Transcript Z-mapp - Moodle Lille 2

EBOLA
2014 OUTBREAK, EXPERIMENTAL TREATMENTS
AND RISK MANAGEMENT
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Presentation plan
 Virus and disease
 West African outbreak in 2014
 Cases outside West Africa and experimental
treatments
 Risk management
 Other treatments and vaccines
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Virus and disease
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Ebola virus = EBOV
 Family : Filoviridae, RNA virus, 5 species, specie now: Zaire
Ebola Virus : ZEBOV
 Ebola virus disease (EVD): fatal hemorrhagic fever in
humans and other mammals
 Ebola was discovered in 1976 in two outbreaks: one in
Sudan and the other near the Ebola river in the Democratic
Republic of Congo
 Scientists believe that bats are the natural reservoir for the
virus
http://www.who.int/mediacentre/factsheets/fs103/en/
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Transmission
Rupa Kanapathipillai et al., N England J Med 2014 ; 371
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Symptoms
 Ebola can only be spread to • Fever fatigue
• Muscle pain
others after symptoms
• Headache
begin.
• Sore throat
 Symptoms can appear from
2 to 21 days after exposure. Followed by :
• Diarrhea
• Vomiting
• Rash
• Symptoms of impaired kidney
and liver function
• In some cases : internal and
external bleeding
cdc.gov
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After diagnosis
 Quarantine
 Symptoms of Ebola are treated as they appear
 Providing IV fluids balancing electrolytes (body
salts)
 Maintaining oxygen status and blood pressure
 Treating other infections if they occur
 Experimental vaccines and treatments for
Ebola are under development
 Recovery from Ebola depends on good
supportive care and the patient’s immune
response
 Countries affected do not have the capacity to
manage an outbreak of this size
cdc.gov
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Historic of outbreaks
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West African outbreak in 2014
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West African outbreak in 2014
Seems to have started in a village near Guéckédou, Guinea, where bat
hunting is common.
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West African outbreak in 2014
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West African outbreak in 2014
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West African outbreak in 2014
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West African outbreak in 2014
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West African outbreak in 2014
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West African outbreak in 2014
CDC : last update October 25, 2014
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Cases of Ebola outside
West Africa and
experimental treatments
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Cases of Ebola outside West
Africa
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August, 2
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
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 3 humanized monoclonal antibodies
 Manufactured in tobacco plant Nicotiana
benthamiana
Z-mapp
Mapp Biopharmaceutical,
Kentucky BioProcessing
subsidiary of Reynolds
American, USA
Experimental
biopharmaceutical drug
 Under development as treatment for
Ebola virus disease
 Tested in primates
 Not been subjected to a randomized
clinical trial to prove its safety or its
efficacy
 Tested in humans during the 2014 West
Africa Ebola virus outbreak
 9 persons treated: 5 recovered and 4 died
 Out of stock
 In trials : Z-mabs (Mapp) : similar to Zmapp
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September
5, Dr Sacra, American,
from Liberia
August, 2
Treated with TKMEbola and Brantly’s
blood
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
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TKM-EBOLA
(TKM 100802)
Tekmira Pharmaceuticals,
Vancouver with the
department of USA
defense
 3 small interfering RNA (siRNA) cause the
destruction of 3 proteins in Ebola virus
 Effectiveness in non human primates
against Zaire Ebola virus (Geisbert et al., Lancet 2010 ; 375 : 1896)
 Clinical trials:
 Phase I: in January 2014 : safety, tolerability
and PK, healthy subjects, single ascending
dose tested
 Consortium TKM with WHO to provide a clinical
trial in West Africa
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Bloodtherapy
 Transfusion of serum of recovered
infected patient
 Contains antibodies against Ebola virus
 Dr Brantly’s blood who recovered from
the disease was used on compatible
patients
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September
5, Dr Sacra, American,
from Liberia
August, 2
Treated with TKMEbola and Brantly’s
blood
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
7, Missionary
Parajes from
Liberia to Spain,
treated by
Z-mapp, died
22, missionary Garcia
from Sierra Leone to
Spain, treated by ?
Died
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September
5, Dr Sacra, American,
from Liberia
August, 2
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
7, Missionary
Parajes from
Liberia to Spain,
treated by
Z-mapp, died
Treated with TKMEbola and Brantly’s
blood
9 : French nurse from
Liberia, treated (?),
recovered
- Favipiravir
- Z-mapp
- TKM-Ebola
22, missionary Garcia
from Sierra Leone to
Spain, treated by ?
Died
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 = Avigan ®
Favipiravir
=T-705
Developed by FujiFilm
subsidiary Toyama
Chemicals Co., Japan
 Oral anti-viral against RNA viruses
 Approved against seasonal influenza
 Inhibits replication of Zaire Ebola Virus
in cell culture
 In mouse model : effective even if
initiated at day 6 post infection
 November: trials in Guinea
 Production to treat 20 000 potential
patients
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September
5, Dr Sacra, American,
from Liberia
August, 2
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
7, Missionary
Parajes from
Liberia to Spain,
treated by
Z-mapp, died
Treated with TKMEbola and Brantly’s
blood
30 : Mr Duncan,
Liberian man, tested
positive in Dallas,
treated with
brincidofovir
9 : French nurse from
Liberia, treated (?),
recovered
- Favipiravir
- Z-mapp
- TKM-Ebola
22, missionary Garcia
from Sierra Leone to
Spain, treated by ?
Died
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 Oral anti-viral drug active against DNA
viruses
Brincidofovir
(CMX001)
Chimerix (USA)
 In phase III for adenovirus and
cytomegalovirus
 Potential treatment of Ebola virus
disease shown in preliminary in vitro
tests (RNA virus)
 Patient in US (Mr Duncan) received it
but was very ill and died
 Approval by FDA in October 16 to start
Phase II trials for Ebola (emergency
investigational new drug applications)
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October
8, Mr Duncan died
September
5, Dr Sacra, American,
from Liberia
August, 2
2 aid workers (Dr
Brantly), from
Liberia, treated
by Z-mapp, both
recovered
7, Missionary
Parajes from
Liberia to Spain,
treated by
Z-mapp, died
Treated with TKMEbola and Brantly’s
blood
9 : French nurse from
Liberia, treated (?),
recovered
30 : Mr Duncan,
Liberian man, tested
positive in Dallas,
treated with
brincidofovir
October:
Contamination of 2
nurses Vinson and
Pham, recovered
- Favipiravir
- Z-mapp
- TKM-Ebola
22, missionary Garcia
from Sierra Leone to
Spain, treated by ?
Died
October:
Contamination of
spanish nurse Romero,
treated with Z-mapp,
recovered
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Risk management
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Outbreak control
 Prevention :
 Reduce the risk of wildlife-to-human transmission
 Contact with infected fruits, animals
 Animal products should be cooked
 Reduce the risk of human-to-human transmission
 Direct contact with people with Ebola symptoms
 Gloves, personal protective equipment
 Outbreak containment measures
 Prompt and safe burial of the dead
 Identifying people in contact and monitoring
Who.int
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Health-care settings
 Health-care workers have frequently been infected
while treating patients
 Precautions:
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Basic hand hygiene
Personal protective equipment
Safe injection practices
Safe burial practices
 Guidelines from CDC (USA), eCDC (Europe),
Ministery of health (France) …
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procedure for personal protective equipment
caring for suspect or confirmed patients
environmental infection control in hospitals
safe handling of human remains
…
Who.int
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cdc.org
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Other treatments
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AVI-6002
Developped by Sarepta
Therapeutics,
Cambridge,USA
 Antisense drug
 Combinaison AVI-7537 and AVI-7539
against viral matrix proteins VP 24 and
VP 35
 Effectiveness in non human primates
against Zaire Ebolavirus
 Phase I: favorable safety
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cAd3ZEBOV
Vaccine
GSK (UK)
 Adenovirus carrying two genes of the
Ebola virus
 Animal testing: production of proteins
that stimulate the immune system to
produce antibodies
 Fast tracked in human studies in
August
 First Phase I in USA, UK and Mali
 Results by the end of 2014
 If successful: vaccination of healthcare
workers in Sierra Leone, Guinea and
Liberia
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VSV-ZEBOV
Vaccine
Developped by the
Canadian National
Microbiology Laboratory,
collaboration with
NewLink Genetics
 Vesicular stomatitis virus and Ebola gp
 provoke an immune response
 Protective efficacy against Ebola in
animals (80-100 %)
Phase I allows in USA, Canada results
previous December 2014
 October: 800-1000 vials sent to WHO:
3 shipments for precautions, (-80°),
tested previous with volunteers from
Germany, Switzerland, Gabon, Kenya
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Conclusion
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Conclusion
 Important Ebola outbreak
 Experimental treatments and vaccines
 USA, UK, France, Germany, Italy : discussion
for organization : aid workers and resources
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Thanks for your attention
Any questions ?
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