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I just returned from a mad dash to Orlando, FL. No, I wasn't paying Mickey and Minnie a visit, just putting in an almost cameo appearance at the American Academy of Pediatrics National Conference and Exhibition. Apparently they were desperate for speakers because they invited me to give a talk about how to approach reading journal articles. A few dozen attendees politely endured my presentation, but I, and I think even most of the attendees, had a fun time. I also got to chat with a few old friends, always nice.

Although the trip was nice, I was most excited about the notice I received from my bird feeder while I was away. More on that later.

Potpourri

I came across a smattering of unrelated items this past week, grouped here.

I think we could all use some good news from the Middle East now. The WHO announced that Jordan has become the first country in the world to be certified to have eliminated autochthonous (locally-acquired) leprosy. That is no mean feat and required tremendous efforts and resources both from the country of Jordan as well as the WHO. It has been over 20 years since they've had an autochthonous case in Jordan.

The CDC has sent out a notice about mpox prevention through their Health Alert Network. It's not new, but worth reviewing to understand risk groups and to remind us to ask about international travel plans of our patients.

I've deliberately avoided commenting on the possible person-to-person spread of influenza A H5N1 in Missouri, but it's been in the lay press. Close contacts of 1 confirmed case had illnesses that could be consistent with this form of bird flu, but we don't have any test results from the contacts. I just mention it to stress that this is an evolving story. It would be a change for this organism if human-to-human transmission is now common.

Vaccine News

A couple intriguing reports last week from the CDC via the weekly MMWR. First are survey results that give us a glimpse at what happened with childhood immunization rates during the pandemic. It should surprise no one that vaccination coverage at 24 months of age declined by a few percentage points from birth year 2018-19 to birth year 2020-2021. For the combined 7-dose series (doesn't include covid vaccination) the rate dropped from 70.1% to 66.9%. This just adds to the possibility for sustained epidemics especially if clusters of poorly immunized children are grouped together. Here's a list of the national data for the 2020-2021 birth year cohort:

The entire table was too large to put in everything here, but Montana had the lowest numbers followed by California at second worst. You can look up your state and region in the article.

The same MMWR also had some new data on covid in children under 6 months of age. It provides compelling rationale for maternal immunization. First, here's what age-associated covid hospitalization rates look like from the surveillance network:

Further data showed that infant hospitalization rates are higher than rates in the elderly (75 years and above). In a subset of 1148 infant records that underwent extensive review, 9 deaths were recorded. Overall 22% of the hospitalizations involved intensive care admissions. Looking just at the 1065 infants for whom maternal vaccination status was available, it appears that maternal vaccination during pregnancy could be an important preventive measure for severe infant covid illness.

Note the careful wording: "No record of maternal vaccination during pregnancy." This points to the fact that these records might have been incomplete or even wrong - the providers may have recorded information incorrectly, or the mother may have been mistaken about vaccination status and timing. I'm still impressed with the information, especially since these numbers are very recent, from the omicron period when virtually every adult had some sort of immunity either via natural infection, vaccination, or both. Maternal covid vaccination is important to protect both the pregnant person, itself a high risk group, as well as the infant who is too young to receive covid vaccine.

A New Antiviral for RSV?

A placebo-controlled, randomized, double-blind trial of a few hundred infants hospitalized for RSV in China suggests that a newer antiviral agent, ziresovir, might be an effective treatment.

The main endpoint is change in the "Wang score" which is a relatively unvalidated scoring scale for assessing RSV severity. You can see the decline in the score is a bit better with the treatment group compared to placebo, but is the change in score clinically important? As a still wet-behind-the-ears ID attending, I witnessed early studies of randomized, double-blind, placebo-controlled trials of aerosolized ribavirin for hospitalized infants with bronchiolitis; my boss, a renowned pediatric infectious diseases physician named Bill Rodriguez, headed up these multi-center studies. I witnessed potential pitfalls in using scoring systems for bronchiolitis, particularly the problem with intra- and inter-rater reliability in assessments: it's hard to be consistent with scoring when the events you're looking at are somewhat subjective. Also, the aerosolized ribavirin left a fine powder on the infants, difficult to disguise even when the nurse tried to remove it before the investigator did the scoring. So, it wasn't perfectly double-blinded, in some cases not blinded at all. At blinding wasn't a problem with ziresovir, which is administered orally. Aerosolized ribavirin did work, but ultimately the costs outweighed the benefits (plus some risk to providers of inhaling the medication if the patient room was not well-ventilated and potential for teratogenicity), so the practice didn't last long.

I'll wait to see more data about this intriguing new agent. In the meantime, remember we have very effective methods of preventing severe RSV disease in infants by either maternal vaccination or administration of long-acting monoclonal antibody (nirsevimab) to infants whose mothers were not immunized.

Crystal Ball Time

What's coming this winter, and how bad will it be? Don't place any big bets on the CDC's latest predictions, they have only low to moderate confidence with their model, but it's by far the best data we have.

Here goes: "CDC expects the upcoming fall and winter respiratory disease season will likely have a similar or lower number of combined peak hospitalizations due to COVID-19, influenza, and RSV compared to last season."

That's good news. The experts were moderately confident of predictions for individual infections, but it's not really possible to anticipate all of the variables that could change the predictions dramatically, such as immunization uptake. Of course, if a new covid variant arises with a very effective immune escape mechanism, no one will be betting and we'll be in for a bad time.

Here's some more tidbits:

For example, if our summer covid activity peaks early (which it seems to be doing), they predict a milder winter season than if covid continues to rise now.

If you're a nerd like me, you can look at their description of how they developed this prediction model.

For the Birds

Getting back to my bird feeder, regular readers will recall my travails discussed in prior posts, including battling squirrel seed raiders. Things have settled down now, and I seldom see new species, but the past 2 days I've had my first sightings of a red-bellied woodpecker. The first thing I noted from my feeder's video (still photo taken below) is that I don't see a prominent red belly.

Other views show the typical zebra-like striping on the wings - why not call it the zebra woodpecker? - and the Cornell app quickly identified its call as the red-bellied variety. As usual, I couldn't help but see what new woodpecker tidbits I could learn from the worlds of literature and music. My childhood and adolescent "career" playing tenor saxophone made me a fan of big band music, particularly of Glenn Miller, and I discovered he had recorded The Woodpecker Song. It's not that great in my opinion, but at least I learned something new. One of my other musical heroes, Chuck Berry, recorded a purely instrumental (with saxophone solo!) song called Woodpecker. My favorite find, though, was a new-to-me poet, Elizabeth Madox Roberts. She was a Kentucky-born daughter of a Confederate soldier, active as a poet and novelist in the late nineteenth and early twentieth centuries. She seems to have the largest numbers of poetry web sites extolling her virtues for poems about woodpeckers. Here's her poem The Woodpecker in its entirety:

The woodpecker pecked out a little round hole
And made him a house in the telephone pole.

One day when I watched he poked out his head,
And he had on a hood and a collar of red.

When the streams of rain pour out of the sky,
And the sparkles of lightning go flashing by,

And the big, big wheels of thunder roll,
He can snuggle back in the telephone pole.

It's my usual Sunday to put the final touches on this week's post though working on it earlier than my usual late morning start since I had to watch the Women's World Cup soccer match. In case you recorded it to watch later, I won't reveal any spoilers.

It's Official for Nirsevimab

On August 3 the ACIP voted to recommend the long-acting monoclonal antibody nirsevimab (brand name Beyfortus) to prevent RSV. It is recommended for use in all infants under 8 months of age, just before or during the RSV season, and also for infants 8-19 months of age with the usual high-risk medical conditions just before their second RSV season. Dr. Mandy Cohen, the new CDC director, formally adopted those recommendations. It will eventually replace the current product, palivizumab (Synagis), which has been administered just to the high-risk groups monthly during RSV season.

I didn't log in to the ACIP meeting but did review the slides and reports (available here). Most of the information had already seen the light of day at the prior FDA meeting that approved the product, but a few items are noteworthy.

First, authorities now refer to this product as a vaccine, although that's not quite true in the scientific sense. This is a strategy to try to have this funded by the Vaccines for Children program. The product will be very expensive (probably around $450 - 500 for a dose), and even standard health insurance companies are notorious in avoiding reimbursement for new products.

For infants born just before or during RSV season, nirsevimab would best be administered by the birthing hospital prior to discharge. I was surprised to learn that only 10% of US birthing hospitals participate in the VFC program. Most provide bundled services for deliveries; hepatitis B vaccine is often covered in this manner, but that cost is only $13-16 per dose. Will bundling work for a much more expensive product? These payment issues could impact ability to administer the new therapy particularly for the upcoming RSV season. There isn't much time to figure out these details.

Presentations from CDC personnel helped show the potential impact of nirsevimab, using a Number Needed to Immunize (again with the vaccine nomenclature). Based on the available 2 randomized controlled trials in mostly healthy infants, where ICU admissions were rare and deaths thankfully absent in the study infants, NNI was favorable particularly for preventing hospitalization but also for prevention of medically-attended illness.

In other words, 128 infants would need to receive nirsevimab to prevent 1 additional child from being hospitalized for RSV. Various cost-effectiveness analyses showed this to be a good use of funds.

Data are not yet available to perform similar analyses for high-risk infants receiving therapy prior to their second RSV season, but antibody levels in those infants following treatment strongly suggest it will be effective.

CDC will provide us with more detailed recommendations soon. They did provide an example of timing for "vaccination" with nirsevimab. As mentioned above, for children born just before or during RSV season (October 1 through March 31 in most parts of the US), nirsevimab would be administered at birth. Otherwise, administration would be timed for the well-child checks in primary care provider offices, perhaps in October and November. The October batch could include infants born the previous April (at their 6-month visit), June (4-month visit), and August (2-month visit). Infants born the previous May (6-month visit), July (4-month visit), and September (2-month visit) would receive their dose in November. A bit complicated, but at the moment I can't think of a better plan to make this run smoothly for office practices.

We also need guidance if FDA approves the maternal RSV vaccine for pregnant people. Providing nirsevimab to infants whose mothers were vaccinated during pregnancy is probably unnecessary. FDA is supposed to decide this month on the maternal RSV vaccine once they receive updated results from the ongoing trials.

Regardless, all pediatric healthcare providers need to stay tuned; this could be a major change in office practice this fall.

Don't Go Home With the Armadillo, etc.

A case report of possble authochthonous leprosy in central Florida reminds us that, Jerry Jeff Walker notwithstanding, one can acquire leprosy in the US without having contact with humans or armadillos with leprosy. The report and other epidemiologic evidence suggests that leprosy may be endemic in southeastern US.

Cold air might aid in croup treatment according to a new randomized controlled trial in an emergency department. In addition to treatment with dexamethasone, children with croup were randomized (not in a blinded fashion, obviously) to outside cold air for 30 minutes, compared to room temperature indoors. The cold air kids seemed to improve faster.

Conflict in My Favorite Medical Feed

I've been reading ProMED posts several times a day for years and have donated funds to them during that time. They were the first to report all 3 coronavirus outbreaks this century. I was a bit disappointed to learn recently that they will start charging a subscription fee but was resigned to the fact that I'd be shelling out a few more bucks. Now I've learned there's a big kerfuffle in the background. The frontline folks who do all the work are protesting new management moves. I hope this is resolved, I can't imagine life without ProMED.

'Demic Doldrums

No big changes this week, CDC numbers are similar to last week and all indicators point to an increase in SARS-CoV-2 activity in the US and elsewhere. Not to rely too much on anecdotal data, but my own primary care provider remarked to me at a visit last week that he has seen an upswing in positive tests in his practice. Let's hope this will be a minor blip and not the start of a large new wave.

Some Good News From Down Under

Again, no soccer spoilers from me. But, maybe flu has peaked in Australia; if so, this season is a bit better than 2022 and might bode well for our own flu season.