Epidemic: Killer at Large
Ajay K. Singh, Editor-in-Chief, Scientific
Colorized scanning electron micrograph of
filamentous Ebola virus particles (blue)
budding from a chronically infected VERO E6 cell (yellow-green).
Courtesy of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
At the time of writing this column, the US government
had begun screening for clinical cases of Ebola at
five major airports. Other countries are taking a
similar approach. Over 8,500 people have been
affected, largely in West Africa, and there have been
nearly 4,000 deaths. The United States has reported
its first death, and it is likely, according to
experts, that there will be many more in the US
mainland. Earlier this August, the World Health
Organization (WHO) declared the Ebola epidemic to be
a Public Health Emergency of International Concern
(PHEIC) (1). Read
A lot is already known
about the Ebola virus (officially called EBOV) from
previous epidemics. EBOV is named after the Ebola
River in the Democratic Republic of Congo (formerly
Zaire), where one of the first outbreaks occurred in
1976. Since then there have been several outbreaks.
EBOV is highly infectious — human-to-human
transmission by just a handshake. And it is deadly.
The current epidemic is larger than all of the
previous EBOV epidemics combined. What we know from
a September 2014 New England Journal of
Medicine (NJEM) article (2) by
the WHO Ebola response team and an article by Briand
et al in August 2014 also in NJEM (3) is that the current epidemic
started in Guinea during December 2013, and most of
the cases originated from five West African
countries: Guinea, Liberia, Nigeria, Senegal, and
Sierra Leone. We also know that the incubation
period is approximately 11 days and that 95% of the
cases had symptom onset within 21 days after
exposure. The most common symptoms are fever (in ≈
87%), fatigue (in ≈ 76%), loss of appetite or
vomiting or diarrhea, (in ≈ 65%), headache (in ≈
50%), and abdominal pain (in ≈ 45%). Unexplained
bleeding was reported in approximately 18%.
The clinical presentation of Ebola virus disease
(EVD) was not initially recognized in the only
person who has died so far in the United States. A
Liberian man returning from West Africa presented to
a Dallas emergency department with a high fever and
a history of travel from Africa. Because the
significance of his travel history and the
importance of the high fever at presentation were
not recognized, he was discharged home without
precautions, potentially exposing dozens of other
individuals to EVD (4). His
illness and subsequent death have fueled a national
sense of alarm and a media frenzy (5).
Perhaps the most worrisome finding from the
September NEJM article is the 70% mortality
among reported cases (2). Still
more alarming perhaps is the absence of a specific
treatment. The illness in patients with EVD is
brief, to say the least. The mean time to death
after admission to the hospital in the NJEM
report was only 4.2±6.4 days. The mean length of
stay in hospital was 6.4 days in Guinea, Liberia,
and Sierra Leone. Ergo, EVD is a vicious killer.
The other tragic aspect
of the current epidemic is that hundreds of health
care workers have contracted EBOV from patients, and
over half have died, making this a truly deadly
disease among caregivers. The WHO has issued
guidance advising first responders and health care
workers to wear impermeable gowns and gloves and
facial protection. But it does not seem to be 100%
For many years, "virus hunters" have tried without
much success to track down the natural reservoir for
EBOV (6). As a National
Geographic article from 10 years back points out,
"Finding out where the virus is hiding between
outbreaks would help predict how often it will
strike and could aid in the adoption of safety
measures. The genetic variability of the virus in
its natural host may help design a vaccine" (6). Some data support fruit bats
as the natural reservoir; however although these
bats may have carried the virus west from Central
Africa, there is skepticism that they are
responsible for transmission of EBOV to humans (7).
A study published in August in Science by
Gire and colleagues from Harvard and the Broad
Institute in Boston provides unique insights into
the genetic origins of Ebola (8).
(Notably, five of the 50 collaborators in this
article had died from EVD by the time it was
published). These investigators sequenced 99 Ebola
virus genomes from 78 patients in Sierra Leone.
Their research shows that there is genetic
similarity across the sequenced genome, suggesting a
single transmission from an as yet unknown natural
reservoir, followed by human-to-human transmission
with no evidence of additional zoonotic sources
during the outbreak. Furthermore, Gire and
colleagues wrote: "The West African variant likely
diverged from central African lineages around 2004,
crossed from Guinea to Sierra Leone in May 2014, and
has exhibited sustained human-to-human transmission
In a remarkable feat of
Poirot proportions, Gire and the colleagues
suggested that the Sierra Leone outbreak originated
from the introduction of two genetically distinct
viruses from Guinea around the same time; Sierra
Leone victims all seemed to have attended the same
funeral of an Ebola case from Guinea.
The other important but problematic finding from the
Gire and colleagues study published in Science
is that they provided evidence that the genome of
the West Africa EBOV is mutating fairly quickly (8, 9). These
articles in Science raise major questions
about the accuracy of polymerase chain
reaction–based diagnostic tests but also about
the development of an effective vaccine. So we are
certainly not out of the woods, unfortunately, and
screening at five airports in the United States is
not going to be the end of the Ebola tragedy.
I leave you with a quotation from Albert Camus'
novel The Plague: “I have no idea what's
awaiting me, or what will happen when this all ends.
For the moment I know this: there are sick people
and they need curing.”
WHO Ebola Response Team. Ebola Virus Disease in
West Africa - The First 9 Months of the Epidemic
and Forward Projections. N Engl J Med. 2014 Sep 22.
[Epub ahead of print]
Briand S, Bertherat E, Cox P, et al. The
international Ebola emergency. N Engl J Med.
2014:371:1180–3. doi: 10.1056/NEJMp1409858.
[Epub 2014 Aug 20].
Vogel G. Infectious disease. Are bats spreading
Ebola across sub-Saharan Africa? Science
2014;344:140. doi: 10.1126/science.344.6180.140.
Gire SK, Goba A, Andersen KG, et al. Genomic
surveillance elucidates Ebola virus origin and
transmission during the 2014 outbreak. Science
Vogel G. Infectious Disease. genomes reveal start
of Ebola outbreak. Science 2014;345:989–90.
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