the host tissue during this feeding. Cellular invasion Orientia tsutsugamushi initially attacks the myelocytes (young white blood cells) in the area of inoculation, and then the endothelial cells lining the vasculature. The process of cellular invasion is shown in Figure 5. In the blood circulation, it targets professional phagocytes ("cell eaters", white blood cells) such as dendritic cells and macrophages in all organs as the secondary targets. The parasite first attaches itself to the target cells using surface proteoglycans present on the host cell and bacterial surface proteins such as type specific protein 56 (or type specific antigen, TSA56) and surface cell antigens (ScaA and ScaC, which are membrane transporter proteins). These proteins interact with the host fibronectin to induce phagocytosis (the process of ingesting the bacterium). The ability to actually enter the host cell depends on integrin-mediated signaling and reorganisation of the actin cytoskeleton. Orientia tsutsugamushi has a special adaptation for surviving in the host cell by evading the host immune reaction. Once it interacts with the host cells, it causes the host cell membrane to form a transportation bubble called a clathrin-coated vesicle by which it gets transported into the cytoplasm. Inside the cytoplasm, it makes an exit from the vesicle (now known as an endosome) before the endosome is destroyed (in the process of cell-eating called autophagy) by the lysosomes. It then moves towards the nucleus, specifically at the perinuclear region, where it starts to grow and multiply. Unlike other closely related bacteria which use actin-mediated processes for movement in the cytoplasm (called intracellular trafficking or transport), O. tsutsugamushi is unusual in using microtubule-mediated processes similar to those employed by viruses such as adenoviruses and herpes simplex viruses. Further, the escape (exocytosis) from an infected host cell is also unusual. It forms another vesicle using the host cell membrane, gives rise to a small bud, and releases itself from the host cell surface while still enclosed in the vesicle. The membrane-bound bacterium is formed by interaction between cholesterol-rich lipid rafts as well as HtrA, a 47-kDa protein on the bacterial surface. However, the process of budding and importance of the membrane-bound bacterium are not yet understood. Strains Orientia tsutsugamushi is a diverse species of bacteria. Ida A. Bengtson of the United States Public Health Service was the first to note the existence of different strains using antigen-antibody interaction (complement fixation test) in 1944. She observed that different