Chapter 11 : Lyme Borreliosis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Lyme Borreliosis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816490/9781555812386_Chap11-1.gif /docserver/preview/fulltext/10.1128/9781555816490/9781555812386_Chap11-2.gif


Lyme disease or Lyme borreliosis is recognized as an important infectious disease in North America, Europe, and Asia. The formerly designated has now been subdivided into multiple species, including three that cause human infection. In the United States, the sole cause of infection is . Although all three pathogenic species are found in Europe, most disease there is caused by or ; these two species also seem to be responsible for the illness in Asia. This chapter presents biology and enzootic cycles of and related species. As with other spirochetal infections, human Lyme borreliosis generally occurs in stages, with remissions, exacerbations, and different clinical manifestations at each stage. Early infection consists of stage 1 (localized skin infection), followed within days to weeks by stage 2 (disseminated infection). Late infection, or stage 3 (persistent or progressive infection), usually begins months to years after the disease onset, sometimes following long periods of latent infection. To gain a better understanding of pathogenetic mechanisms, animal models of Lyme disease have been developed in mice, hamsters, guinea pigs, dogs, and nonhuman primates. Each animal model is imperfect in that it does not express all features of human Lyme disease. The plethora of inbred mouse strains, including genetically modified animals, and the depth of knowledge of the murine immune system have made studies of the mouse particularly valuable. The chapter presents the diagnosis, treatment, and prevention of the Lyme disease.

Citation: Steere A, Glickstein L, Coburn J. 2005. Lyme Borreliosis, p 176-206. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch11

Key Concept Ranking

Major Histocompatibility Complex Class II
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

A scanning electron micrograph of spirochetes in the mid-gut of a nymphal tick. The picture was a kind gift of Dr. Willy Burgdorfer.

Citation: Steere A, Glickstein L, Coburn J. 2005. Lyme Borreliosis, p 176-206. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Western blots of the IgM antibody responses to are shown in 25 patients with EM (a); the IgG responses are demonstrated in 25 patients with Lyme arthritis (b). Patients with EM most commonly had IgM responses to the 23-kDa OspC protein and the 41-kDa flagellar antigen of the spirochete, whereas the patients with Lyme arthritis almost always had IgG reactivity with all 10 bands used for diagnosis with the CDC criteria ( ).

Citation: Steere A, Glickstein L, Coburn J. 2005. Lyme Borreliosis, p 176-206. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ackermann, R.,, P. Horstrup,, and R. Schmidt. 1984. Tick-borne meningopolyneuritis (Garin-Bujadoux, Bannwarth). Yale J. Biol. Med. 57:485490.
2. Ackermann, R.,, J. Kabatzki,, H. P. Boisten,, A. C. Steere,, R. L. Grodzicki,, S. Hartung,, and U. Runne. 1984. Spirochaten- Atiologie der Erythema-chronicum-migrans-Krankheit. Dtsch. Med. Wochenschr. 109:9297.
3. Ackermann, R.,, B. Rehse-Kupper,, E. Gollmer,, and R. Schmidt. 1988. Chronic neurologic manifestations of erythema migrans borreliosis. Ann. N. Y. Acad. Sci. 539:1623.
4. Afzelius, A. 1921. Erythema chronicum migrans. Acta Derm. Venereol. 2:120125.
5. Agger, W. A.,, S. M. Callister,, and D. A. Jobe. 1992. In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. Antimicrob. Agents Chemother. 36: 17881790.
6. Akin, E.,, J. Aversa,, and A. C. Steere. 2001. Expression of adhesion molecules in synovia of patients with treatmentresistant Lyme arthritis. Infect. Immun. 69:17741780.
7. Akin, E.,, G. L. McHugh,, R. A. Flavell,, E. Fikrig,, and A. C. Steere. 1999. The immunoglobulin (IgG) antibody response to OspA and OspB correlates with severe and prolonged Lyme arthritis and the IgG response to P35 correlates with mild and brief arthritis. Infect. Immun. 67:173181.
8. Alexopoulou, L.,, V. Thomas,, M. Schnare,, Y. Lobet,, J. Anguita,, R. T. Schoen,, R. Medzhitov,, E. Fikrig,, and R. A. Flavell. 2002. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat. Med. 8:878884.
9. Alitalo, A.,, T. Meri,, H. Lankinen,, I. Seppala,, P. Lahdenne,, P. S. Hefty,, D. Akins,, and S. Meri. 2002. Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs. J. Immunol. 169:38473853.
10. Alpert, L. I.,, P. Welch,, and N. Fisher. 1985. Gallium-positive Lyme disease myocarditis. Clin. Nucl. Med. 10:617.
11. Anderson, J. F. 1991. Epizootiology of Lyme borreliosis. Scand. J. Infect. Dis. 77:2324.
12. Anderson, J. F. 1988. Mammalian and avian reservoirs for Borrelia burgdorferi. Ann. N. Y. Acad. Sci. 539:180191.
13. Anguita, J.,, M. Rincon,, S. Samanta,, S. W. Barthold,, R. A. Flavell,, and E. Fikrig. 1998. Borrelia burgdorferi-infected, interleukin-6-deficient mice have decreased Th2 responses and increased Lyme arthritis. J. Infect. Dis. 178:15121515.
14. Anguita, J.,, S. Samanta,, S. W. Barthold,, and E. Fikrig. 1997. Ablation of interleukin-12 exacerbates Lyme arthritis in SCID mice. Infect. Immun. 65:43344336.
15. Anguita, J. S.,, S. K. Samanta,, B. Ananthanarayanan,, G. P. Revilla,, S. W. Geba,, S. W. Barthold,, and E. Fikrig. 2002. Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. FEMS Immunol. Med. Microbiol. 34:187191.
16. Asbrink, E.,, E. Brehmer-Anderson,, and A. Hovmark. 1986. Acrodermatitis chronica actrophicans—a spirochetosis. Am. J. Dermatopathol. 8:209219.
17. Asbrink, E.,, and A. Hovmark. 1985. Successful cultivation of spirochetes from skin lesions of patients with erythema chronica migrans afzelius and acrodermatitis chronica atrophicans. Acta Pathol. Microbiol. Immunol. Scand. B 93: 161163.
18. Atlas, E.,, S. N. Novak,, P. H. Duray,, and A. C. Steere. 1988. Lyme myositis: muscle invasion by Borrelia burgdorferi. Ann. Intern. Med. 109:245246.
19. Bacon, R. M.,, B. J. Biggerstaff,, M. E. Schriefer,, R. D. Gilmore,, M. T. Philipp,, A. C. Steere,, G. P. Wormser,, A. R. Marques,,and B. J. B. Johnson. 2003. Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J. Infect. Dis. 187:11871199.
20. Bailasiewicz, A. A.,, K. W. Ruprecht,, G. O. Naumann,, and H. Blenk. 1988. Bilateral diffuse choroiditis and exudate retinal detachments with evidence of Lyme disease. Am. J. Ophthalmol. 105:419420.
21. Bannwarth, A. 1944. Zur Klinik und Pathogenese der “chronischen lymphocytaren Meningitis.” Arch. Psychiatr. Nervenkr. 117:161185.
22. Baranton, G.,, D. Postic,, I. Saint-Girons,, P. Boerlin,, J. C. Piffaretti,, M. Assous,, and P. A. Grimont. 1992. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int. J. Syst. Bacteriol. 42:378383.
23. Baranton, G.,, G. Seinost,, G. Theodore,, D. Postic,, and D. Dykhuizen. 2001. Distinct levels of genetic diversity of Borrelia burgdorferi are associated with different aspects of pathogenicity. Res. Microbiol. 152:149156.
24. Barbour, A. G. 1984. Isolation and cultivation of Lyme disease spirochetes. Yale J. Biol. Med. 57:521525.
25. Barbour, A. G.,, W. Burgdorfer,, E. Grunwaldt,, and A. C. Steere. 1983. Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete. J. Clin. Investig. 72:504515.
26. Barbour, A. G.,, and C. F. Garon. 1987. Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science 237:409411.
27. Barbour, A. G.,, and S. F. Hayes. 1986. Biology of Borrelia species. Microbiol. Rev. 50:381400.
28. Barthold, S. W.,, D. S. Beck,, G. M. Hansen,, G. A. Terwilliger,, and K. D. Moody. 1990. Lyme borreliosis in selected strains and ages of laboratory mice. J. Infect. Dis. 162:133138.
29. Barthold, S. W.,, M. S. DeSouza,, J. L. Janotka,, A. L. Smith,, and D. H. Persing. 1993. Chronic Lyme borreliosis in the laboratory mouse. Am. J. Pathol. 143:959971.
30. Barthold, S. W.,, C. L. Sidman,, and A. L. Smith. 1992. Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. Am. J. Trop. Med. Hyg. 47:605613.
31. Benach, J. L.,, E. M. Bosler,, J. P. Hanrahan,, J. L. Coleman,, G. S. Habicht,, T. F. Bast,, D. J. Cameron,, J. L. Ziegler,, A. G. Barbour,, W. Burgdorfer,, R. Edelman,, and R. A. Kaslow. 1983. Spirochetes isolated from the blood of two patients with Lyme disease. N. Engl. J. Med. 308:740742.
32. Berger, B. W.,, R. C. Johnson,, C. Kodner,, and L. Coleman. 1992. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J. Clin. Microbiol. 30: 359361.
33. Berglund, J.,, R. Eitrem,, K. Ornstein,, A. Lindberg,, A. Ringner,, H. Elmrud,, M. Carlsson,, A. Runehagen,, C. Svanborg,, and R. Norrby. 1995. An epidemiologic study of Lyme disease in southern Sweden. N. Engl. J. Med. 333:13191324.
34. Bloom, B. J.,, P. M. Wyckoff,, H. C. Meissner,, and A. C. Steere. 1998. Neurocognitive abnormalities in children after classic manifestions of Lyme disease. Pediatr. Infect. Dis. J. 17:189196.
35. Bockenstedt, L. K.,, J. Mao,, E. Hodzic,, S. W. Barthold,, and D. Fish. 2002. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J. Infect. Dis. 186:14301437.
36.Bono, J. L., A. F. Elias, J. J. Kupko III, B. Stevenson, K. Tilly, and P. Rosa. 2000. Efficient targeted mutagenesis in Borrelia burgdorferi. J. Bacteriol. 182:2445-2452.
37. Bosler, E. M.,, B. G. Ormiston,, J. L. Coleman,, J. P. Hanrahan,, and J. L. Benach. 1984. Prevalence of the Lyme disease spirochete in populations of white-tailed deer and white-footed mice. Yale J. Biol. Med. 57:651659.
38. Bradley, J. F.,, R. C. Johnson,, and J. L. Goodman. 1994. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann. Intern. Med. 120:487489.
39. Brown, C. R.,, V. A. Blaho,, and C. M. Loiacono. 2003. Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2. J. Immunol. 171:893901
40. Brown, C. R.,, and S. L. Reiner. 1999. Experimental Lyme arthritis in the absence of interleukin-4 or gamma interferon. Infect. Immun. 67:33293333.
41. Brown, C. R.,, and S. L. Reiner. 1999. Genetic control of experimental Lyme arthritis in the absence of specific immunity. Infect. Immun. 67:19671973.
42. Brown, E. L.,, R. M. Wooten,, B. J. Johnson,, R. V. Iozzo,, A. Smith,, M. C. Dolan,, B. P. Guo,, J. J. Weis,, and M. Hook. 2001. Resistance to Lyme disease in decorin-deficient mice. J. Clin. Investig. 107:845852.
43. Brown, J. P.,, J. F. Zachary,, C. Teuscher,, J. J. Weis,, and R. M. Wooten. 1999. Dual role of interleukin-10 in murine Lyme disease: regulation of arthritis severity and host defense. Infect. Immun. 67:51425150.
44. Brown, R. N.,, and R. S. Lane. 1992. Lyme disease in California: a novel enzootic transmission cycle of Borrelia burgdorferi. Science 256:14391442.
45. Brunet, L. R.,, C. Sellitto,, A. Spielman,, and S. R. Telford III. 1995. Antibody response of the mouse reservoir of Borrelia burgdorferi in nature. Infect. Immun. 63:30303036.
46. Bunikis, J.,, B. Olsen,, G. Westman,, and S. Bergstroom. 1995. Variable serum immunoglobulin responses against different Borrelia burgdorferi sensu lato species in a population at risk for and patients with Lyme disease. J. Clin. Microbiol. 33: 14731478.
47. Burchill, M. A.,, D. T. Nardelli,, D. M. England,, D. J. DeCoster,, J. A. Christopherson,, S. M. Callister,, and R. F. Schell. 2003. Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi. Infect. Immun. 71:34373442.
48. Burgdorfer, W.,, A. G. Barbour,, S. F. Hayes,, J. L. Benach,, E. Grunwaldt,, and J. P. Davis. 1982. Lyme disease—a tickborne spirochetosis? Science 216:13171319.
49. Burgess, E. C. 1988. Borrelia burgdorferi infection in Wisconsin horses and cows. Ann. N. Y. Acad. Sci. 539:235243.
50. Busch, D. H.,, C. Jassoy,, U. Brinckmann,, H. Girschick,, and H. I. Huppertz. 1996. Detection of Borrelia burgdorferispecific CD8+ T cytotoxic T cells in patients with Lyme arthritis. J. Immunol. 157:3534.
51. Cabello, F. C.,, M. L. Sartakova,, and E. Y. Dobrikova. 2001. Genetic manipulation of spirochetes—light at the end of the tunnel. Trends Microbiol. 9:245248.
52. Cadavid, D.,, T. O’Neill,, H. Schaefer,, and A. R. Pachner. 2000. Localization of Borrelia burgdorferi in the nervous system and other organs in a nonhuman primate model of Lyme disease. Lab. Investig. 80:10431054.
53. Campbell, G. L.,, W. S. Paul,, M. E. Schriefer,, R. B. Craven,, K. E. Robbins,, and D. T. Dennis. 1995. Epidemiologic and diagnostic studies of patients with suspected early Lyme disease, Missouri, 1990-1993. J. Infect. Dis. 172:470480.
54. Canica, M. M.,, F. Nato,, L. DuMerle,, J. C. Mazie,, G. Baranton,, and D. Postic. 1993. Monoclonal antibodies for identification of Borrelia afzelii sp. nov. associated with late cutaneous manifestations of Lyme borreliosis. Scand. J. Infect. Dis. 25:441448.
55. Carlson, D.,, J. Hernandez,, B. J. Bloom,, J. Coburn,, J. M. Aversa,, and A. C. Steere. 1999. Lack of Borrelia burgdorferi DNA in synovial samples in patients with antibiotic treatment-resistant Lyme arthritis. Arthritis Rheum. 42:27052709.
56. Carroll, J. A.,, P. E. Stewart,, P. Rosa,, A. F. Elias,, and C. F. Garon. 2003. An enhanced GFP reporter system to monitor gene expression in Borrelia burgdorferi. Microbiology 149:18191828.
57. Casjens, S.,, N. Palmer,, R. VanVugt,, W. Mun Huang,, B. Stevenson,, P. Rosa,, R. Lathigra,, G. Sutton,, J. Peterson,, R. J. Dodson,, D. Haft,, E. Hickey,, M. Gwinn,, O. White,, and C. M. Fraser. 2000. A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol. Microbiol. 35:490516.
58.Centers for Disease Control and Prevention. 1990. Case definitions for public health surveillance. Morb. Mortal. Wkly. Rep. 39(RR-13):143.
59.Centers for Disease Control and Prevention. 1995. Recommendations for test performance and interpretation from the Second International Conference on serologic diagnosis of Lyme disease. Morb. Mortal. Wkly. Rep. 44:590591.
60. Chen, J.,, J. A. Field,, L. Glickstein,, P. J. Molloy,, B. T. Huber,, and A. C. Steere. 1999. Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer-surface protein A (OspA) of Borrelia burgdorferi. Arthritis Rheum. 42:18131822.
61. Christopherson, J. A.,, E. L. Munson,, D. M. England,, C. L. Croke,, M. C. Remington,, M. L. Molitor,, D. J. DeCoster,, S. M. Callister,, and R. F. Schell. 2003. Destructive arthritis in vaccinated interferon gamma-deficient mice challenged with Borrelia burgdorferi: modulation by tumor necrosis factor alpha. Clin. Diagn. Lab. Immunol. 10:4452.
62. Clark, J. R.,, R. D. Carlson,, C. T. Sasaki,, A. R. Pachner,, and A. C. Steere. 1985. Facial paralysis in Lyme disease. Laryngoscope 95:13411345.
63. Coburn, J.,, S. W. Barthold,, and J. M. Leong. 1994. Diverse Lyme disease spirochetes bind integrin αIIbβ3 on human platelets. Infect. Immun. 62:55595567.
64. Coburn, J.,, W. Chege,, L. Magoun,, S. C. Bodary,, and J. M. Leong. 1999. Characterization of a candidate Borrelia burgdorferi β3-chain integrin ligand identified using a phage display library. Mol. Microbiol. 34:926940
65. Coburn, J.,, and C. Cugini. 2003. Targeted mutation of the outer membrane protein P66 disrupts attachment of the Lyme disease agent, Borrelia burgdorferi, to integrin αvβ3. Proc. Natl. Acad. Sci. USA 100:73017306.
66. Coburn, J.,, J. M. Leong,, and J. K. Erban. 1993. Integrin αIIbβ3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. Proc. Natl. Acad. Sci. USA 90: 70597063.
67. Coburn, J.,, L. Magoun,, S. C. Bodary,, and J. M. Leong. 1998. Integrins αvβ3 and α5β1 mediate attachment of Lyme diseasespirochetes to human cells. Infect. Immun. 66:19461952.
68. Coleman, J. L.,, J. A. Gebbia,, J. Pieman,, J. L. Degen,, T. H. Bugge,, and J. L. Benach. 1997. Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89:11111119.
69. Comstock, L. E.,, and D. D. Thomas. 1991. Characterization of Borrelia burgdorferi invasion of cultured endothelial cells.Microb. Pathog. 10:137148.
70. Cox, D. L.,, D. R. Akins,, K. W. Bourell,, P. Lahdenne,, M. V. orgard,, and J. D. Radolf. 1996. Limited surface exposure of Borrelia burgdorferi outer surface lipoproteins. Proc. Natl. Acad. Sci. USA 93:79737978.
71. Croke, C. L.,, E. L. Munson,, S. D. Lovrich,, J. A. Christopherson,, M. C. Remington,, D. M. England,, S. M. Callister,, and R. F. Schell. 2000. Occurrence of severe destructive Lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. Infect. Immun. 68:658663.
72. Crowley, H.,, and B. T. Huber. 2003. Host–adapted Borrelia burgdorferi in mice expresses OspA during inflammation. Infect. Immun. 71:40034010.
73. Curran, K. L.,, D. Fish,, and J. Piesman. 1993. Reduction of nymphal Ixodes dammini (Acari: Ixodidae) in a residential suburban landscape by area application of insecticides. J. Med. Entomol. 30:107113.
74. Dai, Z.,, H. Lackland,, S. Stein,, Q. Li,, R. Radziewicz,, S. Williams,, and L. H. Sigal. 1993. Molecular mimicry in Lyme disease: monoclonal antibody H9724 to B. burgdorferi flagellin specifically detects chaperonin-HSP60. Biochim. Biophys. Acta 1181:97100.
75. Dattwyler, R. J.,, J. J. Halperin,, D. J. Volkman,, and B. J. Luft. 1988. Treatment of late Lyme borreliosis—randomized comparison of ceftriaxone and penicillin. Lanceti 111:11911194.
76. Dattwyler, R. J.,, B. J. Luft,, M. J. Kunkel,, M. F. Finkel,, G. P. Wormser,, and G. P. Rush. 1997. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N. Engl. J. Med. 337:289294.
77. Dattwyler, R. J.,, D. J. Volkman,, S. M. Conaty,, S. P. Platkin,, and B. J. Luft. 1990. Amoxicillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 336:14041406.
78. de Silva, A. M.,, and E. Fikrig. 1997. Arthropod- and hostspecific gene expression by Borrelia burgdorferi. J. Clin. Investig. 100:S3S5.
79. Defosse, D. L.,, and R. C. Johnson. 1992. In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi. Infect. Immun. 60:11091113.
80. Dennis, D. T.,, and E. B. Hayes,. 2002. Epidemiology of Lyme borreliosis, p. 251280. In O. K. J. S. Gray,, R. S. Lane,, and G. Stanek (ed.), Lyme Borreliosis: Biology, Epidemiology and Control. CABI Publishing, Oxford, England.
81. DeSouza, M. S.,, E. Fikrig,, A. L. Smith,, R. A. Flavell,, and S. W. Barthold. 1992. Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens. J. Infect. Dis. 165:471478.
82. Dever, L. L.,, J. H. Jorgensen,, and A. G. Barbour. 1993. In vitro activity of vancomycin against the spirochete Borrelia burgdorferi. Antimicrob. Agents Chemother. 37:11151121.
83. Dever, L. L.,, J. H. Jorgensen,, and A. G. Barbour. 1992. In vitro antimicrobial susceptibility testing of Borrelia burgdorferi: a microdilution MIC method and time-kill studies. J. Clin. Microbiol. 30:26922697.
84. Dinerman, H.,, and A. C. Steere. 1992. Lyme disease associated with fibromyalgia. Ann. Intern. Med. 117:281285.
85. Dong, Z.,, M. Edelstein,, and L. J. Glickstein. 1997. CD8_ T cells are activated during the early Th1 and Th2 immune responses in the murine Lyme disease model. Infect. Immun. 65:53345337.
86. Dressler, F.,, J. A. Whalen,, B. N. Reinhardt,, and A. C. Steere. 1993. Western blotting in the serodiagnosis of Lyme disease. J. Infect. Dis. 167:392400.
87. Duray, P. H. 1987. The surgical pathology of human Lyme disease: an enlarging picture. Am. J. Surg. Pathol. 11:4760.
88. Duray, P. H.,, and A. C. Steere. 1988. Clinical pathologic correlations of Lyme disease by stage. Ann. N. Y. Acad. Sci. 539:6579.
89. Eckman, M. H.,, A. C. Steere,, R. A. Kalish,, and S. G. Pauker. 1997. Cost effectiveness of oral as compared with intravenous antibiotic therapy for patients with early Lyme disease or Lyme arthritis. N. Engl. J. Med. 337:357363.
90. Eggers, C. H.,, B. J. Kimmel,, J. L. Bono,, A. F. Elias,, P. Rosa,, and D. S. Samuels. 2001. Transduction by phiBB-1, a bacteriophage of Borrelia burgdorferi. J. Bacteriol. 183:47714778.
91. Eggers, C. H.,, and D. S. Samuels. 1999. Molecular evidence for a new bacteriophage of Borrelia burgdorferi. J. Bacteriol. 181:73087313.
92. Engstrom, S. M.,, E. Shoop,, and R. C. Johnson. 1995. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J. Clin. Microbiol. 33:419427.
93. Ettestad, P. J.,, G. L. Campbell,, S. F. Welbel,, C. A. Genese,, K. C. Spitalny,, C. M. Marchetti,, and D. T. Dennis. 1995. Biliary complications in the treatment of unsubstantiated Lyme disease. J. Infect. Dis. 171:356361.
94. Fahrer, H.,, S. M. VanderLinden,, M. J. Sauvain,, L. Gern,, E. Zhioua,, and A. Aeschlimann. 1991. The prevalence and incidence of clinical and asymptomatic Lyme borreliosis in a population at risk. J. Infect. Dis. 163:305310.
95. Feng, S.,, E. Hodzic,, and S. W. Barthold. 2000. Lyme arthritis resolution with antiserum to a 37-kilodalton Borrelia burgdorferi protein. Infect. Immun. 68:41694173.
96. Fikrig, E.,, S. W. Barthold,, M. Chen,, C. H. Chang,, and R. A. Flavell. 1997. Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4_ T cells. J. Immunol. 159:56825686.
97. Fikrig, E.,, S. W. Barthold,, F. S. Kantor,, and R. A. Flavell. 1990. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA.Science 250:553556.
98. Fikrig, E.,, S. W. Barthold,, W. Sun,, W. Feng,, S. R. Telford III,, and R. A. Flavell. 1997. Borrelia burgdorferi P35 and P37 proteins, expressed in vivo, elicit protective immunity. Immunity 6:531537.
99. Filgueira, L.,, F. O. Nestle,, M. Rittig,, H. I. Joller,, and P. Groscurth. 1996. Human dendritic cells phagocytose and process Borrelia burgdorferi. J. Immunol. 157:29983005.
100. Fischer, J. R.,, N. Parveen,, L. Magoun,, and J. M. Leong. 2003. Decorin-binding proteins A and B confer distinct mammalian cell type-specific attachment by Borrelia burgdorferi, the Lyme disease spirochete. Proc. Natl. Acad. Sci. USA 100:73077312.
101. Franz, J. K.,, O. Frize,, M. Rittig,, G. Keyßer,, S. Priem,, J. Zacher,, G. R. Burmester,, and A. Krause. 2001. Insights from a novel three-dimensional in vitro model of Lyme arthritis. Arthritis Rheum. 44:151.
102. Fraser, C. M.,, S. Casjens,, W. M. Huang,, G. G. Sutton,, R. Clayton,, R. Lathigra,, O. White,, K. A. Ketchum,, R. Dodson,, E. K. Hickey,, M. Gwinn,, B. Dougherty,, J. F. Tomb,, R. D. Fleischmann,, D. Richardson,, J. Peterson,, A. R. Kerlavage,, J. Quackenbush,, S. Salzberg,, M. Hanson,, R. van Vugt,, N. Palmer,, M. D. Adams,, J. Gocayne,, J. C. Venter, et al. 1997. Genomic sequence of a Lyme disease spirochete, Borrelia burgdorferi. Nature 390:580586.
103. Fuchs, H.,, R. Wallich,, M. M. Simon,, and M. D. Kramer. 1994. The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor. Proc. Natl. Acad. Sci. USA 91:1259412598.
104. Fukunaga, M.,, A. Hamase,, K. Okada,, and M. Nakao. 1996. Borrelia tanukii sp. nov. and Borrelia turdae sp. nov. found from ixodid ticks in Japan: rapid species identification by 16S rRNA gene-targeted PCR analysis. Microbiol. Immunol. 40:877881.
105. Garcia-Monco, J. C.,, B. F. Villar,, J. C. Alen,, and J. L. Benach. 1990. Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion. J. Infect. Dis. 161:1187.
106. Gardner, P. 1998. Lyme disease vaccines. Ann. Intern. Med. 129:583585.
107. Gebbia, J. A.,, J. L. Coleman,, and J. L. Benach. 2001. Borrelia spirochetes upregulate release and activation of matrix metalloproteinase gelatinase B (MMP-9) and collagenase 1 (MMP-1) in human cells. Infect. Immun. 69:456462.
108. Georgilis, K.,, M. Peacocke,, and M. S. Klempner. 1992. Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J. Infect. Dis. 166:440444.
109. Gern, L.,, A. Estrada-Peña,, F. Frandsen,, J. S. Gray,, T. G. Jaenson,, F. Jongejan,, O. Kahl,, E. Korenberg,, R. Mehl,, and P. A. Nuttall. 1998. European reservoir hosts of Borrelia burgdorferi sensu lato. Zentralbl. Bakteriol. 287:196204.
110. Gern, L.,, and H. Pierre-Francois,. 2002. Ecology of Borrelia burgdorferi sensu lato in Europe, p. 149174. In O. K. J. S. Gray,, R. S. Lane,, and G. Stanek (ed.), Lyme Borreliosis: Biology, Epidemiology and Control. CABI Publishing, Oxford, England.
111. Glatzel, A.,, F. Entschladen,, T. M. Zollner,, P. Kraiczy,, V. Brade,, R. Kaufmann,, O. Janssen,, B. Lengl-Janssen,, D. Wesch, andD. Kabelitz. 2002. The responsiveness of human Vδ1 γδ T cells to Borrelia burgdorferi is largely restricted to synovialfluid cells from patients with Lyme arthritis. J. Infect. Dis. 186:10431046
112. Glavanakov, S.,, D. J. White,, T. Caraco,, A. Lapenis,, G. R. Robinson,, B. K. Szymanski,, and W. A. Maniatty. 2001. Lyme disease in New York State: spatial pattern at a regional scale. Am. J. Trop. Med. Hyg. 65:538545.
113. Glickstein, L.,, M. Edelstein,, and J. Z. Dong. 2001. Gamma interferon is not required for arthritis resistance in the murine Lyme disease model. Infect. Immun. 69:37373743.
114. Glickstein, L.,, B. Moore,, T. Bledsoe,, N. Damle,, V. Sikand,, and A. C. Steere. 2003. Inflammatory cytokine production predominates in early Lyme disease in patients with erythema migrans. Infect. Immun. 71:60516053.
115. Goldstein, S. F.,, N. W. Charon,, and J. A. Kreiling. 1994. Borrelia burgdorferi swims with a planar waveform similar to that of eukaryotic flagella. Proc. Natl. Acad. Sci. USA 91: 3433-3437
116. Gomes-Solecki, M. J.,, G. P. Wormser,, D. H. Persing,, B. W. Berger,, J. D. Glass,, X. Yang,, and R. J. Dattwyler. 2001. A first-tier rapid assay for the serodiagnosis of Borrelia burgdorferi infection. Arch. Intern. Med. 161:20152020
117. Granter, S. R.,, R. L. Barnhill,, M. E. Hewins,, and P. H. Duray. 1994. Identification of Borrelia burgdorferi in diffuse fasciitis with peripheral eosinophilia: borrelial fasciitis. JAMA 272:12831285.
118. Gross, D. M.,, T. Forsthuber,, M. Tary-Lehman,, C. Etling,, K. Ito,, Z. A. Nagy,, J. A. Field,, A. C. Steere,, and B. T. Huber. 1998. Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 281:703706.
119. Gross, D. M.,, A. C. Steere,, and B. T. Huber. 1998. T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis. J. Immunol. 160:10221028.
120. Guo, B. P.,, E. L. Brown,, D. W. Dorward,, L. C. Rosenberg,, and M. Hook. 1998. Decorin-binding adhesins from Borrelia burgdorferi. Mol. Microbiol. 30:711723.
121. Guo, B. P.,, S. J. Norris,, L. C. Rosenberg,, and M. Hook. 1995. Adherence of Borrelia burgdorferi to the proteoglycan decorin. Infect. Immun. 63:34673472.
122. Gustafson, R.,, B. Svenungsson,, M. Forsgren,, A. Gardulf,, and M. Granstrom. 1992. Two-year survey of the incidence of Lyme borreliosis and tick-borne encephalitis in a high-risk population in Sweden. Eur. J. Clin. Microbiol. Infect. Dis. 11:894900.
123. Gustafson, R.,, B. Svenungsson,, A. Gardulf,, G. Stiernstedt,, and M. Forsgren. 1990. Prevalence of tick-borne encephalitis and Lyme borreliosis in a defined Swedish population. Scand. J. Infect. Dis. 22:297306.
124. Halperin, J. J.,, B. W. Little,, P. K. Coyle,, and R. J. Dattwyler. 1987. Lyme disease: cause of a treatable peripheral neuropathy. Neurology 37:17001706.
125. Halperin, J. J.,, D. J. Volkman,, and P. Wu. 1991. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 41:15711582.
126. Hanrahan, J. P.,, J. L. Benach,, J. L. Coleman,, E. M. Bosler,, D. L. Morse,, D. J. Cameron,, R. Edelman,, and R. A. Kaslow. 1984. Incidence and cumulative frequency of endemic Lyme disease in a community. J. Infect. Dis. 150:489496.
127. Hansen, K.,, M. Cruz,, and H. Link. 1990. Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis. J. Infect. Dis. 161:11941202.
128. Hansen, K.,, and A. M. Lebech. 1991. Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi—specific immunoglobulin G, A, and M. Ann. Neurol. 30:197205.
129. Hanson, M. S.,, D. R. Cassatt,, B. P. Guo,, N. K. Patel,, M. P. McCarthy,, D. W. Dorward,, and M. Hook. 1998. Activeand passive immunity against Borrelia burgdorferi decorin binding protein A (DbpA) protects against infection. Infect. Immun. 66:21432153.
130. Hanson, M. S.,, and R. Edelman. 2003. Progress and controversy surrounding vaccines against Lyme disease. Expert Rev. Vaccines 2:683703.
131. Hardin, J. A.,, A. C. Steere,, and S. E. Malawista. 1979. Immune complexes and the evolution of Lyme arthritis: dissemination and localization of abnormal C1q binding activity. N. Engl. J. Med. 301:13581363.
132. Hayes, E. B.,, and J. Piesman. 2003. How can we prevent Lyme disease? N. Engl. J. Med. 348:24242430.
133. Hefty, P. S.,, S. E. Jolliff,, M. J. Caimano,, S. K. Wikel,, and D. R. Akins. 2002. Changes in temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi. Infect. Immun. 70:34683478.
134. Hellwage, J.,, T. Meri,, T. Heikkila,, A. Alitalo,, J. Panelius,, P. Lahdenne,, I. J. Seppala,, and S. Meri. 2001. The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J. Biol. Chem. 276:84278435.
135. Hemmer, B.,, B. Gran,, Y. Zhao,, A. Marques,, J. Pascal,, A. Tzou,, T. Kondo,, I. Cortese,, B. Bielekova,, S. E. Straus,, H. F. McFarland,, R. Houghten,, R. Simon,, C. Pinilla,, and R. Martin. 1999. Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat. Med. 5:13751382.
136. Henriksson, A.,, H. Link,, M. Cruz,, and G. Stiernstedt. 1986. Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth’s syndrome). Ann. Neurol. 20:337345.
137. Hinnebusch, J.,, S. Bergstrom,, and A. G. Barbour. 1990. Cloning and sequence analysis of linear plasmid telomeres of the bacterium Borrelia burgdorferi. Mol. Microbiol. 4: 811820.
138. Hovind-Hougen, K.,, E. Asbrink,, G. Stiernstedt,, A. C. Steere,, and A. Hovmark. 1986. Ultrastructural differences among spirochetes isolated from patients with Lyme disease and related disorders, and from Ixodes ricinus. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263:103111
139. Hu, L. T.,, G. Perides,, R. Noring,, and M. S. Klempner. 1995. Binding of human plasminogen to Borrelia burgdorferi. Infect. Immun. 63:34913496
140. Hubner, A.,, X. Yang,, D. M. Nolen,, T. G. Popova,, F. C. Cabello,, and M. V. Norgard. 2001. Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc. Natl. Acad. Sci. USA 98:1272412729.
141. Humair, P. F.,, O. Peter,, R. Wallich,, and L. Gern. 1995. Strain variation of Lyme disease spirochetes isolated from Ixodes ricinus ticks and rodents collected in two endemic areas in Switzerland. J. Med. Entomol. 32:433438.
142. Isaacs, R. D. 1994. Borrelia burgdorferi bind to epithelial cell proteoglycans. J. Clin. Investig. 93:809819.
143. Jacobs, J. C.,, M. Stevens,, and P. H. Duray. 1986. Lyme disease simulating septic arthritis. JAMA 256:11381139.
144. Johnson, R. C.,, C. Kodner,, and M. Russell. 1986. Active immunization of hamsters against experimental infection with Borrelia burgdorferi. Infect. Immun. 54:887891.
145. Johnson, R. C.,, C. Kodner,, and M. Russell. 1987. In vitro and in vivo susceptibility of the Lyme disease spirochete, Borrelia burgdorferi, to four antimicrobial agents. Antimicrob. Agents Chemother. 31:164167.
146. Johnson, R. C.,, C. Kodner,, and M. Russell. 1986. Passive immunization of hamsters against experimental infection with Borrelia burgdorferi. Infect. Immun. 53:713715.
147. Johnson, R. C.,, G. P. Schmid,, F. W. Hyde,, A. G. Steigerwalt,, and D. J. Brenner. 1984. Borrelia burgdorferi sp. nov.: etiologic agent of Lyme disease. Int. J. Syst. Bacteriol. 34:496497.
148. Kalish, R. A.,, R. F. Kaplan,, E. Taylor,, L. Jones-Woodward,, K. Workman,, and A. C. Steere. 2001. Evaluation of study patients with Lyme disease, 10-20-year follow-up. J. Infect. Dis. 183:453460.
149. Kalish, R. A.,, J. M. Leong,, and A. C. Steere. 1993. Association of treatment resistant chronic Lyme arthritis with HLADR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi. Infect. Immun. 61:27742779.
150. Kalish, R. A.,, J. M. Leong,, and A. C. Steere. 1995. Early and late antibody responses to full-length and truncated constructs of outer-surface protein A of Borrelia burgdorferi in Lyme disease. Infect. Immun. 63:22282235.
151. Kalish, R. A.,, G. McHugh,, J. Granquist,, B. Shea,, R. Ruthazer,, and A. C. Steere. 2001. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin. Infect. Dis. 33:780785.
152. Kang, I.,, S. W. Barthold,, D. H. Persing,, and L. K. Bockenstedt. 1997. T-helper-cell cytokines in the early evolution of murine Lyme arthritis. Infect. Immun. 65:31073111.
153. Kaplan, R. F.,, and L. Jones-Woodward. 1997. Lyme encephalopathy: a neuropsychological perspective. Semin. Neurol. 17:3137.
154. Karlsson, M.,, S. Hammers-Berggren,, L. Lindquist,, G. Stiernstedt,, and B. Svenungsson. 1994. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology 44:12031207.
155. Karlsson, M.,, K. Hovind-Hougen,, B. Svenungsson,, and G. Stiernstedt. 1990. Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis. J. Clin. Microbiol. 28:473479.
156. Karma, A.,, I. Seppala,, H. Mikkila,, S. Kaakkola,, M. Viljanen,,and A. Tarkkanen. 1994. Diagnosis and clinical characteristicsof ocular Lyme borreliosis. Am. J. Ophthalmol. 119: 127135.
157. Kawabata, H.,, T. Masuzawa,, and Y. Yanagihara. 1993. Genomic analysis of Borrelia japonica sp. nov. isolated from Ixodes ovatus in Japan. Microbiol. Immunol. 37:843848.
158. Keane-Myers, A.,, and S. P. Nickell. 1995. Role of IL-4 and IFN-gamma in modulation of immunity to Borrelia burgdorferi in mice. J. Immunol. 155:20202028.
159. Keller, D.,, F. T. Koster,, D. H. Marks,, P. Hosbach,, L. F. Erdile,, and J. P. Mays. 1994. Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. JAMA 271:17641768.
160. Klempner, M. S.,, L. T. Hu,, J. Evans,, C. H. Schmid,, G. M. Johnson,, R. P. Trevino,, D. Norton,, L. Levy,, D. Wall,, J. McCall,, M. Kosinski,, and A. Weinstein. 2001. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N. Engl. J. Med. 345:8592.
161. Klempner, M. S.,, C. H. Schmid,, L. Hu,, A. C. Steere,, G. Johnson,, B. McCloud,, R. Noring,, and A. Weinstein. 2001. Intralaboratory reliability of serologic and urine testing for Lyme disease. Am. J. Med. 110:217219.
162. Kochi, S. K.,, and R. C. Johnson. 1988. Role of immunoglobulin G in killing Borrelia burgdorferi by the classical complement pathway. Infect. Immun. 56:314321.
163. Korenberg, E. I. 1994. Comparative ecology and epidemiology of Lyme disease and tick-borne encephalitis in the former Soviet Union. Parasitol. Today 10:157160
164. Korenberg, E. I.,, N. B. Gorelova,, and Y. V. Kovalevskii,. 2002. Ecology of Borrelia burgdorferi sensu lato in Russia. p. 175200. In O. K. J. S. Gray,, R. S. Lane,, and G. Stanek (ed.), Lyme Borreliosis: Biology, Epidemiology and Control. CABI Publishing, Oxford, England.
165. Kornblatt, A. N.,, P. H. Urband,, and A. C. Steere. 1985. Arthritis caused by Borrelia burgdorferi in dogs. J. Am. Vet. Med. Assoc. 186:960964.
166. Kornmehl, E. W.,, R. L. Lesser,, P. Jaros,, E. Rocco,, and A. C. Steere. 1989. Bilateral keratitis in Lyme disease. Ophthalmology 96:11941197.
167. Kraiczy, P.,, C. Skerka,, M. Kirschfink,, V. Brade,, and P. F. Zipfel. 2001. Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and factor H. Eur. J. Immunol. 31:16741684
168. Kramer, N.,, R. R. Rickert,, R. H. Brodkin,, and E. D. Rosenstein. 1986. Septal panniculitis as a manifestation of Lyme disease. Am. J. Med. 81:149152.
169. Krause, P. J.,, K. McKay,, C. A. Thompson,, V. K. Sikand,, R. Lentz,, T. Lepore,, L. Closter,, D. Christianson,, S. R. Telford,, D. Persing,, J. D. Radolf,, and A. Spielman. 2002. Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin. Infect. Dis. 34:11841191.
170. Krause, P. J.,, S. R. Telford III,, A. Spielman,, V. Sikand,, R. Ryan,, R. N. Christianson,, G. Burke,, P. Brassard,, R. Pollack,, J. Peck,, and D. H. Persing. 1996. Concurrent Lyme disease and babesiosis: evidence for increased severity and duration of illness. JAMA 275:16571660.
171. Kumar, H.,, A. Belperron,, S. W. Barthold,, and L. K. Bockenstedt. 2000. Cutting edge: CD1d deficiency impairs murine host defense against the spirochete, Borrelia burgdorferi. J. Immunol. 165:47974801.
172. Labandeira-Rey, M.,, and J. T. Skare. 2001. Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect. Immun. 69:446455.
173. Lahdenne, P.,, S. F. Porcella,, K. E. Hagman,, D. R. Akins,, T. G. Popova,, D. L. Cox,, L. I. Katona,, J. D. Radolf,, and M. V. Norgard. 1997. Molecular characterization of a 6.6- kilodalton Borrelia burgdorferi outer membrane-associated lipoprotein (lp6.6) which appears to be downregulated during mammalian infection. Infect. Immun. 65:412421.
174. Lane, R. S.,, J. Piesman,, and W. Burgdorfer. 1991. Lyme borreliosis: relation of its causative agent to its vectors and hosts in North America and Europe. Ann. Rev. Immunol. 36:587609.
175. Lardieri, G.,, A. Salvi,, F. Camerini,, M. Cinco,, and G. Trevisan. 1993. Isolation of Borrelia burgdorferi from myocardium. Lancet 342:8869.
176. Lastavica, C. C.,, M. L. Wilson,, V. P. Berardi,, A. Spielman,, and R. D. Deblinger. 1989. Rapid emergence of a focal epidemic of Lyme disease in coastal Massachusetts. N. Engl. J. Med. 320:133137.
177. Lawrenz, M. B.,, H. Kawabata,, J. E. Purser,, and S. J. Norris. 2002. Decreased electroporation efficiency in Borrelia burgdorferi containing linear plasmids lp25 and lp56: impact on transformation of infectious B. burgdorferi. Infect. Immun. 70:47984804
178. Le Fleche, A.,, D. Postic,, K. Girardet,, O. Peter,, and G. Baranton. 1997. Characterization of Borrelia lusitaniae sp. nov. by 16S ribosomal DNA sequence analysis. Int. J. Syst. Bacteriol. 47:921925.
179. Lengl-Janssen, B.,, A. F. Strauss,, A. C. Steere,, and T. Kamradt. 1994. The T helper cell response in Lyme arthritis: differential recognition of Borrelia burgdorferi outer surface protein A (OspA) in patients with treatment-resistant or treatmentresponsive Lyme arthritis. J. Exp. Med. 180:20692078.
180. Leong, J. L.,, P. E. Morrissey,, E. Ortega-Barria,, M. E. A. Pereira,, and J. Coburn. 1995. Hemagglutination and proteoglycan binding by the Lyme disease spirochete, Borrelia burgdorferi. Infect. Immun. 63:874883.
181. Leong, J. M.,, H. Wang,, L. Magoun,, J. A. Field,, P. E. Morrissey,, D. Robbins,, J. B. Tatro,, J. Coburn,, and N. Parveen. 1998. Different classes of proteoglycans contribute to the attachment of Borrelia burgdorferi to cultured endothelial and brain cells. Infect. Immun. 66:994999.
182. Liang, F. T.,, A. C. Steere,, A. R. Marques,, B. J. Johnson,, J. N. Miller,, and M. T. Philipp. 1999. Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi VlsE. J. Clin. Microbiol. 37: 39903996.
183. Lim, L. C. L.,, D. M. England,, B. K. DuChateau,, N. J. Glowacki,, J. R. Creson,, S. D. Lovrich,, S. M. Callister,, D. A. Jobe,, and R. F. Schell. 1994. Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi. Infect. Immun. 62:28252833.
184. Lipschutz, B. 1923. Weiterer Beitrag zur Kenntnis des “Erythema chronicum migrans.” Arch. Dermatol. 143:365374.
185. Logigian, E. L. 1997. Peripheral nervous system Lyme borreliosis. Semin. Neurol. 17:2530.
186. Logigian, E. L.,, R. F. Kaplan,, and A. C. Steere. 1990. Chronic neurologic manifestations of Lyme disease. N. Engl. J. Med. 323:14381444.
187. Logigian, E. L.,, R. F. Kaplan,, and A. C. Steere. 1999. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J. Infect. Dis. 180:377383.
188. Logigian, E. L.,, and A. C. Steere. 1992. Clinical and electrophysiologicfindings in chronic neuropathy of Lyme disease.Neurology 42:303311.
189. LoGiudice, K.,, R. S. Ostfeld,, K. A. Schmidt,, and F. Keesing. 2003. The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk. Proc. Natl. Acad. Sci. USA 100:567571.
190. Luft, B. J.,, R. J. Dattwyler,, R. C. Johnson,, S. W. Luger,, E. M. Bosler,, D. W. Rahn,, E. J. Masters,, E. Grunwaldt,, and S. D. Gadgil. 1996. Azithromycin compared with amoxicillin in the treatment of erythema migrans: a double-blind, randomized, controlled trial. Ann. Intern. Med. 124:785791.
191. Ma, Y.,, K. P. Seiler,, E. J. Eichwals,, J. H. Weis,, C. Teuscher,, and J. J. Weiss. 1998. Distinct characteristics of resistance to Borrelia burgdorferi-induced arthritis in C57BL/6N mice. Infect. Immun. 66:161168.
192. Ma, Y.,, A. Sturrock,, and J. J. Weis. 1991. Intracellular localization of Borrelia burgdorferi within human endothelial cells. Infect. Immun. 59:671678.
193. Ma, Y.,, and J. J. Weis. 1993. Borrelia burgdorferi outer surface lipoproteins OspA and OspB possess B cell mitogenic and cytokine stimulatory properties. Infect. Immun. 61:38433853.
194. Magnarelli, L. A.,, and J. F. Anderson. 1988. Ticks and biting insects infected with the etiologic agent of Lyme disease, Borrelia burgdorferi. J. Clin. Microbiol. 26:14821486.
195. Magnarelli, L. A.,, J. F. Anderson,, C. S. Apperson,, D. Fish,, R. C. Johnson,, and W. C. Chappell. 1986. Spirochetes in ticks and antibodies to Borrelia burgdorferi in white-tailed deer from Connecticut, New York State, and North Carolina. J. Wildlife Dis. 22:178188.
196. Magnarelli, L. A.,, J. F. Anderson,, W. Burgdorfer,, and W. A. Chappell. 1984. Parasitism by Ixodes dammini (Acari: Ixodidae) and antibodies to spirochetes in mammals in Lyme disease foci in Connecticut, USA. J. Med. Entomol. 21: 5257.
197. Magnarelli, L. A.,, J. F. Anderson,, and W. A. Chappell. 1984. Antibodies to spirochetes in white-tailed deer and prevalence of infected ticks from foci of Lyme disease in Connecticut. J. Wildlife Dis. 20:2126.
198. Marconi, R. T.,, D. Liveris,, and I. Schwartz. 1995. Identification of novel insertion elements, restriction fragment length polymorphism patterns, and discontinuous 23S rRNA in Lyme disease spirochetes: phylogenetic analyses of rRNA genes and their intergenic spacers in Borrelia japonica sp. nov. and genomic group 21038 (Borrelia andersonii sp. nov.) isolates. J. Clin. Microbiol. 33:24272434.
199. Marcus, L. C.,, M. M. Patterson,, R. E. Gilfillan,, and P. H. Urband. 1985. Antibodies to Borrelia burgdorferi in New England horses: serologic survey. Am. J. Vet. Res. 46:25702571
200. Marcus, L. C.,, A. C. Steere,, P. H. Duray,, A. E. Anderson,,and E. B. Mahoney. 1985. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis: demonstration ofspirochetes in the myocardium. Ann. Intern. Med. 103:374376.
201. Markowitz, L. E.,, A. C. Steere,, J. L. Benach,, J. D. Slade,, and C. V. Broome. 1986. Lyme disease during pregnancy. JAMA 255:33943396
202. Marshall, W. F., III, S. R. Telford III, P. N. Rys, B. J. Rutledge, D. Mathiesen, S. E. Malawista, A. Spielman, and D. H. Persing. 1994. Detection of Borrelia burgdorferi DNA in museum specimens of Peromyscus leucopus. J. Infect. Dis. 170:10271032.
203. Massarotti, E. M.,, S. W. Luger,, D. W. Rahn,, R. P. Messner,, J. B. Wong,, R. C. Johnson,, and A. C. Steere. 1992. Treatment of early Lyme disease. Am. J. Med. 92:396403.
204. Mast, W. E.,, and W. M. J. Burrows. 1976. Erythema chronicum migrans in the United States. JAMA 236:859860.
205. Masuzawa, T.,, N. Takada,, M. Kudeken,, T. Fukui,, Y. Yano,, F. Ishiguro,, Y. Kawamura,, Y. Imai,, and T. Ezaki. 2001. Borrelia sinica sp. nov., a Lyme disease-related Borrelia species isolated in China. Int. J. Syst. Evol. Microbiol. 51:18171824.
206. Matuschka, F. R.,, and A. Spielman. 1986. The emergence of Lyme disease in a changing environment in North America and central Europe. Exp. Appl. Acarol. 2:337353.
207. Mbow, M. L.,, N. Zeidner,, R. D. J. Gilmore,, M. Dolan,, J. Piesman,, and R. G. Titus. 2001. Major histocompatibility complex class II-independent generation of neutralizing antibodies against T-cell-dependent Borrelia burgdorferi antigens presented by dendritic cells: regulation of NK and γδ T cells. Infect. Immun. 69:24072415.
208. McAlister, H. F.,, P. T. Klementowicz,, C. Andrews,, J. D. Fisher,, M. Feld,, and S. Furman. 1989. Lyme carditis: an important cause of reversible heart block. Ann. Intern. Med. 110:339345.
209. McDowell, J. V.,, J. Wolfgang,, E. Tran,, M. S. Metts,, D. Hamilton,, and R. T. Marconi. 2003. Comprehensive analysis of the factor H binding capabilities of borrelia species associated with Lyme disease: delineation of two distinct classes of factor H binding proteins. Infect. Immun. 71: 35973602.
210. McKisic, M. D.,, and S. W. Barthold. 2000. T-cell-independent responses to Borrelia burgdorferi are critical for protective immunity and resolution of Lyme disease. Infect. Immun. 68:51905197.
211. Meltzer, M. I.,, D. T. Dennis,, and K. A. Orloski. 1999. The cost effectiveness of vaccinating against Lyme disease. Emerg. Infect. Dis. 5:321328.
212. Meyer, A. L.,, C. Trollmo,, F. Crawford,, P. Marrack,, A. C. Steere,, B. T. Huber,, J. Kappler,, and D. A. Hafler. 2000. Direct enumeration of Borrelia-reactive CD4_ T cells ex vivo by using MHC class II tetramers. Proc. Natl. Acad. Sci. USA 97:1143311438
213. Modolell, M.,, U. E. Schaible,, M. Rittig,, and M. M. Simon. 1994. Killing of Borrelia burgdorferi by macrophages is dependent on oxygen radicals and nitric oxide and can be enhanced by antibodies to outer surface proteins of the spirochete. Immunol. Lett. 40:139146..
214. Montgomery, R. R.,, S. E. Malawista,, K. J. M. Feen,, and L. K. Bockenstedt. 1996. Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease. J. Exp. Med.183:261269.
215. Montgomery, R. R.,, M. H. Nathanson,, and S. E. Malawista. 1993. The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery. J. Immunol. 150:909915.
216. Motaleb, M. A.,, L. Corum,, J. L. Bono,, A. F. Elias,, P. Rosa,, D. S. Samuels,, and N. W. Charon. 2000. Borrelia burgdorferi periplasmic flagella have both skeletal and motility functions. Proc. Natl. Acad. Sci. USA 97:1089910904.
217. Mullegger, R. R.,, G. McHugh,, R. Ruthazer,, B. Binder,, H. Kerl,, and A. C. Steere. 2000. Differential expression of cytokine mRNA in skin specimens from patients with erythema migrans or acrodermatitis chronica atrophicans. J. Investig. Dermatol. 115:11151123.
218. Nadelman, R. B.,, S. W. Luger,, E. Frank,, M. Wisniewski,, J. J. Collins,, and G. P. Wormser. 1992. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann. Intern. Med. 117:273280.
219. Nadelman, R. B.,, J. Nowakowski,, D. Fish,, R. C. Falco,, K. Freeman,, D. McKenna,, P. Welch,, R. Marcus,, M. E. Aguero–Rosenfeld,, D. T. Dennis,, and G. P. Wormser. 2001. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345:7984.
220. Nadelman, R. B.,, J. Nowakowski,, G. Forseter,, N. S. Goldberg,, S. Bittker,, D. Cooper,, M. Aguero-Rosenfeld,, and G. Wormser. 1996. The clinical spectrum of early Lyme borreliosisin patients with culture-confirmed erythema migrans. Am. J. Med. 100:502508.
221. Neubert, U.,, M. Schaller,, E. Januschke,, W. Stolz,, and H. Schmieger. 1993. Bacteriophages induced by ciprofloxacin in a Borrelia burgdorferi skin isolate. Zentralbl. Bakteriol. 279:307315.
222. Nguyen, T. P.,, T. T. Lam,, S. W. Barthold,, S. R. Telford III,, R. A. Flavell,, and E. Fikrig. 1994. Partial destruction of Borrelia burgdorferi within ticks that engorged on OspEor OspF-immunized mice. Infect. Immun. 62:20792084.
223. Nocton, J. J.,, B. J. Bloom,, B. J. Rutledge,, D. H. Persing,, E. L. Logigian,, C. H. Schmid,, and A. C. Steere. 1996. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in patients with Lyme neuroborreliosis. J. Infect. Dis. 174:623627.
224. Nocton, J. J.,, F. Dressler,, B. J. Rutledge,, P. N. Rys,, D. H. Persing,, and A. C. Steere. 1994. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid in Lyme arthritis. N. Engl. J. Med. 330:229234.
225. Nowakowski, J.,, D. McKenna,, R. B. Nadelman,, D. Cooper,, S. Bittker,, D. Holmgren,, C. Pavia,, R. C. Johnson,, and G. P. Wormser. 2000. Failure of treatment with cephalexin for Lyme disease. Arch. Fam. Med. 9:563567.
226. O’Connell, S.,, M. Granstrom,, J. S. Gray,, and G. Stanek. 1998. Epidemiology of European Lyme borreliosis. Zentralbl. Bakteriol. 287:229240.
227. Ohnishi, J.,, J. Piesman,, and A. M. de Silva. 2001. Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. Proc. Natl. Acad. Sci. USA 98: 670675.
228. Oksi, J.,, J. Savolainen,, J. Pene,, J. Bousqet,, P. Laippala,, and M. K. Viljanen. 1996. Decreased interleukin-4 and increased gamma interferon production by peripheral blood mononuclear cells of patients with Lyme borreliosis. Infect. Immun. 64:36203623.
229. Olsen, B.,, T. G. Jaenson,, and S. Bergstrom. 1995. Prevalence of Borrelia burgdorferi sensu lato-infected ticks on migrating birds. Appl. Environ. Microbiol. 61:30823087.
230. Oransky, S.,, B. Roseman,, D. Fish, et al. 1989. Seizures temporarily associated with the use of DEET insect repellent— New York and Connecticut. Morb. Mortal. Wkly. Rep. 38:678.
231. Orloski, K. A.,, E. B. Hayes,, G. L. Campbell,, and D. T. Dennis. 2000. Surveillance for Lyme disease—United States, 1992-1998. Morb. Mortal. Wkly. Rep. 49:111.
232. Oschmann, P.,, W. Dorndorf,, C. Hornig,, C. Schafer,, H. J. Wellensiek,, and K. W. Pflughaupt. 1998. Stages and syndromes of neuroborreliosis. J. Neurol. 245:262272.
233. Pachner, A. R.,, and A. C. Steere. 1985. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology 35:4753.
234. Parveen, N.,, and J. M. Leong. 2000. Identification of a candidate glycosaminoglycan-binding adhesin of the Lyme disease spirochete Borrelia burgdorferi. Mol. Microbiol. 35:12201234
235. Patel, R.,, K. L. Grogg,, W. D. Edwards,, A. J. Wright,, and N. M. Schwenk. 2000. Death from inappropriate therapy for Lyme disease. Clin. Infect. Dis. 31:11071109.
236. Peltomaa, M.,, G. McHugh,, and A. C. Steere. 2003. Persistence of antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease. J. Infect. Dis. 187:11781186.
237. Peltomaa, M.,, I. Pyykko,, I. Seppala,, and M. Viljanen. 2002. Lyme borreliosis and facial paralysis—a prospective analysis of risk factors and outcome. Am. J. Otolaryngol. 23:125132.
238. Persing, D. H.,, S. R. Telford III,, P. N. Rys,, D. E. Dodge,, T. J. White,, S. E. Malawista,, and A. Spielman. 1990. Detection of Borrelia burgdorferi DNA in museum specimens of Ixodes dammini ticks. Science 249:14201423.
239. Pfister, H. W.,, V. Preac-Mursic,, B. Wilske,, and K. M. Einhaupl. 1989. Cefotaxime vs penicillin G for acute neurologic manifestations of Lyme borreliosis: a prospective randomized study. Arch. Neurol. 46:11901194.
240. Pfister, H. W.,, V. Preac-Mursic,, B. Wilske,, E. Schielke,, F. Sorgel,, and K. M. Einhaupl. 1991. Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. J. Infect. Dis. 163:311318.
241. Piesman, J.,, T. N. Mather,, R. J. Sinsky,, and A. Spielman. 1987. Duration of tick attachment and Borrelia burgdorferi transmission. J. Clin. Microbiol. 25:557558.
242. Posey, J. E.,, and F. C. Gherardini. 2000. Lack of a role for iron in the Lyme disease pathogen. Science 288:16511653.
243. Postic, D.,, N. M. Ras,, R. S. Lane,, M. Hendson,, and G. Baranton. 1998. Expanded diversity among California borrelia isolates and description of Borrelia bissettii sp. nov. (formerly Borrelia group DN127). J. Clin. Microbiol. 36: 34973504.
244. Potter, M. R.,, S. R. Rittling,, D. T. Denhardt,, R. J. Roper,, J. H. Weis,, C. Teuscher,, and J. J. Weis. 2002. Role of osteopontin in murine Lyme arthritis and host defense against Borrelia burgdorferi. Infect. Immun. 70:13721381.