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Lyme Disease

  • Infectious Disease Epidemiology (AL Reingold, Section Editor)
  • Published:
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Abstract

Lyme disease is caused by the spirochetal bacteria Borrelia burgdorferi and transmitted by ticks in the genus Ixodes. The key reservoirs for the spirochete include rodents and birds, and the primary hosts for ticks include rodents, birds, and lizards for immature stages and large mammal for the adults. Since its recognition in the USA in the 1970s, it has continued to emerge, increasing both in case numbers and geographic distribution. In the last two decades, a number of new findings have been observed, including a vast increase in disease distribution, additional Borrelia species causing disease in humans, and newly recognized clinical presentations of the disease. Areas of greatest need include (1) new diagnostic tests, including tests that detect Borrelia DNA, antigens, or metabolites, (2) a better understanding of disease pathogenesis particularly in the case of post-treatment Lyme disease syndrome, and (3) the development of safe and effective interventions.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum. 1977;20(1):7–17.

    Article  CAS  PubMed  Google Scholar 

  2. Steere AC, Broderick TF, Malawista SE. Erythema chronicum migrans and Lyme arthritis: epidemiologic evidence for a tick vector. Am J Epidemiol. 1978;108(4):312–21.

    CAS  PubMed  Google Scholar 

  3. Steere AC, Malawista SE. Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini. Ann Intern Med. 1979;91(5):730–3.

    Article  CAS  PubMed  Google Scholar 

  4. Afzelius A. Report to Verhandlungen der dermatologischen Gesellschaft zu Stockholm on December 16, 1909. Arch Dermatol Syph. 1910;101:405–6.

  5. Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP. Lyme disease—a tick-borne spirochetosis? Science. 1982;216(4552):1317–9.

    Article  CAS  PubMed  Google Scholar 

  6. Steere AC, Grodzicki RL, Kornblatt AN, Craft JE, Barbour AG, Burgdorfer W, et al. The spirochetal etiology of Lyme disease. N Engl J Med. 1983;308(13):733–40.

    Article  CAS  PubMed  Google Scholar 

  7. Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest. 2004;113(8):1093–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Piesman J, Eisen L. Prevention of tick-borne diseases. Annu Rev Entomol. 2008;53:323–43.

    Article  CAS  PubMed  Google Scholar 

  9. Spielman A, Levine JF, Wilson ML. Vectorial capacity of North American Ixodes ticks. Yale J Biol Med. 1984;57(4):507–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Lane RS, Loye JE. Lyme disease in California: interrelationship of Ixodes pacificus (Acari: Ixodidae), the western fence lizard (Sceloporus occidentalis), and Borrelia burgdorferi. J Med Entomol. 1989;26(4):272–8.

    Article  CAS  PubMed  Google Scholar 

  11. Eisen L, Eisen RJ, Lane RS. The roles of birds, lizards, and rodents as hosts for the western black-legged tick Ixodes pacificus. J Vector Ecol. 2004;29(2):295–308.

    PubMed  Google Scholar 

  12. Mead PS. Epidemiology of Lyme disease. Infect Dis Clin North Am. 2015;29(2):187–210.

    Article  PubMed  Google Scholar 

  13. Centers for Disease Control and Prevention. Summary of notifiable diseases—United States, 2012. Morbid Mortal Wkly Rep. 2014;61(53):1–121.

    Google Scholar 

  14. Meek JI, Roberts CL, Smith Jr EV, Cartter ML. Underreporting of Lyme disease by Connecticut physicians, 1992. J Public Health Manag Pract. 1996;2(4):61–5.

    Article  CAS  PubMed  Google Scholar 

  15. Coyle BS, Strickland GT, Liang YY, Pena C, Mccarter R, Israel E. The public health impact of Lyme disease in Maryland. J Infect Dis. 1996;173(5):1260–2.

    Article  CAS  PubMed  Google Scholar 

  16. Naleway AL, Belongia EA, Kazmierczak JJ, Greenlee RT, Davis JP. Lyme disease incidence in Wisconsin: a comparison of state-reported rates and rates from a population-based cohort. Am J Epidemiol. 2002;155(12):1120–7.

    Article  PubMed  Google Scholar 

  17. Hinckley AF, Connally NP, Meek JI, Johnson BJ, Kemperman MM, Feldman KA, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis. 2014(doi: 10.1093/cid/ciu397).

  18. Nelson CA, Saha S, Kugeler KJ, Delorey MJ, Shankar MB, Hinckley AF, et al. Incidence of clinician-diagnosed Lyme disease, United States, 2005–2010. Emerg Infect Dis. 2015;21(9):1625–31. This article establishes the current estimate for Lyme disease cases in the USA to be over 320,000, which is approximately ten times higher than the number of cases that are reported each year.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kugeler KJ, Farley GM, Forrester JD, Mead PS. Geographic distribution and expansion of human Lyme Disease, United States. Emerg Infect Dis. 2015;21(8):1455–7. This paper documents the significant increase in the numbers of high-incidence counties for Lyme disease over the last 20 years in the USA. The number of high-incidence counties in the northeastern USA increased by over 320 % during this time period and in the north-central USA by close to 250 %.

    Article  PubMed  Google Scholar 

  20. Spielman A, Wilson ML, Levine JF, Piesman J. Ecology of Ixodes dammini-borne human babesiosis and Lyme disease. Annu Rev Entomol. 1985;30:439–60.

    Article  CAS  PubMed  Google Scholar 

  21. Wood CL, Lafferty KD. Biodiversity and disease: a synthesis of ecological perspectives on Lyme disease transmission. Trends Ecol Evol. 2013;28(4):239–47.

    Article  PubMed  Google Scholar 

  22. Stafford KC, 3rd. Tick Management Handbook 2007 [cited 2014 October 21]. Available from: http://www.ct.gov/caes/lib/caes/documents/publications/bulletins/b1010.pdf.

  23. Allan BF, Keesing F, Ostfeld RS. Effect of forest fragmentation on Lyme disease risk. Conserv Biol. 2003;17(1):267–72.

    Article  Google Scholar 

  24. Eisen RJ, Eisen L, Ogden NH, Beard CB. Linkages of weather and climate with Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), enzootic transmission of Borrelia burgdorferi, and Lyme disease in North America. J Med Entomol. 2016;53(2):250–61.

  25. Eisen RJ, Eisen L, Beard CB. County-scale distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the continental United States. J Med Entomol. 2016;53(2):349–86.

  26. Margos G, Vollmer SA, Ogden NH, Fish D. Population genetics, taxonomy, phylogeny and evolution of Borrelia burgdorferi sensu lato. Infect Genet Evol. 2011;11(7):1545–63.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pritt BS, Mead PS, Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis. 2016;16(5):556–64. This article describes a new tick-borne disease agent Borrelia mayonii, causing Lyme borreliosis in the upper Midwest. The paper discusses a series of patients and the corresponding clinical and diagnostic findings.

  28. Golovchenko M, Vancova M, Clark K, Oliver Jr JH, Grubhoffer L, Rudenko N. A divergent spirochete strain isolated from a resident of the southeastern United States was identified by multilocus sequence typing as Borrelia bissettii. Parasit Vectors. 2016;9(1):68.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rudenko N, Golovchenko M, Vancova M, Clark K, Grubhoffer L, Oliver Jr JH. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. Clin Microbiol Infect. 2016;22(3):267. e9–e15.

    Article  PubMed  Google Scholar 

  30. Girard YA, Fedorova N, Lane RS. Genetic diversity of Borrelia burgdorferi and detection of B. bissettii-like DNA in serum of north-coastal California residents. J Clin Microbiol. 2011;49(3):945–54.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, 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(9):1089–134.

    Article  PubMed  Google Scholar 

  32. Schutzer SE, Berger BW, Krueger JG, Eshoo MW, Ecker DJ, Aucott JN. Atypical erythema migrans in patients with PCR-positive Lyme disease. Emerg Infect Dis. 2013;19(5):815–7.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Stanek G, Strle F. Lyme disease: European perspective. Infect Dis Clin North Am. 2008;22(2):327–39. vii.

    Article  PubMed  Google Scholar 

  34. Forrester JD, Meiman J, Mullins J, Nelson R, Ertel SH, Cartter M, et al. Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death—United States. MMWR Morb Mortal Wkly Rep. 2014;63(43):982–3.

    PubMed  Google Scholar 

  35. Forrester JD, Mead P. Third-degree heart block associated with lyme carditis: review of published cases. Clin Infect Dis. 2014;59(7):996–1000.

    Article  PubMed  Google Scholar 

  36. Hu L. Lyme arthritis. Infect Dis Clin North Am. 2005;19(4):947–61.

    Article  PubMed  Google Scholar 

  37. CDC. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR. 1995;44(31):590–1.

    Google Scholar 

  38. Marques AR. Laboratory diagnosis of Lyme disease: advances and challenges. Infect Dis Clin North Am. 2015;29(2):295–307.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ. Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay. Clin Infect Dis. 2011;53(6):541–7.

    Article  CAS  PubMed  Google Scholar 

  41. Wormser GP, Levin A, Soman S, Adenikinju O, Longo MV, Branda JA. Comparative cost-effectiveness of two-tiered testing strategies for serodiagnosis of lyme disease with noncutaneous manifestations. J Clin Microbiol. 2013;51(12):4045–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Branda JA, Aguero-Rosenfeld ME, Ferraro MJ, Johnson BJ, Wormser GP, Steere AC. 2-tiered antibody testing for early and late Lyme disease using only an immunoglobulin G blot with the addition of a VlsE band as the second-tier test. Clin Infect Dis. 2010;50(1):20–6.

    Article  CAS  PubMed  Google Scholar 

  43. Wormser GP, Schriefer M, Aguero-Rosenfeld ME, Levin A, Steere AC, Nadelman RB, et al. Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease. Diagn Microbiol Infect Dis. 2013;75(1):9–15.

    Article  CAS  PubMed  Google Scholar 

  44. Bacon RM, Biggerstaff BJ, Schriefer ME, Gilmore Jr RD, Philipp MT, Steere AC, 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(8):1187–99.

    Article  CAS  PubMed  Google Scholar 

  45. Theel ES. The past, present and (possible) future of serologic testing for Lyme disease. J Clin Microbiol. 2016;54(5):1191–96.

  46. Halpern MD, Jain S, Jewett MW. Enhanced detection of host response antibodies to Borrelia burgdorferi using immuno-PCR. Clin Vaccine Immunol. 2013;20(3):350–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lahey LJ, Panas MW, Mao R, Delanoy M, Flanagan JJ, Binder SR, et al. Development of a multiantigen panel for improved detection of Borrelia burgdorferi infection in early Lyme disease. J Clin Microbiol. 2015;53(12):3834–41.

    PubMed  PubMed Central  Google Scholar 

  48. Molins CR, Ashton LV, Wormser GP, Hess AM, Delorey MJ, Mahapatra S, et al. Development of a metabolic biosignature for detection of early Lyme disease. Clin Infect Dis. 2015;60(12):1767–75.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tugwell P, Dennis DT, Weinstein A, Wells G, Shea B, Nichol G, et al. Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med. 1997;127(12):1109–23.

    Article  CAS  PubMed  Google Scholar 

  50. Forrester JD, Brett M, Matthias J, Stanek D, Springs CB, Marsden-Haug N, et al. Epidemiology of Lyme disease in low-incidence states. Ticks Tick Borne Dis. 2015;6(6):721–3.

    Article  PubMed  Google Scholar 

  51. Lantos PM, Branda JA, Boggan JC, Chudgar SM, Wilson EA, Ruffin F, et al. Poor positive predictive value of Lyme disease serologic testing in an area of low disease incidence. Clin Infect Dis. 2015;61(9):1374–80.

    Article  PubMed  Google Scholar 

  52. Ljostad U, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, et al. Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial. Lancet Neurol. 2008;7(8):690–5.

    Article  PubMed  Google Scholar 

  53. Borg R, Dotevall L, Hagberg L, Maraspin V, Lotric-Furlan S, Cimperman J, et al. Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis. Scand J Infect Dis. 2005;37(6–7):449–54.

    Article  CAS  PubMed  Google Scholar 

  54. Dotevall L, Hagberg L. Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis. Clin Infect Dis. 1999;28(3):569–74.

    Article  CAS  PubMed  Google Scholar 

  55. Karlsson M, Hammers-Berggren S, Lindquist L, Stiernstedt G, Svenungsson B. Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis. Neurology. 1994;44(7):1203–7.

    Article  CAS  PubMed  Google Scholar 

  56. Bremell D, Dotevall L. Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis, myelitis, vasculitis or intracranial hypertension. Eur J Neurol. 2014;21(9):1162–7.

    Article  CAS  PubMed  Google Scholar 

  57. Marques A. Chronic Lyme disease: a review. Infect Dis Clin N Am. 2008;22(2):341–60.

  58. Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Eng J Med. 2001;345(2):85–92.

    Article  CAS  Google Scholar 

  59. Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992–1003.

    Article  CAS  PubMed  Google Scholar 

  60. Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.[see comment]. Neurology. 2003;60(12):1923–30.

    Article  CAS  PubMed  Google Scholar 

  61. Berende A, ter Hofstede HJ, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016;374(13):1209–20.

    Article  CAS  PubMed  Google Scholar 

  62. Feng J, Shi W, Zhang S, Zhang Y. Persister mechanisms in Borrelia burgdorferi: implications for improved intervention. Emerg Microbes Infect. 2015;4(8), e51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Caskey JR, Embers ME. Persister development by Borrelia burgdorferi populations in vitro. Antimicrob Agents Chemother. 2015;59(10):6288–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob Agents Chemother. 2015;59(8):4616–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wood TK, Knabel SJ, Kwan BW. Bacterial persister cell formation and dormancy. Appl Environ Microbiol. 2013;79(23):7116–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cohen NR, Lobritz MA, Collins JJ. Microbial persistence and the road to drug resistance. Cell Host Microbe. 2013;13(6):632–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015;10(3), e0117207.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Wagh D, Pothineni VR, Inayathullah M, Liu S, Kim KM, Rajadas J. Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition. Drug Des Devel Ther. 2015;9:805–16.

    PubMed  PubMed Central  Google Scholar 

  69. Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, et al. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS One. 2012;7(1), e29914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52(5):1728–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hodzic E, Imai D, Feng S, Barthold SW. Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice. PLoS One. 2014;9(1), e86907.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Bockenstedt LK, Mao J, Hodzic E, Barthold SW, Fish D. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis. 2002;186(10):1430–7.

    Article  PubMed  Google Scholar 

  73. Wormser GP, Baker PJ, O’Connell S, Pachner AR, Schwartz I, Shapiro ED. Critical analysis of treatment trials of rhesus macaques infected with Borrelia burgdorferi reveals important flaws in experimental design. Vector Borne Zoonotic Dis. 2012;12(7):535–8.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Marques A, Telford SR, Turk SP, Chung E, Williams C, Dardick K, et al. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clinical Infectious Diseases. 2014;in press.

  75. Poland GA. Prevention of Lyme disease: a review of the evidence. Mayo Clin Proc. 2001;76(7):713–24.

    Article  CAS  PubMed  Google Scholar 

  76. Mead P, Hinckley A, Hook S, Beard CB. TickNET-a collaborative public health approach to tickborne disease surveillance and research. Emerg Infect Dis. 2015;21(9):1574–7.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thanks Dr. Marty Schriefer for his critical feedback on the manuscript. The findings and conclusions in this report have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.

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Authors and Affiliations

  1. Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, 3156 Rampart Road, Fort Collins, 80521, CO, USA

    Charles B. Beard, Alison F. Hinckley & Paul S. Mead

  2. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA

    Linden T. Hu

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  1. Charles B. Beard
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Charles B. Beard, Alison F. Hinckley, and Paul S. Mead declare that they have no conflict of interest.

Linden T. Hu declares personal fees for acting as a consultant for Abzyme, contracts to his institution from Massbiologics and Sanofi, and royalties from Uptodate.

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Beard, C.B., Hu, L.T., Hinckley, A.F. et al. Lyme Disease. Curr Epidemiol Rep 3, 252–258 (2016). https://doi.org/10.1007/s40471-016-0082-8

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