The pathophysiology of rickettsial disease in Southeast Asia. (360G-Wellcome-078990_Z_06_Z)

The rickettsioses are clinically important but understudied arthropod-borne infections common in the Asia-Pacific region. Scrub typhus (caused by Orientia tsutsugamushi), and murine typhus (Rickettsia typhi) are the most common rickettsial illnesses in the region, although other rickettsial diseases are also seen. An estimated 1 billion individuals are exposed to scrub typhus and 1 million cases occur each year. This may be the most prevalent yet neglected treatable infection in the world. Scrub and murine typhus have different arthropod vectors, epidemiology, clinical manifestations and death rates, though intracellular growth within vascular endothelial cells is a feature common to both. Ongoing clinical treatment trials conducted by our unit provide a unique opportunity for studying the epidemiology and pathophysiology of these poorly understood diseases. The proposed study aims to facilitate the diagnosis of rickettsial pathogens causing disease in Thailand and Laos, and to elucidate the pathological role of the infected endothelial cell and its interactions with the immune system in the disease process. I will study host-pathogen interactions and their consequences in a large cohort of patients with rickettsial disease, predominantly examining the immunpathology both locally in the eschar with skin biopsies, and systemically, by using surrogate markers of endothelial cell dysfunction.