pneumococcal vaccine – Pediatric Infection Connection

I’m Optimistic

Bud WiedermannMarch 3, 2024March 3, 2024Leave a comment

It was a busy week for infectious diseases, not in the sense of more outbreaks but rather more epidemiologic and vaccine data that point to better health for the future.

The big topic of the week was the Advisory Council on Immunization Practices regular February 2-day meeting. In retrospect, pediatric healthcare providers won't have any major new recommendations to work with; those are likely coming following the next meeting the end of June. I wasn't able to view as much of the meeting as I had hoped, patient care interfered a bit, but I did review all the presentations for those that I missed hearing live. Let's dive in.

ACIP

The Council discussed 9 different topics, but only 3 involved voting: COVID-19 vaccines (vote in favor of a spring vaccine for some high-risk people), Chikungunya vaccine (vote for use in some US adult travelers and in laboratory workers), Td vaccine availability for those with contraindications to receiving pertussis vaccine (discussion followed by a vote regarding the Vaccines for Children progam), influenza vaccines, polio vaccines, RSV vaccines for adults, meningococcal vaccines, pneumococcal vaccines, and the new Vaxelis combined product for diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B. I'll expand on just a few of these topics. (Note all of the graphs/figures below are from the ACIP web site presentation slide link for the February meeting.)

RSV

We saw the most up-to-date representation of RSV epidemiology, showing that the epidemic curve for this year looks a lot like prepandemic years (see last presentation in RSV session).

A good part of the discussion centered on risk of Guillain-Barre syndrome following vaccine, compared to risks of GBS in the baseline population. Both are rare events, but I think at this point it is reasonable to conclude that GBS is a rare risk of RSV vaccination, though not enough to outweigh benefits for high risk populations.

A quick look at the benefits versus GBS risks for adults > 60 years of age (Melgar presentation from RSV session):

Note risks might vary with vaccine type - hard to know with rare events and large confidence intervals, plus both in the ballpark of background GBS numbers.

Influenza

This session was interesting for me to see a preliminary assessment of vaccine effectiveness for the 2023-2024 flu season. I'll just show you an overview of VE in the pediatric population; note that multiple methodologies are used to measure VE. (See slides from Frutos presentation in the influenza section.)

This is good VE for flu, certainly the CDC and WHO were on track for choosing the best combination of strains for this season. Look for the vote for next season's vaccine composition in June.

Meningococcal Vaccines

The focus of the discussion was how best to incorporate meningococcal B vaccine now that we have an approved combination vaccine containing this serogroup. Here are the main options discussed, from the 1st Schillie presentation:

The issues are complex, primarily due to 3 factors. First, meningococcal group B infections are extremely rare; traditional cost-effectiveness models show that meningococcal B vaccination in the US is by far the most expensive vaccine; very few cases are prevented due to the rarity of infection. Second, vaccination at age 11-12 risks significant waning of immunity by the age for peak meningococcal disease in adolescents; it might make sense to move the first dose to a later age. (The main argument against this is the confusion caused by eliminating the long-standing practice for vaccination at age 11-12, perhaps lowering overall vaccine acceptance.) Third, it is clear that not all meningococcal disease risk in adolescents is equal: college attendance is prime, but there are other behavioral risk factors (1st Schillie presentation):

The discussion was mainly to hear input from all stakeholders and then go back to the drawing board. Expect a vote on this at the June meeting - it will greatly impact your summer vaccine guidance for adolescents and young adults.

COVID Vacines

This section of the meetings seemed to garner the most publicity. Of course most of the results presented dealt with adults, given the relatively lower risk for bad outcomes in children plus low rates of vaccinations. Most helpful I thought were the discussions about covid VE in recent months looking at the fall monovalent vaccine.

These are great numbers. Also mentioned was the fact that waning of efficacy hasn't been seen yet, but that could just be a result of not having enough time to pass since the fall vaccine. Other good news is that in vitro studies suggest that the current monovalent vaccine is likely to protect against newer variants.

The official recommendations from CDC now state

Special situation for people ages 65 years and older: People ages 65 years and older should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 4 months following the previous dose of updated (2023–2024 Formula) COVID-19 vaccine. For initial vaccination with Novavax COVID-19 Vaccine, the 2-dose series should be completed before administration of the additional dose.

That "should" wording was the subject of much debate, finally choosing this wording more for simplicity of recommendations. The gnashing of teeth came about for a good reason - people in the lower end of this age population who do not have underlying risk factors will have less benefit from a spring vaccine because rates of bad outcomes in the post-pandemic period are lower.

Recommendations for younger people with moderate or severe immunocompromise have slightly different wording:

People ages 12–64 years who are moderately or severely immunocompromised may receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) COVID-19 vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
People ages 65 years and older who are moderately or severely immunocompromised should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
For all age groups, the dosage for the additional doses is as follows: Moderna, 0.5 mL/50 ug; Novavax, 0.5 mL/5 ug rS protein and 50 ug Matrix-M adjuvant; Pfizer-BioNTech, 0.3 mL/30 ug.

As an aside and not receiving much media attention, a new report showed that vaccine mandates didn't help and probably hurt. States with vaccine mandates didn't have higher covid vaccination rates and actually had lower covid booster uptake and flu vaccination rates. Yikes!

Nipah Virus

Never heard of it, or hard-pressed to find facts at the tip of your tongue? Most providers in the US don't need to know much about this bat-borne virus, but if you have any patients planning a trip to Bangladesh you may want to advise them not to consume raw date palm sap (not on my list of delicacies so far) and to stay away from pigs.

NiV gets its name from the village of Sugai Nipah in Malaysia, site of a 1999 outbreak highlighted by cases of encephalitis in pig farmers. Outbreaks typically occur in Bangladesh and India. Now, the World Health Organization reports that 2 individuals, including a 3-year-old girl, have died from the infection after consuming raw date palm sap. The sap likely was contaminated with fruit bat droppings laced with NiV. In addition to signs and symptoms of encephalitis, typical findings are those of nonspecific febrile illness. Diagnosis is difficult until/unless encephalitis findings appear. It's a relatively uncommon infection even in Bangladesh, but mortality is high.

Good Attitudes

It's a sign of our times that I was pleasantly surprised to see a vaccine attitude survey with good news. Investigators from RAND corporation, University of Iowa, and CDC performed an online survey of 1351 parents to assess their willingness to have their children 5-18 years of age receive a vaccine to prevent Lyme disease. About two-thirds of parents definitely or probably would vaccinate their children. The boldface numbers below show statistically significant predictors of willingness to have their children receive Lyme vaccine, with willingness of the parent to receive the vaccine the strongest predictor.

In case you were wondering, for the purposes of this survey the high incidence states were Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington D.C. (yes, I don't need to be reminded it's not a state), West Virginia, and Wisconsin. They also looked at states characterized as "emerging" Lyme disease states (Iowa, Ohio, Illinois, Indiana, Michigan, North Carolina), but this group had a slightly lower rate of willingness than in high incidence states. Lyme vaccine trials in the pediatric and adult populations are ongoing, so don't be surprised if parents and children have this option in the next year or so.

Speaking of attitudes, take a look at AAP's new guidance for improving vaccine communication and uptake. It has an excellent literature review and describes various strategies that pediatric healthcare providers can use to improve vaccine acceptance. It is still true that different studies sometimes have reported different conclusions on how best to discuss vaccine hesitancy with parents, likely because it is very difficult to design studies that deal with such subjective issues in a uniform manner.

WRIS

Winter respiratory infection season is still chugging along, mostly due to influenza which is stubbornly persisting in scattered areas in the US. What a crazy patchwork!

New Covid Isolation Guidelines

Maybe this has overshadowed everything in the news. I've discussed this recently in the blog and was expecting the new guidelines to come in April, but CDC bumped it up by a month. It incorporates new information about covid epidemiology, hospitalization rates, and outcomes with balancing for impacts on the economy and on school and work attendance into a comprehensive guideline for all respiratory infections. So, no longer do we have a specific number of days after covid diagnosis to remain out of school or work. The document has multiple links and is pretty complicated. The CDC's press release is a good summary, however. Note that vaccination is still stressed heavily, though I expect it will be ignored by the same hardcore group of antivaxxers. Here's the quick blurb:

"When people get sick with a respiratory virus, the updated guidance recommends that they stay home and away from others. For people with COVID-19 and influenza, treatment is available and can lessen symptoms and lower the risk of severe illness. The recommendations suggest returning to normal activities when, for at least 24 hours, symptoms are improving overall, and if a fever was present, it has been gone without use of a fever-reducing medication."

I am very much in favor of these new recommendations. Circumstances have changed, and we have learned a lot from management of the pandemic these past few years. I just hope our vaccination rate will improve and that people with any respiratory symptoms at all will be aware that they can pose a significant risk to others who may have circumstances putting them at high risk for hospitalization or death from respiratory viruses. Also, please note this only applies to community settings; there are no changes for healthcare settings.

Squirrel Redux

If I were superstitious, I wouldn't mention the fact that my neighborhood squirrels still have not attacked my newly-positioned bird feeder. I was bemused by an article in the Local Living section of the Washington Post last Thursday, clearly written by a squirrel lover. Squirrels do have value, and I have no desire to wipe them off the face of the earth. I just don't want them eating all my bird seed.

A friend of mine in South Carolina with an array of bird feeders and birds also has come to terms with squirrels, albeit somewhat differently than my crazy solution. He just monitors things, and when the squirrels reach a point that he feels they become a significant barrier to maintaining bird happiness and seed access, he uses a humane trap to collect squirrels and then release them far from his neighborhood. I won't disclose where he releases them, but it sounded like a good place for squirrels and unlikely to bother too many people. I wonder if any of them found their way back to him.

A downy woodpecker said hello to me last week.

To Rake or Not To Rake

Bud WiedermannOctober 29, 2023October 29, 2023Leave a comment

A lot going on in the world of infectious diseases this past week, enough to challenge my ability to sort out and explain the key points. That's probably why my mind, and eyes, keep drifting to the window next to my desk. The neighborhood leaf pickup is coming any day now, and many leaves cover the ground. The number of fallen leaves is still far less than remain on the old maple tree just outside the window. Yes, it's too early to rake, I would just need to do it again in another week.

Here's my stab at summarizing recent ID events.

RSV and Nirsevimab Shortage

CDC issued a HAN (Health Alert Network) advisory statement on October 23 with a plan for prioritization of nirsevimab use in the face of limited supply.

I won't attempt to summarize everything here because the recommendations are detailed and depend highly on individual circumstances impacting nirsevimab access; please read the advisory. The 100 mg dose is the most severely restricted, and practitioners should not combine 2 50 mg doses to make up the difference because you are essentially depriving 2 younger/smaller children from access in order to treat 1 other child. Note that palivizumab (Synagis) is still available and is the go-to product for infants 8 - 19 months of age, the same as in previous RSV seasons.

At last week's Advisory Council on Immunization Practices (ACIP) meeting (see more below), the nirsevimab company representative completely avoided answering a request to provide details for the cause of the shortage, other than to invoke a supply versus demand problem. I'm hoping those details appear down the road so mistakes like this can be prevented in the future.

Remember COVID-19?

I hope nobody has forgotten, but never underestimate our short attention spans. Thankfully things are relatively calm compared to pandemic times.

I felt the lay press got things a bit wrong when reporting findings of a study by FDA and others regarding safety of monovalent covid vaccines given to children before early 2023 (i.e. NOT the current vaccines). Unfortunately the report has not been peer-reviewed, but it appears pretty sound from my brief reading. The risk of myocarditis/pericarditis in adolescent boys was pretty much the same as we've heard about all along. Also mentioned was seizure risk in younger children, and this part was over-hyped by some news agencies. The association merits further study, but currently is very uncertain: "...seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates." The exact numbers were 72 children with seizures, most fulfilling the case definition of febrile seizures, out of 429,119 doses administered to that age group. Thus, it is very close to the background rate of febrile seizures, without vaccination, in that population.

Tripledemic Status

Well, more like a weak monodemic now, with RSV still the only one of our RSV/Influenza/Covid triumvirate to appear in appreciable numbers in most places. RSV-NET shows some hospitalizations in young infants below, but note that hospitalizations are only the tip of the iceberg for infections.

FluView activity is similarly low in most locales.

Biobot wastewater tracking for covid remains low.

New Immunization Schedules for 2024

As mentioned above, the ACIP met October 25 and 26 to cover a variety of subjects and reveal proposed immunization schedules for 2024 which were approved. This approval is awaiting some tweaking and then final signoff by the CDC director. The new schedules will have many new options, which is both good and bad. It's always nice to have more choices, but at the same time those choices create new complexities that aren't easy to explain; CDC doesn't have a great track record for making recommendations understandable. Potential changes include vaccines for COVID-19, influenza, meningococcus, mpox, pneumococcus, polio, and RSV (monoclonal antibody and vaccine). Release is planned for January 2024, earlier than usual.

Pediatric healthcare providers should take note of proposed new mpox vaccine recommendations, now just applying to age 18 and older but likely to eventually include ages as young as 12 years once NIH trials are completed, perhaps as early as next year. Like most outbreaks/epidemics/pandemics, mpox has evolved from the 2022 epidemic into a 2023 endemic problem now at about 1-4 cases per week on average.

Because of this, and the fact that a highly effective and safe vaccine is available, the new guidelines likely will recommend immunization for those at high risk:

Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who
in the past 6 months have had one of the following:

A new diagnosis of ≥ 1 sexually transmitted disease
More than one sex partner
Sex at a commercial sex venue
Sex in association with a large public event in a geographic area where mpox
transmission is occurring
Sexual partners of persons with the risks described in above
Persons who anticipate experiencing any of the above

We will also see new recommendations for pneumococcal vaccine now that a 20-valent pneumococcal conjugate vaccine is approved. PCV13 will phase out and infant immunization will include just PCV15 or PCV20. The 23-valent pneumococcal vaccine also will phase out, except perhaps for a stockpile kept for use in immunologic diagnostic testing.

Covid vaccination will be a little easier for young children, with clarifications for which vaccines to use for children undergoing age transitions in the midst of vaccine cycle as well as greater allowance for interchangeability of vaccines (e.g. administering Pfizer vaccine when previous vaccine was Moderna) for children 6 months through 4 years of age:

COVID-19 vaccine doses from the same manufacturer should be administered whenever recommended. In the following circumstances, an age-appropriate COVID-19 vaccine from a different manufacturer may be administered:

Same vaccine not available at the vaccination site at the time of the clinic visit
Previous dose unknown
Person would otherwise not receive a recommended vaccine dose
Person starts but unable to complete a vaccination series with the same COVID-19 vaccine due to a contraindication

The changes for meningococcal vaccination are the most confusing. A pentavalent vaccine was approved recently by FDA for use as a 2-dose regimen for ages 10 through 25 years. The confounding factor for meningococcal vaccination is that the disease is relatively uncommon, particularly for serogroup B where we see only a handful of cases annually. Furthermore, vaccine immunity wanes fairly quickly following group B vaccination, and we are potentially faced with healthcare offices needing to stock 3 different meningococcal vaccines to cover all circumstances. Here are the current recommendations for meningococcal vaccination:

Here's a look at the serogroup distribution by age (June 2023 ACIP meeting, presentation 3 slide 9 for meningococcus):

How best to add in the pentavalent vaccine? Just using that vaccine alone isn't a good idea. Trying to incorporate immunization against group B into the current schedule that starts at age 11 is likely too early to be effective. ACIP has been struggling for several months to come up with a plan for meningococcal vaccination that takes into account the relative rarity of the disease as well as the need to provide a pragmatic plan that can be implemented in diverse healthcare settings. They focused on 3 policy questions that were debated by working groups over the past several months:

PICO 2 was deemed unfavorable for a variety of reasons. We are left with deciding how best to use the pentavalent vaccine for situations 1 and 3, knowing that stocking 3 different meningococcal vaccine products may not be feasible for many practice settings. I expect continued tweaking of the options before we see the final guidelines in January, but it appears that routine immunization will still be recommended at age 11-12 years with second dose at 16 years. Group B vaccination options will variously allow use of the monovalent or pentavalent products, but it may be that the pentavalent product will be recommended for a slightly different age range (16 - 23 years) than what was approved by FDA (10 - 25 years). Regardless, the Menactra vaccine (covering groups A, C, W, Y) will be withdrawn so at least some simplification there.

A concluding disclaimer to this section: all we have now from ACIP are proposed changes. They are not approved and very likely will undergo some changes before we see them in print. Please don't act on the above until we have the updated guidelines from CDC.

Staring Out the Window Again

You can perhaps understand my tendency to wander after reading the section above. The meningococcal vaccination options are almost endless, and I didn't necessarily agree with the way the discussions were going at the ACIP meeting.

The title of this posting is a lame riff on Shakespeare, and his Sonnet 73 mentions leaves prominently. However, it is primarily a poem about aging and I didn't necessarily want to be reminded of that! I found a more playful ode to autumn in a poem by James Whitcomb Riley; he has a children's hospital named after him although he was a very complex individual who suffered from alcoholism and wasn't exactly a model citizen. His poems often are written with a child-like voice and lend themselves well to reading aloud.

"But the air’s so appetizin’; and the landscape through the haze

Of a crisp and sunny morning of the airly autumn days

Is a pictur’ that no painter has the colorin’ to mock—

When the frost is on the punkin and the fodder’s in the shock."

Summer!

Bud WiedermannJune 25, 2023June 25, 2023Leave a comment

We are officially in summer as of last week, and it certainly feels like it. Barring a mid-day thunderstorm, I'm going to sweat my way through mowing the lawn after I finish this post.

An Almost Marathon ACIP Meeting

The Advisory Committee on Immunization Practices met June 21 through 23 and covered a lot of ground. I was neither able (nor highly motivated, given the number of hours involved) to tune in to everything, but I did review all the slides and attend most of the discussions dealing with pediatric issues. I came up with some take-home messages. Note that the slides are all posted at the web link, and the meeting recording should be available in a few days.

General Thoughts

For influenza next season, egg allergy is further clarified: "Egg allergy in and of itself necessitates no additional safety measures for influenza vaccination beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg." Allergy to the vaccine itself is an important consideration, but mere egg allergy is not. This statement conforms to existing scientific data and will make things much easier for healthcare providers and vaccine recipients.

A general overview of vaccine safety was presented on Friday, and it might be worthwhile for all healthcare providers to review at least the first portion so that they can better explain this extensive safety network to vaccine recipients and providers. Also, the latter portion discussed data on a possible link between vaccine aluminum cumulative exposure and subsequent asthma diagnoses. At this point, the association using US data is very weak but is being studied further. A study from Denmark using much better data (the benefits of a national health system) showed absolutely no association, but of course that's a different population from the US and also different vaccine schedule. Providers who are questioned specifically about this could refer to those slides.

Remember my June 11 post when I was grumbling about a movement in Congress to ban use of QALY (Quality Adjusted Life Years) by CMS? If you removed QALY analysis from this meeting, the ACIP couldn't have moved forward on anything. I'm hoping this congressional movement will get ditched, but keep an eye on it.

Also in general, we are lacking information about co-administration of newer vaccines with existing vaccines. This isn't unusual, but in some instances it could be pertinent. Prominent among those is the RSV vaccine for older adults, of course not a pediatric issue, and also lacking is efficacy information in the 85 and older and frail groups. For those specific items we will have more information eventually.

Pneumococcal Vaccine

Most of this segment centered around Pfizer's 20-valent conjugate vaccine in children. Because there are already several versions of pneumococcal vaccines available, both polysaccharide and conjugate forms, the possibilities seem endless. The committee discussed various options for children who are in the midst of their vaccine series and included regimens and combinations that have not been studied. Probably we will see formal recommendations soon, but pneumococcal vaccination is clearly the most confusing set of guidance in all of vaccinology even before the 20-valent option surfaced. This is because recommendations vary with age and specific risk groups. I can't even keep it straight in my head what I'm supposed to do for myself. Fortunately, there's an app for that. CDC has a wonderful tool called PneumoRecs, available for use on a computer or for download for Apple and Android phones. It works for all ages and risk factors, you just input specifics about your patient's age, risk factors, and prior vaccine history and poof you know what to do.

Meningococcal Pentavalent Vaccine

Meningococcal vaccination guidelines are very confusing as well, but also it is by far the most expensive (based on cost-effectiveness) vaccine recommended for routine use. This is because meningococcal disease is actually pretty uncommon, so vaccination doesn't prevent much morbidity and mortality particularly for meningococcal B disease. Meningococcus group B protection is more important for certain types of immune compromise (e.g. asplenia or terminal complement component deficiency) but used commonly for the college student age group. Many years ago I accepted the fact that many colleges are requiring it for their incoming freshmen, it is now more of a legal liability protection and I guess a measure of reassurance to parents whenever a college dormitory mini-cluster occurs.

The pentavalent vaccine combines the groups A, C, W, and Y in the existing quadrivalent vaccine with group B which now exists as a separate vaccine. ACIP did not have a vote on the pentavalent vaccine, it is still a work in progress. I did find a few epidemiologic graphs very informative. The graph below shows that meningococcal disease was declining significantly before the introduction of any vaccines in the US, making it difficult to know how much vaccination contributed to any further decline.

Second, the current number of cases is very low, and the numbers of cases in the 11-15 year olds would suggest that we should revise current recommendations.

The problem is that meningococcal immunity likely wanes significantly within a couple years after vaccination. So, giving a first dose of quadrivalent (or potentially pentavalent) vaccine in that 11-12 year old group is providing protection at the time they need it the least. That first dose should come later.

Regardless of the current vaccine recommendations, it is very clear that active and passive smoking is a significant risk factor for invasive meningococcal disease. Smoking increases binding of meningococci to respiratory epithelial cells, a major initiating event for invasive infection. Smoking reduction, including vaping though no specific vaping studies are available, is the most effective preventive measure against meningococcal disease in healthy adolescents.

Also keep in mind that epidemiologic trends might be different post-covid, as we saw initially for influenza and RSV.

RSV Prevention for Infants

This was primarily a discussion of the Pfizer RSV vaccine for pregnant people, without a vote by the committee meaning more to come on this decision. A major question regarding maternal vaccination is a possible association with premature delivery in recipients. The forest plot below shows a slight increased risk of preterm births.

What is particularly tough is that another maternal RSV vaccine study with a different manufacturer was stopped because of an increase in preterm births in the vaccine recipients compared to placebo. It's still not clear what the potential biologic mechanism would be for such an association, but for now this is a significant concern. Thankfully we are likely to have the long-acting monoclonal antibody, nirsivemab, available for the upcoming RSV season.

What I'm not including in this post, because I'm not smart enough to summarize effectively for a nonstatisticians and similar geeks, is the very elegant and thorough discussion of costs of various scenarios for RSV prevention in young infants. These considerations included using maternal vaccine and infant monoclonal antibody treatment, both separately and in combination. The combination is likely not going to be clinically- or cost-effective. Separate use (e.g. nirsevimab for mothers who did not receive vaccine, or infants born prematurely prior to maternal antibody transfer across the placenta) is difficult because providers may have difficulty accessing accurate maternal vaccine records. It's a bit of a messy consideration. Still, I wanted to at least introduce one new concept of tornado diagrams. I had great trouble even finding a user-friendly explanation for the link, but keep in mind that it is a method to determine the major factors driving cost-effectiveness. As stated in the link, big bars are the big drivers, small bars aren't. (The name comes from the shape of the graph - imagination required, nothing to with the weather.) Here is a tornado graph for nirsevimab.

It sort of looks like a tornado shape? The biggest drivers, which translate to a sensitivity analysis of how accurate the cost-effectiveness analysis is, include cost of nirsevimab, costs of hospitalizations, and our old friend QALYs lost. As you can see from the Incremental Cost-Effectiveness Ratio (ICER, the ratio of differences in cost between 2 options divided by the difference in effects such as QALYs) scale at the top, these are big bucks. I'm certainly no expert in ICERs and tornado diagrams, but this type of analysis is critical in choosing among various healthcare interventions at the population level.

I'll continue to keep my eyes peeled for better explanations of ICERs and tornado diagrams.

'Demic Doldrums

Hooray, we are still in a covid lull, including most places around the world including southern hemisphere. You can look at the good news in detail on the WHO website.

ACIP did discuss covid vaccines, briefly, but no significant new data to report. We are likely on target for monovalent XBB.1.5 vaccines available from all 3 US manufacturers by September. Also, look for some dosing simplification for the 2-4 year olds.

Off to the mower, after I drench myself in DEET.

A Noisy Week

Bud WiedermannFebruary 26, 2023February 26, 2023Leave a comment

Lots of pediatric infection-related meetings and reports this week, but actionable items for front-line care providers were sparse. It's not that the information wasn't interesting, but when all was said and done I couldn't come up with anything to change clinical practice. That type of noise is good, but I'll be more excited a few months from now when we might have actionable events from ongoing studies.

A 3-Day CDC Advisory Council on Immunization Practices (ACIP) Meeting

This ACIP meeting covered a lot of vaccine topics including vaccines for mpox, influenza, pneumococcus, meningococcus, polio, RSV (both pediatric/maternal and elderly adults), chikungunya, dengue, varicella, and our old friend covid. I wasn't able to view the sessions live but have reviewed many of the slides that were posted. The only vote at the meeting was to continue use of mpox vaccination pretty much as before; the rest of the meeting primarily consisted of updates. In the next few months we should be approaching some decisions particularly for RSV immunization of pregnant people to protect their newborns, long-acting monoclonal antibody treatment to prevent RSV in high-risk and/or all infants, 20-valent pneumococcal vaccines for children, and more.

With regard to RSV prevention, in the past I was struck by ACIP wording about anti-RSV monoclonal antibody therapy being labelled a "vaccine" when it really is a therapy. I now understand that the vaccine label would have made it easier to provide the intervention through the Vaccines for Children program; if it is a therapy, some infants will fall through the cracks in terms of access. AAP had a nice summary of these issues.

Pfizer presented data that they have submitted to FDA for maternal RSV immunization during pregnancy to prevent RSV in their newborns, but I won't show that data since it was only from the pharmaceutical company without separate analysis by ACIP or CDC. FDA/VRBPAC will discuss RSV vaccines for people 60 years of age and older (this also was discussed at the ACIP meeting) on February 28 and March 1, but it doesn't look like they will cover any pediatric issues at this meeting. However, if studies look good it is possible we will have new interventions to prevent RSV in young infants prior to next winter's RSV season.

Post-Acute Sequelae of COVID-19 (PASC)

I did attend a February 23 webinar on PASC in children and adolescents hoping to see some new data, but ultimately I was disappointed. That's not to say that progress hasn't been made, but the session was mainly a review of previous data and guidelines. I did learn that risk factors for PASC in children and adolescents include age greater than 12 years, unvaccinated status, and history of allergic disease. PASC symptoms were less common in vaccinated individuals than in the unvaccinated. Here's a peek at main symptom frequencies:

It was a good review session of general evaluation and treatment options, check out the complete slide deck.

PASC is really a tough issue, likely because it is still a mixture of at least 2 different processes. One includes all the end-organ damage from the infection itself, while the other comprises more vague manifestations such as brain fog, fatigue, and dysautonomia symptoms. I've been seeing children with these conditions long before the covid era, seemingly following a wide variety of otherwise run of the mill infections. I'm hoping the intense research focused on PASC will yield something useful for the larger body of individuals affected with what has been called myalgic encephalomyelitis/chronic fatigue syndrome. I dislike that term, it still sounds somewhat pejorative to my ears. Of note, the National Academies of Science, Engineering and Medicine is planning a series of workshops to better characterize a working definition for Long COVID.

We Still Have a Failure to Communicate

Just a quick mention of a study that reviewed US state and territory public health sites for readability and accessibility of their covid treatment information. Broadly speaking, most sites fell short of effective communication - wording too technical or at a high reading level, not helpful for individuals with communication barriers, etc. South Dakota was the best site, followed by Maine and Tennessee (would you have guessed these states coming out on top?). You might want to look at where your state scored. I'm hoping public health units see this article and work to improve their sites.

Enough Ivermectin Already?

Well, yet another study has shown no benefit of ivermectin as a covid therapy, this time using a higher dose. I was more enthralled with one of the accompanying editorials about the ethical principle of equipoise in performing clinical trials to deal with uncertainty in medicine. Simply put, it's a good idea to perform clinical trials to deal with uncertainty, but given that we always have uncertainty in medicine, when should we call it quits for these trials? Specifically, when does it become unethical to perform studies of ivermectin for covid in the hopes of finding some small niche where there might be benefit? That question has no easy answer. Ivermectin became a political pawn early in the pandemic; I fear the end result of that conflict is now wasted resources and unnecessary risks for trial subjects.

Better Data on Paxlovid Rebound

We were just talking about this last week, and now we have results of a prospective study that gives us perhaps even better data. Both viral and symptom rebound were slightly higher in the Paxlovid group compared to controls, but pretty much still in the same ballpark. For example, symptom rebound was about 14% in the treatment group and 9% in the controls. The prospective design of the study is more likely than retrospective studies to give "truer" numbers, and I think what we are seeing is that rebound is more common in untreated people than originally thought. From my viewpoint, the slight increase in rebound from Paxlovid is far outweighed by the benefit of treatment in preventing complications in high-risk individuals.

White Noise

Speaking of noise, this past week my wife and I watched Noah Bambach's adaptation of Don DeLillo's novel, White Noise. Buried somewhere in the few hundred books in our house is a copy of the novel, but neither of us could remember plot details. Fifteen minutes into the movie, we realized neither of us had ever read it!

It's an understatement to say that reviews of the movie were mixed; in fact, many were at the extremes of love or hate. This isn't surprising for a book that was said to be impossible to translate to the screen. Yes, the movie had its dragging and confusing moments, but I loved it so much that I decided to read the book. I'm almost done with it, and it's very interesting for me to see what elements Baumbach left out or changed substantially, versus other parts taken nearly verbatim from the book.

The book, written in 1985 and dealing with fears of mortality, a college professor and his family, and an "airborne toxic event," sadly translates very well to today's chaotic world. The movie was mostly true to the book's central themes, and the song and dance ending, a backdrop to the closing credits, made me smile. I'd recommend both the novel and the movie to folks who might enjoy a quirky, reflective view of modern life and be able to put up with some unevenness in presentation.

Tag: pneumococcal vaccine