. "6 Pathogenesis." Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes: Workshop Report. Washington, DC: The National Academies Press, 2011.
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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report
also allow scientists to examine host pathogen interactions concerning the progression of Lyme disease in deeper tissues such as the joints and heart.
Infection with rickettsial pathogens, including those in the Anaplasma,Ehrlichia, Orientia, and Rickettsia genera, can progress so rapidly that patients require immediate hospitalization and intensive care—along with antimicrobial therapy—to prevent death. The acuteness and severity of these infections highlight the need for better educating medical professionals in regions where the organisms are endemic. Investigators also need to better define these endemic regions and determine the risk that infectious bacteria and their animal hosts as they shift their range and distribution, and the likelihood that new pathogens will emerge.
Finally, we need more accurate tools for clinical and laboratory diagnosis of these diseases. The reasons underlying differences in the severity and rapidity of progression in patients is a major scientific gap—both on the pathogen side (diversity of species and strains) and the host side (genetic background and immune status).
With only a few exceptions, the pathogenesis of the broad group of rickettsial diseases is understudied—typical of many neglected diseases of significant but underappreciated significance for public health. Workshop presenters and discussants emphasized all these challenges.
However, two experimental models reveal the progress that scientists can achieve. Experiments using the Ixodes ovatus Ehrlichia are some of the best so far and underscore the dominant theme of the session: that the immune system is responsible for controlling infection but also producing the severe toxic shock–like syndrome when that control gets out of hand. A better understanding of immune mechanisms and effectors is critical to improving therapy once infection has progressed to severe acute disease.
Research on Rickettsia in the spotted fever group has similarly begun to elucidate the pathogenesis of severe disease. Progress in developing animal models illustrates the possibilities. Still, the knowledge gaps regarding the pathogenesis of the rickettsial pathogens are numerous and wide, and the need for experiments that lay the groundwork for translating that knowledge to human disease is strong.
In fact, such translational studies are essential for the full spectrum of tick-borne pathogens. To avoid a “translational canyon” between experimental studies and human treatment and prevention, scientists should consider studying B. burgdorferi in naturally occurring models, such as neuroborreliosis in horses and Rickettsia rickettsii and Ehrlichia canis in dogs. The use of “humanized” organs such as human skin in mouse models—as noted by Valbuena—can accelerate scientists’ understanding of pathogenesis, and speed the application of that understanding to treating patients and preventing infection.