A Reanalysis of IgM Western Blot Criteria for the Diagnosis of Early Lyme Disease

Abstract

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.

Multiplex Immunoassay for Lyme Disease Using VlsE1-IgG and pepC10-IgM Antibodies: Improving Test Performance through Bioinformatics

“…Of all false-positive Western blots in the current study, 79% were due solely to IgM antibody, illustrating the limitations associated with that assay (36). If achieving 99% specificity among the healthy population is an important benchmark from a public health perspective (2), then specificity among our EIA-reactive controls would need to be improved to at least 93.6%.…”

C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

“…Western blots also require subjective interpretations, and some lack specificity (11,36) or are less sensitive than IFA or ELISA (6,18,35). This can cause confusion, especially during early Lyme disease or when patients have less specific symptoms or little risk of a tick bite (29,31). Tests that confirm Lyme disease by detecting borreliacidal antibodies can be more accurate than the two-test system (6), but the technical complexity and requirement for live spirochetes remain problematic.…”

Outer Surface Protein C Peptide Derived from Borrelia burgdorferi Sensu Stricto as a Target for Serodiagnosis of Early Lyme Disease

“…Early intervention is therefore critical to disease outcome. Unlike most bacterial diseases, in which the presence of the pathogen can be defined microbiologically by direct observation, culture, or PCR, Lyme disease is defined indirectly (9)(10)(11)(12). EM is the classic marker of early infection and is considered pathognomonic in areas of endemicity (9).…”