Epidemiological methods are needed to evaluate community exposure to Borrelia burgdorferi, the causative agent of
Lyme disease (LD). For LD serodiagnosis, the Centers for
Disease Control and Prevention (CDC) recommends a 2-test approach that involves enzyme immunoassay (EIA) testing and Western immunoblotting (WB) of EIA-equivocal and EIA-positive specimens. The specificity of this approach was evaluated among residents of a LD-endemic community and was compared with WB alone and with a simplified 2-test approach (WB of equivocal EIA only). Participants reporting no previous diagnosis of LD were recruited during a community-wide serosurvey on Block Island, Rhode Island. Of 80 eligible participants, 20 had received LD vaccine. Seven (35%) of 20 vaccinees and 22 (37%) of 60 nonvaccinees reported nonspecific symptoms compatible with LD in the previous year. In this highly LD-endemic community, the overall specificity of the CDC-recommended approach was highest (100%), followed by WB alone (98.7%), then the simplified approach (95%).