Fusobacterium necrophorum - from tonsillar carriage to Lemierre’s syndrome

Sammanfattning: Fusobacterium necrophorum is the main causative agent of Lemierre’s syndrome, where the bacteria, following a benign initial oropharyngeal infection, cause septic thrombophlebitis of the internal jugular vein with subsequent pulmonary embolisation. Despite that data are lacking to suggest so, F. necrophorum has been described as normal tonsillar flora for decades. We investigated tonsillar carriage in Sweden and Zambia among mainly adolescents and young adults (Paper I). These are the age groups most affected by its infections. F. necrophorum was found to be present in one in five asymptomatic participants in Sweden, yet was rarely identified in Zambia. Given the finding of a relatively high tonsillar carriage rate in Sweden, the impact of a finding of F. necrophorum in pharyngotonsillitis was evaluated (Paper II). Interestingly, F. necrophorum was found to be a very prevalent finding and equally associated with the development of complications as Streptococcus pyogenes. Antibiotic therapy in non-streptococcal pharyngotonsillitis has decreased in recent decades, yet simultaneously concerns of an increase in complications have been suggested. To investigate the incidence rate of invasive infections with F. necrophorum, an eight-year nationwide study in Sweden was performed (Paper III). All invasive presentations of F. necrophorum increased, including Lemierre’s syndrome. Finally, the hallmark of Lemierre’s syndrome was studied, i.e., the septic thrombophlebitis. We investigated the effects of anticoagulant therapy in Lemierre’s syndrome and found that while harm due to treatment was rare, so were the benefits (Paper IV). Finally, plasma from all patients with Lemierre’s syndrome in Skåne in 2017-2021 was compared with controls with other severe infections to investigate differentially expressed proteins by mass spectrometry and generate hypotheses on thrombogenesis (Paper V). Several thrombogenic pathways were identified, including endothelial injury, platelet activation, and linkage of innate immunity with coagulation. These thrombogenic pathways are hypothesised to be important in the development of septic thrombophlebitis and specific proteins highlighted.In this thesis, we trail F. necrophorum from tonsillar carriage (Paper I) to pharyngotonsillitis (Paper II) and onwards to Lemierre’s syndrome and other invasive infections (Papers III-V). We highlight the specifics of each presentation, evaluate the treatment and hypothesise on pathogenesis through epidemiological and translational studies. Our most important findings include reporting a nationwide increase of incidence across all invasive presentations, a geographical difference in tonsillar carriage, the establishment of F. necrophorum as a pathogen in pharyngotonsillitis, and generation of hypothesised thrombogenic pathways in Lemierre’s syndrome.