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Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.
An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding pr...
Contexts in source publication
Context 1
... in CSF. Reactivity to DbpA, BBK32, OspC, and IR6 in classified patient groups and controls are shown in Figure 1 and Table 3. ...Context 2
... the "Not Determined" group, 2 patients (12%) were positive to both DbpA and OspC, but the rest (88%) only showed reactivity to 1 antigen or none. All controls were either negative to all antigens or showed low reactivity to one of the antigens (Table 3 and 4). Antibodies in CSF as Related to Serum. ...Similar publications
Objectives:
Lyme disease is a vector-associated infectious disease, caused by the agent, spirochete Borrelia burgdorferi. Neurologic findings are observed in approximately 12% of the cases and termed Lyme neuroborreliosis (LNB). Lyme neuroborreliosis may manifest with different clinical neurologic manifestations.
Methods:
The study was conducted...
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Background
Current guidelines regarding Lyme neuroborreliosis [LNB] require the presence of intrathecal Borrelia burgdorferi-specific antibody production for the definite diagnosis of LNB. However, about 20% of early stage infections present without an elevated antibody index. Moreover, intrathecal B. burgdorferi specific antibody synthesis may per...
Background: Lyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.
Methods: Cultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12,...
Background and purpose
Residual symptoms after treatment of Lyme disease, sometimes called post‐treatment Lyme disease symptoms (PTLDs), are a matter of ongoing controversy. To guide treatment recommendations, a systematic review was performed of the available literature on specific treatment for PTLDs.
Methods
A systematic literature search of ME...
Neurological manifestations of Lyme disease are reported in 3%-12% of patients, with the most common form of presentation being meningoradiculitis. Other symptoms involving the central nervous system, such as myelitis or encephalitis, are rare (< 5 %). We report a case of a 66-year-old male, with a subacute extensive transverse myelitis, secondary...
Citations
... Of all performance characteristics determined in this study (i.e., sensitivity, specificity, PPV, and NPV), the sensitivity of the seven antibody assays to diagnose LNB among definite and possible LNB patients showed the largest variation (range: 47.1% to 100%), although none of the differences were statistically significant. In general, differences in sensitivity between antibody assays can be influenced by several factors, such as the antigens present in the assay (24,38,46). These antigens might be expressed at different time points (20, 21) or might not match the antigens expressed by the B. burgdorferi sensu lato strain causing disease due to inter-and intraspecies heterogeneity and/ (Table S3), which had an effect on the test result (Table 3 and S2). ...
The diagnosis of LNB is established by clinical symptoms, pleocytosis, and proof of intrathecal synthesis of Borrelia -specific antibodies. Laboratory diagnosis of LNB is challenging, and validated diagnostic algorithms are lacking.
... Fifty-seven of these had a case-control design, comparing a group of well-defined cases with a group of healthy controls or controls with diseases that could lead to cross-reactivity of the tests . Eighteen had a crosssectional design in which a more homogeneous sample of patients underwent both the serological assay(s) and the reference standard [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82]. Three studies were not used in the meta-analyses, either because they used immunoblot as a reference standard [76,79], or included asymptomatic cross-country runners with high IgG titers as controls [47]. ...
Background
Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe.
Methods
We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy.
Results
Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50 % (95 % CI 40 % to 61 %); neuroborreliosis 77 % (95 % CI 67 % to 85 %); acrodermatitis chronica atrophicans 97 % (95 % CI 94 % to 99 %); unspecified Lyme borreliosis 73 % (95 % CI 53 % to 87 %). Specificity was around 95 % in studies with healthy controls, but around 80 % in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches.
Conclusions
The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.
... In children in Europe, acute facial palsy and meningitis are common manifestations of LNB, even without preceding erythema migrans. [6][7][8] However, these manifestations are not specific to LNB. 6,[9][10][11][12] Thus, laboratory testing (serum and cerebrospinal fluid (CSF)) is needed to confirm the diagnosis of LNB and exclude other aetiologies of the neurological manifestations. ...
... Different types of antigen have been used for ELISA and immunoblotting methods on serum and CSF samples. 5,13,14 RevA, DbpA, DbpB, OspC, OspC peptide, VlsE, and IR6 peptide have been studied for diagnostic purposes in LD. 9,[15][16][17][18][19][20] Such antigens, produced as recombinant proteins or synthetic peptides, have increased the specificity of laboratory testing for LD, but the sensitivity of new antigens has been unsatisfactory. Our earlier study on adult patients suggested that antibodies to decorinbinding protein B (DbpB) in CSF might be beneficial in the diagnosis of LNB, especially as a marker of active infection. ...
... Laboratory testing included CSF cell counts and the measurement of anti-flagella antibodies in serum and CSF, together with exclusion of other neurological aetiologies. 9 Based on clinical features at admission and laboratory results, patients were divided into three groups: confirmed LNB (n = 24), possible LNB (n = 16), and non LNB (originally not determined) (n = 17). 9 In brief, the classification of patients with clinical symptoms indicative of LNB was as follows: The confirmed LNB group of patients had pleocytosis (median 195, range 7-442 Â 10 6 mononuclear cells/l in CSF) and either IgG or IgM or both anti-flagella antibodies in CSF. ...
Background: Laboratory support is needed to confirm the clinical diagnosis of Lyme neuroborreliosis (LNB). Antibodies to Borrelia-specific proteins have been used to improve serological diagnostics. The aims of this study were to assess the occurrence of antibodies to decorin-binding protein B (DbpB) in serum and cerebrospinal fluid (CSF) in children with LNB and to evaluate the performance of DbpB variants in the diagnosis of LNB in children.
Methods: Serum and CSF sample pairs were available from 57 children evaluated for LNB. Based on the presence of anti-flagella antibodies and pleocytosis in the CSF, patients were divided into three different groups: confirmed LNB (n = 24), possible LNB (n = 16), and non LNB (n = 17). Recombinant DbpBs from three Borrelia burgdorferi sensu lato species – Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii – were used in an ELISA to detect IgG antibodies.
Results: The sensitivity of variant recombinant DbpBs in serum and CSF samples varied between 0% and 46% and between 0% and 42%, respectively. In CSF, the most sensitive antigen was the DbpB variant from B. garinii.
Conclusions: Serum or CSF antibodies to DbpB do not appear to be beneficial in the laboratory diagnosis of LNB in children.
... In all patients, the routine laboratory testing for LNB in clinical practice -in addition to exclusion of other aetiologies by serology -includes assessment of CSF cell counts and serum and CSF anti-fl agella antibodies [10]. Based on the presence or absence of anti-fl agella antibodies and lymphocytic pleocytosis in CSF, patients were divided into 3 different groups: confi rmed LNB ( n ϭ 24), possible LNB ( n ϭ 16), and non-LNB ( N ϭ 17), as described previously [5,9]. In brief, patients with confi rmed LNB had pleocytosis (median 195, range 7 -442 ϫ 10 6 mononuclear cells per litre of CSF) and IgG and/or IgM anti-fl agella antibodies in CSF. ...
... 10.3109/00365548.2013.776700) . All patients were treated according to European guidelines (patients with confi rmed and possible LNB received antibiotic treatment) [1,9]. ...
... Characteristics of the 57 patients with clinical features indicative for LNB (modifi ed from Skogman et al.[9]).Table S1. Characteristics of the 57 patients with clinical features indicative for LNB (modifi ed from Skogman et al.[9]). ...
Background:
The diagnosis of Lyme neuroborreliosis (LNB) requires laboratory confirmation because neurological symptoms indicative of LNB are not specific. Recent studies have suggested that a chemokine, CXCL13, could have an important role in the diagnosis of LNB. The aim of this study was to assess CXCL13 levels in the cerebrospinal fluid (CSF) of children with LNB.
Methods:
CSF samples were available for 57 children with symptoms indicative of LNB. Based on the presence of anti-flagella antibodies and pleocytosis in CSF, patients were divided into 3 different groups: confirmed LNB (n = 24), possible LNB (n = 16), and non-LNB (n = 17). CXCL13 levels were determined with a commercial kit (Quantikine).
Results:
All 24 patients with confirmed LNB had elevated CXCL13 levels in CSF. Elevated CXCL13 was also observed in the majority of patients without anti-flagella antibodies in the CSF (possible LNB). Of the 17 non-LNB and 50 control samples, 1 was positive.
Conclusions:
In LNB, the production of CXCL13 in CSF seems to precede antibody production. Assessment of CSF CXCL13 may improve the diagnostics for children with possible LNB.
... More recently, since late 2010, all microbiology laboratories in England have been required to report diagnoses of Lyme disease under the Health Protection (Notification) Regulations. More sensitive diagnostic tools have also been developed [7][8][9][10] and there are now a greater number of diagnostic facilities in the UK. It is also possible that the number of people visiting Lyme endemic areas has increased due to the popularity of outdoor activity schemes [11,12]. ...
... The commercially available C6-peptide ELISA has been validated only for serum samples. Data on the performance of the C6-peptide ELISA performed on CSF for the diagnosis of LNB are limited and conflicting [14][15][16]. The aim of this study was to determine whether a C6-peptide-based ELISA can be used on CSF samples to diagnose early and late LNB patients, using a large cohort of well-defined patients and controls. ...
Clin Microbiol Infect 2011; 17: 1495–1500
Lyme neuroborreliosis (LNB) is a serious but treatable disease. The diagnosis of LNB poses a challenge to clinicians, and improved tests are needed. The C6-peptide ELISA is frequently used on serum but not on cerebrospinal fluid (CSF). Data on the sensitivity of the C6-peptide ELISA in CSF in patients suffering from LNB have been conflicting. Serum–CSF pairs from 59 LNB patients, 36 Lyme non-neuroborreliosis cases, 69 infectious meningitis/encephalitis controls and 74 neurological controls were tested in a C6-peptide ELISA. With the optimal cut-off of 1.1, the sensitivity of the C6-peptide ELISA for LNB patients in CSF was 95%, and the specificity was 83% in the Lyme non-neuroborreliosis patients, 96% in the infectious controls, and 97% in the neurological controls. These results suggest that the C6-peptide ELISA has a high sensitivity and good specificity for the diagnosis of LNB patients in CSF. The C6-peptide ELISA can be used on CSF in a clinical setting to screen for LNB.
Background
Lyme neuroboreliosis (LNB) is a tick-borne infection caused by the spirochete Borrelia burgdorferi sensu lato complex with various neurological manifestations. The recommended treatment for LNB in Swedish children has been ceftriaxone i.v. 50-100 mg/kg x 1 (< 8 years of age) or doxycycline p.o. 4 mg/kg x 1 (≥ 8 years of age) for 10-14 days. Studies on adult LNB patients have shown equal efficacy for ceftriaxone i.v. and doxycycline p.o., but no such studies have been performed on pediatric LNB patients. The aim of this study is to retrospectively evaluate clinical outcome in children with LNB who have received ceftriaxone i.v. as compared to doxycycline p.o.
Results
Clinical and laboratory data from three previously performed prospective studies on children with LNB (three cohorts, 1998-2014) were collected and retrospectively analyzed. A total of 321 Swedish children (1-19 years of age), who had received antibiotic treatment for LNB, were included. Clinical outcome at the 2-month follow-up (recovery/non-recovery) was evaluated, using Chi2 test and logistic multivariate regression analysis.
Out of 321 LNB patients, 194 children (60%) had received ceftriaxone i.v. and 127 children (40%) had received doxycycline p.o.. When comparing recovery/non-recovery between treatment groups, no difference in clinical outcome was found (p=0,217). Results did not change when incorporating relevant clinical and laboratory data into the logistic multivariate regression analysis.
Conclusion
In this large retrospective study, no difference in clinical outcome (recovery/non-recovery) was found, independent of age, when comparing children who received ceftriaxone i.v. with children who received doxycycline p.o., supporting an equal effectiveness for treatment of pediatric LNB patients. However, future randomized comparative treatment studies with non-inferiority design are warranted for evaluation of efficacy and safety of antibiotic treatment in pediatric LNB patients.
Introduction
Central nervous system (CNS) infections can be life-threatening and are often associated with disabling sequelae. One important factor in most CNS infections is a timely pathogen-specific treatment. The diagnostic methods available, however, do not always reach a satisfying sensitivity and specificity. In these cases, there is need for additional diagnostic biomarkers. Chemokines represent potential candidates as biomarkers, since they are an important pillar of the host immune response. The aim of this review is to discuss the diagnostic potential of cerebrospinal fluid (CSF) CXCL13 in patients with CNS infections.
Areas covered
Data were obtained from a literature search in PubMed up to October 2019. This review focusses on articles on the potential of CXCL13 as a diagnostic tool. The majority of identified studies aimed to characterize its role in two diseases, namely Lyme neuroborreliosis and neurosyphilis.
Expert opinion
CSF CXCL13 has a significant potential as a diagnostic and monitoring add-on marker in Lyme neuroborreliosis. Differences in study design, control groups and clinical parameters between studies, however, affect sensitivity, specificity and cutoff values, underlining the need of further studies to address these issues and pave the way for a generalized clinical practice.
The clinical diagnosis of Lyme borreliosis can be supported by various test methodologies; test kits are available from many manufacturers. Literature searches were carried out to identify studies that reported characteristics of the test kits. Of 50 searched studies, 18 were included where the tests were commercially available and samples were proven to be positive using serology testing, evidence of an erythema migrans rash, and/or culture. Additional requirements were a test specificity of ≥85% and publication in the last 20 years. The weighted mean sensitivity for all tests and for all samples was 59.5%. Individual study means varied from 30.6% to 86.2%. Sensitivity for each test technology varied from 62.4% for Western blot kits, and 62.3% for enzyme-linked immunosorbent assay tests, to 53.9% for synthetic C6 peptide ELISA tests and 53.7% when the two-tier methodology was used. Test sensitivity increased as dissemination of the pathogen affected different organs; however, the absence of data on the time from infection to serological testing and the lack of standard definitions for “early” and “late” disease prevented analysis of test sensitivity versus time of infection. The lack of standardization of the definitions of disease stage and the possibility of retrospective selection bias prevented clear evaluation of test sensitivity by “stage”. The sensitivity for samples classified as acute disease was 35.4%, with a corresponding sensitivity of 64.5% for samples from patients defined as convalescent. Regression analysis demonstrated an improvement of 4% in test sensitivity over the 20-year study period. The studies did not provide data to indicate the sensitivity of tests used in a clinical setting since the effect of recent use of antibiotics or steroids or other factors affecting antibody response was not factored in. The tests were developed for only specific Borrelia species; sensitivities for other species could not be calculated.
The prognosis of course and outcome of inflectional inflammatory diseases of central nervous system, indicators of inflammatory reaction and immune response in cerebrospinal liquor in patients has been investigated.
