eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Scrub Typhus

Author: David J Cennimo, MD, FAAP, AAHIVS, Fellow in Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School
Coauthor(s): Arry Dieudonne, MD, Associate Professor of Pediatrics, Division of Pulmonology, Allergy, Immunology and Infectious Diseases, University of Medicine and Dentistry of New Jersey-New Jersey Medical School; Clinical Director, Francois-Xavier Bagnold Center for Children, University Hospital
Contributor Information and Disclosures

Updated: Jan 5, 2010

Introduction

Background

Scrub typhus is an acute, febrile, infectious illness that was first described in China in 313 AD. This illness is caused by Orientia (formerly Rickettsia) tsutsugamushi, an obligate intracellular gram-negative bacterium, which was first isolated in Japan in 1930. Although it was originally recognized as one of the tropical rickettsial diseases, O tsutsugamushi has a different cell wall structure and genetic composition than that of the rickettsiae. Western medicine became more interested in this infection during military campaigns fought in East Asia. During World War II, 18,000 cases were observed in Allied troops.1 It was the second or third most common infection reported in US troops stationed in Vietnam2 and continues to infect troops in the region.3,4

A photomicrograph of O tsutsugamushi is shown in the image below.

A transmission electron micrograph depicting a pe...

A transmission electron micrograph depicting a peritoneal mesothelial cell of a mouse that had been experimentally infected intraperitoneally with Orientia tsutsugamushi rickettsial micro-organisms. In this photomicrograph, several organisms are visible within the mesothelial cell's cytoplasm. O tsutsugamushi is the cause of scrub typhus.

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A transmission electron micrograph depicting a pe...

A transmission electron micrograph depicting a peritoneal mesothelial cell of a mouse that had been experimentally infected intraperitoneally with Orientia tsutsugamushi rickettsial micro-organisms. In this photomicrograph, several organisms are visible within the mesothelial cell's cytoplasm. O tsutsugamushi is the cause of scrub typhus.


The term scrub is used because of the type of vegetation (ie, terrain between woods and clearings) that harbors the vector. However, the name is not entirely correct because certain endemic areas can also be sandy and semiarid. Cases diagnosed in the United States have been imported from regions of 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, where the disease is endemic. The range includes tropical and temperate regions, extending to altitudes of more then 3200 meters in the Himalayas. Scrub typhus is often acquired during occupational/agricultural exposures5 because active rice fields are an important reservoir for transmission.1

An estimated one million cases occur annually and as many as one billion people living in endemic areas may have been infected at some time.4 Because of reports of O tsutsugamushi strains with reduced susceptibility to antibiotics,6 as well as reports of interesting interactions between this bacterium and HIV, a renewed interest in this illness has emerged.7,8

Pathophysiology

O tsutsugamushi is very similar and indeed meets all of the classifications of the genus Rickettsia;  it is a small (0.5 x 1.2-3 μm), arthropod born, obligate intracellular bacteria. This connection is demonstrated by the high degree of homology (90-99%) noted in 16S ribosomal sequencing. However, the cell walls are quite different as Orientia lack peptidoglycan and lipopolysaccharide.1

O tsutsugamushi is transmitted to humans through the bite of an infected chigger, the larval stage of trombiculid mites (Leptotrombidium deliense and others). These 6-legged, 0.2-mm larvae are not host specific and feed for 2-10 days on the skin fluids of the host. Wild rats serve as the natural reservoir for the chiggers (and represent a risk factor for human infection5 ), but are rarely infected with O tsutsugamushi.1 When the chiggers feed on humans, infection occurs.

Orientia is also transmitted transovarially in the mite population and can unbalance the sex ratio of offspring in favor of females, further propagating infection.1,9 Chigger activity and subsequent human infection rates are determined by the species of Leptotrombidium, as well as local conditions. In tropical regions, the disease may be acquired year round. In Japan, the chigger of L akamushi is only active between July and September, when the temperature is above 25ºC. In contrast, L Palladium which is found over a wide range, is active at temperatures of 18-20ºC (spring into early summer and autumn).1,10

Image of a chigger. Image taken from "Food and En...

Image of a chigger. Image taken from "Food and Environmental Hygiene Department" Web site and is reproduced under license from the Government of Hong Kong Special Administrative Region.

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Image of a chigger. Image taken from "Food and En...

Image of a chigger. Image taken from "Food and Environmental Hygiene Department" Web site and is reproduced under license from the Government of Hong Kong Special Administrative Region.


Humans acquire the disease when an infected chigger bites them while feeding and inoculates O tsutsugamushi pathogens. The bacteria multiply at the inoculation site with the formation of a papule that ulcerates and becomes necrotic, evolving into an eschar, with regional lymphadenopathy that may progress to generalized lymphadenopathy within a few days. In experimental infection, humans developed an acute febrile illness within 8-10 days of the chigger bite. Bacteremia was present 1-3 days before onset of fever.11 As in rickettsial diseases, perivasculitis of the small blood vessels occurs. The endothelium is involved; however, the basic histopathologic lesions suggest that macrophages might be more affected.12

O tsutsugamushi stimulates phagocytosis by the immune cells then escapes the phagosome. It replicates in the cytoplasm and then buds from the cell. The bacteria are able to harness the microtubule assembly inside the human cell for movement. Antibody opsonized bacteria are still able to escape the phagosome but cannot effectively move on the microtubule which decreases the overall infectivity.1

Frequency

United States

Reported cases are imported by travelers, military personnel, and persons who have emigrated from abroad.10,13

International

Scrub typhus is endemic in regions of eastern Asia and the southwestern Pacific (Korea to Australia) and from Japan to India and Pakistan.12,14,15,16,17,18

It is generally a disease of rural villages and suburban areas and is normally not encountered in the cities. Although most cases are undiagnosed, prospective studies in endemic areas reveal in incidence of 18-23%.1,19 Community surveys in Malaysia reported an incidence of 3.2-3.5% per month and a seroprevalence of more than 80% in those older than 44 years.20 Surveillance of military personal deployed in southeast Asia demonstrated seroconversion in 484 per 1000 population.3 Recently, cases have been noted earlier in the season due to increased mite activity as the weather warms.21

Mortality/Morbidity

Mortality rates in untreated patients range from 0-30% and tend to vary with the patient's age and region of infection. In the preantibiotic era, mortality rates in Japan averaged 30%. The mortality was 15% in patients aged 11-20 years, 20% in those aged 21-30 years, and 59% in those older than 60 years. In Taiwan, the overall mortality was estimated at 11% but was only 5% in children and 45% in the elderly. With appropriate treatment, mortality is quite rare.1,21 However, mortality is still approximately 15% in some areas due to missed or delayed diagnosis.22 If severe complications such as adult respiratory distress syndrome (ARDS) arise, mortality may still be high.23

Clinical

History

  • Patients with scrub typhus may present early or later in the course of their disease. In the United Sates, a history of travel to the endemic area must be sought, specifically probing for exposures in rural areas and contact with vegetation or the ground.10,4,1
  • The inoculation through the bite of the chigger is often painless and unnoticed. The incubation period lasts 6-20 days (average 10 d). A small painless papule initially appears at the site of infection and enlarges gradually. An area of central necrosis develops and is followed by eschar formation. The eschar (if present) is well developed at the initiation of the fevers, which may drive the patient to seek medical attention.1,2,24,9,25

Physical

  • Approximately 50% of patients with primary infection and 30% of patients with recurrent infection develop an eschar at the inoculation site. Given the appropriate history, the eschar is often pathognomonic but may be missed by inexperienced observers. In prospective studies, trained investigators were able to locate an eschar on 68-87% of patients.6,24 In adults, the eschar is often truncal, whereas children may have lesions in the perineum.26 Multiple eschars may be present.2 The eschar may also abrade leaving an ulcer reminiscent of primary syphilis.
  • Patients experience abrupt onset of high fever (104-105°F), headache, malaise, and myalgia approximately 10 days after infection. At that time, the eschar (if present) is well formed. Fever is the most commonly reported complaint, occurring more than 98% of the time.1,9 Tender regional or generalized lymphadenopathy may provide a clue to diagnosis and is reported in 40-97% of cases. Less frequently, ocular pain, wet cough, malaise, and injected conjunctiva are present.2,6,24,9,27
  • Toward the end of the first week, approximately 35% (reported ranges 15-93%) of patients develop a centrifugal macular rash on the trunk. The rash may progress to become papular.2,9,25 It may be transient and easily missed.1
  • Some patients may have CNS involvement with tremors, nervousness, slurred speech, nuchal rigidity, or deafness during the second week of the disease. However, results from the cerebrospinal fluid (CSF) examination are either normal or indicate a low number of monocytes. Severe CNS involvement such as seizure or coma are rare. If acute hearing loss is present (reported in as many as one third of patients in some reports), it strongly points toward scrub typhus.1,4
  • Some evidence of pulmonary involvement such as cough, tachypnea, or pulmonary infiltrates is often present.24 Respiratory compromise may progress to adult respiratory distress syndrome (ARDS), especially in the elderly.23
  • Cardiac involvement is often minor and rare; however, cases of fatal myocarditis have been reported.28 Infection with O tsutsugamushi may cause a relative bradycardia,29 which, when combined with rash, may raise concern for typhoid fever.6
  • Scrub typhus may rarely cause acute renal failure, shock, and disseminated intravascular coagulation (DIC).1

Causes

  • O tsutsugamushi
    • This is an obligate intracellular gram-negative bacterium that has a large number of serotypes. Five serotypes, Karp, Gilliam, Kawazaki, Boryon, and Kato, are helpful in serologic diagnosis.
    • This pathogen does not have a vacuolar membrane; thus, it freely grows in the cytoplasm of infected cells.

More on Scrub Typhus

Overview: Scrub Typhus
Differential Diagnoses & Workup: Scrub Typhus
Treatment & Medication: Scrub Typhus
Follow-up: Scrub Typhus
Multimedia: Scrub Typhus
References
Further Reading
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References

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  2. Berman SJ, Kundim WD. Scrub Typhus in South Vietnam: A Study of 87 Cases. Annals Internal Med. July 1973;79:26-30.

  3. Corwin A, Soderquist R, Suwanabun N, Sattabongkot J, Martin L, Kelly D, et al. Scrub typhus and military operations in Indochina. Clin Infect Dis. Oct 1999;29(4):940-1. [Medline].

  4. Raoult D. Scrub typhus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Vol 2. 6th ed. Philadelphia, PA: Elsever Churchill Livingstone; 2005:2309-10.

  5. Sharma PK, Ramakrishnan R, Hutin YJ, et al. Scrub typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans R Soc Trop Med Hyg. Mar 13 2009;[Medline].

  6. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, et al. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet. Jul 13 1996;348(9020):86-9. [Medline].

  7. Watt G, Kantipong P, de Souza M, Chanbancherd P, Jongsakul K, Ruangweerayud R, et al. HIV-1 suppression during acute scrub-typhus infection. Lancet. Aug 5 2000;356(9228):475-9. [Medline].

  8. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis. Oct 2003;16(5):429-36. [Medline].

  9. Ogawa M, Hagiwara T, Kishimoto T, Shiga S, Yoshida Y, Furuya Y. Scrub typhus in Japan: epidemiology and clinical features of cases reported in 1998. Am J Trop Med Hyg. Aug 2002;67(2):162-5. [Medline].

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  11. Shirai A, Saunders JP, Dohany AL, et al. Transmission of Scrub Typhus to Human Volunteers by Laboratory Raised Chiggers. Jpn J Med Sci Biol. 1982;35(9).

  12. Suputtamongkol Y, Suttinont C, Niwatayakul K, et al. Epidemiology and clinical aspects of rickettsioses in Thailand. Ann N Y Acad Sci. May 2009;1166:172-9. [Medline].

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  14. Matsumura Y, Shimizu T. [Case of imported scrub typhus contracted in Myanmar]. Kansenshogaku Zasshi. May 2009;83(3):256-60. [Medline].

  15. Liu Y, Feng D, Suo J, et al. Clinical characteristics of the autumn-winter type scrub typhus cases in south of Shandong province, northern China. BMC Infect Dis. Jun 4 2009;9(1):82. [Medline].

  16. McGready R, Blacksell SD, Luksameetanasan R, et al. First Report of an Orientia tsutsugamushi Type TA716-Related Scrub Typhus Infection in Thailand. Vector Borne Zoonotic Dis. Jun 3 2009;[Medline].

  17. Sharma PK, Ramakrishnan R, Hutin YJ, et al. Scrub typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans R Soc Trop Med Hyg. Mar 13 2009;[Medline].

  18. Kramme S, An le V, Khoa ND, et al. Orientia tsutsugamushi bacteremia and cytokine levels in Vietnamese scrub typhus patients. J Clin Microbiol. Mar 2009;47(3):586-9. [Medline].

  19. Brown GW, Robinson DM, Huxsoll DL, Ng TS, Lim KJ. Scrub typhus: a common cause of illness in indigenous populations. Trans R Soc Trop Med Hyg. 1976;70(5-6):444-8. [Medline].

  20. Brown GW, Robinson DM, Huxsoll DL. Serological evidence for a high incidence of transmission of Rickettsia tsutsugamushi in two Orang Asli settlements in Peninsular Malaysia. Am J Trop Med Hyg. Jan 1978;27(1 Pt 1):121-3. [Medline].

  21. Cao M, Guo H, Tang T, Wang C, Li X, Pan X, et al. Spring scrub typhus, People's Republic of China. Emerg Infect Dis. Sep 2006;12(9):1463-5. [Medline].

  22. Watt G, Jongsakul K, Chouriyagune C, Paris R. Differentiating dengue virus infection from scrub typhus in Thai adults with fever. Am J Trop Med Hyg. May 2003;68(5):536-8. [Medline].

  23. Wang CC, Liu SF, Liu JW, Chung YH, Su MC, Lin MC. Acute respiratory distress syndrome in scrub typhus. Am J Trop Med Hyg. Jun 2007;76(6):1148-52. [Medline].

  24. Chanta C, Chanta S. Clinical study of 20 children with scrub typhus at Chiang Rai Regional Hospital. J Med Assoc Thai. Dec 2005;88(12):1867-72. [Medline].

  25. Sirisanthana V, Puthanakit T, Sirisanthana T. Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children. Pediatr Infect Dis J. Apr 2003;22(4):341-5. [Medline].

  26. Kim DM, Won KJ, Park CY, Yu KD, Kim HS, Yang TY. Distribution of eschars on the body of scrub typhus patients: a prospective study. Am J Trop Med Hyg. May 2007;76(5):806-9. [Medline].

  27. Edwards MS, Feigen RD. Rickettsial and Erlichial Diseases. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2009:2677-2678.

  28. Sittiwangkul R, Pongprot Y, Silviliarat S, Oberdorfer P, Jittamala P, Sirisanthana V. Acute fulminant myocarditis in scrub typhus. Ann Trop Paediatr. Jun 2008;28(2):149-54. [Medline].

  29. Aronoff DM, Watt G. Prevalence of relative bradycardia in Orientia tsutsugamushi infection. Am J Trop Med Hyg. Apr 2003;68(4):477-9. [Medline].

  30. Chanta C, Triratanapa K, Ratanasirichup P, Mahaprom W. Hepatic dysfunction in pediatric scrub typhus: role of liver function test in diagnosis and marker of disease severity. J Med Assoc Thai. Nov 2007;90(11):2366-9. [Medline].

  31. Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother. Sep 2007;51(9):3259-63. [Medline].

  32. Phetsouvanh R, Blacksell SD, Jenjaroen K, Day NP, Newton PN. Comparison of indirect immunofluorescence assays for diagnosis of scrub typhus and murine typhus using venous blood and finger prick filter paper blood spots. Am J Trop Med Hyg. May 2009;80(5):837-40. [Medline].

  33. Paris DH, Aukkanit N, Jenjaroen K, Blacksell SD, Day NP. A highly sensitive quantitative real-time PCR assay based on the groEL gene of contemporary Thai strains of Orientia tsutsugamushi. Clin Microbiol Infect. May 2009;15(5):488-95. [Medline].

  34. Tsai CC, Lay CJ, Wang CL, Ho YH, Wang LS, Chen LK. Levofloxacin versus tetracycline antibiotics for the treatment of scrub typhus. Int J Infect Dis. Jun 3 2009;[Medline].

  35. Mathai E, Rolain JM, Verghese GM, Abraham OC, Mathai D, Mathai M. Outbreak of scrub typhus in southern India during the cooler months. Ann N Y Acad Sci. Jun 2003;990:359-64. [Medline].

  36. Kim YS, Lee HJ, Chang M, Son SK, Rhee YE, Shim SK. Scrub typhus during pregnancy and its treatment: a case series and review of the literature. Am J Trop Med Hyg. Nov 2006;75(5):955-9. [Medline].

  37. Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, Strickman D. Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial. Lancet. Sep 23 2000;356(9235):1057-61. [Medline].

  38. Lee KY, Lee HS, Hong JH, Hur JK, Whang KT. Roxithromycin treatment of scrub typhus (tsutsugamushi disease) in children. Pediatr Infect Dis J. Feb 2003;22(2):130-3. [Medline].

  39. Olson JG, Bourgeois AL, Fang RC, Coolbaugh JC, Dennis DT. Prevention of scrub typhus. Prophylactic administration of doxycycline in a randomized double blind trial. Am J Trop Med Hyg. Sep 1980;29(5):989-97. [Medline].

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Keywords

scrub typhus, chigger fever, tsutsugamushi fever, akamushi disease, flood fever, inundation fever, island disease, island fever, HIV infection, adult respiratory distress syndrome, ARDS, treatment, diagnosis

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Contributor Information and Disclosures

Author

David J Cennimo, MD, FAAP, AAHIVS, Fellow in Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School
David J Cennimo, MD, FAAP, AAHIVS is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Medical Association, HIV Medicine Association of America, Infectious Diseases Society of America, Medical Society of New Jersey, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Coauthor(s)

Arry Dieudonne, MD, Associate Professor of Pediatrics, Division of Pulmonology, Allergy, Immunology and Infectious Diseases, University of Medicine and Dentistry of New Jersey-New Jersey Medical School; Clinical Director, Francois-Xavier Bagnold Center for Children, University Hospital
Arry Dieudonne, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Medical Editor

José Rafael Romero, MD, Director of Pediatric Infectious Diseases Fellowship Program, Associate Professor, Department of Pediatrics, Combined Division of Pediatric Infectious Diseases, Creighton University/University of Nebraska Medical Center
José Rafael Romero, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, New York Academy of Sciences, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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