Chronic lyme disease in the rhesus monkey.
BACKGROUND
We have previously reported the clinical, pathologic, and immunologic features of "early" Borrelia burgdorferi infection in rhesus monkeys (3). We have now evaluated these features during the chronic phase of Lyme disease in this animal model.


METHODS
Clinical signs, and pathologic changes at the gross and microscopic levels, were investigated 6 months post-infection in several organ systems of five rhesus macaques (Macaca mulatta), which were infected with Borrelia burgdorferi by allowing infected Ixodes scapularis nymphal ticks to feed on them. A sixth animal was used as an uninfected control. Borrelia antigens recognized by serum antibody were identified longitudinally by Western blot analysis, and C1q-binding immune complexes were quantified. Localization of the spirochete in the tissues was achieved by immunohistochemistry and in vitro culture. The species of spirocheta cultured was confirmed by the polymerase chain reaction.


RESULTS
Chronic arthritis was observed in five out of five animals. The knee and elbow joints were the most consistently affected. Articular cartilage necrosis and/or degenerative arthropathy were the most severe joint structural changes. Synovial cell hyperplasia and a mononuclear/lymphocyte infiltrate were commonly seen. Nerve lesions were also observed, including nerve sheath fibrosis and focal demyelinization of the spinal cord. Peripheral neuropathy was observed in five out of five animals and could be correlated in the most severely affected monkey with the presence of higher levels of circulating immune complexes. Differences in disease severity did not correlate with differences in the antigens recognized on Western blot analysis.


CONCLUSIONS
B. burgdorferi infection in rhesus macaques mirrors several aspects of both the early and chronic phases of the disease in humans. This animal model will facilitate the study of the pathogenesis of Lyme arthritis and neuroborreliosis.
Roberts
E D
ED
Department of Pathology, Tulane Regional Primate Research Center, Tulane University Medical Center, Covington, Louisiana.
Bohm
R P
RP
Cogswell
F B
FB
Lanners
H N
HN
Lowrie
R C
RC
Povinelli
L
L
Piesman
J
J
Philipp
M T
MT
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology; D001170:Arthritis, Infectious / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000276:immunology; D002358:Cartilage, Articular / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007596:Joints / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008193:Lyme Disease / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D009336:Necrosis; D009420:Nervous System / Q000473:pathology; D016133:Polymerase Chain Reaction; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D013987:Ticks
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004269:DNA, Bacterial