Borrelia burgdorferi is the causative agent of Lyme disease - the most common tick-borne disease in North America. However, the diagnosis of the disease has been problematic. Steere et al.2a reported that at least 80% of Lyme disease patients have a characteristic “bulls-eye', erythema migrans (EM) rash, and generally, the presence of this rash is considered the earliest and best indicator of infection. Recent health department statistics from Texas, Connecticut. and California, however, show that only 35-59% of Lyme disease patients present with an EM rash. rz, Detection is limited by the location of the tick-bite, the awareness of the person who was bitten, and the form of the rash. r2,26 If untreated, patients can go on to develop late Lyme disease characterized by . urdiu. ,
musculoskeletal, and neurological manifestations months to years ifter the initial tick bite. r8.20-23.22 Diagnosis at this stage can be even more difficult,
since the history of the rash and tick bite may be lacking and the symptoms are shared with a number of other diseases. Direct detection of the agent of Lyme disease using microscopy, culture, nucleic acid amplification. and antigen detection have limited sensitivity and/or specificitv.3 Therefore, the clinical presentation is usually supported by antibody detection using a two-tiered testing system in the United States.6 In this system, an enzyme-linked immunosorbent assay (ELISA) or immunofluorescence antibody (lFA) test is performed u, u , . . ""n.
Following a positive or indeterminate test, the diagnosis is confirmed using a Western Blot (WB) assay. However, even in early Lyme disease, only 33-
49% of patients have a positive ELISA test, r,2 and in late Lyme disease, the ELISA sensitivity may be as low as 79%. s Thus the screening assay can
miss truly positive patients. In an attempt to standardize Lyme testing, the Dearborn Conference held by the Centers for Disease Control and Prevention (CDC) and the Association of State and Territorial Public Health Laboratory Directors(ASTPHLD) in i995 recommended that all indeterminate and positive ELISA tests be confirmed by WB6 using the criteria published by Engstrom et al. Ior the IgM WBro and Dressler et al. for the IgG WB. s Neither of these academic studies valuated specimens from patients with other tick-borne diseases, nor did they attempt to diagnose late Lyme disease in patients months or years after the
initial tick bite. The Dearborn CDC criteria have been the standard for WB interpretation since that time.7 The CDC guidelines additionally state that IgM or IgG WB criteria should be used during the first four weeks ol illness, but only IgG criteria should be used beyond four weeks after the onset of disease, and WB testing should only be performed if the ELISA or IFA is positive or indeterminate. T To add to the problem of laboratorydiagnosis of Lyme disease, some B.
burgdorferi antigens are specific to the organism, while some antigens are shared with other microorganisms, and antibodies induced by these nonspecific
antigens may not necessarilyindicate Lyme disease. Lysates used to prepare WB tests vary in their composition with the strain used, and the antigenic composition of .8. burgdorferi proteins have variable expression under different culture conditions of the organism. T To add to the limitations of Lyme testing, antibody expression varies at different stages of the disease. era Because of these complex issues and the difficulties of laboratory diagnosis, Lyme disease can be underdiagnosed, especiallyin patients who present months after the initialbite with symptoms that mimic other conditions.
In an attempt to add to the current interpretation of Lyme WB assays, we determined the IGeneX WB assay specificity and sensitivity using IGeneX criteria and CDC criteria for both IgG and IgM WB using specimens from three groups of patients: those known to be infected with B. burgdorferi, those with other tick-borne diseases, and negative controls.