Orientia tsutsugamushi
"O. tsutsugamushi" causes a complex and dangerous infection scrub typhus. Infection starts when chiggers bite on the skin during their feeding. The bacteria are deposited at the site of feeding (inoculation), where they multiply. They cause progressive tissue damage (necrosis). Necrosis progresses to inflammation of the blood vessels called vasculitis. This in turn causes inflammation of the lymph nodes, called lymphadenopathy. Within a few days, vasculitis extends to various organs including liver, brain, kidney, meninges and the lung. The disease is responsible for nearly a quarter of all the febrile (high fever) illness in endemic areas. Mortality in severe case or due to improper treatment or misdiagnosis may be as high as 30-70%. About 6% of infected people die untreated, and 1.4% of the patients die even with medical treatment. Moreover, death rate can be as high as 13% where medical treatment is not properly handled. In cases of misdiagnosis and failure of treatment, systemic complications rapidly develop including acute respiratory distress syndrome, acute kidney failure, encephalitis, gastrointestinal bleeding, hepatitis, meningitis, myocarditis, pancreatitis, pneumonia, septic shock, sub-acute thyroiditis, and multi-organ dysfunctions. Harmful symptoms involving multiple organ failure and neurological impairment are difficult to treat, and can be lifelong debilitation or directly fatal. The central nervous system is often affected and result in various complications including cerebellitis, cranial nerve palsies, meningoencephalitis, plexopathy, transverse myelitis, neuroleptic malignant syndrome, and Guillan-Barré syndrome. Death rates due to complications can be up to 14% in brain infections, and 24% with multiple organ failure. It is the major cause of acute encephalitis syndrome in India, where viral infection Japanese encephalitis has been regarded as the main factor.
Orientia tsutsugamushi
"O. 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 in the cytoplasm moves. Inside the cytoplasm, it makes an exit from the vesicle (now known as an endosome) before it is destroyed (in the process of cell-eating called autophagy) by the lysosome. 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 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 membrane-bound bacterium are not yet understood.
"O. tsutsugamushi" is a diverse species of bacteria. Ida A. Bengtson of the United States Public Health Services was the first to note the existence of different strains using antigen-antibody interaction (complement fixation test) in 1944. He observed that different strains had varying degree of virulence, and that the blood sera having different strains could cross react. By 1946 he established that there were three principal strains (serotypes), namely Karp (New Guinea), Gilliam (from India) and Seerangay (from British Malaya). Akira Shishido discovered Kato strain, in addition to Gilliam and Karp, in Japan in 1958. Since then six basic antigenic strains are recognised, namely Gilliam, Karp, Kato, Shimokoshi, Kawasaki, and Kuroki. Karp is the most abundant strain accounting for about 50% of all infections. But in Korea, the major strain is Boryong. So far, more than 30 different strains have been established in humans. The number is much higher if the strains in rodents and mites are taken into account. For example, a study in Japan in 1994 reported 32 strains, 14 from human patients, 12 from wild rodents, and 6 from trombiculid mites. The different strains exert different levels of virulence, and the most virulent is KN-3, which is predominant among wild rodents. Another study in 1996 reported 40 strains. Genetic methods have revealed even greater complexity than had been previously described (for example, Gilliam is further divided into Gilliam and JG types). Due to immunological differences of the serotypes, simultaneous and repeated infection with different strains is possible.