Orientia tsutsugamushi infection was first reported in Japan by Hakuju Hashimoto in 1810, and to the Western world by Theobald Adrian Palm in 1878.

[6] 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.

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.

[9] 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.

"[12] Discovering the similarities with the bacterium R. prowazekii, Mataro Nagayo and colleagues gave a new classification with the name Rickettsia orientalis in 1930.

Akira Tamura and colleagues reported in 1991 the structural differences of the bacterium from Rickettsia species that warranted a separate genus, and proposed the name Orientia tsutsugamushi.

Although its cell wall has a classic bacterial double layer, its outer leaflet is much thicker than the inner one, which is just the opposite in Rickettsia species.

Due to the absence of peptidoglycan, the bacterium is naturally resistant to all β-lactam antibiotics (such as penicillin), to which Rickettsia species are normally sensitive to.

O. tsutsugamushi specifically can be grown only in the yolk sacs of developing chicken embryos and in cultured cell lines such as HeLa, BHK, Vero, and L929.

Infection to rodents and humans is an accidental transmission from the bite of mite larvae, and not required for reproduction or survival of the bacterium.

In addition, L. akamushi is an endemic carrier in Japan, L. chiangraiensis and L. imphalum in Thailand, L. gaohuensis in China, and L. arenicola in Malaysia and Indonesia.

The larvae, commonly referred to as chiggers, are the only ectoparasitic stage feeding on the body fluids of rodents and other opportunistic mammals.

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.

By 1946, she established that there were three principal strains (serotypes), namely Karp (from New Guinea), Gilliam (from India) and Seerangay (from British Malaya).

[48] Since then, six basic antigenic strains are recognised, namely Gilliam, Karp, Kato, Shimokoshi, Kawasaki, and Kuroki.

[49] As of 2009, more than 20 different strains have been established in humans based on antigenic variation using serological tests such as complement fixation and immunofluorescence assay.

A 56-kDa type specific antigen (TSA56) is the most important because it is not produced by any other bacteria, and is responsible for making the genetic diversity in different strains.

The 22-kDa, 47-kDa or 110-kDa antigens are not strain specific so that TSA56 is the main target in sophisticated diagnostic tests such as immunoblotting, ELISA and DNA analysis.

It varies in size from 516 to 540 amino acid residues between different strains, and its gene is approximately 1,550 base pairs long.

DNA analyses have shown that the GroES and GroEL genes are indeed present in O. tsutsugamushi with slight variation in different strains, and they produce the 11-kDa and 60-kDa proteins.

[60] 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, subacute thyroiditis, and multiple organ dysfunction syndrome.

[61] Harmful effects involving multiple organ failure and neurological impairment are difficult to treat, and can cause lifelong debilitation or be directly fatal.

[61] The central nervous system is often affected and results in various complications including cerebellitis, cranial nerve palsies, meningoencephalitis, plexopathy, transverse myelitis, and Guillan-Barré syndrome.

[63] The World Health Organization in 1999 stated that: Scrub typhus is probably one of the most underdiagnosed and underreported febrile illnesses requiring hospitalization in the region.

[64]Scrub typhus is historically endemic to the Asia-Pacific region, covering the Russian Far East and Korea in the north, to northern Australia in the south, and Afghanistan in the west, including islands of the western Pacific Oceans such as Japan, Taiwan, Philippines, Papua New Guinea, Indonesia, Sri Lanka, and the Indian Subcontinent.

[65] One billion people are estimated to be at risk of infection at any moment and an average of one million cases occur every year in the Tsutsugamushi Triangle.

[38] The burden of scrub typhus in rural areas of Asia is huge, accounting for up to 20% of febrile sickness in hospital, and seroprevalence (positive infection on blood test) over 50% of the population.

[58] A simple visual diagnosis is the presence of an inflamed scar-like scab called eschar, which is regarded as "the most useful diagnostic clue in patients with acute febrile illness".

[37][28] IFA is regarded as the gold standard test, as it gives a reliable result; however, it is expensive and not specific for different rickettsial bacteria.

[86] A vaccine targeting the 47-kDa outer membrane protein (OMP) is a promising candidate with experimental success in mice against the Boryong strain.