Download Ebola the Evolving Epidemic: From Africa to Europe & US

Rashid A. Chotani, MD, MPH
Adjunct Professor, GWU
[email protected]
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Outline



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History
Reservoir
How does the disease spread
Current Epidemic
• West Africa
• Europe
• US
 Treatment Modalities
 State of the Art of Current Vaccines, Therapeutics and Diagnostic
Devices
 Discussion
History
 Ebola virus disease (EVD) (formerly known as Ebola haemorrhagic fever) is a
severe disease caused by a virus of the filovirus family, which occurs in humans and
non-human primates
 1976: It first appeared simultaneously in Nzara, Sudan and Yambuku in the
Democratic Republic of Congo (DRC)

Two strains were identified; Sudan & Zaire
 1989: The third strain, was discovered in Reston, VA

It caused severe illness in non-human primates but not in humans. Virus was found in a
colony of monkeys imported from the Philippines


Subsequently caused outbreaks in non-human primates in Pennsylvania (Philadelphia), Texas (Alice)
and Italy (Sienna)
Several research workers became infected with the virus during these outbreaks, but did not become
ill
 1994: The forth strain was discovered during necropsy in Cote D’Ivoire, and
outbreaks have been occurring with increasing frequency since.
 2008: A fifth strain, from Uganda called the Bundibugyo was identified.
 In Africa, outbreaks of EVD primarily occur in remote villages close to tropical
rainforests in Central and West Africa
 Confirmed cases of EVD have been reported in the Democratic Republic of the
Congo (DRC, formerly Zaire), Sudan, Gabon, Uganda, Republic of Congo, Cote
d’Ivoire, and for the first time in Guinea, Liberia and Sierra Leone in 2014.
History
 There are 5 species of Ebola virus
 Human Disease:




Zaïre ebolavirus (EBOV)
Sudan ebolavirus (SUDV)
Tai Forest (TAFV) (formerly known as Ebola Ivory Coast)
Bundibugyo ebolavirus (BDBV)
 Non-Human Primate Disease
 Reston ebolavirus (RESTV)
Year
Country
Ebola virus species
Cases
Deaths
Case fatality rate
1976
1976
Zaire (DRC)
Zaire
318
280
88%
Sudan
Sudan
284
151
53%
1976
England
Sudan
1
0
0%
1977
Zaire (DRC)
Zaire
1
1
100%
1979
Sudan
Sudan
34
22
65%
1989
USA
Reston
0(a)
0
0%
1990
USA
Reston
0(a)
0
0%
1992
Italy
Reston
0(a)
0
0%
1994
Gabon
Zaire
52
31
60%
1994
Côte d’Ivoire
Tai Forest
1
0
0%
1995
Zaire (DRC)
Zaire
315
254
79%
1996
Gabon
Zaire
31
21
57%
1996
Gabon
Zaire
60
45
75%
1996
South Africa
Zaire
1
1
100%
2000-1
Uganda
Sudan
425
224
53%
2001-2
Gabon and Zaire (DRC)
Zaire
124
97
78%
2002-3
Zaire (DRC)
Zaire
143
128
89%
2003
Zaire (DRC)
Zaire
35
29
83%
2004
Sudan
Sudan
17
7
41%
2005
Zaire (DRC)
Zaire
12
10
75%
2007
Zaire (DRC)
Zaire
264
187
71%
2007
Uganda
Bundibugyo
149
37
25%
2008
Philippines
Reston
0(b)
0
0%
2008-9
Zaire (DRC)
Zaire
32
14
47%
2011
Uganda
Sudan
1
1
100%
2012a
Uganda
Sudan
24
17
70%
2012b
Uganda
Sudan
7
4
40%
2012
Zaire (DRC)
Bundibugyo
57
29
55%
2388
1590
67%
Total
Ebola & Marburg Outbreaks in Africa
1976 to 2014
Reservoir
•
•
•
•
New evidence strongly implicates fruit-bats as the reservoir host for
ebolavirus, thought the means of local enzootic maintained and transmission
within bat population remains unknown
Epizootics caused by ebolavirus appear sporadically, causing high mortality
among non-human primates and duikers and may precede human
outbreaks
Little is known about how the virus first passes to humans, triggering waves
of human-to-human transmission, and epidemics
With the current evolving epidemic there is an urgent need to better
understand the ecology of Ebola virus in nature.
How Does the Disease Spread?
Geographic Distribution of EVD and
Fruit Bats of Pteropodidae Family
Geographic Distribution of EVD
Outbreaks in Humans & Animals
Human to Human Transmission
•
•
•
•
The way in which the virus first appears in a
human at the start of an outbreak is unknown
The first patient becomes infected through
contact with an infected animal, such as a
fruit bat or primate (apes and monkeys),
which is called a spillover event
Person-to-person transmission follows and
can lead to large numbers of affected people
In some past Ebola outbreaks, primates were
also affected by Ebola, and multiple spillover
events occurred when people touched or
ate infected primates.
Human to Human Transmission
•
Once infection occurs in humans, the virus can be spread in several
ways to others:
• Through direct contact
•
•
Through blood or body fluids of a person who is sick with Ebola
•
•
Including but not limited to urine, saliva, sweat, feces, vomit, breast
milk, and semen
Objects
•
•
Broken skin or mucous membranes in, for example, the eyes, nose, or
mouth
Like needles and syringes that have been contaminated with the virus
From infected fruit bats or primates
•
Apes and monkeys
Human to Human Transmission
•
•
•
•
•
Ebola is not spread through the air or by water, or in general, by food
In Africa, Ebola may be spread as a result of handling bushmeat (wild
animals hunted for food) and contact with infected bats
There is no evidence that mosquitos or other insects can transmit
Ebola virus
Only a few species of mammals (for example, humans, bats, monkeys,
and apes) have shown the ability to become infected with and spread
Ebola virus
Once someone recovers from Ebola, they can no longer spread the
virus. However, Ebola virus has been found in semen for up to 3
months
•
Abstinence from sex (including oral sex) is recommended for at least 3
months. If abstinence is not possible, condoms may help prevent the
spread of disease.
Ebola Cases Globally: 17-July to 17October 2014 (weekly)
The number of cases in Nigeria,
Senegal, USA, Spain, DRC (separate
strain) are small and shown on the
next slide
Ebola Cases Globally: 17-July to 17October 2014 (weekly)
The number of cases in Nigeria,
Senegal, USA, Spain, DRC (separate
strain) are small and shown on the
next slide
Confirmed & Probable Cases of Ebola
29 August 2014, WHO
Confirmed & Probable Cases of Ebola 16
September 2014, WHO
Confirmed & Probable Cases of Ebola 03
October 2014, WHO
Confirmed & Probable Cases of Ebola 20
October 2014, WHO
Status as of 29 October 2014 (WHO)
Status as of 24 November 2014 (WHO)
•
•
•
•
•
•
•
•
•
•
•
Total # of EVD Cases:
14,414
Total # of Deaths: 5,178
Case-Fatality Rate:
~36%
Senegal declared outbreak free:
17 October
Nigeria declared outbreak free:
19 October
Spain declared outbreak free: 2
December
The outbreak remains intense in
Guinea, Liberia & Sierra Leone
All districts in Liberia & Sierra Leone
have now reported one case of EDV
High risk to Ivory Coast due to
proximity of cases in Guinea
= Ebola Free
Status as of EVD in HCW 17 November 2014
(WHO)
•
•
•
•
Total # of EVD Cases:
588
Total # of Deaths:
337
Case-Fatality Rate:
~57%
Early indication: Cause of
infection occurred outside the
context of EVD Treatment and
care
WHO declares end of Ebola outbreak in Nigeria
•
Ebola virus was introduced into Nigeria on 20 July 2014 when
an infected Liberian man arrived by airplane into Lagos,
Africa's most populous city
•
•
According to WHO recommendations, the end of an Ebola
virus disease outbreak in a country can be declared once 42
days have passed and no new cases have been detected
•
•
The man, who died in hospital 5 days later, set off a chain of
transmission that infected a total of 19 people, of whom 7 died
The 42 days represents twice the maximum incubation period for
Ebola (21 days). This 42-day period starts from the last day that
any person in the country had contact with a confirmed or probable
Ebola case
19 October, Nigeria reached that 42-day mark and is now
considered free of Ebola transmission.
Europe
• October 6, a 44 year old Spanish nurse assistant
became the first person known to have contracted
Ebola in Europe
• The nurse had treated two Spanish missionaries who
died of the disease after being flown home from the
region
• Three other people, including the nurse's husband, have
been quarantined
• October 20, was clear of all traces of the virus.
USA: Chronology of Events
• September 30, 2014, the first laboratory-confirmed case of Ebola to be
diagnosed in the United States in Thomas Eric Duncan (Index Case) who
had traveled to Dallas, Texas from Liberia
•
•
•
•
•
•
•
He did not have symptoms when leaving Liberia, but developed symptoms approximately four days after
arriving in the United States
He was missed diagnosed at Texas Presbyterian Hospital of Dallas and sent home
On his second visit, after developing symptoms consistent with Ebola and based on his travel history,
CDC recommended testing for Ebola
The medical facility isolated the patient (i.e., index patient) and sent specimens for testing at CDC and
at a Texas laboratory
Local public health officials identified all close contacts of the index patient for daily monitoring for 21
days after exposure
The index patient passed away on October 8
Doctor & HCW brought to Emory for treatment
• October 8, Duncan
USA: Chronology of Events
• October 10, a HCW (Nina Pham) at Texas Presbyterian
Hospital who provided care for the index case tested
positive for Ebola.
•
•
She was isolated and subsequently moved to the National Institutes for Health
(NIH) Clinical Center
October 24, she recovered and discharged
• October 15, second HCW (Amber Vinson) who provided
care for the index patient at Texas Presbyterian Hospital
tested positive for Ebola
•
•
•
•
She was transferred to Emory University Hospital in Atlanta, Georgia
She had traveled by air October 13, the day before reporting symptoms
All passengers and crew on the two flights (Dallas to Cleveland on October 10, and
Cleveland to Dallas on October 13) have since been contacted by public health
professionals and are being monitored
Doctors can no longer detect the virus in her body.
USA: Chronology of Events
•
October 23, the New York City Department of Health and
Mental Hygiene reported a case of Ebola in a medical aid
worker (Craig Spencer) who had returned to New York City
October 17 from Guinea, where the medical aid worker had
served with Doctors Without Borders.
•
•
•
October 26, the New York City Department of Health and
Mental Hygiene reported a possible case of Ebola in a 5 year
old child who had temperature and he and his family had visited
Guinea for a month he had arrived at JFK Airport on October 25
•
•
Diagnosis was confirmed by CDC on October 24
He is in isolation in a New York City hospital, and public health officials are
investigating and conducting contact tracing
October 27, Patent tested negative
October 27, the Maryland Department of Health & Mental
Hygiene reported a suspected case of Ebola admitted to
University of Maryland Medical Center
•
October 28, Patent tested negative
USA: Chronology of Events
• October 27, CDC outlines plan to monitor travelers
•
•
Most healthcare workers returning from West Africa's Ebola hot zone would be considered to
be at "some risk" for infection, while healthcare workers tending to Ebola patients at U.S.
facilities would be seen as "low but non-zero" risk
Guidelines short of controversial mandatory quarantines being imposed by some U.S. states
• October 27, US DOD comes up with its own policy
•
•
•
Well beyond previously established military protocols
U.S. Army isolates about a dozen soldiers at part of a U.S. base in Vicenza, Italy, including
Major General Darryl Williams, who oversaw the initial response to the Ebola outbreak
Dozens more will be isolated in the coming days as they rotate out of West Africa, where the
military has been building infrastructure to help health authorities treat Ebola victims.
USA: Ebola Contact Tracing, Dallas, Texas
Date: 10/27/2014
Confirmed Cases: 4
Contacts*
Current: 1
Completed Surveillance†: 10
Total: 11
Possible Contacts**
Current: 96
Completed Surveillance†: 69
Total: 165
Totals
Current: 97
Completed Surveillance†: 79§
Total: 176
Contacts are defined as people who had recognized
exposure to an Ebola patient, blood, bodily fluids,
specimens of an Ebola patient or potentially
contaminated surfaces.
Possible contacts are defined as people who had
possible exposure to an Ebola patient, blood, body
fluids, specimens of an Ebola patient or potentially
contaminated surfaces.
*Contacts: Definite exposure
**Possible Contacts: Possible exposure
†Completed active surveillance
§Data for last date of exposure is still in progress
6 November, The World Health Organization reports that, of the 177 possible
contacts identified, only 53 remain under monitoring. The other 124 have
completed their 21-day monitoring period without symptoms
USA: Chronology of Events
• November 8, All contacts of the three Ebola cases in Texas have
completed 21 days of monitoring. None had Ebola
• November 11, The doctor who was treated at Bellevue Hospital Center
in New York is free of Ebola. He has been discharged from the hospital
• November 13, The latest World Health Organization Ebola Response
Roadmap has confirmed that all the three healthcare workers have been
treated and discharged. Overall, there have been four cases and one
death. Currently, no contacts are being monitored in the country
• November 15, a surgeon from Sierra Leone infected with Ebola was
evacuated to the Nebraska Medical Center
• November 17, The Nebraska Medical Center has announced that the
doctor evacuated from Sierra Leone has died. He was in a critical
condition when he arrived on 15 November and despite being treated
with convalescent plasma and ZMapp, he passed away as a result of his
Ebola disease
India: Possible Case
• November 18, CDC outlines plan to
monitor travelers
•
•
•
•
a 26-year-old man who recovered from Ebola and
returned from Liberia was admitted to the Raiganj
District Hospital in West Bengal for testing. He arrived in
Dehli on November 10.
Three blood samples from the man tested negative for
the disease, which means he is considered recovered
according to standards set by the WHO and the CDC
The CDC advises Ebola survivors to avoid sex for three
months or use condoms because the virus can continue
to be found in semen for seven weeks after recovery
from the disease. Sexual transmission of Ebola has not
been definitively established, though multiple studies
have shown that the virus can persist in semen for
longer than in blood or other body fluids
Delhi airport quarantined six people at high-risk
suspected with Ebola on November 17. Health officials
at airport are monitoring the situation very closely.
As of October 21, 18 cases were being treated
outside of West Africa
• Symptoms may appear
anywhere from 2 to 21 days
after exposure to Ebola, but
the average is 8 to 10 days.
• Recovery from Ebola
depends on good supportive
clinical care and the patient’s
immune response.
• People who recover from
Ebola infection develop
antibodies that last for at
least 10 years.
CDC: Management of Possible Ebola Cases in
a Hospital Setting
1. Identify Exposure History:
Has patient lived in or travelled to a country with widespread Ebola transmission or had contact with an individual with
confirmed EVD within the previous 21 days
Y
E
S
2. Identify Signs & Symptoms:
Fever: >100.4 F or 38.0 C or Ebola compatible
Symptoms: Headache, weakness, muscle pain, vomiting, diarrhea, abdominal pain or hemorrhage
Y
Y
E
E
S
S
3. Isolate and determine personal protective equipment
(PPE) needed:
Place patent in private room or separate enclosed area with
private bathroom or covered, bedside commode. Only
essential personnel with designated roles should evaluate
patent and provide care to minimize transmission risk. The
use of PPE should be determined based on patient critical
status
Y
E
S
NO
NO
Continue with usual triage & assessment
A.
B.
C.
Continue with usual triage &
assessment
B. Notify relevant Health Department
Monitor fever and symptoms for 21
days after last exposure in
consultation with relevant Health
Department
4. Inform:
IMMEDIATELY inform the hospital
infection control program and other
appropriate staff
IMMEDIATELY report to the Health
Department
Use PPE designated for the care of hospitalized patients http://www.cdc.gov/vhf/ebola/hcp/procedures-forppe.html If the patient requires active resuscitation, this should be done in a pre-designated area using predesignated equipment.
For clinically stable patients, healthcare
worker should at a minimum wear:
A. Face shield & surgical face mask
B. Impermeable gown
C. 2 pairs of gloves If patient’s condition
changes, reevaluate PPE
5. Further evaluation and management
A. Complete history and physical examination; decision to test for Ebola should be made in consultation with relevant health department
B. Perform routine interventions (e.g. placement of peripheral IV, phlebotomy for diagnosis) as indicated by clinical status
C. Evaluate patient with dedicated equipment (e.g. stethoscope)
EDPLN Laboratories for Ebola or Marburg
Diagnostics
Diagnosing
Diagnosing Ebola in an person who has been infected for
only a few days is difficult, because the early symptoms,
such as fever, are nonspecific to Ebola infection and are
seen often in patients with more commonly occurring
diseases, such as malaria and typhoid fever
However, if a person has the
• Early symptoms of Ebola and has had
•
•
•
Contact with the blood or body fluids of a person sick with
Ebola
Contact with objects that have been contaminated with the
blood or body fluids of a person sick with Ebola, or
Contact with infected animals,
They should be isolated and public health professionals
notified.
Samples from the patient must be collected and tested to
confirm infection.
Laboratory Findings at Admission
•
•
•
•
•
•
Leukopenia frequently with lymphopenia followed later by
elevated neutrophils and a left shift
Platelet counts are often decreased in the 50,000 to 100,000
range
Amylase may be elevated, reflecting pancreatic involvement
(inflammation/infection)
Hepatic transaminases are elevated with aspartate
aminotransferase (AST) exceeding alanine aminotransferase
(ALT); these values may peak at more than 1,000 IU/L.
Proteinuria may be present
Prothrombin (PT) and partial thromboplastin times (PTT) are
prolonged and fibrin degradation products are elevated,
consistent with disseminated intravascular coagulation (DIC).
Diagnostics Test
Timeline of Infection
Diagnostic tests available
•
•
•
•
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
Within a few days after symptoms
begin
Diagnostics
•
•
August 5, FDA issued an emergency-use authorization for the Defense
Department’s real-time polymerase chain reaction assay for Ebola
October 25, FDA issues emergency authorization for two new Ebola tests
•
•
BioFire's tests can detect Ebola in a blood or urine sample in one hour, compared with
the 24 to 48 hours current tests take to deliver results
The test can also be performed in a hospital with BioFire lab equipment, whereas
current tests need to be sent to specialized labs.
Diagnostics
•
The new tool, developed by France's Atomic Energy Commission, could allow
doctors to diagnose a patient with suspected Ebola in under 15 minutes
•
•
French pharmaceutical company Vedalab is turning the process into a user-friendly kit
called Ebola eZYSCREEN. Similar to a DIY pregnancy test, a positive result sees a
small stripe showing up in a results window on the hand-held device
The kit is simple to use in the field without any additional equipment, said the CEA,
which also does non-nuclear research with a possible military or security application.
Treatment Modalities
• There are no approved treatments available
for EVD
• Clinical management should focus on
supportive care of complications, such as
hypovolemia, electrolyte abnormalities,
hematologic abnormalities, refractory shock,
hypoxia, hemorrhage, septic shock, multiorgan failure, and DIC
• Recommended care includes volume
repletion, maintenance of blood pressure (with
vasopressors if needed), and maintenance of
oxygenation, pain control, nutritional support,
as well as treating secondary bacterial
infections and pre-existing comorbidities.
Treatment Modalities
• Among patients medically evacuated from
West Africa with EVD, large volumes of
intravenous fluids have often been required
to correct dehydration due to diarrhea and
vomiting
• Some patients may develop profound thirdspacing of fluids due to vascular leak.
•
Some organizations have suggested the
addition of broad-spectrum antimicrobials,
particularly in patients with evidence of septic
shock
• Infection prevention and control measures
are a critical part of clinical management – all
bodily fluids and clinical specimens should
be considered potentially infectious.
Treatment Modalities: Vaccines
• 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...
Treatment Modalities: Vaccines Under
Development
Vaccine Type
How does it
work
State of
Research
Safety in Humans
Availability
Chimpanzee
adenovirus
serotype 3 (ChAd3)
vaccine
Uses a
chimpanzee
adenovirus that
does not grow,
containing the
gene for EVD
surface protein
A single dose of the
vaccine given one
month in advance
protected 16/16
animals from a lethal
dose of EVD
Over 1,300 humans have received similar
vaccines for other diseases, with over 1,000
in Burkina Faso, Gambia, Kenia, and
Senegal. These other vaccines seem so far
to be safe. However, there is no safety
information on an EDV vaccine in humans
No information on human trials. An
early trial of an EVD vaccine
containing two EVD strains (Zaire &
Sudan) started in Sep 2014 in the
USA. A vaccine against the Zaire
strain may be evaluated in the UK
and then in two African countries this
month. The earliest availability
depends on results of the trial and
manufacturing timelines.
Approximately 15,000 doses might
be available by the end of 2014
Recombinant
vesicular stomatitis
virus (rVSV) vaccine
Aims to induce
EVD-specific
immune
responses.
A single does of the
vaccine given one
month in advance
protected 16/16
animals from lethal
dose. Animals with
weak immunity were
not harmed. Was safe
when directly injected
into the brain of the
animal.
It is unknown is rVSV will grow in humans,
especially with weak immunity. Too little
growth could make a weak vaccine, while
too much could cause illness or possible
spread to unvaccinated people or animals.
One lab worker was given rVSV after a
needle stick injury and remained well. The
lab worker had a small but detectable
amount of vaccine in plasma for a short time
after vaccination.
Safety, efficacy, and duration of
protection are unknown. A trial is due
to start soon in the USA. Currently,
800 doses are available and more is
in production
Treatment Modalities: Therapeutics
Several investigational therapeutics for Ebola virus disease are in
development…
Treatment Modalities: Therapeutics Available
or Under Development
Therapy
How does it
work
State of
Research
Safety in Humans
Availability
Convalescent
plasma
Studies
Blood transfusions
from EVD
survivors might
prevent or treat
Ebola virus
infection in others,
but the results of
the studies are still
difficult to interpret
It is not known
whether antibodies in
the plasma of
survivors are sufficient
to treat or prevent the
disease. More
research is needed.
Safe if provided by well-managed blood
banks. Risks are like those associated with
the use of any blood products, such as the
transmission of blood-borne pathogens that
cause disease. There is a theoretical
concern about antibody- dependent
enhancement of EVD infection, which can
increase infectivity in the cells.
Transfusion is culturally acceptable in
West Africa. Potential donors are
Ebola survivors, but the logistics of
blood collection are an issue. Options
to conduct studies in patients are
being explored. The first batches of
convalescent plasma might be
available by the end of 2014.
ZMapp Cocktail of
three chimeric
mouse- human
monoclonal
antibodies (Mapp
Biopharmaceutical
Inc.)
The three
antibodies in this
mixture block or
neutralize the virus
by binding to or
coating a different
site on the
covering or
“envelope” of the
virus.
Studies in non human
primates (NHPs)
showed a strong
survival up to five days
after infection, when
virus and/or fever
were present.
There have been no formal safety studies in
humans. Very small numbers of EVDinfected people have been given ZMapp on
a compassionate basis and no safety issues
have been reported to date. Clinical
effectiveness is still uncertain
A very limited supply (fewer than 10
treatment courses) has been
deployed to the field. At the date of
publication of this revised document
no doses remain. Efforts to scale up
production may yield increased
supplies of potentially few hundred
doses by the end of 2014.
Treatment Modalities: Therapeutics Available
or Under Development
Vaccine Type
How does it
work
State of
Research
Safety in Humans
Availability
Hyperimmune
globulin prepared
by purifying and
concentrating
plasma of
immunized animals
or previously
infected humans
with high titres of
neutralizing
antibody against
EVD
Antibodies that can
neutralize the
different EVD
strains have been
produced
shown to be protective
in NHPs when
treatment begins 48
hours after exposure
to EVD.
Generally safe. There has been extensive
experience with the use of hyperimmune
globulin against other infectious agents in
humans. Inactivation and purification
procedures effectively eliminate blood-borne
pathogens that cause disease.
Not currently available. Several
months are needed to immunize
animals, collect plasma, and make the
purified product. Work is starting on
the production of immune globulin in
horses and of human immune globulin
in cattle. Studies in horses could take
place within six months, but largescale batches for use in humans
TKM-100802 Lipid
nanoparticle small
interfering
Ribonucleic acid
(siRNA) (Tekmira
These target two
essential viral
genes to stop the
virus from
replicating
Effective in guinea
pigs and monkeys. In
NHPs, there is an 83%
survival rate, if
administered 48 hours
after infection and
67% survival 72 hours
after infection.
A single-dose study in healthy volunteers
found side effects include headache,
dizziness, chest tightness, and increased
heart rate at high doses. At lower doses,
projected to be the dose used for treatment,
the drug was better tolerated.
The US Food and Drug
Administration (FDA) has
authorized emergency use in EVDinfected patients and several such
patients have received treatment with
this product. A limited number of
treatment courses (15-20) are
available. There is potential for the
production of up to 900 courses by
early 2015.
Treatment Modalities: Therapeutics Available
or Under Development
Vaccine Type
How does it
work
State of
Research
Safety in Humans
Availability
AVI 7537 (Sarepta)
Phosphorodiamidate
oligonucleotide
In NHP studies, doses
of 14 to 40 mg/kg for
14 days showed
typical survival ranging
from 60% to 80%
when given at the time
of infection.
Human tolerability has been demonstrated
in early studies
The active pharmaceutical
ingredient is available for 20-25
courses by mid-October 2014.
Potential production of approximately
100 treatment courses by early
2015.
Favipivavir/T-705
(Toyama
Chemical/Fuji Film
This has shown
effectiveness against
EVD in mice, but in a
NHP study only one
out of six survived.
Another study of
animals using a
different dose regimen
is underway
Approved in Japan for influenza treatment
under special circumstances. Remains
under study in other countries. Has been
tested in more than 1 000 people, with no
major adverse effects reported. But the
dose proposed for treatment of EVD could
be 2-5 times higher than that tested so far
and duration of treatment might be longer
than in current influenza studies. It should
not be used during pregnancy due to
potential birth defects. It has not been
studied in humans for Ebola.
Use for field post-exposure
prophylaxis is under discussion. More
than 10,000 treatment courses may
be available, pending determination
of the dose for treatment of EVD.
Future supply is not limited.
Treatment Modalities: Therapeutics Available
or Under Development
Vaccine Type
How does it
work
BCX4430 (Biocryst)
Interferons
Induces an antiviral
state in exposed
cells and regulates
the immune
system.
State of
Research
Safety in Humans
Availability
Studies of this antiviral
in animals indicate
83% to 100% survival
in rodents with EVD. It
is also effective in
animals 48 hours after
infection with the lethal
Marburg virus, which
belongs to the same
family as Ebola.
Testing for EVD in
NHPs is underway.
No human safety studies or data available.
Safety studies are planned
Needs NHP protection data for EVD
before it can be considered. No
material is currently available for field
use.
A study showed
delayed time to death
in NHPs but no overall
increased survival.
Early administration
enhances the
effectiveness of
treatment in animals
and lengthens the time
after the viral infection
at which antibodies
show effectiveness.
Various forms approved for treating chronic
hepatitis and multiple sclerosis. Higher
doses are associated with increased
adverse effects but no greater efficacy.
Commercially available. There are
several types of interferons. Decisions
regarding which one to use, when to
use, and the dose regimen need
careful consideration
Prevention
If you travel to or are in an area affected by an Ebola outbreak, make
sure to do the following:
•
•
•
•
•
•
Practice careful hygiene. For example, wash your hands with soap and
water or an alcohol-based hand sanitizer and avoid contact with blood and
body fluids.
Do not handle items that may have come in contact with an infected
person’s blood or body fluids (such as clothes, bedding, needles, and
medical equipment).
Avoid funeral or burial rituals that require handling the body of someone
who has died from Ebola.
Avoid contact with bats and nonhuman primates or blood, fluids, and raw
meat prepared from these animals.
Avoid hospitals in West Africa where Ebola patients are being treated. The
U.S. embassy or consulate is often able to provide advice on facilities.
After you return, monitor your health for 21 days and seek medical care
immediately if you develop symptoms of Ebola
Prevention for HCWs
Healthcare workers who may be exposed to people
with Ebola should follow these steps:
•
•
•
•
•
•
Wear appropriate PPE
Practice proper infection control and sterilization
measures
Isolate patients with Ebola from other patients
Avoid direct contact with the bodies of people who
have died from Ebola
Notify health officials if you have had direct contact with
the blood or body fluids, such as but not limited to,
feces, saliva, urine, vomit, and semen of a person who
is sick with Ebola
The virus can enter the body through broken skin or
unprotected mucous membranes in, for example, the
eyes, nose, or mouth.
Discussion
• The 2014 Ebola Virus Disease (EVD, or “Ebola”) outbreak is the
largest and most complex Ebola outbreak on record, with an
unprecedented number of affected countries, thousands of cases
and deaths in the general population, and hundreds of infected
health care workers
• The escalating scale and mortality of the outbreak has reinforced
the urgent need for the accelerated development and availability of
specific effective medical interventions for EVD
• Subject to the outcome of initial safety and immunogenicity trials –
expected in December 2014 - Ebola vaccine may be available for
efficacy trials and large-scale use during the first months of 2015
• Predictions of up to 10,000 cases per week expected starting
December if disease not contained.
Discussion: Global Response
•
US Response:
•
•
Ebola Czar was appointed by President Obama
A 30-member U.S. military team that could be called on to respond
to new cases of Ebola in the United States started specialized
training at Fort Sam Houston in Texas.
•
•
•
•
•
The weeklong training includes infection control and how to use
personal protective gear
Paul Allen foundation pledged $100 USD million
Bill Gates, pledged $50 million USD through his foundation
Mark Zuckerberg, added $25 million USD to the Centers for
Disease Control and Prevention Foundation coffers to help buy
personal protective equipment, ready-to-eat meals, generators,
vehicles and motorcycles, and thermal scanners to detect fever
These donations are in addition to the US government
spending and sending 3,000 troops, supplies and expertise
to the affected area.
Discussion: Global Response
• The EU pledged to increase its aid to help fight Ebola by $380 million to
$1.2 billion
• China pledged to boost its aid to the three West African nations fighting
the Ebola outbreak
•
•
The Chinese government will provide a fourth round of assistance to Liberia,
Sierra Leone and Guinea that will include emergency funding and supplies
worth the equivalent of $82 million
China will also dispatch quarantine experts and medical personnel, and it will
set up a new treatment center in Liberia.
Discussion: Countries Donations in US Dollars
(Tracked by the UN)
Discussion: NGOs, Corporation & International
Institutions Donations in US Dollars (Tracked
by the UN)
Discussion: Needed Funds
•
•
•
•
WHO requires $US 260 million to meet the objectives of its response to
the Ebola outbreak in the affected areas
To date, WHO has received 49% of those funds, while 15% of the funds
required have been pledged
This leaves a gap of 36% of the funds needed
WHO continues to appeal to Member States to provide funding and other
resources to assist in containing the Ebola outbreak.
Discussion: NIH Funding as a Share of GDP, FY
1950-2019
Source: Erosion of Funding for the National Institutes of Health Threatens U.S. Leadership in Biomedical Research , Center for American Progress
Discussion: NIH Funding
• NIH-funded biomedical research has played a critical role in improving the
physical and mental health of Americans, which in turn has yielded
significant societal economic benefits
• Federal funding has turned NIH into the cornerstone of an American
biomedical research sector that leads the world in investment and
innovation
• NIH budgets began stagnating after 2003 and declining in 2010, the costs
of conducting biomedical research continued to rapidly increase
• This was further hurt by recent budgetary cuts and sequestration
• In order to secure America’s position as the global leader in biomedical
research for the foreseeable future, Congress must pursue significant
new investments.
Discussion: Travel
Travel Restrictions
• No evidence that travel bans have been effective in
limiting the spread of infectious disease
Three-week monitoring for some travelers
• All travelers coming to the United States from Ebolaaffected areas will be actively monitored for 21 days.
Also, all U.S.-bound passengers from Liberia, Sierra
Leone and Guinea must land in one of the five U.S.
airports with enhanced screening for Ebola:
1.
2.
3.
4.
5.
New York's John F. Kennedy International,
Washington Dulles,
New Jersey's Newark Liberty International,
Chicago's O'Hare International and
Hartsfield-Jackson International in Atlanta.
Beds Needed: What is being done?
•
•
•
Preliminary
Analysis
Existing ETC
Beds
Required ETC
Beds
Existing ETC
Beds (%)
Guinea
160
260
61%
Liberia
620
2690
23%
Sierra Leone
346
1198
29%
Around 150 local construction workers have been working 3 shifts a day to build an Ebola
treatment center (ETC) at the former Ministry of Defense compound on the outskirts of
Monrovia.
The 6 large tents, that can house 50 patients each, are now in place and the center is set to
open at the end of October. This will add at least 200 additional beds for Ebola patients in
Liberia.
Latest data indicate that 22% of 4,707 planned ETC beds and 4% of 2,685 planned
Community Care Center (CCC) beds are now in operation.
•
•
•
A health-care partner has already been identified for the construction of 2,110 beds,
accounting for 58% of the gap between planned and existing ETC beds.
Another 1,550 beds remain at the planning stage, without an identified health-care
partner.
Efforts are being made by WHO to identify partners to construct, supervise and
operate ETC and CCC beds.
Discussion: Critical Questions to Address
• Who should be vaccinated as a priority?
• How much vaccine will there be and by when?
• How and when will we know that the vaccines
“work”?
• Who will finance vaccines and vaccination
campaigns?
Discussion: WHO Vaccine Development
Meeting Summary
• Impact: Vaccines will have a significant impact on the further evolution of the epidemic in any
scenario, from best-case to worst-case
• Financing: Funding issues should not be allowed to dictate the vaccine agenda. The funds will
be found
• Liability: Neither affected countries nor industry should be left alone to bear the burden should
lawsuits arise following possible adverse reactions to an Ebola vaccine. Establish a “club” of
donors, in collaboration with the World Bank
• Timing & Quantity: Timing and quantity of vaccine doses should not constrain the design of
clinical trials. Industry confirms that enough vaccine doses would be available
• GlaxoSmithKline’s monthly production capacity for purified bulk vaccine was expected to rise from the current figure of
24,000 doses to 230,000 by April 2015, if they can be filled for release
• NewLink’s bulk vaccine manufacturing capacity for the Canadian vaccine was noted to vary, according to the dose
selected, from 52,000 doses to 5.2 million doses anticipated for the first quarter of 2015
• Priority: Health care workers, including medical staff, laboratory staff, burial teams, and facility
cleaners, should have first call on vaccine doses while supplies remain limited
• Vaccination of health care workers in the three countries is feasible during the first quarter of
2015.
Conclusion







The World is “making this up” as we go and we have to become more comfortable
with uncertainty
The current epidemic in West Africa which struggled to meet the basic healthcare
needs of populations has made it impossible to managing acute care for Ebola
patients
The first focus needs to be on relatively simple things to decrease mortality in West
Africa. Data suggest aggressive intravenous hydration, replacing electrolytes,
managing nausea, fever, and superimposed bacterial infection are relatively
inexpensive measures that can be part of the bundle of care
There is a critical need for ETC & CCC beds in the three most affected countries
Proper training and protective gear needs to be provided to the hospital staff taking
care of EVD cases & burial staff dealing with corpses is critical
Behavioral changes that increase exposure to infected animals needs to be
modified
Complex ethical challenges abound related to the use of untested interventions,
quarantines, special care, and other issues
Conclusion

There is no evidence that travel bans have been effective in limiting the spread of infectious disease in any previous
infectious disease outbreak and it is unlikely that any such ban on Ebola-infected countries will limit the spread of Ebola
•

Post-Arrival in the US 21 Day self-quarantine
•
•
•
•
•

Attention should be on how best to help Ebola-infected countries where the outbreak is raging rather than spending any
human or financial resources required to enforce a travel ban
Is not only be ethically permissible, but even ethically obligatory
Ethically, 'right conditions' are key; the well-being of the quarantined person must be guaranteed
People in quarantine need to be provided the resources to maintain as decent a quality of life as possible
Above all they need to be treated with respect
They need to feel secure that their needs and the needs of their family will be met and that they will have reliable and
regular access to appropriate information about any ill loved ones, as well as their own risks
Airlift foreign health workers
• Yes, this should be ethically acceptable
• We must make special commitments to the healthcare providers who are willing to serve
• In this outbreak, these people agreed to help out in an epidemic that has a very high mortality rate. These doctors and nurses,
must be promised not only high quality training and protective equipment going forward, but also that if something happens,
we must take care of them
• Someone must take care of the heroes who are volunteering to take care of people in West Africa, and within a very
challenging context; they absolutely must be guaranteed first-rate treatment should they become sick.




Although there are signs that the epidemic is slowing down in some areas, if not met with an effective and sustainable
international response it will case much more devastation in West Africa
A safe & efficacious vaccine is the only hope of containing the outbreak but characterized the U.S. investment in vaccine
research is "a drop in the bucket”
A non-patrician effort in the US is needed to increase funding support to NIH and DOD for R&D and Advanced
Development of Vaccines, Therapeutics and Diagnostics as well as Manufacturing Facilities for diseases such as Ebola
and other infectious diseases
Countries, NGO’s and Funding Agencies (Private or Public) need to fulfill their pledges as soon as possible.
!!!!Remember diseases do not observe boundaries!!!!