Orientia tsutsugamushi (from Japanese tsutsuga meaning "illness", and mushi meaning "insect") is a mite-borne bacterium belonging to the family Rickettsiaceae and is responsible for a disease called scrub typhus in humans. It is a natural and an obligate intracellular parasite of mites belonging to the family Trombiculidae. With a genome of only 2.0–2.7 Mb, it has the most repeated DNA sequences among bacterial genomes sequenced so far. The disease, scrub typhus, occurs when infected mite larvae bite humans. This infection can prove fatal if prompt doxycycline therapy is not started.

Orientia tsutsugamushi infection was first reported in Japan by Hakuju Hashimoto in 1810, and to the Western world by Theobald Adrian Palm in 1878. Naosuke Hayashi first described it in 1920, giving the name Theileria tsutsugamushi. Owing to its unique properties, it was renamed Orientia tsutsugamushi in 1995. Unlike other Gram-negative bacteria, it is not easily stained with Gram stain, as its cell wall is devoid of lipophosphoglycan and peptidoglycan. With highly variable membrane protein, a 56-kDa protein, the bacterium can be antigenically classified into many strains (sub-types). The classic strains are Karp (which accounts for about 50% of all infections), Gilliam (25%), Kato (less than 10%), Shimokoshi, Kuroki and Kawasaki. Within each strain, enormous variability further exists.

Orientia tsutsugamushi is naturally maintained in the mite population by transmission from female to its eggs (transovarial transmission), and from the eggs to larvae and then to adults (transtadial transmission). The mite larvae, called chiggers, are natural ectoparasites of rodents. Humans get infected upon accidental contact with infected chiggers. A scar-like scab called eschar is a good indicator of infection, but is not ubiquitous. The bacterium is endemic to the so-called Tsutsugamushi Triangle, a region covering the Russian Far East in the north, Japan in the east, northern Australia in the south, and Afghanistan in the west. One million infections are estimated to occur annually. Antibiotics such as azithromycin and doxycycline are the main prescription drugs; chloramphenicol and tetracyclin are also effective. Diagnosis of the infection requires techniques such as Weil–Felix test, rapid immunochromatographic test, immunofluorescence assays, and polymerase chain reaction. There is no vaccine for the infection.

The earliest record of O. tsutsugamushi infection was in the 3rd century (313 C.E.) in China. Japanese were also familiar with the link between the infection and mites for centuries. They gave several names such as shima-mushi, akamushi (red mite) or kedani (hairy mite) disease of northern Japan, and most popularly as tsutsugamushi (from tsutsuga meaning fever or harm or illness, and mushi meaning bug or insect). Japanese physician Hakuju Hashimoto gave the first medical account from Niigata Prefecture in 1810. He recorded the prevalence of infection along the banks of the upper tributaries of Shinano River. The first report to the Western world was made by Theobald Adrian Palm, a physician of the Edinburgh Medical Missionary Society at Niigata in 1878. Describing his first-hand experience, Palm wrote:

Last summer [i.e. 1877], I had the opportunity of observing a disease which, so far as I know, is peculiar to Japan, and has not yet been, described. It occurs, moreover, in certain well-marked districts, and at a particular season of the year, so that the opportunities of investigating it do not often occur. It is known here as the shima-mushi, or island-insect disease, and is so-named from the belief that it is caused by the bite or sting of some insect peculiar to certain islands in the river known as Shinagawa, which empties itself into the sea at Niigata.

The aetiology of the disease was unknown until the early 20th century. In 1908, a mite theory of the transmission of tsutsugamushi disease was postulated by Taichi Kitashima and Mikinosuke Miyajima. In 1915, a British zoologist, Stanley Hirst, suggested that the larvae of mite Microtrombidium akamushi (later renamed Leptotrombidium akamushi) which he found on the ears of field mice could carry and transmit the infection. In 1917, Mataro Nagayo and colleagues gave the first complete description of the developmental stages such as egg, nymph, larva, and adult of the mite. They also asserted that only the larvae bites mammals, and are thus the only carriers of the parasites. But then, the actual infectious agent was not known, and it was generally attributed to either a virus or a protozoan.

The causative pathogen was first identified by Naosuke Hayashi in 1920. Confident that the organism was a protozoan, Hayashi concluded, stating, "I have reached the conclusion that the virus of the disease is the species of Piroplasma [protozoan] in question... I consider the organism in Tsutsugamushi disease as a hitherto undescribed species, and at the suggestion of Dr. Henry B. Ward designate it as Theileria tsutsugamushi." Discovering the similarities with the bacterium R. prowazekii, Mataro Nagayo and colleagues gave a new classification with the name Rickettsia orientalis in 1930. (R. prowazekii is a causative bacterium of epidemic typhus first discovered by American physicians Howard Taylor Ricketts and Russell M. Wilder in 1910, and described by a Brazilian physician Henrique da Rocha Lima in 1916.)

The taxonomic confusion worsened. In 1931, Norio Ogata gave the name Rickettsia tsutsugamushi, while Rinya Kawamüra and Yoso Imagawa independently introduced the name Rickettsia akamushi. Kawamüra and Imagawa discovered that the bacteria are stored in the salivary glands of mites, and that mites feed on body (lymph) fluid, thereby establishing the fact that mites transmit the parasites during feeding.