Host-pathogen interactions in typhoid fever

This thesis focuses on host-pathogen interactions in Salmonella Typhi and Burkholderia pseudomallei infections and explores the interplay between these bacteria and the innate immune system. Typhoid fever is one of the most common causes of bacterial infection in low-income countries. With adequate antibiotic treatment it has a low mortality rate. Melioidosis also commonly causes community-acquired sepsis in Southeast Asia and northern Australia but even with appropriate antibiotic treatment the mortality is high. During severe bacterial infections such as these, uncontrolled activation of the innate immune response can lead to detrimental systemic inflammation, intravascular coagulation, tissue injury, and eventually death. This thesis presents clinical and experimental studies in which the effects of a variety of proteins involved in the hyper-inflammatory response of the innate immune system during severe typhoid fever and melioidosis are investigated and compared.