Hemorrhagic Fever with Renal Syndrome (Hantaviruses)

Hantaviruslar Bunyaviridae ailesinin Hantavirus cinsinde yer alan zarflı RNA viruslarıdır. Bu etkenler vahşi kemirgen ve böcekçigillerin bilinen parazitlerindendir. Dünya genelinde birçok tür bu viruslarla enfektedir. Her Hantavirus tipi kendine özgül kemirgen türü ile taşınır. İnsan bulaşı virus içeren aerosolleşmiş partiküllerin inhalasyonu veya enfekte kemirgenin idrar, dışkı veya sekresyonları ile direkt temas sonucu gerçekleşir. Hantaviruslar iki tip zoonotik enfeksiyona neden olur; Hemorajik ateşle seyreden renal sendrom (HFRS) ve Hantavirus pulmoner sendrom (HPS). Ekolojik ve çevresel değişimler, kemirici populasyonundaki değişiklikler, virusun dış ortama dayanıklığı ve kemirici maruziyetini artıran insan yaşam tarzındaki değişimler HFRS insidansını artıran en önemli nedenlerdendir. HFRS enfeksiyonlarının en belirgin özelliği ateş, hipotansiyon, kanama ve akut tübülointerstisiyal nefritle seyreden akut böbrek yetmezliğidir. Hastalığın kliniği HFRS virus tiplerine göre değişir. Avrupada sık görülen PUUV enfeksiyonu en hafif seyirli tiptir ve olguların 90% kadarı asemptomatiktir. HFRS tanısında serolojik testler, moleküler testler ve virolojik hücre kültürü kullanılmaktadır. HFRS için Food and Drug Administration (FDA) tarafından onaylanmış antiviral ilaç, immünolojik tedavi veya aşı yoktur. Ribavirin hayvan modellerinde mortaliteyi azaltıyor gibi görülse de HFRS enfeksiyonlarında deneyim azdır. HFRS tedavisinde destek tedavisi temel yaklaşımdır. Korunmada kemirgenlerle maruziyetin sıklığı ve şiddetini azaltıcı yöntemler çok önemlidir

Hemorrhagic Fever with Renal Syndrome (Hantaviruses)

Hantaviruses are enveloped RNA viruses belonging to the genus Hantavirus, family Bunyaviridae. These agents are usual parasites of wild rodents and insectivores. Many species worldwide are infected with these viruses and each Hantavirus type is carried by its own type specific rodent species. Human transmission occurs accidentally by inhalation of aerosolized virus containing particles, contact with urine, feces or secretions of infected rodents. Hantavirus leads to two type of zoonotic infections; Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS). Ecological and environmental changes, alterations in rodent population size, viral durability in nature, and changes in human life style that augment rodent exposure are the main causes that may affect the incidence of HFRS infection. The hallmarks of HFRS infection are fever, hypotension, hemorrhage and acute renal failure with acute interstitial nephritis. Clinical course of the disease varies between HFRS virus types. PUUV infection that is mostly seen in Europe has the mildest course and up to 90% of the cases are asymptomatic. Serological tests, molecular tests and virologic cell culture are used for HFRS diagnosis. There is no specific antiviral drug, immunotherapy or vaccine approved by Food and Drug Administration (FDA). Although ribavirin seems to decrease mortality in animal models; there are few data in the literature considering the effect of ribavirin on HFRS infections. Control and management of the symptoms with supportive care is the main modality for HFRS treatment. Reduction of the frequency and intensity of rodent exposure is very important for the prevention.

___

  • 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;7:205-217.
  • Jonsson CB, Figueiredo LT, Vapalahti O. A global perspective on Hantavirus ecology, epidemiology, and disease. Clin Mi- crobiol Rev 2010;23:412-41.
  • Appel GB, Mustonen J. Renal involvement with Hantavirus in- fection (hemorrhagic fever with renal syndrome). UpToDate. Available from: http://www.uptodate.com/online/content/ topic.do?topicKey=renlfail/9308&selectedTitle=2%7E20&so urce=search_result.
  • Korukluoglu G. Hantavirus. Türk Hij Den Biyol Derg 2011;68 (Suppl. 1):29-33.
  • Lee HW, Lee PW, Johnson KM. Isolation of the etiologic agent of Korean Hemorrhagic fever. J Infect Dis 1978;137:298– 308.
  • Smadel JE. Epidemic hemorrhagic fever. Am J Public Health Nations Health 1953;43:1327–1330.
  • Schmaljohn C, Hjelle B. Hantaviruses: a global disease prob- lem. Emerg Infect Dis 1997;3:95–104.
  • Simpson SQ, Spikes L, Patel S, Faruqi I. Hantavirus pulmo- nary syndrome. Infect Dis Clin North Am 2010;24:159-173.
  • Hjelle B. Hantavirus cardiopulmonary syndrome. UpToDate. Available from: “http://www.uptodate.com/contents/Hantavi- rus-cardiopulmonary-syndrome?source=related_link.
  • Nichol ST, Spiropoulou CF, Morzunov S, et al. Genetic identi- fication of a Hantavirus associated with an outbreak of acute respiratory illness. Science 1993;262:914–917.
  • Ksiazek TG, Peters CJ, Rollin PE, et al. Identification of a new North American Hantavirus that causes acute pulmo- nary insufficiency. Am J Trop Med Hyg 1995;52:117–123.
  • Fulhorst CF, Koster FT, Enría DA, Peters CJ. Hantavirus Infections. In: Guerrant LG, Walker DH, Weller PF. Tropical Infectious Diseases: Principles, Pathogens and Practice, Third Edition. 2011:470-480.
  • Kariwa H, Yoshimatsu K, Arikawa J. Hantavirus infection in East Asia. Comp Immunol Microbiol Infect Dis 2007;30:341- 356.
  • Manigold T, Vial P. Human Hantavirus infections: epidemiol- ogy, clinical features, pathogenesis and immunology. Swiss Med Wkly 2014;144:w13937.
  • Çelebi G. Hantavirus Infections. Klimik Journal 2011;24:139- 149.
  • Ertek M, Buzgan T. An outbreak caused by Hantavirus in the Black Sea region of Turkey, January-May 2009. Eurosurveil- lance 14,20.
  • Gozalan A, Kalaycioğlu H, Uyar Y, et al. Human Puumala and Dobrava Hantavirus Infections in the Black Sea Region of Turkey: A Cross-Sectional Study. Vector-Borne Zoon. Dis 2013;13:111-118.
  • Kaya S, Yılmaz G, Erensoy S, et al. Hantavirus Infection: Two Case reports from a province in the eastern blacksea region, Turkey. Mikrobiyol Bul 2010;44:479-487.
  • Kebapcı N, Mıstık R, Heper Y, et al. Renal sendromla seyre- den bir hantavirus infeksiyonu olgusu. In: Akhan S. ed. 15. Türk Mikrobiyoloji ve Infeksiyon Hastalıkları Kongresi (23-27 Mart 2011, Antalya) Kongre Kitabı. Istanbul: Türk Klinik Mi- krobiyoloji ve Infeksiyon Hastalıkları Dernegi, 2011:322-323. (Congress book, in Turkish).
  • Oncul O, Atalay Y, Onem Y, et al. Hantavirus infection in Istanbul,Turkey [Letter] Emerg Infect Dis 2011;17:303-304.
  • Sunbul M, Yılmaz H, Cetinkaya H, et al. Two cases of Hanta- virus infection in Crimean-Congo Haemorrhagic Fever en- demic region. J Microbiol Infect Dis 2012;2:117-120.
  • Ulu Kılıc A, Caglayık Yagcı D, Dede G, et al. A Hantavirus in- fection case report from rural area of Kazan district, Ankara. Turk Hij Den Biyol Derg 2013;70:27-32.
  • Jameson LJ, Taori SK, Atkinson B, et al. Pet rats as a source of Hantavirus in England and Wales, 2013. Euro Surveill; 2013;18:8–10.
  • Taori SK, Jameson LJ, Campbell A, et al. UK Hantavirus, renal failure, and pet rats. Lancet 2013;381(9871):1070.
  • Lundkvist A, Verner-Carlsson J, Plyusnina A, et al. Pet rat harbouring Seoul Hantavirus in Sweden, June 2013. Euro Surveill 2013;18:20521.
  • Olsson GE, Dalerum F, Hörnfeldt B, et al. Human Hantavirus infections, Sweden. Emerg Infect Dis 2003;9:1395-1401.
  • Heyman P, Vaheri A; ENIVD Members. Situation of Hantavi- rus infections and haemorrhagic fever with renal syndrome in European countries as of December 2006. Euro Surveill 2008;13:18925.
  • Palo RT. Time series analysis performed on nephropathia epidemica in humans of northern Sweden in relation to bank vole population dynamic and the NAO index. Zoonoses Pub- lic Health 2009;56:150-156.
  • Pettersson L, Boman J, Juto P, et al. Outbreak of Puumala virus infection, Sweden. Emerg Infect Dis 2008;14:808-810.
  • Dearing MD, Dizney L. Ecology of Hantavirus in a changing world. Ann NY Acad Sci 2010;1195:99-112.
  • Evander M, Ahlm C. Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever vi- rus. Glob Health Action 2009;2:16.
  • Klempa B. Hantaviruses and climate change. Clin Microbiol Infect 2009;15:518-523.
  • Yan L, Fang LQ, Huang HG, et al. Landscape elements and Hantaan virus-related hemorrhagic fever with renal syndrome, People’s Republic of China. Emerg Infect Dis 2007;13:1301-1306.
  • Hjelle B. Epidemiology and diagnosis of Hantavirus infec- tions. UpToDate. Available from: http://www.uptodate. com/contents/epidemiology-and-diagnosis-of-Hantavirus- infections?source=related_link.
  • Torres-Pérez F, Wilson L, Collinge SK, et al. Sin Nombre Vi- rus Infection in Field Workers, Colorado, USA. Emerg Infect Dis 2010;16:308-310.
  • Merino C, Arias A, Castillo C. First Case of Hantavirus Car- diopulmonary Syndrome Occurring after a Rodent Bite. Rev Chil Enf Respir 2002;18:199-205.
  • Bi Z, Formenty PB, Roth CE. Hantavirus infection: a review and global update. J Infect Dev Ctries 2008;2:3-23.
  • Bhimma R. Hemorrhagic Fever With Renal Failure Syn- drome. Medscape Available from: http://emedicine.med- scape.com/article/982142-overview
  • Mustonen J, Helin H, Pietila K, et al. Renal biopsy findings and clinicopathologic correlations in nephropathia epidemi- ca. Clin Nephrol 1994;41:121.
  • Collan Y, Mihatsch MJ, Lähdevirta J, et al. Nephropathia epidemica: mild variant of hemorrhagic fever with renal syn- drome. Kidney Int Suppl 1991;35:S62.
  • Heiske A, Anheier B, Pilaski J, et al. Polymerase chain reac- tion detection of Puumala virus RNA in formaldehyde-fixed biopsy material. Kidney Int 1999;55:2062.
  • Schonrich G, Rang A, Lutteke N, et al. Hantavirus-induced immunity in rodent reservoirs and humans. Immunol Rev 2008;225:163-189.
  • Nichol ST. Bunyaviruses. In: Knipe DM, Howley PM, eds. Field’s Virology Vol 2, 4th ed. Philadelphia, Pa Lippincott Wil- liams Wilkins 2001:1603–1633.
  • Vaheri A, Strandin T, Hepojoki J, et al. Uncovering the myster- ies of Hantavirus infections. Nat Rev Microbiol 2013;11:539- 550.
  • Peters CJ. California Encephalitis, Hantavirus Pulmonary Syndrome, and Bunyavirid Hemorrhagic Fevers In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed. 2009:2289-2293.
  • Al Hazmi M, Ayoola EA, Abdurahman M, et al: Epidemic Rift Valley fever in Saudi Arabia: a clinical study of severe illness in humans. Clin Infect Dis 2003;36:245-252.
  • Burt FJ, Swanepoel R, Shieh W-J, et al. Immunohistochemi- cal and in situ localization of Crimean-Congo hemorrhagic fever virus in human tissues and pathogenic implications. Arch Pathol Lab Med 1997;121:839.
  • Deyde VM, Khristova ML, Rollin PE, et al. Crimean-Congo hemorrhagic fever virus genomics and global diversity. J Vi- rol 2006;80:8834-8842.
  • Lee JS, Cho BY, Lee MC, et al. Clinical features of sero- logically proven Korean hemorrhagic fever patients. Seoul J Med 1980;21:163.
  • Laine O et al. Enhanced thrombin formation and fibrinoly- sis during acute Puumala Hantavirus infection. Thromb Res 2010;126:154.
  • Peters CJ, Simpson G, Levy H, et al. Spectrum of Hantavirus infection: hemorrhagic fever with renal syndrome and Hanta- virus pulmonary syndrome. Annu Rev Med 1999;50:531-545.
  • Kleinknecht D, Rollin PE. Hypertension after hemorrhagic fe- ver with renal syndrome. Nephron 1992;61:121.
  • Novo R, Gagnadoux MF, Le Guenno Y, et al. Chronic re- nal failure after Puumala virus infection. Pediatr Nephrol 1999;13:934.
  • Mäkelä S, et al. Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala Hantavirus infec- tion than the tumor necrosis factor-alpha(-308) G/A polymor- phism. J Infect Dis 2002;186:843.
  • Mustonen J, Partanen J, Kanerva M, et al. Genetic suscepti- bility to severe course of nephropathia epidemica caused by Puumala Hantavirus. Kidney Int 1996;49:217-221.
  • Mustonen J, Partanen J, Kanerva M, et al. Association of HLA B27 with benign clinical course of nephropathia epi- demica caused by Puumala Hantavirus. Scand J Immunol. 1998;47:277-279.
  • Geimonen E, LaMonica R, Springer K, et al. Hantavirus pulmonary syndrome-associated Hantaviruses contain conserved and functional ITAM signaling elements. J Virol 2003;77:1638-1643.
  • Plyusnin A, Horling J, Kanerva M, et al. Puumala Hantavirus genome inpatients with nephropathia epidemica: Correla- tion of PCR positivity with HLA haplotype and link to viral sequences in local rodents. J Clin Microbiol 1997;35:1090- 1096.
  • Evander M, Eriksson I, Pettersson L. et al. Puumala Hanta- virus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome. J Clin Microbiol 2007;45:2491-2497.
  • Vaheri A, Vapalahti O, Plyusnin A. How to diagnose Hanta- virus infections and detect them in rodents and insectivores. Rev Med Virol 2008;18:277-288.
  • Machado AM, de Figueiredo GG, dos Santos Jr GS, Moraes Figueiredo LT. Laboratory diagnosis of human Hantavirus infection: novel insights and future potential. Future Virol 2009;4:383-389.
  • 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;164:1119-1127.
  • 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; 81: 68-76.
  • Bharadwaj M, Nofchissey R, Goade D, et al. Humoral im- mune responses in the Hantavirus cardiopulmonary syn- drome. J Infect Dis 2000;182:43-48.
  • Ye C, Prescott J, Nofchissey R, et al. Neutralizing Antibodies and Sin Nombre Virus RNA after Recovery from Hantavirus Cardiopulmonary Syndrome. Emerg Infect Dis 2004;10:478- 482.
  • Kariwa H, Arikawa J, Takashima I, Hashimoto N. Development and application of protein G antibody assay for the detection of antibody to Hantavirus. J Virol Methods 1992;37:345–354.
  • Schmaljohn CS, Chu YK, Schmaljohn AL, Dalrymple JM. An- tigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants. J Virol 1990;64:3162–3170.
  • Klingstrom J, Stoltz M, Hardestam J, et al. Passive immu- nization protects cynomolgus macaques against Puumala Hantavirus challenge. Antivir Ther 2008;13:125–133.
  • Schmaljohn C. Vaccines for Hantaviruses. Vaccine, 2009;27 (Suppl 4):61-64.
  • Hooper JW, Li D: Vaccines against Hantaviruses. Curr Top Microbiol Immunol 2001;256:171-191.
  • Dong GM, Han L, An Q, et al. Immunization effect of purified bivalent vaccine to haemorrhagic fever with renal syndrome manufactured from primary cultured hamster kidney cells. Chin Med J (Engl) 2005;118:766-768.
  • Schmaljohn C, Hasty SE, Dalrymple JM, et al: Preparation of candidate vaccinia-vectored vaccines for haemorrhagic fever with renal syndrome. Vaccine 1992;10:10-13.
  • McClain DJ, Summers PL, Harrison SA, et al: Clinical evalu- ation of a vaccinia-vectored Hantaan virus vaccine. J Med Virol 2000;60:77-85.
  • Chu YK, Jennings GB, Schmaljohn CS, et al. A vaccinia vi- rus-vectored Hantaan virus vaccine protects hamsters from challenge with Hantaan and Seoul viruses but not Puumala virus. J Virol 1995;69:6417-6423.
  • Hooper JW, Custer DM, Thompson E, et al. DNA vaccination with the Hantaan virus M gene protects Hamsters against three of four HFRS Hantaviruses and elicits a high-titer neutralizing antibody response in Rhesus monkeys. J Virol 2001;75:8469-8477.