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Tag: RSV

Published on Leave a comment on No Spoilers From Me

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.

Published on Leave a comment on Summer!

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.

2

Published on 2 Comments on Happy Holidays!

I'm putting this post together on Father's Day, and tomorrow is Juneteenth, a holiday increasingly recognized in the US. Today two of my 3 sons are farther away than usual, one in Berlin, Germany, at the Special Olympics World Games and another working in healthcare in Mekele, Ethiopia. The third member of the triumvirate remains in the eastern US time zone.

Can anyone guess which state was the first to make Juneteenth a permanent state holiday?

Influenza Rising in Southern Hemisphere

The most recent World Health Organization update on influenza, published on June 12 with data current as of May 14, not surprisingly shows an uptick in flu activity in sections of the southern hemisphere. The influenza AH1N1 2009 pandemic strain and B Victoria lineages predominate, meaning we are likely in good shape from a vaccine standpoint for next winter in the US.

RSV and covid haven't increased to the same extent as flu in the south, for the most part.

Polio Vaccine for Travelers

'Tis the season for world travel, but I'm thinking many folks aren't aware of newer polio risks around the world. Spurred by the pandemic and various war zones, polio vaccination has waned. Also, as I've noted in the past we're seeing vaccine-derived polio disease via transmission from recipients of the oral live polio vaccine. The CDC continues to update polio vaccine recommendations for travelers. Twenty-nine countries around the world have circulating poliovirus, but in addition to the "usual suspects" the list now includes both Canada and the United Kingdom.

Certainly the risk can vary in settings within these countries, but primary care providers should remember to discuss vacation plans with families, not just out of interest but to make sure they are informed of any risks and where to find resources. Make sure all children are up to date on immunizations, including polio, and some adults may wish to receive a one-time killed polio vaccine booster if traveling to a high risk country.

'Demic Doldrums

Here in the US we continue with our low levels of SARS-CoV-2 circulation in most jurisdictions; now we rely primarily on ED visits and hospitalization rates for any early warning given our lack of other good community monitoring tools. The FDA VRBPAC group met on June 15 to advise on composition of the next covid vaccine, and I was able to attend most of the meeting including the important parts of the discussion sessions. All 3 US vaccine manufacturers (Moderna, Pfizer, and Novavax) presented data.

As most providers know, the XBB sublineages (XBB represents a recombination of omicron strains) now predominate; the ancestral strain has virtually disappeared from circulation in humans, as have all subsequent strains except for the omicron lineage. Without going into perhaps agonizing detail, most authorities agree that covid vaccines for the near future should focus on the XBB sublineage. The vaccine manufacturers have a fair amount of preliminary data on immunogenicity of XBB-containing vaccines. Results suggest good safety signals and good neutralizing antibody activity against currently circulating XBB strains. Less data are available for memory B- and T-cell responses to these vaccines, and nothing substantial so far on XBB vaccination of children. Work continues, and we should see more about pediatric XBB vaccination in the next month or 2.

A very important part of the presentation has to do with cross-reactivity of antibody among the various XBB strains that were tested. Because of this, a monovalent vaccine with any XBB strain is likely to be effective against these closely related sublineages. Since among other reasons all 3 companies had the most experience with the XBB.1.5 vaccine and can readily ramp up vaccine production for this product, the VRBPAC members unanimously voted to go this route and the FDA officially signed off on this recommendation. Next up is a discussion at the ACIP meeting on June 23, but don't expect any vote or final recommendations at this session. That should come a bit later. In particular, we will need guidance on pediatric use, combined use with other vaccines such as for influenza and RSV, and whether to recommend for all or just for certain high-risk populations.

Last week I perhaps dissed the CDC's use of color in their depiction of variants, but now I need to acknowledge I was wrong. The most recent MMWR had some nice graphics. The graph below not only shows the colorful distribution of variants but also the relatively low numbers of cases recently (with the caveat that testing in general is less now than in 2022).

As can be seen, we have been in an omicron world for some time, with XBB now in charge.

Quickly, a few other covid notables from last week:

Juneteenth

Perhaps not what you would have guessed, but my home state of Texas was the first to make Juneteenth a permanent state holiday, in 1980, which was decades before most of the rest of the country. I left Texas in 1984 and parts of it now are unrecognizable to me, but it's easy to understand why that state was out in front on Juneteenth. The original event was June 19, 1865, in Galveston, TX, when Union troops arrived and finally enacted the January 1, 1863, Emancipation Proclamation and freed slaves in Texas. In my childhood, unless you kept yourself under a rock, if you lived in Texas you knew about Juneteenth.

Happy Father's Day to all fathers out there, and to everyone please use Juneteenth to reflect on its many lessons that continue to challenge us to do better.

Published on Leave a comment on Always Something Entertaining

Last week I was watching my new washing machine at work. This week it was our "airborne toxic event" as Canadian wildfire haze, fumes, and particulate matter settled over the DC area for a couple days. I'll pick the washing machine any time.

Nirsevimab - Likely a Big Change for Pediatric Practice

Last Thursday the FDA's AMDAC (Antimicrobial Drugs Advisory Committee, expert panel advisors to CDER, the Center for Drug Evaluation and Research), met to discuss potential approval of a long-acting monoclonal antibody injection to prevent and modify RSV infection in infants. The panel voted unanimously to approve nirsevimab for this purpose in infants experiencing their first RSV season and favorably (19 yes, 2 no) to approve it in a second season for high-risk infants. The FDA has yet to announce any action on the panel's votes. However, the Advisory Council on Immunization Practices (ACIP) of the CDC is scheduled on June 22 to discuss nirsevimab along with the recently approved RSV vaccine for pregnant individuals to protect their infants.

I could only attend part of the AMDAC meeting on Thursday, but it was the most important part involving the panel's discussions of the data presented. Virtually all the data have already been published and it is pretty clear that a single dose of IM nirsevimab is safe and effective during a child's first RSV season, including infants at high risk (e. g. prematurity with or without BPD or other chronic lung disease, significant cardiac disease) but also for normal healthy infants born at term. I am departing from my usual practice of avoiding any suggestion of bias by not displaying any slides presented by the pharmaceutical sponsor. In this case I felt the FDA slides weren't good visual summaries. The sponsor's slides (at least the ones I'm showing) didn't overhype the data. Here's how nirsevimab works:

(Of course there is a little hype here - the title sneaks in their hope that nirsevimab will be approved for all infants, not just those at high risk for RSV complications. The items in the slide have nothing to do with that comparison. A typical pharmaceutical company subtle advertising ploy.)

Note that these trials (essentially 3 separate ones) started before the pandemic and then hit some real bumps in the road, with shutdowns in enrollment and absence of RSV disease during a couple winter seasons. Finally the main randomized trials were completed and showed favorable results.

MA RSV LRTI = medically attended RSV lower respiratory tract infection

I'm showing this Trial 04 because all of the subjects were at least 35 weeks gestational age, so not our traditional high risk population. Thus we see relatively low rates of medically attended disease and hospitalization but still primarily favoring use of nirsevimab.

Two big questions remain. First, how could this product be used (or not) for infants born to mothers who received the RSV vaccine during pregnancy? No studies address this. Second, what about administering the medication to high risk infants before their second RSV season? Although neutralizing antibody levels weren't zero a year after one injection, it isn't clear how much protection would remain. Normal healthy infants have even less risk of serious RSV disease during a second season, so the question really is just for the high risk kids. Those studies are ongoing but antibody studies of a second dose do suggest it would be protective.

I'm very interested to hear the ACIP discussion on June 22. From a practical standpoint, nirsevimab could be administered at hospital discharge for newborns born during or just before RSV season, but for others born at other times it could be given in healthcare offices as an outpatient sometime in the fall. We have a few months before RSV may return, I think it is likely nirsevimab will be part of our armamentarium in the fall. Stay tuned.

Deciding When to Administer Post-Exposure Rabies Vaccine

This has always been a tough issue: the disease is basically 100% fatal, so one would need to be pretty certain there was no significant exposure in order to withhold the vaccine series. An article trying to quantify risk appeared last week and reminded me of a former patient of mine. I saw a very intelligent high school student with pre-existing anxiety and other neurobehavioral issues who had developed something of a pathologic fear of rabies. (S)he had a recent concern for rabies exposure, but in the discussion of the events it was very clear that there was no exposure at all and no vaccine was indicated. Complicating the picture, however, was that later on (s)he was awarded a chance to study abroad in a country that had a higher rate of rabies in dogs and other animals, particularly in rural settings. The posting was actually in a major city with essentially no increased risk of rabies compared to the US, but the student asked for pre-exposure prophylaxis. I exhaustively reviewed everything about rabies in that country and presented my data to him/her and parent, stating that pre-exposure prophylaxis wasn't indicated. I never had follow-up for what happened, it was a tough situation and I couldn't help thinking that this setting was not a great choice for this student's learning.

If this situation presented itself to me again, particularly with a patient with high numeracy skills, I'd try to incorporate this article. The researchers used 24 different clinical scenarios and 10-year rabies rates in animals in the US to obtain opinions from 50 local and state public health practitioners who regularly advise on rabies prophylaxis. It's an interesting but complicated read that provides some quantification for risk.

Looking just at the graph on the left for Number Needed to Treat, you can see that for a low risk event such as a single bite to the arm from a vaccinated cat in Michigan that was ill and provoked, the graph becomes asymptotic. Using even more complicated logistic regression methods, the researchers concluded the best cutoff for providing prophylaxis was at a risk threshold (probability that a person was exposed to a rabid animal) of 0.0004. This is an appropriately very low number.

The bottom line for healthcare providers still is that they should discuss all rabies prophylaxis questions with their local health department experts. These folks do this all the time and are our best resources.

Checked Your QALY Lately?

That's Quality Adjusted Life Years, a commonly used measurement to aid in assessing value of a particular intervention such as a medication or vaccine. It attempts to place a number on how much better a person's life would be with the intervention and how long the benefit would last. So, QALY for a 70-year old usually is lower than for the same intervention in a 7-year old, assuming the intervention has equal benefits at both ages and that they both die at age 80. Shame on me for not realizing, until I read this opinion piece, that Congress is trying to forbid use of QALY in government health programs like Medicaid and Medicare!. Usually I try to stay away from politics, but this move is so ridiculous that I couldn't control myself. QALY is just one of many tools to use in judging effectiveness of health interventions, and it was never intended to be used for individual decision-making anyway. Banning it would only hinder healthcare program decisions.

Remember Where You Were on July 16, 1969?

Most medical students I've interacted with over the past couple decades weren't born yet and don't recognize anything about that date. For many years, I had a monthly session with groups of third-year medical students during their pediatric rotation. It was a game of sorts, guessing the disease from a CDC graph or map liberally sprinkled with hints from me. I used it to demonstrate the effect of vaccines, the lack of public health services in the Deep South, and other public health principles. For extra credit, I had this photo:

Most had no idea. A few times someone would recognize President Nixon. What's pictured is the quarantine station where the Apollo 11 astronauts were kept after splashing down in the Pacific, in case they were carrying moon germs. My next question was, "What is the incubation period of moon germs?" That met with a lot of blank stares, but the answer is 21 days since that is how long the astronauts were kept in isolation.

I mention this date of the first humans landing on the moon now, rather than next month, due to publication of even more details about this moment in history. Apparently there were so many leaks and other problems with the quarantine systems put in place that, if there were pathogens on the moon, likely we'd all have been caught up in a Moonicus germii pandemic that would have changed things forever.

'Demic Doldrums

Speaking of pandemics, thankfully we continue in the covid doldrums, with a few updates. We have even more data about vaccine safety in the 6 month to 5 year old age groups, courtesy of post-marketing systems in place maintaining our pharmacovigilance. Side effects are very minor.

WHO continues to report little covid activity worldwide.

The southern hemisphere has begun flu and RSV seasons in many places; Australia and South Africa have yet to see much of a bump in covid.

I logged into a CDC/COCA call on June 6 that included how our post-pandemic disease monitoring should be viewed. Here is a nice summary slide:

Wastewater is still a nice tool, but in the US this is still a voluntary reporting system and leaves much of the US without any data, so it's less helpful. Emergency room visits and hospitalizations for covid likely are the most effective indicators to signal a new wave.

Variant modeling continues, albeit with less specimens to test since less disease is going on. I included the latest from the UK (I think it's prettier than the US graphs).

XBB sublineages continue to predominate and may drive vaccine selection for the fall. The FDA VRBPAC meets on this on June 15. Will it be a monovalent vaccine focused on just 1 XBB strain? More on that next week.

Published on Leave a comment on Default Dedebt?

Living in the DC area, it's impossible to ignore the news on the looming debt ceiling deadline. Thankfully, we don't have a lot of infectious diseases causing immediate worry.

It's RSV Week

No, we haven't had any bizarre spring outbreak of RSV disease, just a spring outbreak of RSV news.

I wasn't able to view the FDA VRBPAC meeting about the Pfizer RSV vaccine for pregnant women, but I've gone over the documents, slides, and news reports. From a superficial view, the committee members voted unanimously that the vaccine, administered to pregnant people at 24-36 weeks gestation, was efficacious in preventing medically-attended lower respiratory tract infection (MA-LRTI) in their newborns from birth through 6 months of age. They also voted that the vaccine was safe, although 4 of the 14 panel members voted "No" for the safety issue.

Looking at the efficacy numbers, the vaccine efficacy was 57.1% (95% CI 14.7-79.8%) for RSV+ MA-LRTI and 81.8% (40.6-96.3%) for severe (defined as tachypnea, oxygen desaturation, need for high flow cannula or ventilatory support, ICU admission, or unresponsiveness) RSV+ MA-LRTI. The main trial involved about 7000 mothers, randomized equally to vaccine or placebo. As you can see, the confidence intervals are quite large, indicating the relatively low numbers of the outcomes of interest. Efficacy for severe disease dropped to 69.4% at 6 months of age, again with a wide confidence interval. The numbers are pretty good for a respiratory viral vaccine. Here's a screenshot of one of the FDA presentation slides for severe disease:

For safety evaluation, both mothers and infants were studied. The main concern that arose had to do with a higher rate of premature delivery in the vaccine group. Here's the safety summary from the FDA presentation:

You can see that the premature births/deliveries percentages are close to one another, and the differences did not reach statistical significance. Still, it is notable if in fact there is some causal association - remember, it would be a vaccine potentially given to all pregnant people. Also, it's a bit more concerning because over a year ago GlaxoSmithKline paused their trials of a maternal RSV vaccine over safety concerns. The safety concern with the Pfizer vaccine would likely require tens of thousands of participants in new clinical trials to have enough power to see if the relationship holds; rather, this would be something to focus on with post-marketing surveillance if the vaccine is approved.

At the time I write this, FDA has not yet issued an approval statement for the vaccine. Of course, we have plenty of time since the next RSV season is likely months away. Also, we must remember there is another potential new alternative for RSV severity mitigation in young infants, the long-acting antibody preparation nirsevimab. The CDC's ACIP will discuss maternal/pediatric RSV prevention at their meeting on June 22. It may be that nirsevimab is a better choice than vaccine at this point. I'll be very interested to follow that June ACIP meeting.

But Wait, More RSV

A couple new studies appeared last week. One longitudinal cohort study in Tennessee demonstrated an association between lack of RSV infection in the first year of life and lower risk of asthma developing within a 5-year followup. This isn't the first study revealing that early RSV infection can lead to subsequent asthma diagnosis. The study involved only term infants, suggesting significant potential benefit of RSV preventive measures beyond just premature infants.

Another study from Colorado reported that lack of exposure to RSV during the bulk of the covid pandemic could be the reason we saw such a severe RSV season this past fall and winter. We'll need to see the results replicated in other locales, but the study was well done and the mechanism is biologically plausible.

Covid News

Not much has changed in the past week, but a few items of interest appeared. First, the World Health Organization has recommended the next iteration of vaccine be a monovalent product targeting the XBB lineage, abandoning any inclusion of the ancestral strain. I'll be interested to see if the US follows suit when FDA meets June 15 to discuss composition.

A recent modeling study also caught my attention. As I've said before, modeling studies have many assumptions and can end up being totally off base, but this one from multiple institutions shows that, if we had done a better job with covid booster vaccinations in fall of 2022, we would have seen a significant decrease in both hospitalizations and school absenteeism in the pediatric population last winter. Perhaps I'm cherry-picking this study because it agrees with my bias that covid vaccination benefits all age groups, but the study methodology seems sound given the limitations of any modeling study.

Lurking in the Shadows

Mpox remains a problem, particularly for men who have sex with men. The vaccine is highly effective.

Influenza H5N1 continues to lurk, causing sporadic infection primarily among those with very close contact with fowl including chickens. The US Department of Agriculture is studying a vaccine for poultry as well as use of other mitigation strategies.

CDC has some new guidance on building ventilation, maybe one of the lessons learned from the pandemic that would be useful to implement now in your office and/or home, depending on need and available financing.

I'll keep my eye on all these shadows, but in the meantime I'm turning my attention to a more practical matter of my carport's battle with carpenter bees. Listen to the soundtrack in the link, it sounds like it came from a bad horror film.

Unless otherwise indicated, the content and opinions expressed on this web site are those of the author(s). They are not endorsed by and do not necessarily reflect the views of the George Washington University.
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