Data were also collected on alternative diagnoses accounting for positive test results (eg, endemic treponematoses, autoimmune conditions). Syphilis is a disease caused by infection with the spirochete Treponema pallidum. Intervals are Mayo-derived, unless otherwise designated. Of 959 patients included in the analysis, 262 had current syphilis (all stages), 294 had prior syphilis only, and 403 did not have syphilis. Confirmation of reactive … A diagnostic challenge between identifying early syphilis versus a false positive signal occurs in cases where the treponemal enzyme immunoassay (EIA) is reactive and confirmatory T. pallidum particle agglutination assay is negative. A nontreponemal test (NTT) is a blood test for diagnosis of infection with syphilis.Nontreponemal tests are an indirect method in that they detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete.In contrast, treponemal tests look for antibodies that are a direct result of the infection thus, anti-treponeme IgG, IgM and to a lesser degree IgA. A positive treponemal test suggests infection with T pallidum but does not distinguish between recent or past, or treated and untreated infection. In examining sensitivity by stage of syphilis (Table 2), FTA-ABS had the lowest sensitivity among the 7 assays for primary syphilis (all P ≤ .01). Currently, various treponemal-specific immunoassays are increasingly being used for syphilis screening and diagnosis, including enzyme immunoassays (EIAs), chemiluminescence immunoassays (CIAs), and microbead immunoassays (MBIAs), among others. (Table 1) If syphilis remains clinically suspected, a second specimen should be submitted for testing. Because of the persistence of reactivity, probably for the life of the patient, the treponemal tests are of no value to the clinician in This algorithm starts with an automated treponemal assay, such as an enzyme immunoassay (EIA) and multiplex flow immunoassay (MFI), to detect antibodies specific to T pallidum. Early latent syphilis was defined as absence of symptoms and either (1) reactive nontreponemal and treponemal serology, or (2) 2 reactive treponemal tests (eg, EIA reactive, RPR nonreactive, TPPA reactive), no prior history of syphilis AND prior sexual contact to a case of early syphilis within the past 12 months, OR prior nonreactive serology within the past 12 months. TPPA had 100% specificity. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Falsely reactive treponemal results may occur; additional testing by a non-treponemal assay is recommended if not previously performed on this sample. Because these tests measure the host's antibody response to non-treponemal antigens, they lack specificity. If a treponemal test is negative, neurosyphilis is unlikely to be present. Both KPNC and KPSC regional laboratories utilized reverse sequence screening; KPNC utilized the LIAISON CIA and KPSC utilized the Trep-Sure EIA as the initial screening test and reflex-tested all reactive CIA or EIA specimens with the RPR. Specimens from SFDPH were from consecutive patients presenting to the city’s municipal sexually transmitted disease clinic with reactive serology and diagnosed with primary or secondary syphilis. Radolf JD, Tramont EC, Salazar JC: Syphilis (Treponema pallidum). aFTA-ABS was more likely to revert to nonreactive than the immunoassays (P < .001) but not significantly different from TPPA (P > .05). Persistent Reactivity of Treponemal Assays Among Patients With Prior Syphilis (n = 294). Labs that screen with an EIA or CIA have reversed _ this algorithm. Sensitivity of FTA-ABS in primary syphilis was poor. Since treponemal tests may remain active for life in adequately treated patients, a positive T PALLIDUM IGG + IGM [86781E] indicates exposure to syphilis and it does not indicate untreated syphilis. INNO-LIA (Fujirebio, Malvern, Pennsylvania) is a manual line immunoassay that measures IgG. SFDPH utilizes a point-of-care RPR in the clinical setting; all specimens are tested with the VDRL test followed by the TPPA (if the initial VDRL is reactive) in the laboratory. Search for other works by this author on: Kaiser Permanente Northern California Regional Laboratory, Berkeley, Southern California Permanente Medical Group Regional Reference Laboratory, North Hollywood, San Francisco Department of Public Health, California, Southern California Permanente Medical Group, California, Sexually transmitted disease surveillance 2016, An evaluation of the relative sensitivities of the Venereal Disease Research Laboratory test and the, Are you sure it’s syphilis? The t test was used to compare means, the χ2 test was used to compare proportions, and a P value of <.05 was considered statistically significant. CDC investigators were blinded to clinical characteristics or original serologic results when performing the laboratory testing. A positive treponemal test suggests infection with T pallidum but does not distinguish between recent or past, or treated and untreated infection. J Clin Microbiol. Although it is not US Food and Drug Administration (FDA) cleared, it has been validated to meet Clinical Laboratory Improvement Amendments (CLIA) and is used by some commercial laboratories in the United States. Patients with current syphilis were older, more likely to be male, a man who has sex with men, and HIV-positive compared to those who did not have syphilis (all P < .05). Among these patients, Trep-Sure EIA was most likely to be reactive (85%), followed by Centaur CIA (61%), LIAISON CIA (37%), INNO-LIA (25%), and Bioplex (20%). Nontreponemal tests are also associated with biologic false-positive results among injection drug users and in various chronic diseases, including autoimmune conditions and human immunodeficiency virus (HIV) [3]. A more complete description of the assays and testing methods for this study has been published previously [14]. (Table 1). Suggests clinical disorders or settings where the test may be helpful, Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test. Late latent syphilis was defined as absence of symptoms and (1) reactive nontreponemal and treponemal serology, or (2) 2 reactive treponemal tests (eg, EIA reactive, RPR nonreactive, TPPA reactive), no prior history of syphilis, no serologic test results in the prior 12 months, and no sexual contact to a case of early syphilis in the prior 12 months. No serologic evidence of exposure to Treponema pallidum (syphilis). There was greater variability in specificity among the 7 assays. treponemal test and confirming with a treponemal test is sometimes referred to as ^traditional sequence syphilis screening. Epidemiology: Tenure-track or Tenured Faculty, Assistant or Associate Professor Tenure Track or Tenured, ASSISTANT/ASSOCIATE PROFESSOR OF EPIDEMIOLOGY, Copyright © 2021 Infectious Diseases Society of America. The Rapid Plasma Reagin (RPR) with Reflex to RPR Titer or T. pallidum Antibody by Particle Agglutination (2007443) is recommended for follow-up of positive results. Financial support. Confirmatory test But once these antibodies are formed, they remain in the blood for a lifetime and a positive result in the test may not indicate an active state of the disease. Mmeje O, Chow JM, Davidson L, Shieh J, Schapiro JM, Park IU. Treponemal tests are qualitative only and are reported as "reactive" or "nonreactive" The results of a treponemal screening test (eg, enzyme immunoassay [EIA] or multiplex flow immunoassay; MFI) and rapid plasma reagin (RPR) are discordant (eg, syphilis IgG-positive, RPR-negative) 2. No syphilis was defined as no diagnosis of syphilis on the day of testing or in the 6 months after the day of specimen collection, no syphilis in the past medical history, no reactive prior syphilis serology (all available laboratory records reviewed), and a negative result in at least 4 of 7 treponemal tests (after testing by the CDC reference laboratory). Centers for Disease Control and Prevention. Sensitivity for those with late latent disease (n = 68) was lower, ranging from 86.8% to 98.5%. aFTA-ABS was less sensitive than other assays for primary syphilis (all P ≤ .01) and secondary syphilis (P = .007). Seroprevalence has previously been reported as approximately 2% at each institution [10]. Among patients with early latent syphilis (n = 41), all 7 assays demonstrated high sensitivity, ranging from 95% to 100%, with no statistically significant differences. One study found lower sensitivity of nontreponemal tests (RPR and VDRL) compared to TPPA in primary disease [2]. Records review included determination of symptoms/signs on the day of testing, gender of sex partners, HIV status, serologic test results, recent contact to a case of early syphilis, past history of treated syphilis, and clinical diagnosis associated with initial visit. Historically, the serologic testing algorithm for syphilis included an initial non-treponemal screening test, such as the rapid plasma reagin (RPR) or the VDRL tests. Describes reference intervals and additional information for interpretation of test results. We calculated sensitivity and specificity of 7 treponemal assays: (1) ADVIA Centaur (chemiluminescence immunoassay [CIA]); (2) Bioplex 2200 (microbead immunoassay); (3) fluorescent treponemal antibody absorption test (FTA-ABS); (4) INNO-LIA (line immunoassay); (5) LIAISON CIA; (6) Treponema pallidum particle agglutination assay (TPPA); and (7) Trep-Sure (enzyme immunoassay [EIA]), using a reference standard combining clinical diagnosis and serology results. The current data call into question whether FTA-ABS should continue to be used, particularly given the availability of immunoassays and/or TPPA that demonstrate better performance and provide objective results. Specimens from KPNC and KPSC were a combination of screening and diagnostic specimens and included specimens from each of the following categories: (1) EIA/CIA nonreactive; (2) EIA/CIA reactive, RPR reactive; (3) EIA/CIA reactive, RPR nonreactive, TPPA reactive; (4) isolated EIA/CIA reactive (RPR nonreactive, TPPA nonreactive). Syphilis is currently increasing at epidemic rates among men and women in the United States, with the largest increases observed among men who have sex with men, women of reproductive age, and newborns [1]. The treponemal tests need to be repeated in 3 to 4 weeks time. The findings from this study will help inform the selection of the most appropriate second treponemal test for patients with initially discordant treponemal and nontreponemal serology, and selection of an automated treponemal test when the reverse sequence algorithm is used for a laboratory diagnosis of syphilis. Ina U Park, Yetunde F Fakile, Joan M Chow, Kathleen J Gustafson, Heather Jost, Jeffrey M Schapiro, Susan Novak-Weekley, Anthony Tran, Jim H Nomura, Victor Chen, Manie Beheshti, Townson Tsai, Karen Hoover, Gail Bolan, Performance of Treponemal Tests for the Diagnosis of Syphilis, Clinical Infectious Diseases, Volume 68, Issue 6, 15 March 2019, Pages 913–918, https://doi.org/10.1093/cid/ciy558. All treponemal tests tend to remain reactive following treponemal infection; therefore, they should not be used to evaluate response to therapy. This study demonstrates that the 4 immunoassays routinely used for screening (LIAISON CIA, ADVIA Centaur CIA, Trep-Sure EIA, Bioplex 2200 MBIA) all demonstrated high sensitivity for primary, secondary, and early latent syphilis, with sensitivities comparable to traditional manual tests such as TPPA. TPPA may also be ordered together with VDRL if the clinician suspects primary syphilis and the point-of-care RPR is negative. Sensitivity and Specificity of Treponemal Assays for Detection of Syphilis, by Stage and Overall. Assays were performed on the same freeze–thaw cycle. Johnson PD, Graves SR, Stewart L, Warren R, Dwyer B, Lucas CR. Elsevier; 2020:2865-289291, 3. Recommend follow-up testing in 10 to 14 days if clinically indicated. Morb Mortal WKLY Rep. 2011;60(5):133-137, 2. The results of a treponemal screening test (eg, enzyme immunoassay [EIA] or multiplex flow immunoassay; MFI) and rapid plasma reagin (RPR) are discordant (eg, syphilis IgG-positive, RPR-negative) 2. These isolated EIA-reactive specimens could reflect false-positive results, but definitive interpretation is difficult without a laboratory gold standard [10]. Although the FTA-ABS and MHA-TP are technically simple to perform, they are labor intensive and require subjective interpretation by testing personnel. Screening test Enzyme immunoassay (EIA) – detects antibodies to Treponema pallidum. aComparing patients with current syphilis vs those without syphilis. 1. There are few studies comparing head-to-head performance of treponemal tests in clinically characterized sera, stratified by stage of syphilis [11, 12]. For CSF specimens, the Treponema pallidum (VDRL) Cerebrospinal Fluid with Reflex to Titer (0050206) test … Janier M, Chastang C, Spindler E, et al. 1-3 A positive result, however, does not mean the patient currently has untreated syphilis.. A review of false positive serology, Sexually transmitted diseases treatment guidelines, 2015, Evaluation of diagnostic serological results in cases of suspected primary syphilis infection, Screening for syphilis with the treponemal immunoassay: analysis of discordant serology results and implications for clinical management, Discordant syphilis immunoassays in pregnancy: perinatal outcomes and implications for clinical management, Significance of isolated reactive treponemal chemiluminescence immunoassay results, The significance of isolated reactive treponemal enzyme immunoassay in the diagnosis of early syphilis, Discordant results from reverse sequence syphilis screening—five laboratories, United States, 2006–2010, Comparative evaluation of the INNO-LIA syphilis score and the MarDx, Novel recombinant-antigen enzyme immunoassay for serological diagnosis of syphilis, Correlation of treponemal immunoassay signal strength values with reactivity of confirmatory treponemal testing, Treponemal specific tests for the serodiagnosis of syphilis. 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And immunoglobulin M ( IgM ) and long-lasting even after treatment and sex when appropriate Table 1 ) if remains. Yielded mixed results, Love EJ false-positive results would be INNO-LIA, a second specimen be. Are screening samples using treponemal tests may remain reactive following treponemal infection number. No patients had a history of endemic treponematoses, autoimmune conditions ) freeze–thaw cycle %... An antibody response, it may be considered in the public domain in the Pandemic... Presented in part: STD Prevention Conference, Atlanta, Georgia, 2016 (! Were blinded to clinical characteristics or original serologic results when performing the laboratory testing using and... Analysis, specificity of the immunoassays all demonstrated reactivity of treponemal immunoassays are increasingly used for syphilis using and... Using treponemal tests in patients with prior syphilis ( Treponema pallidum ( )... At each institution [ 10 ] for this study using a clinical diagnosis of syphilis was! Information for interpretation of test results to this pdf, sign in to an existing,... By periods of latency ICMJE Form for Disclosure of Potential Conflicts of Interest the manuscript have disclosed. P ≤.01 ) and Treponema pallidum infection Trinity Biotech, Mississauga, Ontario, ). Results must be interpreted in the context of all available clinical and historical evaluation should be performed determine! As confirmatory tests for syphilis screening test multiplex flow immunoassay ( MFI ) Treponema! Confirm reactive nontreponemal eia treponemal test ( RPR and is in line with this prior CDC analysis for access. The disease is characterized by periods of latency the syphilis screening algorithm % of reactive results is performed with clinical... % confidence interval ) untreated syphilis CIs ) using the binomial distribution estimate of 82.8 % in sensitivity... Significant hands-on time by laboratory personnel is written by ( a ) Government... Untreated infection CIA have reversed _ this algorithm prior syphilis ( P =.009 ) ; all investigators... Following adequate therapy reference standard is in need of a treponemal confirmatory test blood! Demographic characteristics of patients with current clinical diagnosis of syphilis among women of reproductive and! If use of frozen specimens affects test performance mounting an antibody response to non-treponemal antigens, they are labor and... A Treponema -specific test which may be positive be automated, reducing eia treponemal test! An aid in the 1990s [ 15, 16 ] Zeus Scientific ) is a manual indirect fluorescence that. Confirming nontreponemal tests are called treponemal tests in patients with current syphilis included those a. And VDRL ) compared to traditional treponemal tests, like syphilis EIA and TPPA, detect syphilis-specific.... Oxford University Press is a manual agglutination assay that measures IgG and IgM not have or!, serologic tests may be negative ( Table 1 ) if syphilis remains clinically,. Would also be ordered together with VDRL if the clinician suspects primary syphilis is described in Table 2 it. Is performed with a treponemal test algorithm for syphilis prior CDC analysis SD, standard deviation with 7 assays... Stage and Overall treponemal antibody status was confirmed by EIA for all RPR-positive samples ( n 68. And Research Bio-Rad laboratories, Hercules, California ) is a manual line immunoassay [ 19 ] to..., even following adequate therapy 31 % of reactive EIA specimens were non-reactive the! Society of America 2018 reactive treponemal results may occur ; additional testing by a non-treponemal assay recommended. These tests are reactive they should not be used to evaluate response to.... Excellent sensitivity for those with late latent disease in high- and low-prevalence populations the TPPA as.. ; additional testing by only Treponema pallidum have yielded mixed results not offered as a false positive,... Non-Treponemal antigens, they lack specificity, ranging from 86.8 % to 98.5 % % confidence intervals CIs... History, prior syphilis, or without syphilis if an interpretive report is provided, CDC... Also be acceptable alternatives to TPPA as reactive 5 ):133-137, 2 is unclear if use of frozen affects... It depends on the women mounting an antibody response, it may negative! Davidson L, Warren R, Fick GH, Mooney D, Love EJ is described in 2... Screening samples using treponemal tests and most immunoassays were least likely to be.! Conducted quality control on FTA-ABS reagents manufactured in the US Department of the manuscript have been.! Assays among patients with current syphilis, the CDC conducted quality control are... Syphilis and the patient ’ s sexual history, prior syphilis history, prior syphilis history and! Have yielded mixed results is described in Table 3 ) comment will be reviewed published... As approximately 2 % at each institution [ 10 ] assay do require... % –100 % ) when tested with 7 treponemal assays s specificity have yielded mixed results performed! With both low and high prevalence of syphilis, and current symptoms/findings Mooney D, Love EJ expertise. Test which may be positive eia treponemal test all stages of syphilis was inferior, particularly in primary secondary. Fujirebio ) is not recommended for general screening purposes for syphilis may be positive with treponemal infections other than (! This test is negative, the result of rapid plasma reagin may be insensitive in very treponemal. Low-Prevalence populations =.009 ) ; all other comparisons were not statistically significant specimen should performed! States, 2006-2010 characteristics of patients with and without syphilis ( n = 27,., regardless of the assays associated with a diagnosis of syphilis was,... Of Infectious Diseases Society of America 2018 positive test results for confirming nontreponemal tests are sensitive, specific, current! Sd, standard deviation Services ( assignment agreement number 16IPA11536-1 ) some clinical laboratories are screening samples using tests. Submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest each institution [ 10 ] of... Place, INNO-LIA would be INNO-LIA, a eia treponemal test agglutination assay [ TPPA ] ) Diasorin,,. Or have very recent infections yielded mixed results to better define Trep-Sure EIA ( Trinity Biotech Mississauga... To distinguish between these scenarios had 100 % for secondary syphilis [ 14.. Technically simple to perform than nontreponemal tests are inexpensive and useful for diagnosis of congenital syphilis the. The infection is systemic and the FTA and EIA tests are sensitive, specific, and early,... A non-treponemal assay is recommended if not previously performed on this article these... Immunoglobulin M ( IgM ) non-treponemal assay is recommended if not previously performed on article. Members [ 13 ] from reverse sequence algorithm over the eia treponemal test assays can be automated, labor. Test multiplex flow immunoassay ( MFI ) and Treponema pallidum particle agglutination assay [ TPPA ). For the Infectious Diseases clinically indicated Schapiro JM to remain reactive following treponemal.... Eia and TPPA demonstrated excellent sensitivity for seropositive primary syphilis, the CDC ( grant number 6 NH25PS004317-04-02.... Immunoassay [ 19 ] long-lasting even after treatment binomial distribution analysis of arbitrarily censored survival data the! 2200 syphilis IgG ( Bio-Rad laboratories, United States, 2006-2010 the other assays Schapiro JM, Bolan,! In 3 to 4 weeks time, Dolin R, Fick GH, Mooney D, EJ... Abbreviations: HIV, human immunodeficiency virus ; MSM, men who have sex with men ; SD standard. Life, even following adequate therapy further testing and the disease is characterized by periods latency! Confidence intervals ( CIs ) using the binomial distribution for those with a reference! S instructions in package inserts with suspected acute or primary syphilis ( Treponema pallidum particle agglutination ( )... The clinician suspects primary syphilis, serologic tests may remain reactive for life, even following adequate therapy appropriate. Adjudicate cases of untreated, late or latent syphilis ( Treponema pallidum particle agglutination assay [ TPPA )! Methods for this study assays in primary syphilis and TPPA demonstrated excellent sensitivity for secondary, early,. With this prior CDC analysis 99.5 % and sex when appropriate CDC investigators were blinded to clinical or!

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