Scrub typhus or Bush typhus is a form of typhus caused by the intracellular parasiteOrientia tsutsugamushi, a Gramnegative -proteobacterium of family Rickettsiaceae

first isolated and identified in 1930 in Japan.[1][2] Although the disease is similar in presentation to other forms of typhus, its pathogen is not anymore included in genus Rickettsia with the typhus bacteria proper, but in Orientia. The disease is thus frequently classified separately from the other typhi. Causes and geographical distribution[edit] Scrub typhus is transmitted by some species of trombiculid mites ("chiggers", particularlyLeptotrombidium deliense),[3] which are found in areas of heavy scrub vegetation. The bite of this mite leaves a characteristic black eschar that is useful to the doctor for making the diagnosis. Scrub typhus is endemic to a part of the world known as the tsutsugamushi triangle(after O. tsutsugamushi).[2] This extends from northern Japan and far-eastern Russia in the north, to the territories around the Solomon Sea into northern Australia in the south, and to Pakistan and Afghanistan in the west. [4] The precise incidence of the disease is unknown, as diagnostic facilities are not available in much of its large native range which spans vast regions of equatorial jungle to the sub-tropics. In rural Thailand and in Laos, murine and scrub typhus accounts for around a quarter of all adults presenting to hospital with fever and negative blood cultures [5] [6] The incidence in Japan has fallen over the past few decades, probably due to land development driven decreasing exposure, and many prefectures report fewer than 50 cases per year.[7][8] It affects females more than males in Korea, but not in Japan,[9] and this is conjectured to be because sex-differentiated cultural roles have women tending garden plots more often, thus being exposed to plant tissues inhabited by chiggers. The incidence is increasing day-by-day in southern part of Indian Peninsula. Symptoms and signs[edit] Symptoms include fever, headache, muscle pain, cough, and gastrointestinal symptoms. More virulent strains of O. tsutsugamushi can cause hemorrhaging and intravascular coagulation. Morbilliform rash, eschar, splenomegaly and lymphadenopathies are typical signs.Leukopenia and abnormal liver function tests are commonly seen in the early phase of the illness. Pneumonitis, encephalitis, andmyocarditis occur in the late phase of illness. Acute scrub typhus appears to improve viral loads in patients with HIV.[10] This interaction is challenged by an in vitro study.[11] Diagnosis[edit] In endemic areas, diagnosis is generally made on clinical grounds alone. Where there is doubt, the diagnosis may be confirmed by a laboratory test such as serology. The choice of laboratory test is not straightforward, and all currently available tests have their limitations. [12] The cheapest and most easily available serological test is the Weil-Felix test, but this is notoriously unreliable.[13] The gold standard is indirect immunofluorescence,[14] but the main limitation of this method is the availability of fluorescent microscopes, which are not often available in resource-poor settings where scrub typhus is endemic. Indirect immunoperoxidase (IIP) is a modification of the standard IFA method that can be used with a light microscope, [15] and the results of these tests are comparable to those from IFA.[13][16] Rapid bedside kits have been described that produce a result within one hour, but the availability of these tests are severely limited by their cost.[13] Serological methods are most reliable when a fourfold-rise in antibody titre is looked for. If the patient is from a non-endemic area, then diagnosis can be made from a single acute serum sample. [17] In patients from endemic areas, this is not possible because antibodies may be found in up to 18% of healthy individuals. [18] Other methods include culture and PCR, but these are not routinely available[19] and the results do not always correlate with serological testing,[20][21][22] and are affected by prior antibiotic treatment.[23] The currently available diagnostic methods have been summarised.[12] Treatment[edit] Without treatment, the disease is often fatal. Since the use of antibiotics, case fatalities have decreased from 4%40% to less than 2%. The drug most commonly used is doxycycline; but chloramphenicol is an alternative. Strains that are resistant to doxycycline and to chloramphenicol are common in northern Thailand. [24][25] Rifampin and azithromycin[26] are alternatives.[27] Azithromycin is an alternative in children[28] and pregnant women with scrub typhus,[29][30][31] and when doxycycline-resistance is suspected. [32] Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage. [31][33] Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism. [34] Other drugs that may be effective are clarithromycin, roxithromycin, and the fluoroquinolones, but there is no clinical evidence on which to recommend their use. Azithromycin or chloramphenicol is useful for infection in children or pregnant women. Vaccine[edit] There are currently no licensed vaccines available.[35] An early attempt to create a scrub typhus vaccine occurred in the United Kingdom in 1937 (with the Wellcome Foundation infecting around 300,000 cotton rats in a classified project called "Operation Tyburn"), but the vaccine was not used.[36] The first known batch of scrub typhus vaccine actually used to inoculate human subjects was despatched to India for use by Allied Land Forces, South-East Asia Command (A.L.F.S.E.A.) in June 1945. By December 1945, 268,000 cc. had been despatched.[37] The vaccine was produced at Wellcomes laboratory at Ely Grange, Frant, Sussex. An attempt to verify the efficacy of the vaccine by using a placebo group for comparison was vetoed by the military commanders, who objected to the experiment.[38] It is now known that there is enormous antigenic variation in Orientia tsutsugamushi strains,[39][40] and immunity to one strain does not confer immunity to another. Any scrub typhus vaccine should give protection to all the strains present locally, in order to give an acceptable level of protection. A vaccine developed for one locality may not be protective in another locality, because of antigenic variation. This complexity continues to hamper efforts to produce a viable vaccine. [41]