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Network Modeling Meeting: Ebola
NIH Highlights
•Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a
severe, often fatal illness in humans.
•The virus is transmitted to people from wild animals and spreads in the human
population through human-to-human transmission.
•The average EVD case fatality rate is around 50%. Case fatality rates have varied
from 25% to 90% in past outbreaks.
•The first EVD outbreaks occurred in remote villages in Central Africa, near tropical
rainforests, but the most recent outbreak in west Africa has involved major urban as
well as rural areas.
•Community engagement is key to successfully controlling outbreaks. Good outbreak
control relies on applying a package of interventions, namely case management,
surveillance and contact tracing, a good laboratory service, safe burials and social
mobilisation.
•Early supportive care with rehydration, symptomatic treatment improves survival.
There is as yet no licensed treatment proven to neutralise the virus but a range of
blood, immunological and drug therapies are under development.
•There are currently no licensed Ebola vaccines but 2 potential candidates are
undergoing evaluation.
A Brief History:
•
The first known outbreak of EVD occurring between June and November 1976 in Nzara, South
Sudan, and was caused by Sudan virus (SUDV). The Sudan outbreak infected 284 people and
killed 151.
•
On 26 August 1976, a second outbreak of EVD began in Yambuku, DRC. This outbreak was
caused by EBOV, formerly designated Zaire ebolavirus, which is a different member of the genus
Ebolavirus than in the first Sudan outbreak.
•
EVD in humans is caused by four of five viruses of the genus Ebolavirus. The four are Bundibugyo
virus (BDBV), Sudan virus (SUDV), Tai Forest virus (TAFV) and one simply called Ebola virus
(EBOV, formerly Zaire Ebola virus). EBOV, species Zaire ebolavirus, is the most dangerous of the
known EVD-causing viruses, and is responsible for the largest number of outbreaks. The fifth
virus, Reston virus (RESTV), is not thought to cause disease in humans.
•
The current outbreak in west Africa, (first cases notified in March 2014), is the largest and most
complex Ebola outbreak since the Ebola virus was first discovered in 1976. There have been
more cases and deaths in this outbreak than all others combined. It has also spread between
countries starting in Guinea then spreading across land borders to Sierra Leone and Liberia, by air
to Nigeria and the United States, and by land to Senegal.
•
As of November 11, 2014
(Updated November 14, 2014)
Total Cases: 14413
Laboratory-Confirmed Cases: 8920
Total Deaths: 5177
•
•
•
2014 Ebola Outbreak in West Africa - Outbreak Distribution Map
Transmission
•
Initial patient becomes infected through a spillover event - contact with an infected animal, such
as a fruit bat or primate (apes and monkeys)
•
Between people, Ebola disease spreads only by direct contact with the blood or body fluids of a
person who has developed symptoms of the disease.
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saliva, mucus, vomit, feces, sweat, tears, breast milk, urine and semen
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•
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–
–
–
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Only people who are very sick are able to spread Ebola disease in saliva
whole virus has not been reported to be transmitted through sweat.
Most people spread the virus through blood, feces and vomit.
Contact with surfaces or objects contaminated by the virus, particularly needles and syringes, may also transmit the
infection.
The virus is able to survive on objects for a few hours in a dried state and can survive for a few days within body
fluids.
The Ebola virus may be able to persist for up to 7 weeks in the semen of survivors after they recovered
Ebola may also occur in the breast milk of women after recovery, and it is not known when it is safe to breastfeed
again
Entry points for the virus include the nose, mouth, eyes, open wounds, cuts and abrasions.
60% of the cases of Ebola infections in Guinea during the 2014 outbreak are believed to have
been contracted via unprotected (or unsuitably protected) contact with infected corpses during
certain Guinean burial rituals
Health-care workers / family members treating those who are infected are at greatest risk of
getting infected themselves.
Infection
•
Symptoms may appear anywhere from 2 to 21 days after exposure to Ebola, but the
average is 8 to 10 days.
•
First symptoms are the sudden onset of fever fatigue, muscle pain, headache and
sore throat. This is followed by vomiting, diarrhoea, rash, symptoms of impaired
kidney and liver function, and in some cases, both internal and external bleeding (e.g.
oozing from the gums, blood in the stools).
•
People who recover from Ebola infection develop antibodies that last for at least 10 years.
CDC's Model for West Africa Ebola Outbreak
Summarized by Li Wang, 11/14
SIIR compartmental model
• Deterministic model with 4 compartments (susceptible,
incubation, infectious, recovery)
• Time step = 1 day. Model period is from 2/14 to 12/14.
• Model population is homogenous (no distinction of sex, age,
location, etc.), of entire country (10 mil).
• Model parameters are chosen by inspection to fit data
through 6/18/14.
Disease model
• New cases go into Incubation compartment
• Can come from transmission or imported; initially set to 25
• Length of incubation follow log-normal distribution (max 25
days)
Incubationi Distribution
0.180
0.160
0.140
0.120
0.100
0.080
0.060
0.040
0.020
0.000
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Days
Disease model
• After incubation period, case moves to Infectious
compartment
• Remain infectious for 6 days, including burial period. Has a
large effect on epidemic.
• Then the case moves to Recovery compartment. This covers
both recovery and death.
Transmission model
• Infectious cases are assigned to 3 categories: Hospitalized,
Home isolation, or No isolation
• The proportion of cases in each category changes to reflect
public health response to the epidemic
1.00
% Patients by category over time
0.90
0.80
% Patients
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Days
Hospitalization
Eff Home Isolation*
No Isolation
Transmission
• The daily transmission risk is the probability of a person to
transmit, per day. This is done deterministically, so if the risk is
0.3, then the number of new cases = 0.3 x number of
infectious.
• Different by category:
– Hospitalized: 0.02
– Home isolation: 0.03
– Non isolated: 0.30
• Importance of public health response! Effective isolation will
stop the epidemic.
Assumptions and limits
• The model parameters are chosen to fit data from the first
135 days.
• Under-reporting: the corrected model assumes that the
number of actual cases are 2.5 times the reported.
• CDC's deterministic model does not provide any measure of
uncertainty. The WHO report does.
•
"The mean time from the onset of symptoms to hospitalization, a measure of the
period of infectiousness in the community, was 5.0±4.7 days ... The mean time to
death after admission to the hospital was 4.2±6.4 days, and the mean time to
discharge was 11.8±6.1 days." - WHO
Projection
Daily clinical cases of Ebola
350
Ebola cases per day: Estimates based on data from Generic, uncorrected and
corrected for potential under -reporting
300
250
200
Daily cases (corrected)
150
Daily cases (uncorrected)
Total:
- - 19,957
—51,962
100
50
0
Days
1.00
% Patients by category over time
% Patients
0.80
0.60
0.40
0.20
0.00
Hospitalization
Days
Eff Home
Isolation*
No Isolation
Daily clinical cases of Ebola
Projection - Delayed response
1,800
1,600
1,400
1,200
1,000
800
600
400
200
0
Ebola cases per day: Estimates based on data from Generic, uncorrected and
corrected for potential under -reporting
Daily cases (corrected)
Total:
- - 72,754
—190,717
Daily cases (uncorrected)
Days
1.00
% Patients by category over time
% Patients
0.80
0.60
0.40
0.20
0.00
Hospitalization
Days
Eff Home
Isolation*
No Isolation
Model improvements
• What more can be done with available data? (location of
cases, size of communities)
• Model the delay between infectious symptoms and
hospitalization or isolation
• Simulate the transmission process to get a measure of
uncertainty.
References
• http://www.cdc.gov/mmwr/preview/mmwrhtml/su6303a1.htm
• EbolaResponse model spreadsheet: http://dx.doi.org/10.15620/cdc.24900
• WHO article:
http://www.nejm.org/doi/full/10.1056/NEJMoa1411100?query=featured_
home&&#t=article