Articles, Blog

The Flu Outbreak: What You Need to Know

November 12, 2019


[MUSIC PLAYING] PETER THOMPSON: Good afternoon. Thanks for joining
us, and welcome to the forum at the Harvard T.H.
Chan School of Public Health. My name is Peter Thompson. I’m the Livable Planet editor at
the Public Radio International daily news program The World,
and I’m today’s moderator. I am also a recipient of
a belated flu shot, which I got just the other day after I
was invited to join this panel. I had no reason to be here
if I hadn’t gotten my shot. We’re here today to discuss
the flu, this year’s outbreak. What do we need
to know about it? Our panelists starting
from my immediate right are Yonatan Grad. He’s assistant professor
in the Department of Immunology and
Infectious Diseases here at the Harvard Chan School. To his right, Alfred DeMaria. He’s the medical
director of the Bureau of Infectious Diseases
of the Massachusetts Department of Public Health. To Alfred’s right,
Marc Lipsitch. He’s a professor of
epidemiology and the director of the Center for
Communicable Disease Dynamics, also at the Harvard Chan School. And joining us remotely
from Atlanta is Tim Uyeki– I hope I pronounced
that correctly. He’s the chief medical officer
of the influenza division at the National Center for
Immunization and Respiratory Diseases at the CDC, that’s
the Centers for Disease Control in Atlanta. We’re streaming live
on Facebook today, on the websites of the
forum and PRI’s The World. And our program will include
a brief Q&A toward the end. So you can send us your
questions by email, please, at
[email protected] And you can also participate
in a live chat that’s happening right now on the forum website. So to get to our topic. Seasonal flu is pretty
much a regular thing. It comes pretty much every year. Some years are
worse than others. This year seems to be a
little worse than usual, although it’s as far from
as bad as you can get. This happens to be the 100th
anniversary of the global flu pandemic of 2018,
when estimates ranged from 20 to 100
million people died around the world of the flu. We’re nowhere near that,
of course, this year. But where are we? And why does this
year’s flu seem so bad? Is it worse this
year than what’s been expected in
the US and globally? If so, how can surveillance,
response, vaccines help us? These are some of
the questions we’re going to be hoping to get
to in the next few minutes. And to get things
started, though, we’re going to start with a news
clip from Reuters TV, which is going to give us an
overview of where we are today. SPEAKER 2 (VOICEOVER):
This season’s flu epidemic is taking a heavy
toll on children. The latest data from the
Centers for Disease Control shows 16 more kids died
from the flu last week. SPEAKER 3: You take
necessary precautions, and just encourage hand-washing. SPEAKER 2 (VOICEOVER): Parents
in this close-knit community of Columbus, Indiana,
are still in shock after seven-year-old Savannah
Jessie passed away on Thursday, possibly due to
complications related to influenza B. She is
one of 53 children who have died since the flu
season began in October. With the number of
flu cases rising, doctors are reporting shortages
of anti-viral medications like Tamiflu, and an
uptick in hospitalizations. A frustrated nurse in
Pensacola, Florida, recorded this
YouTube flu warning that now has more
than 3 million views. SPEAKER 4: A cesspool of
funky flu at the ER right now. So please don’t
bring your teen in. Please don’t be bring your
healthy children, especially your newborn babies. SPEAKER 2 (VOICEOVER): And
at Atlanta’s Grady Memorial Hospital, which has been
overwhelmed by the H3N2 virus, staff have quarantined
new flu patients in this separate mobile
waiting room typically reserved for disasters like hurricanes. While the flu
vaccine is only 34% effective against the
most dominant strain of the virus in the
US, health officials are still urging everyone
to get their shots. They say the flu
season’s peak is still two to three weeks away,
and getting vaccinated could prevent future
infections and lower the severity of the symptoms. PETER THOMPSON: OK. So that’s a quick bit
of news, and now we’re going to turn to folks who can
help us get behind that news. About three minutes
each to start, please. We’re going to start
with you, Yonatan, from the Grad School
of Public Health here at Harvard University. Put it in context for us. What’s so unusual
about this year’s flu, and why are we here
talking about it? YONATAN GRAD: So, as we
heard in this Reuters clip, and I think everyone
is familiar with, this is a particularly
bad season. Some numbers that the
CDC put out recently at the end of last week
indicated that nearly 8% of outpatient visits
were attributable to influenza-like illness. And that’s clinical
manifestations of respiratory illness
that could be attributable to influenza or to other
respiratory viruses. There was also the
report that 10% of deaths were attributable to
influenza and pneumonia. So these numbers really
put this flu season amidst the more severe that we’ve seen
over the past decade or so. So I’d like to take a step
back and just describe what influenza is. So as a clinical
syndrome, influenza is predominantly manifest as
fever, cough, and muscle aches. And then influenza the
clinical syndrome is caused by influenza the virus. And there are a number
of different types. So there are two main types
that infect humans and cause the clinical disease. There’s influenza A and
influenza B. Within influenza A there are two subtypes– H3N2 and H1N1. And then there are a couple
of dominant strains of B that all co-circulate. And that’s what we see
in seasonal influenza like in this year. Usually one of the
influenza A subtypes dominate, and this
year it’s H3N2. H3N2 is also associated
with more severe infections and worse numbers of
people being infected. So it’s consistent
with what we’re seeing relative to H1N1 and B. Seasonal flu like
we’re seeing this year is distinct from
pandemic influenza. So pandemic
influenza we see when there is a new
strain that’s being introduced to a population
that has little or no immunity. That’s happened a few times–
you mentioned the 1918 flu, the Spanish influenza. That happened a few times. And so there are a few
pandemics in the last century. The most recent one was
the 2009 H1N1 pandemic. But what we’re seeing this year
is a seasonal flu outbreak– severe, but not a pandemic. The clip we just saw also
mentioned some of the tools in our toolkit
for interventions. Predominant among them
is influenza vaccination, and that’s gotten quite a bit
of attention this year, too, because of low vaccine
effectiveness numbers that have come out of Australia, and
then more recently from Canada. So I wanted to take
a little bit of time to describe the flu
vaccine, just briefly to mention some of the
other interventions. So there’s anti-virals,
also, as mentioned. And then basic hygiene
and public health measures, including
washing your hands and staying home if you’re sick. The flu vaccine is comprised
of several components. So there are strains for
each of the flu subtypes that we expect to circulate– H3N2, H1N1, and B. When we
hear the numbers about vaccine effectiveness, that refers
to either the overall flu vaccine– how it’s doing at
protecting against all of the different strains
that are circulating– or for particular subcomponents. The low numbers that we’ve
heard for Australia and Canada, this number 10%, is
particularly for H3N2. And I bring up this point
because the effectiveness against B, influenza
B, is higher– estimated between 55% and 60%. And as we’re seeing from the
most recent epidemiology, there’s increasing
circulation of B. So even though the
flu vaccine isn’t perfect it provides benefit,
not only against H3N2 but also against B. If you haven’t
been vaccinated yet, it’s still something that
we’d recommend doing, because the flu
season we anticipate will continue for a while. The flu vaccine poses
a number of challenges, or coming up with
the strains that we want to put in the flu vaccine. Flu mutates, and so
each year we have to predict what strains
to put in the vaccine. And that prediction happens
six months before we can even distribute the vaccine,
because of the time to manufacture enough doses
to give to the population. So one of the big
challenges in the field is predicting which type
of flu will circulate. When we get it wrong
and there’s a mismatch, we think that the flu vaccine
effectiveness suffers. The greater the mismatch,
the worse the effectiveness. This is something that’s
exacerbated, as well, by how flu vaccine is made. Most of it is made
in chicken eggs. And as the flu virus adapts
to growing in chicken eggs, it can further mutate and
exacerbate the mismatch. And then the last point
about the flu vaccine is, even when there
are good matches, it doesn’t have
perfect effectiveness. And this is perhaps
due to, we think that the vaccine
isn’t necessarily as immunogenic– or able to
elicit a protective response– as some other
vaccines out there. So again, I’d emphasize that
even though it’s not perfect, it provides some protection,
and some is better than none. PETER THOMPSON: Great. Thanks, Yonatan. So an immense amount of
work going into every year– what’s coming, how
can we respond to it. And then on the
ground, we have folks like Al DeMaria with the Mass
Department of Public Health. What are some of the
most basic things that you need to
do to respond when a flu epidemic– well,
not a flue epidemic, but a flu outbreak– hits? ALFRED DEMARIA: Well,
I think you can call it the annual epidemic. And every flu season is
bad from my perspective. And this is a particularly
bad flu season, there’s no question. And state health departments,
local health departments spend a lot of time in an
effort to prevent influenza in the first place
by encouraging people to get vaccinated. The vaccine isn’t,
as Yonatan said, it isn’t as good as we
would like it to be. But it’s the best we
have at the present. So we encourage that and we
encourage preventive behaviors. And one preventive behavior
is coughing into your sleeve. I see people still
coughing into their hands, and potentially more
effectively spreading the virus. So we try to get the messages
out there about prevention, and we also do a
lot of surveillance, and try to monitor flu activity. We have basic systems in place. Like influenza-like illness,
we monitor the proportion of people presenting
from care in a variety of Sentinel clinical sites
who have fever and respiratory symptoms. And that correlates
extraordinarily well with flu activity. We know that because we also do
surveillance for a flu virus. So we do surveillance
based on testing that gets done in the
community and testing that gets done in our state
public health laboratory. And we can correlate that
with influenza-like illness quite effectively. We also monitor
hospitalizations of people who have a positive test. So we get the
information they have a positive test
and the information that they were hospitalized
as an indicator of the morbidity
that’s being caused by influenza at any given time. And we have cities and
towns in Massachusetts that participate in the
CDC’s 122-city surveillance system for pneumonia
and influenza deaths. Now, not everybody who dies
with one of those diagnoses necessarily has influenza. But again, it correlates. Because we can’t really monitor
everybody with influenza, because most people aren’t
presenting for care, or getting tested even when they
do present for care. So we have no way of
knowing about that. It’s almost impossible to
count the number of people who die from influenza,
because they’re dying of the consequences
of influenza, and frequently that
connection to influenza doesn’t get connected. And this year we’re dealing
with a lot of public concern about influenza. In fact, for example, our
influenza-like illness depends on people behaving the
same way as they always behave. And what we’re
seeing anecdotally, and what we’re seeing in terms
of the proportion of people presenting for care
at our Sentinel sites, is that the proportion of
how many tests get done that are positive is changing. So we’re seeing people
presenting with respiratory illness who would
not have presented– they may very well have flu– but they probably
in another year wouldn’t have presented
with influenza. And we have to take
that into consideration when we deal with this. Because frequently
in public health, it’s the public perception
and the public reaction that is what we need to
deal with in addition to the actual disease entity
and the actual spread of illness in the community. PETER THOMPSON: OK. Thanks, Al. Now, down to Al’s left, to Marc. You had a communicable
disease center. Tell us first of all, what the
role of something like that is– how it fits into our
whole response system– and what your take is
on what the priorities ought to be in
terms of response. MARC LIPSITCH: Thanks. So the Center for
Communicable Disease Dynamics here at Harvard Chan is
a general purpose center that studies infectious
diseases and their transmission, including influenza. And we are especially
interested in emergent threats like anti-microbial resistance
and pandemics and outbreaks when they occur. And so it’s a research base
on which to enhance responses to unusual events. And Yonatan and others in the
audience are a part of that. In terms of the
priorities, I think I want to talk for a
moment about the vaccine. Yonatan gave a good introduction
to the issues there. But we’ve become unfortunately
a little bit used to the idea that flu vaccine is
not a great vaccine. I would add my voice to those
saying it’s worth getting. The B, influenza
B is increasing. There’s still value
in getting it. But if you take measles
vaccine, you get it once, and then you get it
again in childhood, and you are protected for life. And it doesn’t need to
be repeated every year, and it works really, really
well, almost perfectly. For flu, we’re used to the
idea that a good flu vaccine is about 60% protective. A not-so-good one is
maybe 10% protective. So we’ve just gotten
used to this idea of mediocre protection. We also have the
problem that it has to target the right
strain every year, and that we have to use
a combination of expert opinion and computerized
evolutionary studies to try to figure out
what strain to put in. And we don’t always
get it right. Even when we get it right it’s
not always effective, highly effective, as Yonatan said. And we don’t produce it fast. It takes, as he
mentioned, six months, often in eggs, which
is an old-fashioned way to produce them. And then we have to
repeat it every year. So this is really not
the kind of vaccine that you would
design if you could. And I think the good
news is that there is a lot of work being done
along the lines of trying to solve some of those
concerns of speed and efficacy and duration of
protection and others. The bad news is that I
think it’s too little. There’s a lot of discussion
lately about the possibility of a universal flu vaccine
that could solve maybe all of those problems. But it’s really becoming
fairly clear to most experts that that’s a long way off at
current levels of investment. So I think we need a
real push to enhance the quality of
seasonal flu vaccines, with that universal vaccine out
there as a kind of holy grail and goal to work towards. But there’s a lot of
incremental improvement that will take money and
investment and research, but needs to be done. I think there are two issues of
priorities that are misplaced. And as a citizen,
and as somebody who’s concerned about the way
that science funding is used, one concern I have is that
some of the work, some of the federal funding
for flu research, has now been directed towards
a set of a type of experiment that I think actually
increases risks rather than decreases risks. And a number of
scientists have objected to this type of
research, which is to enhance flu
viruses artificially in the lab as a way of trying
to understand how they become pandemic strains. I think that’s a
highly risky strategy. It was paused– federal
funding for it was paused for three and a half years. And, unfortunately in my
view, the federal government has decided to
reinstate that funding and continue funding
the work that in my view really puts us at risk
of a dangerous accident, without much helping
our flu preparedness. The last thing I would
say is a more sort of general issue, which is that,
if you look at the budget that was proposed by the president
a couple of days ago, it contains major cuts to the
Centers for Disease Control and Prevention. It contains really, and
even before that, the CDC was saying that it was going to
reduce its presence overseas. Not specifically related
to flu, but nonetheless for all diseases,
including flu, our presence around the world as a
leading public health actor, as a federal
government, is crucial to not only the health
security of those places, but to our own security. Because those diseases
travel, and we know that. The global health
security funding in the Trump budget
that was just released is among the
largest of the cuts. So I think there’s a real
misallocation of priorities away from the things
that keep us safe, that may not be immediately
apparent every day, but are essential
to keeping us safe. So I think that’s
the broader context. PETER THOMPSON: Great. Thanks very much, Marc. So we’ll move on to our final
panelist for our opening comments. It’s Tim Uyeki at
CDC in Atlanta. And it would be nice if
we could get some response from a government
spokesman on the challenge that Marc just laid down. I don’t imagine you’re in a
position to speak to that. So I’d love to just
have you get on to talk about the role of the
CDC and the federal government in addressing this problem,
both within the United States and helping to monitor and
prevent outbreaks globally. TIM UYEKI: Yes, thanks. So in terms of
influenza surveillance, there’s a number of
components to surveillance. And I think Yonatan and Al
have alluded to some of this. So one component
is in monitoring influenza-like illness. And as Yonatan
mentioned, that’s really a syndrome of fever and/or
cough or sore throat. It doesn’t necessarily mean
that the patient has influenza. But when we look at when
influenza-like illness visits peak in the US, that
tends to correlate with the peak of
influenza season. So we have thousands
of Sentinel providers throughout the US that are
reporting during influenza season the number of
patients that week and the percentage of visits
for influenza-like illness. What we’re doing
at CDC is really coordinating all this data. We’re working very
closely with our state health and local health
department colleagues. Another component
which is very important is the state epidemiologists’
assessment of– it’s really a
qualitative assessment– of influenza activity in the US. For example, most of
January, and frankly, most of this month to
date, most states in the US have reported high
influenza activity. We don’t typically see
that all at the same time for so many weeks in a season. Now, a very critical part
of influenza surveillance is monitoring the viruses, what
we call virologic surveillance. And so throughout the US, there
are many clinical laboratories and WHO laboratories that will
submit specimens to the CDC. They’re also going to
report the percentage positive for influenza viruses
that they found per week. So we assemble all that data. We analyze it. And we typically see, in
the peak of influenza season at the national level, when
it’s the highest percentage positive it might be
anywhere from 25% to 30% or higher positive. That tends to be
the peak nationally. But that’s the national
picture, and we know that regionally there
are going to be differences and locally there
can be differences. The other thing about
virologic surveillance that’s so important is we get viruses,
we get a subset of viruses from state health
laboratories that come to CDC. And then we can do
detailed analysis. For example, looking at the
genetic characteristics, the antigenic characteristics,
how much the viruses are evolving, or how similar
they are to the vaccine virus strains. We also can look at
anti-viral resistance. What is the prevalence
of circulating viruses that are resistant
to our main anti-virals? That is critical for
making recommendations on the use of anti-virals. The other thing we monitor
is laboratory-confirmed hospitalizations. And this is a population-based
surveillance in 10 states. And that is really quite
valuable, because it’s not just a syndrome, it’s actually
laboratory-confirmed influenza hospitalizations. And we look at that at
different age groups, and we can see where
the biggest impact is. And as you all know, this season
is a predominantly influenza A H3N2 dominant season. And we see the highest impact
on hospitalizations in people 65 years and older, but
also a significant impact on people 50 to 64. We also monitor mortality
through looking at pneumonia and influenza reported deaths. There is some lag
to those deaths. But what we can do is,
we look at those deaths, and we can compare
to previous seasons. And we can project
a seasonal baseline based upon previous
seasons, and we can see when actually
reported deaths for pneumonia and influenza exceed that. And we’re seeing
that this season, which is reflective
of a severe season. So we have outpatient illness
for influenza-like illness. We have the states
that are reporting qualitative assessments
of influenza activity. We’re monitoring deaths from
pneumonia and influenza. We’re monitoring the viruses. The other component
of mortality reporting is, we have pediatric
influenza associated deaths. And this became a national
reportable condition in 2004. So tragically, every
season, unfortunately, we do have children that die from
complications of influenza each year that are reported
to us from the state health department. Another component that
we’re always working on is looking for viruses that are
not seasonal viruses, but are what we call novel
influenza viruses, typically of animal origin. So it represents
zoonotic transmission from animals to people. Typically either from a
swine influenza virus– we call that variant viruses– or in avian influenza A viruses. So national reporting for
novel influenza A viruses became reportable in 2007. And we have had cases, sporadic
cases, of people in the US who were infected with variant
viruses of swine origin. And in the past 10
to 15 years we’ve also had some very sporadic
reports of human infections with avian influenza A viruses. So this is a part of
pandemic preparedness, of monitoring the
emergence of a virus that poses potential to cause
an influenza pandemic. The other thing that I would
say is that, we– and I’m just speaking about US surveillance–
but we are intimately tied into global
influenza surveillance. For example, the World Health
Organization’s surveillance network, which is called
the Global Influenza Surveillance and
Response System, this is comprised of more
than 140 national influenza centers in 113 member states. And these national
influenza centers then share influenza
viruses and report data to WHO collaborating
centers for influenza. And there are six
of those worldwide– Tokyo, in Melbourne,
in London, in Beijing. And CDC’s national– my
division, the influenza division– is the CDC’s
WHO collaborating center for surveillance epidemiology
and control of influenza. There is one more WHO reference
center at St. Jude’s Research Hospital in Tennessee
that is a reference center for the ecology of
influenza viruses in animals, and particularly looking at
the animal-human interface. So all these national
influenza centers share data on viruses, including
novel influenza A viruses with
pandemic potential, through the WHO influenza
surveillance system, with the WHO
collaborating centers. And these data are used to
make the recommendations for influenza vaccine
strain selection. And at CDC, we’re also funding– right now we have 50
cooperative agreements in different
countries, 50 countries actually, to help build
influenza surveillance and response capacity. And over many years, this
has helped many countries in the world to be able to
detect influenza viruses. And in particular,
one illustration is, during 2009 it actually
enabled many countries to monitor the spread
of the pandemic. So I think we’re
involved in trying to support both domestic
and global surveillance for influenza
viruses, to understand not just the viruses, but
disease burden, as well. PETER THOMPSON: Great. Thanks so much, Tim. So let’s take a look
a little bit deeper at some of the global picture. We’ve got a video here
from the World Health Organization about flu
surveillance and vaccines around the world. SPEAKER 9 (VOICEOVER): Influenza
is one of the world’s most common diseases. It affects millions
of people each year. Many different influenza
viruses circulate. Some are benign,
some more dangerous. And they can evolve
very rapidly. Influenza can be deadly
in the young, the old, and in people with chronic
illnesses, especially when a new influenza
virus emerges to which no one has immunity. Influenza can emerge
anywhere and at any time, and can quickly become
a dangerous pandemic. For all these reasons,
for the past 65 years, the World Health Organization’s
global influenza surveillance and response system,
known as GISRS, has been continuously monitoring
which viruses are circulating and where. Twice a year, experts
from the GISRS network come together to pool data and
recommend which constituents should go into the influenza
vaccine for the upcoming flu season. The influenza vaccine, one of
the safest and longest standing in the world, has
saved millions of lives thanks to the work of the
World Health Organization and the GISRS network. PETER THOMPSON: OK. So we’re going to turn to
the discussion section now between our panelists here. We’ll talk for 10 or 12
minutes, and then we’re going to turn to questions
from the audience and from our viewers online. So we’ve gotten a little bit of
a picture of the global picture here. We’ve also heard a lot about how
the vaccines just aren’t always a good match. And this year is one
case in point on that. So how can we change the
efficacy of the vaccines? How can we improve the process
to make them more effective? Are there any
other things we can do to improve the
ability of the vaccine to actually tamp
down these outbreaks? MARC LIPSITCH: I think
there are a number of short-term, small
things that we can do. And then there’s a
larger research agenda. So the short-term issues
include improving our ability to predict the strains
that will be circulating. So this is evolving
from a matter of combining expert opinion
into a more scientific process that involves understanding
the evolution of the virus and using computational
tools to try to predict which flu strains are coming. So I think that’s one area
where we can do better, and it’s just a matter of
improving the tools that we have. Relatedly, in the
production process there is beginning to be a
move from egg-based production, where the vaccine
virus is grown in eggs and then killed, to a
cell-culture-based production system, which is in principle
both faster and less likely to cause changes
in the virus that would move it away from being
the strain that we intend. So that’s another thing
that’s within view and already happening. In the longer term, there
is a broader research agenda of trying to figure
out ways to improve the human immune response
in terms of either using adjuvants, which are substances
that you add to a vaccine to enhance the immune response,
or finding parts of the virus to immunize with that are
more immunogenic and more likely to provide
broad protection. As I mentioned earlier, there’s
the notion of a universal flu vaccine, which would
be a single shot that would provide broad protection. And there’s been a lot of
interest in that right now. The expert consensus seems to
be forming around the notion that that’s still
a long ways off. But there is, nonetheless,
that’s the goal. And if we can chip away at the
issues of duration of immunity, breadth of immunity,
strength of immunity, and speed of production,
I think all of that will lead in the
right direction. PETER THOMPSON: Tim, you want to
weigh in on that from Atlanta? TIM UYEKI: I tend to
agree with everything that was just said by Mark. You know, I think a lot of
this takes a lot more funding. And I think what
we’re trying to do is understand the impact
of influenza and, I think, improved surveillance. So better surveillance is going
to improve more timely sharing and more sharing of viruses. I think the issue of
improving the timeliness and predictive capacity. But there have been
a lot of improvements in the last 10 to 15 years,
but we need to do much better. I just want to sound a
little bit of a positive note to say that, although you’re
hearing that influenza vaccine effectiveness is not as
good as we would like even in the best of years,
there is still benefit from influenza vaccination. Some estimates that we have
done over a number of seasons have suggested a really large
number of averted illnesses, hospitalizations, and
deaths due to the influenza. This ranges from several
million illnesses averted to averted medical
visits, hundreds of thousands to millions of visits, thousands
of hospitalizations and deaths averted. So there’s still benefit in our
current vaccination strategies. But it’s also useful to
note that a lot of people are still not
vaccinated, including those that are at high risk
for complications of influenza. And we need to do a better job
at vaccinating those people. So no one would
argue that we need better, effective vaccines. We also need to track
vaccines much better, and do a better matching,
as Marc suggested, in predicting what virus
strains are evolving, and a better match to
the vaccine strains. I do agree that we
need to move away from just production in eggs. It’s hundreds of millions
of eggs are used every year, and this is a laborious process. So there have been developments
in vaccine technology– recombinant vaccines,
high-dose vaccines, as Mark mentioned,
adjuvanted vaccines. But we need to do better. PETER THOMPSON: I want
to pick right up on that and move to Yonatan,
and come back to the question of the public
interface and access, better access to vaccines. But Yonatan, what are the main
obstacles to better vaccines, and what are some of the
possibilities that are in play? I remember Marc and I were here
on a similar panel about five years ago talking about
flu viruses and pandemics, and there was
optimism at the time that there was going
to be a breakthrough within the next five years. It’s almost five years. It doesn’t seem
to have happened. What are the obstacles and
what are the possible routes that people are exploring for
that kind of breakthrough? YONATAN GRAD: So I
would echo basically what Marc and Tim have said,
that understanding more about what flu strains
are circulating, or being able to predict
them more successfully. Coming up with a
flu vaccine that can elicit a strong
immune response continues to be one
of the big challenges. I think we are making
progress on both fronts. The computational tools
that Marc mentioned are improving in
sophistication and nuance. And our understanding
of the relationship between the types of influenza
that individuals have seen and their immune repertoire,
how their immune system has responded historically– and
the impact of that repertoire on susceptibility to subsequent
flu exposure– that is also deepening, and I think will be
helpful in trying to understand how to build a better vaccine. All of this also requires
more funding and research. So to echo both Tim
and Marc’s points, these are extremely important
areas that need more support. And also to echo
Tim’s point again, I think even though the
vaccines are not perfect, they contribute immensely
to public health, both at an individual level
and at a population level. And maybe we need to get
people to be on panels to make sure they get vaccinated. But– PETER THOMPSON: Another
one at 2 o’clock. YONATAN GRAD: Yeah. But whatever the
effort, that’s something that I think we can
do better, as well. PETER THOMPSON: So that
leads right back to you, Al. Clearly, we’ve heard
that there are benefits to getting a vaccine even
when the effectiveness rate is very low. What can we be doing differently
to get more people vaccinated? I mean, myself, I got a note
from my health care provider in the fall, get your flu shot. Here it is February– I just got it. I’ve been to the doctor a
couple of times since then. Once for my eyes, which are
getting worse as I get older. And never a mention of
flu from anybody who wasn’t my primary
care physician. It seems to me that you could,
at every engagement with the health care system– no
matter who the doctor is, no matter who you are– have the flu be
front and center when you’re coming into flu season. That doesn’t seem to happen. Why not? Can we do that? Can we do other things? ALFRED DEMARIA: Well, yeah. One of our major
initiatives is to try to reduce the barriers to
people getting flu shots or any vaccine
that’s recommended. And one of the things we did in
Massachusetts that other states have done, as well, is
try to reduce the barriers by allowing more
pharmacy-based immunization, and having pharmacists
give flu shots. I think that’s helped, because
it’s made it more convenient. I think we can make it more
convenient in many other ways. We work very closely with
local boards of health, to support them in
their flu clinics or in their flu clinic
efforts, and also helping them get out into the community. Because you can set
up a flu clinic, but that depends on people
coming for their flu shot. To actually go out
into senior housing, to go out to group homes where
particularly vulnerable people may live. And we’re working very closely
with long-term care facilities to enhance immunization not
only of their residents, which actually they do a
pretty good job of, but also for the health
care workers that work in those facilities, and
for the health care workers that work in acute care inn
other health care delivery sites. So we work with all
of those partners to try to enhance immunization. I think we’ve had some
success over the years. In acute care, we’ve
gone from 30% to 40% of the health care workers
getting vaccinated to, right now, we’re at 94% in terms
of the average for acute care facilities. The other thing
that we’ve done– and you have to think
about where people interact with places where
they get immunized– is that every hospital
now in Massachusetts has an opt-out flu shot
during flu immunization season for anybody being
discharged from the hospital. So there is a standing order
that everybody being discharged is offered a flu shot. And those are the kinds of
things– to make it routine, to make it automatic, to provide
standing orders so that people don’t have to go looking
for a prescription– to enhance access in a variety
of sites where people are, rather than waiting for people
to show up for a clinic. PETER THOMPSON: I want
to throw this out real quick to the bunch of you,
and anybody can answer. But I also don’t want to
take too long with it. I’m wondering if,
in addition to lack of enough sufficient
access and information, there isn’t actually
also a public antipathy toward vaccines these days. And we have a lot of concern
about childhood immunizations and a lot of anti-vaxxers
as they’re called. We have a president
who is at best very skeptical and indifferent
to science in general, and has expressed anti-vaccine
sentiments from time to time. So we have that on the one hand. On the other hand, we have
a flu vaccine this year which is maybe
10%, 20% effective. I wonder how many people are
looking at that and saying, well, the thing’s
not going to help me. It might hurt me. I’m not going to do it. How do we respond to that? Are you seeing that? And how do we respond
to it if it’s true? ALFRED DEMARIA:
Well, we do see that. And it is not as bad as
maybe it seems to be, but it is bad enough
that we really need to spend a
lot of time trying to counter the myths that
are out there about vaccines. Fortunately we have
the advisory committee on immunization practices
that very strenuously looks at the evidence base and
makes recommendations on a national basis. And we can use those data
to try to convince people. But we’re struggling
against material on the internet that
is hard to keep up with and hard to refute
as it comes up. So basically we just have to
have a consistent message, and to point out to some people
that, if you don’t get a flu shot, it’s 100% ineffective. PETER THOMPSON: Anybody else
want to weigh in on that? Or we should just move to
questions from the audience? We have a few coming in already. I’m going to turn
to Lisa Mirowitz, she’s the director of
this whole program. LISA MIROWITZ: Yes,
thanks everyone. We have a lot of
questions coming in. We’re going to only
have time for a few. And you’ve covered a lot of the
substance of these questions, so I’ll pick a few. This is a question from
a viewer in South Africa. In the Western Cape
of South Africa, we are in year three
of a severe drought. The city of Cape
Town will shut off the water supply on day zero,
currently projected to be May 11. This is a scenario that could be
a reality for other big cities in the future. There is an expectation that
infections related to lack of sanitation will spike. How would an early flu
season with a lethal strain of the virus fit
into this scenario? Marc, maybe? PETER THOMPSON: Who
wants to handle that? MARC LIPSITCH: Both
lack of water and lack of sanitation and a
bad influenza season are problematic. And they would feed
off of one another in the sense that each time
you get an infection, say influenza, it makes you
vulnerable to other infections. And similarly, actually
some of the best evidence about why infectious
disease mortality declined in the United States in the
middle of the 20th century is that it correlated city
by city with the introduction of clean water. So clean, abundant water
is essential for health, as we all know. And it’s hard to say that
flu is the major reason to be concerned about the
situation in the Western Cape, but it is yet another
reason to be concerned about drought and about the
broader picture of climate change that’s threatening
drought in other places. LISA MIROWITZ: Thank you. We’ve had a number of questions
related to climate change. So thank you. Here’s another one from New
Hampshire state representative Dr. Valerie Frazier. There should not be a
presumption that any vaccine is safe and effective,
nor a presumption that any flu-like symptoms are
indeed the flu, which causes inaccurate data collection. Therefore, why is
there a recommendation to vaccinate pregnant
women and babies with the flu
vaccine that is only reported at best 10% effective? TIM UYEKI: Well, I’m happy
to try to address that. LISA MIROWITZ: Thank you. TIM UYEKI: So, let me just say
that every season is variable. It’s predictable in that we
know if we’re going to have an influenza seasonal epidemic. We don’t exactly know when
the season is going to peak. Some seasons are milder,
some seasons are more severe. We’re experiencing a
more severe season. But when we track
disease burden, laboratory-confirmed
influenza, so not syndromic, we see that the highest risk
groups for hospitalizations are people 65 and older,
people 50 to 64– and that’s because of
the increasing prevalence of comorbid conditions
as you age– and young children, particularly
under two years of age. And the younger you
are, particularly less than six months of
age, the mortality rates are the highest
among all children. We also know that, especially
from the 2009 H1N1 pandemic, that pregnant women were
disproportionately impacted in terms of hospitalizations. And there were a fair
amount of pregnant women who died from severe
complications of 2009 H1N1 viral flu infection. And globally, we know
that pregnant women are at risk for hospitalization
for influenza during pregnancy. So we know that
pregnant women and women up to two weeks postpartum
are what we would consider in a high-risk group. We know that young infants
are in a high-risk group for complications,
hospitalizations, and deaths. The question is how
to best protect them. So vaccinating pregnant
women can actually protect both the pregnant
woman from influenza, but actually as a bonus,
there’s transfer of antibodies to the developing fetus. And so that when
the baby is born, there are randomized
controlled studies conducted in different countries– these are not
effectiveness studies, these are efficacy studies– that have shown
protection of the infant from laboratory-confirmed
influenza, in some studies out to
four months, in some out to six months after birth
to a woman who was vaccinated during pregnancy. And influenza vaccination
is not recommended, it’s contraindicated,
for infants less than six months old. So how can we protect
such a vulnerable group? We can vaccinate the
mother during pregnancy. We can vaccinate all
other household members six months and older,
and especially all caregivers in the home. And so the point is that
there’s abundant data for laboratory-confirmed
influenza to establish that
very young infants are at high risk for
influenza-associated hospitalization and mortality,
and that pregnant women are also, if they get
influenza, are at high risk for hospitalization. So I think the disease-burden
data are there. And so as part of a
strategy for all high-risk, the Advisory Committee on
Immunization Practices, which is an advisory
group to CDC, does recommend annual
vaccination actually of everyone six months
and older in the US, and that includes
pregnant women. And that will help protect
their infants after six months. YONATAN GRAD: And
if I may, I’d also like to add on to that
excellent description by addressing one
of the other points in that question, which is I
think a misconception that I tried to mention
at the beginning, and that is the
effectiveness of the vaccine. The 10% effectiveness
is particularly for the H3N2
component, and that’s what’s been estimated
in Australia and Canada. But there is a higher
vaccine effectiveness against influenza B,
which as I mentioned, we’re starting to see more
and more of circulating in the season. So it’s important
for the vaccination not only to be
protected against H3N2, but to be protected against
all of the different influenza viruses that are circulating. So there’s additional
benefit to be noted, and that 10% only refers to
a subcomponent of the vaccine overall. PETER THOMPSON: I also wanted– There was also an
assumption, an assertion, embedded in that question,
that I want a truth– well, I want a reality check. I believe the
questioner said, and she was a state representative
from New Hampshire, which gives me a little bit of pause. She said there’s no proof
that a vaccine is not harmful. I think that’s
roughly what she said. LISA MIROWITZ: That
there should not be an assumption, a
presumption that any vaccine is safe and effective. PETER THOMPSON: There
should not be an assumption that a vaccine is safe. Given that you cannot
prove a negative, is there in fact any evidence
that flu vaccines are not safe? ALFRED DE MARIA:
You know, I tend to compare flu vaccines to
over-the-counter medications that we buy and take every
day without thinking. I think if you actually look
at the safety profile of most of those over-the-counter
medications, it’s actually worse
than flu vaccine. I’ve been involved with
probably thousands of flu shots over the years in various– directly injecting them
or supervising them. And I don’t remember
one serious reaction. Now there have been
reactions, and people do. You know, there was
this great study in the ’90s where they
vaccinated 800 healthy workers. Or it was a study with
800 healthy workers. They gave 400 a flu shot and
400 a half cc of normal saline. So they got a placebo. And they didn’t know
what they were giving, the people didn’t know
what they were getting. And it was really
a study to look at cost effectiveness
of vaccinating healthy young workers. But one of the interesting
things they did was they, without
knowing what people got, they called them a week later. And 35% of the people who
got vaccines said, oh yeah, I got the flu from the vaccine. I have flu symptoms
from the vaccine. And 35% of the people who go
normal saline said, oh yeah, I got the flu. I got the flu from the vaccine. Demonstrating in a very,
I think eloquent way, that whatever happens after a
flu shot that people associate with a flu shot may not
really be due to the vaccine. TIM UYEKI: I’d just like to add
to that that CDC and the Food and Drug Administration
administer a vaccine-adverse event
surveillance system. And so there are reports
of potential adverse events that are reported. And CDC does monitor
vaccine-associated reports of side effects. But in fact, this is actually
quite a safe vaccine. The most common side
effects are going to be pain at the
injection site. But some people do experience
some more severe side effects, but actually the
rates are quite low. And just to echo a point that
Yonatan just made, you know, it’s really important to realize
that influenza vaccination prevents influenza. It doesn’t prevent
influenza-like illness that’s caused by other
respiratory viruses. And during the winter there are
many kinds of human respiratory viruses that are circulating
that can cause similar illness. But influenza vaccine
only prevents influenza. The other point is that we have
not reported out our vaccine estimates, but
later this week we will have some preliminary
interim influenza vaccine estimates. And as Yonatan
points out, that what you’ve heard in the media– and actually our Canadian
colleagues to the north have released preliminary
data to suggest that the H3N2 component
of the vaccine had much lower effectiveness
than the B component. We also have to look
at different ages. And so we know that vaccinating
elderly people is always a challenge in
terms of protection with any of the
vaccine components, although some are
better than the H3N2. So I think we have
to look at the fact that there are multiple
viruses circulating and that the effectiveness
overall we can look at, but also we need to look
at the effectiveness at particular strains. So if you haven’t been
vaccinated this season, there’s still a lot of the
influenza season to go. There’s multiple
viruses circulating. And you can still benefit
from influenza vaccination. PETER THOMPSON: Great. Thanks. We’ve got about
five minutes left. No way we’re going to get to
everything we’ve got in here. We’ve got about three hours
worth of questions and answers here. But we did want to get to one
more question from online, and then we’re going to go
to just a quick round up on the panel. LISA MIROWITZ: I do, I just
want to give our studio audience an opportunity to ask a
question if anyone has one. If not, I’ll do one
more from online that I think we’ve discussed,
and then we’ll wrap up. PETER THOMPSON:
Question over here. AUDIENCE: Thank you. Yes, this question is for Marc. You were talking about
federal funds allocated for research for influenza. And you were mentioning that
there is federal money that is going to be used to enhance
flu viruses in the lab, and this is a change
from recent years. So why do you think that is? MARC LIPSITCH: It’s a
long standing discussion. But the brief summary is
that a number of researchers in the US and elsewhere,
but with US funding, had been doing studies, the
scientific purpose of which was to understand how
flu viruses go from being bird-adapted, which is where
all flu viruses ultimately come from, to being adapted
to mammals like people. And they study them in
ferrets, because ferrets are the organism
you use in the lab. There are a lot of ways
you could study that. And the controversial
type of way to study that, or a way to study that, is by
evolving the virus in the lab to become more transmissible
through the air between ferrets. A group of colleagues and I,
about four or five years ago when this was reported,
raised some concerns about both the
scientific premise that that’s actually a
very useful thing to do. Because there are a lot
of ways things can happen, and learning one way in the lab
maybe doesn’t tell you much. But also the risk
of an accidental, or in fact a deliberate,
release by somebody of one of these viruses. It’s really, it’s a tiny
subset of influenza research. It’s a quite expensive subset
because of the containment you have to do. But it’s a small amount. But it’s uniquely dangerous. There are dozens
of things you can do to study the way
the flu evolves, and this is the only one that
has the risk of a pandemic. It was paused,
federal funding was paused three and a half years
ago, and about a month or two ago that pause was lifted
and funding was resumed. So US funds are now
being used to do that kind of work, which
I think is a mistake. PETER THOMPSON:
Anyone else really quickly want to weight on that? We’ve basically got two minutes. So real quick takeaway
from each one of you. And we’ll just go on down
the line here starting with Yonatan. YONATAN GRAD: So again, I’d
emphasize the importance of getting vaccinated,
and also the importance of continuing to invest
in efforts to improve the vaccine through both
the study of the virus and the study of the immune
response to the virus and to the vaccine. ALFRED DEMARIA: And I think a
lot of young, healthy people say, well, flu is
no big deal for me. But I think they need
to think about where are the vulnerable people with
underlying conditions, which we really want to vaccinate. But where do they acquire
their infection frequently is from caregivers. And if there’s an
infant in the family, I think people
should be thinking about not getting the flu. Not only because they don’t want
to get sick, but also because of the potential for exposure. MARC LIPSITCH: I would
echo both of those, and just add the
global perspective that we are in an incredibly
well-connected world in which infectious disease
anywhere can become infectious disease anywhere
else by one plane ride. And it’s more important
than ever right now, in a time of falling budgets, to
reverse that fall for the most important aspects
of global health, which are not just other-focused
and beneficial to the world, but the US is a
leader for a reason. Or the US has been a leader
for a reason in that area, and that’s because
it benefits us to have a robust network around
the world of laboratories and scientists and
epidemiologists studying these things. And to cut that at
this point, I think is a really catastrophically
foolish decision. PETER THOMPSON:
And on to you, Tim. TIM UYEKI: I would agree with
all of what’s been said so far. And really we need
better surveillance, I think both in the
US and worldwide. I think that better
understanding of what viruses are
circulating and better predictive capacities for
vaccine strain selection, this will contribute to
improvements in public health. I think we need
to understand what happened this season better. And particularly,
look at better ways to monitor vaccine
effectiveness. And one thing we
haven’t talked about, actually the focus has
really been on vaccines, but I want to just say a
word about therapeutics. And so a lot of people get sick. Millions of people get sick,
hundreds of thousands of people get hospitalized. People die in this country. And so there’s a real need for
better and new therapeutics to treat influenza illness,
and in particular to treat severe influenza illness–
people who are hospitalized. And right now,
we’re really focused on one class of
anti-viral drugs, but we really need to
look at other modalities– combination treatment
and other therapies, including host-directed
therapies. So I think there’s
really a lot of need for more developments for
treating the patient better. PETER THOMPSON: OK, great. Well, I’m afraid that’s
all we have time for. And as usual, I
feel like we’ve just really begun the conversation. I want to thank
everybody on the panel here from Harvard School of
Public Health, from the CDC, from Massachusetts
Department of Public Health, Yonatan Grad from the Harvard
School of Public Health, Alfred DeMaria of Massachusetts
Department of Public Health, Marc Lipsitch of the Harvard
Chan School, as well. And Tim Uyeki joined us
from the CDC in Atlanta. So that’s it for now. We hope you’ll tune in
for our next forum, which will be in a little
more than two weeks. The topic will be heart and
brain disease in women, sex and gender connections. It’s on February 28, also
from noon to 1:00 PM. And as always, you can catch
it online at ForumHSPH.org. I’m Peter Thompson
of PRI’s The World. Thanks for tuning in. [MUSIC PLAYING]

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