BODY & BRAIN
Ebola outbreak is
a testing ground
Clinical trial in Congo is
evaluating four therapies
B Y AIMEE CUNNINGHAM
Amid the second largest Ebola outbreak
ever, the hunt for a lifesaving treatment
is on. A clinical trial in Congo is gathering evidence on experimental therapies
to provide a proven option the next time
the deadly virus emerges.
The first multidrug clinical trial of Ebola
therapies, which began in November,
is comparing three different antibody
treatments and one antiviral drug. One of
these therapies was tested briefly during
the 2014–2016 outbreak in West Africa,
the largest ever, and has shown promise.
With the trial data, though, “we’ll be
able to say, ideally, that this drug or that
drug actually does work, not just we
think or hope it does work,” says Richard
Davey, one of the principal trial investigators and the deputy clinical director
at the U.S. National Institute of Allergy
and Infectious Diseases in Bethesda, Md.
Death rates from Ebola range from
25 to 90 percent. In the current outbreak, about 63 percent of those infected
have died, or 546 out of the 869 cases
reported as of February 23.
The multidrug trial began at a treatment unit in the city of Beni, with plans to
add additional units. Enrollees get one of
the four therapies plus standard supportive care, including painkillers. Scientists
will compare death rates between groups
In Congo, public health efforts against Ebola
infection include posters with information on
stopping the spread of the disease.
to determine each drug’s effectiveness. If
the trial doesn’t enroll enough patients to
get statistically significant results, it will
continue recruiting patients in future
The antibody treatments “jump-start
the immune system to have an immediate presence of antibodies directed
against the virus,” Davey says. One, called
mAb114, was cloned from a sample taken
from an Ebola survivor. The treatment
targets a protein on Ebola’s surface and
hampers entry into cells. All macaques
given a lethal dose of Ebola and treated
with mAb114 survived even when the
drug was given five days after infection,
researchers reported in Science in 2016.
The two other antibody treatments,
REGN-EB3 and ZMapp, each contain
three different antibodies. Certain dosing regimes of REGN-EB3 prevented
death in all or most macaques infected
with Ebola, researchers reported in 2018
in the Journal of Infectious Diseases.
ZMapp showed some benefit in a study
conducted at the end of the West African
outbreak. Eight of 36 patients receiving the drug and supportive care died,
compared with 13 of 35 patients who
received only supportive care, researchers reported in 2016 in the New England
Journal of Medicine. That trial was too
small to really demonstrate that the drug
works better than supportive care alone.
The antiviral drug under study, called
remdesivir, or GS-5734, appears to target a step in the virus’s “owner’s manual”
for making copies of itself. The drug suppressed replication and in certain doses
helped Ebola-infected macaques survive,
researchers reported in 2016 in Nature.
People not yet exposed to Ebola but
considered at high risk in Congo and
surrounding countries are receiving an
experimental vaccine, rVSV-ZEBOV, to
prevent infection. Nearly 81,000 people
have gotten the shot so far.
“The one silver lining” of this outbreak is the availability of the vaccine
and the therapeutics, says infectious
disease epidemiologist Mosoka Fallah
of the National Public Health Institute
of Liberia in Monrovia. “As much as it is
a bleak situation, it is hopeful.” s
split the difference, spending time in
both states to varying degrees.
The team then looked for these signals in a group of 11 patients in London,
Canada, some of whom were conscious
but unable to communicate. Sure enough,
patients who were aware of their environment spent more time in the complex
state of brain activity. When a different
group of 23 patients was anesthetized,
their brains spent less time in the complex state, suggesting that it does come
along with consciousness.
People flitted between the two distinct
states occasionally. Healthy people’s
brains sometimes slipped into the simple
form of behavior, perhaps representing
temporary “mind blanks,” the team says.
And unconscious patients exhibited the
complex pattern now and then. Whether
the brief blips come with a temporary
increase in consciousness is unknown,
Sitt says. If so, “is it a window of opportunity of communication?” he asks. s
finds. Thousands of “passage graves,”
consisting of a narrow stone passage
connected to one or more burial chambers covered in earth or stone, were
built at coastal sites in Portugal, Spain,
Ireland, England, Scotland and France.
Sea voyagers plying established trade
routes must have linked those areas and
led to a major change in burial practices,
signified by the proliferation of passage
graves, Schulz Paulsson says.
After about 5,500 years ago, passage
graves reached Scandinavia and north-central Europe, and other megalithic
structures spread to more coastal sites.
In England, massive boulders were raised
about 4,400 years ago at Stonehenge.
These general trends in the spread of
megaliths appear likely, says archaeologist Alasdair Whittle of Cardiff University
in Wales. It’s not surprising that sea
travel was involved, since megaliths are
found in England and Ireland as well as
in continental Europe, he says. More
radiocarbon dates are needed to specify,
for example, when people in France built
huge earthen mounds that later became
spots for megalith construction. s