Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 25 , ISSUE S2 ( May, 2021 ) > List of Articles


Scrub Typhus and Other Rickettsial Infections

Karthik Gunasekaran, Deepti Bal, George M. Varghese

Citation Information :

DOI: 10.5005/jp-journals-10071-23841

License: CC BY-NC 4.0

Published Online: 01-05-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Scrub typhus and other rickettsial infections contribute to 25 – 50% of acute undifferentiated febrile illnesses in endemic regions. Delayed recognition and therapy increase the morbidity and mortality. The constellation of fever with eschar or rash and multisystem involvement should facilitate the diagnosis and initiation of appropriate therapy. The pathological hallmark of rickettsial infections is endothelial infection and inflammation causing vasculitis. Endothelial inflammation results in microvascular dysfunction and increased vascular permeability. Immune and endothelial activation may worsen microvascular dysfunction, predisposing to multi-organ failure. Serology is the mainstay of diagnosis, although false negatives occur early in the disease. Point-of-care rapid diagnostic tests and molecular techniques, such as quantitative polymerase chain reaction (qPCR), can hasten diagnostic processes. Intravenous doxycycline with a loading dose is the most widely used antibiotic in critically ill patients, with azithromycin as a suitable alternative. Early appropriate treatment and organ support can decrease the duration of illness and be life-saving.

  1. John R, Varghese GM. Scrub typhus: a reemerging infection. Curr Opin Infect Dis 2020;33(5):365–371. DOI: 10.1097/QCO.0000000000000664. PMID: 32868511.
  2. The Indian Society of Critical Care Medicine Tropical fever Group, Singhi S, Chaudhary D, Varghese GM, Bhalla A, Karthi N, et al. Tropical fevers: management guidelines. Indian J Crit Care Med 2014;18(2):62–69. DOI: 10.4103/0972-5229.126074. PMID: 24678147; PMCID: PMC3943129.
  3. Taylor AJ, Paris DH, Newton PN. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 2015;9(8):e0003971. DOI: 10.1371/journal.pntd.0003971. PMID: 26274584; PMCID: PMC4537241.
  4. Varghese GM, Trowbridge P, Janardhanan J, Thomas K, Peter JV, Mathews P, et al. Clinical profile and improving mortality trend of scrub typhus in South India. Int J Infect Dis 2014;23:39–43. DOI: 10.1016/j.ijid.2014.02.009. PMID: 24661931.
  5. Bagshaw RJ, Stewart AGA, Smith S, Carter AW, Hanson J. The characteristics and clinical course of patients with scrub typhus and queensland tick typhus infection requiring intensive care unit admission: a 23-year case series from Queensland, Tropical Australia. Am J Trop Med Hyg 2020;103(6):2472–2477. DOI: 10.4269/ajtmh.20-0780. PMID: 32959771; PMCID: PMC7695075.
  6. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin Infect Dis 1995;20(5):1118–1121. DOI: 10.1093/clinids/20.5.1118. PMID: 7619985.
  7. Griffith M, Peter JV, Karthik G, Ramakrishna K, Prakash JA, Kalki RC, et al. Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission. Indian J Crit Care Med 2014;18(8):497–502. DOI: 10.4103/0972-5229.138145. PMID: 25136187; PMCID: PMC4134622.
  8. 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 1995;45(3):589–591. DOI: 10.1099/00207713-45-3-589. PMID: 8590688.
  9. Kocher C, Morrison AC, Leguia M, Loyola S, Castillo RM, Galvez HA, et al. Rickettsial disease in the Peruvian Amazon Basin. PLoS Negl Trop Dis 2016;10(7):e0004843. DOI: 10.1371/journal.pntd.0004843. PMID: 27416029; PMCID: PMC4944934.
  10. Díaz FE, Abarca K, Kalergis AM. An update on host-pathogen interplay and modulation of immune responses during Orientia tsutsugamushi infection. Clin Microbiol Rev 2018;31(2):e00076-17. DOI: 10.1128/CMR.00076-17. PMID: 29386235; PMCID: PMC5967693.
  11. Salje J. Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle. Nat Rev Microbiol 2021. DOI: 10.1038/s41579-020-00507-2. PMID: 33564174.
  12. Moron CG, Popov VL, Feng HM, Wear D, Walker DH. Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus. Mod Pathol 2001;14(8):752–759. DOI: 10.1038/modpathol.3880385. PMID: 11504834.
  13. Rajapakse S, Weeratunga P, Sivayoganathan S, Fernando SD. Clinical manifestations of scrub typhus. Trans R Soc Trop Med Hyg 2017;111(2):43–54. DOI: 10.1093/trstmh/trx017. PMID: 28449088.
  14. Faccini-Martínez ÁA, García-Álvarez L, Hidalgo M, Oteo JA. Syndromic classification of rickettsioses: an approach for clinical practice. Int J Infect Dis 2014;28:126–139. DOI: 10.1016/j.ijid.2014.05.025. PMID: 25242696.
  15. Varghese GM, Janardhanan J, Trowbridge P, Peter JV, Prakash JA, Sathyendra S, et al. Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome. Int J Infect Dis 2013;17(11):e981–e987. DOI: 10.1016/j.ijid.2013.05.017. PMID: 23891643.
  16. Abhilash K, Mannam PR, Rajendran K, John RA, Ramasami P. Chest radiographic manifestations of scrub typhus. J Postgrad Med 2016;62(4):235–238. DOI: 10.4103/0022-3859.184662. PMID: 27763480; PMCID: PMC5105208.
  17. Kirkland KB, Marcom PK, Sexton DJ, Dumler JS, Walker DH. Rocky Mountain spotted fever complicated by gangrene: report of six cases and review. Clin Infect Dis. 1993 May;16(5):629-34. doi: 10.1093/clind/16.5.629. PMID: 8507753.
  18. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003;16(5):429–436. DOI: 10.1097/00001432-200310000-00009. PMID: 14501995.
  19. Karthik G, Sudarsan TI, Peter JV, Sudarsanam T, Varghese GM, Kundavaram P, et al. Spectrum of cardiac manifestations and its relationship to outcomes in patients admitted with scrub typhus infection. World J Crit Care Med 2018;7(1):16–23. DOI: 10.5492/wjccm.v7.i1.16. PMID: 29430404; PMCID: PMC5797972.
  20. Sedhain A, Bhattarai GR. Renal manifestation in scrub typhus during a major outbreak in Central Nepal. Indian J Nephrol 2017;27(6):440–445. DOI: 10.4103/ijn.IJN_133_17. PMID: 29217880; PMCID: PMC5704408.
  21. Attur RP, Kuppasamy S, Bairy M, Nagaraju SP, Pammidi NR, Kamath V, et al. Acute kidney injury in scrub typhus. Clin Exp Nephrol 2013;17(5):725–729. DOI: 10.1007/s10157-012-0753-9. PMID: 23292176.
  22. Kannan K, John R, Kundu D, Dayanand D, Abhilash KPP, Mathuram AJ, et al. Performance of molecular and serologic tests for the diagnosis of scrub typhus. PLoS Negl Trop Dis 2020;14(11):e0008747. DOI: 10.1371/journal.pntd.0008747. PMID: 33180784; PMCID: PMC7660479.
  23. Aung AK, Spelman DW, Murray RJ, Graves S. Rickettsial infections in Southeast Asia: implications for local populace and febrile returned travelers. Am J Trop Med Hyg 2014;91(3):451–460. DOI: 10.4269/ajtmh.14-0191. PMID: 24957537; PMCID: PMC4155544.
  24. Lee SC, Cheng YJ, Lin CH, Lei WT, Chang HY, Lee MD, et al. Comparative effectiveness of azithromycin for treating scrub typhus: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 2017;96(36):e7992. DOI: 10.1097/MD.0000000000007992. PMID: 28885357; PMCID: PMC6392745.
  25. Rajapakse S, Rodrigo C, Fernando SD. Drug treatment of scrub typhus. Trop Doct 2011;41(1):1–4. DOI: 10.1258/td.2010.100311. PMID: 21172901.
  27. Fang Y, Huang Z, Tu C, Zhang L, Ye D, Zhu BP. Meta-analysis of drug treatment for scrub typhus in Asia. Intern Med 2012;51(17):2313–2320. DOI: 10.2169/internalmedicine.51.7816. PMID: 22975540.
  28. Ormsbee RA, Parker H, Pickens EG. The comparative effectiveness of aureomycin, terramycin, chloramphenicol erythromycin, and thiocymetin in suppressing experimental rickettsial infections in chick embryos. J Infect Dis 1955;96(2):162–167. DOI: 10.1093/infdis/96.2.162. PMID: 14367887.
  29. Raoult D, Roussellier P, Vestris G, Tamalet J. In vitro antibiotic susceptibility of Rickettsia rickettsii and Rickettsia conorii: plaque assay and microplaque colorimetric assay. J Infect Dis 1987;155(5):1059–1062. DOI: 10.1093/infdis/155.5.1059. PMID: 3104481.
  30. Holman RC, Paddock CD, Curns AT, Krebs JW, McQuiston JH, Childs JE. Analysis of risk factors for fatal Rocky Mountain spotted fever: evidence for superiority of tetracyclines for therapy. J Infect Dis 2001;184(11):1437–1444. DOI: 10.1086/324372. PMID: 11709786.
  31. Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S, et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother 2007;51(9):3259–3263. DOI: 10.1128/AAC.00508-07. PMID: 17638700; PMCID: PMC2043199.
  32. Raoult D, Gallais H, De Micco P, Casanova P. Ciprofloxacin therapy for Mediterranean spotted fever. Antimicrob Agents Chemother 1986;30(4):606–607. DOI: 10.1128/aac.30.4.606.
  33. Raoult D, Zuchelli P, Weiller PJ, Charrel C, San Marco JL, Gallais H, et al. Incidence, clinical observations and risk factors in the severe form of Mediterranean spotted fever among patients admitted to hospital in Marseilles 1983-1984. J Infect 1986;12(2):111–116. DOI: 10.1016/s0163-4453(86)93508-5.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.