We consider the crux of Masters' comments to be (1) Lyme disease must occur in the southern United States because there are patients in this part of the country who have EM-like lesions and (2) despite negative microbiological evidence for Lyme disease in humans in the southern United States, "absence of proof is not proof of absence."
Lyme disease is caused by infection with B burgdorferi sensu lato. Although environmental conditions exist for limited transmission of the agent of Lyme disease to humans in the southeastern United States, convincing documentation of that transmission has not been obtained.1 In contrast, in Lyme disease–endemic areas of North America and Eurasia, Lyme disease is readily confirmed in patients with EM lesions by cultural isolation of the causative agent and by serologic response to discrete B burgdorferi antigens.2- 5 Our study of 14 cases of EM-like rash illness among campers in North Carolina showed a lack of evidence of infection with B burgdorferi using standard cultural isolation procedures and serologic testing. Clinical, epidemiological, and entomological data suggest that the rash may be caused by an agent transmitted by A americanum, the most common human-biting tick at the study site. We cautioned that although such illnesses should clinically be treated as early Lyme disease, EM-like rash illness should no longer be considered definitive evidence of early Lyme disease. Similarly, comprehensive epidemiological and microbiological studies of patients with EM-like rash illness in Missouri6 conclude that the cause of these lesions remains idiopathic, and that possible causes include infection with novel A americanum–transmitted pathogens and an atypical toxic or immunologic response to tick-associated proteins. One possible candidate is a spirochete that cannot be cultivated, provisionally designated Borrelia lonestari sp nov, identified in the midgut of A americanum ticks and characterized by polymerase chain reaction and sequencing of the amplified products.7 Studies of the patients from Missouri and North Carolina ruled out infection with several known tick-borne infectious pathogens other than B burgdorferi . Tools are not yet available to test for possible infection of humans with B lonestari.