Contagion | 1 of 5 | Infectious Disease || Radcliffe Institute


[MUSIC PLAYING] – Good morning, everyone. It’s great to see you all here. I’m Liz Cohen. I’m Dean of the Radcliffe
Institute for Advanced Study. And I am so pleased to welcome
you to our annual science symposium which focuses
our attention this year on modern epidemics. Radcliffe is Harvard’s
Institute for advanced study, and we have a two-fold mission. We are dedicated to advancing
deep inquiry and pathbreaking research that cuts
across the boundaries of traditional
academic disciplines. And we are also
committed to sharing this multi-disciplinary
work with a broad public through a full calendar of free
events like today’s symposium. I am especially glad to
have science teacher John Ruggiero and his students
from Eugene Wright Science and Technology Academy in
Chelsea here with us today. If they’re here,
would they wave? Have they come? There they are. [APPLAUSE] It’s never too soon to
come to an event like this. Epidemics is an ideal topic for
interdisciplinary exploration. Today, we will probe challenges
and innovations in epidemiology with the help of
epidemiologists, data scientists, physicians,
journalists, public officials, infectious disease
researchers, and sociologists from across the United
States and around the world. We at the Radcliffe
Institute are particularly proud of our long tradition
of supporting programming and research in
the sciences, not only at an annual
symposium like this one, but throughout the year. For example, we have an
ongoing lecture series on epidemics that complements
today’s symposium. Last week, Dean Sandro
Galea of the School of Public Health at
Boston University delivered the first installment
to a standing-room-only crowd. In the spring, we will continue
the series with lectures on fibromyalgia, poverty,
obesity, and Alzheimer’s. For more information on these
and other upcoming events, please visit the Radcliffe
Institute website or take one of
our calendar cards which are available at the
back of the room or downstairs at the registration table. All of Radcliffe’s
events are made possible by our supporters, many of
whom are here with us today. And I’m particularly
happy to see members of the Radcliffe Institute’s
Dean’s Advisory Council this morning. Thank you all for
your generosity which ensures that
we can continue to make our lectures,
our exhibitions, our conferences like today,
and many other aspects of our programming free
and open to the public. Now, today’s topic
is urgent and timely. Our panelists will offer
insight into the science and the social roots
behind the epidemics that we read about
on a regular basis, from Ebola, Zika, HIV/AIDS,
malaria, and Lyme disease, to gun violence, opioid
addiction, and depression. We all come to this subject
with our own perspective. As an historian,
my orientation is to locate events in the larger
social and historical context in which they arise. Whether an epidemic unfolds
during China’s Tang dynasty or amid preparations for the
Rio Olympics just last year, a society’s response to
a fast-spreading illness is shaped not just by the
capabilities and limitations of medical science at that
particular moment in time, but also by complex social
factors such as race, class, gender, and religion. For an historian, epidemics
can provide a revealing window into a society at a
particular moment in history. Let me give you one example
from our own backyard here in Boston, the smallpox
epidemic in Boston of 1721. By the 1700s,
smallpox inoculation had been practiced for
centuries in parts of Africa, as well as in
China and in India. In colonial Boston,
however, the practice was virtually unheard of. That changed when an enslaved
man, called Onesimus, told the Puritan religious
leader, Cotton Mather, about a practice common among
his tribe in North Africa, a procedure that protected
him against smallpox, leaving only a small scar on his arm. A few years later, when
a smallpox epidemic broke out in Boston
in 1721, Mather recalled Onesimus’s words. And he became an outspoken
advocate for inoculation. Many white Christians
in Boston mocked Mather for relying on the
testimony of an enslaved man and denounced inoculation for
its roots in Africa and Asia, calling it a heathen practice. Other Bostonians simply
rejected the idea of deliberately infecting
healthy people with a disease. By August of 1721,
the controversy had become so heated that
someone threw a grenade through Mather’s window. The grenade didn’t
detonate, but Mather found a note attached
to it, which read, and I quote, “I’ll inoculate you
with this with a pox to you,” end quote. A few Bostonians did
support immunizations, including Dr.
Zabdiel Boylston, who would go on to perform
America’s first inoculations on his own child and
two enslaved people. But Mather’s appeals
were largely ignored. Smallpox spread unchecked. And by the end of the
epidemic in 1722, over half of Boston’s population
had fallen ill. More than 800 died. The story of Boston’s
smallpox outbreak reveals much more than
the spread of a pathogen. It is a story about racial
prejudices in colonial New England, about the rigidities
of Boston’s society, and about the
forgotten contributions of enslaved Africans to
American medical practice. Still today, how
epidemics unfold around the world is shaped by
complicated interactions between medical advancements
and the social and political factors that inform
and complicate the work of epidemiology. 50 years ago, many
scientists considered the age of infectious
disease to be over. The rise of antibiotics
and vaccines was considered a triumph
of modern medicine. But today, diseases
we thought were gone seem to be reappearing. For example, mumps
went from being common to being unheard
of after the introduction of the measles, mumps, and
rubella vaccine in 1971. But it has returned to Harvard
and elsewhere in recent years. Other contagious diseases
are also on the rise, thanks in part to globalization
and global travel, environmental change, population
growth, and many other factors. In addition, we are increasingly
aware of non-infectious disease epidemics, often with
complicated social roots. We will explore these topics
during our afternoon session today with experts on guns,
opioids, and mental health. With all of that
in mind, I am very grateful that today’s symposium
will offer us a chance to wrestle with these
complex issues which are no less urgent and
less challenging today than they were in 1721. Today, however, we are
armed with big data, new analytical tools, new
technology, and new expertise, which our distinguished
panelists, I am sure, will bring to bear. Here’s how the day
is going to work. Professor Janet Rich-Edwards,
the symposium’s organizer, will offer framing
remarks in just a moment. And then we will dive
right into the first panel. After each panel or
individual speaker, we will open the floor
to your questions. We’ll put a microphone
in the center aisle. We invite you to step
up to introduce yourself and then to ask your question. During the lunch
break, I invite you to pick up a bag lunch, which
we will have available for you downstairs, and then to
join us for a student poster session next door in Fay House. Students from the Harvard TH
Chan School of Public Health, Harvard Medical School, the
Faculty of Arts and Sciences, and the Division of
Continuing Education will be present to
share their research with you, with our speakers,
and with other guests. The poster session
will be open as well during the reception, which
will also be in Fay House at the conclusion of
today’s symposium. And I very much hope you
will stay and join us for that as well. Finally, I want to
express my deep thanks to Janet Rich-Edwards
for organizing such an outstanding symposium. Janet is Radcliffe’s Faculty
Director for the Life Sciences, as well as an alum of Harvard
and Radcliffe colleges. She is an epidemiologist with
dual faculty appointments at Harvard’s Medical School
and the Harvard TH Chan School of Public Health. She also serves as director
of developmental epidemiology at the Connors Center for
Women’s Health and Gender Biology at Brigham
and Women’s Hospital. So, please join me now in
warmly welcoming Janet. [APPLAUSE] – Thank you, Liz. I am so thrilled to
see a full house today because this is going to be
a really exciting program. I’m going to take just a few
minutes to frame the agenda and give you some context
for our young science of epidemiology. Chances are when you
think of epidemics, you think of infectious disease. And indeed, you’d be correct
that the roots of epidemiology lie in concerns about diseases
like the bubonic plague, cholera, and the flu. These diseases
have long captured our imagination and our fears. Here is a 17th century
painting by Flemish artist, Michael Sweerts of one of the
first epidemics ever recorded in history. The date is 430 BC,
and we’re in Athens, in the middle of the
Peloponnesian War. 1/3 to 2/3 of the
city of Athens was struck by a strange disease. And most who became ill died. Thucydides, the
historian, himself survived to describe
the epidemic, a disease so severe and
deadly that no one could recall anywhere it’s like. And naive physicians were
the first to contract the disease due to their
contact with the sick. Thucydides recounted tales of
terrifying social upheaval, of the disappearance
of social morals, because people felt they were
living under a death sentence. Citizens started spending
money indiscriminately. Plus, some of the
poor, he noted, unexpectedly became wealthy
by inheriting the property of their relatives. Got to watch out for
those nouveau riche. [LAUGHTER] In fact, the disease
changed history. Although the Spartans,
seeing the funeral pyres burning in Athens,
retreated rather than come in contact
with the disease, Athens itself was weakened. Pericles, the general,
succumbed, and was followed by a series of weak leaders. The next offensive Athens
launched was a disaster. But Thucydides was
no epidemiologist. So the cause of the plague
of Athens was, and still is, a medical mystery. Epidemiologists today debate
what caused the epidemic, whether it was the
bubonic plague, typhoid fever, or
perhaps even Ebola. It wasn’t until the
mid-18th century before Westerners began to take
a systematic look at epidemics. John Graunt, here, the
son of a London draper, had a native curiosity and
a knack for statistics, and made his way into the
Fellowship of the Royal Society. He published the first analyses
of the bills of mortality, London’s death registry. Here’s what he recorded for
December 1742 to December 1743. The leading causes of death, you
can see here, are convulsions, which I’m wondering if
that might be heart disease because it’s so prevalent;
consumption, which, of course, we know of as tuberculosis–
see if I can see this here– fever, no surprise,
old age, smallpox– they apparently hadn’t
heard of the vaccine yet– and, horribly, teeth. I think that must be a
terrible way to go, frankly. Conspicuously absent are our
modern diseases– cancer, only 61 deaths, and
diabetes, one death. In fact, you were more
likely to die from evil than you were from diabetes. [LAUGHTER] Some exotic
diseases, including– I can’t read that from here– headmold shot, horseshoe
head, and water in the head. And my favorite, I
think the only way to go is a rising of the lights. [LAUGHTER] John Graunt made these
lists in an attempt to predict waves of the
plague, which he didn’t quite manage to do. But he’s the father of
the most fundamental of epidemiologic tasks,
the classification and counting of disease. Some hundred years later
in London, John Graunt would be followed by one
John Snow, a physician. Now, the epidemiologists
in the audience would be permitted
a collective groan because this story is the
equivalent of our Washington and the cherry trees. This is our first known
use of medical statistics to actually resolve the
cause of an epidemic. It focuses on a particular
neighborhood of London which was experiencing
an outbreak of cholera. At the time, the advice
of the Medical Council was to avoid vegetables
and unripe fruit and to abstain from cold water
when heated and ardent spirits, unless, of course, habit
made that impossible. In fact, boiled water
and ardent spirits may have been the safest
beverages in London to drink at the time. But the prevailing theory
among the people of London was that cholera arose
from miasma, or vapors from the Thames. This is 1854 London. And although the
concept of germ theory had been proposed by Wu Youke
at the turn of the 16th century in Ming Dynasty
China, in 1854 London, the germ theory of
disease wouldn’t grab hold for another 50 years. John Snow took it
upon himself to obtain a map of the effected district
and to plot every cholera death on that map. This is what we call
shoe-leather epidemiology, the close, geographic
investigation of outbreaks. The basic principle of
shoe-leather epidemiology is one we still
use, whether we’re tracing syphilis contacts,
the spread of Ebola, or investigating the
quintessential foodborne illness we classically call
the church picnic problem. John Snow went one step further
than just mapping the cases. He also mapped the lines that
supplied London’s drinking water through
neighborhood pumps. There were two companies
supplying water to the neighborhood. The Lambeth Waterworks,
here in blue, drew its water upstream from
the London sewage effluent in the Thames, while the
Southwark and Vauxhall Company, shown here in gold,
drew its water downstream from the Thames sewage. Snow traced the source
of cholera to the latter, and in particular, to a
hand pump on Broad Street. Now, you might ask
about the women who died from cholera– those
who lived next door to a pump from the cleaner Lambeth line. Turns out she had just moved
there from Broad Street and sent for water daily from
the old Broad Street pump because she preferred its taste. Famously, John Snow removed the
handle of the Broad Street pump and cured London of cholera. He’s considered
by most Westerners to be the father of
modern epidemiology. Here is a map of modern London. And you could still visit
the old Broad Street pump– it’s now Broadwick Street– which is located right between
the Anthropologie store and Chipotle Mexican Grill. [LAUGHTER] But the second greatest
plague the world has ever known– the first was
actually the Black Death, the plague itself, bubonic
plague in the 14th century. The second greatest plague
is the influenza of 1918, also known as the Spanish flu
It swept the globe, infecting nearly a third of all people
and killing between 20 and 50 million, more than died
in all of World War I. Downton Abbey fans
will recall that the Spanish flu with the
demise of Miss Lavinia Swire. Critics of the show complained
that the entire household of Lord Grantham would
have been gripped in fear of catching the disease. And dear Matthew
would probably not have been quite as
attentive as pictured here. [LAUGHTER] In fact, the decline of
infectious disease mortality due to the advent of
antibiotics and vaccines in the mid-20th century
is one of public health’s great triumphs. You can see here that
diphtheria, typhoid, and whooping cough,
also known as pertussis, declined quickly due to the
DPT vaccine we give children. Measles, too, is
prevented by vaccine, and scarlet fever is
treated by antibiotics. But we are still in
the grip of contagion, including some new diseases
and modern causes of mortality. Can anyone guess
which one this is? Feel free to call out. And if you have a– Zika. Very good. This is Zika. We’ll be hearing today
about the Zika virus from Dr. Celina Turchi
Martelli in the first panel. How about this one? No fair calling it out
if you have funding. – Lyme. – Lyme, exactly. Lyme disease. Dr. Kevin Esfelt
of MIT will tell us about Lyme and some
provocative ways to combat it. This one, which
has local issues– here is our dear commonwealth
2011 to 2013, 2014 to 2016– exactly, opiates. These are deaths
from drug overdose. We’ll be talking about that. Dr. Andrew Kolodny will
join us in the afternoon in a session devoted to
epidemics with social roots. And this one. – Gun violence. – Good guess, gun violence. This his gun ownership. But owning a gun does not mean
you will be injured by a gun. Here, you can see homicides by
firearms per 1 million people. We really– oh, bad choice
of words– trump everybody else in this arena. Dr. Andrew Papachristos,
a sociologist from Yale, will address the application
of epidemiologic principles to understand and combat
the spread of gun violence. The good news is that we have
new tools as epidemiologists. Through our understandings
of pathogens and DNA, we now use techniques with names
like molecular epidemiology and genetic epidemiology,
about which you’ll hear throughout the day. We also have new
techniques of manipulating the genome of disease vectors
like mosquitoes and mice. You’ll hear about the concept
of gene drive before lunch. And after lunch,
the panel will– well, after lunch, a panel
will address the exciting gains and the analytic
challenges of big data epidemiology, where everything
from the legions of bacteria in the microbiome of your
gut to cell phone records can be used to trace,
understand, and predict epidemics. We’ll also discuss
the tension between private and public sector
data and the concept of open science. At the end of the day,
our keynote speaker, Laurie Garrett, author
of The Coming Plague and member of the Council
on Foreign Relations, will address the role of
international politics, of globalization and isolation
in the role of countries responding to epidemics. This is CDC’s list of
the top 10 public health victories of the 20th century. Epidemiology, the young
science, played a central role in achieving all 10 of them. After all, epidemiology is
the science of public health, whether we’re talking
about diseases caused by pathogens or diseases
with pathogenic social causes. I’m excited about the chance
to learn about the coming challenges, and hopefully
victories, of epidemiology in the 21st century. And now, it’s my pleasure
to invite our first panel to the stage. Why don’t you guys come on up? And I will introduce to
you Dr. Marcia Castro. Throughout the day,
we’ll just give really quick introductions. You’ve got in your program
full bios for each speaker. So, Marcia Castro is
an Associate Professor in the Department
of Global Health and Population at the Harvard
TH Chan School of Public Health, and a Faculty Associate
at the Harvard University Center for the Environment. She’s published extensively on
the epidemiology and control of infectious diseases,
environment and health, spatial methods, and health,
particularly in Brazil. Please join me in
welcoming Marcia Castro. [APPLAUSE] – Thanks, Janet. Good morning, everybody. Once again, thank you so
much for putting together an event with such an
incredible and important topic. And our first panel
we will go straight into infectious diseases in
this new era of epidemics. And I think what really makes
it a new era is that we’re not discussing anymore of if we’re
going to have another outbreak. We know we will. It’s just a matter of
when and what pathogen is going to be this new outbreak. We live in a time that
everything moves faster– people, information,
goods, but also pathogens. And that makes it
really challenge when we have one of those outbreaks. And in the very first
moment of an epidemic when cases are going up and
everything is under chaos, we have many challenges
that we have to address. How do you find those cases? How do you contain? Do you have tools to
be able to treat them? How do you deliver
this treatment? Do you have health systems
that are strong enough to be able to be in the
field finding the people and delivering the response? We can’t forget
all the challenges of blending the different
institutions in the government. But also different bodies,
national and international– they’re going to be in the field
of responding to this epidemic. Let’s not forget also
about the ethical and the legal challenges
in prioritizing responses depending on the epidemic
we are talking about. So there are also another
phase that comes afterwards, which is when people basically
say the outbreak is over, which raises the
question, when is it over? Is it ever over? Which is an important one– tends to be neglected, which
is to look at the aftermath. So what happens after
the epidemic is not in the spotlight anymore? What are the consequences? What are the sequela
of the disease? But above all, let’s look
at the social, the economic, and the broad, demographic
impacts of the epidemic. We don’t have much
attention to that, but we are lucky that we do
have some research groups that stay on the ground and
try to bring information about this aftermath when
everybody thinks it’s over, but we’re not quite there yet. So, our panel has
three stellar speakers that will talk a
little bit about this. I’m not going to read their
bios you have in your program. And you should read
because they are terrific. But I’ll give you
an overview of what they are going to touch
upon in those issues that I briefly mentioned. So, we’re going to start
with Dr. Christian Happi. And he’s going to bring how this
top-notch technology that we have now can help us
in those epidemics. So, he’s going to talk
about how genomics can be used for
pathogen discovery, but also for surveillance. Then we’re going to move
to Dr. Anne Rimoin, who has one of those
research groups that actually stay on the ground when
everybody is saying, it’s over. And she’s going to talk to
us about her phenomenal work of tracking the survivors of the
1976 Ebola outbreak in the DRC and share with us
some of the findings that she had about the
long-term effects of the Ebola outbreak, the long-term
sequela that those people are experiencing. Then we are going to
have Dr. Celina Turchi Martelli from Brazil,
who played a really important role in the
Brazilian response to Zika. And in the middle
of all the chaos, she is going to tell us how you
can actually design and conduct epidemiological studies, how
you can foster collaborations between many different
bodies of research– and everybody wants to come
first and be the first one to say something new– and how you actually
promote sharing of data. All those three issues are hard
to do in normal conditions. Under an epidemic, they
are way much harder. So Celina is going to tell us
how she managed to do this. So together, those
three different talks, we’re going to walk us through
three different aspects. So the first one is how we
can mobilize researchers to do the right thing
at the right time and generate much-needed
evidence to be able to respond with the right policies. Second, we’re going to
see how we can better track new and
re-emerging pathogens, leveraging on the very best
technology we have available. And last but not
least, we’re going to see how we can assess
the long-term consequences of epidemic, largely neglected,
but extremely important. So without further
ado, let’s get started. Dr. Happi. [APPLAUSE] – Thank you, Marcia. And also, I want to
use the opportunity to thank the Radcliffe College
Institute for this invitation. So basically, I will
be talking about how we use genomics to characterize
and set up a surveillance system in West Africa and
how this has helped us and especially in
Nigeria dramatically to contain the last
Ebola outbreak in 2014. So, and we do this
within a framework. And that is the African Center
of Excellence for Genomics of Infectious Diseases. And the center is a consortium
of academic and clinical studies in Africa. But in addition to that, we
have partners here, especially at Harvard at Broad Institute,
Tulane University, and then also partnering in the industry. And we work together
with these partners in order to not only
develop genomic technology, but also translate those high
court technologies into tools that enable us to develop
rapid diagnostic tests to track these outbreaks, to track
diseases in the field. So this partnership
is actually built on a very solid foundation
on the strong long-term collaboration between partners. And this partnership, because
of its success as a [INAUDIBLE],, it has attracted
new collaborations within the region. So, and why do we
focus on genomics? Basically because
of one single thing. It’s the fact that the genome–
the whole genome project, and then the sequencing
of various organisms has brought tremendous progress
in the field of health, for instance. And Africa, you know,
really is not participating. And the lack of
participation of Africa is basically due to the
fact that there’s no scale. There’s no know-how. And there’s a huge divide
between the West and Africa. And that’s the
reason why we just decided to use the
genomic approach in order to narrow down the
gap, and also provide a needed knowledge in order
for African scientists to participate in the
genomic revolution. So our mission
actually is twofold. One is educational,
as I mentioned. And that is actually to
create a vibrant environment that is free of
external influence and that transcends
national boundaries in order to ensure relevant,
responsive, ethical, and high-quality genomic
research in Africa. And the specific
aims of the program is actually to develop– you know, train a critical
mass of well-trained African scientists to use
genomic knowledge to address important issues such
as elimination or eradication of infectious disease, and also
to create genomic curricula on the continent to address the
issue of infectious diseases, and also to engage communities
in prevention and public health education. And this particular
aspect of this program that I’m going to be presenting
[INAUDIBLE] the achievement is actually supported
by the World Bank. But the research
component of this program is supported by NIH. And the goal is actually
to use field-deployable, state-of-the-art technology
to identify pathogens driving febrile illnesses. The reason why we talk
about febrile illness is that fever is
actually the denominator for pretty much all infectious
diseases in the continent. In Africa, most of the time,
when you go down to hospital with a fever, the first
culprit is malaria. And after malaria, if
you’re not getting better, they say it’s typhoid. And when you go
through that process, if you have any other infection,
then the disease progresses, and eventually, you end
up in a very bad situation or you end up dead. And we’ve just
realized over the years that malaria is what
I call over-diagnosed and also anti-malaria
drugs are over-prescribed. And that actually
drive the whole process of drug resistance
on the continent. And we’ve heard that there
are many other pathogens circulating around that are
truly responsible for fevers that we see in 60% or 70%
of African patients that find themselves in hospitals. So and as such, this
goal is actually to create a foundation
for Africans to actually carry out
very [INAUDIBLE] research on the African continent. The reason for
creating the foundation is basically because we’ve
noticed over the years that not– I mean, Africans are
really not participating on the research involving
diseases on the continent. Samples are often
shipped out of Africa. And then they lose track. They have no idea of what’s
going on with a sample band. And then the next thing they see
is actually publications out. So, and it is high time
that we can actually set up on the continent facility
to enable diagnosis and enable research so that
Africans can start addressing their problems. These two programs that I
just mentioned, if you see, actually cross in
one particular area, and that is the area
of capacity building in the field of genomics. And what we do with
these two programs is basically to just ensure that
we have genomic teaching labs that we’ve set up
on the continent. Develop that core
diagnostic facility to track infectious
diseases, and then also encourage
sustainable careers among African scientists. Through this program,
with our [INAUDIBLE],, we’ve made some major progress. We’ve been able to add value
to what happens in Africa by reversing the brain drain. I also make what
I call brain gain. We’ve been able to track some
from young Africans in diaspora returning back and then
working together to address these major challenges. So overall, the overall goal
is actually to develop– I mean, to build the next
generation of African pathogen hunters. The reason being
that because we’ve been playing defense in Africa. And I think it’s high time
to start playing offense. We’ve always been at
the receiving end. We’ve heard about it. Zika, malaria, typhoid, Lassa
fever, Ebola virus disease– name it. We’re always at
the receiving end. I believe that now
it is high time to use the knowledge and
the technologies that are available to go down in
the dead bushes of Africa and hunt these pathogens,
characterize them, and of lab diagnosis
against them before they come hunting us. I think it is high time. And that is one of–
that is a major goal, and the ultimate
goal, of our program. So, what are our achievements? I will take you back as just
the 2014 Ebola outbreak. As far back as March
2014 when Ebola was brewing in the [INAUDIBLE]
confinement of Guinea. And the world was looking away. The major health organization
were not bothered about this. We’re very ambitious. I invited a group
of friends of mine from Harvard from
the Broad Institute, from Tulane, and some
other institution. You can see the picture here. We sat in my lab. And we thought that we could
solve the Ebola problem if it ever spread. We were very ambitious. We thought that
with a little skill and knowledge that
we have, we could address that major problem. But there was something that
came out of that meeting. And that thing was we had
a premonition that Ebola was going to spill over. And if Ebola spilled
over, what could we do? We identified diagnosis
as one of the major gaps. And what we did was
actually to go back on the side of
developing diagnostics– better diagnosis
for Ebola, and then train people in Nigeria,
Sierra Leone, and Senegal to diagnose Ebola. And as we rightly predicted, by
May 20, one of the technicians that we trained diagnosed
the first case of Ebola in Sierra Leone. And subsequently,
on July 22, I led a team in [INAUDIBLE] that
knew the first case of Ebola in Nigeria. The fact that we were
prepared and the fact that we were ready, for the case
of Nigeria, that single act, or that single fact
that we had this, was very critical to avert
one of the major health disasters that
could have happened in the history of mankind. That is preventing
the spread of Ebola in the city of 20 million,
22 million individuals in Lagos, Nigeria. We provided a
result within hours. And then we activated what I
call an emergency operation center. I worked with the
government for isolation and the containment
of individuals. And that alone
was very critical. The other thing that
we did was actually what I call
[INAUDIBLE] because we had the technology, because
we believed in ourselves. So when the agencies that
were parachuted in Nigeria– you know [INAUDIBLE]
had control– arrived, we told them that
we knew what we were doing. And then we were able
to contain the outbreak. [APPLAUSE] Interestingly, we went
on in the first three weeks of the outbreak. But we were able to
do this basically because we’ve been able to– we
achieved this feat in Nigeria because we were working on
a pathogen, a Category A agent like Lassa fever. And this agent is also supposed
to be as deadly as Ebola. But we were actually doing
this in [INAUDIBLE] facilities because we devised
ways of working with these pathogens in very
poor and limited-resource cities. And this is what you’ll see
what we’re doing in Sierra Leone and in Nigeria. What we did in
Sierra Leone that was unique was the fact that because
we’ve been working on Lassa fever, when we identified
our first case, we also activated what we call
a contact-tracing mechanism that we used Lassa fever. And they were able to trace
the first case of Ebola in Sierra Leone to a
traditional healer who thought that he had all the
power to do to cure Lassa, not to cure Ebola, and
through that process, was spreading that
across the region. But what we did in the
process was for the fact that we were actually
using– doing some research and then understand use
metagenomics, for instance, as a way to understand what
was responsible for fevers during the outbreak. As you can see, one of those– I mean, as you can see
that in the diagram below, you see many of
the cases that used to come to the Ebola
treatment center were not necessarily Ebola. But they were things like
malaria, HIV, and everything. So what happened in the
outbreak is that there’s a lot of sense of panic. And everybody that
comes down with fever actually is sent to the
Ebola treatment center. What happened– I mean, and then
the danger and the consequence of that is that you leave
your home very healthy, but then you come back. You’re actually
infected with the virus, and then spread an outbreak. So what we also did
during the outbreak was actually to
convert a process that used to take a very long time
in a laboratory that would take a few months in laboratory. We did that in 10 days. That is basically from
collecting the sample to generate sequence data. And we were be able to
achieve this in 10 days. So we generated about
99 sequence data. Within 10 days, and within the
first few days of the outbreak, I made these sequences available
to international community. We’re not concerned
about generating data for publication. We’re not concerned about fame. We’re more concerned
about making information available to the
international community so that they can
use the sequence data to generate drugs,
develop vaccines, or develop diagnostics. And the publication
came back months after. We’re also in the process– you know, went on and then
work on developing methods to sequence Ebola
and then Lassa fever. I mean, this was
in collaboration with colleagues at Harvard
and at the Broad Institute. And this method will actually
publish more or less like SOPs where anybody could
actually use it actively to repeat or
replicate what would we were doing in the laboratory. And that was also
very important. We use genomics
actually to understand the spread and the transmission
of Ebola in Sierra Leone during the outbreak. And as you can
see in this chart, you could see that you have
two different strains of Ebola entering Sierra Leone in-between
March and June 20, 2014. And I could see it through
the process by June 2013, the third strain that actually
entered, SL3, has taken over. So this was a strain
that was better adapted and had a better
transmission efficiency. We identified multiple
snips the strains. And they [INAUDIBLE]
confirmed from human-to-human transmission,
and also confirmed the fact that there was no sources
outside the human-to-human transmission. Over time, we were able
to use genomic data to actually reconstitute
transmission in the region. And I don’t know this
map will show it, but this was just
a video actually to show how this happened. The outbreak in Nigeria
was a little bit smaller– four months. But within the four
months, we were able to actually
use genomic data and then use contact tracing. As you can see in those
two panels, A and B, you can actually
superimpose very well the genetic data and then
the contact-tracing data. And that actually
shows the power of genomics,
actually, in the field in order to understand
epidemiology and transmission of disease. So what we’ve been
doing over the years is actually to identify a
pathogen based on sequences and then use these
sequences as a way to develop new
tools for diagnosis. And that also was
being very helpful. During the four months of
the outbreak in Nigeria, we worked with partners, having
these sequences, in Africa, having the Ebola
sequences to generate a rapid diagnostic
test that could diagnose Ebola in 10 minutes. The reason why we actually
spent a lot of time developing that test is basically
because during an outbreak, we need to two main
things, speed and accuracy. We realized that it would
have taken about four hours to do one single diagnostics. And then we have
to think about– be creative about
ways of actually producing diagnostic
data almost in real time. And that– when we actually did
that, we actually realized– I told them it was major
game changer in the field because clinicians
could actually have this information
in near real time. We also used the– I mean, what we’re also doing
is basically use genomic data, actually, to understand and
then discover pathogens. And in this case,
for instance, we’re looking at patients
with febrile illness. And as you can see
in these two panels, you see healthy patients
and in febrile patients, you could see that you have
more in febrile patients in terms of viruses, 8%– you know, 2% in people
that are healthy. So that shows that
viruses actually also could be very responsible for
many other febrile illness that I would see. And in the process, because
we also see some pathogen that have no heat. In this study, this is just
to illustrate how it’s really what you use [INAUDIBLE]
to make a major discovery, for instance, Nigeria. And in this case, control
study, for instance, we discovered two new
viruses in Nigeria. And these two new
viruses, we actually called them the
ipomovirus 1, it’s a rhabdovirus that’s
similar to rabies. And these viruses share
some very strong similarity to the [INAUDIBLE] virus
that was discovered in DRC Congo in 2012. And that is all–
that was shown to be responsible for some kind
of viral hemorrhagic fevers. But then that shows,
actually, the power behind the public
discovery platform that we have because having
discovered these viruses, we also went on and then
developed new diagnostics for them. But what is interesting
about this story is basically that when we went
back to develop the diagnosis and went back to the community,
even though these viruses were new, 80% of people in those
communities were highly exposed and had a lot of antibodies
against this virus. So it shows clearly that
there are many pathogens that are circulating in our
community– are circulating around that we don’t know about. But then we need
to use technology to actually discover them and
see how we can actually develop diagnostics and [INAUDIBLE]. So using, again,
genomic technology, we are able to understand– I mean, the origin and the
spread of a very old virus in Nigeria– not very old, but a
Lassa fever virus that is very similar to
Ebola in many ways. And this diagram
actually shows you– and this is a study
by Kristian Andersen, a friend, a colleague of mine. So, and here, we could show
you that this virus that we’ll call Lassa fever
has been circulating in present-day Nigeria
about 1,600 years ago, and circulating within
Nigeria for 600 years, and then moved out of
Nigeria about 400 years, moving westward. And then in the
field, we can actually see the differences
between an old virus that is very old in one country,
and then moved freshly into a new country. When you look at the
pathogenesis of– or philosophy between
Sierra Leone and Nigeria, they are very different. We also used that to
develop new technologies. But then we use the epitome that
we sequenced in those viruses to develop a rapid
diagnostic test. We called it [INAUDIBLE]. And that– we use that now
as a way to help the Nigerian government to look at– to set up a surveillance system. What we’ve done over the years
is not just only do science, but also to train the next
generation of pathogen hunters. So we set up with a
genomic training program. And we do this in
collaboration with Harvard. And then we started in 2014 with
11 students from two countries. As you can see, the list
is growing over the years. And this year, we’re
actually at 23 students from eight different countries. And here, you can
see, for instance, the training programs, the
kind of topics the we cover. And pictures here could
show you very young Africans that we’re training. But apart from just training
them, what we train them to do is– we worked with
the Derek Bok Center here at Harvard to enable
them to use videos. And it is videos
I actually posted. And then they serve as
MOOCs so that people that are not privileged
to be in a place in like Harvard at least could
have access to those videos and then learn and
educate themselves. So, what we’ve done is
actually training them. But not just training them,
but we also accompany them with infrastructure. So we’ve set up
next-generation sequencing in Nigeria, in Senegal, and in
Sierra Leone early this year. So the trainings
actually have facilities that they can go back and use. We also organize workshops
and genomics workshop series in Nigeria or in Africa. And we’ve trained over 600
students over the past three years. And then we have 21
doctoral students and then 46 master’s degree students
within the program. The whole idea is actually to
translate genomic sciences, for instance, into tools that
will enable us in the future. As you could see
here, that it’s coming from a high court,
high-tech technology, and then bring it
down to a level that we can actually
use in the field with small, portable
equipment that enable diagnosis in the field. So, whatever we’re doing
actually is not stopping. What we’ve also done is actually
to set up an outreach program. And this outreach
program that we’ve set up is actually to take it
outside the university and outside the ivory tower. As you can see here,
we have a program where we take it in high
school and inspire the kids at a high-school level. But what we also do is actually
to educate science teachers in Africa because you can’t
give what you don’t have. So we spent time
training these kids, bringing them in
our labs, and then inspire them at that tender
age, and work with their teacher so they can go back with
biology, DNA, RNA, and protein models so that they
can use that to teach. And the students will also
have a summer training program that student comes
in, and then have training in our laboratories. We’ve received support from
many institutions for the work that we’re doing. But this– what we’ve
done is actually– I mean, it has a
lot of challenges. And one of those things,
one of the major challenges in the world is supply chain. Supply chain is a major problem. We’re doing this kind of work in
Africa and we produce nothing. So how do we maintain
the supply chain? So what we do basically to
maintain our supply chain is actually to
convert our trainees that come to Harvard for
the summer training program into courier. So we load them with
[INAUDIBLE] and then with supplies and [INAUDIBLE]. And then when they get back,
then they can take them. But then we’ll
also have problems. When you get back, then you
have an issue with customs. So, and customs will not
allow you to come in. So what we did in 2014
was actually to enable– we’d print them
a T-shirt, and it would say Ebola diagnostic
trainee is coming back. When they got to the border
and they were disturbing them, they all just saw Ebola. And then eventually, customs
asked them to [INAUDIBLE].. [LAUGHTER] So I just want to
end this presentation to thank all my colleagues and
my partners here at Harvard and all over the world. And eventually, I just
want to thank you again for give me the opportunity. Thanks. – Very good. [APPLAUSE] Thank you. OK. Thank you so much, Christian. This was phenomenal. So now we’re going to
move to the following up after the epidemic
with Dr. Rimoin. – Thanks. [INAUDIBLE] – Thank you. – Great. Perfect. All right. Well, thank you very much. I am here to tell you a
little bit about the work that I’ve been doing in
the Democratic Republic of the Congo. The Democratic
Republic of the Congo, for those of you
who are not aware, is the largest country
in sub-Saharan Africa. I spent the last
15 years of my life working on emerging viruses
and doing what many people have told me over and over
again was impossible, which was to do really good
science in one of the most difficult places in the world. DRC, as you can see
from this slide here, just to give you some
context, is really big. It’s a third of the size
of the United States. But unlike the United
States, there’s only about a thousand miles
of road in the entire country, which can make it very, very
difficult to get much done. The DRC is also a place
where we’ve seen Ebola, not just in 2014, but all the
way back to 1976, 40 plus years ago, when the very
first outbreak of Ebola that occurred both on
the DRC side and in Sudan right across the border happened. Now, we all know today
that between December 2013 and April 2016, the largest
epidemic of Ebola to date generated more than 28,000
cases that we know of and more than 11,000 deaths in the large
mobile populations of Guinea, Liberia, and Sierra Leone, and
just barely in Nigeria as well. This outbreak was very
important and provided a lot of opportunity to track
and understand survivors and generated a lot
of new insights. And that’s very, very important. And it’s very, very important
because the outbreak was able to end and did not
create more cases than we originally were worried about. Now, we were all thrilled when
the outbreak was declared over. And we– but we’ve
heard this before– the outbreak is over. The outbreak was over in
Liberia, and all of a sudden, there were several
cases that reemerged. And since that
outbreak has been over, there was actually
another outbreak in the Democratic Republic
of the Congo just in May. So just because the
outbreak ended– this very large
one– doesn’t mean that Ebola isn’t still there. So, let’s see here. How do I do this? OK, here we go. But what we do know now is
that for Ebola survivors, the outbreak isn’t really over. We now know that
more than 50% or so of the infected who pull through
still have long term effects. Many of these people have
resumed their normal lives, but many of them are
still traumatized. They’re struggling to process
the horrors they’ve seen, rejoin societies that
have shunned them. And the after-effects are
not just psychological. We know that there are many,
many after-effects of Ebola. We just don’t know
exactly what they are. The studies that have been
ongoing in West Africa have showed us just a few
years after the outbreak that there are
ocular side effects. There are neurological
side effects, that people are actually
able to carry the virus and potentially shed the virus
from immune-protected sites for much longer than
anybody ever anticipated. And it’s interesting that
nobody ever anticipated this because it turns out there are
a lot of survivors to study. What we know about right now
from these studies from 2014 going forward is there a lot
of things that can happen. But the question is, what else? I think that it’s
important for me to invoke a little
bit of baseball since the Dodgers are
actually in the World Series. But it’s really true that
what we’ve learned about Ebola is that it really– it
isn’t over until it’s over. And the big question
is, when is it over? Well, and there are a lot
more questions about Ebola that we still have to answer. We don’t know how long can
somebody transmit Ebola virus. How long does it
stay in these sites? For example, if
we can still find Ebola in the fluids
of the eye, are ophthalmologists at risk
for acquiring infection long after survival from infection? Are survivors protected
from long term– from future outbreaks? How long does the immunity last? Is there anything
that can be done to reduce these after-effects? And what aside from the
clinical effects are there? We know that there
are economic effects. We know that there
are societal effects. None of these things do
we have any information about further than four
years after this outbreak. Now, one would think there
have been outbreaks since 1976. So we ought to have
a lot of information. But actually, until this
recent Ebola outbreak, the longest study
looking at survivorship was only 2 and 1/2
years after an outbreak. And that was done in 1995. The 1995 outbreak–
there were studies that were done 2 and
1/2 years afterwards. And much like what we’ve
been hearing about, the outbreak happens,
we think it’s over, and we move onto the next thing. Well, we do have cohorts
in the Democratic Republic of the Congo that are there
and can provide very, very important information. In DRC, we’ve had
eight outbreaks– 1976 all the way
through now, to 2017. So what my program
is doing is we’re going back and looking
at these survivors from 1976, 1995, and 2014. So we have three really
unique groups that are roughly 20 years apart. And what we hope is to better
understand the long-term health consequences of infection to
determine if survivors develop immunity that will protect
them from future infections, assess whether previously
infected people can transmit the virus still, to
understand all of these things that I just brought up. We really don’t have
any information. So we think, great, no problem. You just go. You’re going to find
these survivors. You get their phone number. You get their address. Maybe you send them an email. No problem. Well, it’s not so easy in DRC. The ’76 survivors and
the 1995 survivors happened before the
civil war in DRC. And so, all of the
records were lost. There were no records. So I went back to the
original investigators from the ’76 and ’95 outbreaks
and asked them for their notes. Well, for especially
from the ’76 outbreak, there were no
electronic records. And so, I had some
very, very nice help from people like Peter
Piot and David Heymann who went into their garages
and their basements and their attics and found
their handwritten notes. And with this
information and the map that you can see
up here, which was about the same as the
map that still existed in Yambuku in this site,
I went about the business of finding survivors. And to my surprise and
to everybody else’s, we found of 38 people that we
knew were infected in 1976, we found 14 of them still alive
in these very small villages. And so one by one, we
went through the forest, found these people,
and asked if we can study them and understand
their experience a little bit better. Well, but finding
them is one thing. But then you have to take
some samples from them. And we’re not just talking
about taking some blood and putting it on a
dried blood spot card or taking a couple
tubes of blood and putting it in
my refrigerator. You know, it takes a
little bit more than that. And what I think our
study site has proven is that it is possible to do
really good science in very, very difficult situations. So this here is our
nice, little lab that we were offered by the
Ministry of Health in Yambuku. And so we brought all of these
supplies in this nice hut. We cleaned it up a
little bit and made sure that the goats and the
chickens were out of the room. And so that it was really
possible to do great science, to be able to isolate
B cells and T cells, which might be able to lead
to vaccines and therapeutics in these conditions. And we only have the
preliminary data at this point. There’s a lot more to do. But thus far, one of the
very interesting things that we’ve found is that these
survivors from 40 years ago still have strong
antibody responses– every single one of them. And not only that,
50% of these people had the ability to
neutralize Ebola virus all of these years later. We’ve also found that there are
evidence of long-term effects. There’s a lot more
work to be done. But we have just
started to find out all of this very
important information that has the opportunity to shed
light on what these 16,000 plus survivors in West
Africa may be facing, and all the other survivors
from all the other outbreaks. So, once we started
that work, we also realized that there
was a lot of questions about asymptomatic
infection– about people that might get infected but never
show any signs or symptoms and how many of them existed. And over the last couple of
years with the Ebola outbreak in West Africa, we’ve
now gotten good evidence that people who get Ebola
don’t always show symptoms. So I thought, well, health
care workers are a really good population to look at. They’re on the front lines. They’re at greatest
risk for infection, in particular in the
kind of conditions that they’re working
in, without the kind of personal protective equipment
that people in this room may be used to when
they go into a hospital. So we started taking samples
from health care workers in all of these sites
where there had been Ebola outbreaks and a few
sites where there hadn’t been, just to compare. And we found some very,
very interesting results. We found that health
care workers had very, very high rates of Ebola,
surprisingly high rates of Ebola antibody evidence
that they had been previously exposed to Ebola, and much, much
more so than in the sites where there had never been
an outbreak reported, suggesting that not only
did these people have the opportunity to get
infected more often– which isn’t really surprising– but that there is
something going on. Now, “health care worker”
is a very broad term, and can mean many, many things. To most of us here, you
think of a doctor or a nurse or a midwife or a lab tech. But in places like
Central and West Africa, those are not necessarily
the most common providers. We really, really
see a lot more people going to informal
health care workers– to what we would consider
traditional healers, to pastors, to local figures who
can go and help them in a way that people understand
much better. They’re more accessible. They’re less expensive. They may take for
payment instead of money you could work in their fields. You can give them food
that you grow yourself. So those are– those
informal health care workers are actually
very, very important. And once again,
interestingly, we found that these informal,
traditional health care providers were also
people who were highly exposed. What’s interesting is you
think, OK, well, fine. There have been Ebola
outbreaks in these sites. So it makes sense
that people who were in that area at the time
might have been infected. But interestingly, in
Yambuku, where the outbreak happened in 1976,
those people who were born after 1977, after the
outbreak was declared over– and I know now we
all know that “over” doesn’t necessarily mean over– but “over.” Those people that were
born after the outbreak– we found almost as high rates
of antibody in those people as the people who had been
alive during the outbreak, which suggests that Ebola
is still circulating in these populations long
after it disappears from view. So of course, now there are
more questions than answers. We wonder is Ebola virus
circulating silently in DRC? Well, our preliminary
results suggest that that may be the case. How are asymptomatically
infected people acquiring infection? Are there certain
groups that are more likely to be
infected than others? Can asymptomatically
infected individuals transmit the virus as well? What role do they play
in Ebola transmission? And do these people also
have long-term after-effects? We really have no idea. And although we have known about
Ebola for a very long time, we’ve not gotten to the
bottom of these questions. The thing is is we’re
really running out of time. The aperture for doing
these studies is closing. The populations that we’re
working with are aging. And the natural life expectancy
for a Congolese person is 57. The outbreak now
happened 42 years ago. And many of these
people were adults. In fact, when I started
doing this study, I said I found 14 survivors. Those were the 14
survivors that we were able to collect
samples from, where there were two
other survivors that we found and made contact
with, but were not able to get back to in time
before they passed away. One was 95 and one was 59. So the aperture
really is closing to do these kinds
of studies, not just for the survivors
that we know about, but for those asymptomatically
infected survivors from these very,
very early outbreaks. And so, this is the
kind of work that we are trying to move forward
with as quickly as we possibly can to gather as
much information and to be able to capture
samples in history and epidemiologic data– everything that we
possibly can and archive it so that as technologies
improve, as we understand more about Ebola in general, not only
can we make use of the samples that we’re collecting
now and the information we’re collecting now,
but that we’re banking it for the future
so we don’t again have this problem of forgetting
to look at what we should have looked at a long time ago. Thank you. [APPLAUSE] – Terrific, Anne. So now, we’re going to move
to our last speaker, Celina Turchi, who is really
going to talk about how you respond to a
major epidemic when you are in the middle of it. – Good morning. What a challenge to
talk after those two. But I would like to first
thank the organizers for this opportunity, To name
a few, crews in Pernambuco, Brazil, and the Microcephaly
Epidemic Research Group. I’m here to present some
insights of the public house response in the
recent Zika outbreak. And I love the title of
this symposium, “Contagion– Exploring Modern Epidemics.” Because I think that Zika
was a very good example. So first, I would like
to have a brief context. What are vector-borne diseases
in complex, urban areas? So, in 2015, dengue
was considered a major problem in Brazil. 1.5 million cases, 900 deaths
for dengue in one year. Since the ’80s, we have been
having dengue epidemics. And Brazil was one of the
most affected countries in Latin America, with the
four circulating serotypes from DEN-1 to DEN-4. So what we could say that
urban environments, climate– and favors all-way
around transmission of dengue with marked
seasonal patterns and explosive epidemics in
different areas of the country. That was the
scenario for dengue, and was the public
health’s concern in 2015. But there was an alert
about the introduction of another virus that were
coming from the Caribbean. That was the chikungunya
virus that’s an alpha virus. But this alert was just that
this disease was important because it gave– it brings this ability and could
cause these large epidemics. That was really known. And then something comes
as a mystery disease that was called by the public and by
the media, a mysterious disease that was a benign disease. It was a fever like most
of infectious disease. People didn’t feel ill, so
it was considered kind of, don’t worry about this disease. Let’s call it
dengue-like illness. That’s how doctors were
taught by the public house at the moment because
we knew nothing about the neurologic
context of the effects. So, that what happens. I need to go to this
map just to show you. Actually what we had– the green circles
is chikungunya. And red circles is Zika. And imagine in 2015, there was
The Lancet journal just wrote, Zika virus with a
question mark, following dengue and chikungunya. There was still
this question mark. Was it going to occur? And if we look at
the map, the alert was for chikungunya,
not for dengue. The big circles in
Brazil and elsewhere was for chikungunya
in the Americas, not for the dengue epidemics. But here, it is very
important to say that we’ve been hearing the
last speakers about Africa. Zika was known to be
in Africa since 1947. But for 60 years, the
epidemiology world just knew very little about it. I may say that we had
14 cases in humans published for 60 years. That was really a
medical curiosity. I imagine that moves
think infectious disease and trained
epidemiologists never heard about Zika, like myself. I had never heard about Zika. And virologists, the book– virologists had
just one paragraph saying about the zoonoses. But the first epidemic– the history of the
epidemic is started in [INAUDIBLE] of Ireland
and French Polynesia Islands. But they were a small
population areas. There were cases. There were cases. There were a lot of
asymptomatic cases. And the French
Polynesia reported the first neurologic
effect of Guillain-Barre. So if we go to that
dark spot here, that’s Recife, the
northeast of Brazil. That’s where we were at the
beginning of the epidemic. It was August. So, what was going on? The capital of
Recife in Pernambuco, northeast of Brazil,
was the epicenter of this microcephalic epidemic. We were at the front line. And what– there
was a microcephaly with unknown etiology. We didn’t know what to
look for because all the infectious disease and all
of the genetic disease supposed to cause microcephaly
were negative and didn’t test positive
among these babies. So for that time, it
was an unknown cause. And remember when
those babies are born, and when the mothers were
affected several months before. So we couldn’t get genetic
proofs at the moment to find it, nor we
did have lab tests so we could test immediately. Lab– they weren’t lab tests. There were lab tests in the CDC
that would take weeks to get. And even if we get
them, IGM and RTPCR aren’t always positive
after such a long time. So looking back
in retrospective, we may say that Zika virus found
a large pool of susceptible individuals, abundant
presence of Aedes, good environmental conditions
in a densely urban population. This is good enough,
OK, to make it possible a range of possible
neurological outcomes, including Guillain-Barre
[INAUDIBLE] syndrome and also microcephaly in babies. So, the timeline is almost
like an old epidemic. Good doctors spot something
that they see that’s not usual. They contact health
authorities, there’s something very
important going on. And in November 2015, the
Brazilian Ministry of Health declared a situation of national
public health emergency. We saw very few evidence. We just have short evidence,
some cases, some stillbirths with virus in their brain. But there was a no
epidemiological study to think about causality. Causality is very important
for us epidemiologists. It’s a very serious business. So, what I want to say is
that the emergency in Brazil was a turning point for
the public health response. It really was a turning point. Researchers and health care
workers working together, they developed new protocols
and research instruments for field work. The magnitude of the
event to put attention on this [INAUDIBLE]. I mean, it was so
important that broke personal and
institutional barriers, creating a collective
solidarity feeling, a commitment of sharing data and knowledge. That was the status. Nobody wanted to publish a
paper first like said before. We want to have a group. We want to be known as a group
that just could do things as a group, as a team,
independently in which institution [INAUDIBLE]. So, I think here that I have to
say the intense collaboration of several institutions around
the world and within Brazil. And this morning, I had some
very nice thoughts like, epidemiology is a sign of
[INAUDIBLE] public health. And I fully agree. And that’s what we saw on the
field exactly where we were, trying to do good
epidemiology in the situation. And I always learn
a term– yesterday, a terminology that
I found it very appropriate for this moment. We were not doing
peacetime research. We were doing wartime research. So time was so important. Collaboration was so important. So I wanted to just briefly
to show that was the features. We had almost like a phenotype. I can’t go into details. But you can see the
disproportional face and how bad– how small these children,
and how bad it was. Here, you can see the
tomography of these children, it’s so easy to see the
calcification and the damage of the brain and how
important and how would be the developing of
these children considering this situation. So we entered this– the Ministry of Health
proposed for the group– for our group to design
and do a case-control study that was funded by the Brazilian
Ministry of Health and Pan American Health Organization. The idea is that
epidemiologists, in our toolbox, we have
the case control as one of the first options because
we can get from the outcome to the exposure. It means almost doing
like research in reverse. You don’t expect
things to happen. But you just go from
back to going to– next page. So we had many hypotheses. And two of these
hypotheses were very– let’s see– very important
considering public health. One was that a larvicide
that the government had put in the tank water that
was called pyriproxyfen was the cause of
the microcephaly. So this was a very
important issue because during an
epidemic, you would have to take out
the control measure because it was supposed to be
the cause of the microcephaly. And the other very important
[INAUDIBLE] hypothesis that came about
was about vaccine. So it got really in the media
that vaccine, like the rubella vaccine, was something
that was doing again– kind of having an epitome. Like, say, we have an outbreak
due to the vaccination. So you can imagine
what the panic and the what the amount
of confusion and rumor that was going on. So those pipe waters
had to be tested. Of course, our main hypothesis
was really the Zika virus infection. Why? Because it had been proven to
be very neurotrophic in animals, we had the right temporal
sequence, and so on. So we designed a
case-control study that was the first
case-control study we designed. We couldn’t get
retrospective [INAUDIBLE] because we had to be sure that
they were congenitally infected and we choose the
right controls. And laboratory confirmation–
it just brought it here because it was so important. We didn’t have good lab tests. We still don’t have
a good lab test. And what do I mean is that
Zika and dengue, being from the same virus,
like the same flavivirus, they cross-react. So remember that this population
had been exposed to virus for 30 years for dengue. So when you get a positive
serological result, you don’t know if it
was dengue or not. But we are very lucky to
have in our institutions– like you said before– preparedness, like
with this lab, it was a reference
lab for flavivirus, and could do more lab
[INAUDIBLE] tests like PRNT Just for Zika and
for dengue in order to know for sure if we’re
having a Zika-positive case or a dengue-positive case. I’m just going to show
that these factors– I just made a big jump and I
excuse the epidemiologists. So you can see the odds one
doesn’t have any difference between cases and controls. So you can see here
smoking was a confounder– actually was a confounder. Alcohol, vaccine,
and larvicide had nothing to do with
this epidemic at least. And when we have
this cartoon here, what we see in
this case-control– it’s something very strong,
a very, very powerful association– only
cases had been infected or had been congenitally
infected with microcephaly. So we’re talking about in that
day’s epidemic of microcephaly and not all microcephalies. And another very important
result from this case-control study– then we measured the past
exposure of this Zika in the mothers of
control that will be kind of our population control. Even if it’s not such
a large sample size, 60% of these mothers
had been exposed. What does it mean? It means that in the
first wave of Zika virus, there was these huge exposures. I mean, we did have a naive
population, a huge population, that were struck by
this wave of Zika and become infected
and were infected and had an antibody response. So those are published papers. The ones who work in research
know this is very fast. I mean, we did it in
a fast-track approval that went under the emergency. And so, that’s
the situation now. And what now? You’ll see the first map
shows the first wave. When you see the first,
very focused point, the epitome just in the first
in the northeast in two very spots in the south. And later on in
the next year, you can see that it’s not
too much transmission. It doesn’t look like
too much transmission. If we think about
surveillance, we just have surveillance data for 2016. That’s the red line that
means the Zika infection. And we can see in this pic what
we see is seasonal epidemics, and you have a flat plateau. That transmission– we don’t
see too much transmission there. Now it’s chikungunya time. It’s not Zika time anymore. But what we see now– is it going? This is what I found. It was more surprising
of the epidemic was the use of WhatsApp
for good and for bad. I mean, for good,
for communication between the doctors
and patients, and for bad, for
rumors, for fake news, for everything you can imagine. So this was kind of a nightmare. So, just brief remarks here. What were the challenges? I think there are now ongoing
cohorts all over the world monitoring pregnant
women and newborn babies. We know very little
about the risks. I mean, if the risk is a
stable or we have varying risks according to
different populations. We don’t know very little about
this fraction of the disease we’re talking about. We don’t know how these
children are going to develop. There are a lot– there’s much, much
room to improve in diagnostics for management
and also for research. I think that we are in a point
that we really need improvement in this kind of diagnosis. And there are other
very important research being carried on. Now, I want really to
thank our group here and to present our group. That’s Microcephaly
Epidemic Research Groups. I mean, a lot of people
from many institutions, many public institutions,
from all over the world, and especially from Brazil. A special thanks to
Dr. Laura Rodrigues from London School of Hygiene
and Tropical Medicine. And here are all
the institutions. And here are all
of our supporters– NIH, there is a cohort of
pregnant women with NIH and a lot to work with
ZikaPLAN in many fields. Thank you very much
for your attention. [APPLAUSE] – OK, so we’re going to have
just a brief discussion. And then we’re going to open
the floor for questions. So please start thinking
about your question because we’re going to need
your participation in a moment. So, I think there are
sort of three things that became pretty obvious across
the three presentations. One is really the importance
of local capacity. That’s absolutely crucial. And it’s not that we are
solving all the problems for the next outbreak, but as
you build up the local capacity to respond, to
have the knowledge, to have the tools, that’s
absolutely crucial. The second one is each one
of this work is basically about overcoming challenges. And they are many. either because everybody tells
you you can’t work in the DRC or because you are in
the middle of an outbreak when nobody knows what to do,
but you have to do something. And I think, to me, the
most important thing that comes across– and fortunately, this
is true for many of us– is that if you really want to
do the right thing in the middle of an outbreak, you really have
to go against the brutal tenure system and focus about saving
lives and not writing papers. And this is crucial. And some of us do that. We may get– I’m not saying
what I’m going to– anyway. [LAUGHTER] We may not be very
successful at the end, but at least we can
sleep well at night with our head on the
pillow because we are trying to save lives, not
to get a paper in [INAUDIBLE].. This is crucial. And I cannot thank you
enough for bringing that up. So, I’m just going to have
one question for each speaker just to warm us
up, and then we’re going to open to the floor. So, Happi, I want to
ask you a question. You do all this training. You have people coming from
all those different countries. Training there, training here
and abroad, then those people go back to their countries. You can guarantee
what goes to Nigeria. Are they able to actually build
the same kind of infrastructure and have the same
kind of response fast as you can
provide in Nigeria? So, is this training
that you’re providing being translated into really
resources in the countries when they go back? Anne, I wonder if
you’ve found something on sort of the social side. So how about stigma? How about social consequences
in the lives of those people? And many of them
have been surviving for more than four years. So were you able to learn
something about this? And one thing that
got me curious is, do we know anything if
the asymptomatic infections– if those people are infectious? Because if we do have
so many transmission is still going on although
everybody think it’s over, why don’t we have
another outbreak? And Celina, I’m kind of
going to put you on the spot, but we are both Brazilian
so I think I can do that. – Friendly fire. [LAUGHTER] – So, I think another
thing that is obvious is context matters always. We are never going to
have two outbreaks that are going to be the same in the
way they happen and in the way we respond to them. So, I think you
highlighted the importance of the front-line workers,
of the government declaring an emergency even not
with so much evidence, but he did, and
in supporting you to lead this incredible work,
this epidemiological work, to respond to the epidemic. The context now, 2017,
is very different. The leadership, both in the
government and in the ministry is different. So I would like you to reflect
how this whole crisis would unfold if Zika had
arrived in Brazil not in 2015, but in 2017. I told you I was going
to put you on the spot. [LAUGHTER] So, Christian. – All right. I don’t– – Oh, you have your
microphone, so go for it. – Yeah. I think one of the
questions was are there facilities for trainees
to use after training so that they can respond as fast
as we did in Nigeria in 2014? The answer is yes. In [INAUDIBLE],,
you saw we ensured that the trainees actually
get back and use facilities. So one thing that we did
basically in the countries where we have this [INAUDIBLE]
network across a region. We’ve set up a
reference laboratory with state-of-art
facility, for instance. In Nigeria, we have
next-generation sequences installed. We have the same in
Sierra Leone and we have the same in Senegal. And those operating
those systems received the same training. And we use the same protocol
for any eventuality. So [INAUDIBLE] apart from
using those high-end equipment, we’ve also translated this
into middle-end and low-end facilities that it can use. For instance, for the
rapid diagnostic tests, we’ve done extensive training
for high-tech workers that can use those for diagnosis. And we also have the
medial [INAUDIBLE] that can use that
qPCR for diagnosis, for confirmational purposes. And in [INAUDIBLE],, for
instance, or Nigeria or in Dakar, you’ll see
the very high-end equipment where we can actually
do confirmation. And that is the reason
why, for instance, because we have that– we’ve had cases in [INAUDIBLE]
suspected cases of Lassa fever in [INAUDIBLE] weeks back. Those were sent to those
facilities in Senegal. And actually, we confirm
it wasn’t Lassa fever. Presently in my lab, we’re
dealing with monkeypox outbreak in Nigeria. So, and we’re basically
confirming cases and also responding
to the outbreak and facilitating
government intervention in all those areas. I think in a way– I think in a way, we’ve
kind of addressed that. And that’s one of the reasons
why we’re not just framing, but we’re also ensuring that
there are facilities that will accompany the trainees. – Wonderful. Thank you. Anne? – OK, so you asked me
two different questions. Is this mic– OK. I think this mic’s on. So, you asked me two
different questions. The first one was about the
social effects of Ebola. And I just recently came
back from the 1995 outbreak. So this is something that’s
very, very fresh in my mind right now. I spend a lot of
time doing interviews and talking to these people
about their experience. And I think it’s very,
very interesting. First of all,
meeting these people and giving them the opportunity
to talk in this case just 22 years later, it’s the
first time anybody had come to them in
20 years to ask them. You know, in West Africa–
and this was a point that they made and really
was driven home to me. In West Africa
after the outbreak, there are 16,000 survivors. And so, there are
support groups. There are social services. There is a huge investment
on the part of the US and other governments to study
them, to enroll them in trials, to enroll them in studies,
which also gives them the benefit of having quality
of care, whereas people in West or in Congo,
all of these cohorts– there’s nothing. There are no studies. There are no trials. There’s no support. And even to go to these
sites and to do these studies in ’76 and ’95 outbreaks,
we needed to have labs. And we had big negotiations
with the hospitals and the local government because
they didn’t want the survivors all in the same place. And they were worried
about what happens when the survivors come. And in fact, the survivors
were very nervous about coming to the hospital. They felt the issue of
stigma is so great even in trying to do
studies with them. It’s something that’s
very, very important. And so even just the fact of how
hard doing these studies were is all attributable to
this issue of stigma. And the stories that
still need to be understood in greater detail– and we hope to do much more
with ethnographic studies and really delving
into their experiences so it doesn’t happen again. So yes, stigma is
very, very important and not explored at all. The second question
you asked me about was asymptomatic infections. And you asked a very
important question which is something that we
hoped to be able to answer, which is do people are still–
what role do these people play in transmission. And we don’t know
the answer yet. But we hope to learn. – Thank you. Celina? – Well, you asked me a
very difficult question because prediction
what’s going– what could have happened if you
have a different government. But it gives me the
opportunity to say that when the Zika
epidemic started, we were in an intense
economic and political crisis. I don’t know if you remember. It was under Dilma
Rousseff’s impeachment. So it was right to– and of a period and
starting a new government. And at that time, it was such in
intense scientist mobilization. I mean, we were asked
to write reports and to look and go to the front
line to see what was going on. So it just got to
the point that I think the scientists
influence when they can. And when the situation– to take responsibility. There is nothing
that you can call for in a situation like this. But I think we must be concerned
about the next government that’s cutting the
public health– I mean, support and
research funding. So we must be concerned
because we’re just starting to understand
the full development and the full spectrum
of the disease now. And I don’t think that we could
say that transmissions stopped and it shouldn’t worry
about it any longer. I think we must watch out
because arbovirus epidemiology arbovirus is changing,
and is changing fast. So, the first maps
we saw in the world, we just have the tropical
areas saying the vector-borne with population. Now it’s much wider. I mean, we have different
things, which just give me the opportunity also to see what
range of intervention actions were proposed since the
first, and were very hard to keep for a long time. The range of interventions
for the epidemic was mosquito control strategies,
postponing pregnancy, travels recommendations,
safe sex, and so on. So, you really need
to build knowledge to make these recommendations
in long term possible. So thank you for giving me
this opportunity to complete. – OK, so the floor is open. Please state your name
and frame your question. – Thank you, yes. Paul Beninger. I’m at Tufts. And I want to thank you for
your groundbreaking work with regard to the
lookbacks in ’76 in ’95. In both the groups
that you looked at– the survivors as well as
the health care workers– what do you know about the
families of the survivors and health care workers? Do they have titers? Do they have any
histories that are suggestive of any type
of communicability, particularly with close families
and the intimacy and the food preparation and all the
other types of activities? And of course, sex with
spouses and the like. So the question is,
is there anything that you know about
those close contacts and families of the survivors– children, grandchildren,
and health care workers? – Thank you. Let’s take three questions
and then we’ll answer. So the next one. We’ll take another question
from the person behind you. Thank you. – Just real quick. – Got it noted. – I’m James Wilson. I’m one of the speakers
in the next panel. Christian, we talked
about the differences between the Nigerian
experience with Ebola, which was superlative and
the Guinea experience, right? And so, I want– I think it’s important
to maybe raise that with the audience
as to why were there tremendous differences. Because obviously the gaps
in diagnostics and response and the intelligence failures
that we observed in Guinea were very important to
precipitate all the outcomes we saw in West Africa. And then Celina, we talked about
the intelligence out of Tahiti and the emergence of Zika there. And could have,
should have, would have– if we had known
what was going on in Tahiti before the
experience in Brazil, how could that have
changed the outcomes? So again, focusing your
comments on how can we improve our intel? How can we improve our
ability to anticipate these kinds of problems? Thank you. – Thanks. So, one more question, and
then we’ll have answers. – How would your
role of a researcher change if you were to
propose to the folks that you’re trying to get the
information a stipend to combat this war? In other words,
you would pay them to enter the area without
being harassed or freely– – Can you say your name, please? – Oh, sure. I’m not a clinician. – That’s fine. – My name is
[? Gladiver ?] Santiago. – Thank you. – OK. – All right, so Christian,
you want to start? – OK. Yeah, the question is
what was the difference between the Nigeria and the
Guinea experience in terms of Ebola response. Well, there are
two major things. One was yes, we understand
that in the case of– I mean, infrastructure was one. But then I think what I
saw there as most important in that was in the case of
Nigeria, there were two things. One was probably an element
of luck in the sense that when the [INAUDIBLE]
case arrived at the airport in Lagos, he was already sick
and he stumbled at the airport. Then at that moment and at that
time, he was probably a VIP. He was taken to one of the
best hospitals in Nigeria. It also happened
that at that time, the health sector
in Nigeria was– public sector was paralyzed
because the doctors were on strike. So he had no choice but to
go to a private hospital. And he received treatment there. But the difference
though, is the fact that in Nigeria,
we had that ability to diagnose on the ground. In Guinea, it was
the other way around. In Guinea, the samples
were from over to France and diagnosed in France
and result turned down to Conakry, and
then from Conakry down to the
confinements of Guinea. And that on the average,
was taking 10 to 14 days. So within that period, then
the disease was spreading. But in the case of Nigeria, we
had all that it took on-site. But then most importantly,
it was self-reliance. The Nigerian health authority
believed in themselves, unlike happened in
Guinea, where they were pretty much dictated upon. In Nigeria, for
instance, when we did our diagnosis and many of
the international organizations came in with their
views and their opinions with their suggestion that
they need to confirm first before we decide what to
do, the Nigerian government told them we do things
the way we want. And that was a major
game changer because for a long time, if you
went to WHO website, it was still unconfirmed. But if you were
going by WHO rule, we’d have been in big trouble. So we’re very,
very self-reliant, very confident about
what we’re doing. And we went and then
took the bull by the horn and addressed those
things immediately. And eventually we
were vindicated. Thank you. – Anne? – Thank you. So, the question
that you asked was about what do we know about
long-term sequelae in family members, in health care
workers, and what do we know about transmission,
essentially. And the answer is not much yet. And I hope you’re
on my study section for the grant I’ve submitted
to be able to really understand in greater detail about this. You know, one of
the big issues is when you talk about asymptomatic
infection is what does that really mean? I mean, asymptomatic
infection means that we’ve found that
there were seroreactive. But one of the questions that
we did ask these people as well is, did you have signs
or symptoms of anything during that time period
or at any point later? Some people would
remember some things. Some people might not. And so the question is, were
they symptomatically infected? Did they truly
not have symptoms, or were they
minimally symptomatic, or was it just something
that was unrecognized? Because what we now know
about the Ebola outbreak or about Ebola as a disease
is that it can manifest itself in a variety of ways. It’s not just the apocalyptic,
hemorrhagic version that has been so well publicized. So there’s a lot to
understand, first of all, whether or not people actually
were symptomatic, minimally symptomatic, asymptomatic,
or unrecognized, and then what that will mean. – Celina? – OK, I was just about improved
ability of seeing or detecting an outbreak. If you think about very
urbanized places that were environmental,
in Brazil, we do have quite a
public health system, and with family practitioners
and there was a structure. So if you have those people
at the front line, well aware and knowing that if
they report something, it’s going to be looked– [INAUDIBLE] something that’s
going to be investigated. I think that’s the
beginning of everything of what community approach. Maybe there are some now with
big data or things like this. I think I’m going to
join your section just to see what you’re
going to say about it. But normally, what
we tend to see is the patient when he
comes to, and someone just spots that something different
or unusual in large numbers, or whatever. So, I feel that training and
having good house workers and good community support– all those things
are essential for– I mean, if we can
improve this ability to see the outbreaks
in a shorter time. – Universal health care, primary
health care, the backbone of the SDGs? So, let’s get two or
three more questions. – Hi, I’m John [? Rigero. ?] I’m
representing the Eugene Wright Science and Technology Academy
in Chelsea, Massachusetts and Northeastern University. My question is you talked about
a plethora of transmission factors, both environmental
and genetic, in your respected epidemics. What my question is is
that is there any research or is there any research
you’re aware of being done on the epigenomic factors
in these disease transmissions? Thank you. – Thank you. The next one? – If Zika virus
creates complications for pregnant women and birth
defects for their children, what are some ways mothers can
prevent this from happening? – OK. One more and then I’ll
go to the answers. – My name is Ethel Jackson. And I just have to say
I’ve had a 40-year career in molecular
genetics of microbes in university and in
industrial settings. And I am awed and humbled by
what I’ve heard from this panel this morning. I congratulate
you and thank you. A quick question
though going forward about how technology might help. Is there work ongoing
to develop vaccines against Ebola and Zika? Do you think that is
a promising approach, or do you think that it
will be in the future solely up to public health
and epidemiology to protect us from
these diseases? – Thank you. So, folks, we have three
minutes when you [INAUDIBLE]—- if you want to answer. – Well, as far as the epigenomic
factors involving transmission of disease is concerned, there
may be some work out there, but not that I am aware of. But it’s very possible that
there is work going on. But often, I think, in the
context in which we’re working, the context of outbreak, it’s
very difficult at that time to sit down and then design an
experiment that will actually take into account all of this– I mean, investigate
the epigenomic– especially in the context of
an Ebola or Lassa outbreak. But it’s very possible that
there is some work out there that I’m not aware of. – I’ll respond to the
question about vaccines and therapeutics. Certainly, there have
been major strides in the last several years
with vaccines of therapeutics with regard to Ebola. And certainly there are
candidates out there. We also believe that the
people that we’re working with may have very, very
interesting antibodies that are developed long over time. But the bigger question
that you asked was, do you think that this
is the way forward? And we had a long discussion
about this yesterday. And I think that while
vaccines and therapeutics are very important and something
that does need to be pursued, the real issue is
lack of infrastructure in these countries and
the ability of the people in these countries to be able
to have infrastructure required to have adequate disease
reporting so that people understand what’s going on
in real time in the places where you need to
understand it most, and have the well-trained and equipped
people on the ground who have the ability to respond quickly. And if you have those
things, then the vaccines and therapeutics are a
nice secondary response, but they are not the primary
thing that will save us. – OK. – Thank you. Celina? – OK. Prevention– I think that from
now we have recommendations for pregnant women. If you go to a CDC– I mean, all sites. I mean, there are preventions. And you should not– if you want to be– if you’re planning
to be pregnant, you shouldn’t visit areas
with the virus circulation. Without a vaccine,
that’s what we can do. Think about transmission by
vector-borne, by a vector, by a mosquito, and by
sexual transmission. So if you have a partner
that visits an endemic area– so, you have to have safe sex
for six months, whatever– we don’t know
exactly for how long. [LAUGHTER] So, I think that vaccine
is something to look for and to see how transmission
is going to progress during the following years. – Thank you. So, I want to thank
all the speakers because we are right on time. So we’re not going to get a
red card from the organizers. Look at that. So, thank you for
your participation. And please join me in thanking
all the speakers for really a phenomenal discussion. [APPLAUSE] [MUSIC PLAYING]


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