October 17 in San Francisco was a landmark day for Lyme disease, with stellar presentations being provided by leading investigators from the U.S. and Canada. At the annual conference co-sponsored by Columbia University and the Lyme Disease Association, several presentations paved the way for new inroads into our understanding of Lyme and other Tick-borne Diseases.
The keynote presentation by Dr. Steven Barthold from UC Davis highlighted that the Bb spirochete has evolved to persist within its reservoir hosts. Dr. Barthold's work in the mouse model in conjunction with prior work by researchers at Yale, Univ of Turku in Finland, and Cornell demonstrates that Bb can persist even after antibiotic therapy, although in smaller numbers and in a less active state; this work supports the hypothesis that Bb persist in the host not because of an antimicrobial resistance but through the process of "antimicrobial tolerance" in which spirochetes are metabolically less active and thus less vulnerable to antibiotic killing.
Dr. Steven Schutzer from UMDNJ discussed the application of a cutting edge pathogen detection system (IBIST5000) which uses a broad range PCR followed by mass spectrometry to identify unknown infections; applying this methodology to adult ticks Dr. Schutzer identified several pathogens in ticks - not just B.burgdorferi; for example, Borrelia miyamotoi was seen frequently.
Dr. Armin Alaedini from Weill Medical College of Cornell University reviewed various hypotheses that might explain post-treatment chronic symptoms and presented recent data showing patients with persistent symptoms after treatment of Lyme disease have elevated levels of anti-neural antibodies when compared to those who responded well to antibiotics and are no longer symptomatic. This work provides evidence for an ongoing abnormally activated immune response in patients with persistent symptoms.
Dr. Diego Cadavid from Biogen Idec and Massachusetts General Hospital described his work on the borrelial agent of relapsing fever which highlighted the neuroprotective importance of the anti-inflammatory cytokine IL10 (produced by microglia) - protecting the blood vessels of the brain from hemorrhage and thrombosis.
Dr. Patricia Conrad from UC Davis discussed what is known about Babesia duncani, a rare cause of human babesiosis reported in California; she emphasized that they have never been able to document persistent parasitic infection in patients with titers less than 1:5120.
Dr. Mario Philipp from U Tulane reported on the impact of Bb on freshly collected slices from the brain cortex of rhesus macaques, demonstrating markedly elevated levels of pro-inflammatory cytokines (e.g., IL8 and TNF) and neuronal and oligodendrocyte apoptosis; these findings support the hypothesis that neurologic disturbances in Lyme disease may be mediated by the induction in the CNS of inflammatory mediators.
Dr. Brian Fallon from Columbia University reviewed the literature on biomarkers of CNS Lyme disease and reported on findings of potential marked clinical significance which suggested that the C6 index and a brain neural network may be helpful in distinguishing that subgroup of patients more likely to benefit from a repeated course of antibiotic therapy from the non-responder subgroups who may need other non-antimicrobial treatment approaches.
Dr. Chris Contag from Stanford University reported on the use of in vivo bioluminescence imaging (BLI) as a non-invasive means of noninvasively detecting low levels of infection in tissues of living animal models; this method has been used to study a large number of infectious agents. Dr. Contag used infection by Listeria monocytogenes as an example of how an organism that was thought to primarily cause acute infections can lead to long term infections, in this case of the gall bladder and bone marrow. This same imaging method can be applied to Bb infected mice to identify previously unsuspected areas of Bb sequestration and to reveal the effects of therapy on these chronic infections. He also demonstrated how perinatal infections can be studied and suggested that perinatal infections by Bb and its consequences in the mouse model could be evaluated. Imaging in this manner can provide a guide to sample the appropriate tissues at the the appropriate time, and, thus used to direct microarray analyses, to examine how microbial physiology is altered at different tissue sites and in chronic vs. acute infections.
Dr. George Chaconas from the University of Calgary in Canada presented perhaps the most popular talk because of its visual impact, describing the use of spinning disk confocal intravital microscopy to directly visualize fluorescently stained Bb in real-time, three dimensions, in living mice; spiraling spirochetes were visualized interacting with and disseminating out of the vasculature of a living mouse – the first time there has been a high resolution 3D view of dissemination of any bacterial pathogen in a living mammalian host.
Dr. John Keilp from Columbia University revealed findings from a neurocognitive study comparing patients with post-treatment Lyme disease and major depression; while deficits in processing speed were common in both groups, patient with histories of Lyme disease were more likely to show deficits in language fluency and memory.
Dr. Fabio Tavora of the Armed Forces Institute described a case of Lyme carditis in a 37 year old male who died one month after a febrile illness with a second-degree AV block; on post-mortem, severe, diffuse inflammation was seen in both the right and left ventricles, accompanied by mononuclear infiltrates of the endocardium, myocardium, and epicardium; serology was positive by Western blot and the tissue was positive for Bb by PCR.
Dr. Suzanne Vernon from the CFIDS Association of America reviewed recent research on CFS, including clinical biomarkers such as acute illness severity as a predictor of longer course of illness, abnormalities in the HPA axis, differentiating genetic expression of immune markers in CFS and immune network modeling; much of this research has advanced rapidly through the application of genomic methods, revealing a tool that may be of major clinical benefit in the study of patients with persistent Lyme disease symptoms.
Closing the conference,
Dr. Ben Luft from Stony Brook University described a few research ventures, including studies of different strains of Bb to identify virulence markers and non-human studies of a novel antibiotic (Tigecycline) that by inhibiting the efflux pump may be more effective in eradicating Bb spirochetes than current antibiotics. |
