Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women.Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results.Although this analysis found screening using RPR to be relatively cheap, most (>70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women.This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings.
Project description:In this study, we aimed to investigate the performance of nontreponemal antibody tests in cerebrospinal fluid (CSF) specimens from syphilis patients. From September 2009 to September 2012, CSF specimens were collected at the Shanghai Skin Disease Hospital in Shanghai, China, from 1,132 syphilis patients without HIV infection, including 154 with symptomatic and 56 with asymptomatic neurosyphilis. All of the CSF specimens underwent testing with a rapid plasma reagin (RPR) test, an RPR-V (commercial RPR antigen diluted 1:2 in 10% saline) test, the toluidine red unheated serum test (TRUST), and the Venereal Disease Research Laboratory (VDRL) test. Specificities, sensitivities, positive predictive values (PPVs), negative predictive values (NPVs), and kappa values were calculated to determine the performances of the tests. We compared results of the CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST among patients with symptomatic and asymptomatic neurosyphilis who had reactive CSF-Treponema pallidum particle agglutination (TPPA) test results. Overall, the CSF-VDRL test was reactive in 261 patients (23.1%). There were no cases in which the CSF-VDRL was nonreactive and CSF-RPR, CSF-RPR-V, or CSF-TRUST was reactive. Agreement between the results of CSF-TRUST and CSF-RPR was almost perfect (?=0.861), with substantial agreement between the results of CSF-RPR and CSF-RPR-V (?=0.740). The sensitivities of CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST were 81.4%, 76.2%, 79.5%, and 76.2%, respectively. Compared to CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST had comparable PPVs and NPVs. However, the specificity of CSF-VDRL (90.3%) was significantly lower than those of the other tests (92.7 to 93.4%). Therefore, CSF-RPR, CSF-RPR-V, and CSF-TRUST can be considered alternative tests for neurosyphilis diagnosis in HIV-negative populations, particularly when the CSF-VDRL is not available.
Project description:INTRODUCTION:Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. METHODS:This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. RESULTS:A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA. DISCUSSION:In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.
Project description:A diagnostic performance study comparing the only Food and Drug Administration-approved, point-of-care (POC) treponemal test (Syphilis Health Check) and the World Health Organization pre-qualified SD Bioline POC treponemal test against a treponemal hemagglutination test (TPHA) and a sequential algorithm of nontreponemal rapid plasma reagin and TPHA found both POC tests had >85% sensitivity compared with the TPHA and >85% sensitivity and >95% specificity compared with the rapid plasma reagin and TPHA standards.
Project description:BackgroundCurrent point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis.MethodsThe TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests.FindingsIn sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15–88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis.InterpretationThe TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test.FundingSaving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme.