Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States

Abstract

In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%-40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%-100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics.

Keywords: Borrelia burgdorferi; Lyme disease; PCR; United States; bacteria; guidelines; laboratory diagnosis; public health; serologic analysis; vector-borne infections.

Figure 1

Lyme disease cases (black dots) reported by surveillance, United States, 2005–2010. One dot is placed randomly within the county of residence for each confirmed case. States with the highest incidence of clinician-diagnosed Lyme disease in a large health insurance claims database (gray areas) are also shown. Transmission also occurs in small regions of northern California, Oregon, and Washington. Adapted from (4).

Figure 2

Two-tiered testing for Lyme disease, United States. Adapted from (7).

Figure 3

Clinical approach to diagnosis of early Lyme disease, United States. *See Figure 1. †Given the gradual geographic expansion of Lyme disease, testing may be warranted for patients with signs and symptoms of Lyme disease who were exposed in areas that border known disease-endemic regions. ‡For a more detailed discussion of symptoms as they relate to pretest probability, see section on exposure and pretest probability. §For recommended 2-tiered testing protocol, see Figure 2. STARI, Southern tick−associated rash illness; EM, erythema migrans.