Dissecting Lyme borreliosis; Clinical aspects, pathogenesis and prevention

Lyme borreliosis (LB) is the most prevalent vector-borne disease in Western Europe and Northeastern parts of the USA. The causative agents of LB are spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes ticks. Since the late 1970’s, researchers in the United States and Europe have extensively investigated the clinical manifestations and pathogenesis of LB as well as strategies to prevent B. burgdorferi transmission. The aim of this thesis is to ‘dissect’ three different aspects of LB; namely I) challenging clinical aspects of LB, II) further insights in tick-pathogen-host interactions and III) novel vaccine strategies to prevent LB. The diagnosis of LB is based on a history of potential exposure to ticks and the risk of infection with B. burgdorferi, development of specific symptoms, exclusion of other causes, and when appropriate, combined with serological and/or other diagnostic tests. Here we examine the challenges for physicians to establish or exclude the diagnosis of LB. Secondly, a better understanding of tick-host-pathogen interactions could contribute to our understanding of the pathogenesis of LB. Here we focus on the interaction between the tick salivary gland protein TSPI and the mammalian immune system. Finally, there is currently no human vaccine available to prevent LB. In this thesis we investigate whether tick gut proteins can be used as vaccines to prevent LB. The data described in this thesis may improve care for patients suspected of LB, increase our understanding of LB pathogenesis and identify new vaccine candidates to prevent LB.