Xenodiagnosis by ticks was used to determine whether spirochetes persist in mice after 1 month of antibiotic therapy for vectorborne Borrelia burgdorferi infection. Immunofluorescence and polymerase chain reaction (PCR) were used to show that spirochetes could be found in Ixodes scapularis ticks feeding on 4 of 10 antibiotic-treated mice up to 3 months after therapy. These spirochetes could not be transmitted to naive mice, and some lacked genes on plasmids correlating with infectivity. By 6 months, antibiotic-treated mice no longer tested positive by xenodiagnosis, and cortisone immunosuppression did not alter this result. Nine months after treatment, low levels of spirochete DNA could be detected by real-time PCR in a subset of antibiotic-treated mice. In contrast to sham-treated mice, antibiotic-treated mice did not have culture or histopathologic evidence of persistent infection. These results provide evidence that noninfectious spirochetes can persist for a limited duration after antibiotics but are not associated with disease in mice.
"Embers et al138 addressed several of the key issues identified by Wormser and Schwartz140 in their 2009 review that focused on studies by Bockenstedt et al,141 Hodzic et al,142 and Straubinger et al,143 all of which documented the persistence of Bb in the tissues of animals despite the antibiotic challenge. "
[Show abstract][Hide abstract] ABSTRACT: Is chronic illness in patients with Lyme disease caused by persistent infection? Three decades of basic and clinical research have yet to produce a definitive answer to this question. This review describes known and suspected mechanisms by which spirochetes of the Borrelia genus evade host immune defenses and survive antibiotic challenge. Accumulating evidence indicates that Lyme disease spirochetes are adapted to persist in immune competent hosts, and that they are able to remain infective despite aggressive antibiotic challenge. Advancing understanding of the survival mechanisms of the Lyme disease spirochete carry noteworthy implications for ongoing research and clinical practice.
International Journal of General Medicine 04/2013; 6:291-306. DOI:10.2147/IJGM.S44114
"Serological data as well as our culture results suggest that initial infections were cleared. Positive PCR signals in two mice 7 days after inoculation and, even more importantly, in one animal 28 days post-inoculation imply the presence of non-culturable spirochaetes in these cases.37–39 It was shown that B. burgdorferi remains localized for >2 days at the site of infection before the organisms start to disseminate.19 "
[Show abstract][Hide abstract] ABSTRACT: Systemic antibiotic treatment of Lyme borreliosis is effective during the early stages of the infection, while chronic manifestations of the disease may remain refractory and difficult to treat. This study was carried out in order to evaluate the potential of topically applied azithromycin to eliminate the spirochaetal organisms in the skin of the freshly bitten host and thereby prevent Lyme borreliosis.
Laboratory mice were challenged with Borrelia burgdorferi sensu stricto by needle inoculation or via infected ticks as vectors. Then, an azithromycin-containing formulation was applied once daily to the sites of exposure for three consecutive days. In the case of needle inoculation, a 5% azithromycin formulation was applied starting 1 h, 3 days and 5 days after infection. In the case of tick exposure, 4%, 10% and 20% azithromycin formulations were applied, starting directly after the detachment of the engorged ticks. Subsequently, the infection status of the mice was determined.
Concentrations of azithromycin in murine skin were >3800-fold higher than the published minimal inhibitory concentration for B. burgdorferi as soon as 3 h after the first application. After needle inoculation, spirochaetes were not detectable in all infected mice after treatment, if the first application started 1 h or even after 3 days post-infection. Furthermore, no borrelial organisms were detected after topical treatment when ticks were used for spirochaete inoculation.
Our data indicate that topical treatment with a formulation containing azithromycin is a promising approach to prevent Lyme borreliosis shortly after a tick bite.
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