Pediatric Viral Hemorrhagic Fevers
- Author: Martha L Muller, MD; Chief Editor: Russell W Steele, MD more...
The 12 distinct enveloped RNA viruses that cause most viral hemorrhagic fever (VHF) cases are members of 4 families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. Disease severity resulting from infection by these agents varies widely, but the most extreme manifestations include circulatory instability, increased vascular permeability, and diffuse hemorrhage. In May 1995, these diseases came to worldwide attention with an outbreak of Ebola virus near the city of Kikwik, Zaire. With increased international travel, these primarily tropical viruses may now be imported into nonendemic countries. Furthermore, several of these agents have been associated with nosocomial outbreaks involving health care workers and laboratory personnel.
See Ebola: Care, Recommendations, and Protecting Practitioners, a Critical Images slideshow, to review treatment, recommendations, and safeguards for healthcare personnel.
Viral hemorrhagic fevers share many common features. Infectious agents that are arthropod-borne (usually mosquitoes) cause many viral hemorrhagic fevers. For several viral hemorrhagic fevers, person-to-person transmission may occur through direct contact with infected patients, their blood, or their secretions and excretions. Animal reservoirs are generally rats and mice, but domestic livestock, monkeys, and other primates may also serve as intermediate hosts.
Yellow fever (the prototype virus of the Flaviviridae family), dengue, Hantavirus pulmonary syndrome (HPS), and hemorrhagic fever with renal failure syndrome (HFRS) are discussed in separate chapters (see Differentials). The other flaviviral hemorrhagic fevers (HFs), Alkhurma HF virus,[2, 3, 4] Kyasanur Forest disease, and Omsk HF, are described only in cursory detail because they have very limited geographic distribution and/or have virtually disappeared from the endemic zones in which they were previously found.
Novel viruses have recently been identified.[6, 7]
Although common themes occur, the different viruses display variable pathophysiology. Hemorrhage is typically present in many organs, and effusions are common in serous cavities (although they may be minimal or absent in some patients). Widespread necrosis generally occurs, may be present in any organ system, and varies from modest and focal to massive in extent. Liver and lymphoid systems are usually extensively involved, and the lung regularly demonstrates varying degrees of interstitial pneumonitis, diffuse alveolar damage, and hemorrhage. Acute tubular necrosis and microvascular thrombosis may also be observed. The inflammatory response is usually minimal.
Aside from the bunyaviral HPS (Bayou, Black Creek Canal, Four Corners, Muleshoe, Sin Nombre), which appears to be associated with rodent-contaminated, abandoned, and closed buildings, and rare cases of HFRS, the only viral hemorrhagic fever to occur in the United States are imported cases, most frequently Lassa fever. The first imported case of Lassa fever in more than 20 years occurred in New Jersey in 2004. More recently, imported Marburg virus disease was identified in a Colorado woman who traveled to Uganda. Lassa fever imported to the US was again reported in 2010.
Arenaviridae, including Guanarito (Venezuelan HF), Junin (Argentine HF), Machupo (Bolivian HF), Sabia (Brazilian HF), and Lassa viruses, are found throughout South America, particularly in the Argentine pampas, Bolivia, Venezuela, and rural Brazil near Sao Paulo. The Chapare virus was recently identified in Bolivia. More recently, a novel arenavirus was identified in 5 patients in southern Africa. Arenaviridae are also found in West Africa (eg, Lassa in Nigeria, Sierra Leone, Guinea, Liberia, and Mali). Chronic infection of small field rodents makes rural residents and farmers the most frequently infected, with a strong seasonal predominance for the fall. In Argentina, agricultural workers are disproportionately infected. In Bolivia, rodents can invade towns and cause epidemics. In West Africa, Lassa fever is spread to humans when infected rodents are captured for consumption, as well as by person-to-person exposures. Currently, outbreaks of Lassa fever are occurring in West Africa.
Bunyaviridae (Crimean-Congo HF [CCHF], Rift Valley fever [RVF]) are seen throughout Africa, the Middle East, the Balkans,[15, 16, 17] southern Russia, and western China.[18, 19] CCHF has the widest geographic distribution of the tickborne infections and is increasingly reported in Europe,[20, 21, 22] and Turkey, as well.
Filoviridae (Ebola, Marburg viruses) are found in Africa and possibly in the Philippines. The vector is unknown, but infected primates sometimes provide a link for spread to humans. Later spread among humans or primates by close contact may also occur. Aerosol transmission is suspected in some monkey infections. It appears that outbreaks of Ebola disease often follow uncommonly dry periods, when rainfall resumes and reaches unusually high levels. Outbreaks of Marburg in Angola have been recently identified,[25, 26] as have outbreaks of Ebola in Congo and Uganda.[28, 29, 30]
Flaviviridae include Alkhurma HF virus, Kyasanur Forest disease , and Omsk HF. Alkhurma HF virus is a variant of Kyasanur Forest disease virus found in Saudi Arabia and reported in a small number of patients since the 1990s.[32, 2, 33] Recent reports describe the infection in travelers returning from Egypt, suggesting that the geographic range of the virus may be increasing.[3, 34] Kyasanur Forest disease follows a tick bite in rural areas of the endemic zone, Karnataka, India. Monkey die-offs may accompany increased virus activity. Omsk HF was observed in western Siberia and has a poorly understood vector and reservoir cycle that involves ticks, voles, muskrats, and, possibly, water-borne and mosquito transmission. Very few cases have been reported in recent years.
Ebola and Marburg are considered the most severe viral hemorrhagic fevers, with 25-100% mortality rates. The infection rate is high, particularly for the Zaire subtype of Ebola virus. During pregnancy, Ebola infection has been universally fatal. The South American HF has a case-infection ratio of more than 50% of those exposed. The mortality rate is 15-30%. Lassa fever is a milder infection, with a fatality rate of 2-15%, and is probably much more common than is recognized. Approximately 1% of individuals exposed to RVF virus become infected, but the mortality rate of persons infected is 50%. CCHF has an infection rate of 20-100% and a fatality rate of 15-30%.
No racial predilection has been reported.
No known sex predilection for viral hemorrhagic fever has been noted, except as occupational exposures dictate.
Persons affected are frequently those who have the most occupational exposure, although susceptibility in endemic regions is often highest for young children.
Gonzalez JP, Pourrut X, Leroy E. Ebolavirus and other filoviruses. Curr Top Microbiol Immunol. 2007. 315:363-87. [Medline].
Alzahrani AG, Al Shaiban HM, Al Mazroa MA, Al-Hayani O, Macneil A, Rollin PE. Alkhurma hemorrhagic Fever in humans, najran, saudi arabia. Emerg Infect Dis. 2010 Dec. 16(12):1882-8. [Medline].
Carletti F, Castilletti C, Di Caro A, et al. Alkhurma hemorrhagic Fever in travelers returning from egypt, 2010. Emerg Infect Dis. 2010 Dec. 16(12):1979-82. [Medline].
Memish ZA, Fagbo SF, Assiri AM, Rollin P, Zaki AM, Charrel R, et al. Alkhurma viral hemorrhagic fever virus: proposed guidelines for detection, prevention, and control in Saudi Arabia. PLoS Negl Trop Dis. 2012. 6(7):e1604. [Medline]. [Full Text].
Kasabi GS, Murhekar MV, Yadav PD, Raghunandan R, Kiran SK, Sandhya VK. Kyasanur forest disease, India, 2011-2012. Emerg Infect Dis. 2013 Feb. 19(2):278-81. [Medline].
Grard G, Fair JN, Lee D, Slikas E, Steffen I, Muyembe JJ. A novel rhabdovirus associated with acute hemorrhagic fever in central Africa. PLoS Pathog. 2012 Sep. 8(9):e1002924. [Medline].
Zhang YZ, He YW, Dai YA, Xiong Y, Zheng H, Zhou DJ, et al. Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis. 2012 Feb 15. 54(4):527-33. [Medline].
CDC. Imported Lassa fever--New Jersey, 2004. MMWR Morb Mortal Wkly Rep. 2004 Oct 1. 53(38):894-7. [Medline].
Imported case of Marburg Hemorrhagic Fever --- Colorado, 2008. MMWR Morb Mortal Wkly Rep. 2009 Dec 18. 58(49):1377-81. [Medline].
Amorosa V, Macneil A, McConnell R, Patel A, Dillon KE, Hamilton K, et al. Imported lassa Fever, pennsylvania, USA, 2010. Emerg Infect Dis. 2010 Oct. 16(10):1598-600. [Medline].
Charrel RN, Zaki AM, Fakeeh M, et al. Low diversity of Alkhurma hemorrhagic fever virus, Saudi Arabia, 1994-1999. Emerg Infect Dis. 2005 May. 11(5):683-8. [Medline].
Paweska JT, Sewlall NH, Ksiazek TG, Blumberg LH, Hale MJ, Lipkin WI, et al. Nosocomial outbreak of novel arenavirus infection, southern Africa. Emerg Infect Dis. 2009 Oct. 15(10):1598-602. [Medline].
Safronetz D, Lopez JE, Sogoba N, Traore' SF, Raffel SJ, Fischer ER. Detection of Lassa virus, Mali. Emerg Infect Dis. 2010 Jul. 16(7):1123-6. [Medline].
Sang R, Lutomiah J, Koka H, Makio A, Chepkorir E, Ochieng C, et al. Crimean-Congo hemorrhagic fever virus in Hyalommid ticks, northeastern Kenya. Emerg Infect Dis. 2011 Aug. 17(8):1502-5. [Medline]. [Full Text].
Knust B, Medetov ZB, Kyraubayev KB, Bumburidi Y, Erickson BR, MacNeil A, et al. Crimean-Congo hemorrhagic fever, Kazakhstan, 2009-2010. Emerg Infect Dis. 2012 Apr. 18(4):643-5. [Medline]. [Full Text].
Christova I, Gladnishka T, Taseva E, Kalvatchev N, Tsergouli K, Papa A. Seroprevalence of Crimean-Congo hemorrhagic fever virus, Bulgaria. Emerg Infect Dis. 2013 Jan. 19(1):177-9. [Medline]. [Full Text].
Dilber E, Cakir M, Acar EA, Orhan F, Yaris N, Bahat E, et al. Crimean-Congo haemorrhagic fever among children in north-eastern Turkey. Ann Trop Paediatr. 2009 Mar. 29(1):23-8. [Medline].
Overturf GD. World arboviruses: the bunyaviridae. Pediatr Infect Dis J. 2009 Nov. 28(11):1014-5. [Medline].
Tezer H, Sucakli IA, Sayli TR, et al. Crimean-Congo hemorrhagic fever in children. J Clin Virol. 2010 Jul. 48(3):184-6. [Medline].
Papa A, Tzala E, Maltezou HC. Crimean-congo hemorrhagic Fever virus, northeastern Greece. Emerg Infect Dis. 2011 Jan. 17(1):141-3. [Medline].
Heyman P, Cochez C, Hofhuis A, van der Giessen J, Sprong H, Porter SR, et al. A clear and present danger: tick-borne diseases in Europe. Expert Rev Anti Infect Ther. 2010 Jan. 8(1):33-50. [Medline].
Bodur H, Akinci E, Ascioglu S, Onguru P, Uyar Y. Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey. Emerg Infect Dis. 2012 Apr. 18(4):640-2. [Medline].
Feldmann H, Geisbert T, Kawaoka Y. Filoviruses. November 1, 2011.
Roddy P, Thomas SL, Jeffs B, Nascimento Folo P, Pablo Palma P, Moco Henrique B, et al. Factors associated with Marburg hemorrhagic fever: analysis of patient data from Uige, Angola. J Infect Dis. 2010 Jun 15. 201(12):1909-18. [Medline].
Grolla A, Jones SM, Fernando L, et al. The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg Outbreak in Angola. PLoS Negl Trop Dis. 2011 May. 5(5):e1183. [Medline]. [Full Text].
Nkoghe D, Kone ML, Yada A, Leroy E. A limited outbreak of Ebola haemorrhagic fever in Etoumbi, Republic of Congo, 2005. Trans R Soc Trop Med Hyg. 2011 Aug. 105(8):466-72. [Medline].
Outbreak news.Ebola, Uganda. Wkly Epidemiol Rec. 2011 May 27. 86(22):221. [Medline].
Outbreak news. Ebola haemorrhagic fever, Uganda – update. Wkly Epidemiol Rec. 2012 Dec 7. 87(49/50):493. [Medline].
Ambrosio AM, Riera LM, Saavedra Mdel C, Sabattini MS. Immune response to vaccination against Argentine hemorrhagic Fever in an area where different arenaviruses coexist. Viral Immunol. 2006. 19(2):196-201. [Medline].
Memish ZA, Albarrak A, Almazroa MA, Al-Omar I, Alhakeem R, Assiri A, et al. Seroprevalence of Alkhurma and other hemorrhagic fever viruses, Saudi Arabia. Emerg Infect Dis. 2011 Dec. 17(12):2316-8. [Medline]. [Full Text].
Kaya A, Engin A, Guven AS, et al. Crimean-Congo hemorrhagic fever disease due to tick bite with very long incubation periods. Int J Infect Dis. 2011 Jul. 15(7):e449-52. [Medline].
Trombley AR, Wachter L, Garrison J, Buckley-Beason VA, Jahrling J, Hensley LE. Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and new world hantaviruses. Am J Trop Med Hyg. 2010 May. 82(5):954-60. [Medline].
Vanhomwegen J, Alves MJ, Zupanc TA, Bino S, Chinikar S, Karlberg H. Diagnostic assays for crimean-congo hemorrhagic fever. Emerg Infect Dis. 2012 Dec. 18(12):1958-65. [Medline].
Erduran E, Bahadir A, Palanci N, Gedik Y. The treatment of crimean-congo hemorrhagic fever with high-dose methylprednisolone, intravenous immunoglobulin, and fresh frozen plasma. J Pediatr Hematol Oncol. 2013 Jan. 35(1):e19-24. [Medline].
Warren TK, Warfield KL, Wells J, et al. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med. 2010 Sep. 16(9):991-4. [Medline].
Michelow IC, Dong M, Mungall BA, et al. A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus. J Biol Chem. 2010 Aug 6. 285(32):24729-39. [Medline]. [Full Text].
Michelow IC, Lear C, Scully C, et al. High-dose mannose-binding lectin therapy for ebola virus infection. J Infect Dis. 2011 Jan. 203(2):175-9. [Medline].
Bausch DG, Hadi CM, Khan SH, Lertora JJ. Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever. Clin Infect Dis. 2010 Dec 15. 51(12):1435-41. [Medline].
Radoshitzky SR, Kuhn JH, de Kok-Mercado F, Jahrling PB, Bavari S. Drug discovery technologies and strategies for Machupo virus and other New World arenaviruses. Expert Opin Drug Discov. 2012 Jul. 7(7):613-32. [Medline].
Shurtleff AC, Nguyen TL, Kingery DA, Bavari S. Therapeutics for filovirus infection: traditional approaches and progress towards in silico drug design. Expert Opin Drug Discov. 2012 Oct. 7(10):935-54. [Medline].
Izadi S, Salehi M. Evaluation of the efficacy of ribavirin therapy on survival of Crimean-Congo hemorrhagic fever patients: a case-control study. Jpn J Infect Dis. 2009 Jan. 62(1):11-5. [Medline].
Baize S, Marianneau P, Georges-Courbot MC, Deubel V. Recent advances in vaccines against viral haemorrhagic fevers. Curr Opin Infect Dis. Oct 2001. 14(5):513-8. [Medline].
Heinz FX, Stiasny K. Flaviviruses and flavivirus vaccines. Vaccine. 2012 Jun 19. 30(29):4301-6. [Medline].
van Paassen J, Bauer MP, Arbous MS, Visser LG, Schmidt-Chanasit J, Schilling S. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012 Aug. 12(8):635-42. [Medline].
Gul I, Kaya A, Güven AS, Karapinar H, Küçükdurmaz Z, Yilmaz A, et al. Cardiac findings in children with Crimean-Congo hemorrhagic fever. Med Sci Monit. 2011 Aug. 17(8):CR457-460. [Medline].
Sensoy G, Caltepe Dinler G, Kalkan G, Ates A, Belet N, Albayrak D. Crimean-Congo haemorrhagic fever: peritoneal and pleural effusion. Ann Trop Paediatr. 2011. 31(2):169-72. [Medline].
Naderi H, Sheybani F, Bojdi A, Khosravi N, Mostafavi I. Fatal nosocomial spread of crimean-congo hemorrhagic Fever with very short incubation period. Am J Trop Med Hyg. 2013 Mar. 88(3):469-71. [Medline].
Timen A, Koopmans MP, Vossen AC, van Doornum GJ, Gunther S, van den Berkmortel F, et al. Response to imported case of Marburg hemorrhagic fever, the Netherland. Emerg Infect Dis. 2009 Aug. 15(8):1171-5. [Medline]. [Full Text].
Gilsdorf A, Morgan D, Leitmeyer K. Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation. BMC Public Health. 2012 Nov 21. 12:1014. [Medline]. [Full Text].
Akyol M, Ozcelik S, Engin A, Hayta SB, Bicici F. Cutaneous manifestations of Crimean-Congo haemorrhagic fever: morbilliform eruptions may reflect a favorable outcome and not low platelet levels. Eur J Dermatol. 2010 Jul-Aug. 20(4):523-4. [Medline].
Aleksandrowicz P, Wolf K, Falzarano D, Feldmann H, Seebach J, Schnittler H. Viral haemorrhagic fever and vascular alterations. Hamostaseologie. 2008 Feb. 28(1-2):77-84. [Medline].
Ali F, Saleem T, Khalid U, Mehmood SF, Jamil B. Crimean-Congo hemorrhagic fever in a dengue-endemic region: lessons for the future. J Infect Dev Ctries. 2010 Apr 15. 4(7):459-63. [Medline].
American Academy of Pediatrics. Hemorrhagic Fevers Caused by Arenaviruses and Hemorrhagic Fevers and Related Syndromes Caused by Viruses of the Family Bunyaviridae. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th. Elk Grove Village, IL: American Academy of Pediatrics; 2009. 325-9.
Aradaib IE, Erickson BR, Mustafa ME, Khristova ML, Saeed NS, Elageb RM, et al. Nosocomial outbreak of Crimean-Congo hemorrhagic fever, Sudan. Emerg Infect Dis. 2010 May. 16(5):837-9. [Medline].
Atkinson B, Latham J, Chamberlain J, Logue C, O'Donoghue L, Osborne J, et al. Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012. Euro Surveill. 2012 Nov 29. 17(48):[Medline].
Viral Hemorrhagic Fever. Spector JM, Gibson TE. Atlas of Pediatrics in the Tropics and Resource-Limited Settings. Elk Grove Village, IL: American Academy of Pediatrics; 2009. 301-304.
Bausch DG. Ebola virus as a foodborne pathogen? Cause for consideration, but not panic. J Infect Dis. 2011 Jul 15. 204(2):179-81. [Medline].
Bausch DG, Borchert M, Grein T, et al. Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo. Emerg Infect Dis. Dec 2003. 9(12):1531-7. [Medline].
Bausch DG, Nichol ST, Muyembe-Tamfum JJ, et al. Marburg hemorrhagic fever associated with multiple genetic lineages of virus. N Engl J Med. Aug 31 2006. 355(9):909-19. [Medline].
Bausch DG, Sprecher AG, Jeffs B, Boumandouki P. Treatment of Marburg and Ebola hemorrhagic fevers: a strategy for testing new drugs and vaccines under outbreak conditions. Antiviral Res. 2008 Apr. 78(1):150-61. [Medline].
Becquart P, Wauquier N, Mahlakoiv T, et al. High prevalence of both humoral and cellular immunity to Zaire ebolavirus among rural populations in Gabon. PLoS One. 2010 Feb 9. 5(2):e9126. [Medline]. [Full Text].
Berger SA, Calisher CH, Keystone JS. Exotic Viral Diseases: A Global Guide. Ontario, Canada: BC Decker Inc; 2003.
Bodur H, Akinci E, Onguru P, et al. Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever. Int J Infect Dis. 2010 Aug. 14(8):e704-7. [Medline].
Borchert M, Mulangu S, Van der Stuyft P. Lessons from the outbreak of Marburg virus. N Engl J Med. Sep 15 2005. 353(11):1185. [Medline].
Bray M. Highly pathogenic RNA viral infections: challenges for antiviral research. Antiviral Res. 2008 Apr. 78(1):1-8. [Medline].
Bray M, Mahanty S. Ebola hemorrhagic fever and septic shock. J Infect Dis. 2003 Dec 1. 188(11):1613-7. [Medline].
Briese T, Palacios G, Kokoris M, Jabado O, Liu Z, Renwick N. Diagnostic system for rapid and sensitive differential detection of pathogens. Emerg Infect Dis. 2005 Feb. 11(2):310-3. [Medline].
Celikbas A, Ergonul O, Dokuzoguz B, et al. Crimean Congo hemorrhagic fever infection simulating acute appendicitis. J Infect. 2005 May. 50(4):363-5. [Medline].
Cevik MA, Erbay A, Bodur H, et al. Viral load as a predictor of outcome in Crimean-Congo hemorrhagic fever. Clin Infect Dis. 2007 Oct 1. 45(7):e96-100. [Medline].
Charrel RN. Arenaviridae. Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. WB Saunders Co; 2004. 2364-79.
Charrel RN, Fagbo S, Moureau G, Alqahtani MH, Temmam S, de Lamballerie X. Alkhurma hemorrhagic fever virus in Ornithodoros savignyi ticks. Emerg Infect Dis. 2007 Jan. 13(1):153-5. [Medline].
Chiodini J. Mosquito-borne viral infections and the traveller. Nurs Stand. 2008 May 7-13. 22(35):50-7; quiz 58. [Medline].
Christova I, Di Caro A, Papa A, Castilletti C, Andonova L, Kalvatchev N, et al. Crimean-Congo hemorrhagic fever, southwestern Bulgaria. Emerg Infect Dis. 2009 Jun. 15(6):983-5. [Medline].
de la Torre JC. Reverse genetics approaches to combat pathogenic arenaviruses. Antiviral Res. 2008 Dec. 80(3):239-50. [Medline].
Delgado S, Erickson BR, Agudo R, Blair PJ, Vallejo E, Albarino CG. Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. PLoS Pathog. 2008 Apr. 4(4):e1000047. [Medline].
Dilber E, Cakir M, Erduran E, et al. High-dose methylprednisolone in children with Crimean-Congo haemorrhagic fever. Trop Doct. 2010 Jan. 40(1):27-30. [Medline].
Djavani MM, Crasta OR, Zapata JC, et al. Early blood profiles of virus infection in a monkey model for Lassa fever. J Virol. 2007 Aug. 81(15):7960-73. [Medline].
Doganci L. New insights on the bleeding disorders in CCHF. J Infect. 2007 Oct. 55(4):379-81. [Medline].
Dong J, Olano JP, McBride JW, Walker DH. Emerging pathogens: challenges and successes of molecular diagnostics. J Mol Diagn. 2008 May. 10(3):185-97. [Medline].
Doyle TJ, Bryan RT, Peters CJ. Viral hemorrhagic fevers and hantavirus infections in the Americas. Infect Dis Clin North Am. 1998 Mar. 12(1):95-110. [Medline].
Ebihara H, Zivcec M, Gardner D, Falzarano D, Lacasse R, Rosenke R, et al. A Syrian golden hamster model recapitulating ebola hemorrhagic Fever. J Infect Dis. 2013 Jan. 207(2):306-18. [Medline]. [Full Text].
Ehichioya DU, Hass M, Olschlager S, Becker-Ziaja B, Onyebuchi Chukwu CO, Coker J. Lassa Fever, Nigeria, 2005-2008. Emerg Infect Dis. 2010 Jun. 16(6):1040-1. [Medline].
Enria DA, Briggiler AM, Sanchez Z. Treatment of Argentine hemorrhagic fever. Antiviral Res. 2008 Apr. 78(1):132-9. [Medline].
Ergonul O. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. Apr 2006. 6(4):203-14. [Medline].
Ergonul O. Treatment of Crimean-Congo hemorrhagic fever. Antiviral Res. 2008 Apr. 78(1):125-31. [Medline].
Ergonul O, Celikbas A, Dokuzoguz B, et al. Characteristics of patients with Crimean-Congo hemorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy. Clin Infect Dis. 2004 Jul 15. 39(2):284-7. [Medline].
Estrada-Pena A, Zatansever Z, Gargili A, et al. Modeling the spatial distribution of crimean-congo hemorrhagic Fever outbreaks in Turkey. Vector Borne Zoonotic Dis. 2007. 7(4):667-78. [Medline].
Fair J, Jentes E, Inapogui A, et al. Lassa virus-infected rodents in refugee camps in Guinea: a looming threat to public health in a politically unstable region. Vector Borne Zoonotic Dis. 2007. 7(2):167-71. [Medline].
Feldmann H. Marburg hemorrhagic fever--the forgotten cousin strikes. N Engl J Med. Aug 31 2006. 355(9):866-9. [Medline].
Fontanarosa PB, Flanagin A, DeAngelis CD. Reporting conflicts of interest, financial aspects of research, and role of sponsors in funded studies. JAMA. 2005 Jul 6. 294(1):110-1. [Medline].
Garrison AR, Alakbarova S, Kulesh DA, et al. Development of a TaqMan minor groove binding protein assay for the detection and quantification of Crimean-Congo hemorrhagic fever virus. Am J Trop Med Hyg. 2007 Sep. 77(3):514-20. [Medline].
Geisbert TW, Hensley LE, Geisbert JB, Leung A, Johnson JC, Grolla A, et al. Postexposure treatment of marburg virus infection. Emerg Infect Dis. 2010 Jul. 16(7):1119-22. [Medline].
Ghosh D, Basu A. Present perspectives on flaviviral chemotherapy. Drug Discov Today. 2008 Jul. 13(13-14):619-24. [Medline].
Gould EA, Solomon T. Pathogenic flaviviruses. Lancet. 2008 Feb 9. 371(9611):500-9. [Medline].
Gowen BB, Holbrook MR. Animal models of highly pathogenic RNA viral infections: hemorrhagic fever viruses. Antiviral Res. 2008 Apr. 78(1):79-90. [Medline].
Gozalan A, Esen B, Fitzner J, et al. Crimean-Congo haemorrhagic fever cases in Turkey. Scand J Infect Dis. 2007. 39(4):332-6. [Medline].
Groseth A, Feldmann H, Strong JE. The ecology of Ebola virus. Trends Microbiol. 2007 Sep. 15(9):408-16. [Medline].
Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. New York, NY: Churchill Livingstone; 1999.
Gunther S, Weisner B, Roth A, et al. Lassa fever encephalopathy: Lassa virus in cerebrospinal fluid but not in serum. J Infect Dis. Aug 1 2001. 184(3):345-9. [Medline].
Haas WH, Breuer T, Pfaff G, et al. Imported Lassa fever in Germany: surveillance and management of contact persons. Clin Infect Dis. May 15 2003. 36(10):1254-8. [Medline].
Hall RC, Hall RC. The 1995 Kikwit Ebola outbreak--model of virus properties on system capacity and function: a lesson for future viral epidemics. Am J Disaster Med. 2007 Sep-Oct. 2(5):270-6. [Medline].
Hampton T. Vaccines against Ebola and Marburg viruses show promise in primate studies. JAMA. Jul 13 2005. 294(2):163-4. [Medline].
Hatipoglu CA, Bulut C, Yetkin MA, et al. Evaluation of clinical and laboratory predictors of fatality in patients with Crimean-Congo haemorrhagic fever in a tertiary care hospital in Turkey. Scand J Infect Dis. 2010 Jul. 42(6-7):516-21. [Medline].
Howard CR. Viral Haemorrhagic Fevers: Perspectives in Medical Virology. Amsterdam: Elsevier; 2005. Vol 11:
Isaacson M. Viral hemorrhagic fever hazards for travelers in Africa. Clin Infect Dis. Nov 15 2001. 33(10):1707-12. [Medline].
Jones SM, Feldmann H, Stroher U, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med. 2005 Jul. 11(7):786-90. [Medline].
Kerneis S, Koivogui L, Magassouba N, et al. Prevalence and risk factors of Lassa seropositivity in inhabitants of the forest region of Guinea: a cross-sectional study. PLoS Negl Trop Dis. 2009 Nov 17. 3(11):e548. [Medline]. [Full Text].
Khabbaz RF. Emerging viral infections. Adv Pediatr Infect Dis. 1999. 14:1-27. [Medline].
Khan AS. Lymphocytic choriomeningitis virus, lassa fever, and new world arenaviruses. Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone; 2003. 1168-71.
Khan AS. Ebola and Marburg viruses. Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone; 2003. 1166-8.
Khan SH, Goba A, Chu M, et al. New opportunities for field research on the pathogenesis and treatment of Lassa fever. Antiviral Res. 2008 Apr. 78(1):103-15. [Medline].
Kobinger GP, Leung A, Neufeld J, Richardson JS, Falzarano D, Smith G, et al. Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs. J Infect Dis. 2011 Jul 15. 204(2):200-8. [Medline].
Kuhn JH. Calisher CH. Filoviruses: a compendium of 40 years of epidemiological, clinical, and laboratory studies. New York: Springer-Verlag Wien; 2008. [Full Text].
Kurosaki Y, Takada A, Ebihara H, et al. Rapid and simple detection of Ebola virus by reverse transcription-loop-mediated isothermal amplification. J Virol Methods. 2007 Apr. 141(1):78-83. [Medline].
Lacy MD, Smego RA. Viral hemorrhagic fevers. Adv Pediatr Infect Dis. 1996. 12:21-53. [Medline].
Ligon BL. Outbreak of Marburg hemorrhagic fever in Angola: a review of the history of the disease and its biological aspects. Semin Pediatr Infect Dis. Jul 2005. 16(3):219-24. [Medline].
Lima EQ, Nogueira ML. Viral hemorrhagic fever-induced acute kidney injury. Semin Nephrol. 2008 Jul. 28(4):409-15. [Medline].
Macher AM, Wolfe MS. Historical Lassa fever reports and 30-year clinical update. Emerg Infect Dis. May 2006. 12(5):835-7. [Medline].
Macneil A, Farnon EC, Wamala J, et al. Proportion of deaths and clinical features in bundibugyo ebola virus infection, Uganda. Emerg Infect Dis. 2010 Dec. 16(12):1969-72. [Medline].
Magill AJ. Fever in the returned traveler. Infect Dis Clin North Am. 1998 Jun. 12(2):445-69. [Medline].
Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis. 2004 Aug. 4(8):487-98. [Medline].
Mairuhu AT, Brandjes DP, van Gorp EC. Treating viral hemorrhagic fever. IDrugs. Nov 2003. 6(11):1061-6. [Medline].
Marburg haemorrhagic fever, Uganda--update. Wkly Epidemiol Rec. 2007 Sep 7. 82(36):317. [Medline].
Mardani M, Jahromi MK, Naieni KH, Zeinali M. The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran. Clin Infect Dis. 2003 Jun 15. 36(12):1613-8. [Medline].
Midilli K, Gargili A, Ergonul O, Elevli M, Ergin S, Turan N, et al. The first clinical case due to AP92 like strain of Crimean-Congo Hemorrhagic Fever virus and a field survey. BMC Infect Dis. 2009 Jun 10. 9:90. [Medline]. [Full Text].
Morikawa S, Saijo M, Kurane I. Recent progress in molecular biology of Crimean-Congo hemorrhagic fever. Comp Immunol Microbiol Infect Dis. 2007 Sep. 30(5-6):375-89. [Medline].
Moureau G, Temmam S, Gonzalez JP, et al. A real-time rt-PCR method for the universal detection and identification of flaviviruses. Vector Borne Zoonotic Dis. 2007. 7(4):467-78. [Medline].
Ogbu O, Ajuluchukwu E, Uneke CJ. Lassa fever in West African sub-region: an overview. J Vector Borne Dis. 2007 Mar. 44(1):1-11. [Medline].
Outbreak news. Ebola virus haemorrhagic fever, Democratic Republic of the Congo--update. Wkly Epidemiol Rec. 2007 Oct 5. 82(40):345-6. [Medline].
Outbreak news. Marburg haemorrhagic fever, Uganda. Wkly Epidemiol Rec. 2007 Aug 17. 82(33):297-8. [Medline].
Outbreak of Marburg haemorrhagic fever: Uganda, June-August 2007. Wkly Epidemiol Rec. 2007 Oct 26. 82(43):381-4. [Medline].
Ozturk B, Kuscu F, Tutuncu E, Sencan I, Gurbuz Y, Tuzun H. Evaluation of the association of serum levels of hyaluronic acid, sICAM-1, sVCAM-1, and VEGF-A with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever. J Clin Virol. 2010 Feb. 47(2):115-9. [Medline].
Palacios G, Briese T, Kapoor V, et al. MassTag polymerase chain reaction for differential diagnosis of viral hemorrhagic fever. Emerg Infect Dis. 2006 Apr. 12(4):692-5. [Medline].
Papa A, Christova I, Papadimitriou E, Antoniadis A. Crimean-Congo hemorrhagic fever in Bulgaria. Emerg Infect Dis. Aug 2004. 10(8):1465-7. [Medline].
Peters CJ. Marburg and Ebola--arming ourselves against the deadly filoviruses. N Engl J Med. Jun 23 2005. 352(25):2571-3. [Medline].
Peters CJ, LeDuc JW. An introduction to Ebola: the virus and the disease. J Infect Dis. 1999 Feb. 179 Suppl 1:ix-xvi. [Medline].
Peterson AT, Bauer JT, Mills JN. Ecologic and geographic distribution of filovirus disease. Emerg Infect Dis. 2004 Jan. 10(1):40-7. [Medline].
Pigott DC. Hemorrhagic fever viruses. Crit Care Clin. 2005 Oct. 21(4):765-83, vii. [Medline].
Pugachev KV, Guirakhoo F, Monath TP. New developments in flavivirus vaccines with special attention to yellow fever. Curr Opin Infect Dis. Oct 2005. 18(5):387-94. [Medline].
Robertson J, Shilkofski N. Drug doses. The Harriet Lane Handbook: A Manual for Pediatric House Officers. Philadelphia, Pa: Mosby; 2005. 679-1009.
Schuster FL, Honarmand S, Visvesvara GS, Glaser CA. Detection of antibodies against free-living amoebae Balamuthia mandrillaris and Acanthamoeba species in a population of patients with encephalitis. Clin Infect Dis. 2006 May 1. 42(9):1260-5. [Medline].
Sharifi-Mood B, Mardani M, Keshtkar-Jahromi M, Rahnavardi M, Hatami H, Metanat M. Clinical and Epidemiologic Features of Crimean-Congo Hemorrhagic Fever Among Children and Adolescents From Southeastern Iran. Pediatr Infect Dis J. 2008 Apr 23. 27(6):561-3. [Medline].
Sheikh AS, Sheikh AA, Sheikh NS, et al. Bi-annual surge of Crimean-Congo haemorrhagic fever (CCHF): a five-year experience. Int J Infect Dis. 2005 Jan. 9(1):37-42. [Medline].
Smego RA, Sarwari AR, Siddiqui AR. Crimean-Congo hemorrhagic fever: prevention and control limitations in a resource-poor country. Clin Infect Dis. Jun 15 2004. 38(12):1731-5. [Medline].
Stein DA, Shi PY. Nucleic acid-based inhibition of flavivirus infections. Front Biosci. 2008 Jan 1. 13:1385-95. [Medline].
Tarantola A, Nabeth P, Tattevin P, et al. Lookback exercise with imported Crimean-Congo hemorrhagic fever, Senegal and France. Emerg Infect Dis. Sep 2006. 12(9):1424-6. [Medline].
Tezer H, Tavil B, Sucakli IA, et al. Concurrent Crimean-Congo hemorrhagic fever and visceral leishmaniasis in a Turkish girl. Vector Borne Zoonotic Dis. 2011 Jun. 11(6):743-5. [Medline].
Tsai TF, Halstead SB. Tropical viral infections. Curr Opin Infect Dis. 1998 Oct. 11(5):547-53. [Medline].
Tutuncu EE, Gurbuz Y, Ozturk B, Kuscu F, Sencan I. Serum nitric oxide levels in patients with Crimean-Congo haemorrhagic fever. Scand J Infect Dis. 2010 May. 42(5):385-8. [Medline].
Uysal IO, Kaya A, Guven AS, Altuntas EE, Muderris S. Evaluation of cochlear involvement by transient evoked otoacoustic emission test in children with Crimean-Congo hemorrhagic fever. Int J Pediatr Otorhinolaryngol. 2011 Jun. 75(6):858-60. [Medline].
Vorou R, Pierroutsakos IN, Maltezou HC. Crimean-Congo hemorrhagic fever. Curr Opin Infect Dis. 2007 Oct. 20(5):495-500. [Medline].
Wamala JF, Lukwago L, Malimbo M, Nguku P, Yoti Z, Musenero M. Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007-2008. Emerg Infect Dis. 2010 Jul. 16(7):1087-92. [Medline].
Wang CC, Liu SF, Liao SC, et al. Acute respiratory failure in adult patients with dengue virus infection. Am J Trop Med Hyg. 2007 Jul. 77(1):151-8. [Medline].
WHO. Marburg haemorrhagic fever, Angola. Wkly Epidemiol Rec. 2005 May 6. 80(18):158-9. [Medline].
WHO. Update on Lassa fever in West Africa. Wkly Epidemiol Rec. 2005 Mar 11. 80(10):86-8. [Medline].
Wolfel R, Paweska JT, Petersen N, Grobbelaar AA, Leman PA, Hewson R. Virus detection and monitoring of viral load in Crimean-Congo hemorrhagic fever virus patients. Emerg Infect Dis. 2007 Jul. 13(7):1097-100. [Medline].
Woodrow CJ, Eziefula AC, Agranoff D, et al. Early risk assessment for viral haemorrhagic fever: experience at the Hospital for tropical diseases, London, UK. J Infection. 2007. 54:6-11. [Medline].
Yang C, Ye L, Compans RW. Protection against filovirus infection: virus-like particle vaccines. Expert Rev Vaccines. 2008 Apr. 7(3):333-44. [Medline].
Yilmaz R, Kundak AA, Ozer S, Esmeray H. Successful treatment of severe Crimean-Congo hemorrhagic fever with supportive measures without ribavirin and hypothermia. J Clin Virol. 2009 Feb. 44(2):181-2. [Medline].
Zampieri CA, Sullivan NJ, Nabel GJ. Immunopathology of highly virulent pathogens: insights from Ebola virus. Nat Immunol. 2007 Nov. 8(11):1159-64. [Medline].