pISSN 2093-2340   eISSN 2092-6448
Indexed in ESCI, PubMed, Scopus, DOAJ and more
Open Access, Peer-reviewed
    Infect Chemother. 2009 Nov-Dec;41(6):323-332. Korean.
    Published online Dec 31, 2009.
    https://doi.org/10.3947/ic.2009.41.6.323
    Copyright © 2009 The Korean Society of Infectious Diseases; The Korean Society for Chemotherapy
    Review

    Hemorrhagic Fever with Renal Syndrome

    Hyo Youl Kim, M.D.
      • Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
    • Corresponding author: Hyo Youl Kim, M.D., Ph.D. Division of Infectious Diseases, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162, Ilsan-dong, Wonju, Gangwon-do 220-701, Korea. Tel: +82-33-741-1206, Fax: +82-33-748-1206, Email: hyksos@yonsei.ac.kr
    Received September 19, 2009.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Hemorrhagic fever with renal syndrome (HFRS) is an acute febrile illness caused by Eurasian hantaviruses and characterized by renal insufficiency, hemorrhage, thrombocytopenia, and shock. Each hantavirus is primarily associated with a single rodent host species or genus, and is transmitted to human via aerosols of rodent excreta. During the last decades, clinical features of HFRS in Korea have changed with mild degree of hypotension and very low prevalence of oliguria. Treatment of HFRS is mainly supportive. Recently, however, treatment of HFRS patients with ribavirin in China and Korea, within 7 days after the onset of fever, resulted in a reduced mortality as well as shortened course of illness. Although a commercial inactivated Hantaan virus vaccine has been on the market in Korea for more than 15 years, the effect of vaccination is not clear. Further efforts are necessary to develop safer and more effective hantavirus vaccines.

    Keywords
    Hemorrhagic fever with renal syndrome; Hantavirus; Hantaan virus

    Figures

    Figure 1
    Reported cases of hemorrhagic fever with renal syndrome by year in Korea (Data source: Korea centers for disease control and prevention).

    Figure 2
    Schematic representation of hantavirus morphology. The single-stranded RNA segments S (small), M (medium), and L (large) are encoded for the nucleocapsid protein, the glycoprotein G1 and G2, and the RNA-dependent RNA polymerase, respectively.

    Tables

    Table 1
    Main Natural Reservoirs and Geographic Distribution of Hantaviruses

    Table 2
    Hantavirus Vaccines Tested in Humans

    References

      1. Krüger DH, Ulrich R, Lundkvist AA. Hantavirus infections and their prevention. Microbes Infect 2001;3:1129–1144.
      1. Lee JS. Clinical features of hemorrhagic fever with renal syndrome in Korea. Kidney Int Suppl 1991;35:S88–S93.
      1. Muranyi W, Bahr U, Zeier M, van der Woude FJ. Hantavirus infection. J Am Soc Nephrol 2005;16:3669–3679.
      1. Lee NS, Kim HY, Chae MH, Kim EM, Park SY, Han SH, Kwon OG, Uh Y. The influence of vaccination on the clinical features of hemorrhagic fever with renal syndrome in the last 5 years. Korean J Med 2009;76:459–466.
      1. Kim HJ, Han SW. Diagnostic challenge of hemorrhagic fever with renal syndrome on admission before its serological confirmation. Korean J Nephrol 2004;23:82–91.
      1. Johnson KM. Hantaviruses: history and overview. Curr Top Microbiol Immunol 2001;256:1–14.
      1. Lee JK, Hwang SI. Hemorrhagic fever with renal syndrome: Historical aspects. Korean J Med Hist 2004;13:37–61.
      1. Smadel JE. Epidemic hemorrhagic fever. Am J Public Health Nations Health 1953;43:1327–1330.
      1. Lee HW, Lee PW, Johnson KM. Isolation of the etiologic agent of Korean Hemorrhagic fever. J Infect Dis 1978;137:298–308.
      1. Gajdusek DC. Virus hemorrhagic fevers. Special reference to hemorrhagic fever with renal syndrome (epidemic hemorrhagic fever). J Pediatr 1962;60:841–857.
      1. World Health Organization. Bull World Health Organ. 61. 1983. Haemorrhagic fever with renal syndrome: memorandum from a WHO meeting; pp. 269-275.
      1. Nichol ST, Spiropoulou CF, Morzunov S, Rollin PE, Ksiazek TG, Feldmann H, Sanchez A, Childs J, Zaki S, Peters CJ. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 1993;262:914–917.
      1. Vapalahti O, Mustonen J, Lundkvist A, Henttonen H, Plyusnin A, Vaheri A. Hantavirus infections in Europe. Lancet Infect Dis 2003;3:653–661.
      1. Lee HW. Hemorrhagic fever with renal syndrome in Korea. Rev Infect Dis 1989;11 Suppl 4:S864–S876.
      1. Bruno P, Hassell LH, Brown J, Tanner W, Lau A. The protean manifestations of hemorrhagic fever with renal syndrome. A retrospective review of 26 cases from Korea. Ann Intern Med 1990;113:385–391.
      1. Kim YK, Lee SC, Kim C, Heo ST, Choi C, Kim JM. Clinical and laboratory predictors of oliguric renal failure in haemorrhagic fever with renal syndrome caused by Hantaan virus. J Infect 2007;54:381–386.
      1. Kim YS, Ahn C, Han JS, Kim S, Lee JS, Lee PW. Hemorrhagic fever with renal syndrome caused by the Seoul virus. Nephron 1995;71:419–427.
      1. Lee HW. Epidemiology and epizoology. In: Lee HW, Calisher C, Schmaljohn C, editors. Manual of Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Seoul: ASAN Institute for Life Sciences; 1999. pp. 39.
      1. Song JY, Chun BC, Kim SD, Baek LJ, Kim SH, Sohn JW, Cheong HJ, Kim WJ, Park SC, Kim MJ. Epidemiology of hemorrhagic fever with renal syndrome in endemic area of the Republic of Korea, 1995-1998. J Korean Med Sci 2006;21:614–620.
      1. Lednicky JA. Hantaviruses. a short review. Arch Pathol Lab Med 2003;127:30–35.
      1. Zeier M, Handermann M, Bahr U, Rensch B, Müller S, Kehm R, Muranyi W, Darai G. New ecological aspects of hantavirus infection: a change of a paradigm and a challenge of prevention-a review. Virus Genes 2005;30:157–180.
      1. Maes P, Clement J, Gavrilovskaya I, Van Ranst >M. Hantaviruses: immunology, treatment, and prevention. Viral Immunol 2004;17:481–497.
      1. Song JW, Moon SS, Gu SH, Song KJ, Baek LJ, Kim HC, Kijek T, O'Guinn ML, Lee JS, Turell MJ, Klein TA. Hemorrhagic fever with renal syndrome in 4 US soldiers, South Korea, 2005. Emerg Infect Dis 2009;15:1833–1836.
      1. Baek LJ, Kariwa H, Lokugamage K, Yoshimatsu K, Arikawa J, Takashima I, Kang JI, Moon SS, Chung SY, Kim EJ, Kang HJ, Song KJ, Klein TA, Yanagihara R, Song JW. Soochong virus: an antigenically and genetically distinct hantavirus isolated from Apodemus peninsulae in Korea. J Med Virol 2006;78:290–297.
      1. Song KJ, Baek LJ, Moon S, Ha SJ, Kim SH, Park KS, Klein TA, Sames W, Kim HC, Lee JS, Yanagihara R, Song JW. Muju virus, a novel hantavirus harboured by the arvicolid rodent Myodes regulus in Korea. J Gen Virol 2007;88(Pt 11):3121–3129.
      1. Song JW, Kang HJ, Gu SH, Moon SS, Bennett SN, Song KJ, Baek LJ, Kim HC, O'Guinn ML, Chong ST, Klein TA, Yanagihara R. Characterization of Imjin virus, a newly isolated hantavirus from the Ussuri white-toothed shrew (Crocidura lasiura). J Virol 2009;83:6184–6191.
      1. Nemirov K, Henttonen H, Vaheri A, Plyusnin A. Phylogenetic evidence for host switching in the evolution of hantaviruses carried by Apodemus mice. Virus Res 2002;90:207–215.
      1. Cosgriff TM. Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome. Rev Infect Dis 1991;13:97–107.
      1. Van Epps HL, Schmaljohn CS, Ennis FA. Human memory cytotoxic T-lymphocyte (CTL) responses to Hantaan virus infection: identification of virus-specific and cross-reactive CD8(+) CTL epitopes on nucleocapsid protein. J Virol 1999;73:5301–5308.
      1. Linderholm M, Ahlm C, Settergren B, Waage A, Tärnvik A. Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J Infect Dis 1996;173:38–43.
      1. Groeneveld PH, Colson P, Kwappenberg KM, Clement J. Increased production of nitric oxide in patients infected with the European variant of hantavirus. Scand J Infect Dis 1995;27:453–456.
      1. Papadimitriou M. Hantavirus nephropathy. Kidney Int 1995;48:887–902.
      1. Lee EJ, Kim YS, Kwon HM, Kwon YJ, Cho WY, Kim HK, Won NH. Clinical significance of renal biopsy in hemorrhagic fever with renal syndrome. Korean J Med 1991;40:642–652.
      1. Mäkelä S, Mustonen J, Ala-Houhala I, Hurme M, Partanen J, Vapalahti O, Vaheri A, Pasternack A. Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha (-308) G/A polymorphism. J Infect Dis 2002;186:843–846.
      1. Mustonen J, Partanen J, Kanerva M, Pietilä K, Vapalahti O, Pasternack A, Vaheri A. Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus. Scand J Immunol 1998;47:277–279.
      1. Kim YO, Yoon SA, Ku YM, Yang CW, Kim YS, Kim SY, Choi EJ, Chang YS, Bang BK. Serum albumin level correlates with disease severity in patients with hemorrhagic fever with renal syndrome. J Korean Med Sci 2003;18:696–700.
      1. Kim BN, Choi BD. Hemorrhagic fever with renal syndrome complicated with pregnancy: a case Report. Korean J Intern Med 2006;21:150–153.
      1. Hujakka H, Koistinen V, Kuronen I, Eerikäinen P, Parviainen M, Lundkvist A, Vaheri A, Vapalahti O, Närvänen A. Diagnostic rapid tests for acute hantavirus infections: specific tests for Hantaan, Dobrava and Puumala viruses versus a hantavirus combination test. J Virol Methods 2003;108:117–122.
      1. Woo HJ, Cheong HJ, Kim WJ, Kim MJ, Park SC, Baek LJ. Diagnosis of acute Hantaan virus infection by IgG avidity assay. Korean J Med 1999;56:629–635.
      1. Nam JH, Yu CH, Hwang KA, Ju YR. Real-time rt-PCR of hantaan virus RNA used for the detection of virus response to antiviral drugs. Acta Virol 2008;52:67–70.
      1. Huggins JW, Hsiang CM, Cosgriff TM, Guang MY, Smith JI, Wu ZO, LeDuc JW, Zheng ZM, Meegan JM, Wang QN, Oland DD, Gui XE, Gibbs PH, Yuan GH, Zhzng TM. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis 1991;164:1119–1127.
      1. Rusnak JM, Byrne WR, Chung KN, Gibbs PH, Kim TT, Boudreau EF, Cosgriff T, Pittman P, Kim KY, Erlichman MS, Rezvani DF, Huggins JW. Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea. Antiviral Res 2009;81:68–76.
      1. Lee CH, Byun KS, Kim WJ, Woo YD, Lee HW. Persistence of antibodies after immunization with the inactivated vaccine against hemorrhagic fever with renal syndrome in humans. J Korean Soc Virol 1992;22:239–243.
      1. Sohn YM, Rho HO, Park MS, Kim JS, Summers PL. Primary humoral immune responses to formalin inactivated hemorrhagic fever with renal syndrome vaccine (Hantavax®): consideration of active immunization in South Korea. Yonsei Med J 2001;42:278–284.
      1. The Korean Society of Infectious Diseases. Vaccination for adults. Seoul: Koonja Publishing Co.; 2007.
      1. Park K, Kim CS, Moon KT. Protective effectiveness of hantavirus vaccine. Emerg Infect Dis 2004;10:2218–2220.
      1. Woo YD, Chu YK, Baek LJ, Lee HW. An immunoserological study of vaccine against haemorrhagic fever with renal syndrome. J Korean Soc Virol 2000;30:11–18.
      1. Cho HW, Howard CR. Antibody responses in humans to an inactivated hantavirus vaccine (Hantavax). Vaccine 1999;17:2569–2575.
      1. Chu YK, Woo YD, Lee HW. Immune response and antibody persistence against Hantaan virus of vaccinees with Hantavax™. Korean J Infect Dis 1998;30:317–324.
      1. Chu YK, Gligic A, Tomanovic S, Bozovjc B, Obradovic M, Woo YD, An CN, Kim H, Jiang YS, Park SC, Kim MJ, Lee EI, Lee HW. A field efficacy trial of inactivated Hantaan virus vaccine (Hantavax™) against hemorrhagic Fever with Renal Syndrome (HFRS) in the Endemic Areas of Yugoslavia from 1996 to 1998. J Korean Soc Virol 1999;29:55–64.
      1. Schmaljohn C. Vaccines for hantaviruses. Vaccine 2009;27 Suppl 4:D61–D64.
      1. McClain DJ, Summers PL, Harrison SA, Schmaljohn AL, Schmaljohn CS. Clinical evaluation of a vaccinia- vectored Hantaan virus vaccine. J Med Virol 2000;60:77–85.
    Cited by
    Crossref 8
    Google Scholar 
    MeSH Terms
    Aerosols
    China
    Fever
    Hantaan virus
    Hantavirus
    Hemorrhage
    Hemorrhagic Fever with Renal Syndrome
    Humans
    Hypotension
    Korea
    Oliguria
    Prevalence
    Renal Insufficiency
    Ribavirin
    Rodentia
    Shock
    Thrombocytopenia
    Vaccination
    Vaccines
    Metrics
    Share
    Figures
    slide
    slide

    1 / 2

    Tables
    slide
    slide

    1 / 2

    PERMALINK