Diagnosis Of Early Lyme Disease Research Articles

Detection of Immune Complexes Is Not Independent of Detection of Antibodies in Lyme Disease Patients and Does Not Confirm Active Infection with Borrelia burgdorferi

The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine. Using a B. burgdorferi whole-cell enzyme-linked immunosorbent assay (ELISA), we obtained positive PEG-IC results not only in patients with a history of LD, but also in individuals vaccinated with OspA vaccine. The frequency of positive PEG-IC ELISAs in OspA vaccinees was significantly higher with ELISA-reactive than with ELISA-negative unprocessed serum samples (P=0.001), demonstrating dependency between the tests. Similar results were found using samples from rhesus macaques infected with B. burgdorferi, uninfected macaques vaccinated with OspA, and controls. Therefore, testing for the presence of antibodies against B. burgdorferi in PEG-IC preparations is not more likely to reflect active infection than testing in unprocessed serum and should not be used in individuals who received the OspA vaccine.

A reanalysis of IgM Western blot criteria for the diagnosis of early Lyme disease.

A two-step approach for diagnosis of Lyme disease, consisting of an initial EIA followed by a confirmatory Western immunoblot, has been advised by the Centers for Disease Control and Prevention (CDC). However, these criteria do not examine the influence of the prior probability of Lyme disease in a given patient on the predictive value of the tests. By using Bayesian analysis, a mathematical algorithm is proposed that computes the probability that a given patient's Western blot result represents Lyme disease. Assuming prior probabilities of early Lyme disease of 1%-10%, the current CDC minimum criteria for IgM immunoblot interpretation yield posttest probabilities of 4%-32%. The value of the two-step approach for diagnosis of early Lyme disease may be limited in populations at lower risk of disease or when patients present with atypical signs and symptoms.

Systematic review of the treatment of early Lyme disease.

Lyme disease is a rapidly emerging infectious disease and there are still many unanswered questions with respect to appropriate laboratory tests required for diagnosis of early Lyme disease, types of antimicrobials required for treatment and duration of therapy. A qualitative systematic review was used to summarise the existing data for the treatment of early Lyme disease. Eleven antibacterial therapy trials and 3 cost-effectiveness analyses met the inclusion criteria for this review. Antibacterial regimens that have been studied include phenoxymethylpenicillin (penicillin V), amoxicillin, amoxicillin/probenecid, tetracycline, doxycycline, cefuroxime axetil, erythromycin, roxithromycin, azithromycin and ceftriaxone. The data support the use of oral beta-lactam antibacterials [phenoxymethylpenicillin (penicillin V), amoxicillin, cefuroxime axetil] and oral tetracyclines as effective first-line treatment modalities for early Lyme disease. Oral macrolides are considered second-line agents as their clinical efficacy has been less than that of the beta-lactams and tetracyclines. Courses of therapy ranging from 10 to 21 days are supported by the available evidence, although the optimal duration of therapy is unknown.

Analysis of ROC Curves Applied to the Diagnosis of Lyme Disease

I in the analysis of receiver operating I acteristic (ROC) curves is an ongoing activity in our education of residents in laboratory medicine; therefore, I was interested to see the data presented by Sivak et al 1 concerning the accuracy of IgM immunoblotting in confirming the clinical diagnosis of early Lyme disease. Areas under ROC curves can readily be calculated using spreadsheet methodologies and elementary principles of integral calculus 2 that date to the time of Newton and Leibniz. Many residents in pathology and laboratory medicine have difficulty with numerical images, as opposed to cellular images, and do not easily grasp the concepts of these area calculations. To assist them in appreciating the principle of area under the ROC curve, my colleagues and I developed an empirical technique for such measurements that is extremely accurate (error rate, ±

Accuracy of IgM Immunoblotting to Confirm the Clinical Diagnosis of Early Lyme Disease

A 2-test approach for the serologic diagnosis of Lyme disease has recently been proposed. A positive or equivocal result on a first-stage test (eg, an enzyme immunoassay) is followed by a Western immunoblot test. For a sample to be considered seropositive for Lyme disease, the immunoblot result must be positive. To assess the accuracy of IgM immunoblotting for detection of early Lyme disease and to establish interpretative criteria for a commercially available immunoblot assay. Serum samples from 44 patients with erythema migrans were tested by an IgM immunoblot assay. All patients were culture-positive for Borrelia burgdorferi. Serum samples from 2 different control groups were also tested. Interpretative criteria were developed using receiver operating characteristic curves. The presence of any 2 IgM bands was found to be the optimal criterion for a positive test result, and in patients with illness of less than 7 days' duration, this was significantly more sensitive than the criterion of any 2 of the 3 specific bands defined by the Centers for Disease Control and Prevention/Association of State and Territorial Public Health Laboratory Directors Lyme Disease Workgroup (P < .05). Specificity of the criterion of any 2 bands was 100% for 1 group of controls but only 96% for the more clinically relevant control group; this small difference had a large impact on the positive predictive value in populations at low risk for Lyme disease. Using a commercially available immunoblot test kit, the presence of any 2 IgM bands is proposed as a positive result. The predictive value of a positive IgM immunoblot result, however, is poor in patients with minimal clinical evidence for Lyme disease.

Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease

Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease

Recombinant Outer Surface Protein C Elisa For The Diagnosis Of Early Lyme Disease

To compare the sensitivity of a new ELISA for IgM antibodies to Borrelia burgdorferi that uses a recombinant outer surface protein C (rOspC) with those of a whole cell (WC) ELISA and an immunoblot assay for the diagnosis of early Lyme disease, serum specimens from 82 consecutive patients with physician-documented erythema migrans were analyzed. To compare the specificities of the three assays, serum specimens from 50 patients without a history of Lyme disease and from an area in which B. burgdorferi is not endemic were analyzed. The sensitivities of the WC ELISA, immunoblot assay, and IgM rOspC ELISA were 28%, 29%, and 46%, respectively, while the specificities were 100%, 100%, and 98%, respectively. The IgM rOspC ELISA is a convenient, readily automated, easily standardized serologic test that is significantly more sensitive for the diagnosis of early Lyme disease than either WC ELISA or immunoblot assay.

Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions.

Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease.