influenza – Page 12 – Pediatric Infection Connection

Calm Before the Storm?

Bud WiedermannOctober 30, 2022October 30, 2022Leave a comment

Frontline pediatric healthcare providers probably wouldn't think things are calm given our current onslaught of RSV and influenza cases crowding physician practices, emergency rooms, and hospitals. However, we are in a bit of calm of sorts for covid. Covid cases actually are decreasing in the UK and the US. Lacking a reliable crystal ball, we'll all need to wait to see whether the next few months will bring a significant rise in covid cases. In the meantime, let's explore a couple areas of interest and confusion.

How Well Do the Bivalent Boosters Work?

More time is needed for the definitive answer on this. The discussion has been going on for months, but this past week we saw posting of 2 preprint articles suggesting, based on immunologic testing, that they may not be much better than the original vaccine used as a booster, at least in terms of preventing illness after infection from some of the newer variants. This is actually what was suspected all along. The bivalent vaccine to stimulate immune response to the spike protein from BA.4/BA.5 was hoped to be a bit more effective to prevent severe disease caused by future virus variants. Carolyn Johnson's explanation of the issue in the Washington Post was excellent, please check it out. It is important to recognize that these 2 studies were based on very few individuals and have not undergone peer review. However, the reports are from generally reliable teams at Columbia University/University of Michigan and Beth Israel Deaconess Medical Center. I don't expect big changes in the results once the peer review is completed.

I want to expand on one concept mentioned as an explanation for the findings in both articles, that of immunologic imprinting. This phenomenon also has been referred to as original antigenic sin.

This imprinting is very different from filial imprinting, like baby ducks following the first thing they see after birth. Original antigenic sin refers to the 60+ year old observation that our immune systems like to use the memory of our response to an infection with an antigen (virus in most cases) when infected at some future time with a variant of that antigen. It could potentially interfere with a more robust immune response to that new variant. Of course, covid didn't exist when it was first described; the main subject was influenza at that time. Scientists developing new vaccines have been well aware of this phenomenon for decades. Covid vaccine development has incorporated this concept.

A key point: although it's possible the bivalent vaccines aren't that much better than the original vaccines when used as boosters, any booster is far better than no booster. Please encourage everyone eligible to be fully vaccinated and boosted for COVID-19.

[I realize I haven't mentioned this in a while, but some may wonder about my frequent use of Wikipedia in my links. For many medical issues, I find Wikipedia to be highly accurate plus a little more understandable to non-medical folks than virtually all other sources.]

Should We Worry About Polio in the US?

In general, no, but anyone lacking full vaccination against polio needs to beware. A few years ago it would have been hard for me to imagine ever saying that, but a combination of war, politics, natural disasters, and apathy make paralytic polio a real possibility now. Wild-type polio transmission was eliminated in the western hemisphere in 1991, and it still is, but failure to eradicate it elsewhere has led to vaccine-derived poliovirus causing paralytic polio across the world, including in the US. (Paralytic disease, the most severe form of polio, develops in less than 1% of infected individuals.)

For those unfamiliar with the disease (few clinicians have seen an active case of paralytic polio, unless they have worked abroad), remember that we have had 2 types of polio vaccine for many years. The live polio vaccine (aka Sabin vaccine, developed in 1961) is a weakened version of the wild virus, given by mouth, and requires viral replication in our bodies to produce immunity. It is particularly helpful in achieving immunity in populations difficult to reach by widespread immunization because the vaccine virus is excreted in stool and can be spread to others. That's mostly a good thing, but sometimes this vaccine-derived strain can undergo transformation to increased virulence and actually cause disease in others. A killed vaccine given by injection (aka Salk vaccine, developed in 1955) also is effective though slightly less so than the live vaccine. The live vaccine has not been used in the US since 2000; all polio immunizations in the US, and in most other developed countries, utilize the killed vaccine.

Even though most of us in the US are immunized and therefore protected against polio, wastewater surveillance in New York City suggests that the vaccine-derived virus is circulating in at least 5 counties, putting un- or under-immunized people at risk for paralytic polio. This situation likely is occurring elsewhere in the US, but so far we lack comprehensive wastewater polio reports. Data from London suggest the problem is widespread.

The pandemic and ongoing anti-vaccine rhetoric has disrupted vaccination programs in the US. Let's hope we don't see more cases of paralytic polio in the US.

Interested readers can learn more about the history of polio from the Global Polio Eradication Initiative.

A Failure to Communicate

Bud WiedermannOctober 17, 2022October 17, 2022Leave a comment

Regular blog readers know I've taken a few months respite from posting to get my newly retired status figured out (still working on that) and deciding whether to continue blogging (affirmative, as indicated by this posting).

Even before the COVID-19 pandemic I was struck by how poorly we healthcare providers communicate risks, benefits, and management choices to each other and to our patients. We haven't done a good job of communicating the uncertainties inherent in medical science and practice; for multiple reasons, the pandemic has transformed this communication gap into a wide chasm. I'll be trying harder to be an effective communicator, not only to pediatric healthcare providers as before but also to patients, families, and the public in general.

The title of this post comes from the 1967 movie "Cool Hand Luke" starring Paul Newman and depicting the lives of jailers and inmates in the Deep South shortly after World War II. Having never watched the movie in its entirety before, I forced myself to do so recently. More on that later.

Bivalent COVID-19 Vaccines for 5-year-olds and Up

I hope all pediatric healthcare providers are now well aware that both Pfizer-BioNTech (ages 5 and up) and Moderna (ages 6 and up) bivalent vaccines are authorized for booster doses. Note that the bivalent part of the terminology just means it contains proteins from both the original strain of the SARS-CoV-2 virus that appeared in late 2019 as well that from the more recent omicron variants BA.4 and BA.5 that have some ability to evade the immune protection of the original vaccine.

Although we don't yet have peer-reviewed publications of the data leading to this authorization, know that it was based primarily on safety and antibody data, rather than a prolonged trial looking at how effective the boosters are in preventing severe COVID-19 disease in children - that information will take many more months to accumulate, and studies are ongoing as are studies in younger children.

At this point in the pandemic, the scientific data on the benefits of vaccination are clear. Compared to outcomes of natural infection with the SARS-CoV-2 virus, vaccines come out ahead for all age groups and risk factors, including for children. Of course, the magnitude of the benefit (bang for the buck) is greater for older individuals and those with underlying conditions leaving them at higher risk for COVID-19 complications. Risk for a poor outcome in a healthy child with COVID-19 disease is much lower than in an old geezer like me, for example. Still, it's a slam dunk from my perspective: every child eligible for vaccination should receive the primary series and available boosters. Reliable information is available from the CDC website. Vaccine Recipient Information also is available. 'Nuff said.

Variations on a Theme

Regardless of what COVID-19 variants are up to, we are in for a tough winter of respiratory virus illness, including for children. Our usual seasonal patterns have changed since the pandemic started, but maybe this season will be more normalized. We have already had a very busy enteroviral illness season; this virus usually peaks in August/September and came back with a vengeance recently. Influenza is ramping up mostly in the southern US but will soon involve the entire country, and respiratory syncytial virus (RSV) activity is already up - usually RSV is a late fall/winter virus. In the days before the pandemic every winter I (selfishly) hoped that RSV season would taper off before flu season started; if they came at the same time, we'd all be working overtime. Now, we're layering COVID-19 on top of all this. I strongly recommend annual influenza vaccine for everyone who is eligible.

Everything so far is pointing to an increase in COVID-19 cases this winter season. For example, cases in the United Kingdom and elsewhere in Europe are already rising, and with so many unvaccinated children out there all going back to school, we can expect a lot of SARS-CoV-2 transmission. How much, and how severe, are unanswered questions so far. In part this depends on the behavior of the so-called virus variants.

The graph at the right depicts the most recent CDC data for circulating variants of SARS-CoV-2, as of October 15, 2022. First, the good news. These are all subvariants of the omicron variant; this has been the case for several months (remember the delta variant?). Omicron seems to be a variant that causes less severe illness in general.

Now for the bad news. Some of these subvariants show early indications that they are resistant to some of the therapies now very helpful in managing or preventing infections. Secondly, some of those now increasing, like the dark blue BA.4.6, may not be prevented by the original COVID-19 vaccines. That's why there was a big push to produce the bivalent vaccines that include components that could be more effective for these newer subvariants. Again, everyone eligible for the bivalent COVID-19 booster should receive it.

The real concern is that we are waiting for the next major change in the virus that could portend something that could evade our existing treatments and vaccines and cause more severe disease. As long as we have humans being infected, this virus will continue to mutate; the more infections, the more mutations and the more likely we'll see a worse version of the virus come to the forefront.

But enough of this doom and gloom! Sometime, maybe about a year ago when it became clear that SARS-CoV-2 had incredible ability to produce new variants, I was reminded of the Goldberg Variations, a set of keyboard pieces written by J. S. Bach. Johann Gottlieb Goldberg studied under Bach and likely was the first person to perform Bach's variations. My favorite pianist playing these variations (not that I've sampled all the recordings) is Glenn Gould. It is my never-fail stress reliever, especially needed during pandemic times.

Cool Hand Luke

Retirement has given me more freedom to go down rabbit holes, and when I found out the "failure to communicate" quote came from this movie (though not present in the book from which it was adapted) I had to watch the full movie. I said at the start of this post that I had to force myself to watch the entire movie; the emotional and physical brutality depicted was a bit tough for me. However, I enjoyed performances of all the lead actors plus a few "hey, doesn't he look like ..." moments that I discovered were younger versions of future stars, their names buried in a long list of cast credits.

The quote itself, delivered by the great character actor Strother Martin in his role as prison warden, is: "What we've got here is failure to communicate." (It is #11 on the American Film Institute's list of 100 greatest American movie quotes.)

Whirlwind Week

Bud WiedermannDecember 19, 2021Leave a comment

Somebody pushed the reset button this past week. Although we don't yet have the weekly variant reports from CDC (they are published on Tuesdays) it is very clear from just my small world at Children's National Hospital that omicron has hit with a vengeance. I was speaking in the hallway on Friday with my longtime friend and esteemed colleague Dr. Larry D'Angelo who likened what we are seeing to the early situation in South Africa where omicron increased exponentially even while delta was still very much present. An important caveat, however: it's risky to make too much out of day-to-day data, many factors affect case rates and sometimes we can be misled by "hot off the presses" numbers.

A Triple Whammy Ahead?

Most winters in pre-pandemic times I kept my fingers crossed that we would not have our RSV and influenza seasons occur concurrently; the few years we had a double whammy like that it really strained our resources. This winter could be worse. The good news is that although RSV is still around it seems to be on a downward trend. However, influenza A numbers have been increasing both at Children's National and nationally, suggesting we will hit full-blown flu season soon. The second and third components of the trifecta are delta and omicron. If we see all 3 of these viruses causing infections in large numbers at the same time it will be very tough. One silver lining of the omicron era is that it may stimulate more individuals to seek out primary series and booster vaccinations. Also, with school winter break and perhaps a bit more caution on the part of the public, we might have less viral circulation the next couple of weeks. We'll see.

For now clinicians should remember we have two effective influenza antiviral medications, oseltamivir (Tamiflu) and baloxivir marboxil (Xofluza), available. From a treatment perspective we don't have a lot of choices for outpatient therapy for pediatric SARS-CoV-2 infections, and the monoclonal antibody combination bamlanivimab and etesivimab just authorized for use down to newborn ages but isn't likely to be effective against omicron. (Note that currently Children's National is not using age under 1 year as an independent risk factor for use of this combination.) NIH has a nice web site to check the latest on effects of different therapeutics for SARS-CoV2 variants, much based on in vitro data rather than solid efficacy studies because it's just too soon in the omicron wave for reliable analysis.

Setback and Hope for Pediatric COVID-19 Management

On December 17 we all learned via a press release that the Pfizer vaccine trial failed to reach the pre-established noninferiority margin for children 2 - 4 years of age, although that goal was reached in the 6 - 23 month old age group. As you know I am an investigator in that trial, at the time of this writing still waiting to hear specific plans for modification of the trial presumably to administer third doses to those children.

Also on December 17, CDC released reports of 2 studies of the "Test to Stay" (TTS) strategy for managing school attendance with positive covid cases, one from Los Angeles County, CA, and the other from Lake County, IL. A lot of us have been waiting for high-quality published data on this approach. The basic approach to TTS is described on the CDC web site, suffice to say ready access to testing must be available as well as compliance with masking and other prevention methods. We of course do not have data available for TTS efficacy in the omicron era but at the moment this seems to be a reasonable approach.

Bottom line for all of this, we are entering another worrisome time for COVID-19, no reason to panic but be careful and stay abreast of new developments. Please encourage everyone to get their influenza and COVID-19 vaccinations, including boosters for the latter.

Hello Flu Season

Bud WiedermannDecember 5, 2021Leave a comment

I'm sorry to disappoint those of you expecting an omicron variant update this week. Although we've seen a lot of commentary in the lay press and some preliminary reports from around the world, in fact we still don't have anything substantive to answer our outstanding questions about transmissibility, disease severity, and immune evasion. Maybe next week.

Home for the Holidays with Flu?

At Children's National for the week ending November 28 we had a slight uptick in influenza cases, though not enough to declare our official start of flu season. CDC surveillance suggests the beginning of increases nationally. Conveniently the CDC published a detailed account of a what has been reported across the country: flu outbreaks on college campuses. The December 3 MMWR report was of an outbreak on the University of Michigan campus occurring in October and November. All the isolates were influenza A H3N2 and should be covered by this year's vaccine. However, H3N2 is a bit more troublesome than other strains in that it is more prone to drift as the season progresses. It is somewhat concerning that individuals with positive and negative tests for flu had similar vaccination rates, suggesting not great protection against mild infection, at least in this one relatively small outbreak. Watch out for spikes in flu following holidays as college students and other travelers add fuel to flu season.

COVID-19 Monoclonal Antibody Use in Young Children?

I was caught completely unaware when I learned on December 3 the FDA extended emergency use authorization down to the newborn period for the monoclonal antibody combination of bamlanivimab and etesevimab for children at high risk of developing COVID-19 complications. Previously this combination had EUA only for high risk individuals 12 years and above with weight at least 40 kg. This extension was based on some new data from an open-label (i.e. no control arm) trial looking at treatment effects on viral load as well as some pharmacokinetic data on weight-based dosing for younger age groups. The EUA covers both therapeutic and post-exposure indications. Note also that, for children above age 2 years of age, this is only for outpatient use.

I have one main concern about this EUA related to use in children in the first year of life. First, the notice lists age < 1 year as defining a high risk group, without need for any other risk factors. To my knowledge no study has found this age group to represent high risk for COVID-19 complications. Second, the youngest child in the trial was 10 months and weighed 8.6 kg; only 5 children in the trial were less than 2 years of age. We know that metabolism in newborns and young infants is very different from older children and, coupled with the fact that I can't find evidence that otherwise healthy young infants represent a high risk group, I'm reluctant to sign on to use in otherwise healthy children in the first year of life. Our team at Children's National is looking at the data and will come up with guidelines incorporating this new EUA.

Is There a Problem with This Year’s Flu Vaccine? 2

Bud WiedermannDecember 15, 2017December 16, 20172 Comments

I know I'm in trouble when I first hear about an infectious disease problem through the lay press. In the case of this year's flu vaccine, it was NPR, about a week ago. It looks like it started turning up on some national news feeds a few days earlier, and the message was that estimates of vaccine efficacy from Australia (the southern hemisphere flu season is winding down) were around 10%.

As is my usual practice, I go to the source data, which in this instance wasn't easy since virtually none of the lay press announcements included a link to that source. I finally traced it back to an online publication from October 26, 2017, and I'm still wondering why it didn't make more a splash back then, rather than 6 weeks later.

Based on interim reports of flu activity in Australia through late September, investigators did determine vaccine efficacy to be 10% (95% confidence interval -16 to 31) for influenza A H3 strains for all age groups; A H3 are the most common strains circulating this season. They used a test-negative study design for flu-positive patients seeking medical attention in sentinel clinics, which is a standard approach for flu vaccine efficacy research. Overall vaccine efficacy against all subtypes of influenza A and B was a more respectable 33% (17 to 46). Efficacy against A H3 strains varied by age. Children under 15 years of age and adults 15-64 years experienced rates of about 15% efficacy, while adults 65 and older having essentially no efficacy for A H3 strains. These numbers, if true, are not unprecedented with A H3 strains and have resulted in heavier flu seasons in the past.

It's too early to tell whether these estimates will hold for Australia once all data are available, and of course it's still too early to make an estimate for the US. A season with lower vaccine efficacy can mean greater risk of serious outcomes in high-risk populations, and this risk will be even greater if news about the lower efficacy results in fewer people seeking immunization this year. For now, it's important to stress that everyone should be immunized for influenza.

You can keep track of influenza season at the CDC and the Maryland Department of Health websites.

Tag: influenza