eMedicine Specialties > Dermatology > Bacterial Infections
Scrub Typhus
Updated: Aug 31, 2009
Introduction
Background
Scrub typhus typically occurs in Southeast Asia and Japan, where the disease was first described in 1899. During World War II, scrub typhus killed or incapacitated thousands of troops who were stationed in rural or jungle areas of the Pacific theatre. The disease is called scrub typhus because it generally occurs after exposure to areas with scrub vegetation because this is where the rodents predominantly live. Scrub typhus can also be prevalent in areas such as sandy beaches, mountain deserts, and equatorial rain forests.
Rickettsial diseases such as scrub typhus have forced the American military to continue work on countermeasures to control the arthropod vectors and participate in the development of rapid, accurate diagnostic tests, vaccines, and improved surveillance methods.[1 ]
Also see the eMedicine Pediatrics article Scrub Typhus.
Pathophysiology
Scrub typhus is caused by Rickettsia tsutsugamushi (Orientia tsutsugamushi). It is a tiny intracellular parasite that lives primarily in mites (the primary reservoir) belonging to the species Leptotrombidium (Trombicula) akamushi and Leptotrombidium deliense. The Rickettsia organisms are found throughout the mite's body, but the highest number is present in the salivary glands. When the mite feeds on rodents (eg, rats, moles, and field mice, which are the secondary reservoirs) or humans, the parasites are transmitted to the host. Only larval Leptotrombidium mites (eg, chiggers) transmit the disease.
Scrub typhus, a zoonotic disease, may disseminate into multiple organs through endothelial cells and macrophages, resulting in the development of fatal complications.[2,3 ]In 2009, an apparent association was reported apparent between high O tsutsugamushi blood polymerase chain reaction (PCR)–determined DNA loads and disease severity.[4 ]
In 2009, phenotypic and genotypic variants of O tsutsugamushi were reported.[5 ]DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. About half of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain.[6 ]
In 2009, behavioral factors were shown to be associated with scrub typhus during an autumn epidemic season in South Korea.[7 ] Taking a rest directly on the grass, working in short sleeves, working with bare hands, and squatting to defecate or urinate posed the highest risks. Wearing a long-sleeved shirt while working, keeping work clothes off the grass, and always using a mat to rest outdoors showed protective associations.
Frequency
United States
The United States is not affected by scrub typhus. The only cases of scrub typhus in the United States are in travelers who have recently been to one of the endemic areas.
International
Scrub typhus is limited to eastern and southeastern Asia, India, and northern Australia and the adjacent islands. The seasonal occurrence of scrub typhus varies with the climate in different countries because the mites are able to thrive as conditions change. The mites prefer the rainy season and certain areas (eg, forest clearings, riverbanks, grassy regions). Areas in which the mites thrive pose a greater risk to humans. The prevalence of scrub typhus in Japan has been rising, and much of the current research has been based in Japan.
Mortality/Morbidity
The mortality rate from scrub typhus ranges from 1-60%, depending on the geographic area and the rickettsial strain. Death can occur from the primary infection or from secondary complications (eg, pneumonitis, encephalitis, circulatory failure). Most fatalities occur by the end of the second week of infection.
Race
All races are affected equally by scrub typhus.
Sex
Both men and women are affected equally by scrub typhus.
Age
People of all ages are affected equally by scrub typhus.
Clinical
History
- Once transmitted to the host, R tsutsugamushi incubates for about 10-12 days (although this can vary from as little as 6 d or as long as 21 d).
- After incubation, persons may experience headaches, shaking chills, lymphadenopathy, conjunctival infection, fever, anorexia, and general apathy.
- The fever usually reaches 104-105°F.
- Diagnosing this disease early in its course can be difficult because many conditions can present with a high fever; however, the presentation of the rash, a history of exposure to endemic areas, and the presentation of the sore caused by the bite can be diagnostic.
Physical
- The site of infection is marked by a chigger bite.
- This initial lesion has been said to be most easily discernible in whites. However, the presence or absence of eschar was thoroughly examined among 176 Korean patients with scrub typhus confirmed by immunofluorescent assay[8 ]; 162 (92%) cases had eschar, with 128 (79.5%) on the front of the body. Eschars were detected in men within 30 cm below the umbilicus (19 patients, 35.8%). Distribution on the lower extremities and the chest above the umbilicus were 22.6% (12 patients) and 20.8% (11 patients), respectively. In women, the most prevalent area was the chest above the umbilicus, which accounted for 40.7% (44 patients) of all the detected eschars.
- The infection begins as a red indurated lesion that eventually enlarges to 8-12 mm in diameter, vesiculates and ruptures, and becomes dark and necrotic in the center.
- Scarring may occur.
- From 5-8 days after infection, a dull red rash may appear all over the body, especially starting on the trunk and extending to the extremities.
- Additional symptoms at this time include enlargement of the spleen, cough, and delirium.
- Pneumonitis or encephalitis may develop during the second week.
- In severe cases, the patient's pulse rate increases and the blood pressure decreases.
- The patient may become delirious and lose consciousness.
- Other complications, such as splenomegaly, muscle twitching, or interstitial myocarditis, may develop.
- If the patient does not receive treatment, symptoms may last for more than 2 weeks; with treatment, the patient recovers within 36 hours.
- The patient's recovery is usually rapid and without sequelae.
Causes
- Scrub typhus is caused by R tsutsugamushi (O tsutsugamushi). It is a tiny parasite that lives primarily in mites belonging to the species L (Trombicula) akamushi and L deliense.
Differential Diagnoses
Dengue
Other Problems to Be Considered
Other rickettsial infections
Leptospirosis
Typhoid
Hemorrhagic fever[9 ]
Scrub typhus may rarely be first seen with fever and a tender neck swelling, mimicking a deep neck infection.[10 ]
Diagnosing scrub typhus and rickettsial diseases in international travelers can be challenging.[11 ]Such travelers may become sick before or within a few days of return from an endemic region. An illness that begins more than 18 days after return is unlikely to be rickettsial. If empiric therapy does not result in defervescence within 48 hours, an alternative diagnosis should be strongly considered.
Workup
Laboratory Studies
- Laboratory studies of choice are serologic tests for antibodies because actual isolation and culture of rickettsiae is difficult, expensive, and dangerous. Several tests are available.
- The fluorescent antibody test is used most often because it can identify antibodies to R tsutsugamushi, and it is a specific test.
- The Weil-Felix test is another widely used test. This test can be used to aid in diagnosis of scrub typhus because antibodies to Rickettsia species react with certain strains of Proteus species and agglutinate. This test unfortunately is not very specific and is not positive until the second week of illness; therefore, it often does not detect early cases of disease.
- Enzyme-linked immunosorbent assay, indirect immunoperoxidase, and polymerase chain reaction (PCR)[12 ]are available as research tests only.
- New duplex PCR methods based on the groEL gene were developed and investigated for the diagnosis of rickettsial infections.[13 ]One duplex PCR assay amplified the 229-bp and the 366-bp DNAs of 6 strains, including the typhus group and spotted fever group rickettsiae, and 5 scrub typhus group (STG) rickettsiae, respectively. Another duplex PCR assay amplified the 397-bp and the 213-bp DNAs of 6 Rickettsia strains and 5 STG strains. Use of these duplex PCR methods may allow simultaneously rapid identification of rickettsiae and the differential diagnosis of STG and other groups of rickettsiae.
- Performing nested PCR on the eschar might be a rapid diagnostic test for scrub typhus in the early, acute stage.[14 ]
- In 2007, Cao et al reported on the development of a rapid diagnostic reagent for scrub typhus.[15 ]
Imaging Studies
- No imaging studies are required for scrub typhus.
Histologic Findings
The basic pathologic change is focal or disseminated vasculitis caused by the destruction of endothelial cells and the perivascular infiltration of leukocytes.[16 ]
Treatment
Medical Care
- The current treatment for scrub typhus is doxycycline. Chloramphenicol is also effective.
- Relapses may occur if the antibiotics are not taken for a long enough period.
- Intravenous antibiotics may be administered to patients who are seriously ill and unable to swallow pills.
Consultations
- Consider consultation with an infectious diseases specialist if the patient does not improve on antibiotics or has atypical symptoms.
Diet
- Diet is as tolerated.
Activity
- Activity is as tolerated.
Medication
Antibiotics are necessary to eradicate the rickettsial infection. In a prospective, open-label, randomized trial of Korean patients with mild-to-moderate scrub typhus, the efficacy and safety of a 5-day telithromycin regimen compared favorably with a 5-day doxycycline regimen.[17 ]Telithromycin is a promising new antibacterial agent for patients with scrub typhus.
Antibiotics
Doxycycline or chloramphenicol is effective in treating scrub typhus.
Doxycycline (Bio-Tab, Vibramycin, Doryx)
Synthetic antibiotic derived from tetracycline. Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Effective against a large number of pathogens.
Dosing
Adult
100 mg PO bid for 7-14 d
Pediatric
<8 years: Not recommended
>8 years: Administer as in adults
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can possibly decrease effects of oral contraceptives by reducing the enterohepatic circulation of estrogens, causing breakthrough bleeding and increased risk of pregnancy
Contraindications
Documented hypersensitivity; severe hepatic dysfunction
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Chloramphenicol (Chloromycetin)
Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. Very inexpensive.
Dosing
Adult
500 mg PO qid for 7-14 d
Pediatric
Not established
Interactions
Administered concurrently with barbiturates, serum levels may decrease while barbiturate levels may increase causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; hydantoins may either increase or decrease chloramphenicol levels
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (eg, aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue on appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects to the fetus (gray syndrome)
Follow-up
Deterrence/Prevention
Advise patients who plan to visit endemic areas to take precautions (eg, wearing protective clothing, using insect repellent). Antibiotic prophylaxis with a single oral dose of chloramphenicol or tetracycline given every 5 days for a total of 35 days, with 5-day nontreatment intervals, produces active immunity to scrub typhus.
Reports of scrub typhus outbreaks in endemic areas and a decreased effectiveness of antibiotic treatment suggest a continued need for a suitable vaccine.[18 ]A scrub typhus vaccine is being developed.
Complications
Scrub typhus patients who are not treated can develop encephalitis, pneumonitis, and circulatory failure, and they can even die.
Prognosis
In patients who are not treated, the mortality rate for scrub typhus varies from 1-60%, depending on the geographic area and the rickettsial strain. With the proper antibiotic treatment, deaths from scrub typhus are rare and the recovery period is short and usually without complications.
Patient Education
Educate travelers to endemic areas about the importance of being aware of bites and seeking treatment immediately if they are affected.
Miscellaneous
Medicolegal Pitfalls
- Failure to treat scrub typhus patients with the proper antibiotics as soon as possible is a pitfall. Serious complications can develop if treatment is delayed.
Special Concerns
- When patients who are HIV positive become infected with certain strains of scrub typhus, their viral load can dramatically decrease. This is an important area of research. A proposed hypothesis is that patients infected with HIV who acquire scrub typhus have a powerful immune response raised to the scrub typhus and that is being turned against the HIV.[19 ]
References
Bavaro MF, Kelly DJ, Dasch GA, Hale BR, Olson P. History of U.S. military contributions to the study of rickettsial diseases. Mil Med. Apr 2005;170(4 Suppl):49-60. [Medline].
Cracco C, Delafosse C, Baril L, et al. Multiple organ failure complicating probable scrub typhus. Clin Infect Dis. Jul 2000;31(1):191-2. [Medline].
Tseng BY, Yang HH, Liou JH, Chen LK, Hsu YH. Immunohistochemical study of scrub typhus: a report of two cases. Kaohsiung J Med Sci. Feb 2008;24(2):92-8. [Medline].
Sonthayanon P, Chierakul W, Wuthiekanun V, et al. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol. Feb 2009;47(2):430-4. [Medline].
Kelly DJ, Fuerst PA, Ching WM, Richards AL. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis. Mar 15 2009;48 Suppl 3:S203-30. [Medline].
Blacksell SD, Luksameetanasan R, Kalambaheti T, et al. Genetic typing of the 56-kDa type-specific antigen gene of contemporary Orientia tsutsugamushi isolates causing human scrub typhus at two sites in north-eastern and western Thailand. FEMS Immunol Med Microbiol. Apr 2008;52(3):335-42. [Medline].
Kweon SS, Choi JS, Lim HS, et al. A community-based case-control study of behavioral factors associated with scrub typhus during the autumn epidemic season in South Korea. Am J Trop Med Hyg. Mar 2009;80(3):442-6. [Medline].
Kim DM, Won KJ, Park CY, et al. 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].
Liu YX, Feng D, Zhang Q, et al. Key differentiating features between scrub typhus and hemorrhagic fever with renal syndrome in northern China. Am J Trop Med Hyg. May 2007;76(5):801-5. [Medline].
Tsai CC, Chiang DH, Duh RW. Scrub typhus mimicking deep neck infection. Intern Med. 2008;47(22):1997-2000. [Medline].
Hendershot EF, Sexton DJ. Scrub typhus and rickettsial diseases in international travelers: a review. Curr Infect Dis Rep. Jan 2009;11(1):66-72. [Medline].
Sugita Y, Nagatani T, Okuda K, Yoshida Y, Nakajima H. Diagnosis of typhus infection with Rickettsia tsutsugamushi by polymerase chain reaction. J Med Microbiol. Nov 1992;37(5):357-60. [Medline].
Park HS, Lee JH, Jeong EJ, et al. Rapid and simple identification of Orientia tsutsugamushi from other group rickettsiae by duplex PCR assay using groEL gene. Microbiol Immunol. 2005;49(6):545-9. [Medline].
Lee SH, Kim DM, Cho YS, Yoon SH, Shim SK. Usefulness of eschar PCR for diagnosis of scrub typhus. J Clin Microbiol. Mar 2006;44(3):1169-71. [Medline].
Cao M, Guo H, Tang T, et al. Preparation of recombinant antigen of O. tsutsugamushi Ptan strain and development of rapid diagnostic reagent for scrub typhus. Am J Trop Med Hyg. Mar 2007;76(3):553-8. [Medline].
Jeong YJ, Kim S, Wook YD, Lee JW, Kim KI, Lee SH. Scrub typhus: clinical, pathologic, and imaging findings. Radiographics. Jan-Feb 2007;27(1):161-72. [Medline].
Kim DM, Yu KD, Lee JH, Kim HK, Lee SH. Controlled trial of a 5-day course of telithromycin versus doxycycline for treatment of mild to moderate scrub typhus. Antimicrob Agents Chemother. Jun 2007;51(6):2011-5. [Medline].
Chattopadhyay S, Richards AL. Scrub typhus vaccines: past history and recent developments. Hum Vaccin. May-Jun 2007;3(3):73-80. [Medline].
Ariyoshi K, Whittle H. HIV-1 viral load and scrub typhus. Lancet. Nov 18 2000;356(9243):1766; author reply 1766-7. [Medline].
Chang WH. Current status of tsutsugamushi disease in Korea. J Korean Med Sci. Aug 1995;10(4):227-38. [Medline].
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].
Fan MY, Walker DH, Yu SR, Liu QH. Epidemiology and ecology of rickettsial diseases in the People's Republic of China. Rev Infect Dis. Jul-Aug 1987;9(4):823-40. [Medline].
Johnson S, Wilkinson R, Davidson RN. Tropical respiratory medicine. 4. Acute tropical infections and the lung. Thorax. Jul 1994;49(7):714-8. [Medline].
Kostman JR. Laboratory diagnosis of rickettsial diseases. Clin Dermatol. May-Jun 1996;14(3):301-6. [Medline].
Kovacova E, Kazar J. Rickettsial diseases and their serological diagnosis. Clin Lab. 2000;46(5-6):239-45. [Medline].
McBride WJ, Taylor CT, Pryor JA, Simpson JD. Scrub typhus in north Queensland. Med J Aust. Apr 5 1999;170(7):318-20. [Medline].
Panpanich R, Garner P. Antibiotics for treating scrub typhus. Cochrane Database Syst Rev. 2000;CD002150. [Medline].
Shaked Y. Rickettsial infection of the central nervous system: the role of prompt antimicrobial therapy. Q J Med. Apr 1991;79(288):301-6. [Medline].
Silpapojakul K. Scrub typhus in the Western Pacific region. Ann Acad Med Singapore. Nov 1997;26(6):794-800. [Medline].
Tamura A. Invasion and intracellular growth of Rickettsia tsutsugamushi. Microbiol Sci. Aug 1988;5(8):228-32. [Medline].
Tamura A, Ohashi N, Urakami H, Miyamura S. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol. Jul 1995;45(3):589-91. [Medline].
Tange Y, Kobayashi Y. Transfiguration of rickettsial diseases: tsutsugamushi disease and spotted fever group rickettsiosis in Japan. Intern Med. Dec 1993;32(12):937-9. [Medline].
Tay ST, Kaewanee S, Ho TM, Rohani MY, Devi S. Serological evidence of natural infection of wild rodents (Rattus spp and Tupaia glis) with rickettsiae in Malaysia. Southeast Asian J Trop Med Public Health. Sep 1998;29(3):560-2. [Medline].
Walker DH, Fishbein DB. Epidemiology of rickettsial diseases. Eur J Epidemiol. May 1991;7(3):237-45. [Medline].
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].
Yun JH, Koh YS, Lee KH, et al. Chemokine and cytokine production in susceptible C3H/HeN mice and resistant BALB/c mice during Orientia tsutsugamushi infection. Microbiol Immunol. 2005;49(6):551-7. [Medline].
Keywords
scrub typhus, typhus, rickettsial infection, tsutsugamushi disease, tsutsugamushi fever, tropical typhus,
Contributor Information and Disclosures
Author
Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.
Coauthor(s)
Cris Jagar, MD, Staff Physician, Department of Psychiatry, Saint Vincent Catholic Medical Centers
Disclosure: Nothing to disclose.
Medical Editor
Janet Fairley, MD, Professor and Head, Department of Dermatology, University of Iowa
Janet Fairley, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Federation for Medical Research, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Pharmacy Editor
David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Managing Editor
Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.
CME Editor
Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.