Diagnosis of Scrub Typhus

Gavin C. K. W. Koh Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic

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Richard J. Maude Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic

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Daniel H. Paris Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic

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Paul N. Newton Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic

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Stuart D. Blacksell Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic

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Scrub typhus is transmitted by trombiculid mites and is endemic to East and Southeast Asia and Northern Australia. The clinical syndrome classically consists of a fever, rash, and eschar, but scrub typhus also commonly presents as an undifferentiated fever that requires laboratory confirmation of the diagnosis, usually by indirect fluorescent antibody (IFA) assay. We discuss the limitations of IFA, debate the value of other methods based on antigen detection and nucleic acid amplification, and outline recommendations for future study.

Author Notes

*Address correspondence to Gavin C. K. W. Koh, Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. E-mail: gavin.koh@gmail.com

Financial support: Gavin C. K. W. Koh, Daniel H. Paris, Paul N. Newton, and Stuart D. Blacksell are funded by the Wellcome Trust of Great Britain. Richard J. Maude is funded by the Wellcome Trust of Great Britain, The Bill and Melinda Gates Foundation, and a British Infection Society Fellowship. Gavin C. K. W. Koh and Daniel H. Paris both hold Wellcome Trust Clinical Training Fellowships (Grants 086532/Z/08/Z and 078990/Z/06/Z, respectively).

Authors' addresses: Gavin C. K. W. Koh, Richard J. Maude, Daniel H. Paris, and Stuart D. Blacksell, Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mails: gavin.koh@gmail.com, richardmaude@gmail.com, parigi@tropmedres.ac, and stuart@tropmedres.ac. Gavin C. K. W. Koh, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Gavin C. K. W. Koh, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. Paul N. Newton, Wellcome Trust–Mahosot Hospital–Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic, E-mail: paul@tropmedres.ac.

  • 1.

    Groves MG, Harrington KS, 1994. Scrub typhus. Beran GW, ed. Handbook of Zoonoses. Section A: Bacterial, Rickettsial, Chlamydial, and Mycotic Zoonoses. 2nd ed. Boca Raton, FL: CRC Press, 463–474.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Silpapojakul K, Varachit B, Silpapojakul K, 2004. Paediatric scrub typhus in Thailand: a study of 73 confirmed cases. Trans R Soc Trop Med Hyg 98: 354–359.

  • 3.

    Kelly DJ, Wong PW, Gan E, Lewis GE, 1988. Comparative evaluation of the indirect immunoperoxidase test for the serodiagnosis of rickettsial disease. Am J Trop Med Hyg 38: 400–406.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NPJ, 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: 391–401.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kelly DJ, Fuerst PA, Ching W, Richards AL, 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 48: S203–S230.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Miesse M, Diercks F, Danauskas J, 1950. Strain differences among Rickettsia tsutsugamushi. Bacteriological Proc M45: 90–91.

  • 7.

    Ree HI, Kim TE, Lee IY, Jeon SH, Hwang UW, Chang WH, 2001. Determination and geographical distribution of Orientia tsutsugamushi serotypes in Korea by nested polymerase chain reaction. Am J Trop Med Hyg 65: 528–534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Anonymous, 2001. Scrub typhus (Tsutsugamushi disease) in Japan, 1996–2000. Byogen Biseibutsu Kenshutsu Joho Geppo 22: 211–212.

  • 9.

    Luksameetanasan R, Blacksell SD, Kalambaheti T, Wuthiekanun V, Chierakul W, Chueasuwanchai S, Apiwattanaporn A, Stenos J, Graves S, Peacock SJ, Day NPJ, 2007. Patient and sample-related factors that effect the success of in vitro isolation of Orientia tsutsugamushi. Southeast Asian J Trop Med Public Health 38: 91–96.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Casleton BG, Salata K, Dasch GA, Strickman D, Kelly DJ, 1998. Recovery and viability of Orientia tsutsugamushi from packed red cells and the danger of acquiring scrub typhus from blood transfusion. Transfusion 38: 680–689.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Kim DM, Kim HL, Park CY, Yang TY, Lee JH, Yang JT, Shim SK, Lee SH, 2006. Clinical usefulness of eschar polymerase chain reaction for the diagnosis of scrub typhus: a prospective study. Clin Infect Dis 43: 1296–1300.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Saisongkorn W, Chenchittikul M, Silpapojakul K, 2004. Evaluation of nested PCR for the diagnosis of scrub typhus among patients with acute pyrexia of unknown origin. Trans R Soc Trop Med Hyg 98: 360–366.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Paris DH, Blacksell SD, Newton PN, Day NPJ, 2008. Simple, rapid and sensitive detection of Orientia tsutsugamushi by loop-isothermal DNA amplification. Trans R Soc Trop Med Hyg 102: 1239–1246.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Furuya Y, Yoshida Y, Katayama T, Yamamoto S, Kawamura A, 1993. Scrub typhus. J Clin Microbiol 31: 1637–1640.

  • 15.

    Sonthayanon P, Chierakul W, Wuthiekanun V, Blacksell SD, Pimda K, Suputtamongkol Y, Pukrittayakamee S, White NJ, Day NPJ, Peacock SJ, 2006. Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain reaction. Am J Trop Med Hyg 75: 1099–1102.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Sonthayanon P, Chierakul W, Wuthiekanun V, Phimda K, Pukrittayakamee S, Day NPJ, Peacock SJ, 2009. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 47: 430–434.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Jiang J, Chan T-C, Temenak JJ, Dasch GA, Ching W-M, Richards AL, 2004. Development of a quantitative real-time polymerase chain reaction assay specific for Orientia tsutsugamushi. Am J Trop Med Hyg 70: 351–356.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Paris DH, Aukkanit N, Jenjaroen K, Blacksell SD, Day NPJ, 2009. A highly sensitive quantitative real-time PCR assay based on the groEL gene of contemporary Thai strains of Orientia tsutsugamushi. Clin Microbiol Infect 15: 488–495.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Bozeman FM, Elisberg BL, 1963. Serological diagnosis of scrub typhus by indirect immunofluorescence. Proc Soc Exp Biol Med 112: 568–573.

  • 20.

    Pradutkanchana J, Silpapojakul K, Paxton H, Pradutkanchana S, Kelly DJ, Strickman D, 1997. Comparative evaluation of four serodiagnostic tests for scrub typhus in Thailand. Trans R Soc Trop Med Hyg 91: 425–428.

    • PubMed
    • Search Google Scholar
    • Export Citation
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