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Lyme Disease Serology

Lyme disease is caused by the spirochete Borrelia burgdorferi and is the most common tick-borne infection in the United States and in Europe. In the U.S., Lyme disease is endemic in the Northeastern, mid-Atlantic and Upper Midwestern states. The blacklegged tick, Ixodes scapularis, is the vector of Lyme disease in the eastern and upper midwestern United States. The western-blacklegged tick, I. pacificus, is the vector of Lyme disease on the Pacific Coast. Peak incidence for the onset of illness occurs in July.

Lyme disease has been a nationally notifiable condition in the United States since 1991. More than 30,000 Lyme disease cases are confirmed each year in the U.S., but the Centers for Disease Control and Prevention (CDC) estimates that approximately 300,000 cases of presumed Lyme disease go unreported each year.

A B. burgdorferi carrying tick has to be attached for at least 36 hours in order for the bacteria to be efficiently transmitted to an individual. Following transmission, the incubation period is typically 7 to 14 days, but can range from 3 to 32 days. The first phase of infection is the appearance of a erythema migrans rash, which occurs in approximately 80% of individuals. Some patients may also experience fatigue, malaise, myalgia, headache, and lymphadenopathy. During the next few weeks, untreated individuals may develop neurologic disease including meningitis, cranial neuropathy, and motor or sensory radiculoneuropathy. Patients may develop Bell ’s pals, oligoarticular arthritis involving the large joints and carditis with atrioventricular heart block. Patients who are treated early with appropriate antibiotics usually experience full recovery.

Since 2008, a confirmed case of Lyme disease is defined as either 1) erythema migrans in a person who had possible exposure to tick habitat in an area where Lyme disease is endemic or who had laboratory evidence of infection or 2) at least one other defined clinical manifestation of Lyme disease in a person and laboratory evidence of infection. A probable case of Lyme disease is defined as laboratory evidence of infection in a person who had Lyme disease diagnosed by a clinician but with accompanying clinical information that does not meet the clinical criteria for a confirmed case

Because the signs and symptoms of Lyme disease may be nonspecific, serologic tests are helpful in confirming the diagnosis. The Centers for Disease Control and Prevention (CDC) recommends a 2-step approach for the serologic diagnosis of Lyme disease. The first tier consists of an enzyme immunoassay for IgG and IgM antibodies to Borrelia burdorferi. Several screening enzyme immunoassays are available that differ in their antigenic composition. Some use a whole cell Borrelia burgdorferi sonicate while others use a recombinant C6 peptide for antibody detection. These enzyme immunoassays are capable of detecting antibodies to all members of the Borrelia burgdorferi complex.

Sensitivity of any of the screening EIAs is only 70 to 75% in patients with early Lyme disease, but increases to approximately 90% during later stages of disease. For this reason, patients with erythema migrans should not be tested.

A negative result does not exclude Lyme disease, especially if the sample was collected within 2 weeks of symptom onset. If Lyme disease is strongly suspected, a second specimen should be tested 4 to 6 weeks after the first. Early administration of antibiotics may weaken or delay the antibody response.

Specimens that test negative on initial screening do not need further testing. Specimens testing positive by either method should be evaluated further by a standardized Western blot immunoassay. Western blots used in the U.S. contain 3 antigens on the IgM and 10 antigens on the IgG blot. CDC requires reactivity with at least 2 IgM bands and 5 IgG bands for a Western blot to be considered positive.

Sensitivity of Lyme Western blot is also dependent on the stage of the disease when tested. Sensitivity is only 20% -50% during early disease and consists of IgM antibodies. Sensitivity increases to 70% to 100% during later stages and switches to an IgG antibody prevalence. A positive IgM Western blot generally indicates recent infection, but in some patients IgM-class antibodies persist for months to years following infection. IgG antibodies can persist for years. In patients tested within 4 weeks of symptom onset, results of both IgM and IgG Western blot should be used in the interpretation.

Specificity of the 2-tiered testing algorithm, regardless of what screening ELISA is used, is high, over 99% in both healthy individuals and those with other infectious or inflammatory diseases. Because of the specificity of the Western blot for Borrelia burgdorferi, Infection with other Borrelia species is unlikely to be detected by this two tier test strategy.

Specimen requirement is one SST tube of blood.


Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983;99:76–82.

Lantos PM, Branda JA, Boggan JC, et al. Poor positive predictive value of Lyme disease serologic testing in an area of low disease incidence. Clin Infect Dis 2015;61:1374–80.

Hinckley AF, Connally NP, Meek JI, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis 2014;59:676–81.

Council of State and Territorial Epidemiologists. Revised national surveillance case definition for Lyme disease; 2007.

Centers for Disease Control and Prevention. Two-step laboratory testing process.

Schwartz AM. et al. Surveillance for Lyme Disease — United States, 2008–2015. Morbidity and Mortality Weekly Report, Nov 10, 2017;66(22):1-12.

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