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Tick-Borne Encephalopathies

Epidemiology, Diagnosis, Treatment and Prevention

  • Therapy in Practice
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Abstract

Tick-borne encephalopathies constitute a broad range of infectious diseases affecting the brain and other parts of the CNS. The causative agents are both viral and bacterial. This review focuses on the current most important tick-borne human diseases: tick-borne encephalitis (TBE; including Powassan encephalitis) and Lyme borreliosis. Rocky Mountain spotted fever (RMSF) and Colorado tick fever (CTF), less common tick-borne diseases associated with encephalopathy, are also discussed.

TBE is the most important flaviviral infection of the CNS in Europe and Russia, with 10 000–12 000 people diagnosed annually. The lethality of TBE in Europe is 0.5% and a post-encephalitic syndrome is seen in over 40% of affected patients, often producing a pronounced impairment in quality of life. There is no specific treatment for TBE. Two vaccines are available to prevent infection. Although these have a good protection rate and good efficacy, there are few data on long-term immunity.

Lyme borreliosis is the most prevalent tick-borne disease in Europe and North America, with >50 000 cases annually. Localised early disease can be treated with oral phenoxymethylpenicillin (penicillin V), doxycycline or amoxicillin. The later manifestations of meningitis, arthritis or acrodermatitis can be treated with oral doxycycline, oral amoxicillin or intravenous ceftriaxone; intravenous benzylpenicillin (penicillin G) or cefotaxime can be used as alternatives. The current use of vaccines against Lyme borreliosis in North America is under discussion, as the LYMErix™ vaccine has been withdrawn from the market because of possible adverse effects, for example, arthritis.

RMSF and CTF appear only in North America. RMSF is an important rickettsial disease and is effectively treated with doxycycline. There is no treatment or preventative measure available for CTF.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Goodman C, Lazarus AA, Martin GJ. Manifestations of tickborne illness: incidence and variety are increasing worldwide. Postgrad Med 2001; 109(6): 43–6, 51-4, 57-8

    PubMed  CAS  Google Scholar 

  2. Parola P, Raoult D. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis 2001; 32(6): 897–928

    PubMed  CAS  Google Scholar 

  3. Schneider H. Über epidemische akute Meningitis serosa. Wien Klin Wochenschr 1931; 44: 350–2

    Google Scholar 

  4. Monath TP, Heinz FX. Flaviviruses. In: Fields BN, editor. Fields virology. Philadelphia (PA): Lippincott-Raven Publishers, 1996: 961–95

    Google Scholar 

  5. Gresikova M, Kaluzova M. Biology of tick-borne encephalitis virus. Acta Virol 1997; 41(2): 115–24

    PubMed  CAS  Google Scholar 

  6. Calisher CH, Karabatsos N, Dalrymple JM, et al. Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera. J Gen Virol 1989; 70 (Pt 1): 37–43

    PubMed  Google Scholar 

  7. Calisher CH. Antigenic classification and taxonomy of flaviviruses (family Flaviviridae) emphasizing a universal system for the taxonomy of viruses causing tick-borne encephalitis. Acta Virol 1988; 32(5): 469–78

    PubMed  CAS  Google Scholar 

  8. Heinz FX. Molecular aspects of TBE virus research. Vaccine 2003; 21Suppl. 1: S3–S10

    PubMed  CAS  Google Scholar 

  9. Kuno G, Chang GJ, Tsuchiya KR, et al. Phylogeny of the genus Flavivirus. J Virol 1998; 72(1): 73–83

    PubMed  CAS  Google Scholar 

  10. Gould EA, de Lamballerie X, Zanotto PM, et al. Evolution, epidemiology, and dispersal of flaviviruses revealed by molecular phytogenies. Adv Virus Res 2001; 57: 71–103

    PubMed  CAS  Google Scholar 

  11. Gallia F, Rampas J, Hollender J. Laboratori infekce encefalitickym virem. Cas Lek Cesk 1949; 88: 228–9

    Google Scholar 

  12. Dittman S, Jilg W. Tick-borne encephalitis in the European region. Copenhagen, Denmark: WHO Regional Office for Europe, 1998

    Google Scholar 

  13. Kunz C, Heinz FX. Tick-borne encephalitis. Vaccine 2003; 21Suppl. 1: S1–2

    PubMed  Google Scholar 

  14. Lundkvist Å, Vene S, Golovljova I, et al. Characterization of tick-borne encephalitis virus from Latvia: evidence for co-circulation of three distinct subtypes. J Med Virol 2001; 65(4): 730–5

    CAS  Google Scholar 

  15. Silber L, Soloviev V. Far eastern tick-borne spring-summer encephalitis. Am Rev Soviet Med 1946; Special Suppl.: 1-80

  16. Kurane I, Takasaki T, Yamada K. Trends in flavivirus infections in Japan. Emerg Infect Dis 2000; 6(6): 569–71

    PubMed  CAS  Google Scholar 

  17. Takashima I, Morita K, Chiba M, et al. A case of tick-borne encephalitis in Japan and isolation of the the virus. J Clin Microbiol 1997; 35(8): 1943–7

    PubMed  CAS  Google Scholar 

  18. Ecker M, Allison SL, Meixner T, et al. Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol 1999; 80 (Pt 1): 179–85

    PubMed  CAS  Google Scholar 

  19. Hayasaka D, Ivanov L, Leonova GN, et al. Distribution and characterization of tick-borne ecephalitis viruses from Siberia and far-eastern Asia. J Gen Virol 2001; 82 (Pt 6): 1319–28

    PubMed  CAS  Google Scholar 

  20. Suss J. Epidemiology and ecology of TBE relevant to the production of effective vaccines. Vaccine 2003; 21Suppl. 1: S19–35

    PubMed  Google Scholar 

  21. Kohl I, Kozuch O, Eleckova E, et al. Family outbreak of alimentary tick-borne encephalitis in Slovakia associated with a natural focus of infection. Eur J Epidemiol 1996; 12(4): 373–5

    PubMed  CAS  Google Scholar 

  22. Dumpis U, Crook D, Oksi J. Tick-borne encephalitis. Clin Infect Dis 1999; 28(4): 882–90

    PubMed  CAS  Google Scholar 

  23. Suss J, Sinnecker H, Sinnecker R, et al. Epidemiology and ecology of tick-borne encephalitis in the eastern part of Germany between 1960 and 1990 and studies on the dynamics of a natural focus of tick-borne encephalitis. Zentralbl Bakteriol 1992; 277(2): 224–35

    PubMed  CAS  Google Scholar 

  24. Lindgren E, Talleklint L, Polfeldt T. Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus. Environ Health Perspect 2000; 108(2): 119–23

    PubMed  CAS  Google Scholar 

  25. Lindgren E, Gustafson R. Tick-borne encephalitis in Sweden and climate change. Lancet 2001; 358(9275): 16–8

    PubMed  CAS  Google Scholar 

  26. Randolph S. Tick-borne encephalitis in Europe. Lancet 2001; 358(9294): 1731–2

    PubMed  CAS  Google Scholar 

  27. Labuda M, Nuttall PA, Kozuch O, et al. Non-viraemic transmission of tick-borne encephalitis virus: a mechanism for arbovirus survival in nature. Experientia 1993; 49(9): 802–5

    PubMed  CAS  Google Scholar 

  28. Randolph SE, Green RM, Peacey MF, et al. Seasonal synchrony: the key to tick-borne encephalitis foci identified by satellite data. Parasitology 2000; 121 (Pt 1): 15–23

    PubMed  Google Scholar 

  29. Randolph SE. The shifting landscape of tick-borne zoonoses: tick-borne encephalitis and Lyme borreliosis in Europe. Philos Trans R Soc Lond B Biol Sci 2001; 356(1411): 1045–56

    PubMed  CAS  Google Scholar 

  30. Monath TP. Arthropod-borne encephalitides in the Americas. Bull World Health Organ 1979; 57(4): 513–33

    PubMed  CAS  Google Scholar 

  31. Tsai TF. Arboviral infections in the United States. Infect Dis Clin North Am 1991; 5(1): 73–102

    PubMed  CAS  Google Scholar 

  32. Telford III SR, Armstrong PM, Katavolos P, et al. A new tick-borne encephalitis-like virus infecting New England deer ticks, Ixodes dammini. Emerg Infect Dis 1997; 3(2): 165–70

    PubMed  Google Scholar 

  33. Costero A, Grayson MA. Experimental transmission of Powassan virus (Flaviviridae) by Ixodes scapularis ticks (Acari: Ixodidae). Am J Trop Med Hyg 1996; 55(5): 536–46

    PubMed  CAS  Google Scholar 

  34. Gholam BI, Puksa S, Provias JP. Powassan encephalitis: a case report with neuropathology and literature review. CMAJ 1999; 161(11): 1419–22

    PubMed  CAS  Google Scholar 

  35. The Centers for Disease Control and Prevention. Outbreak of powassan encephalitis: Maine and Vermont, 1999-2001. JAMA 2001; 286(16): 1962–3

    Google Scholar 

  36. Günther G, Haglund M, Lindquist L, et al. Tick-borne encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome. J Neurol 1997; 244(4): 230–8

    PubMed  Google Scholar 

  37. Haglund M, Gunther G. Tick-borne encephalitis-pathogenesis, clinical course and long-term follow-up. Vaccine 2003; 21Suppl. 1: S11–8

    PubMed  Google Scholar 

  38. Mickiene A, Laiskonis A, Günther G, et al. Tick-borne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis 2002; 35(6): 650–8

    PubMed  Google Scholar 

  39. Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain 1999; 122 (Pt 11): 2067–78

    PubMed  Google Scholar 

  40. Gustafson R, Svennungsson B, Forsgren M, et al. 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 1992; 11: 894–900

    PubMed  CAS  Google Scholar 

  41. Lotric Furlan S, Strle F. Thrombocytopenia: a common finding in the initial phase of tick-borne encephalitis. Infection 1995; 23(4): 203–6

    PubMed  CAS  Google Scholar 

  42. Schellinger PD, Schmutzhard E, Fiebach JB, et al. Poliomyelitic-like illness in central European encephalitis. Neurology 2000; 55(2): 299–302

    PubMed  CAS  Google Scholar 

  43. von Ziebart A. Frühsommermeningoenzephalitis (FSME). Klinik und besondere verlaufsvormen. Wien Klin Wochenschr 1972; 84: 778–81

    Google Scholar 

  44. Jezyna C, Zajac W, Ciesielski T, et al. Epidemiologische und klinische Untersuchungen von kranken mit zecken-enzephalitis aus Nordostpolen. Zentralbl Bakteriol Mikrobiol Hyg [B] 1984; 178(5–6): 510–21

    CAS  Google Scholar 

  45. Gustafson R. Epidemiological studies of Lyme borreliosis and tick-borne encephalitis. Scand J Infect Dis Suppl 1994; 92: 1–63

    PubMed  CAS  Google Scholar 

  46. Holmgren EB, Forsgren M. Epidemiology of tick-borne encephalitis in Sweden 1956–1989: a study of 1116 cases. Scand J Infect Dis 1990; 22: 287–95

    PubMed  CAS  Google Scholar 

  47. Logar M, Arnez M, Kolbl J, et al. Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults. Infection 2000; 28(2): 74–7

    PubMed  CAS  Google Scholar 

  48. Cizman M, Rakar R, Zakotnik B, et al. Severe forms of tick-borne encephalitis in children. Wien Klin Wochenschr 1999; 111(12): 484–7

    PubMed  CAS  Google Scholar 

  49. Haglund M, Forsgren M, Lindh G, et al. A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature: need for a vaccination strategy. Scand J Infect Dis 1996; 28: 217–24

    PubMed  CAS  Google Scholar 

  50. Smith R, Woodall JP, Whitney E, et al. Powassan virus infection: a report of three human cases of encephalitis. Am J Dis Child 1974; 127(5): 691–3

    PubMed  CAS  Google Scholar 

  51. Holzmann H. Diagnosis of tick-borne encephalitis. Vaccine 2003; 21Suppl. 1: S36–40

    PubMed  Google Scholar 

  52. Treib J, Woessner R, Dobler G, et al. Clinical value of specific intrathecal production of antibodies. Acta Virol 1997; 41(1): 27–30

    PubMed  CAS  Google Scholar 

  53. Treib J, Haass A, Kiessig ST, et al. Tick-borne encephalitis diagnosis in patients with inflammatory changes in the cerebrospinal fluid in a region with very low prevalence. Infection 1996; 24(5): 400–2

    PubMed  CAS  Google Scholar 

  54. Günther G, Haglund M, Lindquist L, et al. Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis: long-term follow-up related to clinical course and outcome. Clin Diagn Virol 1997; 8: 17–29

    PubMed  Google Scholar 

  55. Heinz FX, Roggendorf M, Hofmann H, et al. Comparison of two different enzyme immunoassays for detection of immunoglobulin M antibodies against tick-borne encephalitis virus in serum and cerebrospinal fluid. J Clin Microbiol 1981; 14(2): 141–6

    PubMed  CAS  Google Scholar 

  56. Sonnenberg K, Niedrig M, Steinhagen K, et al. State-of-the-art serological techniques for detection of antibodies against tick-borne encephalitic virus. Int J Med Microbiol 2004; 293Suppl. 37: 148–51

    PubMed  CAS  Google Scholar 

  57. Vene S, Haglund M, Vapalahti O, et al. A rapid fluorescent focus inhibition test for detection of neutralizing antibodies to tick-borne encephalitis virus. J Virol Methods 1998; 73(1): 71–5

    PubMed  CAS  Google Scholar 

  58. Holzmann H, Kundi M, Stiasny K, et al. Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis. J Med Virol 1996; 48: 102–7

    PubMed  CAS  Google Scholar 

  59. Guirakhoo F, Heinz F, Dippe H, et al. Antibody response to gp E tick-borne encephalitis virus: comparison between natural infection and vaccination breakdown. Zentralbl Bakteriol 1990; 272: 477–84

    PubMed  CAS  Google Scholar 

  60. Puchhammer-Stöckl E, Kunz C, Mandl CW, et al. Identification of tick-borne encephalitis virus ribonucleid acid in tick suspensions and in clinical specimens by a reverse transcriptionnested polymerase chain reaction assay. Clin Diagn Virol 1995; 4(5): 321–6

    PubMed  Google Scholar 

  61. Schwaiger M, Cassinotti P. Development of a quantitative realtime RT-PCR assay with internal control for the laboratory detection of tick borne encephalitis virus (TBEV) RNA. J Clin Virol 2003; 27: 136–45

    PubMed  CAS  Google Scholar 

  62. Bobrowska E, Grzeszczuk A, Flisiak R. Tick-borne encephalitis and concomitant infection with Borrelia burgdorferi. Rocz Akad Med Bialymst 1996; 41(1): 40–3

    PubMed  CAS  Google Scholar 

  63. Oksi J, Viljanen M, Kalimo H, et al. Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi. Clin Infect Dis 1993; 16(3): 392–6

    PubMed  CAS  Google Scholar 

  64. Lorenzl S, Poster HW, Padovan C, et al. MRI abnormalities in tick-borne encephalitis. Lancet 1996; 347: 698–9

    PubMed  CAS  Google Scholar 

  65. Alkadhi H, Kollias SS. MRI in tick-borne encephalitis. Neuroradiology 2000; 42(10): 753–5

    PubMed  CAS  Google Scholar 

  66. Pfister HW, Lorenzl S, Yousry T. Neuroradiographic manifestations of encephalitis. N Engl J Med 1997; 337(19): 1393–4

    PubMed  CAS  Google Scholar 

  67. Marjelund S, Tikkakoski T, Tuisku S, et al. Magnetic resonance imaging findings and outcome in severe tick-borne encephalitis: report of four cases and review of the literature. Acta Radiol 2004; 45(1): 88–94

    PubMed  CAS  Google Scholar 

  68. Ackerman ES, Tumeh SS, Charron M, et al. Viral encephalitis: imaging with SPECT. Clin Nucl Med 1988; 13(9): 640–3

    PubMed  CAS  Google Scholar 

  69. Merkelbach S, Muller M, Huber G, et al. Alteration of cerebral blood flow in patients with bacterial and viral meningoencephalitis. AJNR Am J Neuroradiol 1998; 19(3): 433–8

    PubMed  CAS  Google Scholar 

  70. Le Scao Y, Turzo A, Guias M, et al. Changes of Tc-99m HMPAO brain distribution in herpes encephalitis. Clin Nucl Med 1993; 18(5): 452–3

    PubMed  Google Scholar 

  71. Launes J, Hokkanen L, Nikkinen P, et al. Hyperfixation of 99mTc-HMPAO and hypofixation of 123I-iomazenil in acute herpes encephalitis. Neuroreport 1995; 6(8): 1203–6

    PubMed  CAS  Google Scholar 

  72. Launes J, Nikkinen P, Lindroth L, et al. Diagnosis of acute herpes simplex encephalitis by brain perfusion single photon emission computed tomography. Lancet 1988; I(8596): 1188–91

    Google Scholar 

  73. Schmidbauer M, Podreka I, Wimberger D, et al. SPECT and MR imaging in herpes simplex encephalitis. J Comput Assist Tomogr 1991; 15(5): 811–5

    PubMed  CAS  Google Scholar 

  74. Gunther G, Haglund M, Mesko L, et al. Regional cerebral blood flow scintigraphy in tick-borne encephalitis and other aseptic meningoencephalitis. J Nucl Med 1998; 39(12): 2055–61

    PubMed  CAS  Google Scholar 

  75. Wilson ME. Prevention of tickborne bacterial diseases. Med Clin North Am 2002; 86(2): 219–38

    PubMed  Google Scholar 

  76. Leyssen P, De Clercq E, Neyts J. Perspectives for the treatment of infections with Flaviviridae. Clin Microbiol Rev 2000; 13(1): 67–82

    PubMed  CAS  Google Scholar 

  77. Glukhov BN, Jerusalimsky AP, Canter VM, et al. Ribonuclease treatment of tick-borne encephalitis. Arch Neurol 1976; 33(9): 598–603

    PubMed  CAS  Google Scholar 

  78. Barrett AD. Current status of flavivirus vaccines. Ann N Y Acad Sci 2001; 951: 262–71

    PubMed  CAS  Google Scholar 

  79. Demicheli V, Graves P, Pratt M, et al. Vaccines for preventing tick-borne encephalitis. Cochrane Database Syst Rev 1998; (1): CD000977

  80. Rendi-Wagner P. Risk and prevention of tick-borne encephalitis in travelers. J Travel Med 2004; 11: 307–12

    PubMed  Google Scholar 

  81. Heinz FX, Kunz C, Fauma H. Preparation of a highly purified vaccine against tick-borne encephalitis by continuous flow zonal ultracentrifugation. J Med Virol 1980; 6(3): 213–21

    PubMed  CAS  Google Scholar 

  82. Kunze U, Asokliene L, Busse A, et al. Tick borne encephalitis in childhood: conference report and consensus of the International Scientific Working Group on tick-borne encephalitis (ISW-TBE). Vaccine 2004; 23: 729–31

    Google Scholar 

  83. Bock HL, Klockmann U, Jungst C, et al. A new vaccine against tick-borne encephalitis: initial trial in man including a dose-response study. Vaccine 1990; 8(1): 22–4

    PubMed  CAS  Google Scholar 

  84. Harabacz I, Bock H, Jungst C, et al. A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens. Vaccine 1992; 10(3): 145–50

    PubMed  CAS  Google Scholar 

  85. Klockmann U, Krivanec K, Stephenson JR, et al. Protection against European isolates of tick-borne encephalitis virus after vaccination with a new tick-borne encephalitis vaccine. Vaccine 1991; 9(3): 210–2

    PubMed  CAS  Google Scholar 

  86. Girgsdies OE, Rosenkranz G. Tick-borne encephalitis: development of a paediatric vaccine: a controlled, randomized, double-blind and multicentre study. Vaccine 1996; 14(15): 1421–8

    PubMed  CAS  Google Scholar 

  87. Weber W. Germany halts tick-borne encephalitis vaccination [letter]. Lancet 2000; 356(9223): 52

    PubMed  CAS  Google Scholar 

  88. Worm M, Sterry W, Zuberbier T. Gelatin-induced urticaria and anaphylaxis after tick-borne encephalitis vaccine [letter]. Acta Derm Venereol 2000; 80(3): 232

    PubMed  CAS  Google Scholar 

  89. Zent O, Beran J, Jilg W, et al. Clinical evaluation of a polygeline-free tick-borne encephalitis vaccine for adolescents and adults. Vaccine 2003; 21(7–8): 738–41

    PubMed  CAS  Google Scholar 

  90. Beran J, Douda P, Gniel D, et al. Long-term immunity after vaccination against tick-borne encephalitis with Encepur using the rapid vaccination schedule. Int J Med Microbiol 2004; 293Suppl. 37: 130–3

    PubMed  Google Scholar 

  91. Sander D, Scholz C, Eiben P, et al. Plexus neuropathy following vaccination against tick-borne encephalitis and tetanus due to a sports related altered immune state. Neurol Res 1995; 17(4): 316–9

    PubMed  CAS  Google Scholar 

  92. Goerre S, Kesselring J, Hartmann K, et al. Neurological side effects following vaccination of early-summer meningoencephalitis: case report and experiences of the Swiss Center for Adverse Drug Effects [in German]. Schweiz Med Wochenschr 1993; 123(14): 654–7

    PubMed  CAS  Google Scholar 

  93. Kunz C. TBE vaccination and the Austrian experience. Vaccine 2003; 21Suppl. 1: S50–5

    PubMed  Google Scholar 

  94. Press R, Solders G. A case report. A vaccine against tick-borne encephalitis caused polyneuritis. Lakartidningen 1999; 96(30–31): 3341–2

    PubMed  CAS  Google Scholar 

  95. Bohus M, Glocker FX, Jost S, et al. Myelitis after immunisation against tick-borne encephalitis. Lancet 1993; 342(8865): 239–40

    PubMed  CAS  Google Scholar 

  96. Gold R, Wietholter H, Rihs I, et al. Early summer meningoencephalitis vaccination: the indications and a critical assessment of the neurological vaccination complications [in German]. Dtsch Med Wochenschr 1992; 117(3): 112–6

    PubMed  CAS  Google Scholar 

  97. Hofmann H. After vaccination for tick-borne encephalitis must onset of neurologic disorders be expected? Wien Klin Wochenschr 1995; 107(17): 509–15

    PubMed  CAS  Google Scholar 

  98. Scholz E, Wietholter H. Postvaccinal neuritis following prophylactic vaccination against early-summer meningo-encephalitis. Dtsch Med Wochenschr 1987; 112(14): 544–6

    PubMed  CAS  Google Scholar 

  99. Grzeszczuk A, Sokolewicz-Bobrowska E, Prokopowicz D. Adverse reactions to tick-borne encephalitis vaccine: FSME-Immun. Infection 1998; 26(6): 385–8

    PubMed  CAS  Google Scholar 

  100. Zent O, Arras-Reiter C, Broeker M, et al. Immediate allergic reactions after vaccinations: a post-marketing surveillance review. Eur J Pediatr 2002; 161(1): 21–5

    PubMed  CAS  Google Scholar 

  101. Kunz C. Tick-borne encephalitis in Europe. Acta Leiden 1992; 2(60): 1–14

    Google Scholar 

  102. Kunz C, Hofmann H, Dippe H. Early summer meningoencephalitis vaccination, a preventive medicine measure with high acceptance in Austria [in German]. Wien Med Wochenschr 1991; 141(12): 273–6

    PubMed  CAS  Google Scholar 

  103. Barrett PN, Schober-Bendixen S, Ehrlich HJ. History of TBE vaccines. Vaccine 2003; 21Suppl. 1: S41–9

    PubMed  Google Scholar 

  104. Bobrowska E, Grzeszczuk A, Prokopowicz D. Vaccination against tick-borne encephalitis: distant evaluation. Rocz Akad Med Bialymst 1996; 41(1): 44–50

    PubMed  CAS  Google Scholar 

  105. Kunz C, Heinz FX, Hofmann H. Immunogenicity and reactogenicity of a highly purified vaccine against tick-borne encephalitis. J Med Virol 1980; 6(2): 103–9

    PubMed  CAS  Google Scholar 

  106. Haglund M. Tick-borne encephalitis, prognosis, immunization and virus strain characterization [thesis]. Stockholm: Karolinska Institutet, 2000

    Google Scholar 

  107. Rendi-Wagner P, Kundi M, Zent O, et al. Persistence of protective immunity following vaccination against tick-borne encephalitis: longer than expected? Vaccine 2004; 22(21–22): 2743–9

    PubMed  CAS  Google Scholar 

  108. Craig SC, Pittman PR, Lewis TE, et al. An accelerated schedule for tick-borne encephalitis vaccine: the American Military experience in Bosnia. Am J Trop Med Hyg 1999; 61(6): 874–8

    PubMed  CAS  Google Scholar 

  109. Chiba N, Osada M, Komoro K, et al. Protection against tick-borne encephalitis virus isolated in Japan by active and passive immunization. Vaccine 1999; 17(11–12): 1532–9

    PubMed  CAS  Google Scholar 

  110. Holzmann H, Vorobyova MS, Ladyzhenskaya IP, et al. Molecular epidemiology of tick-borne encephalitis virus: cross-protection between European and Far Eastern subtypes. Vaccine 1992; 10(5): 345–9

    PubMed  CAS  Google Scholar 

  111. Dobler G, Treib J, Kiessig ST, et al. Diagnosis of tick-borne encephalitis: evaluation of sera with borderline titers with the TBE-ELISA. Infection 1996; 24(5): 405–6

    PubMed  CAS  Google Scholar 

  112. Adner N, Leibl H, Enzersberger O, et al. Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers. Scand J Infect Dis 2001; 33(11): 843–7

    PubMed  CAS  Google Scholar 

  113. Kunz C, Hofmann H, Kundi M, et al. Efficacy of specific immunoglobulin against TBE (author’s transi) [in German]]. Wien Klin Wochenschr 1981; 93(21): 665–7

    PubMed  CAS  Google Scholar 

  114. Waldvogel K, Bossart W, Huisman T, et al. Severe tick-borne encephalitis following passive immunization. Eur J Pediatr 1996; 155(9): 775–9

    PubMed  CAS  Google Scholar 

  115. Arras C, Fescharek R, Gregersen JP. Do specific hyperimmunoglobulins aggravate clinical course of tick-borne encephalitis? [letter]. Lancet 1996; 347(9011): 1331

    PubMed  CAS  Google Scholar 

  116. Aebi C, Schaad UB. TBE-immunoglobulins: a critical assessment of efficacy [in German]. Schweiz Med Wochenschr 1994; 124(42): 1837–40

    PubMed  CAS  Google Scholar 

  117. Kaiser R, Holzmann H. Laboratory findings in tick-borne encephalitis: correlation with clinical outcome. Infection 2000; 28(2): 78–84

    PubMed  CAS  Google Scholar 

  118. Kluger G, Schottler A, Waldvogel K, et al. Tickborne encephalitis despite specific immunoglobulin prophylaxis [letter]. Lancet 1995; 346(8988): 1502

    PubMed  CAS  Google Scholar 

  119. Valdueza JM, Weber JR, Harms L, et al. Severe tick borne encephalomyelitis after tick bite and passive immunisation. J Neurol Neurosurg Psychiatry 1996; 60(5): 593–4

    PubMed  CAS  Google Scholar 

  120. Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect-Dis 1994; 19(3): 500–12

    PubMed  CAS  Google Scholar 

  121. Phillpotts RJ, Stephenson JR, Porterfield JS. Antibody-dependent enhancement of tick-borne encephalitis virus infectivity. J Gen Virol 1985; 66 (Pt 8): 1831–7

    PubMed  Google Scholar 

  122. Kreil TR, Eibl MM. Pre- and postexposure protection by passive immunoglobulin but no enhancement of infection with a flavivirus in a mouse model. J Virol 1997; 71(4): 2921–7

    PubMed  CAS  Google Scholar 

  123. Calisher CH. Medically important arboviruses of the United States and Canada. Clin Microbiol Rev 1994; 7(1): 89–116

    PubMed  CAS  Google Scholar 

  124. 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(1): 7–17

    PubMed  CAS  Google Scholar 

  125. Burgdorfer W, Barbour AG, Hayes SF, et al. Lyme disease-atick-borne spirochetosis? Science 1982; 216(4552): 1317–9

    PubMed  CAS  Google Scholar 

  126. Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med 1983; 308(13): 733–40

    PubMed  CAS  Google Scholar 

  127. Burgdorfer W, Anderson JF, Gern L, et al. Relationship of Borrelia burgdorferi to its arthropod vectors. Scand J Infect Dis Suppl 1991; 77: 35–40

    PubMed  CAS  Google Scholar 

  128. Wang G, van Dam AP, Le Fleche A, et al. Genetic and pheno-typic analysis of Borrelia valaisiana sp. nov. (Borrelia genomic groups VS116 and M19). Int J Syst Bacteriol 1997; 47(4): 926–32

    PubMed  CAS  Google Scholar 

  129. Stanek G, Strle F. Lyme borreliosis. Lancet 2003; 362: 1639–47

    PubMed  Google Scholar 

  130. Picken RN, Cheng Y, Strle F, et al. Patients isolates of Borrelia burgdorferi sensu lato with genotypic and phenotypic similarities to strain 25015. J Infect Dis 1996; 174: 1112–5

    PubMed  CAS  Google Scholar 

  131. Strle F, Picken RN, Cheng Y, et al. Clinical findings for patients with lyme borreliosis caused by Borrelia burgdorferi sensu lato with genotypic and phenotypic similarities to strain 25015. Clin Infect Dis 1997; 25: 273–80

    PubMed  CAS  Google Scholar 

  132. Ornstein K, Berglund J, Nilsson I, et al. Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden. J Clin Microbiol 2001; 39(4): 1294–8

    PubMed  CAS  Google Scholar 

  133. Ornstein K, Berglund J, Bergstrom S, et al. Three major Lyme Borrelia genospecies (Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii) identified by PCR in cerebrospinal fluid from patients with neuroborreliosis in Sweden. Scand J Infect Dis 2002; 34(5): 341–6

    CAS  Google Scholar 

  134. Hubalek Z, Halouzka J. Distribution of Borrelia burgdorferi sensu lato genomic groups in Europe: a review. Eur J Epidemiol 1997; 13(8): 951–7

    PubMed  CAS  Google Scholar 

  135. Baranton G, Postic D, Saint Girons I, et al. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 1992; 42(3): 378–83

    PubMed  CAS  Google Scholar 

  136. Wang G, van Dam AP, Schwartz I, et al. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications. Clin Microbiol Rev 1999; 12(4): 633–53

    PubMed  CAS  Google Scholar 

  137. Saint Girons I, Gern L, Gray JS, et al. Identification of Borrelia burgdorferi sensu lato species in Europe. Zentralbl Bakteriol 1998; 287(3): 190–5

    PubMed  CAS  Google Scholar 

  138. Shapiro ED, Gerber MA. Lyme disease. Clin Infect Dis 2000; 31(2): 533–42

    PubMed  CAS  Google Scholar 

  139. Nagi KS, Joshi R, Thakur RK. Cardiac manifestations of Lyme disease: a review. Can J Cardiol 1996; 12(5): 503–6

    PubMed  CAS  Google Scholar 

  140. Rahn DW. Lyme disease: clinical manifestations, diagnosis, and treatment. Semin Arthritis Rheum 1991; 20(4): 201–18

    PubMed  CAS  Google Scholar 

  141. Baumgarten JM, Montiel NJ, Sinha AA. Lyme disease: Part I.Epidemiology and etiology. Cutis 2002; 69(5): 349–52

    PubMed  Google Scholar 

  142. Montiel NJ, Baumgarten JM, Sinha AA. Lyme disease: Part II. Clinical features and treatment. Cutis 2002; 69(6): 443–8

    Google Scholar 

  143. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998; 352: 557–65

    PubMed  CAS  Google Scholar 

  144. Berglund J, Hansen BU, Eitrem R. Lyme arthritis: a common manifestation in a highly endemic area in Sweden. J Rheumatol 1995; 22(4): 695–701

    PubMed  CAS  Google Scholar 

  145. 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(5): 502–8

    PubMed  CAS  Google Scholar 

  146. Berglund J, Eitrem R, Ornstein K, et al. An epidemiologic study of Lyme disease in southern Sweden. N Engl J Med 1995; 333(20): 1319–27

    PubMed  CAS  Google Scholar 

  147. Christen HJ, Hanefeld F, Eiffert H, et al. Epidemiology and clinical manifestations of Lyme borreliosis in childhood: a prospective multicentre study with special regard to neuroborreliosis. Acta Paediatr Suppl 1993; 386: 1–75

    PubMed  CAS  Google Scholar 

  148. Weber K, Neubert U. Clinical features of early erythema migrans disease and related disorders. Zentralbl Bakteriol Mikrobiol Hyg [A] 1986; 263(1-2): 209–28

    CAS  Google Scholar 

  149. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987; 107(5): 725–31

    PubMed  CAS  Google Scholar 

  150. Balmelli T, Piffaretti JC. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol 1995; 146(4): 329–40

    PubMed  CAS  Google Scholar 

  151. Busch U, Hizo-Teufel C, Boehmer R, et al. Three species of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto, B afzelii, and B. garinii) identified from cerebrospinal fluid isolates by pulsed-field gel electrophoresis and PCR. J Clin Microbiol 1996; 34(5): 1072–8

    CAS  Google Scholar 

  152. Busch U, Hizo-Teufel C, Böhmer R, et al. Borrelia burgdorferi sensu lato strains isolated from cutaneous Lyme borreliosis biopsies differentiated by pulsed-field gel electrophoresis. Scand J Infect Dis 1996; 28(6): 583–9

    PubMed  CAS  Google Scholar 

  153. Picken RN, Strie F, Picken MM, et al. Identification of three species of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto, B. garinii, and B. afzelii) among isolates from acrodermatitis chronica atrophicans lesions. J Invest Dermatol 1998; 110(3): 211–4

    CAS  Google Scholar 

  154. van Dam AP, Kuiper H, Vos K, et al. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 1993; 17(4): 708–17

    PubMed  Google Scholar 

  155. Jaulhac B, Heller R, Limbach FX, et al. Direct molecular typing of Borrelia burgdorferi sensu lato species in synovial samples from patients with lyme arthritis. J Clin Microbiol 2000; 38(5): 1895–900

    PubMed  CAS  Google Scholar 

  156. Eiffert H, Karsten A, Thomssen R, et al. Characterization of Borrelia burgdorferi strains in Lyme arthritis. Scand J Infect Dis 1998; 30(3): 265–8

    PubMed  CAS  Google Scholar 

  157. Asbrink E, Hovmark A, Hederstedt B. The spirochetal etiology of acrodermatitis chronica atrophicans Herxheimer. Acta Derm Venereol 1984; 64(6): 506–12

    PubMed  CAS  Google Scholar 

  158. Baranton G, Scinost G, Theodore G, et al. Distinct levels of genetic diversity of Borrelia burgdorferi are associated with different aspects of pathogenicity. Res Microbiol 2001; 152(2): 149–56

    PubMed  CAS  Google Scholar 

  159. Steere AC. Lyme disease. N Engl J Med 2001; 345(2): 115–25

    PubMed  CAS  Google Scholar 

  160. Stiernstedt G, Skoldenberg B, Garde A, et al. Clinical manifestations of Borrelia infections of the nervous system. Zentralbl Bakteriol Mikrobiol Hyg [A] 1987; 263(3): 289–96

    CAS  Google Scholar 

  161. Steere AC. Lyme disease. N Engl J Med 1989; 321(9): 586–96

    PubMed  CAS  Google Scholar 

  162. Steere AC. Seronegative Lyme disease [letter]. JAMA 1993; 270(11): 1369

    PubMed  CAS  Google Scholar 

  163. Svenungsson B, Lindh G. Lyme borreliosis: an overdiagnosed disease? Infection 1997; 25(3): 140–3

    PubMed  CAS  Google Scholar 

  164. Berger BW, Johnson RC, Kodner C, et al. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol 1992; 30(2): 359–61

    PubMed  CAS  Google Scholar 

  165. Karlsson M, Hovind-Hougen K, Svenungsson B, et al. Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis. J Clin Microbiol 1990; 28(3): 473–9

    PubMed  CAS  Google Scholar 

  166. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease: the Infectious Diseases Society of America. Clin Infect Dis 2000; 31Suppl. 1: 1–14

    PubMed  Google Scholar 

  167. Schmidt BL. PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Clin Microbiol Rev 1997; 10(1): 185–201

    PubMed  CAS  Google Scholar 

  168. EUCALB. Diagnosis of Lyme Borreliosis in Europe: European Union concerted action on lyme borreliosis 2000 [online]. Available from URL: http://www.dis.strath.ac.uk/vie/LymeEU/ [Accessed 2005 Oct 19]]

  169. The Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease [letter]. JAMA 1995; 274(12): 937

    Google Scholar 

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

    Google Scholar 

  171. Wharton M, Chorba TL, Vogt RL, et al. Case definitions for public health surveillance. MMWR Recomm Rep 1990; 39(RR-13): 1–43

    PubMed  CAS  Google Scholar 

  172. Guidelines for laboratory evaluation in the diagnosis of Lyme disease. American College of Physicians. Ann Intern Med 1997; 127(12): 1106–8

    Google Scholar 

  173. Hansen K, Lebech AM. Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi: specific immunoglobulin G, A, and M. Ann Neurol 1991; 30(2): 197–205

    PubMed  CAS  Google Scholar 

  174. Hansen K. Lyme neuroborreliosis: improvements of the laboratory diagnosis and a survey of epidemiological and clinical features in Denmark 1985–1990. Acta Neurol Scand Suppl 1994; 151: 1–44

    PubMed  CAS  Google Scholar 

  175. Stiernstedt G, Gustafsson R, Karlsson M, et al. Clinical manifestations and diagnosis of neuroborreliosis. Ann N Y Acad Sci 1988; 539: 46–55

    PubMed  CAS  Google Scholar 

  176. Stiernstedt G, Granström M, Hederstedt B, et al. Diagnosis of spirochetal meningitis by means of enzyme-linked immunosorbent assay and indirect immunofluorescence assay in serum and cerebrospinal fluid. J Clin Microbiol 1985; 21: 819–25

    PubMed  CAS  Google Scholar 

  177. Stiernstedt G, Granstrom M, Hederstedt B, et al. Serological diagnosis of Borrelia meningitis. Zentralbl Bakteriol Mikrobiol Hyg [A] 1987; 263(3): 420–4

    CAS  Google Scholar 

  178. Karlsson M. Western immunoblot and flagellum enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis. J Clin Microbiol 1990; 28(9): 2148–50

    PubMed  CAS  Google Scholar 

  179. Karlsson M, Stiernstedt G, Granstrom M, et al. Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis. Eur J Clin Microbiol Infect Dis 1990; 9(3): 169–77

    PubMed  CAS  Google Scholar 

  180. Robertson J, Guy E, Andrews N, et al. A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis. J Clin Microbiol 2000; 38(6): 2097–102

    PubMed  CAS  Google Scholar 

  181. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol 1995; 33(2): 419–27

    PubMed  CAS  Google Scholar 

  182. Dressier F, Whalen JA, Reinhardt BN, et al. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993; 167(2): 392–400

    Google Scholar 

  183. Hauser U, Lehnert G, Lobentanzer R, et al. Interpretation criteria for standardized Western blots for three European species of Borrelia burgdorferi sensu lato. J Clin Microbiol 1997; 35(6): 1433–44

    PubMed  CAS  Google Scholar 

  184. Bruckbauer HR, Preac-Mursic V, Fuchs R, et al. Cross-reactive proteins of Borrelia burgdorferi. Eur J Clin Microbiol Infect Dis 1992; 11(3): 224–32

    PubMed  CAS  Google Scholar 

  185. Fawcett PT, Gibney KM, Rose CD, et al. Frequency and specificity of antibodies that crossreact with Borrelia burgdorferi antigens. J Rheumatol 1992; 19(4): 582–7

    PubMed  CAS  Google Scholar 

  186. Magnarelli LA, Miller JN, Anderson JF, et al. Cross-reactivity of nonspecific treponemal antibody in sérologic tests for Lyme disease. J Clin Microbiol 1990; 28(6): 1276–9

    PubMed  CAS  Google Scholar 

  187. Hammers-Berggren S, Hansen K, Lebech AM, et al. Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study. Neurology 1993; 43(1): 169–75

    PubMed  CAS  Google Scholar 

  188. Hammers-Berggren S, Lebech AM, Karlsson M, et al. Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis. J Clin Microbiol 1994; 32(6): 1519–25

    PubMed  CAS  Google Scholar 

  189. Hammers-Berggren S, Lebech AM, Karlsson M, et al. Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans. Scand J Infect Dis 1994; 26(3): 339–47

    PubMed  CAS  Google Scholar 

  190. Sigal LH. Lyme disease: testing and treatment: who should be tested and treated for Lyme disease and how? Rheum Dis Clin North Am 1993; 19(1): 79–93

    PubMed  CAS  Google Scholar 

  191. Sigal LH. Persisting symptoms of Lyme disease: possible explanations and implications for treatment. J Rheumatol 1994; 21(4): 593–5

    PubMed  CAS  Google Scholar 

  192. Sigal LH. Persisting complaints attributed to chronic Lyme disease: possible mechanisms and implications for management. Am J Med 1994; 96(4): 365–74

    PubMed  CAS  Google Scholar 

  193. Sigal LH. Current recommendations for the treatment of Lyme disease. Drugs 1992; 43(5): 683–99

    PubMed  CAS  Google Scholar 

  194. Loewen PS, Marra CA, Marra F. Systematic review of the treatment of early Lyme disease. Drugs 1999; 57(2): 157–73

    PubMed  CAS  Google Scholar 

  195. Kalish RA, Leong JM, Steere AC. Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi. Infect Immun 1993; 61(7): 2774–9

    PubMed  CAS  Google Scholar 

  196. Berglund J, Stjernberg L, Ornstein K, et al. 5-y follow-up study of patients with neuroborreliosis. Scand J Infect Dis 2002; 34(6): 421–5

    PubMed  Google Scholar 

  197. Cimperman J, Maraspin V, Lotric-Furlan S, et al. Lyme meningitis: a one-year follow up controlled study. Wien Klin Wochenschr 1999; 111(22–23): 961–3

    PubMed  CAS  Google Scholar 

  198. Karkkonen K, Stiernstedt SH, Karlsson M. Follow-up of patients treated with oral doxycycline for Lyme neuroborreliosis. Scand J Infect Dis 2001; 33(4): 259–62

    PubMed  CAS  Google Scholar 

  199. Treib J, Fernandez A, Haass A, et al. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology 1998; 51(5): 1489–91

    PubMed  CAS  Google Scholar 

  200. Benke T, Gasse T, Hittmair-Delazer M, et al. Lyme encephalopathy: long-term neuropsychological deficits years after acute neuroborreliosis. Acta Neurol Scand 1995; 91(5): 353–7

    PubMed  CAS  Google Scholar 

  201. Shadick NA, Phillips CB, Logigian EL, et al. The long-term clinical outcomes of Lyme disease: a population-based retrospective cohort study. Ann Intern Med 1994; 121(8): 560–7

    PubMed  CAS  Google Scholar 

  202. Shadick NA, Phillips CB, Sangha O, et al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med 1999; 131(12): 919–26

    PubMed  CAS  Google Scholar 

  203. Kalish RA, Kaplan RF, Taylor E, et al. Evaluation of study patients with Lyme disease, 10–20-year follow-up. J Infect Dis 2001; 183(3): 453–60

    PubMed  CAS  Google Scholar 

  204. Gustaw K, Beltowska K, Studzinska MM. Neurological and psychological symptoms after the severe acute neuroborreliosis. Ann Agric Environ Med 2001; 8(1): 91–4

    PubMed  CAS  Google Scholar 

  205. Peltomaa M, Saxen H, Seppala I, et al. Paediatric facial paralysis caused by Lyme borreliosis: a prospective and retrospective analysis. Scand J Infect Dis 1998; 30(3): 269–75

    PubMed  CAS  Google Scholar 

  206. EUCALB. Treatment of Lyme Borreliosis in Europe: European Union concerted action on lyme borreliosis 2000 [online]. Available from URL: http://www.dis.strath.ac.uk/vie/LymeEU/ [Accessed 2005 Oct 19]

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  209. Dotevall L, Alestig K, Hanner P, et al. The use of doxycycline in nervous system Borrelia burgdorferi infection. Scand J Infect Dis Suppl 1988; 53: 74–9

    PubMed  CAS  Google Scholar 

  210. Barza M, Brown RB, Shanks C, et al. Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline, and oxytetracycline in dogs. Antimicrob Agents Chemother 1975; 8(6): 713–20

    PubMed  CAS  Google Scholar 

  211. Cunha BA. Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. Clin Infect Dis 2000; 30(1): 237–8

    PubMed  CAS  Google Scholar 

  212. Alestig K, Lindberg J. Studies on the absorption and excretion of minocycline and a comparison with doxycycline. Infection 1974; 2(3): 137–41

    PubMed  CAS  Google Scholar 

  213. Dotevall L, Hagberg L. Adverse effects of minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. Clin Infect Dis 2000; 30(2): 410–1

    PubMed  CAS  Google Scholar 

  214. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001; 345(2): 85–92

    PubMed  CAS  Google Scholar 

  215. Wormser GP, Nowakowski J, Nadelman RB. Duration of treatment for Lyme borreliosis: time for a critical reappraisal. Wien Klin Wochenschr 2002; 114(13–14): 613–5

    PubMed  Google Scholar 

  216. Thorstrand C, Belfrage E, Bennet R, et al. Successful treatment of neuroborreliosis with ten day regimens. Pediatr Infect Dis J 2002; 21(12): 1142–5

    PubMed  Google Scholar 

  217. Asch ES, Bujak DI, Weiss M, et al. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994; 21(3): 454–61

    PubMed  CAS  Google Scholar 

  218. Berglund J, Eitrem R, Norrby SR. Long-term study of Lyme borreliosis in a highly endemic area in Sweden. Scand J Infect Dis 1996; 28(5): 473–8

    PubMed  CAS  Google Scholar 

  219. Salazar JC, Gerber MA, Goff CW. Long-term outcome of Lyme disease in children given early treatment. J Pediatr 1993; 122(4): 591–3

    PubMed  CAS  Google Scholar 

  220. Eiffert H, Hanefeld F, Thomssen R, et al. Reinfection in Lyme borreliosis. Infection 1996; 24(6): 437–9

    PubMed  CAS  Google Scholar 

  221. Nowakowski J, Schwartz I, Nadelman RB, et al. Culture-confirmed infection and reinfection with Borrelia burgdorferi. Ann Intern Med 1997; 127(2): 130–2

    PubMed  CAS  Google Scholar 

  222. Bennet L, Berglund J. Reinfection with Lyme borreliosis: a retrospective follow-up study in southern Sweden. Scand J Infect Dis 2002; 34(3): 183–6

    PubMed  Google Scholar 

  223. Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med 2001; 345(2): 79–84

    PubMed  CAS  Google Scholar 

  224. Magid D, Schwartz B, Craft J, et al. Prevention of Lyme disease after tick bites: a cost-effectiveness analysis. N Engl J Med 1992; 327(8): 534–41

    PubMed  CAS  Google Scholar 

  225. Warshafsky S, Nowakowski J, Nadelman RB, et al. Efficacy of antibiotic prophylaxis for prevention of Lyme disease. J Gen Intern Med 1996; 11(6): 329–33

    PubMed  CAS  Google Scholar 

  226. Stjernberg L, Berglund J. Risk of acquiring tick bites in southeastern Sweden. Scand J Infect Dis 2002; 34(11): 840–4

    PubMed  Google Scholar 

  227. Maes E, Lecomte P, Ray N. A cost-of-illness study of Lyme disease in the United States. Clin Ther 1998; 20(5): 993–1008

    PubMed  CAS  Google Scholar 

  228. Telford III SR, Fikrig E. Progress towards a vaccine for Lyme disease. Clin Immunother 1995; 4(1): 49–60

    Google Scholar 

  229. Chu HJ, Chavez Jr LG, Blumer BM, et al. Immunogenicity and efficacy study of a commercial Borrelia burgdorferi bacterin. J Am Vet Med Assoc 1992; 201(3): 403–11

    PubMed  CAS  Google Scholar 

  230. Aberer E, Brunner C, Suchanek G, et al. Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue. Ann Neurol 1989; 26(6): 732–7

    PubMed  CAS  Google Scholar 

  231. Sigal LH. Cross-reactivity between Borrelia burgdorferi flagellin and a human axonal 64,000 molecular weight protein. J Infect Dis 1993; 167(6): 1372–8

    PubMed  CAS  Google Scholar 

  232. Sigal LH, Zahradnik JM, Lavin P, et al. A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease: Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium. N Engl J Med 1998; 339(4): 216–22

    PubMed  CAS  Google Scholar 

  233. Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N Engl J Med 1998; 339(4): 209–15

    CAS  Google Scholar 

  234. Onrust SV, Goa KL. Adjuvanted Lyme disease vaccine: a review of its use in the management of Lyme disease. Drugs 2000; 59(2): 281–99

    PubMed  CAS  Google Scholar 

  235. 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(5377): 703–6

    PubMed  CAS  Google Scholar 

  236. Akin E, McHugh GL, Flavell RA, et al. 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 1999; 67(1): 173–81

    PubMed  CAS  Google Scholar 

  237. Recommendations for the use of Lyme disease vaccine, recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999; 48(RR-7): 1–17, 21-5

    Google Scholar 

  238. Kalish RS, Wood JA, Golde W, et al. Human T lymphocyte response to Borrelia burgdorferi infection: no correlation between human leukocyte function antigen type 1 peptide response and clinical status. J Infect Dis 2003; 187(1): 102–8

    PubMed  CAS  Google Scholar 

  239. Meurice F, De Bouver JL, Vandevoorde D, et al. Immunogenicity and safety of a live attenuated varicella vaccine (Oka/SB Bio) in healthy children. J Infect Dis 1996; 174Suppl. 3: S324–9

    PubMed  Google Scholar 

  240. Keller D, Koster FT, Marks DH, et al. Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. JAMA 1994; 271(22): 1764–8

    PubMed  CAS  Google Scholar 

  241. Sigal LH. Lyme arthritis: lessons learned and to be learned. Arthritis Rheum 1999; 42(9): 1809–12

    PubMed  CAS  Google Scholar 

  242. Sigal LH. Management of Lyme arthritis. Compr Ther 1999; 25(4): 228–38

    PubMed  CAS  Google Scholar 

  243. Thanassi WT, Schoen RT. The Lyme disease vaccine: conception, development, and implementation. Ann Intern Med 2000; 132(8): 661–8

    PubMed  CAS  Google Scholar 

  244. Poland GA, Jacobson RM. The prevention of Lyme disease with vaccine. Vaccine 2001; 19(17–19): 2303–8

    PubMed  CAS  Google Scholar 

  245. Rahn DW. Lyme vaccine: issues and controversies. Infect Dis Clin North Am 2001; 15(1): 171–87

    PubMed  CAS  Google Scholar 

  246. Hayes EB, Dennis DT. Immunization against Lyme disease. N Engl J Med 1998; 339(22): 1637

    PubMed  CAS  Google Scholar 

  247. Luger S. Immunization against Lyme disease. N Engl J Med 1998; 339(22): 1637–8

    PubMed  CAS  Google Scholar 

  248. Schoen RT, Deshefy-Longhi T, Van-Hoecke C, et al. An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine. Clin Ther 2003; 25(1): 210–24

    PubMed  CAS  Google Scholar 

  249. Wallich R, Jahraus O, Simon MM. Prophylactic vaccination against Lyme borreliosis for man and dogs and new strategies to treat established B. burgdorferi infections. Int J Med Microbiol 2002; 291Suppl. 33: 147–9

    Google Scholar 

  250. Zhong W, Stehle T, Museteanu C, et al. Therapeutic passive vaccination against chronic Lyme disease in mice. Proc Natl Acad Sci U S A 1997; 94(23): 12533–8

    PubMed  CAS  Google Scholar 

  251. Zhong W, Gern L, Stehle T, et al. Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC. Eur J Immunol 1999; 29(3): 946–57

    PubMed  CAS  Google Scholar 

  252. Ricketts HT. Some aspects of Rocky Mountain spotted fever as shown by recent investigations. 1909. Rev Infect Dis 1991; 13(6): 1227–40

    CAS  Google Scholar 

  253. Weber DJ, Walker DH. Rocky Mountain spotted fever. Infect Dis Clin North Am 1991; 5(1): 19–35

    PubMed  CAS  Google Scholar 

  254. Philip RN. Rocky Mountain spotted fever in Western Montana: anatomy of a pestilence. Bitter Root Valley Historical Society. Stevensville (MT): Stoneydale Pr, 2000: 55–69

    Google Scholar 

  255. Paddock CD, Holman BL, Krebs JW, et al. Assessing the magnitude of fatal Rocky Mountain spotted fever in the United States: comparison of two national data sources. Am J Trop Med Hyg 2002; 67(4): 349–54

    PubMed  Google Scholar 

  256. Weisburg WG, Dobson ME, Samuel JE, et al. Phylogenetic diversity of the rickettsiae. J Bacteriol 1989; 171: 4202–6

    PubMed  CAS  Google Scholar 

  257. Walker DH, Fishbein DB. Epidemiology of rickettsial diseases. Eur J Epidemiol 1991; 7(3): 237–45

    PubMed  CAS  Google Scholar 

  258. Marrero M, Raoult D. Centrifugation-shell vial technique for rapid detection of Mediterranean spotted fever rickettsia in blod culture. Am J Trop Med Hyg 1989; 40: 197–9

    PubMed  CAS  Google Scholar 

  259. Spruance SL, Bailey A. Colorado tick fever: a review of 115 laboratory confirmed cases. Arch Intern Med 1973; 131(2): 288–93

    Google Scholar 

  260. Attoui H, Mohd Jaafar F, Biagini P, et al. Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of Old World and New World viruses. Arch Virol 2002; 147(3): 533–61

    PubMed  CAS  Google Scholar 

  261. Bodkin DK, Knudson DL. Genetic relatedness of Colorado tick fever virus isolates by RNA-RNA blot hybridization. J Gen Virol 1987; 68: 1199–204

    PubMed  CAS  Google Scholar 

  262. Klasco R. Colorado tick fever. Med Clin North Am 2002; 86(2): 435–40, ix

    PubMed  Google Scholar 

  263. Bleck TP. Central nervous system involvement in Rickettsial diseases. Neurol Clin 1999; 17(4): 801–12

    PubMed  CAS  Google Scholar 

  264. Hattwick MA, Retailliau H, O’Brien RJ, et al. Fatal Rocky Mountain spotted fever. JAMA 1978; 240(14): 1499–503

    PubMed  CAS  Google Scholar 

  265. Thorner AR, Walker DH, Petri Jr WA. Rocky mountain spotted fever. Clin Infect Dis 1998; 27(6): 1353–9

    PubMed  CAS  Google Scholar 

  266. Heimick CG, Bernard KW, D’Angelo LJ. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis 1984; 150(4): 480–8

    Google Scholar 

  267. Walker DH. Rocky Mountain spotted fever: a seasonal alert. Clin Infect Dis 1995; 20(5): 1111–7

    PubMed  CAS  Google Scholar 

  268. Dumler JS, Walker DH. Diagnostic tests for Rocky Mountain spotted fever and other rickettsial diseases. Dermatol Clin 1994; 12(1): 25–36

    PubMed  CAS  Google Scholar 

  269. Dumler JS, Gage WR, Pettis GL, et al. Rapid immunoperoxidase demonstration of Rickettsia rickettsii in fixed cutaneous specimens from patients with Rocky Mountain spotted fever. Am J Clin Pathol 1990; 93(3): 410–4

    PubMed  CAS  Google Scholar 

  270. Hays PL. Rocky Mountain spotted fever in children in Kansas: the diagnostic value of an IgM-specific immunofluorescence assay. J Infect Dis 1985; 151(2): 369–70

    PubMed  CAS  Google Scholar 

  271. Clements ML, Dumler JS, Fiset P, et al. Serodiagnosis of Rocky Mountain spotted fever: comparison of IgM and IgG enzyme-linked immunosorbent assays and indirect fluorescent antibody test. J Infect Dis 1983; 148(5): 876–80

    PubMed  CAS  Google Scholar 

  272. Philip RN, Casper EA, MacCormack JN, et al. A comparison of serologic methods for diagnosis of Rocky Mountain spotted fever. Am J Epidemiol 1977; 105(1): 56–67

    PubMed  CAS  Google Scholar 

  273. Tzianabos T, Anderson B, McDade J. Detection of Rickettsia rickettsii DNA in clinical specimens by using polymerase chain reaction technology. J Clin Microbiol 1989; 27(12): 2866–8

    PubMed  CAS  Google Scholar 

  274. Carl M, Tibbs C, Dobson ME, et al. Diagnosis of acute typhus infection using the polymerase chain reaction. J Infect Dis 1990; 161(4): 791–3

    PubMed  CAS  Google Scholar 

  275. Sexton D, Kanj S, Wilson K, et al. The use of polymerase chain reaction as a diagnostic test for Rocky Mountain spotted fever. Am J Trop Med Hyg 1994; 50(1): 59–63

    PubMed  CAS  Google Scholar 

  276. Eremeeva M, Dasch GA, Silverman D. Evaluation of a PCR assay for quantitation of Rickettsia rickettsii and closely related spotted fever group Rickettsiae. J Clin Microbiol 2003; 41(12): 5466–72

    PubMed  CAS  Google Scholar 

  277. Goodpasture HC, Poland JD, Francy DB, et al. Colorado tick fever: clinical, epidemiologic, and laboratory aspects of 228 cases in Colorado in 1973–1974. Ann Intern Med 1978; 88(3): 303–10

    PubMed  CAS  Google Scholar 

  278. Attoui H, Billoir F, Bruey JM, et al. Serologic and molecular diagnosis of Colorado tick fever viral infections. Am J Trop Med Hyg 1998; 59(5): 763–8

    PubMed  CAS  Google Scholar 

  279. Johnson AJ, Karabatsos N, Lanciotti RS. Detection of Colorado tick fever virus by using reverse transcriptase PCR and application of the technique in laboratory diagnosis. J Clin Microbiol 1997; 35(5): 1203–8

    PubMed  CAS  Google Scholar 

  280. Cunha BA. Doxycycline re-revisited. Arch Intern Med 1999; 159(9): 1006–7

    PubMed  CAS  Google Scholar 

  281. Gudiol F, Pallares R, Carratala J, et al. Randomized double-blind evaluation of ciprofloxacin and doxycycline for Mediterranean spotted fever. Antimicrob Agents Chemother 1989; 33(6): 987–8

    PubMed  CAS  Google Scholar 

  282. Donovan BJ, Weber DJ, Rublein JC, et al. Treatment of tick-borne diseases. Ann Pharmacother 2002; 36(10): 1590–7

    PubMed  CAS  Google Scholar 

  283. Kenyon RH, Williams RG, Oster CN, et al. Prophylactic treatment of Rocky Mountain spotted fever. J Clin Microbiol 1978; 8(1): 102–4

    PubMed  CAS  Google Scholar 

  284. Holman RC, Paddock CD, Curns AT, et al. Analysis of risk factors for fatal Rocky Mountain Spotted Fever: evidence for superiority of tetracyclines for therapy. J Infect Dis 2001; 184(11): 1437–44

    PubMed  CAS  Google Scholar 

  285. Gayle A, Ringdahl E. Tick-borne diseases. Am Fam Physician 2001; 64(3): 461–6

    PubMed  CAS  Google Scholar 

  286. Kostman JR. Laboratory diagnosis of rickettsial diseases. Clin Dermatol 1996; 14(3): 301–6

    PubMed  CAS  Google Scholar 

  287. Masters EJ, Olson GS, Weiner SJ, et al. Rocky Mountain spotted fever: a clinician’s dilemma. Arch Intern Med 2003; 163(7): 769–74

    PubMed  Google Scholar 

  288. Cale DF, McCarthy MW. Treatment of Rocky Mountain spotted fever in children. Ann Pharmacother 1997; 31(4): 492–4

    PubMed  CAS  Google Scholar 

  289. Tsai TF, Olson JG. Rickettsial spotted fever infections: another pediatric indication for fluoroquinolones? [letter]. Pediatr Infect Dis J 1995; 14(7): 635

    PubMed  CAS  Google Scholar 

  290. Jabarit-Aldighieri N, Torres H, Raoult D. Susceptibility of Rickettsia conorii, R. rickettsii, and Coxiella burnetii to PD 127,391, PD 131,628, pefloxacin, ofloxacin, and ciprofloxacin. Antimicrob Agents Chemother 1992; 36(11): 2529–32

    CAS  Google Scholar 

  291. Maurin M, Raoult D. Bacteriostatic and bactericidal activity of levofloxacin against Rickettsia rickettsii, Rickettsia conorii, ‘Israeli spotted fever group rickettsia’ and Coxiella burnetii. J Antimicrob Chemother 1997; 39(6): 725–30

    PubMed  CAS  Google Scholar 

  292. Clements ML, Wisseman Jr CL, Woodward TE, et al. Reactogenicity, immunogenicity, and efficacy of a chick embryo cell-derived vaccine for Rocky Mountain spotted fever. J Infect Dis 1983; 148(5): 922–30

    PubMed  CAS  Google Scholar 

  293. Dumler JS, Wisseman Jr CL, Fiset P, et al. Cell-mediated immune responses of adults to vaccination, challenge with Rickettsia rickettsii, or both. Am J Trop Med Hyg 1992; 46(2): 105–15

    PubMed  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Infectious Diseases, Department of Medical Sciences, Akademiska Sjukhuset, Uppsala University Hospital, SE-751 85, Uppsala, Sweden

    Göran Günther

  2. Clinic of Infectious Diseases, County Hospital, Kalmar, Sweden

    Mats Haglund

  3. Research Institute of Zoonotic Ecology and Epidemiology (RIZEE), Färjestaden, Sweden

    Mats Haglund

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Günther, G., Haglund, M. Tick-Borne Encephalopathies. CNS Drugs 19, 1009–1032 (2005). https://doi.org/10.2165/00023210-200519120-00004

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