Summary
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.
Zusammenfassung
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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
Pal, G. S., Baker, J. T., Wright, D. J. M. Penicillin — resistant borrelia encephalitis responding to cefotaxime. Lancet i (1988) 50–51.
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.
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.
Diringer, M. N., Halperin, J. J., Dattwyler, R. J. Lyme meningoencephalitis — report of a severe, penicillin resistant case. Arthritis. Rheum. 30 (1987) 705–708.
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.
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.
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.
Steiner G. Modified silver stain of microorganisms in tissue. Am. J. Clin. Path. 20 (1950) 489–490.
Bosma, R. B. De gemodificeerde Gabriel Steiner techniek voor het aantonen van spirochaeten. Histotechniek 3 (1984) 161–166.
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.
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.
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.
Johnson, R. C., Marek, N., Kodner, C. Infection of Syrian hamsters with Lyme disease spirochetes. J. Clin. Microbiol. 20 (1984) 1099–1101.
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.
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.
Burgess, E. C. Experimental inoculation of dogs withBorrelia burgdorferi. Zentralbl. Bakteriol. Mikrobiol. Hyg. A 263 (1986) 49–54.
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.
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.
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.
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.
Meier, C., Grehl, H. Vaskulitische Neuropathie bei Garin-Bujadoux-Bannwarth Syndrom. Deutsch. Med. Woch. 113 (1988) 135–138.
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.
Mac Donald, A. B. Borrelia in the brains of patients dying with dementia. JAMA 256 (1986) 2195–2196.
Halperin, J., Little, B., Coyle, P., Dattwyler, R. Lyme disease: Cause of a treatable peripheral neuropathy. Neurology 37 (1987) 1700–1706.
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.
Pachner, A. R., Duray, P. H., Steere, A. C. Central nervous system manifestations of Lyme disease. Arch. Neurol. 46 (1989) 790–795.
Schaltenbrand, G. Chronische aseptische Meningitis. Nervenarzt 20 (1949) 433–442.
Schmutzhard, E., Willeit, J., Gerstenbrand, F. Meningopolyneuritis Bannwarth with focal nodular myositis. Klin. Wochenschr. 64 (1986) 1204–1208.
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.
Schoenen, J., Sianard-Gainko, J., Carpentier, M., Reznik, M. Myositis duringBorrelia burgdorferi infection (Lyme disease). J. Neur. Neurosury. Psychiatr. 52 (1989) 1001–1005.
Mc Donald, A. Lyme disease: A neuro-ophthalmologic view. J. Clin. Neuroophthalmology 7 (1987) 185–190.
Lampert, F. Infantile multisystem inflammatory disease. Another case of a new syndrome. Eur. J. Pediatr. 444 (1984) 593–596.
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.
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.
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.
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.
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.
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.
Preac-Mursic, V., Wilske, B., Herzer, P., Schierz, G., Bauer, M. Acrodermatitis chronica atrophicans — eine Borreliose. Hautarzt 36 (1985) 691–693.
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.
Waldo, E., Sidhu, G. The spirochete in Erythema chronicum migrans. Am. J. Dermatopath. 5 (1983) 125–127.
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.
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.
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.
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.
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.
Steere, A. C., Gibofsky, A., Patarrono, M. W. Chronic lyme arthritis. Ann. Intern. Med. 90 (1979) 896–901.
Johnston, Y. E., Duray, P. H., Steere, A. C. Lyme arthritis. Spirochetes found in microangiopathic lesions. Am. J. Pathol. 118 (1985) 26–34.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1007/BF01646399
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01646399