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Scrub typhus
Classification and external resources

Orientia tsutsugamushi
ICD-10 A75.3
ICD-9 081.2
DiseasesDB 31715
eMedicine derm/841 ped/2710
MeSH D012612

Scrub typhus is a form of typhus caused by Orientia tsutsugamushi.[1]

Although it is similar in presentation to other forms of typhus, it is caused by an agent in a different Genus, and is frequently classified separately from the other typhi.

Contents

Causes and geographical distribution

Scrub typhus is transmitted by some species of trombiculid mites ("chiggers", particularly Leptotrombidium deliense),[2] 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", which extends from northern Japan and far-eastern Russia in the north, to northern Australia in the south, and to Pakistan and Afghanistan in the west.[3]

The precise incidence of the disease is unknown, as diagnostic facilities are not available in much of its native range. 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.[4][5] The incidence in Japan has fallen over the past few decades, probably due to decreasing exposure, and many prefectures report fewer than 50 cases per year.[6][7] It affects females more than males in Korea, but not in Japan.[8]

Symptoms and signs

Symptoms include fever, headache, muscle pain, cough, and gastrointestinal symptoms. More virulent strains of O. tsutsugamushi can cause hemorrhaging and intravascular coagulation.

  • Signs
Macuopapular rash, eschar, splenomegaly and lymphadenopathies are typical signs.
  • Laboratory findings
Leukopenia and abnormal liver function tests are commonly seen in the early phase of the illness.
  • Complications
Pneumonitis, encephalitis, and myocarditis occur in the late phase of illness.

Acute scrub typhus appears to improve viral loads in patients with HIV.[9] This interaction is refused by an in vitro study.[10]

Diagnosis

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 cheapest and most easily available serological test test is the Weil-Felix test, but this is notoriously unreliable.[11] The gold standard is indirect immunofluorescence,[12] 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,[13] and the results of these tests are comparable to those from IFA.[11][14] 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.[11] 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.[15] In patients from endemic areas, this is not possible because antibodies may be found in up to 18% of healthy individuals.[16]

Other methods include culture and PCR, but these are not routinely available[17] and the results do not always correlate with serological testing,[18][19][20] and are affected by prior antibiotic treatment.[21]

Treatment

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.[22][23] Rifampin and azithromycin[24] are alternatives.[25] Azithromycin is an alternative in children[26] and pregnant women with scrub typhus,[27][28][29] and when doxycycline-resistance is suspected.[30] Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage.[29][31] Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism.[32]

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 (doxycycline is relatively contraindicated in children).

Vaccine

There are currently no licensed vaccines available.[33]

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. [34] 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.[35] 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.[36]

It is now known that there is enormous antigenic variation in Orientia tsutsugamushi strains,[37][38] 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.[39]

History

Severe epidemics of the disease occurred among troops in Burma and Ceylon during World War II (WWII).[40] Several members of the U.S. Army's 5307th Composite Unit (Merrill's Marauders) died of the disease; and in 1944, there were no effective antibiotics or vaccines available.[41][42] The disease was also a problem for US troops stationed in Japan after WWII, and was variously known as "Shichitō fever" (by troops stationed in the Izu Seven Islands) or "Hatsuka fever" (Chiba prefecture).[43]

References

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  2. ^ Pham XD, Otsuka Y, Suzuki H, Takaoka H (2001). "Detection of Orientia tsutsugamushi (Rickettsiales: Rickettsiaceae) in unengorged chiggers (Acari: Trombiculidae) from Oita Prefecture, Japan, by nested polymerase chain reaction". J Med Entomol 38 (2): 308–311. PMID 11296840. http://www.ingentaconnect.com/content/esa/jme/2001/00000038/00000002/art00029?crawler=true.  
  3. ^ Seong S, Choi M & Kim I (2001). "Orientia tsutsugamushi infection: overview and immune responses". Microbes and Infection 3 (1): 11–21. doi:10.1016/S1286-4579(00)01352-6.  
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