Backround and Objectives The preferred antibiotic treatment of chronic Lyme disease, and that of chronic neuroborreliosis in particular, is still not fully defined. In an effort to develop improved and more reliable remedies for chronic Lyme disease, an eclectic treatment regimen has been designed. It includes two antibiotics that are highly effective against both acute and chronic Lyme disease ceftriaxone (2 g, IV, once a day, 30 days) and doxycycline (100 mg/kg, bid, per os, 60 days). The goal of this project is to assess the efficacy of this combination regimen, originally devised for humans, in rhesus macaques. More specifically, to monitor the elimination of a Borrelia burgdorferi infection from all organs commonly targeted by this spirochete, and especially from the central nervous system. Results Six rhesus macaques were inoculated with a neurotropic strain of B. burgdorferi (strain NT1) by exposure to infected ticks, and one control animal was exposed to the bite of uninfect ed ticks. All animals were confirmed to be infected by cultivating spirochetes, and amplifying spirochetal DNA by PCR, from skin biopsy samples. Animals were monitored over a six-month period. Unlike previous experiments, in which animals had been infected by needle inoculation with the NT1 strain, no evidence of infection in the central nervous system was obtained. Success in infecting the CNS may thus depend on the inoculum dose, which is likely higher when animals are infected with 108 spirochetes by needle inoculation than by exposure to the bites of ticks. Future Directions The antibiotic efficacy trial will now begin, but needle-inoculated animals will be employed. FUNDING NIH-NIAID RO1 AI42352-01 and Base grant. PUBLICATIONS None.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-41
Application #
6591729
Study Section
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
41
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

Showing the most recent 10 out of 352 publications