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Scrub typhus


Scrub typhus

Scrub typhus
Classification and external resources
Specialty Infectious disease
ICD-10 A75.3
ICD-9-CM 081.2
DiseasesDB 31715
eMedicine derm/841 ped/2710
MeSH D012612

Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite Orientia tsutsugamushi, a Gram-negative α-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 no longer included in genus Rickettsia with the typhus bacteria proper, but in Orientia. The disease is thus frequently classified separately from the other typhi.


  • Signs and symptoms 1
  • Causes 2
  • Diagnosis 3
  • Treatment 4
  • Vaccine 5
  • History 6
  • See also 7
  • References 8
  • External links 9

Signs and symptoms

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, and myocarditis occur in the late phase of illness.

Acute scrub typhus appears to improve viral loads in patients with HIV.[3] This interaction is challenged by an in vitro study.[4]


Scrub typhus is transmitted by some species of trombiculid mites ("chiggers", particularly Leptotrombidium deliense),[5] 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.[6]

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 subtropics. In rural Thailand and Laos, murine and scrub typhus account for around a quarter of all adults presenting to hospital with fever and negative blood cultures[7] [8] The incidence in Japan has fallen over the past few decades, probably due to land development driving decreasing exposure, and many prefectures report fewer than 50 cases per year.[9] [10] It affects females more than males in Korea, but not in Japan,[11] 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.


In endemic areas, diagnosis is generally made on clinical grounds alone. However, overshadowing of the diagnosis is quite often as the clinical symptoms overlap with other infectious diseases like dengue fever, paratyphoid, and pyrexia of unknown origin (PUO). If the eschar can be identified, it is quite diagnostic of scrub typhus, but this is very unreliable in the native population whom have dark skin, and moreover, the site of eschar which is usually where the mite bites is often located in covered areas. Unless it is actively searched for, the eschar most likely would be missed. History of mite bite is often absent since the bite does not inflict pain and the mites are almost too small to be seen by a naked eye. Usually, scrub typhus is often labelled as PUO in remote endemic areas since blood culture is often negative, yet it can be treated effectively with chloramphenicol. Where doubt exists, the diagnosis may be confirmed by a laboratory test such as serology. Again, this is often unavailable in most endemic areas since the serological test involved is not included in the routine screening tests for PUO, especially in Burma and Myanmar.

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, a modification of the standard IFA method, 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 is severely limited by their cost.[13] Serological methods are most reliable when a fourfold rise in antibody titre is found. If the patient is from a nonendemic 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 polymerase chain reaction, 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]


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 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 no clinical evidence recommends their use. Azithromycin or chloramphenicol is useful for infection in children or pregnant women.


No licensed vaccines are 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 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]

Enormous antigenic variation in Orientia tsutsugamushi strains is now recognized,[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, to give an acceptable level of protection. A vaccine developed for one locality may not be protective in another, because of antigenic variation. This complexity continues to hamper efforts to produce a viable vaccine.[41]


An Australian soldier, Private George "Dick" Whittington, is aided by George Silk)

Severe epidemics of the disease occurred among troops in Burma and Ceylon during World War II (WWII).[42] Several members of the U.S. Army's 5307th Composite Unit (Merrill's Marauders) died of the disease, and before 1944, no effective antibiotics or vaccines were available.[43][44]

World War II provides some indicators that the disease is endemic to undeveloped areas in all of Oceania in the Pacific theater, although war records frequently lack assured diagnoses to desired by epidemiological statics—and many records of "high fever" evacuations were also likely to be other tropical illnesses. In the chapter entitled "The Green War", General MacArthur's biographer William Manchester identifies that the disease was one of a number debilitating afflictions affecting both sides on New Guinea[45] in the running bloody Kokoda battles over unbelievably harsh terrains under incredible hardships— fought during a six-month span[46] all along the Kokoda Track in 1942-43, and mentions that to be hospital-evacuated, Allied soldiers (who cycled forces) had to run a fever of 102°F, and that sickness casualties outnumbered weapons inflicted casualties 5:1.[45] Similarly, the illness was a casualty producer in all the jungle fighting of the land battles of New Guinea campaign and Guadalcanal campaign. Where the allies had bases, they could remove and cut back vegetation or use DDT as a prophylaxis area barrier treatment, so tick-induced sickness rates in forces off the front lines were diminished.

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).[47]

See also


  1. ^ Tseng BY, Yang HH, Liou JH, Chen LK, Hsu YH (February 2008). "Immunohistochemical study of scrub typhus: a report of two cases". Kaohsiung J. Med. Sci. 24 (2): 92–8.  
  2. ^ a b Pediatric Scrub Typhus, accessdate: 16 October 2011
  3. ^ Watt G, Kantipong P, de Souza M, et al. (2000). "HIV-1 suppression during acute scrub-typhus infection". Lancet 356 (9228): 475–479.  
  4. ^ Moriuchi M, Tamura A, Moriuchi H. (2003). "In vitro reactivation of human immunodeficiency virus-1 upon stimulation with scrub typhus rickettsial infection". Am J Trop Med Hyg 68 (5): 557–561.  
  5. ^ Pham XD, Otsuka Y, Suzuki H, Takaoka H (2001). (Rickettsiales: Rickettsiaceae) in unengorged chiggers (Acari: Trombiculidae) from Oita Prefecture, Japan, by nested polymerase chain reaction"Orientia tsutsugamushi"Detection of . J Med Entomol 38 (2): 308–311.  
  6. ^ Seong S, Choi M & Kim I (2001). "Orientia tsutsugamushi infection: overview and immune responses". Microbes and Infection 3 (1): 11–21.  
  7. ^ Phongmany S, Rolain JM, Phetsouvanh R, et al. (February 2006). "Rickettsial infections and fever, Vientiane, Laos". Emerging Infect. Dis. 12 (2): 256–62.  
  8. ^ Suttinont C, Losuwanaluk K, Niwatayakul K, et al. (June 2006). "Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study". Ann Trop Med Parasitol. 100 (4): 363–70.  
  9. ^ Katayama T, Hara M, Furuya Y, Nikkawa T, Ogasawara H (June 2006). "Scrub typhus (tsutsugamushi disease) in Kanagawa Prefecture in 2001–2005". Jpn J Infect Dis. 59 (3): 207–8.  
  10. ^ Yamamoto S, Ganmyo H, Iwakiri A, Suzuki S (December 2006). "Annual incidence of tsutsugamushi disease in Miyazaki prefecture, Japan in 2001-2005". Jpn J Infect Dis. 59 (6): 404–5.  
  11. ^ Bang HA, Lee MJ, Lee WC (2008). "Comparative research on epidemiological aspects of tsutsugamushi disease (scrub typhus) between Korea and Japan". Jpn J Infect Dis 61 (2): 148–50.  
  12. ^ a b Koh GCKW, Maude RJ, Paris DH, Newton PN, & Blacksell SD (2010). "Diagnosis of Scrub Typhus". Am J Trop Med Hyg 82 (3): 368–370.  
  13. ^ a b c Pradutkanchana J, Silpapojakul K, Paxton H, et al. (1997). "Comparative evaluation of four serodiagnostic tests for scrub typhus in Thailand". Trans R Soc Trop Med Hyg 91 (4): 425–8.  
  14. ^ Bozeman FM & Elisberg BL (1963). "Serological diagnosis of scrub typhus by indirect immunofluorescence". Proc Soc Exp Biol Med 112: 568–73.  
  15. ^ Yamamoto S & Minamishima Y (1982). "Serodiagnosis of tsutsugamushi fever (scrub typhus) by the indirect immunoperoxidase technique". J Clin Microbiol 15 (6): 1128–l.  
  16. ^ Kelly DJ, Wong PW, Gan E, Lewis GE Jr (1988). "Comparative evaluation of the indirect immunoperoxidase test for the serodiagnosis of rickettsial disease". Am J Trop Med Hyg 38 (2): 400–6.  
  17. ^ Blacksell SD, Bryant NJ, Paris, DH, et al. (2007). "Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to a lot of confusion". Clin Infect Dis 44 (3): 391–401.  
  18. ^ Eamsila C, Singsawat P, Duangvaraporn A, et al. (1996). "Antibodies to Orientia tsutsugamushi in Thai soldiers". Am J Trop Med Hyg 55 (5): 556–9.  
  19. ^ Watt G, Parola P (2003). "Scrub typhus and tropical rickettsioses". Curr Opin Infect Dis 16 (5): 429–436.  
  20. ^ Tay ST, Nazma S, Rohani MY (1996). "Diagnosis of scrub typhus in Malaysian aborigines using nested polymerase chain reaction". Southeast Asian J Trop Med Public Health 27 (3): 580–3.  
  21. ^ Kim, DM; Yun, NR; Yang, TY; Lee, JH; Yang, JT; Shim, SK; Choi, EN; Park, MY; Lee, SH (2006). "Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice: A prospective study". Am J Trop Med Hyg 75 (3): 542–545.  
  22. ^ Sonthayanon P, Chierakul W, Wuthiekanun V, et al. (December 2006). "Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain reaction". Am. J. Trop. Med. Hyg. 75 (6): 1099–102.  
  23. ^ Kim DM, Byun JN (2008). "Effects of Antibiotic Treatment on the Results of Nested PCRs for Scrub Typhus". J Clin Microbiol 46 (10): 3465–.  
  24. ^ Watt G, Chouriyagune C, Ruangweerayud R, et al. (1996). "Scrub typhus infections poorly responsive to antibiotics in northern Thailand". Lancet 348 (9020): 86–89.  
  25. ^ Kollars TM, Bodhidatta D, Phulsuksombati D, et al. (2003). "Short report: variation in the 56-kD type-specific antigen gene of Orientia tsutsugamushi isolated from patients in Thailand". Am J Trop Med Hyg 68 (3): 299–300.  
  26. ^ Phimda K, Hoontrakul S, Suttinont C, et al. (2007). "Doxycycline versus Azithromycin for Treatment of Leptospirosis and Scrub Typhus". Antimicrob Agents Chemother 51 (9): 3259–63.  
  27. ^ Panpanich R, Garner P (2009). Panpanich, Ratana, ed. "Antibiotics for treating scrub typhus". Cochrane Database Syst Rev (1): CD002150.  
  28. ^ Mahajan SK, Rolain J-M, Sankhyan N, Kaushal RK, Raoult D (2008). "Pediatric scrub typhus in Indian Himalayas". Indian Journal of Pediatrics 75 (9): 947–9.  
  29. ^ Watt, G; Kantipong, P; Jongsakul, K; Watcharapichat, P; Phulsuksombati, D (1999). "Azithromycin Activities against Orientia tsutsugamushi Strains Isolated in Cases of Scrub Typhus in Northern Thailand". Antimicrob Agents Chemother 43 (11): 2817–2818.  
  30. ^ Choi EK, Pai H (1998). "Azithromycin therapy for scrub typhus during pregnancy". Clin Infect Dis 27 (6): 1538–9.  
  31. ^ a b Kim YS, Lee HJ, Chang M, Son SK, Rhee YE, Shim SK (2006). "Scrub typhus during pregnancy and its treatment: a case series and review of the literature". Am J Trop Med Hyg 75 (5): 955–9.  
  32. ^ (2003). "Efficacy of azithromycin for treatment of mild scrub-typhus infections in South Korea". Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother 43: abstract no. L–182. 
  33. ^ Mathai E, Rolain JM, Verghese L, Mathai M, Jasper P, Verghese G, Raoult D (2003). "Case reports: scrub typhus during pregnancy in India". Trans R Soc Trop Med Hyg 97 (5): 570–2.  
  34. ^ Watt G, Kantipong P, Jongsakul K, et al. (2000). "Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial". Lancet 356 (9235): 1057–1061.  
  35. ^ Arguin PM, Kozarsky PE, Reed C (eds.) (2008). "Chapter 4: Rickettsial Infections". CDC Health Information for International Travel, 2008. Mosby.  
  36. ^ "AWIC Newsletter: The Cotton Rat In Biomedical Research". 
  37. ^ (2 April 1946). "Far East Report". Hansard. 
  38. ^ Thomson Walker W (1947). "Scrub Typhus Vaccine". Br Med J 1 (4501): 484–7.  
  39. ^ Shirai A, Tanskul PL, Andre, RG, et al. (1981). "Rickettsia tsutsugamushi strains found in chiggers collected in Thailand". Southeast Asian J Trop Med Public Health 12 (1): 1–6.  
  40. ^ Kang JS, Chang WH (1999). "Antigenic relationship among the eight prototype and new serotype strains of Orientia tsutsugamushi revealed by monoclonal antibodies". Microbiol Immunol 43 (3): 229–34.  
  41. ^ Kelly DJ, Fuerst PA, Ching W-M, Richards AL (2009). "Scrub typhus: The geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi". Clinical Infectious Diseases 48 (s3): S203–30.  
  42. ^ Audy JR (1968). Red mites and typhus. London: University of London, Athlone Press.  
  43. ^ Kearny CH (1997). Jungle Snafus...And Remedies. Cave Junction, Oregon: Oregon Institute of Science & Medicine. p. 309.  
  44. ^ Smallman-Raynor M, Cliff AD (2004). War epidemics: an historical geography of infectious diseases in military conflict and civil strife, 1850–2000. Oxford: Oxford University Press. pp. 489–91.  
  45. ^ a b  
  46. ^ Manchester, p. Six months to recapture Buna and Gona from July 21–22, 1942
  47. ^ Ogawa M, Hagiwara T, Kishimoto T, et al. (1 August 2002). "Scrub typhus in Japan: Epidemiology and clinical features of cases reported in 1998". Am J Trop Med Hyg. 67 (2): 162–5.  

External links

  • A film clip of the 1945 United States training film "Tsutsugamushi Prevention" is available for free download at the Internet Archive
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