Current Allergy and Asthma Reports

, Volume 10, Issue 1, pp 13–20

Lyme Disease: A Review

Article

Abstract

Lyme disease is the most common vector-borne illness in the United States and is also endemic in Europe and Asia. It is caused by the spirochete Borrelia burgdorferi and transmitted by the bite of the Ixodes (deer) tick. It occurs most frequently during spring and summer and may involve the skin, nervous system, heart, and joints. This article reviews the pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease.

Keywords

Lyme disease Borrelia burgdorferi Infection Tick-borne illness 

References

  1. 1.
    Bacon RM, Kugeler KJ, Mead PS: Surveillance for Lyme disease—United States, 1992–2006. MMWR Surveill Summ 2008, 57:1–9.PubMedGoogle Scholar
  2. 2.
    Steere AC, Malawista SE, Snydman DR, et al.: Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum 1977, 20:7–17.CrossRefPubMedGoogle Scholar
  3. 3.
    Burgdorfer W, Barbour AG, Hayes SF, et al.: Lyme disease—a tick-borne spirochetosis? Science 1982, 216:1317–1319.CrossRefPubMedGoogle Scholar
  4. 4.
    Terekhova D, Iyer R, Wormser GP, Schwartz I: Comparative genome hybridization reveals substantial variation among clinical isolates of Borrelia burgdorferi sensu stricto with different pathogenic properties. J Bacteriol 2006, 188:6124–6134.CrossRefPubMedGoogle Scholar
  5. 5.
    Stewart PE, Byram R, Grimm D, et al.: The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen. Plasmid 2005, 53:1–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Pal U, de Silva AM, Montgomery RR, et al.: Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. J Clin Invest 2000, 106:561–569.CrossRefPubMedGoogle Scholar
  7. 7.
    Schwan TG, Piesman J, Golde WT, et al.: Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A 1995, 92:2909–2913.CrossRefPubMedGoogle Scholar
  8. 8.
    Tilly K, Krum JG, Bestor A, et al.: Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection. Infect Immun 2006, 74:3554–3564.CrossRefPubMedGoogle Scholar
  9. 9.
    Lagal V, Postic D, Rubic-Sabljic E, Baranton G: Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness. J Clin Microbiol 2003, 41:5059–5065.CrossRefPubMedGoogle Scholar
  10. 10.
    Seinost G, Dykhuizen DE, Dattwyler RJ, et al.: Four clones of Borrelia burgdorferi sensu stricto cause invasive infection in humans. Infect Immun 1999, 67:3518–3524.PubMedGoogle Scholar
  11. 11.
    Labandeira-Rey M, Seshu J, Skare JT: The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms. Infect Immun 2003, 71:4608–4613.CrossRefPubMedGoogle Scholar
  12. 12.
    Coutte L, Botkin DJ, Gao L, Norris SJ: Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS Pathog 2009, 5:e1000293.CrossRefPubMedGoogle Scholar
  13. 13.
    Hirschfeld M, Kirschning CJ, Schwandner R, et al.: Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by Toll-like receptor 2. J Immunol 1999, 163:2382–2386.PubMedGoogle Scholar
  14. 14.
    Salazar JC, Pope CD, Sellati TJ, et al.: Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans. J Immunol 2003, 171:2660–2670.PubMedGoogle Scholar
  15. 15.
    Bolz DD, Sundsbak RS, Ma Y, et al.: MyD88 plays a unique role in host defense but not arthritis development in Lyme disease. J Immunol 2004, 173:2003–2010.PubMedGoogle Scholar
  16. 16.
    Petzke MM, Brooks A, Krupna MA, et al.: Recognition of Borrelia burgdorferi, the Lyme disease spirochete, by TLR7 and TLR9 induces a type I IFN response by human immune cells. J Immunol 2009, 183:5279–5292.CrossRefPubMedGoogle Scholar
  17. 17.
    Miller JC, Ma Y, Bian J, et al.: A critical role for type I IFN in arthritis development following Borrelia burgdorferi infection of mice. J Immunol 2008, 181:8492–8503.PubMedGoogle Scholar
  18. 18.
    Zeidner NS, Schneider BS, Rutherford JS, Dolan MC: Suppression of Th2 cytokines reduces tick-transmitted Borrelia burgdorferi load in mice. J Parasitol 2008, 94:767–769.PubMedGoogle Scholar
  19. 19.
    Ekerfelt C, Andersson M, Olausson A, et al.: Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice. Clin Exp Immunol 2007, 150:189–197.PubMedCrossRefGoogle Scholar
  20. 20.
    Muller-Doblies UU, Maxwell SS, Boppana VD, et al.: Feeding by the tick, Ixodes scapularis, causes CD4(+) T cells responding to cognate antigen to develop the capacity to express IL-4. Parasite Immunol 2007, 29:485–499.CrossRefPubMedGoogle Scholar
  21. 21.
    Piesman J, Mather TN, Sinsky RJ, Spielman A: Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 1987, 25:557–558.PubMedGoogle Scholar
  22. 22.
    Nadelman RB, Nowakowski J, Forseter G, et al.: The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996, 100:502–508.CrossRefPubMedGoogle Scholar
  23. 23.
    Strle F, Nadelman RB, Cimperman J, et al.: Comparison of culture-confirmed erythema migrans caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann Intern Med 1999, 130:32–36.PubMedGoogle Scholar
  24. 24.
    Steere AC, Dhar A, Hernandez J, et al.: Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease. Am J Med 2003, 114:58–62.CrossRefPubMedGoogle Scholar
  25. 25.
    Steere AC, Schoen RT, Taylor E: The clinical evolution of Lyme arthritis. Ann Intern Med 1987, 107:725–731.PubMedGoogle Scholar
  26. 26.
    Drouin EE, Glickstein LJ, Kwok WW, et al.: Searching for borrelial T cell epitopes associated with antibiotic-refractory Lyme arthritis. Mol Immunol 2008, 45:2323–2332.CrossRefPubMedGoogle Scholar
  27. 27.
    Steere AC, Klitz W, Drouin EE, et al.: Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med 2006, 203:961–971.CrossRefPubMedGoogle Scholar
  28. 28.
    Gross DM, Forsthuber T, Tary-Lehmann M, et al.: Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 1998, 281:703–706.CrossRefPubMedGoogle Scholar
  29. 29.
    Drouin EE, Glickstein LJ, Kwok WW, et al.: Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis. Mol Immunol 2008, 45:180–189.CrossRefPubMedGoogle Scholar
  30. 30.
    Jones KL, McHugh GA, Glickstein LJ, Steere AC: Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: high frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis. Arthritis Rheum 2009, 60:2174–2182.CrossRefPubMedGoogle Scholar
  31. 31.
    Codolo G, Amedei A, Steere AC, et al.: Borrelia burgdorferi NapA-driven Th17 cell inflammation in lyme arthritis. Arthritis Rheum 2008, 58:3609–3617.CrossRefPubMedGoogle Scholar
  32. 32.
    Iliopoulou BP, Alroy J, Huber BT: CD28 deficiency exacerbates joint inflammation upon Borrelia burgdorferi infection, resulting in the development of chronic Lyme arthritis. J Immunol 2007, 179:8076–8082.PubMedGoogle Scholar
  33. 33.
    Halperin JJ, Volkman DJ, Wu P: Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991, 41:1571–1582.PubMedGoogle Scholar
  34. 34.
    Halperin J, Luft BJ, Volkman DJ, Dattwyler RJ: Lyme neuroborreliosis. Peripheral nervous system manifestations. Brain 1990, 113:1207–1221.CrossRefPubMedGoogle Scholar
  35. 35.
    Hemmer B, Gran B, Zhao Y, et al.: Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat Med 1999, 5:1375–1382.CrossRefPubMedGoogle Scholar
  36. 36.
    Feder HM Jr, Johnson BJ, O’Connell S, et al.: A critical appraisal of “chronic Lyme disease.” N Engl J Med 2007, 357:1422–1430.CrossRefPubMedGoogle Scholar
  37. 37.
    Marques A: Chronic Lyme disease: a review. Infect Dis Clin North Am 2008, 22:341–360, vii–viii.Google Scholar
  38. 38.
    Effect of electronic laboratory reporting on the burden of lyme disease surveillance—New Jersey, 2001–2006. MMWR Morb Mortal Wkly Rep 2008, 57:42–45.Google Scholar
  39. 39.
    Klempner MS, Schmid CH, Hu L, et al.: Intralaboratory reliability of serologic and urine testing for Lyme disease. Am J Med 2001, 110:217–219.CrossRefPubMedGoogle Scholar
  40. 40.
    Wormser GP, Liveris D, Hanincova K, et al.: Effect of Borrelia burgdorferi genotype on the sensitivity of C6 and 2-tier testing in North American patients with culture-confirmed Lyme disease. Clin Infect Dis 2008, 47:910–914.CrossRefPubMedGoogle Scholar
  41. 41.
    Strle F, Ruzic-Sabljic E, Cimperman J, et al.: Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. Clin Infect Dis 2006, 43:704–710.CrossRefPubMedGoogle Scholar
  42. 42.
    Wormser GP, Brisson D, Liveris D, et al.: Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008, 198:1358–1364.CrossRefPubMedGoogle Scholar
  43. 43.
    Nowakowski J, Schwartz I, Liveris D, et al.: Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin Infect Dis 2001, 33:2023–2027.CrossRefPubMedGoogle Scholar
  44. 44.
    Cerar T, Rusic-Sabljic E, Glinsek U, et al.: Comparison of PCR methods and culture for the detection of Borrelia spp. in patients with erythema migrans. Clin Microbiol Infect 2008, 14:653–658.CrossRefPubMedGoogle Scholar
  45. 45.
    Liveris D, Wang G, Girao G, et al.: Quantitative detection of Borrelia burgdorferi in 2-millimeter skin samples of erythema migrans lesions: correlation of results with clinical and laboratory findings. J Clin Microbiol 2002, 40:1249–1253.CrossRefPubMedGoogle Scholar
  46. 46.
    Nocton JJ, Dressler F, Rutledge BJ, et al.: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994, 330:229–234.CrossRefPubMedGoogle Scholar
  47. 47.
    Nocton JJ, Bloom BJ, Rutledge BJ, et al.: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1996, 174:623–627.PubMedGoogle Scholar
  48. 48.
    Lebech AM, Hansen K, Brandrup F, et al.: Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis. Mol Diagn 2000, 5:139–150.PubMedGoogle Scholar
  49. 49.
    Zore A, Ruzic-Sabljic E, Maraspin V, et al.: Sensitivity of culture and polymerase chain reaction for the etiologic diagnosis of erythema migrans. Wien Klin Wochenschr 2002, 114:606–609.PubMedGoogle Scholar
  50. 50.
    Bacon RM, Biggerstaff BJ, Schriefer ME, et al.: 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 2003, 187:1187–1199.CrossRefPubMedGoogle Scholar
  51. 51.
    Glatz M, Fingerle V, Wilske B, et al.: Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with erythema migrans. Dermatology 2008, 216:93–103.CrossRefPubMedGoogle Scholar
  52. 52.
    Kalish RA, McHugh G, Granquist, J, et al.: Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis 2001, 33:780–785.CrossRefPubMedGoogle Scholar
  53. 53.
    Guidelines for laboratory evaluation in the diagnosis of Lyme disease. American College of Physicians. Ann Intern Med 1997, 127:1106–1108.Google Scholar
  54. 54.
    Notice to readers: caution regarding testing for Lyme disease. MMWR CDC Surveill Summ 2005, 54:125.Google Scholar
  55. 55.
    Marques A, Brown MR, Fleisher TA: Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin Vaccine Immunol 2009, 16:1249–1250.CrossRefPubMedGoogle Scholar
  56. 56.
    Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995, 44:590–591.Google Scholar
  57. 57.
    Liang FT, Steere AC, Marques AR, et al.: 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 1999, 37:3990–3996.PubMedGoogle Scholar
  58. 58.
    Ledue TB, Collins MF, Young J, Schriefer ME: Evaluation of the recombinant VlsE-based liaison chemiluminescence immunoassay for detection of Borrelia burgdorferi and diagnosis of Lyme disease. Clin Vaccine Immunol 2008, 15:1796–1804.CrossRefPubMedGoogle Scholar
  59. 59.
    Steere AC, McHugh G, Damle N, Sikand VK: Prospective study of serologic tests for lyme disease. Clin Infect Dis 2008, 47:188–195.CrossRefPubMedGoogle Scholar
  60. 60.
    Blanc F, Jaulhac B, Fleury M, et al.: Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology 2007, 69:953–958.CrossRefPubMedGoogle Scholar
  61. 61.
    Bakken JS, Dumler S: Human granulocytic anaplasmosis. Infect Dis Clin North Am 2008, 22:433–448, viii.Google Scholar
  62. 62.
    Vannier E, Gewurz BE, Krause PJ: Human babesiosis. Infect Dis Clin North Am 2008, 22:469–488, viii–ix.Google Scholar
  63. 63.
    Wormser GP, Dattwyler RJ, Shapiro ED, et al.: The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006, 43:1089–1134.CrossRefPubMedGoogle Scholar
  64. 64.
    Masters EJ, Grigery CN, Masters RW: STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness. Infect Dis Clin North Am 2008, 22:361–376, viii.Google Scholar
  65. 65.
    Steere AC: Lyme borreliosis in 2005, 30 years after initial observations in Lyme Connecticut. Wien Klin Wochenschr 2006, 118:625–633.CrossRefPubMedGoogle Scholar
  66. 66.
    Ball R, Shadomy SV, Meyer A, et al.: HLA type and immune response to Borrelia burgdorferi outer surface protein A in people in whom arthritis developed after Lyme disease vaccination. Arthritis Rheum 2009, 60:1179–1186.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA

Personalised recommendations