Persistence of borrelia burgdorferi and histopathological alterations in experimentally infected animals. A comparison with histopathological findings in human Lyme disease

Persistenz von Borrelia burgdorferi und histopathologische Veränderungen in experimentell infizierten Gerbils


Gerbils appear to be susceptible to infection by human isolates ofBorrelia burgdorferi; we obtained 100% infection. Isolation of theB. burgdorferi from different organs six months post infection causes a generalized infection thus demonstrating that borreliae persist in these animals for a long period. Spirochetemia was present for 14 days, apparently in two intervals. TheBorrelia burgdorferi specific antibody titers increased with time after infection thus indicating the persistence of spirochetes. The intraperitoneal inoculation of theB. burgdorferi to six gerbils of groups A and B induced significant histopathologic changes in most of the major organ systems and their surrounding adipose and fibrous connective tissues. The infiltrates consisted mainly of lymphocytes and histiocytes. Various numbers of plasma cells, eosinophils and high numbers of mast cells were also present. Three further animals which served as controls displayed no histological signs of inflammation in any organ system. No significant differences were noted between the histopathological findings seen in the animals of groups A and B (infected with cells from subcultures no. 25 and with no. 5, respectively). The persistence ofB. burgdorferi and the high number of organs involved with slight to severe signs of inflammation in this series can be compared to persistence and to the multiorgan involvement seen in human Lyme disease. Thus gerbils can serve as suitable experimental animals to study the pathogenesis of Lyme disease and the extent of organ damage caused byB. burgdorferi.


Das Humanisolat P/Ko derBorrelia burgdorferi ist infektiös für Gerbils, wir konnten damit eine 100%ige Infektion der Tiere erreichen. Die Isolierung derB. burgdorferi aus verschiedenen Organen, sechs Monate nach der Infektion, bestätigt eine generalisierte Infektion und zeigt, daß Borrelien in diesen Tieren über Monate persistieren können. Die Spirochätemie wurde 14 Tage beobachtet und erfolgte in zwei Intervallen. Die intraperitoneale Inokulation derB. burgdorferi an sechs Gerbils der Gruppen A und B (infiziert mit 25. bzw. 5. Subkultur des Erregers) verursachte signifikante histopathologische Veränderungen in der Mehrzahl der Organsysteme und dem umgebenden Gewebe. Die histologischen Befunde zeigen perivaskuläre, entzündliche Reaktionen mit Lymphozyten, Histiozyten, Plasmazellen und eosinophilen Leukozyten. Bei Kontrolltieren wurden keine Zeichen von Entzündungen in keinem der Organe festgestellt. Die histopathologischen Ergebnisse der Tiergruppen A und B sind nahezu identisch. Die Persistenz derB. burgdorferi und die hohe Zahl der betroffenen Organsysteme in dieser Versuchsserie kann mit Beobachtungen an Patienten mit Lyme-Borreliose verglichen werden. Die Ergebnisse dieser Studie bestätigen, daß Gerbils als Tiermodell für Studien der Pathogenese der Lyme-Borreliose sowie andereIn-vivo-Studien sehr geeignet sind.

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  1. 1.

    Steere, A. C., Malawista, S. E., Newman, J. H., Spieler, P. N., Bartenhagen, N. H. Antibiotic therapy in Lyme disease. Ann. Intern. Med. 93 (1980) 1–8.

    Google Scholar 

  2. 2.

    Steere, A. C., Pachner, A. R., Malawista, S. E. Neurological abnormalities of Lyme disease: successful treatment with high-dose intravenous penicillin. Ann. Intern. Med. 99 (1983) 767–772.

    Google Scholar 

  3. 3.

    Asbrink, E. Erythema chronicum migrans Afzelius and Acrodermatitis chronica atrophicans. Early and late manifestations of Ixodes ricinus-borne Borrelia spirochetes. Acta Derm. Venered (Stockh.) (Suppl. 118) (1985) 1–63.

    Google Scholar 

  4. 4.

    Kristoferitsch, W., Baumhackl, U., Sluga, E., Stanek, G., Zeiler, K. High dose penicillin in meningopolyneuritis Garin-Bujadoux-Bannwarth. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 357–364.

    Google Scholar 

  5. 5.

    Weber, K., Neubert, U., Thurmayr, R. Antibiotic therapy in early erythema migrans disease and related disorders. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 377–388.

    Google Scholar 

  6. 6.

    Weber, K., Preac-Mursic, V., Neubert, U., Thurmayr, R., Herzer, P., Wilske, B., Schierz, G., Marget, W. Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica atrophicans. Ann. N. Y. Acad. Sci. 539 (1988) 324–345.

    Google Scholar 

  7. 7.

    Dattwyler, R. J., Halperin, J. J., Volkman, D. J., Luft, B. J. Treatment of late lyme borreliosis — randomised comparison of ceftriaxone and penicillin. Lancet ii (1988) 1191–1194.

    Google Scholar 

  8. 8.

    Pal, G. S., Baker, J. T., Wright, D. J. M. Penicillin — resistant borrelia encephalitis responding to cefotaxime. Lancet i (1988) 50–51.

    Google Scholar 

  9. 9.

    Pfister, H. W., Preac-Mursic, V., Wilske, B., Einhäupl, K. M. Cefotaxime versus penicillin G for acute neurological manifestations in Lyme-borreliosis: A prospective randomised study. Arch. Neurol. 46 (1989) 1190–1194.

    Google Scholar 

  10. 10.

    Pfister, H. W., Preac-Mursic, V., Wilske, B., Einhäupl, K. M.: Cefotaxime versus ceftriaxone for acute neurological manifestations in Lyme-borreliosis: A prospective randomised study. J. Infect. Dis. In press.

  11. 11.

    Diringer, M. N., Halperin, J. J., Dattwyler, R. J. Lyme meningoencephalitis — report of a severe, penicillin resistant case. Arthritis. Rheum. 30 (1987) 705–708.

    Google Scholar 

  12. 12.

    Preac-Mursic, V., Weber, K., Pfister, H. W., Wilske, B., Groß, B., Baumann, A., Prokop, J. Survival ofBorrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 17 (1989) 355–359.

    Google Scholar 

  13. 13.

    Preac-Mursic, V., Wilske, B., Schierz, G., Holnburger, M., Süß, E. In vitro andin vivo susceptibility ofBorrelia burgdorferi. Eur. J. Clin. Microbiol. 4 (1987) 424–426.

    Google Scholar 

  14. 14.

    Preac-Mursic, V., Wilske, B., Schierz, G. EuropeanBorrelia burgdorferi isolated from humans and ticks. Culture conditions and antibiotic susceptibility. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 112–118.

    Google Scholar 

  15. 15.

    Steiner G. Modified silver stain of microorganisms in tissue. Am. J. Clin. Path. 20 (1950) 489–490.

    Google Scholar 

  16. 16.

    Bosma, R. B. De gemodificeerde Gabriel Steiner techniek voor het aantonen van spirochaeten. Histotechniek 3 (1984) 161–166.

    Google Scholar 

  17. 17.

    Wilske, B., Schierz, G., Preac-Mursic, V., Weber, K., Pfister, H. W., Einhäupl, K. Serological diagnosis of erythema migrans disease and related disorders. Infection 12 (1984) 331–337.

    Google Scholar 

  18. 18.

    Burgdorfer, W. The New Zealand white rabbit. An experimental host for infecting ticks with Lyme disease spirochetes. Yale J. Biol. Med. 57 (1984) 609–612.

    Google Scholar 

  19. 19.

    Burgdorfer, W., Gage, K. L. Susceptibility of the hispid cotton rat (Sigmodon hispidus) to the Lyme disease spirochete(Borrelia burgdorferi). Am. J. Trop. Med. Hyg. 37 (1987) 624–628.

    Google Scholar 

  20. 20.

    Johnson, R. C., Marek, N., Kodner, C. Infection of Syrian hamsters with Lyme disease spirochetes. J. Clin. Microbiol. 20 (1984) 1099–1101.

    Google Scholar 

  21. 21.

    Kornblatt, A. N., Steere, A. C., Brownstein, D. G. Experimental Lyme disease in rabbits. Spirochetes found in erythema migrans and blood. Infect. Immun. 46 (1984) 220–223.

    Google Scholar 

  22. 22.

    Anderson, J. F., Johnson, R. C., Magnarelli, L. A., Hyde, F. W. Involvement of birds in the epidemiology of the Lyme disease agentBorrelia burgdorferi. Infect. Immun. 51 (1986) 394–396.

    Google Scholar 

  23. 23.

    Burgess, E. C. Experimental inoculation of dogs withBorrelia burgdorferi. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 49–54.

    Google Scholar 

  24. 24.

    Stanek, G., Burger, I., Hirschl, A., Wewalka, G., Radda, A. Borrelia transfer by ticks during their life cycle. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 262 (1986) 29–33.

    Google Scholar 

  25. 25.

    Barthold, S. W., Moody, K. C., Terwilliger, J. A., Duray, P. H., Jacoby, R. O., Steere, A. C. Experimental Lyme arthritis of rats infected withBorrelia burgdorferi. J. Infect. Dis. 157 (1988) 842–846.

    Google Scholar 

  26. 26.

    Duray, P. H., Steere, A. C. The spectrum of organ and systems pathology in human Lyme disease. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 169–178.

    Google Scholar 

  27. 27.

    Camponovo, F., Meier, C. Neuropathy of vasculitis origin in a case of Garin-Bujadoux-Bannwarth Syndrome with positive borrelia antibody response. J. Neurol. 233 (1986) 69–72.

    Google Scholar 

  28. 28.

    Meier, C., Grehl, H. Vaskulitische Neuropathie bei Garin-Bujadoux-Bannwarth Syndrom. Deutsch. Med. Woch. 113 (1988) 135–138.

    Google Scholar 

  29. 29.

    Vallat, J. M., Hugon, J., Lubeau, M., Leboutet, M. J., Dumas, M., Deproges-Gotteron, M. Tick-bite meningoradiculoneuritis: clinical, electrophysiologic and histologic findings in ten cases. Neurology 37 (1987) 749–753.

    Google Scholar 

  30. 30.

    Mac Donald, A. B. Borrelia in the brains of patients dying with dementia. JAMA 256 (1986) 2195–2196.

    Google Scholar 

  31. 31.

    Halperin, J., Little, B., Coyle, P., Dattwyler, R. Lyme disease: Cause of a treatable peripheral neuropathy. Neurology 37 (1987) 1700–1706.

    Google Scholar 

  32. 32.

    Rothemund, E., Patsouris, E., Feiden, W., Pfister, W., Mehraein, S. Polyneuropathy in Lyme borreliosis: histological findings in sural nerve biopsy and experimental data. Clin. Neuropathol. 8 (1989) 247.

    Google Scholar 

  33. 33.

    Pachner, A. R., Duray, P. H., Steere, A. C. Central nervous system manifestations of Lyme disease. Arch. Neurol. 46 (1989) 790–795.

    Google Scholar 

  34. 34.

    Schaltenbrand, G. Chronische aseptische Meningitis. Nervenarzt 20 (1949) 433–442.

    Google Scholar 

  35. 35.

    Schmutzhard, E., Willeit, J., Gerstenbrand, F. Meningopolyneuritis Bannwarth with focal nodular myositis. Klin. Wochenschr. 64 (1986) 1204–1208.

    Google Scholar 

  36. 36.

    Reimers, C., Pongratz, D., Neubert, U., Pilz, A., Hübner, G., Naegele, M., Wilske, B., Duray, P., de Koning, K. Mysositis caused byBorrelia burgdorferi: report of four cases. J. Neurol. Sci. 91/1–2 (1989) 215–226.

    Google Scholar 

  37. 37.

    Schoenen, J., Sianard-Gainko, J., Carpentier, M., Reznik, M. Myositis duringBorrelia burgdorferi infection (Lyme disease). J. Neur. Neurosury. Psychiatr. 52 (1989) 1001–1005.

    Google Scholar 

  38. 38.

    Mc Donald, A. Lyme disease: A neuro-ophthalmologic view. J. Clin. Neuroophthalmology 7 (1987) 185–190.

    Google Scholar 

  39. 39.

    Lampert, F. Infantile multisystem inflammatory disease. Another case of a new syndrome. Eur. J. Pediatr. 444 (1984) 593–596.

    Google Scholar 

  40. 40.

    Steere, A. C., Duray, P. H., Kaufmann, D. J. H., Wormser, G. P. Unilateral blindness caused by infection with the Lyme disease spirocheteBorrelia burgdorferi. Ann. Intern. Med. 103 (1985) 382–384.

    Google Scholar 

  41. 41.

    Duray, PH., Johnson, R. The histopathology of experimentally infected hamsters with the Lyme disease spirochete,Borrelia burgdorferi. Proc. Soc. Exp. Biol. Med. 181 (1986) 263–269.

    Google Scholar 

  42. 42.

    Houverzijl, R., Root, J. J., Hoogkamp-Korstanje, J. A. A. A case of Lyme disease with cardiac involvement in the Netherlands. Infection 12 (1984) 358.

    Google Scholar 

  43. 43.

    Marcus, L., Steere, A. C., Duray, P. H., Anderson, A. E., Mahoney, E. B. Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis. Demonstration of spirochetes in the myocardium. Ann. Intern. Med. 103 (1985) 372–376.

    Google Scholar 

  44. 44.

    De Koning, J., Hoogkamp-Korstanje, J. A. A., van der Linde, M. R., Czijns, H. J. Demonstration of spirochetes in cardiac biopsies of patients with Lyme disease. J. Inf. Dis. 160 (1989) 150–153.

    Google Scholar 

  45. 45.

    Koning, J., Hoogkamp-Korstanje, J. A. A. Diagnosis of Lyme disease by demonstration of spirochetes in tissue biopsies. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 179–188.

    Google Scholar 

  46. 46.

    Preac-Mursic, V., Wilske, B., Herzer, P., Schierz, G., Bauer, M. Acrodermatitis chronica atrophicans — eine Borreliose. Hautarzt 36 (1985) 691–693.

    Google Scholar 

  47. 47.

    Berger, B. W., Clemmenren, O. J., Ackermann, A. Lyme disease is a spirochetosis: A review of the disease and evidence for its cause. Am. J. Dermatopathol. 5 (1983) 11–124.

    Google Scholar 

  48. 48.

    Waldo, E., Sidhu, G. The spirochete in Erythema chronicum migrans. Am. J. Dermatopath. 5 (1983) 125–127.

    Google Scholar 

  49. 49.

    Abele, D. C., Anders, K. H., Chandler, F. W. Benign lymphocytic infiltration (Jessner-Kanot) another manifestation of Borreliosis. J. Am. Acad. Dermatol. 21 (1989) 795–797.

    Google Scholar 

  50. 50.

    Kawabata, M., Baba, S., Iguchi, K., Yamaguti, N., Russel, H. Lyme disease in Japan and its possible incriminated tick vector, Ixodes persulcatus. J. Inf. Dis. 156 (1987) 5.

    Google Scholar 

  51. 51.

    Berger, B. W., Kaplan, M. H., Rotenberg, I. R., Barbour, A. G. Isolation and characterisation of the Lyme disease spirochete from the skin of patients with erythema chronicum migrans. J. Am. Acad. Dermatol. 13 (1985) 444–449.

    Google Scholar 

  52. 52.

    Steere, A. C., Malawista, S. E., Hardin, J. A., Rudy, S., Askenase, P. W., Andiman, W. A. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann. Intern. Med. 86 (1977) 685–698.

    Google Scholar 

  53. 53.

    Berger, B. E., Winchester, R. J., Hardin, J. A., Malawista, S. E. Dermatologic manifestations of Lyme disease. Rev. Infect. Dis. Vol. II (Supplement 6) (1989) 1475–1481.

    Google Scholar 

  54. 54.

    Steere, A. C., Gibofsky, A., Patarrono, M. W. Chronic lyme arthritis. Ann. Intern. Med. 90 (1979) 896–901.

    Google Scholar 

  55. 55.

    Johnston, Y. E., Duray, P. H., Steere, A. C. Lyme arthritis. Spirochetes found in microangiopathic lesions. Am. J. Pathol. 118 (1985) 26–34.

    Google Scholar 

  56. 56.

    Chavanet, P., Pillon, D., Lancon, J. P., Waldner-Combernoux, A., Maringe, E., Portier, H. Granulomatous hepatitis associated with Lyme disease. Lancet ii (1987) 523–524.

    Google Scholar 

  57. 57.

    Rank, E., Dias, S., Hasson, J., Duray, P. H., Johnson, R., Magnarelli, L., Fister, R. Human necrotizing splenitis caused byBorrelia burgdorferi. Am. J. Clin. Pathol. 91 (1989) 493–498.

    Google Scholar 

  58. 58.

    Cimmino, M., Azzolini, A., Tobia, F., Pesce, C. Spirochetes in the spleen of a patient with chronic Lyme disease. Am. J. Clin. Pathol. 91 (1989) 95–97.

    Google Scholar 

  59. 59.

    Neubert, U., Krampitz, H. E., Eugl, H. Microbiological findings in erythema (chronicum) migrans and related disorders. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 237–252.

    Google Scholar 

  60. 60.

    Schaad, U. B., Flüeler, U., Schaub, H., Suter, D., Vischer, D., Caflisch, U., Tschumi, A., Wick, M., Vest, M., Durrer, D. Durch lxodes-ricinus Spirochäten(Borrelia burgdorferi) verursachte Krankheitsbilder (Lyme-Krankheit) bei pädiatrischen Patienten in der Schweiz. Schweiz. med. Wschr. 116 (1986) 1426–1430.

    Google Scholar 

  61. 61.

    Benach, J. L., Habicht, G. S., Cosinski, B. L., Coleman, J. L. Phagocytic cell responses toin vivo andin vitro exposure to the Lyme disease spirochete. Lyme Disease-First International Symposium, Yale. J. Biol. Med. New Haven Vol. No. 57 (1984) 149–155.

    Google Scholar 

  62. 62.

    Peterson, P. K., Clawson, C. C., Lee, D. A., Garlich, D. J., Quie, P. G., Johnson, R. C. Human phagocyte interactions with the Lyme disease spirochete. Infect. Immun. 46 (1984) 608–611.

    Google Scholar 

  63. 63.

    Anderson, J. F., Magnarelli, L. A., Burgdorfer, W., Barbour, A. G. Spirochetes in Ixodes dammini and mammals from Connecticut. Amer. J. Trop. Med. Hyg. 32 (1983) 818–824.

    Google Scholar 

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Preac Mursic, V., Patsouris, E., Wilske, B. et al. Persistence of borrelia burgdorferi and histopathological alterations in experimentally infected animals. A comparison with histopathological findings in human Lyme disease. Infection 18, 332–341 (1990).

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  • Mast
  • Histopathological Finding
  • Lyme Disease
  • Borrelia Burgdorferi
  • Fibrous Connective Tissue