Fever After Tick Bite Study

The proposed study is a collaboration between Microbiology, SU/Sahlgrenska and the Infectious Diseases clinic at SU/Östra as well as several Infectious Diseases clinics throughout Sweden aiming at improving microbiological diagnostic assays regarding the early identification of tick-borne microorganisms (including as of yet unidentified pathogens) capable of causing human disease using modern diagnostic tools. At the initial study visit (day 0) plasma, serum, urine, saliva, and PBMCs (and tick, if available) will be collected from patients developing fever within two weeks after a tick bite. Additional follow-up samples will be obtained after 9 and 30 days as well as after 6 months. The initial samples will be analyzed using (a) directed multiplex PCR analysis for Tick-Borne Encephalitis (TBE), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella, Tularemia, and Babesiosis in plasma, whole blood and urine, (b) conventional IgM and IgG serology for TBE, (c) "Next Generation Sequencing" (NGS) for the detection of bacterial 16s rRNA as well as unknown viruses, (d) potential biomarkers, and (e) host genetic factors. Among patients where initial sampling indicates the presence of a potential pathogen or in patients developing neurological symptoms, a lumbar puncture will be performed and CSF will be further analyzed. Samples will also be evaluated regarding potential microbiological factors predisposing for severity of infection. The primary objective of the study is to improve diagnostic tools in the initial early phase of infections caused by tick-borne pathogens, especially TBE prior to the affliction of the central nervous system, and to attempt to identify which factors impact the course of infection as it is believed that approximately 75% of infected individuals resolve their infection in this first phase whereas others develop meningoencephalitis with significant subsequent neurological sequelae. Secondary objectives of the study include investigating for the presence of and treating other tick-borne pathogens, setting the stage for coming clinical trials evaluating novel anti-viral therapies for TBE.