1887

Chapter 42 : Filoviruses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $30.00

Preview this chapter:
Zoom in
Zoomout

Filoviruses, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch42-1.gif /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch42-2.gif

Abstract:

The filoviruses are nonsegmented, negative-sense RNA viruses in the family , order . The genus consists of a single species of related viruses, for which bats in Central Africa have recently been found to be a reservoir. The other genus, , contains four species (Zaire, Sudan, Bundibugyo, and Ivory Coast) indigenous to Africa, and a fifth, Reston virus, found in the Philippines. It is likely that the African Ebola species are also maintained in bats, but attempts to recover infectious virus from captured animals have been unsuccessful. Except for the Reston agent, all filoviruses cause severe disease in humans, with fatality rates in outbreaks often exceeding 50%.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

A. Negative-contrast electron micrograph (EM) of Ebola virions (magnification, ×17,000). B. Transmission EM of viral nucleocapsids in a cytoplasmic inclusion body. C. Scanning EM of virions budding from the surface of an infected cell. (Courtesy of Tom Geisbert, USAMRIID.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Outbreaks of Marburg and Ebola virus disease in Africa, 1976–2014. All Marburg outbreaks have been caused by a single virus species. Most Ebola epidemics have been caused by the Zaire species (EBOV), with the Sudan virus (SUDV) responsible for a smaller number in East Africa. The Bundibugyo (BDBV) virus has been identified only in Uganda and the Ivory Coast virus in a single human infection in the Tai Forest in that country (TAFV). (Courtesy of Eric Leroy, CIRMF, Gabon. Reprinted with permission from Reference .)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

The iconic figure of the West African Ebola epidemic: a health care worker in full personal protective equipment (PPE). The outbreak began in a rural village in Guinea in late 2013, then spread to the largest cities of Guinea, Sierra Leone, and Liberia. By January, 2016, more than 28,000 suspected, probable, and confirmed cases had been reported—more than 10 times the total of all previous Ebola epidemics combined—and 11,000 deaths ( ) (Photo provided by Médecins Sans Frontières, used with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Bayesian coalescent analysis of genomic sequences of the , based on representative viruses chosen from each species and a diverse set of isolates. Values at each node represent years since most recent common ancestor, prior to 2007. The tree indicates the early divergence of the genera , , and . Although the Marburg Ravn and Musoke viruses have followed a separate evolutionary course for approximately 1,000 years, they are still more closely related to each other than any two species in the genus . The Sudan and Reston viruses are the most distantly related to other Ebola viruses. (Reprinted from Reference with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5
FIGURE 5

A. Structure of a filovirus virion, showing the RNA genome with its associated nucleocapsid proteins, enveloped in a lipid bilayer bearing glycoprotein spikes. NP and VP30 bind to virion RNA to make up the nucleocapsid, and VP35 and the RNA polymerase (L protein) join them in forming a replication complex. Matrix proteins VP24 and VP40 link the nucleocapsid to GP on the inner surface of the envelope. B. Schematic representation of the genomes of Marburg and Ebola viruses. The seven genes are drawn roughly to scale. (Courtesy of Eric Leroy, CIRMF, Gabon. Reprinted from Reference with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6
FIGURE 6

The West African Ebola epidemic: patient care in a low-resource setting. A. Medical workers preparing to enter an Ebola treatment unit. A team approach ensures that PPE is donned and removed correctly. B. ELWA-3, the largest Ebola treatment center ever constructed, built by Médecins Sans Frontières adjacent to the ELWA mission hospital in Monrovia, Liberia. The center is designed to isolate persons possibly incubating Ebola virus disease, treat those who have become ill, and prevent the further spread of infection. (Médecins Sans Frontières, used with permission.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 8
FIGURE 8

Pathogenesis of filovirus disease. Monocytes, macrophages, and dendritic cells are the primary sites of replication. Suppression of type I interferon responses permits rapid virus dissemination via the bloodstream to the spleen and other lymphoid tissues and to hepatocytes and parenchymal cells of other organs, resulting in further productive infection and multifocal necrosis. The release of proinflammatory mediators, the production of cell-surface tissue factor, and endothelial dysfunction contribute to coagulopathy, organ-specific vascular leak (e.g. lungs), and eventual multi-organ failure. Lymphocytes remain uninfected but undergo apoptosis, contributing to the failure of adaptive immune responses. Note: observations in patients during the West African Ebola outbreak suggest that damage to renal parenchymal cells and injury within the central nervous system plays a significant role in pathogenesis.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 9
FIGURE 9

Replication of mouse-adapted Ebola virus in a lethally infected mouse. A. hybridization of viral RNA in a splenic follicle; all marginal-zone macrophages contain replicating virus, while lymphocytes remain uninfected. B. Multifocal necrosis in the liver. Some hepatocytes contain acidophilic inclusion bodies (arrow), corresponding to the nucleocapsid aggregates shown in Figure 2B . (Courtesy of Tammy Gibb and Kelly Davis, USAMRIID.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 10
FIGURE 10

Extensive desquamation of the forearm and hand of a survivor of Ebola Sudan virus infection in Gulu, Uganda, 3 weeks after disease onset. (Courtesy of Dan Bausch, Tulane University.)

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7
FIGURE 7

The West African Ebola epidemic: patient care in a high-resource setting. Coauthor DC manipulating a peripherally inserted central catheter line of a critically ill Ebola patient requiring mechanical ventilation in the Special Clinical Studies Unit of the Clinical Center, National Institutes of Health, Bethesda, MD.

Citation: Bray M, Chertow D. 2017. Filoviruses, p 981-1007. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch42
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555819439.ch42
2. Negredo A, Palacios G, Vázquez-Morón S, González F, Dopazo H, Molero F, Juste J, Quetglas J, Savji N, de la Cruz Martínez M, Herrera JE, Pizarro M, Hutchison SK, Echevarría JE, Lipkin WI, Tenorio A. 2011. Discovery of an ebolavirus-like filovirus in Europe. PLoS Pathog 7:e1002304.[PubMed]
3. Daddario-DiCaprio KM, Geisbert TW, Geisbert JB, Ströher U, Hensley LE, Grolla A, Fritz EA, Feldmann F, Feldmann H, Jones SM. 2006. Cross-protection against Marburg virus strains by using a live, attenuated recombinant vaccine. J Virol 80:96599666.[PubMed]
4. Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keïta S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traoré A, Kolié M, Malano ER, Heleze E, Bocquin A, Mély S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Günther S. 2014. Emergence of Zaire ebola virus disease in Guinea. N Engl J Med 371:14181425.[PubMed]
5. Feldmann H, Volchkov VE, Volchkova VA, Klenk HD. 1999. The glycoproteins of Marburg and ebola virus and their potential roles in pathogenesis. Arch Virol Suppl 15:159169.[PubMed]
6. Jasenosky LD, Kawaoka Y. 2004. Filovirus budding. Virus Res 106:181188.[PubMed]
7. Escudero-Pérez B, Volchkova VA, Dolnik O, Lawrence P, Volchkov VE. 2014. Shed GP of ebola virus triggers immune activation and increased vascular permeability. PLoS Pathog 10:e1004509.[PubMed]
8. Panchal RG, Ruthel G, Kenny TA, Kallstrom GH, Lane D, Badie SS, Li L, Bavari S, Aman MJ. 2003. In vivo oligomerization and raft localization of ebola virus protein VP40 during vesicular budding. Proc Natl Acad Sci USA 100:1593615941.[PubMed]
9. Bavari S, Bosio CM, Wiegand E, Ruthel G, Will AB, Geisbert TW, Hevey M, Schmaljohn C, Schmaljohn A, Aman MJ. 2002. Lipid raft microdomains: a gateway for compartmentalized trafficking of ebola and Marburg viruses. J Exp Med 195:593602.[PubMed]
10. Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Mühlberger E, Bray M, Klenk HD, Palese P, García-Sastre A. 2003. The ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77:79457956.[PubMed]
11. Basler CF, Amarasinghe GK. 2009. Evasion of interferon responses by ebola and Marburg viruses. J Interferon Cytokine Res 29:511520.[PubMed]
12. White JM, Schornberg KL. 2012. A new player in the puzzle of filovirus entry. Nat Rev Microbiol 10:317322.[PubMed]
13. Herbert AS, Davidson C, Kuehne AI, Bakken R, Braigen SZ, Gunn KE, Whelan SP, Brummelkamp TR, Twenhafel NA, Chandran K, Walkley SU, Dye JM. 2015. Niemann-pick C1 is essential for ebolavirus replication and pathogenesis in vivo. MBio 6:e00565e15.[PubMed]
14. Mühlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. 1999. Comparison of the transcription and replication strategies of marburg virus and ebola virus by using artificial replication systems. J Virol 73:23332342.[PubMed]
15. Hartlieb B, Weissenhorn W. 2006. Filovirus assembly and budding. Virology 344:6470.[PubMed]
16. Reed PE, Mulangu S, Cameron KN, Ondzie AU, Joly D, Bermejo M, Rouquet P, Fabozzi G, Bailey M, Shen Z, Keele BF, Hahn B, Karesh WB, Sullivan NJ. 2014. A new approach for monitoring ebolavirus in wild great apes. PLoS Negl Trop Dis 8:e3143.[PubMed]
17. Rouquet P, Froment JM, Bermejo M, Kilbourn A, Karesh W, Reed P, Kumulungui B, Yaba P, Délicat A, Rollin PE, Leroy EM. 2005. Wild animal mortality monitoring and human ebola outbreaks, Gabon and Republic of Congo, 2001–2003. Emerg Infect Dis 11:283290.[PubMed]
18. Swanepoel R, Leman PA, Burt FJ, Zachariades NA, Braack LE, Ksiazek TG, Rollin PE, Zaki SR, Peters CJ. 1996. Experimental inoculation of plants and animals with ebola virus. Emerg Infect Dis 2:321325.[PubMed]
19. Towner JS, Amman BR, Sealy TK, Carroll SA, Comer JA, Kemp A, Swanepoel R, Paddock CD, Balinandi S, Khristova ML, Formenty PB, Albarino CG, Miller DM, Reed ZD, Kayiwa JT, Mills JN, Cannon DL, Greer PW, Byaruhanga E, Farnon EC, Atimnedi P, Okware S, Katongole-Mbidde E, Downing R, Tappero JW, Zaki SR, Ksiazek TG, Nichol ST, Rollin PE. 2009. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog 5:e1000536.[PubMed]
20. Amman BR, Carroll SA, Reed ZD, Sealy TK, Balinandi S, Swanepoel R, Kemp A, Erickson BR, Comer JA, Campbell S, Cannon DL, Khristova ML, Atimnedi P, Paddock CD, Crockett RJ, Flietstra TD, Warfield KL, Unfer R, Katongole-Mbidde E, Downing R, Tappero JW, Zaki SR, Rollin PE, Ksiazek TG, Nichol ST, Towner JS. 2012. Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection. PLoS Pathog 8:e1002877.[PubMed]
21. Amman BR, Jones ME, Sealy TK, Uebelhoer LS, Schuh AJ, Bird BH, Coleman-McCray JD, Martin BE, Nichol ST, Towner JS. 2015. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). J Wildl Dis 51:113124.[PubMed]
22. Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A, Yaba P, Délicat A, Paweska JT, Gonzalez JP, Swanepoel R. 2005. Fruit bats as reservoirs of ebola virus. Nature 438:575576.[PubMed]
23. Pourrut X, Souris M, Towner JS, Rollin PE, Nichol ST, Gonzalez JP, Leroy E. 2009. Large serological survey showing cocirculation of ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus. BMC Infect Dis 9:159.[PubMed]
24. Anti P, Owusu M, Agbenyega O, Annan A, Badu EK, Nkrumah EE, Tschapka M, Oppong S, Adu-Sarkodie Y, Drosten C. 2015. Human-bat interactions in rural West Africa. Emerg Infect Dis 21:14181421.[PubMed]
25. Allela L, Bourry O, Pouillot R, Délicat A, Yaba P, Kumulungui B, Rouquet P, Gonzalez JP, Leroy EM. 2005. Ebola virus antibody prevalence in dogs and human risk. Emerg Infect Dis 11:385390.[PubMed]
26. Cross RW, Fenton KA, Geisbert JB, Mire CE, Geisbert TW. 2015. Modeling the disease course of zaire ebolavirus infection in the outbred guinea pig. J Infect Dis 212(Suppl 2):S305S315. [PubMed]
27. Wong G, Qiu X, Richardson JS, Cutts T, Collignon B, Gren J, Aviles J, Embury-Hyatt C, Kobinger GP. 2015. Ebola virus transmission in guinea pigs. J Virol 89:13141323. [PubMed]
28. Bray M, Davis K, Geisbert T, Schmaljohn C, Huggins J. 1998. A mouse model for evaluation of prophylaxis and therapy of ebola hemorrhagic fever. J Infect Dis 178:651661. [PubMed]
29. Bray M, Hatfill S, Hensley L, Huggins JW. 2001. Haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of ebola Zaire virus. J Comp Pathol 125:243253.[PubMed]
30. Wahl-Jensen V, Bollinger L, Safronetz D, de Kok-Mercado F, Scott DP, Ebihara H. 2012. Use of the Syrian hamster as a new model of ebola virus disease and other viral hemorrhagic fevers. Viruses 4:37543784.[PubMed]
31. Raymond J, Bradfute S, Bray M. 2011. Filovirus infection of STAT-1 knockout mice. J Infect Dis 204(Suppl 3):S986S990.[PubMed]
32. Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. 2014. Successful treatment of advanced ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 105:1721.[PubMed]
33. Smith DR, Holbrook MR, Gowen BB. 2014. Animal models of viral hemorrhagic fever. Antiviral Res 112:5979.[PubMed]
34. Thi EP, Mire CE, Lee AC, Geisbert JB, Zhou JZ, Agans KN, Snead NM, Deer DJ, Barnard TR, Fenton KA, MacLachlan I, Geisbert TW. 2015. Lipid nanoparticle siRNA treatment of ebola-virus-Makona-infected nonhuman primates. Nature 521:362365.[PubMed]
35. Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S. 2014. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 508:402405.[PubMed]
36. Wong G, Richardson JS, Pillet S, Racine T, Patel A, Soule G, Ennis J, Turner J, Qiu X, Kobinger GP. 2015. Adenovirus-vectored vaccine provides postexposure protection to ebola virus-infected nonhuman primates. J Infect Dis 212(Suppl 2):S379S383.[PubMed]
37. Piercy TJ, Smither SJ, Steward JA, Eastaugh L, Lever MS. 2010. The survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol. J Appl Microbiol 109:15311539.[PubMed]
38. Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, Sanchez A, Nichol ST, Ksiazek TG, Rollin PE. 2007. Assessment of the risk of ebola virus transmission from bodily fluids and fomites. J Infect Dis 196(Suppl 2):S142S147.[PubMed]
39. Prescott J, Bushmaker T, Fischer R, Miazgowicz K, Judson S, Munster VJ. 2015. Postmortem stability of ebola virus. Emerg Infect Dis 21:856859.[PubMed]
40. EPA-registered_disinfectants. http://www.epa.gov/pesticide-registration/list-l-disinfectants-use-against-ebola-virus. Accessed January 24, 2016.
41. Ksiazek TG, Rollin PE, Williams AJ, Bressler DS, Martin ML, Swanepoel R, Burt FJ, Leman PA, Khan AS, Rowe AK, Mukunu R, Sanchez A, Peters CJ. 1999. Clinical virology of ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 179(Suppl 1):S177S187.[PubMed]
42. Schoepp RJ, Rossi CA, Khan SH, Goba A, Fair JN. 2014. Undiagnosed acute viral febrile illnesses, Sierra Leone. Emerg Infect Dis 20:11761182.[PubMed]
43. Leroy EM, Baize S, Volchkov VE, Fisher-Hoch SP, Georges-Courbot MC, Lansoud-Soukate J, Capron M, Debré P, McCormick JB, Georges AJ. 2000. Human asymptomatic ebola infection and strong inflammatory response. Lancet 355:22102215.[PubMed]
44. Bausch DG, Nichol ST, Muyembe-Tamfum JJ, Borchert M, Rollin PE, Sleurs H, Campbell P, Tshioko FK, Roth C, Colebunders R, Pirard P, Mardel S, Olinda LA, Zeller H, Tshomba A, Kulidri A, Libande ML, Mulangu S, Formenty P, Grein T, Leirs H, Braack L, Ksiazek T, Zaki S, Bowen MD, Smit SB, Leman PA, Burt FJ, Kemp A, Swanepoel R International Scientific and Technical Committee for Marburg Hemorrhagic Fever Control in the Democratic Republic of the Congo. 2006. Marburg hemorrhagic fever associated with multiple genetic lineages of virus. N Engl J Med 355:909919.[PubMed]
45. Martini GA, Siegert R (eds). 1971. Marburg Virus Disease. Springer Verlag, New York.
46. Leroy EM, Souquière S, Rouquet P, Drevet D. 2002. Re-emergence of ebola haemorrhagic fever in Gabon. Lancet 359:712.[PubMed]
47. Leroy EM, Rouquet P, Formenty P, Souquière S, Kilbourne A, Froment JM, Bermejo M, Smit S, Karesh W, Swanepoel R, Zaki SR, Rollin PE. 2004. Multiple ebola virus transmission events and rapid decline of Central African wildlife. Science 303:387390.[PubMed]
48. Alexander KA, Sanderson CE, Marathe M, Lewis BL, Rivers CM, Shaman J, Drake JM, Lofgren E, Dato VM, Eisenberg MC, Eubank S. 2015. What factors might have led to the emergence of ebola in West Africa? PLoS Negl Trop Dis 9:e0003652.[PubMed]
49. WHOZaire. 1978. Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 56:271293.[PubMed]
50. Khan AS, Tshioko FK, Heymann DL, Le Guenno B, Nabeth P, Kerstiëns B, Fleerackers Y, Kilmarx PH, Rodier GR, Nkuku O, Rollin PE, Sanchez A, Zaki SR, Swanepoel R, Tomori O, Nichol ST, Peters CJ, Muyembe-Tamfum JJ, Ksiazek TG. 1999. The reemergence of ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis 179(Suppl 1):S76S86.[PubMed]
51. Gear JS, Cassel GA, Gear AJ, Trappler B, Clausen L, Meyers AM, Kew MC, Bothwell TH, Sher R, Miller GB, Schneider J, Koornhof HJ, Gomperts ED, Isaäcson M, Gear JH. 1975. Outbreake of Marburg virus disease in Johannesburg. BMJ 4:489493.[PubMed]
52. Centers for Disease Control and Prevention (CDC). 2009. Imported case of Marburg hemorrhagic fever—Colorado, 2008. MMWR Morb Mortal Wkly Rep 58:13771381.[PubMed]
53. Jeffs B, Roddy P, Weatherill D, de la Rosa O, Dorion C, Iscla M, Grovas I, Palma PP, Villa L, Bernal O, Rodriguez-Martinez J, Barcelo B, Pou D, Borchert M. 2007. The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. I. Lessons learned in the hospital. J Infect Dis 196(Suppl 2):S154S161.[PubMed]
54. Walsh PD, Abernethy KA, Bermejo M, Beyers R, De Wachter P, Akou ME, Huijbregts B, Mambounga DI, Toham AK, Kilbourn AM, Lahm SA, Latour S, Maisels F, Mbina C, Mihindou Y, Obiang SN, Effa EN, Starkey MP, Telfer P, Thibault M, Tutin CE, White LJ, Wilkie DS. 2003. Catastrophic ape decline in western equatorial Africa. Nature 422:611614.[PubMed]
55. Leroy EM, Epelboin A, Mondonge V, Pourrut X, Gonzalez JP, Muyembe-Tamfum JJ, Formenty P. 2009. Human ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis 9:723728.[PubMed]
56. Washington ML, Meltzer ML, Centers for Disease Control and Prevention. 2015. Effectiveness of ebola treatment units and community care centers—Liberia, September 23-October 31, 2014. MMWR Morb Mortal Wkly Rep 64:6769.
57. Van Kerkhove MD, Bento AI, Mills HL, Ferguson NM, Donnelly CA. 2015. A review of epidemiological parameters from ebola outbreaks to inform early public health decision-making. Sci Data 2:150019.[PubMed]
58. Weitz JS, Dushoff J. 2015. Modeling post-death transmission of ebola: challenges for inference and opportunities for control. Sci Rep 5:8751.[PubMed]
59. Lindblade KA, Kateh F, Nagbe TK, Neatherlin JC, Pillai SK, Attfield KR, Dweh E, Barradas DT, Williams SG, Blackley DJ, Kirking HL, Patel MR, Dea M, Massoudi MS, Wannemuehler K, Barskey AE, Zarecki SL, Fomba M, Grube S, Belcher L, Broyles LN, Maxwell TN, Hagan JE, Yeoman K, Westercamp M, Forrester J, Mott J, Mahoney F, Slutsker L, DeCock KM, Nyenswah T. 2015. Decreased ebola transmission after rapid response to outbreaks in remote areas, Liberia, 2014. Emerg Infect Dis 21:18001807.[PubMed]
60. WHOSudan. 1978. Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 56:247270.[PubMed]
61. Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner KD, Rollin PE. 2004. Analysis of human peripheral blood samples from fatal and nonfatal cases of ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol 78:1037010377.[PubMed]
62. Hutchinson KL, Rollin PE. 2007. Cytokine and chemokine expression in humans infected with Sudan ebola virus. J Infect Dis 196(Suppl 2):S357S363.[PubMed]
63. Sanchez A, Wagoner KE, Rollin PE. 2007. Sequence-based human leukocyte antigen-B typing of patients infected with ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes. J Infect Dis 196(Suppl 2):S329S336.[PubMed]
64. McElroy AK, Erickson BR, Flietstra TD, Rollin PE, Nichol ST, Towner JS, Spiropoulou CF. 2014. Biomarker correlates of survival in pediatric patients with ebola virus disease. Emerg Infect Dis 20:16831690.[PubMed]
65. Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P, Widmer A. 1999. Human infection due to ebola virus, subtype Côte d'Ivoire: clinical and biologic presentation. J Infect Dis 179(Suppl 1):S48S53.[PubMed]
66. Towner JS, Sealy TK, Khristova ML, Albariño CG, Conlan S, Reeder SA, Quan PL, Lipkin WI, Downing R, Tappero JW, Okware S, Lutwama J, Bakamutumaho B, Kayiwa J, Comer JA, Rollin PE, Ksiazek TG, Nichol ST. 2008. Newly discovered ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog 4:e1000212.[PubMed]
67. Kratz T, Roddy P, Tshomba Oloma A, Jeffs B, Pou Ciruelo D, de la Rosa O, Borchert M. 2015. Ebola virus disease outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and symptoms, management and outcomes. PLoS One 10:e0129333.[PubMed]
68. Jahrling PB, Geisbert TW, Dalgard DW, Johnson ED, Ksiazek TG, Hall WC, Peters CJ. 1990. Preliminary report: isolation of ebola virus from monkeys imported to USA. Lancet 335:502505.[PubMed]
69. Barrette RW, Metwally SA, Rowland JM, Xu L, Zaki SR, Nichol ST, Rollin PE, Towner JS, Shieh WJ, Batten B, Sealy TK, Carrillo C, Moran KE, Bracht AJ, Mayr GA, Sirios-Cruz M, Catbagan DP, Lautner EA, Ksiazek TG, White WR, McIntosh MT. 2009. Discovery of swine as a host for the Reston ebolavirus. Science 325:204206.[PubMed]
70. Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK, Colubri A, Sealfon RS, Kanneh L, Moigboi A, Momoh M, Fullah M, Moses LM, Brown BL, Andersen KG, Winnicki S, Schaffner SF, Park DJ, Yozwiak NL, Jiang PP, Kargbo D, Jalloh S, Fonnie M, Sinnah V, French I, Kovoma A, Kamara FK, Tucker V, Konuwa E, Sellu J, Mustapha I, Foday M, Yillah M, Kanneh F, Saffa S, Massally JL, Boisen ML, Branco LM, Vandi MA, Grant DS, Happi C, Gevao SM, Fletcher TE, Fowler RA, Bausch DG, Sabeti PC, Khan SH, Garry RF Program KGHLF, Viral Hemorrhagic Fever C, Team WHOCR, KGH Lassa Fever Program, Viral Hemorrhagic Fever Consortium, WHO Clinical Response Team. 2014. Clinical illness and outcomes in patients with ebola in Sierra Leone. N Engl J Med 371:20922100.[PubMed]
71. Hunt L, Gupta-Wright A, Simms V, Tamba F, Knott V, Tamba K, Heisenberg-Mansaray S, Tamba E, Sheriff A, Conteh S, Smith T, Tobin S, Brooks T, Houlihan C, Cummings R, Fletcher T. 2015. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with ebola virus disease: an observational cohort study. Lancet Infect Dis 15:12921299.[PubMed]
72. Agua-Agum J, Ariyarajah A, Blake IM, Cori A, Donnelly CA, Dorigatti I, Dye C, Eckmanns T, Ferguson NM, Fowler RA, Fraser C, Garske T, Hinsley W, Jombart T, Mills HL, Murthy S, Nedjati Gilani G, Nouvellet P, Pelletier L, Riley S, Schumacher D, Shah A, Van Kerkhove MD, Van Kerkhove MD WHO Ebola Response Team. 2015. Ebola virus disease among children in West Africa. N Engl J Med 372:12741277.[PubMed]
73. Twenhafel NA, Shaia CI, Bunton TE, Shamblin JD, Wollen SE, Pitt LM, Sizemore DR, Ogg MM, Johnston SC. 2015. Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. Vet Pathol 52:2125.[PubMed]
74. Smither SJ, Nelson M, Eastaugh L, Nunez A, Salguero FJ, Lever MS. 2015. Experimental respiratory infection of marmosets (callithrix jacchus) with ebola virus kikwit. J Infect Dis 212(Suppl 2):S336S345.[PubMed]
75. Kobinger GP, Leung A, Neufeld J, Richardson JS, Falzarano D, Smith G, Tierney K, Patel A, Weingartl HM. 2011. Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs. J Infect Dis 204:200208.[PubMed]
76. Weingartl HM, Embury-Hyatt C, Nfon C, Leung A, Smith G, Kobinger G. 2012. Transmission of Ebola virus from pigs to non-human primates. Sci Rep 2:811.[PubMed]
77. Moreau M, Spencer C, Gozalbes JG, Colebunders R, Lefevre A, Gryseels S, Borremans B, Gunther S, Becker D, Bore JA, Koundouno FR, Di Caro A, Wölfel R, Decroo T, Van Herp M, Peetermans L, Camara AM. 2015. Lactating mothers infected with ebola virus: EBOV RT-PCR of blood only may be insufficient. Euro Surveill 20:21017.[PubMed]
78. Liddell AM, Davey RT Jr, Mehta AK, Varkey JB, Kraft CS, Tseggay GK, Badidi O, Faust AC, Brown KV, Suffredini AF, Barrett K, Wolcott MJ, Marconi VC, Lyon GM III, Weinstein GL, Weinmeister K, Sutton S, Hazbun M, Albariño CG, Reed Z, Cannon D, Ströher U, Feldman M, Ribner BS, Lane HC, Fauci AS, Uyeki TM. 2015. Characteristics and clinical management of a cluster of 3 patients with ebola virus disease, including the first domestically acquired cases in the united states. Ann Intern Med 163:8190.[PubMed]
79. Mora-Rillo M, Arsuaga M, Ramírez-Olivencia G, de la Calle F, Borobia AM, Sánchez-Seco P, Lago M, Figueira JC, Fernández-Puntero B, Viejo A, Negredo A, Nuñez C, Flores E, Carcas AJ, Jiménez-Yuste V, Lasala F, García-de-Lorenzo A, Arnalich F, Arribas JR La Paz-Carlos IIIUHIU, La Paz-Carlos III University Hospital Isolation Unit. 2015. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with ebola virus disease contracted in Madrid, Spain. Lancet Respir Med 3:554562.[PubMed]
80. Richards GA, Murphy S, Jobson R, Mer M, Zinman C, Taylor R, Swanepoel R, Duse A, Sharp G, De La Rey IC, Kassianides C. 2000. Unexpected ebola virus in a tertiary setting: clinical and epidemiologic aspects. Crit Care Med 28:240244.[PubMed]
81. Rodriguez LL, De Roo A, Guimard Y, Trappier SG, Sanchez A, Bressler D, Williams AJ, Rowe AK, Bertolli J, Khan AS, Ksiazek TG, Peters CJ, Nichol ST. 1999. Persistence and genetic stability of ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 179(Suppl 1):S170S176.[PubMed]
82. Deen GF, Knust B, Broutet N, Sesay FR, Formenty P, Ross C, Thorson AE, Massaquoi TA, Marrinan JE, Ervin E, Jambai A, McDonald SL, Bernstein K, Wurie AH, Dumbuya MS, Abad N, Idriss B, Wi T, Bennett SD, Davies T, Ebrahim FK, Meites E, Naidoo D, Smith S, Banerjee A, Erickson BR, Brault A, Durski KN, Winter J, Sealy T, Nichol ST, Lamunu M, Ströher U, Morgan O, Sahr F. 2015. Ebola RNA persistence in semen of ebola virus disease survivors—preliminary report. N Engl J Med. epub: October 15, 2015.[PubMed]
83. Mate SE, Kugelman JR, Nyenswah TG, Ladner JT, Wiley MR, Cordier-Lassalle T, Christie A, Schroth GP, Gross SM, Davies-Wayne GJ, Shinde SA, Murugan R, Sieh SB, Badio M, Fakoli L, Taweh F, de Wit E, van Doremalen N, Munster VJ, Pettitt J, Prieto K, Humrighouse BW, Ströher U, DiClaro JW, Hensley LE, Schoepp RJ, Safronetz D, Fair J, Kuhn JH, Blackley DJ, Laney AS, Williams DE, Lo T, Gasasira A, Nichol ST, Formenty P, Kateh FN, De Cock KM, Bolay F, Sanchez-Lockhart M, Palacios G. 2015. Molecular evidence of sexual transmission of ebola virus. N Engl J Med 373:24482454.[PubMed]
84. Thorson A, Formenty P, Lofthouse C, Broutet N. 2016. Systematic review of the literature on viral persistence and sexual transmission from recovered ebola survivors: evidence and recommendations. BMJ Open 6:e008859.[PubMed]
85. Martines RB, Ng DL, Greer PW, Rollin PE, Zaki SR. 2015. Tissue and cellular tropism, pathology and pathogenesis of ebola and Marburg viruses. J Pathol 235:153174.[PubMed]
86. Zinzula L, Tramontano E. 2013. Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I-like receptors: hide, mask, hit. Antiviral Res 100:615635.[PubMed]
87. Towner JS, Rollin PE, Bausch DG, Sanchez A, Crary SM, Vincent M, Lee WF, Spiropoulou CF, Ksiazek TG, Lukwiya M, Kaducu F, Downing R, Nichol ST. 2004. Rapid diagnosis of ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol 78:43304341.[PubMed]
88. de La Vega MA, Caleo G, Audet J, Qiu X, Kozak RA, Brooks JI, Kern S, Wolz A, Sprecher A, Greig J, Lokuge K, Kargbo DK, Kargbo B, Di Caro A, Grolla A, Kobasa D, Strong JE, Ippolito G, Van Herp M, Kobinger GP. 2015. Ebola viral load at diagnosis associates with patient outcome and outbreak evolution. J Clin Invest 125:44214428.[PubMed]
89. Lanini S, Portella G, Vairo F, Kobinger GP, Pesenti A, Langer M, Kabia S, Brogiato G, Amone J, Castilletti C, Miccio R, Zumla A, Capobianchi MR, Di Caro A, Strada G, Ippolito G INMI-EMERGENCY EBOV Sierra Leone Study Group. 2015. Blood kinetics of ebola virus in survivors and nonsurvivors. J Clin Invest 125:46924698.[PubMed]
90. Faye O, Andronico A, Faye O, Salje H, Boëlle PY, Magassouba N, Bah EI, Koivogui L, Diallo B, Diallo AA, Keita S, Konde MK, Fowler R, Fall G, Cauchemez S, Sall AA. 2015. Use of viremia to evaluate the baseline case fatality ratio of ebola virus disease and inform treatment studies: A retrospective cohort study. PLoS Med 12:e1001908.[PubMed]
91. Geisbert TW, Hensley LE, Gibb TR, Steele KE, Jaax NK, Jahrling PB. 2000. Apoptosis induced in vitro and in vivo during infection by ebola and Marburg viruses. Lab Invest 80:171186.[PubMed]
92. Bradfute SB, Swanson PE, Smith MA, Watanabe E, McDunn JE, Hotchkiss RS, Bavari S. 2010. Mechanisms and consequences of ebolavirus-induced lymphocyte apoptosis. J Immunol 184:327335.[PubMed]
93. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Larsen T, Kagan E, Hensley LE. 2003. Pathogenesis of ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells. Am J Pathol 163:23712382.[PubMed]
94. Rollin PE, Bausch DG, Sanchez A. 2007. Blood chemistry measurements and D-Dimer levels associated with fatal and nonfatal outcomes in humans infected with Sudan Ebola virus. J Infect Dis 196(Suppl 2):S364S371.[PubMed]
95. McElroy AK, Erickson BR, Flietstra TD, Rollin PE, Nichol ST, Towner JS, Spiropoulou CF. 2014. Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome. J Infect Dis 210:558566.[PubMed]
96. Mahanty S, Bray M. 2004. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 4:487498.[PubMed]
97. Zaki SR, Shieh WJ, Greer PW, Goldsmith CS, Ferebee T, Katshitshi J, Tshioko FK, Bwaka MA, Swanepoel R, Calain P, Khan AS, Lloyd E, Rollin PE, Ksiazek TG, Peters CJ. 1999. A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of ebola hemorrhagic fever. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis 179(Suppl 1):S36S47.[PubMed]
98. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. 2003. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 188:16181629.[PubMed]
99. Parrino J, Hotchkiss RS, Bray M. 2007. Immune cell apoptosis prevention as potential therapeutic strategy for severe infections. Emerg Infect Dis 13:191198.[PubMed]
100. Hensley LE, Young HA, Jahrling PB, Geisbert TW. 2002. Proinflammatory response during ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily. Immunol Lett 80:169179.[PubMed]
101. Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB, Zaki SR, Swanepoel R, Ansari AA, Peters CJ. 1999. Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal ebola virus infection. J Infect Dis 179(Suppl 1):S188S191.[PubMed]
102. Sobarzo A, Ochayon DE, Lutwama JJ, Balinandi S, Guttman O, Marks RS, Kuehne AI, Dye JM, Yavelsky V, Lewis EC, Lobel L. 2013. Persistent immune responses after ebola virus infection. N Engl J Med 369:492493.[PubMed]
103. McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK, Kraft CS, Lyon GM, Ribner BS, Varkey J, Sidney J, Sette A, Campbell S, Ströher U, Damon I, Nichol ST, Spiropoulou CF, Ahmed R. 2015. Human ebola virus infection results in substantial immune activation. Proc Natl Acad Sci USA 112:47194724.[PubMed]
104. Bah EI, Lamah MC, Fletcher T, Jacob ST, Brett-Major DM, Sall AA, Shindo N, Fischer WA II, Lamontagne F, Saliou SM, Bausch DG, Moumié B, Jagatic T, Sprecher A, Lawler JV, Mayet T, Jacquerioz FA, Méndez Baggi MF, Vallenas C, Clement C, Mardel S, Faye O, Faye O, Soropogui B, Magassouba N, Koivogui L, Pinto R, Fowler RA. 2015. Clinical presentation of patients with ebola virus disease in Conakry, Guinea. N Engl J Med 372:4047.[PubMed]
105. Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. 2014. Ebola virus disease in West Africa—clinical manifestations and management. N Engl J Med 371:20542057.[PubMed]
106. Chertow DS, Uyeki TM, DuPont HL. 2015. Loperamide therapy for voluminous diarrhea in ebola virus disease. J Infect Dis 211:10361037.[PubMed]