influenza vaccine – Page 2 – Pediatric Infection Connection

A Dog Named Clytemnestra 2

Bud WiedermannMarch 26, 2023March 26, 20232 Comments

My recent bedtime reading included a mystery by Ruth Rendell, a much-acclaimed British mystery writer. A dog with a name out of Greek mythology appeared in this one, and I was convinced it was a clue to the murderer's identity. Of course it wasn't.

Pediatric Influenza Vaccine Effectiveness (VE)

This study from CDC and its flu VE partners appeared online this week. It provides a good overview of flu VE over 9 flu seasons plus raises some interesting questions. Investigators analyzed data from active flu surveillance at 5 sites around the country (Michigan, Pennsylvania, Texas, Washington, and Wisconsin), the same data that CDC uses to report flu VE every year. None of the numbers are new, but looking at trends and associations over the years was interesting. Note these numbers are from active surveillance rather than collecting data from passive reporting systems like administrative databases; it is much more accurate. Because it is based in outpatient sentinel sites it specifically gives us VE for medically-attended outpatient respiratory illness.

In Figure 1 below the overall VE was 46% - that may not sound that great, but remember this is VE against medically-attended illness, not digging deeper to hospitalization rates which are very high. As you can see, VE varied somewhat with age (younger kids a little bit better effectiveness) and with flu strain.

Influenza A(H3N2) viruses cause more severe illnesses generally and also have had lower VE rates. Figure 2 looks at seasons where H3N2 was the predominant circulating strain and categorizes them as to whether the vaccine that year was either well-matched or mismatched for the strain that was circulating. The advantage for the younger children is more evident in some of these comparisons, especially for the mismatched 2014-15 season.

Why did the 6 to 59 month-old age group show better VE? The authors offer some speculation, including age-related differences in immune response to other factors such as social interactions or characteristics of families with young children that might further protect from infection and doctor visits. Whether this is a difference in immunity or behavior, or a combination, further studies looking into these factors can help inform future preventive measures.

Variants and MIS-C

A group of Kawasaki Disease investigators from several different institutions reported rates of MIS-C categorized by SARS CoV-2 variant periods. Dr. Ashraf Harahsheh, a cardiologist at Children's National Hospital, is a co-author. I had no involvement in the study except as 1 of perhaps a few hundred or so clinicians who helped care for these children at Children's National.

The Table below is a good summary.

Note that the coronary artery row describes dilatation, different from aneurysms. It is certainly reassuring that disease severity declined somewhat during this period, but severe disease still occurred. The declining relative risks of ICU admission from the alpha to omicron eras might be due in part to more comfort of clinicians managing these cases, though that wouldn't explain the concomitant decrease in shock over the same period. One hopes that further study of these patients will lead to discovery of better management for both Kawasaki Disease and MISC-C.

Can Post-Covid Illness Be Prevented?

A couple of studies in adults looked at factors associated with post-covid illness. One investigation was performed in the VA system on a cohort of almost 300,00 individuals. After correcting for many potentially confounding variables, treatment with nirmatrelvir (combined with ritonavir as Paxlovid) did appear to lower risk of persisting illness.

This was a statistically complicated but excellent study. However, what I still hope to see is some post-covid illness study that effectively separates conditions due to direct end-organ damage from the virus versus the fatigue/malaise/dysautonomia/brain fog symptoms. Does an intervention prevent those complications in patients who do not have end-organ damage?

The other study was a systematic review and meta-analysis of 41 studies to identify risk factors for post-covid conditions. They identified female sex, older age (looking only at 18 years and older), higher BMI, and smoking as significant risk factors.

Neither of these studies included pediatric subjects, but still they shed a little more light on this confusing hodgepodge of illnesses. I hope for some tangible breakthroughs in the coming years.

Detective Stories

Much of medical practice, and maybe especially infectious diseases practice, requires good detective work including being observant and asking the right questions. I love Rendell's books. Her characters are often quoting British literature and historical events that I enjoy looking up, but I clearly chased the wrong clues this past week and totally misidentified the perpetrator. I'll keep practicing.

Hang In There

Bud WiedermannDecember 26, 2021Leave a comment

No point in sugar-coating, things are likely to get worse before they get better. The news is disappointing, but we can at least hope that omicron and influenza will crest quickly and recede somewhat.

Omicron is Different

Yes, you already knew that. We certainly know it is (much) more highly transmissible but we still don't have enough data to know if severity is different. Full vaccination (primary series plus booster) is likely to be helpful against severe illness though much less so against infection itself.

Our most commonly available monoclonal antibody regimens are unlikely to be effective against omicron; at Children's National we have paused offering both the bamlanivimab/etesevimab and casinivimab/imdevimab monoclonal cocktails given the high rate of omicron in our region. Sotrovimab should be effective against omicron, but currently we don't have this agent on hand and availability is likely to be limited for the next few weeks. Note that use is limited to outpatients 12 years of age and older and weight 40 kg and greater with positive SARS-CoV-2 testing and high risk for hospitalization or death.

We now have emergency use authorization for 2 oral medications, molnupiravir and nirmatrelvir/ritonavir (Paxlovid), for treatment of mild-to-moderate COVID-19 illness. Paxlovid, consisting of 2 viral protease inhibitors, is authorized down to the 12 years of age/40 kg weight category with high risk for disease progression. Note that Paxlovid is a CYP3A inhibitor, so beware of drug interactions. Molnupiravir is less effective but can be used in adults at high risk for progression who cannot access or receive other treatment options. In the coming weeks molnupiravir is likely to be more available than Paxlovid, but note that it should not be given to children - concerns for joint problems in juvenile animals likely will delay pediatric trials. Because it is a mutagenic agent, use in pregnancy is an unknown risk and patients of reproductive age should use methods to prevent pregnancy while taking the medication and for either 4 days after (females) or 3 months after (males) the 5-day treatment course.

Another difference for omicron is that some SARS-CoV-2 tests may show false negative results. It is a little tough to keep track of new information about this, but the FDA has a great resource.

Influenza on the Rise

Influenza has been creeping up nationally and also at Children's National Hospital, though at the hospital it has not yet reached numbers that we associate with the official start of flu season. Now a preprint study suggests that the 2021-22 influenza vaccine has reduced ability to inhibit replication of the H3N2 clade most likely to be circulating this year. That could mean an antigenic mismatch for this flu season, but we won't have an estimate of that for at least a few months. Even if this is true, influenza vaccination is still very important and I would encourage everyone to be immunized - it's not too late.

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.

A Lull in the Action

Bud WiedermannOctober 10, 2021Leave a comment

It was a quiet week for new information, at least from my perspective. I didn't see any strikingly new COVID-19 data that hadn't already been discussed at various advisory meetings or appeared online earlier. This week promises some items of interest including FDA VRBPAC meetings for review of Moderna and Janssen vaccine booster doses.

In the meantime, help us avoid at least one form of twindemic by getting flu vaccines for yourselves and your patients.

Bias in Healthcare Continues

An article in the Journal of the Acquired Immune Deficiency Syndrome caught my eye. Investigators enrolled 160 non-pediatric frontline care providers (OB/GYN, family medicine, internal medicine, emergency medicine, and preventive medicine) from 48 "hotspot counties" for HIV infection. Enrollees needed to be aware of HIV pre-exposure prophylaxis (PrEP) and serve populations that included adult Black women. They were randomized to receive 1 of 4 online vignettes and state their likelihood of discussing and prescribing PrEP to the patient in the vignette. The 4 stories were identical except for a history of injection drug use (does/does not) and race (Black/White). The providers also completed the validated Color-Blind Racial Attitudes Scale (CoBRAS). Stated briefly, the investigators did find a significant relationship between patient race and provider racism score with respect to provider expectations of patient adherence to PrEP which in turn appeared to affect their willingness to discuss and provide PrEP. High scores on CoBRAS (i.e. more tendency toward racial bias) correlated with more positive expectations for adherence by the White patient versus the Black patient. The study itself has many limitations, including the problem that answers to an online scenario may not represent real world practice behavior, but it is a cautionary reminder to all of us to be aware of intrinsic bias in medical practice.

Prediciting Flu

In the best of times, predictions of the extent and severity of an upcoming influenza season are, in my opinion, equally well served by astrologists or palm readers as by public health experts (OK, slight exaggeration). It wasn't a big surprise that we had basically no influenza in the US this past winter, but no one has any good idea of what to expect with influenza in the coming months. Recent experience in the southern hemisphere was relatively mild, but that information hasn't been very reliable in the past in predicting rates in the northern hemisphere. The fact that we have so many more individuals who were not exposed to influenza last year would suggest we are in trouble this winter, especially if we see low vaccination rates. Bottom line? The reason you see no web links in this paragraph is because I've found no convincing information that anyone has a line on what to expect in the coming months. Again I say please push those flu vaccines!

Tag: influenza vaccine