Ebola Doctor Reveals How Infected Americans Were Cured

Last week two American aid workers
who had contracted Ebola while
working in west Africa were
released from a U.S. hospital and
pronounced “recovered.” They had
been flown to Emory University
Hospital in Atlanta from Liberia
earlier this month to receive care in
the hospital’s specialized infectious
disease unit. Kent Brantly, a
physician with the humanitarian
group Samaritan’s Purse, and
missionary Nancy Writebol, of SIM
USA, beat the strain of the disease
they had contracted, which kills 52
percent of its victims. Bruce Ribner,
medical director of the hospital's
Infectious Disease Unit, sat down
with Scientific American to explain
how the two Americans were cared
for, the lessons that could be applied
to help patients across Africa and
why the hysteria over flying the two
individuals back to the U.S. was
unfounded.
[An edited transcript of the interview
follows .]
Are Brantly and Writebol now immune
to the Zaire strain of Ebola?
In general, patients who have
recovered from Ebola virus
infection do develop a very robust
immunity to the virus. They develop
antibodies against the virus and
they also develop cell-mediated
immunity—the lymphocytes
important to form viral control of
pathogens. In general, the finding is
it’s basically like being immunized—
it would be unusual to get infection
with the same strain.
Will that immunity afford them
protection against other strains of
Ebola?
We are still evaluating that in our
two patients. Cross-protection is not
quite as robust. There are five
strains of Ebola viruses. Even
though that data is not great, the
feeling is there is potential for being
infected if you go to a different part
of Africa and get exposed to a
different strain.
You said “still evaluating.” Are you
still caring for Brantly and Writebol?
We are going to be following those
two patients as outpatients, and as
part of our evaluation they have
agreed to undergo additional testing
so we can better understand
immunity to Ebola virus. We are
meeting with them periodically.
What sort of lessons has Emory learned
from caring for these two people that
would be transferrable to patients in
west Africa?
We are not being critical of our
colleagues in west Africa. They
suffer from a terrible lack of
infrastructure and the sort of testing
that everyone in our society takes
for granted, such as the ability to do
a complete blood count—measuring
your red blood cells, your white
blood cells and your platelets—
which is done as part of any
standard checkup here. The facility
in Liberia where our two patients
were didn’t even have this simple
thing, which everyone assumes is
done as part of your annual
physical.
What we found in general is that
among our Ebola patients, because
of the amount of fluid they lost
through diarrhea and vomiting, they
had a lot of electrolyte
abnormalities. And so replacing that
with standard fluids [used in
hospital settings] without
monitoring will not do a very good
job of replacing things like sodium
and potassium. In both of our
patients we found those levels to be
very low. One of the messages we
will be sending back to our
colleagues is even if you don’t have
the equipment to measure these
levels, do be aware this is occurring
when patients are having a lot of
body fluid loss.
Our two patients also gained an
enormous amount of fluid in their
tissues, what we call edema. In
Ebola virus disease there is damage
to the liver and the liver no longer
makes sufficient amount of protein;
the proteins in the blood are very
low and there is an enormous
amount of fluid leakage out into the
tissues. So one of the takeaway
messages is to pay closer attention
to that and perhaps early on try to
replace some of these proteins that
patients’ livers lack.
Considering how limited resources are
in some of these facilities, could health
care workers really act on this
information?
I think the world is becoming aware
that issues like this are not going to
go away. The developed countries of
the world will have to do our part to
assist our colleagues with less
developed infrastructure to care for
sick people. I think one of the
messages that is going out from
many sources is we really have to
help countries such as the ones
involved in this outbreak to develop
their medical infrastructure.
Hopefully in five years they will
have this infrastructure.
You have said that you are helping to
develop new Ebola care guidelines
based on your experience. How will
those be disseminated?
We have several articles that we
have submitted to major medical
journals, which are read overseas,
where we will be pointing this out.
We are working with several
government agencies, including the
U.S. State Department, to help them
come up with lessons learned—
guidelines which they will distribute
in turn to other countries. It is our
goal to help our colleagues overseas.
Alternatively, what lessons did you
learn from those health care workers?
Mostly the clinical course of the
patients—much like any physician
sending a patient to a referral
center. They admitted they knew
they were kind of flying blind.
They’d say, “this is what we
observed but we had no way to test
it.”
The World Health Organization
maintains that patients can continue to
be infectious via their sexual fluids for
several months after recovery. What
did you recommend to Brantly and
Writebol?
There are data that go back several
decades—over several outbreaks—
that suggest when you have
individuals that have recovered
from Ebola virus infection they may
still be shedding nuclear material
[genetic material from the virus
which could potentially help spread
it] in semen in males and vaginal
secretions in females and also,
potentially in urine. People have
done this by doing assays looking
specifically at the nuclear material
of the virus. There has been very
little attempt to demonstrate if this
is viable virus that these individuals
are shedding. It’s important when
looking at epidemiological
investigations that no one has been
able to show people shedding these
nuclear materials as a source of
infection after they are discharged.
Looking at Ebola survivors who
were discharged and successfully
resolved the infection, following up
several months later and evaluating
their family members, there has
never been any evidence that family
members became infected. A lot of
the thinking now is this probably
was not live and is not important in
terms of control of infection. We did
give both of our patients the
standard recommendations, which
are contained on the CDC [U.S.
Centers for Disease Control] Web
site—not having unprotected sex for
three months.
How many doctors and nurses were on
your team caring for these two Ebola
patients?
Twenty-one nurses, five physicians
and we had the support of
hundreds. Just making sure all the
disposables coming out of those
rooms were sterilized before we put
them on the federal highway system,
for example—we had to certify to
the contractor that takes our
regulated medical waste that it
didn’t have active Ebola virus inside
it. We didn’t have the equipment to
handle all of the waste but in two
hours facilities brought in industrial
autoclaves [which sterilize materials
with extreme heat] to replace the
system that we had. We would have
been drowning in garbage without
them.
It has been reported that Brantly
received a blood transfusion from a
recovered patient. What role might that
have played and is it being tried in
other contexts?
I wouldn’t be able to tell you what I
read in his chart. The most accurate
thing to say is we don’t have a clue
[what role a blood transfusion could
play]. It’s not part of our standard
treatment in our country. We
wouldn’t have any idea whether he
benefited or it was detrimental.
Are current diagnostics to identify
Ebola virus disease adequate for this
outbreak?
Certainly in the United States they
are adequate. The major way one
would diagnose Ebola virus disease
is through a process called PCR or
polymerase chain reaction, where
you take the patient’s blood, put it
in a machine and it tells you in a
few hours if the nuclear material
from the Ebola virus is present. CDC
is doing that for patients coming
back from infected areas where
virus is a potential. There are a
number of labs, both local and
courtesy of CDC, that are doing this
testing in west Africa, and my sense
is it’s not that difficult to get it done.
This past week WHO announced that
one of its workers has been infected
with Ebola virus disease and that
person was given the option of being
sent to a different country for
treatment. A British nurse also
contracted the virus and went home to
the U.K. for care. What’s the value of
getting treated elsewhere?
Given that there is no treatment for
Ebola virus disease, the main
intervention that will determine if
someone lives or dies with this
infection is supportive care: The
ability to replace fluid and
electrolytes if a patient is losing
them. The ability to replace platelets
if that count is low and a patient is
starting to bleed. The ability to
replace protein in the blood that
may be deficient. A developed
country has the capability because
of our infrastructure to provide that
level of support is at a much higher
level than a hospital dealing with
patients in west Africa.
Among the handful of patients that
received the experimental drug ZMapp,
some have died. Considering the
mortality rate for the current Ebola
strain is almost 50 percent what can we
say about ZMapp?
Experimental drugs are
experimental drugs because we
don’t know if they will work. That is
true both with the preparations
patients received in Liberia and
other preparations that are being
considered for treating patients with
this infectious disease. We are a
long way from being able to say that
someone that received one of these
agents benefited, it had no impact or
it may be that their outcome may be
impeded. Until we have good studies
looking at outcomes of patients who
received these medications,
compared to patients who didn’t
receive them, we should be very
cautious.
I would go further to say that there
is a fair amount of almost hysteria
and people feeling they must have
these preparations to survive. In the
past people thought they needed
agents for treatment, and the agents
actually turned out to impair
people’s ability to survive. The focus
should remain on aggressive
intensive care and the ability to
correct abnormalities metabolically,
rather than receiving any magic
vaccine or product that may or may
not improve survival.
For example, there used to be a
belief that patients who had
bacterial sepsis did much better if
you gave them high doses of
steroids. Now we know that these
may be detrimental instead of
beneficial. We know now since
we’ve done the studies. Again, it was
one of those things where people felt
like “yeah this should be” but when
they did the study in randomized
patients they found it didn’t work at
all.
As you know, two upcoming clinical
trials will be looking at potential Ebola
vaccines, and there are also a variety
of experimental therapies that are
being discussed in the U.S. and
elsewhere beyond ZMapp. How should
such information be coordinated? Does
there need to be an entity overseeing
that?
Given that we have multiple
countries I don’t know that you can
have any one entity. It’s tricky
enough having the FDA [U.S. Food
and Drug Administration] monitor
what is going on in the United
States. Clearly if you are talking
about Canadian studies or European
products, I don’t know that there is
any entity that can provide that sort
of coordination. My guess is that
most of the manufacturers are
aware of what the others are doing
and are comparing notes because
they feel it’s to their benefit to work
together.
An ethics panel from WHO recently
said that it is ethical to give out
experimental treatments to Ebola
patients, but it has not yet specified
who should have priority in such
circumstances or how such drugs
should be doled out. They are taking up
that issue at a meeting next week.
What’s your thought?
I think it’s certainly ethical to study
experimental biologicals and
vaccines but we have to be
extremely cautious. It’s not as
though we have something that we
know works. To say that anyone is
withholding products implies we
know that there’s a benefit, which
gives me pause because we are a
long long way from demonstrating
that these offer any benefit in
humans.
Is there anything you would like to add
about insights you learned from your
Ebola patient care?
The major thing I hope people have
appreciated is there was a lot of
anxiety, a lot of negative comment
about our bringing these two
patients back to our facility to care
for them. Most of that we attribute
to poor education, and I’m hoping
that since we were successful in
helping them resolve their
infections it helps to dispel the idea
that this is a disease that by nature
has to be fatal. As we have been
saying all along, we feel that the
high fatality rates in developing
parts of the world where this
infection occurs are because of the
lack of resources. We had always
felt that the survival of patients with
proper support would be a lot better
than in developing countries.
The other thing I would hope we
would get across to the public is this
is a disease where we don’t have to
have a lot of secondary infections—
if we follow standard infection-
control procedures. We had 26
people giving direct patient care to
these patients and we did not have
any secondary infections at all, and
that’s as we expected.
We were using contact precautions
and droplet precautions.
Fortunately, we don’t have to go to
that level of protection [wearing
protective full-body suits like in
west Africa]. You wear whatever you
need so that the blood and body
secretions don’t come into contact
with you, depending on the quantity
of fluids. We used gowns and gloves
and foot coverings of the health care
workers in order to prevent contact
with the body materials of these
individuals. Our approach was what
CDC recommends: you wear a mask
and goggles or a face shield to
prevent that infection. Some of the
nurses spending three to four hours
in patients’ rooms were more
comfortable wearing hoods than
masks and face shields, though those
would have been adequate. We can
manage care with minimal chance
for secondary spread. It’s not as
though we brought the plague to
American shores.