Lyme Borreliosis in Rhesus Macaques: Effects of Corticosteroids on Spirochetal Load and Isotype Switching of Anti-<i>Borrelia burgdorferi</i>Antibody

Pachner, Andrew R.; Amemiya, Kei; Bartlett, Melanie; Schaefer, Henry; Reddy, K. Siva; Zhang, Weifen

doi:10.1128/cdli.8.2.225-232.2001

Cited by 29 publications

(42 citation statements)

References 29 publications

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“…In some animal models, nervous system disease is more pronounced if corticosteroids are administered. 46 In contrast, anecdotal studies have suggested outcomes in patients with severe radicular pain 47 or encephalomyelitis 48 may be improved if corticosteroids and antibiotics are administered concurrently. One large retrospective review 49 of 101 patients with Lyme disease-associated facial nerve palsy found no significant difference in outcome regardless of treatment (antibiotics in 37, steroids alone or in combination with antibiotics in 44, no treatment in the remainder), although the only patient in the group with severe residua had received steroids.…”

mentioning

confidence: 99%

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology [RETIRED]

Halperin¹,

Shapiro²,

Logigian³

et al. 2007

Neurology

301

142

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Objective: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? Methods: The authors analyzed published studies ) using a structured review process to classify the evidence related to the questions posed. Results: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. Conclusions:There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (Ն8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A). NEUROLOGY 2007;69:91-102

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confidence: 99%

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology [RETIRED]

Halperin¹,

Shapiro²,

Logigian³

et al. 2007

Neurology

301

142

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“…5 The immunoblot for all inoculated NHPs have been reported. 5,16,17 Table 1 also summarizes the immunoblot results for the BbN40-inoculated immunocompetent NHPs: all that were tested had positive Lyme IgG WB at necropsy and none had positive IgM WB when examined later than 6 months after inoculation. All WB from garinii-inoculated NHPs were negative even when tested with homologous sonicates, 5 an indication that NHPs are resistant to syringe inoculation of garinii strains of Lyme disease borrelias.…”

Section: Antibody Responsementioning

confidence: 99%

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Cadavid

Bai

Hodzic

et al. 2004

Laboratory Investigation

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To investigate cardiac involvement in the non-human primate (NHP) model of Lyme disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu stricto strains N40 (BbN40) by needle (N ¼ 22, 14 immunocompetent (IC), seven permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP)) or by tick-bite (N ¼ 4, all TISP) or strain 297 (Bb297) by needle (N ¼ 2 IS), or with B. garinii strains Pbi (N ¼ 4, 2 TISP and 2 IS), 793 (N ¼ 2, TISP) or Pli (N ¼ 2, TISP). Five uninfected NHPs were used as controls. Infection and inflammation was studied in the hearts and the aorta removed at necropsy 2-32 months after inoculation by (1) H&E and trichrome-staining; (2) immunohistochemistry and digital image analysis; (3) Western blot densitometry; and (4) TaqMan RT-PCR. All NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The predominant cells were T cells, plasma cells, and macrophages. There was increased IgG and IgM in the heart independent of immunosuppression. The B-cell chemokine BLC was significantly increased in IS-NHPs. There was increased deposition of the complement membrane attack complex (MAC) in TISP and IS-NHPs. The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis in NHPs infected with B. burgdorferi is frequent and can persist for years but is mild unless they are immunosupressed.

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“…Commercial B. burgdorferi sensu stricto nitrocellulose strips (Microbiology Reference Laboratory, Cypress, CA, USA) were used as previously described 10,14 according to the instructions of the diagnostic kit. The strain used for preparation of these blots was a B. burgdorferi sensu stricto strain CB, an isolate from an erythema migrans lesion from a patient from Valhalla, NY.…”

Section: Immunoblottingmentioning

confidence: 99%

“…For the last several years, we have been studying the pathogenesis of Lyme neuroborreliosis in nonhuman primates (NHP). [8][9][10][11][12][13] Previous studies showed that the localization of B. burgdorferi once it disseminates from the skin can only be studied if immunosuppression is used. 13 Both inflammation and infection are more prominent in the periphery than in the CNS.…”

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confidence: 99%

Spinal cord involvement in the nonhuman primate model of Lyme disease

Bai

Narayan

Dail

et al. 2004

Laboratory Investigation

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Lyme borreliosis is a multisystemic disease caused by infection with various genospecies of the spirochete Borrelia burgdorferi. The organs most often affected are the skin, joints, the heart, and the central and peripheral nervous systems. Multiple neurological complications can occur, including aseptic meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and peripheral neuropathy. To investigate spinal cord involvement in the nonhuman primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta with B. burgdorferi sensu strictu strains N40 by needle (N ¼ 9) or by tick (N ¼ 4) or 297 by needle (N ¼ 2), or with B. burgdorferi genospecies garinii strains Pbi (N ¼ 4), 793 (N ¼ 2), or Pli (N ¼ 4) by needle. Immunosuppression either transiently (TISP) or permanently (IS) was used to facilitate establishment of infection. Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and eosin staining was used to study inflammation, and immunohistochemistry and digital image analysis to measure inflammation and localize spirochetes. The spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord parenchyma itself. T cells and plasma cells were the predominant inflammatory cells. Significantly increased amounts of IgG, IgM, and C1q were found in inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma. C1q mRNA expression was significantly increased in inflamed spinal cord. This is the first comprehensive study of spinal cord involvement in Lyme borreliosis.

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Lyme Borreliosis in Rhesus Macaques: Effects of Corticosteroids on Spirochetal Load and Isotype Switching of Anti-Borrelia burgdorferiAntibody

Cited by 29 publications

References 29 publications

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology [RETIRED]

Practice Parameter: Treatment of nervous system Lyme disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology [RETIRED]

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

Spinal cord involvement in the nonhuman primate model of Lyme disease

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