Good afternoon.
I'm Commander Ibad Khan, and I'm representing the Clinical
Outreach Communication Activity, COCA,
with the Emergency Risk Communication Branch
at the Centers for Disease Control and Prevention.
I'd like to welcome you to today's COCA call:
2019 to 2020 Influenza Season Update
and Recommendations for Clinicians.
Please stay tuned until the end of this COCA call
for more information about two upcoming COCA calls
on HHS guidance on opioid dosage reduction or discontinuation,
as well as another one on the novel Coronavirus outbreak.
Both calls will take place later this week.
You may participate in today's presentation via webinar,
or you may download the slides if you're unable
to access the webinar.
The PowerPoint slides and the webinar link can be found on our
COCA webpage at emergency.cdc.gov/COCA.
Again, that web address is emergency.cdc.gov/COCA.
Once you reach the webinar page,
the PowerPoint slides can be found
under the call materials tab.
Free continuing education is offered for this webinar.
Instructions on how to earn continuing education will be
provided at the end of the call.
In compliance with continuing education requirements, CDC,
our planners, our presenters, and their spouses/partners wish
to disclose they have no financial interests
or other relationships with the manufacturers
of commercial products,
suppliers of commercial services,
or commercial supporters.
Planners have reviewed content to ensure there is no bias.
The presentation will not include any discussion
of the unlabeled use of a product or a product
under investigational use, expect Dr. Angela Campbell would
like to disclose that she will discuss the off-label use
of antiviral medications for treatment of influenza.
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After the presentation, there will be a Q and A session.
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If you are a patient, please refer your questions
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At the conclusion of today's webinar,
participants will be able to accomplish the following.
Describe the current status
of influenza activity in the United States.
Describe the circulating influenza viruses detected this
season, and explain the implications for clinicians.
And describe antiviral testing and treatment recommendations
for patients with suspected and confirmed influenza.
Now I would like to introduce our presenters
for today's webinar.
Our first presenter is Miss Alicia Budd.
Miss Budd is an epidemiologist in CDC's Influenza Division.
Miss Budd has been at CDC for more than 13 years,
and has worked on national influenza surveillance
for most of that time.
She also has experience in infection control,
having spent 6 years at the Johns Hopkins hospital,
in the Hospital Epidemiology and Infection Control department.
Our second presenter is Dr. Angela Campbell.
Dr. Campbell is a medical officer
in CDC's Influenza Division.
Her projects focus on studies of influenza
and antiviral treatment, and antiviral effectiveness,
vaccine effectiveness, pandemic preparedness, and development
of CDC clinical guidance related to treatment and prevention
of seasonal and novel influenza viruses.
She is an adjunct associate professor of pediatrics
at Emory University School of Medicine,
and has a professional staff appointment
at Children's Healthcare of Atlanta.
I will now turn it over to Miss Alicia Budd.
Miss Budd, you may proceed.
>> Thank you.
So today I'll be giving an update
on the current influenza season, based on activity
that we've received-- or data we've received, rather,
about activity occurring through January 18 of this year.
Next.
So before I launch-- oops.
Next slide.
Before I launch into an actual update on activity,
I just wanted to briefly explain how we get all this information
in that I will be talking about.
So flu surveillance
on the national level is really a collaborative effort
between those of us at CDC, and also our public health partners
at the state and local level and territories,
and also numerous other data providers, many of whom are
at the clinical level.
And our role at CDC is really to coordinate the system
that all those various partners make possible.
So we get data from five categories of flu activity
from eight different sources.
Three of those have to do with the virus tracking itself.
Two have to do with flu-related mortality,
and then we have one each that focus on outpatient visits,
hospitalizations and the geographic spread
of flu activity in general.
And every week we analyze that information,
and we make it available to the public in the form of FluView
which is a static report, and FluView Interactive,
which is a system online that really lets you dive deeper
into the data on different geographic levels,
different time frames, and things like that.
And those are both available on the internet,
and in the resource slide at the end,
you'll have those web pages.
Next.
So the goals with the flu surveillance really haven't
changed, even though the system has been in place
over many, many years.
Some of the systems have changed.
Some of the data we get in have changed, but really all along,
we're focused on identifying and characterizing the viruses
that are circulating, with a special eye towards making sure
that any viruses with pandemic potential would be
recognized early.
We also are doing flu surveillance
to provide situational awareness about the onset of the season,
where we are in the season in terms of activity increasing
or decreasing, and where in the country activity is occurring.
We're also of course looking at the severity of the flu season,
and whether it looks like things are what we would expect,
or maybe a bit higher or lower.
And then, we're looking of course
to describe the clinical infections,
and those at most risk, and all of this really
with the eye towards how we can guide decisions
about interventions.
Next.
So now I'm going to move into where we are with this season.
So this slide shows what we're seeing in terms
of influenza virus circulation, based on the data
that have been reported to us from clinical labs
and public health labs across the country.
So clinical labs test specimens primarily
for diagnostic purposes, and we use the data from these labs
to calculate the percent of specimens that they're testing
that are positive for influenza.
And with this data, we can track the timing of the season,
and the intensity of flu activity.
So this season, activity was low in October,
and began to increase in November,
but then really took off in December.
We had a slight decrease in activity the first two weeks
of January, and we're starting to see an increase again now
in the third week of January.
And there's a number of reasons that this might be occurring.
That decrease could be related to a slight decrease
in transmission that occurred because kids were out of school
for a couple of weeks around the holidays.
It could be that that highest peak there is somewhat impacted
by changes in healthcare-seeking behavior over the holidays,
and it was sort of an auto-data correction bit
that we saw there with the decline.
Or it could be, and I'll talk
about this a little bit more later,
it could be that we're switching over from seeing sort
of an increase in B activity, and now we're seeing more
of an increase in A activity.
But things haven't quite evened out yet.
So regardless, we are definitely seeing high levels of activity,
and you can see with this increase
in the most recent week, we're just about back up to
where we were at the highest point this season.
So we don't know yet at this point where things are going
to go from here, but it's definitely something
to continue to monitor.
From the public health labs, that bottom panel there,
you can see the information about the--
what types of flu viruses are circulating.
So this season, we've seen, for the season as a whole,
predominantly B/Victoria lineage virus season.
So that's the most common virus reported
for the season as a whole.
But in the most recent weeks, we've seen nearly equal numbers
of B/Victoria viruses and Influenza A/H1N1 viruses.
Very little B/Yamagata virus circulation,
and not much H3 virus circulation, either.
Next slide.
So this slide is a little busy, but I wanted to put
into perspective how unusual it is that we are seeing
so much Influenza B activity.
So each individual pie chart here represents the distribution
of influenza viruses by Influenza A subtype
and B lineage where we have it,
going back to the 1976-77 season.
And then, on the bottom right there, in the red box,
is this season's data to date.
The red represents H3 viruses.
The blue is the pre-pandemic H1 viruses.
The yellow or orange color is H1pdm09 virus,
our current H1 virus since the last pandemic.
And then the greens are the Influenza B viruses.
Next slide.
So now, that blue circle there is the 1992-'93 season.
And that is the last time
that we have had a B-predominant season here in the U.S.
And it was a B/Yamagata virus.
And it accounted for almost 75% of the viruses that season.
Next.
More recently, there circled, are the 2000-2001
and 2002-2003 seasons.
These seasons were not B-predominant,
but they were the last time that we saw such a significant amount
of Influenza B activity.
And in both seasons,
it was actually H1 that was predominant.
It was the pre-pandemic H1, but it was H1,
just like we're seeing as our other sort
of co-circulating virus this season.
The 2000-2001 B's were of the Yamagata lineage,
and the 2002-2003 B's were the Victoria lineage.
Next slide.
So I think in general people tend
to be a little bit less aware of some of this Influenza B history
than we are of the Influenza A sub-type.
So I just wanted to spend a quick minute talking about that.
So it was the early to mid-1980s
when the two separate B lineages, the Yamagata
and Victoria, were identified.
In 1988, rather, it was the B/Yamagata/16/88 strain was
identified in Japan.
Looking back earlier, it looks like maybe as far
as the early '80s, it was also in some other countries in Asia.
And it's similar to a 1983 virus from Russia.
So the specific date of when it emerged isn't known,
but sometime in the early to mid-'80s.
Despite that, it's still in the U.S. for the '88-'89 season.
Our B viruses were antigenically
like the B/Victoria lineage viruses.
It wasn't until the 1990-'91 season
that we first saw B/Yamagata lineage viruses in the U.S.
And the Yamagata viruses dominated the B circulation
in the U.S. throughout the 1990s.
Victoria viruses were pretty much limited to China and Asia.
Then in 2001-2002,
we saw B/Victoria viruses circulate in the U.S. again.
It was the first time that we had had them
since the '88-'89 season.
And since then, we've seen co-circulation
of the two lineages in the U.S. But both have been
at relatively low levels, when you look
at the relative proportions of the viruses every season.
And typically when we think of B activity in the U.S.,
we think about sort of the later wave of flu activity
that happens toward the end of flu season.
Next slide.
So you know, while in recent seasons, like I just mentioned,
we typically see relatively low levels of flu,
looking a little more closely at that 2000, and 2001,
and 2002-2003 season,
just a couple interesting things to point out.
That first season where we had a predominant,
or-- not predominant.
But a large amount of B viruses circulation,
it was also H1 as I mentioned.
But the A viruses came first, and the B's later, which is sort
of the timing we're more familiar with.
In the '02-'03 season, it was H1 again,
and B/Yamagata viruses this time.
And A's and B's seemed to increase at about the same time.
B's dropped off first.
This season what's even more unusual than seeing
so much B activity is that our B activity increased before our
A activity.
So that's definitely not something that we typically see
with influenza B viruses.
Next.
So another interesting piece of Influenza B viruses epi is
who tends to be more affected
by these two different lineages of viruses?
This slide shows pie charts for the Victoria viruses on top,
Yamagata viruses on the bottom.
Looking back at the last several seasons, back to '15-'16,
and you can see that Victoria viruses impact kids more
than the elderly with those 65 and older only accounting
for 10% or less of the Victoria viruses in these recent seasons.
For the Yamagata viruses, the opposite is true.
We see the elderly accounting for between a quarter and 1/3
of the Yamagata viruses in each season.
That's a larger proportion than we see in the youngest kids,
and it's certainly more than we typically see
for the Victoria viruses.
Next slide.
So this is also looking at age distribution,
but back to looking at just this season.
And with this sort of co-circulation of a large amount
of B/Vic viruses and the H1 viruses,
we're actually seeing a different predominant virus
in the different age groups.
So in our kids, B/Victoria viruses are predominant,
and in our both adult age groups,
it's the H1 virus that are predominant.
Next.
And another thing that I touched on earlier,
just wanted to show a little bit closer,
is while B/Victoria viruses are predominant so far this season,
for the season as a whole,
we are definitely seeing an increase
in flu A activity recently.
You can see that in the clinical lab data on the left,
where we're looking at percent positivity.
That dark line is the overall percent positivity.
But the dashed green line is percent B,
and you can see it had a sharp decline there
for a couple weeks.
Now it's sort of leveled off.
But percent A positivity and the yellow dashed line is continuing
to increase quite steadily.
You can also see that in the public health lab data,
which is in the slide on the right.
This is looking at the relative proportions of each
of the A subtypes and B lineages.
The gray line is the B/Victoria viruses.
It's been relatively high.
A few bumps here and there, but pretty stable for a good part
of the season, and then a slight decline in recent weeks,
while the relative proportion of viruses
from the public health labs that are H1, which are shown
in the blue line, has continued
to increase throughout the season.
So we'll continue to watch and see how that plays
out in the coming weeks as well.
Next.
So the public health labs also,
in addition to reporting their results, they send a subset
of their specimens on to CDC or to a CDC reference lab
for genetic and antigenic characterization,
as well as antiviral susceptibility testing.
And this is used to help monitor how the flu viruses
are evolving.
The pie chart there on the left is the same public health lab
data that we've been looking at.
I just put it in there for perspective,
and a reminder that, you know, what we're seeing a lot
of this season, we have a system in place we call right-sizing,
where we try to get in as much as possible, similar amounts
of all the subtypes and lineages for the characterization.
So just the fact that we are seeing a lot
of a virus being tested for characterization doesn't mean
that necessarily is the virus which is predominant,
which is why I wanted to have
that public health lab pie chart there as well.
So for the H1's and the B/Yamagata viruses,
the story's pretty straightforward
for both of those viruses.
Everything that we have genetically characterized
belongs to a single genetic clade for each
of those viruses respectively.
And it's the same clade as the vaccine reference virus.
All of those that have been tested antigenically are also
considered similar to the cell-grown reference virus.
For the H3 viruses, which again, we're seeing very little
of this season, the vast majority of those
that have been genetically characterized belong
to a different genetic subclade
than our vaccine reference virus.
But even so, we are seeing about 42% of the H3's
that have been antigenically characterized are similar
to the cell-grown vaccine reference virus.
For the B/Victoria viruses, more than 90% belong
to what we call the B1a.3 genetic clade,
and the vaccine reference virus is actually the V1A.1
genetic clade.
But similar to the H3 viruses, despite that difference
in genetic clade between the vaccine reference virus,
and what we're seeing predominance of in circulation,
about 60% of the viruses
that have been antigenically characterized are similar
to the cell-grown vaccine reference virus.
And a last piece of good news on this additional testing front is
that almost all of the viruses tested, and it's been more
than 1,000, have been found to be susceptible to all four
of the licensed antiviral medication.
Next.
Switching gears now to look at flu-related illness.
This is data from our outpatient physicians,
our provider network.
This season is shown in red.
We've been at or above the national baseline
for 11 consecutive weeks now,
taking us back to early November.
And all 10 of the surveillance regions have been
above their region-specific baselines
for several months as well.
We see a similar dip here at the same time period that we did
for the clinical lab data.
Likely for all or any of those reasons that we talked
about with the clinical lab data.
Then of course, we'll have to wait and see how this continues
to play out, whether we're going to increase again,
or start to decrease in the coming weeks.
But either way, we are, again, seeing a lot
of flu virus circulation at this point.
Next.
We also look at the same outpatient ILI data
on a state level, and calculate the intensity
of ILI activity for each state.
The intensity level ranges from minimal to high.
And during Week 3, which was our most recent week,
we had 37 jurisdictions experiencing high ILI activity,
7 at moderate, and the remaining 9 were either low or minimal.
Next.
So we track lab-confirmed flu hospitalizations in addition
to outpatient illness.
And we do this through a multistage population-based
surveillance system.
Just wanted to point out these data are presented somewhat
differently than the rest of our flu surveillance data.
It's weekly data, but the data point for each week is
where we are cumulative through the season up into,
and including that week.
So these data continue to increase
with each week of the season.
This season is again, shown in red, and you can see
where we are with a overall rate
of 24.1 flu-related hospitalizations per 100,000.
Puts us right sort of in the middle of where we have been
at this point in the season in past recent years.
Also not surprisingly, the highest hospitalization rate is
in those 65 and older, at about 58 per 100,000.
Next slide.
So we have two systems for tracking flu-related mortality.
The graph on the left shows data from the National Center
for Health Statistics where we look at death certificates
that have been coded with a cause of death
of either pneumonia or influenza.
We compare that percentage to epidemic--
a baseline epidemic threshold.
And so far this season, with the exception of Week 1,
so that first week of the year,
we have been below the epidemic threshold.
That one week we just touched it, barely.
So as you can see, compared to some of the past seasons,
we are still at quite low levels
of flu-related mortality at this point.
On the right is our second mortality surveillance system,
which looks
at laboratory-confirmed deaths in children.
So far this season, 54 pediatric deaths have been reported
to CDC.
Sixty-nine percent of those were associated
with Influenza B virus infection,
and 31% with Influenza A virus infection.
Only a small proportion of the B's have been lineage tested,
but all those that were are Victoria viruses.
And for the A's, a small number have been subtyped,
and all were H1 viruses.
Next slide.
Actually, I'm sorry.
Could you back one minute?
Just one quick thing to point out,
because I know there's always a lot of interest in this,
is vaccination history for our pediatric deaths.
This is information that we don't have on all the deaths
for this season as of yet.
We do know that typically only about 20%
of the pediatric deaths have been vaccinated, looking back
over a history of this system.
Again, I mentioned we don't have all
of that data for these deaths yet.
That information tends to lag a bit more.
But what we do have so far this season seems to indicate
that that vaccination percentage is even lower this year
than we often see.
So next slide.
The last piece here is our geographic spread
of flu activity.
So this is where each jurisdiction reports,
not the intensity of their activity,
but how widespread it is across their jurisdiction.
And during the week ending January 18, as you can see,
almost all of the country was reporting widespread activity.
Next.
So I just wanted to mention one other quick thing before I turn
this over for the clinical portion,
and that is our estimates of influenza-associated burden
in the U.S. The surveillance systems
that I've just gone through,
are how we track trends of flu activity.
It's how we get sort of real-time indications
of what's happening.
But we take that information and run some mathematical models
to find out what we think those trends might equate
to if you try to estimate flu-related illnesses.
So doing that so far for this season, again, same time period
up through the week ending January 18th, we're estimating
that so far in the U.S. this season, there have been
at least 15 million illnesses,
at least 140,000 hospitalizations,
and at least 8200 influenza-associated deaths.
So these are cumulative numbers.
We put them out this week, and they will continue of course
to increase throughout this season.
On the left-hand side, you can see the burden estimate ranges
from 2010-'11 through '17-'18.
You can see for the most part we are either at
or below the lower end of that spectrum, but again, we are,
you know, only probably about halfway through this season so,
these numbers will continue to increase.
And last slide for me is just a quick summary.
So we are seeing indicators, our surveillance indicators
that track flu activity itself, they're quite high.
And we expect them to remain high,
or at least above baseline levels for many weeks to come.
But despite this high level of flu activity,
our markers of severe illness, the hospitalization
and deaths really aren't high at this point in the season.
By saying not high, it is for course, you know,
it is flu we're talking about, so we are seeing a lot,
but not compared to what we have seen in other seasons.
And this is likely due to the fact that we're seeing
so much B/Victoria and H1N1 circulation.
And these viruses on a whole are more likely to affect children
and younger adults than they are the elderly.
And we know that the majority of hospitalizations
and deaths occur among the elderly.
And so with fewer illnesses in that group,
we expect to see what we're seeing,
which is on a population level,
less impact on hospitalizations and deaths.
So that concludes my activity update portion,
and I will turn it over to Dr. Campbell for her clinical piece.
>> Great. Thank you.
Good afternoon everybody.
My name is Angie Campbell.
And first I'm going to briefly review the clinical
manifestations of influenza, especially in light
of this current season, with the predominance of B viruses
and H1N1pdm09 viruses.
So next.
Influenza, as you know, can cause a spectrum of illness.
And this can range from asymptomatic infection
to a more typical upper respiratory tract illness,
typically consisting of abrupt onset of fever and cough,
with other symptoms that may include chills, muscle aches,
fatigue, headache, sore throat, runny nose.
I should note that the runny nose
and nasal congestion symptoms do tend to occur
with other more common cold viruses as well,
but they may occur in young children with flu.
And GI symptoms such as abdominal pain, vomiting,
and diarrhea also tend to be more common in children.
Young infants may not actually have respiratory symptoms
at all, and they may present with fever alone,
often with irritability.
And then on the other end of the age spectrum, elderly people
and people who are immunosuppressed may have
atypical symptoms, and may not have fever.
And so all of these manifestations can occur
with what we would generally call uncomplicated
influenza illness.
But as we all know too well, and as Miss Budd just showed us,
that flu can also cause complications.
Next.
So common complication is otitis media.
And this can actually develop in up to 40% of children
under the age of 3 with influenza.
Influenza can also exacerbate chronic underlying conditions
such as asthma.
And then other common causes of hospitalization
with flu include dehydration and pneumonia.
And the pneumonia can be a primary viral pneumonia,
or secondary bacterial.
Flu can also cause other respiratory syndromes,
as well as a number of extra-pulmonary complications.
There's a whole list there.
It includes renal failure, myocarditis, pericarditis,
myositis, or extreme rhabdomyolysis.
Flu is known to cause encephalopathy and encephalitis,
particularly in children.
Guillain-Barre syndrome, acute disseminated encephalomyelitis
or ADEM, as well as sepsis and multi-organ failure.
And in fact in a relatively recent review of death reports
of children who died with flu, sepsis was actually found
to be listed as a complication in up to 30% of those reports.
Lastly, I do want to mention invasive bacterial co-infection,
which can cause severe and fulminant disease
when it's present with flu.
The most common bacteria are typically pneumococcus,
which is strep pneumo, staph aureus,
and this is really either methicillin-susceptible
or methicillin-resistant staph aureus,
as well as strep pyogenes, or Group A strep.
Next.
So as you may be aware, on January 10th,
CDC put out this health advisory.
And the point was really to notify clinicians
that influenza activity remained and continues
to remain high in the United States.
At that time, and now, ongoing elevated activity was due
to the Influenza B/Victoria viruses,
with increasing circulation of Influenza A, H1N1pdm09 viruses,
and then we still have very low levels
of B/Yamagata, and A/H3N2 viruses.
And you just saw that demonstrated really nicely
with all of our surveillance data.
Next.
So since this season has been rather unusual
with this early predominance of Influenza B/Victoria viruses,
I wanted to talk about what we know about B viruses,
and specifically what we know regarding differences
between Influenza A and B virus infections.
So there are a few papers that have addressed this question.
This top bullet really is reflective of most.
Among hospitalized adult influenza cases,
and this was data from the '05-'06
through the '12-'13 flu seasons that was collected
through the Flu Servnet Hospitalization Network
that Alicia mentioned.
In this paper, they found no difference in ICU admission,
length of stay, or mortality
between Influenza A and B infections.
And that was after adjusting for high-risk conditions,
antiviral treatment, and seasonality.
Next.
This slide has the same--
you know, I think I didn't really want to say "next" yet.
Could you just go back, please?
I wanted to transition
to children first before I showed you this figure.
So among children, when we look at our surveillance data
over time, it is actually interesting.
The proportion
of influenza-related pediatric deaths associated
with Influenza B viruses has actually generally been higher
than the proportion of Influenza B among circulating viruses.
And so the next slide.
Next.
Will actually show this in a figure from a recent paper.
It has the same words I just said on the side,
and let me just walk you through this.
So the solid light gray lines are the percentage
of Influenza A in the U.S. Flu Virological Surveillance System,
and the solid black are Influenza A among
pediatric deaths.
And I know the colors are not that distinct, but you can see
in the very top line is the gray line
that represents virologic surveillance.
And it shows that the Influenza A viruses were predominant
during all six of the seasons.
It's the top line across the board.
But the percentage of A viruses among children
who died was below that line.
And then, if you look at the dotted lines-- that's switched.
So the dotted lines represent Influenza B.
And among virologic surveillance in the dotted light gray,
and the pediatric deaths in the dotted black,
you can see that the proportion
of Influenza B virus is detected among those children
who died was higher than the proportion
of the Influenza B virus as detected in children
for the overall surveillance for those six seasons.
So it is interesting.
B viruses do tend to cause severe illnesses in children.
OK. Back-- next.
So back to this slide, and one last bullet.
Next.
This was another paper that was recently published.
This was actually in Canada.
And they found that the mortality
from Influenza B-associated hospitalizations was actually
higher than Influenza A-associated hospitalizations
among children.
Next.
The other thing that came out the same day
as the health advisory was this recent MMWR
that you may have seen.
And this described the early season pediatric Influenza
B/Victoria virus infection specifically in Louisiana.
Louisiana had very early activity this season.
And nearly all of the viruses from these children belong
to the recently emerged genetic subclade, the B1a.3 subclade
that Miss Budd mentioned.
And so the objective of this investigation was
to evaluate clinical features of this new subclade in children.
Especially because many young children have never been
previously exposed to this new subclade.
And really, the bottom line
of the investigation is at the bottom.
Next.
It's that the early activity in Louisiana did result
in illnesses that were generally typical to seasonal influenza.
However, even though most of the illnesses were uncomplicated flu,
some illnesses were severe,
and there was actually one death in this study.
Next.
So because we've also now seen this increase in Influenza A/H1N1pdm09
viruses, I wanted to briefly highlight what we know
about illness with these viruses.
There was actually a systematic review done in 2018 to try
to get at this question.
And they found weak evidence
that A/H1N1pdm09 viruses were more often associated
with secondary bacterial pneumonia, ICU admission,
and death in the post-2009 pandemic period.
So this subsequent paper,
which actually the first author was Miss Budd,
who just presented, is really an interesting analysis.
Because this looked at U.S. Influenza Surveillance data
by birth cohort, rather than traditional age groups.
Usually we look at children, adults, and elderly.
And this divided it into different birth cohorts,
depending on the year of birth.
And it suggested that on a population level,
the initial Influenza A virus subtype that you're exposed
to may affect the clinical impact
of influenza in subsequent years.
And so specifically, since the pandemic, more severe disease
and death occurred during H1N1 predominant seasons than H3.
And this was particularly true in adults
who had not originally been exposed
to the currently circulating H1N1pdm09 viruses.
So a really interesting paper to take a look at,
that gets at this idea of your first influenza exposure
which is often termed imprinting.
Next slide.
So now I'm briefly going to discuss vaccination,
and just a little comment on vaccine effectiveness.
Next.
So I think everyone on this call is likely already convinced
that flu vaccination is the best way to protect
against influenza, and you also all likely know that the ACIP
and CDC recommend annual vacation for everyone 6 months
of age and older, who don't have any contraindications.
This is recommended to be received by the end of October,
but we always emphasize that as long
as influenza viruses are circulating,
vaccinations should continue throughout influenza season,
even into January or later.
I think that's really evident this season, with this switch
that we're having from B viruses to H1N1 viruses.
But if you've-- obviously if you've had one viral infection
with B early in the season, you're still at risk
of having another infection.
So even people who've had flu
that have not been vaccinated should be encouraged to do so.
Next.
This slide lists the composition
for vaccines available this season.
Note that there were two changes from the 2018-'19 season.
Both the H1N1 and the H3N2 viruses were updated.
And also note that the B/Victoria virus is included
in both the trivalent and quadrivalent formulations.
Next.
And although we know vaccination's important,
one thing we always struggle with is
that communicating influenza vaccine effectiveness
is challenging.
The VE can vary by population,
as well as by what viruses are circulating,
and vaccine type in any given season.
And so I just want to remind you that CDC has developed a model
to translate VE, or vaccine effectiveness, into the number
of influenza-related outcomes
that are prevented by vaccination.
Next.
So another way to say this is really,
what is the burden averted by influenza vaccination?
And this graphic shows the numbers for the 2018-'19 season.
That it was estimated that 4.4 million illnesses,
58,000 hospitalizations,
and 3,500 deaths were averted by vaccination.
So we expect our preliminary vaccine effectiveness estimates
for this season to be available by the end of February.
And then once we have those VE estimates,
this averted burden graphic,
and these estimates can then be estimated.
Next.
OK. I'm moving on to the diagnosis of influenza.
I have multiple topics I'm squeezing in here.
Next.
I do want to make sure you're all aware
of the IDSA clinical practice guidelines
that were published in December of 2018.
Next.
And I also wanted to draw your attention to the main CDC page
on flu virus diagnostics, which has a lot of information
that I won't touch on today.
Next.
I do just want to remind you
that flu testing should really be performed
in a couple of instances.
One is when results are likely
to influence clinical management,
in that they may decrease unnecessary laboratory testing
for other etiologies.
They may decrease unnecessary use of antibiotics.
The result might facilitate implementation
of infection prevention and control measures.
And it may increase appropriate use
of influenza antiviral medications,
which I'll discuss soon.
And potentially decrease hospital length of stay.
Another reason for testing is,
if it will influence a public health response.
Can be very useful for outbreak identification
and interventions.
And one of the most common situations
where this is the case is in long-term care facility
or nursing home outbreaks.
Next.
So this is an algorithm from the IDSA guidance,
and it's also on our webpage.
It's a guide for considering influenza testing
when flu is circulating in the community.
And this should really be used regardless
of flu vaccination history.
It starts by asking, does the patient have signs
or symptoms suggestive of flu,
including atypical clinical presentation,
or findings suggestive
of complications associated with flu?
And if the answer is no,
then testing is probably not indicated.
But now, moving to the left of this diagram-- next.
If the patient with suspected flu is being admitted
to the hospital, testing is actually recommended both
by IDSA and CDC, along
with empiric antiviral treatment while results are pending.
If not being admitted,
but if results will influence clinical management,
the same recommendation applies.
If results aren't going to influence management, that is,
if the result of the test isn't going
to change whether empiric treatment can be initiated based
on a clinical diagnosis, then there's probably no need for it.
And that's often the case in some outpatient settings.
Also empiric treatment is recommended if the patient is
at high risk or has progressive disease.
I'll get to the treatment recs in just a little bit.
Next.
OK. So if testing is performed, what test should be used?
The main point of this whole slide is
that molecular assays are the most sensitive.
So for outpatients, rapid molecular assays exist now
that have a very high sensitivity,
and will improve detection over rapid influenza diagnostic tests
that use antigen detection.
And for hospitalized patients, molecular assays,
which include both single PCR,
or other multiplex molecular assays should be used
to improve the detection of influenza.
For immunocompromised patients, and often critical care patients
in particular, multiplex molecular panels
are recommended.
Next.
The last topic I'll cover today is our antiviral
treatment recommendations.
Next.
So influenza antiviral medications are an important
adjunct to vaccination.
The focus of CDC's treatment guidance is
on prevention of severe outcomes.
In other words, we treat those with severe disease and people
who are at highest risk of severe disease.
And really these antiviral recommendations are common
to multiple organizations,
including IDSA, PIDS, AAP, and ACOG.
Next.
So in one slide, I did want
to provide a very summarized overview of a lot
of data regarding the efficacy and effectiveness
of antivirals for influenza.
And I do want to preface by saying
that no antiviral is specifically approved
for severe influenza.
All the antivirals are approved for acute uncomplicated flu.
But observational studies do support an effect on reduction
of complications, and most experts support the use.
So what we do now, the first bullet.
Clinical trials and observational data show
that early antiviral treatment can shorten the duration
of fever and flu symptoms.
Next, meta-analyses
of randomized controlled trials have demonstrated
that early treatment reduces the risk of otitis media
in children, and lower respiratory tract complications
that require antibiotics and hospital admission in adult.
And lastly observational studies and meta-analyses
of observational data have reported
that among high-risk outpatient children and adults,
early antiviral treatment reduced the risk
of hospital admission.
Early treatment of hospitalized adult patients
with oseltamivir reduced the likelihood of death,
and shortened hospitalization.
And in hospitalized children, it's been shown
that early antiviral treatment
with oseltamivir shortened duration of hospitalization.
So there's a whole body of evidence,
some on randomized trials, and some observational,
on which we base our recommendations.
Next.
So antiviral treatment is recommended as early as possible
for any patient with suspected or confirmed influenza
who is hospitalized; who has severe, complicated,
or progressive illness; or who is at high risk
for influenza complications.
Next.
So the people who are at high risk for complications,
for whom treatment is recommenced,
include children less than 2 years,
and even though we know all children less
than 5 years are considered at high risk for complications,
the highest risk is for that youngest group.It also includes
adults age 65 and over, pregnant and postpartum women,
American Indians, Alaska Natives,
children who are receiving long-term aspirin therapy.
People with a number of underlying medical conditions,
and residents of nursing homes and chronic care facilities.
Next.
So clinical benefit is absolutely greatest
when antiviral treatment is initiated as close
to illness onset as possible.
Treatment really shouldn't be delayed while testing results
are pending.
An antiviral treatment initiated
after 48 hours can still be beneficial in some patients.
There are been observational studies of hospitalized patients
that suggest that treatment might be beneficial even
when initiated 4 or 5 days after symptom onset.
And similarly, there have been observational data
in pregnant women that have shown treatment
to provide benefit when started 3 to 4 days after onset.
But by and large, the earlier the better,
even within the first 12 hours is better than 24 and 48.
Next.
So this is just to remind you
of the initial recommendation, and then next.
Antiviral treatment can also be considered
for any previously healthy, symptomatic outpatient not
at high risk, who has suspected or confirmed influenza.
And that's on the basis of clinical judgment,
if treatment can be initiated
within 48 hours of illness onset.
Next.
This is a little table of the four FDA-approved antivirals
that are recommended for use this season
in the United States.
Three are neuraminidase inhibitors.
There's oral oseltamivir, inhaled zanamivir,
and intravenous peramivir.
And the fourth is a cap-dependent
endonuclease inhibitor.
It's oral baloxavir.
And so this table really summarizes the differences.
Oseltamivir can be given to anyone of any age.
Zanamivir, for treatment of children age 7 and up.
Peramivir, age 2 and up.
And Baloxavir, 12 years and up.
And the treatment course for oseltamivir
and zanamivir is one dose taken twice daily for 5 days.
For peramivir and baloxavir, a course is just one dose.
And then two of these drugs are approved
and recommended for chemoprophylaxis.
That's oseltamivir for ages 3 months and up,
and zanamivir, 5 years and up.
The most common adverse events are listed.
Oseltamivir can cause GI symptoms.
The most common are nausea and vomiting.
This can be lessened if it can be taken with food.
And it tends to be just about 5% over placebo in studies
that have compared this.
So it's a relatively small increase in nausea and vomiting.
Zanamivir can cause bronchospasm,
and is not recommended for anyone
with underlying airway disease.
And peramivir has been shown in clinical trials
to cause more diarrhea than placebo.
Baloxavir has not actually had adverse events reported more
commonly than placebo in the clinical trials.
Next.
So this just lists the neuraminidase inhibitors.
A reminder that it's actually FDA-approved for treatment
of acute, uncomplicated influenza.
And then I wanted to give you a little more information
about baloxavir.
It interferes with viral RNA transcription,
and it blocks viral replication.
It was first approved in December of 2018,
again for treatment of acute, uncomplicated flu.
And then in October of 2019, FDA added an indication
for treatment of acute, uncomplicated flu specifically
in people at high risk for influenza-related complications.
This was based on a trial in which early initiation
of antiviral treatment in high-risk adolescents
and adults showed that baloxavir was superior to placebo,
and had a similar efficacy to oseltamivir,
with the outcome being time to alleviation of symptoms.
There currently are no available data for baloxavir treatment
of flu in pregnant women, highly immunocompromised people,
those with severe or progressive disease,
or in hospitalized patients.
Next.
So my last slides, I'm going to review the principles
of treatment in some specific groups.
First in hospitalized patients, treatment with oral
or enterically administered oseltamivir is recommended
as soon as possible.
And just to emphasize, there really are insufficient data
for use of inhaled zanamivir, IV peramivir, or oral baloxavir
in patients with severe influenza disease
requiring hospitalization.
For patients who can't tolerate or absorb the oral
or enteric-administered oseltamivir,
the use of IV peramivir should be considered.
And the optimal dosing and duration
of treatment are actually kind of uncertain for severe flu.
It's often given longer than the typical treatment course.
Next.
So for treatment of pregnant women, or women who are
up to 2 weeks postpartum, oral oseltamivir is the preferred
and recommenced agent, because it has the most studies
available to suggest that it is safe and beneficial.
And baloxavir, I just wanted to mention again, isn't recommended
for treatment of pregnant women, or breastfeeding mothers,
because right now, we don't have available efficacy
or safety data in pregnant women, or anything about--
no data on the presence of it in human milk, or the effects
on breastfed infants, or on milk production.
Next.
The last treatment slide just has a couple important
additional considerations.
I mentioned that invasive bacterial infections can occur.
And bacterial co-infection should really be investigated
and empirically treated in patients with suspected
or confirmed flu who initially present with severe disease,
such as extensive pneumonia, respiratory failure, hypotension
and fever, in addition to antiviral treatment.
Bacterial infections should also be investigated,
and empirically treated in patients who deteriorate
after initial improvement.
And it should be considered in patients who fail to improve
after starting antiviral treatment.
And lastly, I just wanted to mention corticosteroids.
They really are not recommended as an adjunctive therapy
for suspected or confirmed flu-associated pneumonia,
respiratory failure, or ARDS, unless they're indicated
for some other reason.
Next.
So this is the slide that has some additional resources.
As Alicia mentioned, the FluView
and FluView Interactive links are there, as well as a number
of our pages for professionals,
including antiviral recommendations,
vaccination recommendations.
And I would be remiss
if I didn't mention this adorable baby who is a friend
of our flu division, and wore her Fight Flu t-shirt
to receive her 6-month influenza vaccine.
So with that, that's the last slide I had today,
and thank you all for attention,
and we're happy to take questions.
>> Thank you so much, Miss Budd and Dr. Campbell
for providing our audience with this important update
on seasonal influenza.
We appreciate your time and value your insights.
We will now begin our Q and A session.
Audience, please remember you may submit questions
to the webinar system by clicking Q and A button
at the bottom of your screen, and then typing your questions.
Again, please do not ask a question asking the Chat button.
Our first question is regarding influenza activity.
When can we expect to see flu activity decline?
[ Inaudible ]
Dr. Campbell, or Miss Budd,
if you're speaking, you might be muted.
Please unmute your phone.
>> I think Alicia was trying to speak,
but I couldn't hear it either.
This is Dr. Campbell.
I think it's really difficult for us to predict that.
We know from last season,
we had one of the longest seasons we had had in years.
And with this season being rather unusual,
it's hard to say how long this current circulating H1N1--
I don't want to call it a peak, but it does seem
that the H1N1 virus is on the rise.
And so I think it's very hard to predict
when we'll see it decline.
>> Thank you.
We have a couple of questions regarding complications.
And I'll try to compile then into sort
of one question with two parts.
The first part is, you mentioned data related
to cases and deaths.
Do you also have data on increasing number
of complications this flu season as well?
And then Part 2 is, out of the complications that you listed,
what are the most serious complications
for young children?
>> This is Angie.
I'm not sure if Alicia's microphone is working,
so I'll take a stab at the data question as well.
I was going to say that while we do get data eventually
on complications of influenza,
this comes from our surveillance systems, and so we tend
to know numbers of people hospitalized
with influenza fairly quickly.
But then, we do get a lot of epidemiologic
and clinical information on those people
that takes a little longer.
And so once we have that, we gain information on heart, lung,
kidney, other organ complications,
but we don't have that right now.
The same is true for the pediatric mortality.
Once the data are all in, that can be reviewed,
but at this point it's too early.
And the second part was--
>> I'm happy to repeat it.
>> Thanks.
>> The second part was what are the most serious complications
that can occur in young children?
You had mentioned complications
in 2-year-old children, or younger.
>> Right. I think that we do see sepsis in children.
We also see the encephalitis
and encephalopathy manifestations associated
with flu tend to be more common in children.
Unfortunately, I think there have even been media reports
to that effect this season.
In particular, I'm thinking of this one child that was reported
to have at least maybe temporary,
but have enough damage to her brain
that she's currently blind.
And that was on the news,
so I'm not really saying anything private.
But you know, children do tend
to have some severe neurologic manifestations of flu.
I would say there's not--
children can have any of the complications listed
if the infection is severe enough,
and really if the subsequent immune response
and cytokine storm is severe enough,
any of the manifestations I listed can actually occur
in children or adults.
>> Thank you.
We also have multiple questions related to oseltamivir.
I'd like to compile them as well into sort of a theme.
One of the themes seems to be a concern
about development of resistance.
The first inquirer asks if there is a concern
that there could be resistance developed in the future
if Tamiflu is used readily in not-at-risk persons.
And the second question related to resistance asks
that is there concern with resistance developing now
that Sanofi is pursuing over-the-counter status
for oseltamivir?
>> Sure. So this is Angie Campbell.
You know, I think it's important to think about resistance
for oseltamivir differently than we think of it for antibiotics
for bacterial infection.
So when someone takes an antibiotic,
all of us have bacterial flora in our bodies all the time,
that live in our respiratory tract, in our GI tract,
and when you take various antibiotics for whatever need,
those bacteria that currently live within you can change
to become resistant to that antibiotic.
And so it's possible when you become sick again,
you could be sick with that resistant bacteria
in your urinary tract, and you have a urinary tract infection
with a resistant organism.
But that's actually a different phenomenon than what happens
with viral infections.
Because influenza is really only present in your body
when you're sick with it.
And so, when someone is being treated for influenza,
and receiving oseltamivir,
it's true that resistance can develop.
When we typically see that,
is in a patient who's immunosuppressed and sheds virus
for a long period of time.
But there have been other reports
where resistance can occur early in the course of treatment.
But the point is that you have to be currently infected
with influenza for resistance to occur.
So someone who takes it, whether or not they're at high risk
for complications, or a previously healthy person,
someone who takes oseltamivir for their influenza,
it treats that infection,
and then the flu eventually goes away.
Likewise, if someone is given oseltamivir,
and they don't currently have an influenza virus infection,
there's no mechanism by which when they do acquire the flu,
it would become resistant from having taken that oseltamivir.
So I think it's a very different process.
One thing we worry about sometimes is
that if chemoprophylaxis is given,
in which a dose is taken only once daily,
instead of treatment dose, which is twice daily.
If chemoprophylaxis, for example, is given to someone
who is already coughing and having symptoms of flu,
that's sort of an undertreatment.
And that is a situation
where resistance is more likely to occur.
Which is actually-- I didn't talk about chemoprophylaxis,
but it's part of the reason
that it's not something we generally recommend.
But when treatment doses are given, it's not something
that is the same as development of resistance with bacteria.
I guess the other thing I should mention is, there are countries
such as Japan where oseltamivir is used much more widely
than here, and there have not been increased levels
of resistance, sort of on a widespread scale.
>> Thank you for that.
And I appreciate you also putting in some information
about chemoprophylaxis, because we did have a couple
of questions on that.
We have time for one more question.
And my question to you is, now that we are as far along
as we are, is there a need to recommend vaccinations
to our patients, even if they may have already had influenza
this season?
>> So this is Angie Campbell.
I think so.
I say that because, kind of dovetailing at the beginning
of the Q and A session,
we really don't know how long the influenza season is going
to go on.
But we expect it still maybe several more weeks,
especially given the data that you saw
where the virologic surveillance is actually increasing again.
So every Friday you want to check FluView and watch
and see what that's doing,
because that's when it's released.
Around noon on Friday.
But I think if someone has had influenza, it's very likely--
I guess if you're a betting person,
odds are that they had Influenza B early in the season,
and right now we're actually seeing more
Influenza A/H1N1pdm09.
So there could still be real benefit from vaccination.
>> Thank you for that explanation.
And that concludes our Q and A session.
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