Comparison of Lyme Disease in the United States and Europe

Adriana R. Marques; Franc Strle; Gary P. Wormser


Emerging Infectious Diseases. 2021;27(8):2017-2024. 

In This Article

Laboratory Diagnosis, Treatment, and Prophylaxis

In the United States and Europe, most laboratory tests performed to diagnose Lyme disease are based on detecting serum antibodies to Lyme borrelia. Because Lyme disease in Europe is caused by a more diverse group of Lyme borrelia, criteria for test interpretation were more challenging to standardize than in the United States. In the United States, the Centers for Disease Control and Prevention has recommended the standard 2-tier algorithm since 1995. This approach typically uses a sensitive enzyme immunoassay (EIA) as the initial step. A negative result requires no further testing. A positive or equivocal result is followed by supplemental testing using separate IgM and IgG immunoblots as the second-tier assay. The interpretation of immunoblot results uses standardized criteria (at least 2 of 3 signature bands for a positive IgM immunoblot and 5 of 10 signature bands for a positive IgG immunoblot). Results from the IgM immunoblot are only relevant when the duration of the illness is <30 days. Of note, testing performed in Europe is more likely to have positive results for patients who acquired Lyme disease in the United States than is testing performed in the United States to diagnose infection acquired in Europe.[42] Recently, a 2-EIA approach has been approved as an alternative (or modified) 2-tier testing strategy (Figure 4). This new approach has higher sensitivity in early disease, similar specificity,[43] greater ability for automation, and offers objective, quantitative values that leads to less variability in interpretation of the result. Also, the 2-EIA approach can be used in the United States and Europe. Moreover, it opens the door for a possible point-of-care test, a development that would be particularly helpful for patients with facial palsy, carditis, and pediatric patients with Lyme arthritis when septic arthritis is part of the differential diagnosis. A disadvantage is that the 2-EIA approach does not establish the extent of IgG seropositivity, which is essential knowledge for diagnosing late Lyme disease.

Figure 4.

Standard 2-tier and modified 2-tier algorithms for serodiagnosis of Lyme disease. The US Centers for Disease Control and Prevention recommended a standard 2-tier algorithm (A) and the modified 2-tier algorithm (B). *For patients with signs or symptoms consistent with Lyme disease for ≤30 days, the provider may treat and follow up with a convalescentphase serum sample. Patients with erythema migrans should receive treatment on the basis of the clinical diagnosis. WB, Western blot.

Recommendations for treating of Lyme disease are generally very similar in guidelines for the United States and Europe. One difference is that phenoxymethylpenicillin (penicillin V) is recommended for treatment of erythema migrans and borrelial lymphocytoma by some of the guidelines in Europe but is not part of the treatment recommendations in the United States.[1,44,45] Another difference is the recommendation by some authorities in Europe to use intravenous ceftriaxone to treat erythema migrans, as well as other manifestations of Lyme disease, in pregnant women; whereas in the United States, antimicrobial drug treatment of Lyme disease for pregnant women is the same as that for nonpregnant patients, except that doxycycline is not recommended for pregnant women.[1,44,46] Postexposure antimicrobial prophylaxis with a single 200-mg dose of doxycycline has been shown to reduce the risk for Lyme disease after an I. scapularis tick bite and is recommended for consideration for tick bite prophylaxis in the United States.[44] A recently published study conducted in Europe has also shown that a single 200-mg dose doxycycline successfully prevented Lyme disease after a tick bite.[47] To what extent doxycycline will be used in Europe after a tick bite is unknown; the standard of care has been observation.[1]