There are a number of reasons for the inaccuracy of Lyme testing, including use of less antigenic laboratory spirochetal strains in the commercial test kits, elimination of important spirochetal target proteins from those kits, and lack of standardization of the commercial Lyme assays. 111 – 113 Gender bias may also be a factor: while chronic Lyme disease is reportedly more common in women, the two-tier test system yields positive results more often in men. 116 Although a newer ELISA targeting the conserved VlsE or C6 peptide of B. burgdorferi has been developed, this test system does not appear to be more sensitive than the two-tier approach. 117 , 118 While molecular testing has been useful for diagnostic confirmation and treatment monitoring in other illnesses, molecular testing for B. burgdorferi has been unreliable, and newer molecular techniques targeting tick-borne agents remain unproven and expensive. 119 , 120 Assays for more accessible surrogate markers of Lyme disease have yet to be accepted by the general medical community. 121 – 125 Thus testing for Lyme disease remains problematic.A newer approach to Lyme testing involves the use of proteomics. 126 , 127 Based on the known genetic make-up of the spirochete, numerous proteins can be generated in vitro and tested for antigenicity using Lyme patient sera. In this manner, novel target proteins can be identified, and conceivably new test systems based on these proteins can be developed without even knowing the function or location of the antigens within the spirochete. 126 Work on these proteomic-based test systems is already in progress, but extensive clinical validation will be required to bring those tests to market. Nevertheless the proteomic approach to Lyme testing holds great promise for more accurate serological diagnosis, and development of proteomic testing for tick-borne diseases provides a useful diagnostic model for other chronic and elusive infections. Beyond proteomics, novel test systems that exploit electromagnetic signals generated by bacterial DNA sequences may also prove to be effective in the diagnosis of chronic Lyme disease. 128 , 129
As we enter a new decade, clinical testing for Lyme disease remains abysmal. 110 – 115 The two-tier algorithm recommended by the Centers for Disease Control and Prevention utilizes a screening enzyme-linked immunosorbent assay (ELISA) or immunofluorescence assay followed by a confirmatory Western blot. Although this approach has a high test specificity, the sensitivity of the two-tier approach in Lyme disease patients tested at least 4 to 6 weeks after infection is only 44% to 56%, which is inadequate for a clinical diagnostic test and, by comparison, far below the 99.5% sensitivity of diagnostic HIV testing. 110 , 114 , 115 Furthermore, the misconception that two-tier testing is highly sensitive for Lyme disease patients with persistent arthritic or neurologic symptoms derives from a study that selected patients based on positive Lyme testing and then showed high levels of two-tier test positivity. 115 This circular reasoning is a systematic problem with the evaluation of Lyme testing.