Biological False Positive Reactions Research Articles

Evolution of Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disease characterized by thrombosis and/or pregnancy complications caused by antiphospholipid antibodies (aPL). The history of APS can be traced back to observations made during screening programs for syphilis conducted in the mid-20th century, with identification of patients with the so-called biological false-positive serological reactions for syphilis. Initial observation linking aPL with recurrent miscarriages was first reported more than 40 years ago. Since then, our understanding of the pathogenesis and management of APS has evolved markedly. Although APS is an autoimmune disease, anticoagulation mainly with vitamin K antagonists (VKAs) rather than immunomodulation, is the treatment of choice for thrombotic APS. Direct acting oral anticoagulants are inferior to VKAs, especially those with triple-positive APS and arterial thrombosis. Inflammation, complement activation, and thrombosis in the placenta may contribute to pathogenesis of obstetric APS. Heparin, mainly low-molecular-weight heparin, and low-dose aspirin represent the treatments of choice for women with obstetric complications. Increasingly, immunomodulatory agents such as hydroxychloroquine for thrombotic and obstetric APS are being used, especially in patients who are refractory to present standard treatment.

COMPARISON STUDY OF SEMI-QUANTITATIVE RPR TEST AND TPHA FOR SERODIAGNOSIS OF SYPHILIS AT A TERTIARY CARE HOSPITAL, UDAIPUR, RAJASTHAN

Areactive RPR should always be conrmed with treponemal test like TPHAin suspected syphilis patients to rule out biological false positive cases. It is important to nd an alternative to TPHA as it is frequently not available in resource limited health care facilities of developing nations like India. Aim:Aim of our study is to evaluate semi-quantitative RPR test and TPHAin serological diagnosis of syphilis in resource limited health care facilities. Methodology: A retrospective cross sectional study from January 2020 to December 2021 was conducted on 116 suspected cases of syphilis. All cases were tested for qualitative RPR test, semi-quantitative RPR test ant TPHA test. Serum samples that are positive in qualitative RPR test but negative in TPHAwere referred to as biologic falsepositive (BFP) reactions. Results:We found 32 (27.58%) biological false positive (BFP) cases in dilutions 1:8 or below on semi quantitative RPR test. No BFP case was found in dilutions 1:16 or more. BFP can occur in any age group. We have noted that female 25(21.55%) were showing more BFP cases in our study. Conclusions: No biological false positive reaction has been found in above 1:8 dilution of RPR test. Semi-quantitative RPR test results in 1:16 or more dilution is equivalent to TPHAresults for diagnosis of syphilis.

Seroprevalence of syphilis by venereal disease research laboratory test and biological false positive reactions in different patient populations: Is it alarming? Our experience from a tertiary care center in India, 2020;41:43-46.

Seroprevalence of syphilis by venereal disease research laboratory test and biological false positive reactions in different patient populations: Is it alarming? Our experience from a tertiary care center in India, 2020;41:43-46.

The characteristics of beta 2-glycoprotein I-dependent anticardiolipin antibody and blood coagulation status in subjects with classical biological false-positive syphilis reactions

Anticardiolipin antibody (ACA) includes beta2-glycoprotein I-dependent (β2-GPI-dependent) and β2-GPI-independent forms. The appearance of β2-GPI-dependent ACA and its association with blood coagulation have never been investigated in subjects with classical biological false-positive syphilis reactions (CBFP). In total, 146 CBFP subjects, 465 syphilis patients and 64 presumed antiphospholipid antibody syndrome (pAPS) patients were enrolled, and β2-GPI-dependent ACA IgA/IgG/IgM and anti-β2-GPI IgA/IgG/IgM antibodies were detected via chemiluminescence assay. Conventional blood coagulation indices were measured to analyze their associations with these autoantibodies. In current study, the positive rate of β2-GPI-dependent ACA in CBFP subjects was 22.60%, which was significantly higher than that in syphilis patients (3.87%) (P < 0.001) and similar to that in pAPS patients (32.81%) (P = 0.119). The predominant autoantibody isotypes were IgG in CBFP subjects and pAPS patients and IgM in syphilis patients. Positive autoantibody rates were independent of rapid plasma reagin titers. CBFP and pAPS subjects had longer prothrombin times (P < 0.001) and activated partial thromboplastin times (APTTs, P < 0.001) but lower fibrinogen concentrations (P = 0.022) and platelet counts (P < 0.001) than syphilis patients. APTTs were prolonged in CBFP, syphilis and pAPS subjects with positive autoantibodies compared with those in subjects with negative autoantibodies (P < 0.05). In conclusion, ACAs in CBFP and syphilis subjects are heterogeneous; β2-GPI-dependent ACA constitutes a significant proportion of ACAs in CBFP subjects, while β2-GPI-independent ACA predominates in syphilis patients. CBFP subjects are more prone to blood coagulation disorders than syphilis patients, and these autoantibodies may impact the intrinsic coagulation cascade in CBFP subjects, similar to pAPS patients.

Seroprevalence of syphilis by VDRL test and biological false positive reactions in different patient populations: Is it alarming? Our experience from a tertiary care center in India.

Introduction:Many centers for sexually transmitted infections in India perform only a single screening assay for diagnosis of syphilis which may yield biological false positive (BFP) reactions.Aims and Objective:The aim of this study was to determine the true picture of seroprevalence of syphilis and BFP reactions in different patient groups.Materials and Methods:A total of 57,308 serial serum samples obtained over a period of 5 years from different patient groups were screened by venereal disease research laboratory (VDRL) test both qualitatively and quantitatively. VDRL reactive sera were confirmed by Treponema pallidum hemagglutination (TPHA) test.Results:The overall seroprevalence of syphilis by VDRL test was 1.27%, and BFP rate in test population was 0.14%. The rate of BFP reactions among total tested male (0.44%) and female (0.1%) patients differs significantly. Out of 733 VDRL reactive samples, 81 were BFP, i.e., BFP reaction is occurring at a frequency of 11% of the total VDRL reactive samples (ratio of 8:1 for true positives/BFP). Similarly, among antenatal cases, almost 24% of the total VDRL reactive samples were BFP, or for every 116 true positives, there were 37 (almost one-third) BFP.Conclusion:Although the overall seroprevalence of syphilis is low; the frequency of occurrence of BFP reactions is quite alarming. Hence, treponemal test must be used for confirmation of VDRL reactive sera.

The chequered history of the antiphospholipid syndrome

Consideration of the chronology of advances in medical knowledge can provide useful insights into the pathogenesis, diagnosis and treatment of diseases. The antiphospholipid syndrome is an enigmatic disorder and this is reinforced by the misleading associated terminology, the adoption of which results directly from early discoveries relating to the condition. Thus the target antigen of the causative autoantibodies in antiphospholipid syndrome does not reside on phospholipid, and the frequently associated lupus anticoagulant is not restricted to subjects with systemic lupus erythematosus and, paradoxically, despite causing prolongation of clotting times in vitro it is associated with a pronounced tendency to thrombosis. Recognition of the antiphospholipid syndrome has its origins in the identification of subjects with so-called biological false-positive serological reactions for syphilis in the middle years of the last century. Since that time there have been considerable advances in our understanding of the pathogenesis of the disease and the clinical manifestations and associations, improved diagnostic accuracy and an evolving evidence base for optimal therapy. However many gaps in our knowledge remain.

Characterization of the classical biological false-positive reaction in the serological test for syphilis in the modern era

To characterize the CBFP reaction in the modern era, we analyzed the results of parallel rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) tests from a total of 63,765 blood samples obtained at Zhongshan Hospital in the Medical College of Xiamen University from May 2008 to February 2013. Among the 63,765 tested blood samples, 206 (0.32%) had the CBFP reaction. In multivariate analysis, an increased likelihood of the CBFP reaction was associated with female subjects, subjects ≥80years old, and subjects between 16 and 35years old (P<0.05). The CBFP reaction occurred in association with 17 categories of disease, including 60 types of diseases, in the 206 subjects. To our knowledge, a number of these diseases had not been previously reported to be associated with the CBFP in the RPR test, including false labor, megaloblastic anemias, aplastic anemias, redundant prepuce, congenital malformation of heart, and salpingitis. Among the 206 patients with the CBFP reaction, 35 patients were subjected to follow-up for five years. 26 out of 35 these patients were at a 1:1 initial RPR titer, 8 out of 35 patients were at a 1:2 initial RPR titer, and 1 out of 35 patients were at a 1:4 initial RPR titer. 30 subjects had their RPR seroreverted. In our opinion, additional CBFP research using a large sample population will contribute to the identification of additional underlying serious disorders that are not related to syphilis. Such results could be useful for the prediction and diagnosis of these diseases.

Evaluation of the usefulness of Treponema pallidum hemagglutination test in the diagnosis of syphilis in weak reactive Venereal Disease Research Laboratory sera

Background and Objectives:Biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test used for diagnosis of syphilis is a cause for concern. The use of the VDRL as a screening procedure is challenged by some studies. The aim of this study is to determine the prevalence of BFP reactions in different subject groups and to assess the usefulness of Treponema pallidum hemagglutination (TPHA) test in low titre VDRL reactive sera.Materials and Methods:A total of 5785 sera from sexually transmitted diseases (STD) clinic attendees, antenatal clinic attendees, husbands of antenatal cases, peripheral health centres attendees (representing community population) and from patients referred from different OPDs/wards were screened for BFP reactions by the VDRL test. Sera reactive in the VDRL test were confirmed by the TPHA test.Results:Out of 80 qualitative VDRL reactive sera, 68 had <1:8 titre on quantitation and TPHA was positive in 59 samples, indicating BFP reactivity in 0.2% in all the subject groups. BFP was nil in the community population. The male-to-female ratio of BFP reactions was 2:1. VDRL and TPHA positivity was highest (76%) in the age group of 20-29 years. The seroprevalence of syphilis varied from 0.4% to 3.5% in different patient groups.Conclusions:The results of this study highlight that the TPHA positivity was high (86.8%) in sera with VDRL titre less than 1:8. Therefore, for the diagnosis of syphilis, it is recommended that a confirmatory test such as TPHA should be performed on all sera with a reactive VDRL regardless of its titre.

Evaluation of the usefulness of Treponema pallidum hemagglutination test in the diagnosis of syphilis in weak reactive Venereal Disease Research Laboratory sera.

Biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test used for diagnosis of syphilis is a cause for concern. The use of the VDRL as a screening procedure is challenged by some studies. The aim of this study is to determine the prevalence of BFP reactions in different subject groups and to assess the usefulness of Treponema pallidum hemagglutination (TPHA) test in low titre VDRL reactive sera. A total of 5785 sera from sexually transmitted diseases (STD) clinic attendees, antenatal clinic attendees, husbands of antenatal cases, peripheral health centres attendees (representing community population) and from patients referred from different OPDs/wards were screened for BFP reactions by the VDRL test. Sera reactive in the VDRL test were confirmed by the TPHA test. Out of 80 qualitative VDRL reactive sera, 68 had <1:8 titre on quantitation and TPHA was positive in 59 samples, indicating BFP reactivity in 0.2% in all the subject groups. BFP was nil in the community population. The male-to-female ratio of BFP reactions was 2:1. VDRL and TPHA positivity was highest (76%) in the age group of 20-29 years. The seroprevalence of syphilis varied from 0.4% to 3.5% in different patient groups. The results of this study highlight that the TPHA positivity was high (86.8%) in sera with VDRL titre less than 1:8. Therefore, for the diagnosis of syphilis, it is recommended that a confirmatory test such as TPHA should be performed on all sera with a reactive VDRL regardless of its titre.

VDRL test and its interpretation

Venereal disease research laboratory (VDRL) test is a nontreponemal test, used for screening of syphilis due to its simplicity, sensitivity and low cost. Prozone phenomenon and biological false positive (BFP) reaction are two shortcomings of this test. Quantitative estimation of VDRL is essential in treatment evaluation. CSF VDRL test is very specific for neurosyphilis though its sensitivity is low. Interpretation of VDRL in HIV infection is incompletely understood.

Hepatitis C virus infection and biological falsepositive syphilis test: a single-center experience

Rapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP). There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) infection. This study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV infection. A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this study. Hepatitis C serology was determined by a second generation ELISA test for HCV antibody. Syphilis serology was determined by the RPR test. Those subjects with reactive RPR positive underwent the TPHA test. Demographics and laboratory data were collected by trained clinicians. Among 2656 patients, 111 (4.2%) had a reactive RPR test. Of the 111 patients who were subjected to reactive RPR test, 30 (27.0%) showed HCV(+)/RPR(+). Of 5600 healthy controls, 80 (1.4%) had a reactive RPR test. Fourteen (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA test. These represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P<0.001). A significantly increased prevalence shown by false-positive tests for syphilis was observed in elderly HCV-seropositive patients. BFP-HCV positive group had a higher prevalence of eosinophilia. The eosinophil abnormality was compared between the patients and controls (66.7% vs 21.4%, P=0.0043). No significant results were observed in antinuclear antibodies, antiphospholipid and complement (C3, C4) (P>0.05). The data of this study demonstrate that HCV infection is associated with a false-positive RPR test. In this study BFPs were significantly more common in HCV positive patients compared to HCV-negative ones. Eosinophil abnormality can be considered as a predictor for BFP. Excessive BFPs must be considered in assessing the frequency of syphilis in a HCV-positive population and the importance of the treponemal specific serologic test should be emphasized for a diagnosis of syphilis in such population.

An immunofiltration device for the simultaneous detection of non-treponemal and treponemal antibodies in patients with syphilis

ObjectiveThe development of a rapid immunofiltration (flow-through) test for the simultaneous detection of non-treponemal and treponemal antibodies in the serum of patients with syphilis.MethodsThe assay is rapid, inexpensive, and requires...

Prevalence of syphilis and biological false positive reactions in VDRL test among injecting drug users: A preliminary study

Prevalence of syphilis and biological false positive reactions in VDRL test among injecting drug users: A preliminary study

Biological false-positive tests comprise a high proportion of Venereal Disease Research Laboratory reactions in an analysis of 300,000 sera

This retrospective study on syphilis screening at the sexually transmitted infection (STI) unit of a University Department emphasizes the necessity of a treponemal-specific test as the appropriate screening test. The Venereal Disease Research Laboratory (VDRL) test for syphilis screening may, under certain circumstances, yield positive results in patients not infected with Treponema pallidum, a phenomenon referred to as biological false-positive (BFP) VDRL test. The aim of this study was to determine the frequency of BFP tests in a large sample of sera. In this retrospective study, we analysed the results of parallel VDRL and T. pallidum haemagglutination (TPHA) testing of a total of 514,940 blood samples obtained from patients at the Vienna General Hospital between January 1988 and November 1999. Patients' sera with incomplete data on stage and sex and duplicate sera were excluded, leaving 300,000 sera for analysis. The seroprevalence for syphilis was 1.77% (n = 5320), as determined by a positive TPHA test. It was significantly higher in male than in female patients (2.03% versus 1.58%, P<0.001). Of the patients reactive in the TPHA test, 3257 (61.2%) were negative in the VDRL. With regard to reactivity in VDRL testing, 2799 patients (0.92%) of the study population were positive, of whom 736 (26%) were biological false positive. BFP reactivity was found in 0.24% of all patients and was significantly higher in women than in men (0.27% versus 0.20%, P<0.001) and in patients over 60 years of age (0.34%) as compared with those under 60 (0.25%, P<0.001). This proportion might be even higher, as reactivity in the VDRL at 1:0 and 1:2 dilutions without a positive treponemal test was not reported. The subgroup of HIV-positive patients (n = 1415) revealed a 10-fold higher rate of BFP tests (2.1% versus 0.24), an effect being statistically significant. In a low syphilis prevalence population, BFP reactions comprise a high proportion of all VDRL reactors. Therefore, the use of the VDRL as a screening procedure is challenged.

Non-lupus nephropathy associated with antiphospholipid antibodies

Renal biopsy was performed in a 12-year-old girl with hematuria and proteinuria which was first detected at the age of 7, and the findings were the mesangial proliferative glomerulonephritis with IgG and C3 deposits. The routine blood examination for the biopsy disclosed the presence of the prolonged activated partial thromboplastin time and the biological false positive reaction in the syphilis test. These results led us to the further investigation, which revealed the presence of high titers of anticardiolipin antibodies. Since this girl presented no extra-renal symptoms of systemic lupus erythematosus (SLE) and had negative serologic tests for SLE, we hypothesize that her nephritis is closely related to antiphospholipid antibodies.

Syphilis serology and HIV infection in Harare, Zimbabwe.

OBJECTIVE: To determine the reliability of serological tests in detecting syphilis in a factory worker cohort and examine the impact of concurrent HIV infection on serological tests for syphilis. METHOD:...

False-positive tests for syphilis associated with human immunodeficiency virus and hepatitis B virus infection among intravenous drug abusers. Valencian Study Group on HIV Epidemiology.

The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76-2.83] was observed for HIV-seropositive intravenous drug abusers; biological false-positive reactions were also more frequent (OR 1.73, 95% CI 1.30-2.31) among intravenous drug abusers who were hepatitis B virus seropositive but not among those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48-1.69). Among homosexuals, the association between HIV and biological false-positive reactions was restricted to subjects who were also intravenous drug abusers, indicating the crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers with a previous biological false-positive reaction yielded a false-positive result in their subsequent visit.

Syphilis serology in human immunodeficiency virus infection: evidence for false-negative fluorescent treponemal testing.

Injection drug users were assessed serologically for human immunodeficiency virus infection and syphilis every 6 months. Treatment histories were reviewed for any high-titer biologic false-positive (BFP) reactors, that is, persons with rapid plasma reagin (RPR) titers > or = 1:4 and negative results for fluorescent treponemal antibody absorption (FTA-ABS) tests. Selected sera were analyzed further by immunoblotting for the presence of antibodies reactive with specific Treponema pallidum antigens. Of 112 BFP reactors, 35 (31%) had at least one RPR test reactive at a dilution >1:8 while the FTA-ABS test remained nonreactive. Five reactors (4.5%) converted from nonreactive to reactive by FTA-ABS test; 4 (3.6%) were reactive by FTA-ABS tests but later became nonreactive. Antibodies to T. pallidum membrane antigens were detected in some samples that were persistently nonreactive by FTA-ABS test. Serologic patterns over time, along with very high-titer BFP reactions and reactivity with T. pallidum-specific antigens, suggest that some BFP reactions may represent FTA-negative syphilis.

Are you sure it's syphilis? A review of false positive serology.

This article on false positive serological reactions for syphilis reviews the rapid developments which have taken place in the serodiagnosis of syphilis in recent years since the advent of the AIDS epidemic. An overview of non-specific and specific treponemal serological tests in relation to acute and chronic biological false positive reactions is followed by closer consideration of syphilis serology in the context of HIV infection, pregnancy and other conditions which may produce false positive reactions.

Measuring cardiolipin antibodies

EDITOR,—Cardiolipin antibodies have been variously cited as a risk factor for cerebral thrombosis1 2 or splanchnic venous thrombosis,3 or as an epiphenomenon loosely associated with vascular disease.4 Cardiolipin antibodies seem to represent a family of low affinity antibodies which share a limited ability to bind to bovine cardiolipin. This rather artificial assay system, dependent on the binding of a low affinity human autoantibody to a non-primate, cross reacting substract of unproved relevance, can lead to some rather bizarre comparisons. Cardiolipin antibodies are probably identical to the chronic biological false positive Wasserman reaction described more than two decades ago in relation to systemic lupus erythematosus …