The document provides information on Ebola virus, including its history, outbreaks, transmission, symptoms, diagnosis and potential treatments. It discusses how Ebola was first identified in 1976 near the Ebola River in Africa. It causes severe hemorrhagic fever in humans with high mortality. While fruit bats are suspected to be the natural reservoir, transmission occurs between humans via contact with bodily fluids. Current efforts are focused on supportive care and experimental therapies like monoclonal antibodies, antivirals and immunomodulators until a vaccine is developed.

1. Presented by
Deepti Singh
Ph.D. (Biotechnology)
Enrol.No. B-1384/14
COLLEGE OF BIOTECHNOLOGY
DUVASU, MATHURA

2. OUTLINE
• INTRODUCTION
• HISTORY
• OUTBREAKS
• TYPES
• TRANSMISSION
• LIFE CYCLE
• SYMPTOMS
• PREVENTION
• DIAGNOSIS
• TREATMENT
• VACCINES
• CONCLUSION
• BIBLIOGRAPHY

3. INTRODUCTION
• Ebola viruses cause a severe illness known as Ebola hemorrhagic
fever that can be lethal to humans.
• Although hemorrhagic fever can be brought on by several types of
viruses, Ebola produces one of the most deadly forms of viral
hemorrhagic fevers.
• Mortality rates for Ebola hemorrhagic fever are high, ranging from
50 percent to 90 percent, with death usually occurring from shock
rather than blood loss.

4. HISTORY
The virus takes its name from the Ebola River in the northern Congo
basin of central Africa, where it first emerged in 1976.
Prevention is through isolation of the infected person/s so it does
not spread.
In Hot Zone in Africa a cave called Kitum cave is found which links
two separate single-incidence occurrences of Ebola. Scientists went to
the cave and took blood samples from everything they can find. They
found nothing at all and the results were never formally published.
Kitum cave was stuffed with bats; so the fruit bat find could explain
how two people died of Ebola in separate incidents after visiting Kitum
cave.

5. Past outbreaks
 EVD first appeared in in 1976 in 2 simultaneous outbreaks – Zaire,
Sudan and Yambuku, DRC.
 The latter occurred in a village near Ebola(origin of name).
Year Country
Ebolavirs
species Cases Deaths Case fatality
2012
Democratic
Republic of Congo Bundibugyo 57 29 51%
2012 Uganda Sudan 7 4 57%
2012 Uganda Sudan 24 17 71%
2011 Uganda Sudan 1 1 100%
2008
Democratic
Republic of Congo Zaire 32 14 44%
2007 Uganda Bundibugyo 149 37 25%
2007
Democratic
Republic of Congo Zaire 264 187 71%

6. Year Country
Ebolavirus
Species Cases Deaths Case fatality
2005 Congo Zaire 12 10 83%
2004 Sudan Sudan 17 7 41%
2003 (Nov-
Dec) Congo Zaire 35 29 83%
2003 (Jan-Apr) Congo Zaire 143 128 90%
2001-2002 Congo Zaire 59 44 75%
2001-2002 Gabon Zaire 65 53 82%
2000 Uganda Sudan 425 224 53%
1996
South Africa
(ex-Gabon) Zaire 1 1 100%
1996 (Jul-Dec) Gabon Zaire 60 45 75%

7. Year Country Ebola
species
Cases Deaths Case fatality
1995
Democratic
Republic of Congo Zaire 315 254 81%
1994 Cote d'Ivoire Taï Forest 1 0 0%
1994 Gabon Zaire 52 31 60%
1979 Sudan Sudan 34 22 65%
1977
Democratic
Republic of Congo Zaire 1 1 100%
1976 Sudan Sudan 284 151 53%
1976
Democratic
Republic of Congo Zaire 318 280 88%

8. PRESENT OUTBREAK
 The recent outbreak (2014) in West Africa is the largest and
complex outbreak since the Ebola virus was first discovered in 1976.
 It has spread between countries starting in Guinea then spreading
across land borders to Sierra leone and Liberia, by air(1 traveller
only) and by land(1 traveller) to Senegal.
 These are the most severly affected countries due to weak health
systems.
 The index case was a pregnant woman who prepared bushmeat
from an animal.
 On Aug 8, 2014 WHO declared it as “Public Health Emergency of
international Concern”.
 Zaire species is involved in the present outbreak of Ebola.

9. IMPORTANT TIMELINE OF EBOLA OUTBREAK
• March 22: Guinea confirms a previously unidentified hemorrhagic fever, which
killed over 50 people in its south eastern Forest Region, is Ebola. One study traces
the suspected original source to a 2-year-old boy in the town of Gueckedou. Cases
are also reported in the capital, Conakry.
• March 30: Liberia reports two Ebola cases; suspected cases reported in Sierra
Leone.
• May 26: WHO confirms first Ebola deaths in Sierra Leone.
• June 23: With deaths above 350, making the West African outbreak the worst
Ebola epidemic on record, MSF says it is "out of control" and calls for massive
resources.
• July 25: Nigeria, Africa's biggest economy, confirms its first Ebola case, a man who
died in Lagos after traveling from Monrovia.
• Aug. 2: A U.S. missionary physician infected with Ebola in Liberia is flown to Atlanta
in the United States for treatment.
• Aug. 5: A second U.S. missionary infected with Ebola is flown from Liberia to
Atlanta for treatment.
• Aug. 8: WHO declares Ebola "international public health emergency," stops short
of urging ban on trade and travel.
• Aug. 12: WHO says death toll has topped 1,000, approves use of unproven drugs
or vaccines.
• A Spanish priest with Ebola dies in a Madrid hospital.

10. • Aug. 24: Democratic Republic of Congo declares Ebola outbreak in a
northern province, apparently separate from larger outbreak.
• An infected British medical worker is flown home from Sierra Leone for
treatment.
• Aug. 29: Senegal reports first confirmed Ebola case
• Sept. 3: Epidemic's pace accelerates; deaths top 1,900. Officials say there
were close to 400 deaths in the past week.
• A third U.S. missionary doctor infected with Ebola is flown out of Liberia for
treatment in Omaha, Nebraska.
• Sept. 26 - New WHO tally: 3,091 dead out of 6,574 probable, suspected and
confirmed cases
• Sept. 30 - CDC confirms the first diagnosis in the United States of a patient
infected with Ebola. The patient, being treated at a hospital in Dallas, had
travelled to West Africa
• Oct. 17 –WHO declares Senegal free of Ebola.
• Oct. 20-WHO declares Nigeria free of Ebola.

12. EPIDEMIOLOGICAL STATUS
• Ebola first emerged in Sudan and Zaire in the year 1976.
• The first outbreak of Ebola (Ebola-Sudan) infected over 284 people,
with a mortality rate of 53%.
• A few months later, the second Ebola virus emerged from Yambuku,
Zaire, (Ebola-Zaire); it had the highest mortality rate of any of the
Ebola viruses (88%), infected 318 people.
• On the basis of available evidence and the nature of similar viruses,
researchers believe that the virus is animal-borne and is normally
maintained in an animal host that is native to the African continent.
• The virus is not known to be native to any other continents,
though.

14. TYPES OF EBOLA
There are five subtypes of Ebola viruses:
1. Bundibugyo virus (BDBV).
2. Sudan virus (SUDV).
3. Taï Forest virus (TAFV).
4. Zaire Ebola virus (EBOV).
5. Reston virus.
Each of these viruses were named after the location in which the
disease had its first out break.

15. WHERE CAN THE VIRUS BE FOUND?
• Originates in primates including gorillas, chimpanzees, and humans
and some domestic pigs, also elephants in central Africa
• Host cell: Ebola interacts specifically with liver cells and cells of the
reticulo-endothelial system. The lining of blood capillaries are
attacked. The capillaries start to leak fluids and plasma proteins.
Some patients experience intravascular coagulation, and loss of
normal clotting capability.

16. The virus kills gorillas and
chimpanzees and other monkeys.
Because it kills apes in such high
percentage – they are not likely
to be its natural host.

17. TOWARDS DETECTING THE NATURAL
HOST OF THE VIRUS

18. HOW IS IT TRANSMITTED?
• Ebola is transmitted by blood, bodily fluids, and tissue of infected
people.
• Ebola can be transmitted in the simplest of ways. If you are walking
in the bush and an elephant has the virus and the elephant sneezes,
the virus can be transmitted by entering your mouth or even
touching an open cut.

21. LIFE CYCLE
• First in the non-human animal.
• Gets transmitted to the human by direct contact with their faeces
and bodily fluids. Animal can sneeze and the virus can make direct
contact with a human mouth or even a cut.
• Gets into the host cell (liver cell).
• The virus multiplies in the cell.
• Then is transferred by the human to another animal or human
through the same way the virus was transferred him/her.

23. THE WEAK LINK
• The transmission and spread can be cut off near the end of stage 4
by isolating the human thus he/she can’t contaminate anyone or
anything else.
• As the man’s body fluids and tissue is not in contact with any other
possible hosts the virus continues to multiply within the person till
death.

24. WHERE DOES EBOLA HIDE?
• Fruit Bats
• Ebola in liver and spleen
cells.
• Fruit bats do not show any
symptoms.
• More research needs to be
done.

25. SYMPTOMS OF DISEASE
Time Frame Symptoms that
occur in most
Ebola patients:
Symptoms that
occur in some
Ebola patients:
Within a few days
of becoming
infected with the
virus:
high fever, head
ache, muscle aches,
stomach pain,
fatigue, diarrhea
Sore throat,
hiccups, rash, red
and itchy eyes,
vomiting blood,
bloody diarrhea
Within one week
of becoming
infected with the
virus:
Chest pain, shock,
and death
Blindness and
bleeding

27. CONTROLLING EBOLA
To control Ebola and make sure it does not spread, one needs to
isolate the person in and enclosed area until he/she dies.
This affects some communities cultural aspects as this means none
of the persons family or friends can give the person a good bye hug,
hold, etc. since the virus is contagious.
This also means a funeral can’t be held and even if it is the best for
people on a global basis, their culture has been invaded and they
weren’t allowed to do what they might have been doing for
generations.

28. CONT…..
 A successful virus does not kill its host and also does not seriously
harm it. When the traditional host of a virus is wiped out, the virus
will try to jump to other species, and it will mutate.
 A virus that is benign to a moth may be a killer of humans.
 Conserving the environment can keep these killers in harmless
hosts inside the rain forests and jungles of the world. Wipe out
their environments and the hosts will die, the viruses will mutate
and jump species, and we could be in serious trouble.

30. EBOLA IS NOT SPREAD BY:

31. DIAGNOSIS OF EBOLA
• Diagnosing Ebola can be difficult at first since early symptoms, such as
fever, are nonspecific to Ebola infection.
• However, if a person has the early symptoms and has had contact with
Ebola they should be isolated and public health professionals notified.
• Samples from the patient can then be collected and tested to confirm
infection.

32. • The diagnosis is confirmed by isolating the virus, detecting its RNA or
proteins, or detecting antibodies against the virus in a person's blood.
• Isolating the virus by cell culture, detecting the viral RNA by polymerase
chain reaction (PCR) and detecting proteins by ELISA is effective early
and in those who have died from the disease.
• Virions can be seen and identified in cell culture by electron
microscopy due to their unique filamentous shapes, but electron
microscopy cannot tell the difference between the various filoviruses
despite there being some length differences.
• Detecting antibodies against the virus is effective late in the disease and
in those who recover.
SPECIFIC METHODS

33. Timeline of Infection Diagnostic tests available
Within a few days after symptoms begin
•Antigen-capture enzyme-linked
immunosorbent assay (ELISA) testing
•IgM ELISA
•Polymerase chain reaction (PCR)
•Virus isolation
Later in disease course or after recovery •IgM and IgG antibodies
Retrospectively in deceased patients
•Immunohistochemistry testing
•PCR
•Virus isolation
Source: Centers for Disease Control and Prevention http://www.cdc.gov/vhf/ebola/diagnosis/index.html
Accessed Oct. 14, 2014
EBOLA DIAGNOSTIC TECHNIQUES

34. Immunochromatographic method

35. EBOLA VIRUS DIAGNOSIS
• Real Time PCR (RT-PCR):
– Used to diagnose acute infection.
– More sensitive than antigen detection ELISA.
– Identification of specific viral genetic fragments.
– Performed in selected certified laboratories.
• RT-PCR sample collection:
– Volume: minimum volume of 4mL whole blood.
– Plastic collection tubes.
– Whole blood preserved with EDTA is preferred .
• Whole blood preserved with sodium polyanethol sulfonate
(SPS), citrate, or with clot activator is acceptable.

36. CONT…..
• Virus isolation
– Requires Biosafety Level 4 laboratory.
– Can take several days.
• Immunohistochemical staining and histopathology
– On collected tissue or dead wild animals; localizes viral antigen.
• Serologic testing for IgM and IgG antibodies (ELISA):
– Detection of viral antibodies in
specimens, such as blood, serum,
or tissue suspensions.
– Monitor the immune response
in confirmed EVD patients.

37. POTENTIAL EBOLA TREATMENTS
1. Antibody therapy
a. Convalescent whole blood and
plasma
b. Monoclonal antibodies (ZMapp)
2. Antiviral therapy
a. RNA-based drugs
b. Brincidofovir (CMX-001)
3. Immunomodulators
4. Coagulation modulators

38. MONOCLONAL ANTIBODIES - ZMapp
• Cocktail of 3 monoclonal antibodies:
– c13C6 and c2G4 and c4G7
• Manufactured in tobacco plants.
• Targets Ebola virus glycoprotein.
• Attaches to the virus and block its infective potential.
• Not yet tested in human trials.
• Small number of cases from current outbreak given drug on
compassionate basis with variable results.
• Current supplies of drug exhausted.
• Efforts being made to scale up production, task difficult due to its
complex production processes.

39. RNA-BASED DRUGS
• Interfere with translation of Ebola virus mRNA to protein.
• Prevent virus from replicating.
Favipiravir (T-705)
• Orally
• Approved for influenza treatment in Japan.
• Efficacy against Ebola in mice (Oestereich et al 2014).
AVI-7537
• Intravenously
• In early stage development for treatment of Ebola virus.
• It is an antisense phosphorodiamidate morpholino oligimers (PMO)
that inhibits VP24 protein of Ebola virus.

40. CONT…..
TKM-Ebola
• Intravenously.
• It is a small interfering RNA (siRNA), affecting 3 of Ebola’s 7
proteins.
• Limited safety and efficacy data are available.
• Clinical hold on phase 1 trials in early 2014, because of increased
cytokine levels in healthy individuals.
• FDA has approved the emergency use of TKM-Ebola during the
current outbreak.
• Risk versus benefit should be estimated when deciding whether to
use this agent.

41. BRINCIDOFOVIR (CMX-001)
• Orally
• Brincidofovir is a prodrug of cidofovir but fewer renal side-effects
than cidofovir.
• In vitro tests have shown its potential for treatment of EVD.
IMMUNOMODULATORS
Interferons
• Commercially available.
• Efficacy in rodents.
• Delayed time to death (Smith et al 2013).

42. COAGULATION MODULATORS
• Severe coagulation disorder occurs in EVD.
• Recombinant Activated Protein C
– Inhibits clotting factors.
– Levels of protein C low in EVD.
• Recombinant Nematode Anticoagulant Protein
– Inhibits clotting factors.
– Limited success with both in NHP studies.
(Hensley et al 2007; Geisbert et al 2003)

43. LINE OF TREATMENT
• There are no approved treatments available for EVD.
• Clinical management focus - supportive care of complications:
– hypovolemia, electrolyte abnormalities, haematologic
abnormalities, refractory shock, hypoxia, haemorrhage, septic
shock, multi-organ failure.
• Recommended care includes:
– volume repletion.
– maintenance of blood pressure (with vasopressors if needed)
– maintenance of oxygenation.
– pain control.
– nutritional support.
– treating secondary bacterial infections.
Source: Centers for Disease Control and Prevention. http://www.cdc.gov/vhf/ebola/hcp/clinician-information-
us-healthcare-settings.html Accessed Oct. 14, 2014

44. CONT….
• Among patients from West Africa, large volumes of intravenous
fluids have often been required to correct dehydration due to
diarrhea and vomiting.
• Several investigational therapeutics for Ebola virus disease are in
development.
• There are no approved vaccines available for EVD.
• Several investigational Ebola vaccines are in development, and
Phase I trials are underway for some vaccine candidates.
Source: Centers for Disease Control and Prevention. http://www.cdc.gov/vhf/ebola/hcp/clinician-information-
us-healthcare-settings.html Accessed Oct. 14, 2014

45. • DNA vaccines, adenovirus-based vaccines, and VSIV-based vaccines
have entered clinical trials.
• No licensed vaccine for EVD is available. Several vaccines are being
tested, but none are available for clinical use.
POSSIBILITY OF VACCINES?

46. EBOLA VACCINES - HISTORICALLY
• Debate about requirement for vaccine previously-
o Rarity of disease.
o Lack of interest from pharmaceutical industry
o Potential cost.
• View has changed in recent years-
o Increasing frequency of outbreaks with high
case fatality rates.
o Number of imported cases of viral
haemorrhagic fever and laboratory exposures.
o Potential misuse of EVD as bioterrorism agent.

47. WHO TO VACCINATE?
• Valuable for:
 Medical personnel
 First responder
 Military personnel
 Researchers
 Ring vaccination in outbreak

48. WHAT’S IN THE PIPELINE?
• Several candidate vaccines being developed.
• Two identified as being at the most advanced stage of
development.
• Both are recombinant vector vaccines:
1. Chimpanzee adenovirus serotype 3 (cAd3-EBO)
2. Recombinant vesicular stomatitis virus (rVSV-EBO)
• Both are being fast-tracked but data on safety and efficacy are
limited.

49. 1. CHIMPANZEE ADENOVIRUS SEROTYPE 3
(cAd3-EBO)
• Based on recombinant adenovirus 3 (cAd3)
technology-
– a surface protein gene of Ebola virus is inserted into a modified
chimpanzee adenovirus
– resulting virus cannot replicate in humans, but is intended to
induce an immune response
• Pre-existing immunity in humans may be a problem, impairing
vaccine efficacy.
• However, cAd3 is a rare adenovirus serotype, with most humans not
having pre-existing immunity.

50. CONT…..
• cAd3-EBO tested in 16 NHPs and found to be 100% protective
(Stanley et al 2014).
• Phase 1 human trials began in September in US and Oxford.
• Being developed by GlaxoSmithKline and US National Institute of
Health.

51. 2. RECOMBINANT VESICULAR STOMATITIS
VIRUS VACCINE (rVSV-EBO)
• VSV causes mild flu-like illness in humans.
• Gene for surface glycoprotein of Ebola inserted into VSV - this
recombinant virus is then intended to induce an immune response
in humans to Ebola virus.
• Jones et al (2005)
– 100% protective against Zaire Ebola virus (ZEBOV) in NHPs after
a single vaccination.
• Feldmann et al (2007)
– demonstrated varying degrees of protection post-exposure in
NHPs if vaccine given up to 24 hours after exposure to a lethal
dose of Ebola virus.

52. CONT….
• Given to lab worker exposed to ZEBOV following needle stick injury
in Hamburg, 2009
– VSV viraemia but did not develop EVD.
– It’s not possible to know if treatment
was effective or if patient was never
infected.
• Phase 1 human trials has began.
• Being developed by Public Health Agency of Canada, NewLink
Genetics and others.

54.  To obtain samples and study the disease in remote areas where
outbreaks occur.
 A high degree of biohazard containment is required for laboratory
studies and clinical analysis.
 CD4+ T cells are important master‐regulators of the immune response
and other cellular compartments to produce more robust and long
lasting immunity.
 Lack of CD4+ T cells in Ebola infection that is thought to underlie the
suboptimal antibody responses in infected subjects and the ultimate
inability to mount sufficient antibody responses to suppress the
infection.
 Potent vaccination strategy against Ebola must include a robust CD4+ T
cell‐mediated response, likely critical in providing T cell help to the B
cell compartment.
DIFFICULTY IN MAKING VACCINES

55. CONCLUSION
Ebola is a threat not only to humans but also to our closest living
relatives - the great apes.
The western lowland gorilla populations have been reduced by Ebola
to such an extent that they are now considered "critically
endangered". About a third of the gorillas in protected areas have died
from Ebola in the past 15 years.
Scientists are concerned that their numbers may not be able to
recover and fear that they could become extinct in decade.

56. BIBLIOGRAPHIES
• "Ebola Haemorrhagic Fever." WHO. N.p., 2013. Web. 12 Oct. 2013.
<http://www.who.int/csr/disease/ebola/en/>.
• "Ebola (virus)." Encyclopedia Britannica Online. Encyclopedia Britannica, 2013. Web. 12 Oct.
2013. <http://www.britannica.com/EBchecked/topic/177623/Ebola>.
• Types of Viruses." Biology4Kids.com: Microorganisms: Viruses. N.p., 2013. Web. 17 Oct. 2013.
<http://www.biology4kids.com/files/micro_virus.html>.
• "Developed Antibodies against Deadly Ebola Vius." NATIONAL GEOGRAPHIC. N.p., 21 Nov.
2011. Web. 17 Oct. 2013. <http://www.nationalgeographic.de/aktuelles/antikoerper-gegen-
toedliches-ebolavirus-entwickelt>.
• Baize S. et al. Emergence of Zaire Ebola Virus Disease in Guinea - Prepminary Report. N Engl
J Med. 2014 Apr 16. epub
• Feldmann H , Geisbert TW. Ebola Haemorrhagic Fever. Lancet. 2011 Mar 5;377(9768):849-
62.
• Fowler RA, Fletcher T, Fischer WA, et al. Caring for Critically Ill Patients with Ebola Virus
Disease: Perspectives from West Africa. Am J Respir Crit Care Med. 2014 Aug 25.
• WHO Ebola Response Team. NEJM 2014; 2Feldman H & Geisbert TW. Lancet 2011; 3Ksiazek
TG et al. JID 1999; 4Sanchez A et al. J Virol 2004; 5Sobarzo A et al. NEJM 2013; and 6Rowe AK
et al. JID 1999.

57. • Kortepeter MG, Bausch DG, Bray M. Basic Cpnical and Laboratory Features of Filoviral
Hemorrhagic Fever. J Infect Dis. 2011 Nov;204 Suppl 3:S810-6
• WHO Ebola Response Team. Ebola Virus Disease in West Africa – The First 9 Months of the
Epidemic and Forward Projections. N Eng J Med. 2014 Sept 23. Epub
• WHO website
• Source: http://www.cdc.gov/vhf/ebola/index.html Accessed Oct. 14, 2014
• http://www.medterms.com/script/main/art.asp?articlekey=6490
• http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/ebolamap.htm
• http://www.psmid.org.ph/vol25/vol25num1topic9.pdf
• http://www.dailygalaxy.com/my_weblog/2009/07/a-hot-zone-sequel-a-new-ebola-virus-
detected-in-pigs.html
• http://www.rkm.com.au/virus/ebola/
• http://www.virtualmedicalcentre.com/diseases.asp?did=321#Prognosis
• http://www.scienceagogo.com/news/20100431010042data_trunc_sys.shtml
• http://health.nytimes.com/health/guides/disease/ebola-hemorrhagic-fever/overview.html
• http://www.cdc.gov/vhf/ebola/outbreaks/guinea/
• http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html
• http://www.who.int/csr/don/archive/disease/ebola/en/
• http://www.who.int/csr/disease/ebola/en/
• http://en.wikipedia.org/wiki/2014_West_Africa_Ebola_virus_outbreak#India
• Ananthanarayan and Paniker’s Textbook of Microbiology, University press, 9th ed.

58. • Statement on the WHO Consultation on potential Ebola therapies and vaccines.
http://www.who.int/mediacentre/news/statements/2014/ebola-therapies-consultation/en/
• Sullivan NJ, Geisbert TW,Geisbert et al. Accelerated vaccination for Ebola virus haemorrhagic
fever in non human primates. Nature. 2003;424:681-4
• Tuffs A. Experimental vaccine may have saved Hamburg scientist from Ebola fever. BMJ.
2009;338:b1223
• Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles
J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly
MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP.
Reversion of advanced Ebola virus disease in non human primates with ZMAPP. Nature.
2014;514(7520):47-53
• Wong G, Qiu X, Olinger GG, Kobinger GP. Post-exposure therapy of filovirus infections. Trends
Microbiol. 2014;22(8):456-63
• Stanley DA, Honko AN, Asiedu C, Trefry JC, Lau-Kilby AW, Johnson JC, Hensley L, Ammendola
V, Abbate A, Grazioli F, Foulds KE, Cheng C, Wang L, Donaldson MM, Colloca S, Folgori A,
Roederer M, Nabel GJ, Mascola J, Cortese R, Koup RA, Sullivan NJ. Chimpanzee adenovirus
vaccine generates acute and durable immunity against ebolavirus challenge. Nat Med.
2014;20(10):1126-9
• Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377(9768):849-62
• Feldmann H, Jones SM, Daddario DiCaprio KM et al. Effective post-exposure treatment of
Ebola infection. Plos Pathog. 2007;3:e2
• Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J, Young HA, Fredking TM,
Rote WE, Vlasuk GP. Treatment of Ebola virus infection with a recombinant inhibitor of
VIIa/tissue factor: a study in rhesus monkeys. Lancet. 2003;362:1953-58

59. • Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, Johnson JC, de Jong S, Tavakoli I,
Judge A, Hensley LE, MacLachlan I. Post exposure protection of non human primates against a
lethal Ebola challenge with RNA interference: a proof of concept study. Lancet. 2010;375:1896-
1905
• Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying
coagulation abnormalities in Ebola haemorrhagic fever: overexpression of tissue factor in primate
monocytes/macrophages is a key event. J Infect Dis. 2003;188(11):1618-1629
• Hensley LE, Stevens EL, Yan SB, Geisbert JB, Macias WL, Larsen T, Daddario-DiCaprio KM, Cassell GH,
Jahrling PB, Geisbert TW. Recombinant human activated protein C for the postexposure treatment
of Ebola haemorrhagic fever. J Infect Dis. 2007; 196(suppl 2):S390-S399
• Iversen PL, Warren TK, Wells JB, Garza NL, Mourich DV, Welch LS, Panchal RG, Bavari S. Discovery
and early development of AVI-7537 and AVI-7288 for the treatment of Enola virus and Marburg
virus infections. Viruses. 2012;4:2806-2830
• Jones SM, Feldmann M, Stroher U, Geisbert JB, Fernando L, Grolla A et al. Live attenuated
recombinant vaccine protects non human primates against Ebola and Marburg viruses. Nature
medicine. 2005;11(7):786-90
• Marzi A, Feldmann H. Ebola virus vaccines: an overview of current approaches. Expert Rev Vaccines.
2014;13(4):521-531
• Mupapa K, Massamba M, Kibadi K, et al. Treatment of Ebola haemorrhagic fever with blood
transfusions from convalescent patients. International Scientific and Technical Committee. J Infect
Dis. 1999;179(suppl 1):S18-S23
• Oestereich L, Ludtke A, Wurr S, Rieger T, Munoz-Fontela C, Gunther S. Successful treatment of
advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res.
2014;105:17-21