Hantavirus Infection: Review of Clinical Management
Keywords:
Hantavirus, hemorrhagic fever, Renal syndrome, Hantavirus Cardiopulmonary SyndromeAbstract
Hantavirus infection is a rodent-borne zoonotic disease that can present as Hemorrhagic Fever with Renal Syndrome (HFRS) or Hantavirus Cardiopulmonary Syndrome (HCPS). Both diseases are associated with substantial morbidity and mortality. The rise of new Hantavirus species and recurrent outbreaks worldwide has renewed interest in the epidemiology, pathogenesis, diagnosis, and management of this viral infection. A narrative literature review was conducted using published articles, review papers, epidemiological reports, and clinical studies on Hantavirus up to 2026. Relevant evidence regarding epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, treatment, complications, and prevention was analyzed and synthesized.Hantaviruses primarily infect endothelial cells, leading to increased vascular permeability, thrombocytopenia, and capillary leakage through immune-mediated mechanisms. HFRS affects the kidneys, and HCPS is characterized by severe cardiopulmonary symptoms, although overlap between the two syndromes has increasingly been observed. Diagnosis is based on clinical suspicion supported by epidemiological exposure history, serological testing, and virological confirmation from reverse transcription polymerase chain reaction (RT-PCR). Current management remains largely supportive, including hemodynamic stabilization, respiratory support, and renal replacement therapy when indicated. Ribavirin may provide benefit in selected HFRS cases when given early, but evidence remains inconclusive, especially for HCPS. Favipiravir has demonstrated promising antiviral activity in vitro and in animal studies, yet clinical data in humans are still lacking. Preventive measures focus primarily on minimizing exposure to infected rodents and contaminated environments, while vaccine development remains ongoing. Hantavirus infection continues to represent an important global public health concern due to its potential for severe disease and high mortality. Improved understanding of disease pathogenesis, advances in diagnostic methods, and ongoing research into antiviral therapies and vaccines are essential to improve patient outcomes and strengthen future prevention strategies.References
Andes Virus Outbreak Working Group. Andes Hantavirus Outbreak on a Cruise Ship, 2026. New England Journal of Medicine. 0(0). doi:10.1056/NEJMc2606496
Avšič-Županc T, Saksida A, Korva M. Hantavirus infections. Clinical Microbiology and Infection. 2019 Apr 1;21:e6–16. doi:10.1111/1469-0691.12291
Jonsson CB, Figueiredo LTM, Vapalahti O. A global perspective on hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev. 2010 Apr;23(2):412–41. doi:10.1128/CMR.00062-09
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(4):419–27. doi:10.1159/000188762
Bi Z, Formenty PBH, Roth CE. Hantavirus infection: a review and global update. J Infect Dev Ctries. 2008 Feb 1;2(1):3–23. doi:10.3855/jidc.317
Klempa B. Hantaviruses and climate change. Clin Microbiol Infect. 2009 Jun;15(6):518–23. doi:10.1111/j.1469-0691.2009.02848.x
Lee HW. Epidemiology and pathogenesis of hemorrhagic fever with renal syndrome. In: Elliott RM, editor. The Bunyaviridae [Internet]. Boston, MA: Springer US; 1996 [cited 2026 May 29]. p. 253–67.
Hart CA, Bennett M. Hantavirus infections: epidemiology and pathogenesis. Microbes Infect. 1999 Dec;1(14):1229–37. doi:10.1016/s1286-4579(99)00238-5
Kementerian Kesehatan Republik Indonesia. Antisipasi peningkatan kasus, kemenkes perkuat kewaspadaan virus hanta [Internet]. 2026 [cited 2026 May 29]. Available from: https://kemkes.go.id/id/antisipasi-peningkatan-kasus-kemenkes-perkuat-kewaspadaan-virus-hanta
Heyman P, Vaheri A, Lundkvist A, Avsic-Zupanc T. Hantavirus infections in Europe: from virus carriers to a major public-health problem. Expert Rev Anti Infect Ther. 2009 Mar;7(2):205–17. doi:10.1586/14787210.7.2.205
Heyman P, Ceianu CS, Christova I, Tordo N, Beersma M, João Alves M, et al. A five-year perspective on the situation of haemorrhagic fever with renal syndrome and status of the hantavirus reservoirs in Europe, 2005-2010. Euro Surveill. 2011 Sep 8;16(36):19961. doi:10.2807/ese.16.36.19961-en
Vapalahti O, Mustonen J, Lundkvist A, Henttonen H, Plyusnin A, Vaheri A. Hantavirus infections in Europe. Lancet Infect Dis. 2003 Oct;3(10):653–61. doi:10.1016/s1473-3099(03)00774-6
Vapalahti O, Lundkvist A, Vaheri A. Human immune response, host genetics, and severity of disease. Curr Top Microbiol Immunol. 2001;256:153–69. doi:10.1007/978-3-642-56753-7_9
Terajima M, Hayasaka D, Maeda K, Ennis FA. Immunopathogenesis of hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome: Do CD8+ T cells trigger capillary leakage in viral hemorrhagic fevers? Immunol Lett. 2007 Nov 15;113(2):117–20. doi:10.1016/j.imlet.2007.08.003
Ala-Houhala I, Koskinen M, Ahola T, et al. Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus. Nephrol Dial Transplant. 2002 Feb;17(2):246–52. doi:10.1093/ndt/17.2.246
Settergren B. Clinical aspects of nephropathia epidemica (Puumala virus infection) in Europe: a review. Scand J Infect Dis. 2000;32(2):125–32. doi:10.1080/003655400750045204
Enria DA, Briggiler AM, Pini N, Levis S. Clinical manifestations of New World hantaviruses. Curr Top Microbiol Immunol. 2001;256:117–34. doi:10.1007/978-3-642-56753-7_7
Vial PA, Ferrés M, Vial C, et al. Hantavirus in humans: a review of clinical aspects and management. The Lancet Infectious Diseases. 2023 Sep 1;23(9):e371–82. doi:10.1016/S1473-3099(23)00128-7
As AK, John J. Hantavirus: A comprehensive contemporary review of virology, global epidemiology, clinical variants, diagnosis, treatment, and intensive care management. Indian Journal of Critical Care Medicine. 2026 May 25;30(5):430–42. doi:10.5005/jp-journals-10071-25215
Aitichou M, Saleh SS, McElroy AK, Schmaljohn C, Ibrahim MS. Identification of Dobrava, Hantaan, Seoul, and Puumala viruses by one-step real-time RT-PCR. J Virol Methods. 2005 Mar;124(1–2):21–6. doi:10.1016/j.jviromet.2004.10.004
Hujakka H, Koistinen V, Kuronen I, et al. Diagnostic rapid tests for acute hantavirus infections: specific tests for Hantaan, Dobrava and Puumala viruses versus a hantavirus combination test. J Virol Methods. 2003 Mar;108(1):117–22. doi:10.1016/s0166-0934(02)00282-3
Kallio-Kokko H, Vapalahti O, Lundkvist A, Vaheri A. Evaluation of Puumala virus IgG and IgM enzyme immunoassays based on recombinant baculovirus-expressed nucleocapsid protein for early nephropathia epidemica diagnosis. Clin Diagn Virol. 1998 May 1;10(1):83–90. doi:10.1016/s0928-0197(97)10019-8
Huggins JW, Hsiang CM, Cosgriff TM, et al. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis. 1991 Dec;164(6):1119–27. doi:10.1093/infdis/164.6.1119
Rusnak JM, Byrne WR, Chung KN, et al. Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea. Antiviral Res. 2009 Jan;81(1):68–76. doi:10.1016/j.antiviral.2008.09.007
Mertz G, Miedzinski L, Goade D, et al. Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2004;39 9:1307–13. doi:10.1086/425007
Vial PA, Valdivieso F, Ferres M, et al. High-dose intravenous methylprednisolone for Hantavirus cardiopulmonary syndrome in Chile: A double-blind, randomized controlled clinical trial. Clin Infect Dis. 2013 Oct 1;57(7):943–51. doi:10.1093/cid/cit394
Moreli ML, Marques-Silva AC, Pimentel VA, da Costa VG. Effectiveness of the ribavirin in treatment of hantavirus infections in the Americas and Eurasia: a meta-analysis. VirusDis. 2014 Sep 1;25(3):385–9. doi:10.1007/s13337-014-0219-7
Safronetz D, Falzarano D, Scott DP, Furuta Y, Feldmann H, Gowen BB. Antiviral efficacy of Favipiravir against two prominent etiological agents of hantavirus pulmonary syndrome. Antimicrob Agents Chemother. 2013 Oct;57(10):4673–80. doi:10.1128/AAC.00886-13
Mayor J, Engler O, Rothenberger S. Antiviral efficacy of Ribavirin and Favipiravir against Hanta virus. Microorganisms. 2021 Jun 15;9(6):1306. doi:10.3390/microorganisms9061306
Karanfilovski V, Gjorgjievski N, Dzekova-Vidimliski P, et al. Beyond the kidneys: Pulmonary-renal involvement in Hantavirus infection - A 10-year experience. Indian Journal of Nephrology. 2026. doi:10.25259/ijn_639_2025
Latus J, Schwab M, Tacconelli E, et al. Clinical course and long-term outcome of Hantavirus-associated nephropathia epidemica, Germany. Emerging Infectious Diseases. 2015;21:76–83. doi:10.3201/eid2101.140861
Yi Y, Park H, Jung J. Effectiveness of inactivated hantavirus vaccine on the disease severity of hemorrhagic fever with renal syndrome. Kidney Res Clin Pract. 2018 Dec;37(4):366–72. doi:10.23876/j.krcp.18.0044.
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