This project, presented by an outstanding group of investigators that includes Drs. M. T. Philipp as P.I. and M. S. Klempner, is designed to complement and expand a human study already in course directed to probe the efficacy of an antibiotic regimen designed to treat chronic Lyme disease. The investigators propose to study in rhesus monkeys the efficacy of ceftriaxone and doxycycline to eliminate B. burgdorferi for tissues, especially from the central nervous system. The protocol is two-tiered. In the first tier, 6 monkeys will be tick infected with neurotropic B. burgdorferi NT1 to confirm the neurotropism of the strain. One monkey will be left uninfected, as a control. In the second tier, 24 animals will be tick infected with strain NT1, with four remaining uninfected. The animals will be divided into two groups (12 + 2) and one will be treated with antibiotics and the other given placebo. The ability of the antibiotic to clear up tissues from infection with B. burgdorferi NT1 will be ascertained by a variety of serially applied procedures that will include: culture and PCR of skin biopsies; PCR and RT-PCR applied to CSF; immunological detection of bacterial antigens in urine, and qualitated and quantitated analysis of anti-borrelial antibodies paired sera and CSF, anti p39 (BmpA) antibody in serum and levels of matrix metalloproteinases in samples from nervous tissues. The analysis will also include postmortem histological examination, culture and PCR studies in tissues from many organs.
|Embers, Monica E; Hasenkampf, Nicole R; Jacobs, Mary B et al. (2012) Dynamic longitudinal antibody responses during Borrelia burgdorferi infection and antibiotic treatment of rhesus macaques. Clin Vaccine Immunol 19:1218-26|
|Embers, Monica E; Barthold, Stephen W; Borda, Juan T et al. (2012) Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS One 7:e29914|
|Narasimhan, Sukanya; Caimano, Melissa J; Liang, Fang Ting et al. (2003) Borrelia burgdorferi transcriptome in the central nervous system of non-human primates. Proc Natl Acad Sci U S A 100:15953-8|