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Tag: RSV vaccine

Published on Leave a comment on Settling Into Winter

I'd been spared from most snow shoveling due to mild winters the past few years. Fortunately, this week I discovered that my outdated acetaminophen still seems to work.

Artificial Intelligence for Pediatric Infectious Disease Diagnosis

Investigators at Baylor College of Medicine (bias alert: my alma mater) developed an interesting method to distinguish the covid-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from endemic typhus, the latter enjoying a bit of a resurgence in south Texas. The rest of us don't have reason very often to consider these 2 entities together since endemic typhus (aka murine or flea-borne typhus) is pretty rare in the US beyond southern California, southern Texas, and Hawaii. However, the results from this preliminary study serve as a proof-of-concept model for other diseases. The methodology is very complex, to say the least. Briefly, they looked at electronic medical record data over a 2-year period for anyone being tested for Rickettsia typhi, the etiologic agent for endemic typhus, or having a rheumatology consult request for MIS-C. All of the typhus-positive patients and a subset of MIS-C patients were included in a preliminary dataset for the AI modeling. A large number of patient variables were tested in an iterative process to come up with a preliminary scoring system which was then validated on another MIS-C patient set. The final scoring system included 15 variables: age of patient, duration of fever, height of fever, highest heart rate, neutrophil to lymphocyte ratio, AST, ALT, sodium, troponin, BNP, fibrinogen, epidemiologic link to COVID-19 case, antecedent illness, conjunctivitis, and rash. The authors claimed their scoring system correctly classified all 220 patients in their training dataset (100% accuracy) and was 99% accurate in the 160-patient MIS-C cohort used as the validation dataset. Of course we still need further evidence that this works well in other settings and institutions. I hope the AI and machine learning process itself, so far published only as a preprint, can be applied to other clinical situations.

Another Tick-borne Virus

Speaking of vector-borne infections, now researchers in China report a novel virus from the Nairoviridae family was found to be a cause of febrile illness in 26 of 252 febrile patients tested in northeastern China. They named it XCV (Xue-Cheng Virus) after the geographic site. (IMHO, I wish we could get away from naming diseases according to a geographic site, it just encourages xenophobia.) They also found evidence that XCV caused cytopathic effect in vitro and was present in 3-6% of ticks in the area. They authors don't provide much clinical information about the cases, and a link to a supplementary appendix didn't contain any more details. Overall it does appear this is a new infectious pathogen.

If you never heard of nairoviruses, don't feel bad. Some infectious diseases physicians may be aware that Crimean-Congo hemorrhagic fever virus is the main human pathogen in this family.

Chronic Wasting Disease

I don't think I've ever mentioned CWD in these pages previously. It is a fatal neurodegenerative disease seen in cervids (deer, elk, moose, reindeer) and caused by an infectious prion. I've been watching reports about spread of CWD in the US and across the globe for many years. I mention it now because of the publication of a new report from CIDRAP concerning for potential for spillover into other species, including humans, similar to what has happened in humans with Creutzfeld-Jakob Disease, kuru, and bovine spongiform encephalopathy (mad cow disease). Here's the North American distribution of CWD.

CWD has been expanding in numbers and in geographic areas in the US the past 20 years, increasing the possibility of spillover into humans. The CWD prion can remain intact in the environment for years, and prions are not inactivated by cooking infected meat.

The report maps out several recommendations for monitoring this situation; the recommendations bullet list alone takes up 5 pages of the 102-page document. It's a good example of how to plan proactively, but of course implementation takes funding of public health endeavors.

Venison steak, anyone?

Good News in the Vaccine Department

Three quick comments on recent vaccine studies.

First, I was somewhat surprised to see a pretty good uptake of RSV prevention modalities for pregnant people and infants. In the 2023-24 RSV season in the Kaiser Permanente Northern California system, around 75% of at risk infants received protection either by maternal vaccination or nirsevimab administration after birth.

I'm hoping it is even better this season. Remember that Kaiser is a health system very well designed to deliver high rates of vaccinations and other preventive interventions to its subscribers. However, individual private medical practices can and should aim to achieve high rates of RSV prevention.

Another study provided more evidence that it is safe to administer 2-month vaccinations to hospitalized preterm infants. It was a randomized controlled trial of preterm (<33 weeks gestation) infants hospitalized at 3 NICUs and eligible for vaccination at 6 - 12 weeks of age. 223 babies were randomized to receive either 2-month vaccines or no vaccine and then monitored for 48 hours. The unvaccinated group of course could receive vaccines after this 2-day period. Although apnea was more common in the vaccinated group, it didn't appear to have any adverse effects.

The vaccines administered were PCV13, DTaP, HBV, IPV, and Hib.

The last vaccine study I'll mention is another estimate of flu vaccine effectiveness last year. Specifically, it looked at outpatients at least 8 months of age in 7 states that were part of a flu VE surveillance system. The target endpoint was outpatient visits with positive influenza testing. VE against any influenza illness was 41% (95% Confidence Interval [CI]: 32 to 49): 28% (95% CI: 13 to 40) against influenza A(H1N1)pdm09, 68% (95% CI: 59 to 76) against B/Victoria, and 30% (95% CI: 9 to 47) against A(H3N2). Protection was found in all age groups except for the 50-64-year-old group. Differences in age groups (and also related to influenza A subtypes) likely are related to imprinting, i.e. what flu strains people are exposed to early in life, but this study wasn't designed to answer this question.

WRIS

As we roll along in the winter respiratory infection season it's worth taking a look at where we are. CDC has some newer data for the "big 3" viruses in pictorial form. (See https://www.cdc.gov/flu-burden/php/data-vis/2024-2025.html, https://www.cdc.gov/rsv/php/surveillance/burden-estimates.html?ACSTrackingID=USCDC_2067-DM142871&ACSTrackingLabel=CDC%20Updates%20%7C%20New%20In-Season%20Estimates%20of%20COVID-19%20and%20RSV%20-%201%2F7%2F2024&deliveryName=USCDC_2067-DM142871, and https://www.cdc.gov/covid/php/surveillance/burden-estimates.html?ACSTrackingID=USCDC_2067-DM142871&ACSTrackingLabel=CDC%20Updates%20%7C%20New%20In-Season%20Estimates%20of%20COVID-19%20and%20RSV%20-%201%2F7%2F2024&deliveryName=USCDC_2067-DM142871.)

Note that the influenza numbers include 2 weeks longer than for RSV and covid. I did a quick calculation of death rates per illnesses for each, using the midpoint of the ranges: influenza 1.3 deaths/1000 illnesses, RSV 2.5, and covid 3.1. Of course these are all ballpark estimations but still show that infections with any of the big 3 are worth preventing.

Here's the most recent look from FluView, which captures respiratory illnesses other than influenza.

Still hoping that flu and RSV reach their peaks before covid ramps up.

Español en la Nieve

My shoveling activities were greatly enhanced by one of my new neighbors, a 3-year-old boy who just moved here from Colombia and only speaks Spanish. I'm forever embarrassed by the fact that the Spanish I've retained from my south Texas childhood can't be used in polite company, but my new friend was speaking his native tongue to me while we shoveled together. The upside if we have a heavy snow winter in Maryland is that I may develop new Spanish fluency!

Published on Leave a comment on Word of the Week: Conundrum

I was very underwhelmed by Oxford University's recently announced Word of the Year. Listening to last week's FDA VRBPAC discussion of RSV vaccines, another word kept cropping up time after time. More on that later.

Covid Updates

I had mixed feelings when I learned that the Netherlands had started a Long COVID Kids Choir, apparently also active in the UK and the US. On the one hand, it's great that these children have on outlet to express themselves, but on the other hand it reminds me how little we know about this condition.

On a more uniformly upbeat note, new data are available for effectiveness of the Pfizer XBB vaccine in children 5 - 17 years of age. This was a retrospective study from Kaiser Permanente Southern California looking at acute respiratory infection visits from October, 2023, through April, 2024. Because of the study design (standard test-negative case-control study) we only have odds ratios to describe results; number needed to vaccinate can be estimated from odds ratios with fudge factors, but I'm reluctant to go there. Here's the summary:

Basically, the vaccine was very effective in preventing hospital admission and ED/urgent care visits in this age group.

Temporal Thermometers Not the Greatest

Temperature measurement using temporal thermometers is pretty much a tradeoff - convenience versus accuracy. A new study from 5 EDs in a single system (apparently Mass General but hard to tell from the article) looked at around 1400 children who had both temporal and oral or rectal temperatures measured at the same time (within 30 minutes). The findings are summarized here; note mean discordance of about 1.5 F. Researchers found that age < 12 years was was associated with discordance.

The authors found that self-reported race was not a risk factor, important because skin color could plausibly affect temporal measurements. As an interesting aside, Black children were more likely to have temporal temps only, even correcting for severity of presenting complaint.

Avian Flu

I'm keeping a wary eye on new progress, mostly because I'm worried that not enough resources are being devoted to monitoring the situation. One new report provides helpful information. Two dairy farms voluntarily allowed investigators to look at prevalence and spread of influenza A H5N1 in their settings. Here's the "graphical abstract::

The authors mention the rarity of these types of studies possibly due to farm owners' worries about harm to their businesses from publicity about avian flu spread in their dairies.

CDC provided genetic sequencing information about the virus infecting the child in California who apparently has no known avian flu exposure risks. Analysis suggested that the strain was very similar to those previously seen in dairy and poultry farms as well as in humans, but they were unable to perform complete sequencing that could have allowed further tracking of the source of this child's infection. I guess due to privacy concerns, we have very little clinical information about this case. I'm even wondering how the child's strain came to be tested for H5N1 in the first place since not every influenza A detection undergoes further testing.

Regardless of uncertainties, these most recent reports do not suggest we need to heighten concern for human to human transmission of A H5N1.

DRC Mystery Disease

Shortly after my post last Sunday, WHO released a new update with a few more details but still no big findings. I can't even find their case definition anywhere. The initial statements that respiratory symptoms predominated would seem to make malaria, where positive tests have been seen in preliminary testing, a less likely explanation. Malnutrition seems to be a significant risk factor.

WRIS

Winter Respiratory Infection Season continues to mount with moderate level activity in the US driven primarily by RSV.

Epidemic trending (modeling data for predictions, from the same link as above) shows continued growth for covid ...

.... and especially for influenza.

It's still not too late for flu vaccine. Expect a surge soon if not already started in your area.

RSV Vaccine Conundrum

I was glued to my screen for much of last Thursday's FDA VRBPAC meeting, with the majority of the session devoted to discussion of pediatric RSV vaccine progress, or lack thereof. As I've mentioned in previous posts, RSV vaccine development for children was set back by a tragic trial in the 1960s where vaccine-associated enhanced respiratory disease (VAERD) resulted in 2 deaths of children who received vaccine and then subsequently were infected with wild-type RSV the following season. Through many scientific advances over the years, researchers determined that the cause of this enhanced disease was immunologic in nature, related to the vaccine causing recipients to develop a strong cellular immune response involving a specific class of T cells (Th2). This finding even influenced development of the mRNA covid vaccines which deliberately avoided this and ensured a Th1-predominant response and very safe vaccines.

Unfortunately, recent experiences in trials for Moderna RSV vaccines suggested that VAERD might be occurring in children under 2 years of age. Moderna was developing 2 mRNA RSV vaccines, 1 for RSV alone and another that also incorporated a human metapneumovirus vaccine. They were enrolling children in a phase 1 study this summer when the concerning signal arose. I am including slides from the FDA presentation. Here's the study overview and timeline of events this summer, from slide numbers 11 and 12.

I included the above to demonstrate that the safety constraints incorporated into the study worked exactly as intended. Enrollment was paused pending evaluation of the events, which is still ongoing. The imbalance between vaccine and placebo recipients is highlighted below:

Note the small number of children in the study, appropriate and typical for phase 1 trials. However, that makes analysis more difficult. I'll cut to the conundrum chase. Preliminary immunologic studies from patients in the Moderna trials suggest that the vaccine, as planned, produced Th1-predominant responses, and that the mechanism of the possible VAERD events is not due to Th2-primed cells. Furthermore, other immunologic data don't provide another plausible information for why this happened.

Of course, with so few trial subjects, it's possible that this imbalance of severe disease could be due to chance alone. Regardless, Moderna officials announced that they would be abandoning the mRNA RSV vaccine development but will continue to follow all the children already enrolled in their studies and perform further immunologic and other testing.

So, where does that leave us with RSV prevention? This took up much of the VRBPAC's discussion time. It's important to understand that the Moderna RSV vaccines were part of a larger group of pediatric RSV vaccines in various stages of development, 26 in all. Fifteen of these are live attenuated vaccines, and it should be noted that live-attenuated vaccines have never been shown to result in VAERD, with extensive validation for why that hasn't occurred. (I might add that your dog's kennel cough vaccine might contain one of these. Although Bordetella bronchiseptica is the most recognized cause of kennel cough, canine adenovirus - 2 and parainfluenza virus 5 are other common causes of kennel cough and also have been included in some intranasal dog vaccines for decades. Presumably most of us have been exposed to our dogs' live attenuated vaccine PIV5 strain many times, yet no human VAERD involving parainfluenza virus has ever been described.)

It is likely that future pediatric RSV trials will need to be judged on an even more individual basis, perhaps with separate constructs governing the various platform differences (live attenuated, viral-vectored, mRNA if anyone moves forward with this, and subunit protein) as well as mode of delivery - mucosal (intranasal) versus systemic by injection. In the meantime, we know that maternal immunization is highly effective, as is the infant monoclonal antibody nirsevimab. In that light, we also need development of newer monoclonal antibody products in case nirsevimab resistance appears, as well as better maternal vaccines that won't be so limited in timing of administration during pregnancy. Work is ongoing in all of these venues.

Conundrum

Of course I had to look into the origins of the word, but it turns out there is a lot of disagreement about this. I was most delighted to see the word explained as a "burlesque imitation of scholastic Latin." I was unaware that it was the title of a Jethro Tull instrumental song (I'm not much of a Tull fan) and an episode of Star Trek: The Next Generation (I am a fan, but don't remember the episode).

Have a great week, and don't forgot to offer flu and covid vaccines to your patients and families.

Published on Leave a comment on Welcome to Our 10th Month!

The first of the month happens to fall on a Sunday, the day I put together my weekly post. I am transiently aware that the root word for December derives from the number 10 yet persists as the name of what is now our 12th month. Having nothing better to do while trying to digest my Thanksgiving excess of wonderful food, I decided to refresh my memory as to how this rather bizarre nomenclature has persisted.

Meanwhile, the CDC had a nice Thanksgiving recess and thus will not have any new updates on the winter respiratory infection activity until December 2. I can only report anecdotally that RSV season is in full swing in the Washington, DC, metropolitan area, with little in the way of influenza or covid cases. Still, there is lots to talk about from last week.

A Rare Mention of Early Phase Studies

I don't often mention results from phase 1 or phase 2 human trials; the studies are important but the findings aren't immediately transferable to clinical practice. Generally we need to wait for phase 3 trials to be completed so that we know how effective the intervention is likely to be. However, I couldn't hold myself back from these 2 reports because of the novel approaches and the likelihood that they represent what the future will look like.

The first report is of bacteriophage therapy for infections caused by multiply-resistant bacteria. Clinicians may recall that bacteriophages are viruses that exclusively infect bacterial cells and can destroy them. Bacteriophage use for treating infections resistant to all known antibiotics isn't new, it's being used by most tertiary medical institutions for the past few years at least. It requires painstaking hunting for a bacteriophage that is effective for the particular patient's infecting bacterium. What was enlightening to me was how CRISPR technology was used in this phase 2 trial to custom-design a bacteriophage, in this case for use in E. coli urinary tract infections. The resulting product is, unlike classical therapeutic bacteriophages, independent of the infecting organism's susceptibility pattern and can be used off-the-shelf, eliminating a patient-specific and very expensive, cumbersome, time-consuming search for an effective phage. Note, however, this still is a fairly cumbersome therapy. The actual treatment consisted of 2 days of intraurethral and 3 days of intravenous phage therapy, plus oral trimethoprim-sulfamethoxazole. The subjects were all adults and numbers were small, but relatively good responses were seen in the treatment groups.

A second part of the phase 2 trial is underway and one hopes we will see further results from this trial.

The other preliminary study is a phase 1 trial of a diphtheria antitoxin (DAT) developed as a monoclonal antibody. Currently DAT is an equine antibody and is in short supply worldwide. Having a ready supply of human monoclonal antibody could alleviate the shortage plus reduce the allergic reactions related to use of horse serum. In 41 adult subjects in this trial, the monoclonal product produced higher neutralizing antibody concentrations than that seen with the equine DAT and strongly suggests that it will be highly effective. Needless to say in our rapidly-advancing anti-vaccination environment, this could be an important advancement not just in resource-poor countries but also in the United States as well.

Tonsillectomy for PFAPA

Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenopathy syndrome has been one of the dilemmas of my clinical practice for decades. It is likely a genetic periodic fever syndrome, but no precise gene mutation has yet been identified and thus there is no definitive diagnostic test available. PFAPA eventually resolves spontaneously with no known clinical sequelae. If all of the clinical components are present, the diagnosis is fairly easy, but likely there are variants of this syndrome, including those presenting with periodic fever alone. Tonsillectomy was effective in a randomized controlled trial but usually is employed only after other, simpler, therapies fail. Now we have an observational study on long-term (median 8.8 years) follow-up of 86 children in Sweden who underwent tonsillectomy for PFAPA. Entry criteria required periodic fever with at least 1 other finding of aphthous stomatitis, cervical lymphadenitis, or pharyngitis as part of their usual symptom complex. Here's the bottom line in (not pumpkin) pie format:

This information will be helpful in discussing treatment options, but it should be noted that, because this is a genetic disease that could have multiple gene variants, results may not be applicable to other populations beyond this Swedish cohort. The authors did not report the subjects' racial or ethnic backgrounds.

Parvovirus B19

Last week the CDC gave us a bolus of reports on parvovirus infections in MMWR. In a study of clinical and donor plasma testing in 2024, the percentage of samples showing positive parvo B19 antibody and/or PCR showed a significant jump. Below are the results for PCR testing of blood donor plasma.

In addition to the above, this MMWR issue also had 2 other parvo B19 reports focusing on high risk populations. Aplastic crises in sickle cell disease patients showed an upswing in an Atlanta children's healthcare organization:

Another report focusing on pregnant people in Minnesota this year showed increases across younger age groups:

Five laboratory-confirmed infections occurred in pregnant people at 13 - 20 weeks gestation, with the following characteristics:

Perhaps this is all part of the "immunity debt" catch-up we are seeing in so many infections occurring post-pandemic. Pregnant people often are infected by their own school-aged children. A good time for clinicians to brush up on parvovirus B19.

Cost Effectiveness of RSV Prevention

I've discussed how covid vaccination recommendations vary by country, such as the UK restricting vaccination of lower-risk groups due to cost concerns even though being vaccinated has lower risk of sequelae than with natural infection in these groups. Now we have some numbers for RSV prevention through maternal vaccination or with administration of monoclonal antibody to infants, courtesy of 2 CDC-funded analyses.

For maternal immunization during weeks 32-36 gestation, incorporating various estimates of newborn outcomes and maternal side effects from vaccination, vaccination of mothers year-round cost $396 280 per quality-adjusted life-year (QALY) saved. If vaccination were limited to the September through January period, the cost dropped to $163 513 per QALY saved. Changing various inputs to the model resulted in ranges from a net cost savings up to $800 000 per QALY saved.

For infant nirsevimab utilization using similar analyses and looking at single RSV season benefits in infants 0 - 7 months and 8 - 19 months of age, assuming half the US birth cohort received nirsevimab, cost savings were $153 517 per QALY saved. "Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved."

Clearly the costs to society vary widely depending on what assumptions are made for effectiveness, outcome rates, and costs of product and hospitalizations, etc. As noted in the accompanying editorial, these costs are so high because the products themselves are very expensive, much more so than our other vaccines. If nirsevimab were to cost $50 instead of almost $500 per dose this would certainly be a net savings to society, but don't hold your breath for the cost to decrease anytime soon. Still, both of these products have very high clinical effectiveness, and pediatric healthcare providers should provide nirsevimab to all eligible infants whose mothers did not receive RSV vaccine during pregnancy.

Hiding in Plain Sight

Somewhere buried in the back of my mind is the fact that the word December contains the Latin root for 10, decem. This dates back to about 750 BCE and the calendar of Romulus, the first king of Rome. The calendar had only 10 months, starting with March and ending with December, with some sort of in-between period that became January and February during the reign of the next king, Numa Pompilius, who took over in 715 BCE. Various rearrangements appeared over the next few centuries. What I should have known but didn't, September, October, and November kept their names derived from the Latin names for numbers 7, 8, and 9. So, we're stuck with outdated names for 4 of our months that date back to use during a brief 50-year period occurring almost 3 centuries ago.

Also, I'd be remiss if I didn't report back to you about the Wiedermann Thanskgiving Massacree of 2024; thankfully, there was none. The most amazing thing that happened was that for the first time in modern history, not quite dating back to Romulus, I didn't make a written minute-by-minute oven and stove schedule for Thanksgiving day. Such activity was rendered moot largely because the 3 primary cooks (my sister-in-law, my wife, and me) were too organized from the start. It was a breeze, except for a brief cursing episode by yours truly when a new bird-carving technique proved to be less than desirable.

Happy 10th Month.

Published on Leave a comment on Spring is … Springing

I actually had to pull out the lawnmower this week, to cut some weedy grass running amok in the yard. Nonetheless, I'm buoyed by the approach of the vernal equinox next Tuesday, the official start of spring. Winter will be done, and with it the winter respiratory viruses. They will reliably be replaced with spring respiratory viruses.

Here's a look at the pediatric infectious disease news the past week.

Details on the Failed GSK RSV Vaccine Trial

We've known for about a year that GlaxoSmithKline's RSV vaccine trial in pregnant people was stopped due to safety concerns: a higher rate of preterm births in the vaccine group compared to placebo. Now we have more details, similar to what was reported to FDA and shared in various meetings. Preterm birth rate was 6.8% (237 of 3494 infants) in the vaccine group and 4.9% (86/1739) in the placebo group; it was statistically significant. Neonatal mortality was higher in the vaccine group, 0.4% versus 0.2%, but did not reach statistical significance.

On the other hand, vaccine effectiveness was pretty good:

The currently approved maternal RSV vaccine from Pfizer also had a hint of a safety signal for preterm birth, less so than the GSK product, and these signals combined resulted in the Pfizer vaccine being approved for a later time in gestation, at 32 weeks at the earliest. Postmarketing surveillance is ongoing. Perhaps the most difficult part of assessing this safety signal is whether it is real or not. We are lacking a key factor in making this assessment: biologic plausibility, i.e. the mechanism by which these vaccines might cause preterm birth. Without that, it is still possible this represents just a chance observation. From my perspective, I would still encourage RSV vaccination for pregnant people as well as nirsevimab therapy for at risk infants born to unvaccinated mothers. We have time for more discussions of any new data prior to our next RSV season this fall.

Waterborne Disease Outbreaks Associated With Drinking Water

I'm a big fan of CDC's Surveillance summaries, and this one published last week is of interest. The report concerns 214 outbreaks from 2015-2020. I wasn't thrilled to see my home state represented prominently.

Outbreaks occurred year-round, and biofilm exposures predominated.

In case you aren't familiar with biofilm-associated outbreaks, here's the quick explanation from the text:

"...microbial communities that attach to moist surfaces (e.g., water pipes) and provide protection and nutrients for many different types of pathogens, including Legionella and NTM [non-tuberculous mycobacteria]... Biofilm can grow when water becomes stagnant or disinfectant residuals are depleted, resulting in pathogen growth... Furthermore, biofilm pathogens are difficult to control because of their resistance to water treatment processes (e.g., disinfection)... Exposure to biofilm pathogens can occur through contact with, ingestion of, or aerosol inhalation of contaminated water from different fixtures (e.g., showerheads) and devices (e.g., humidifiers)..."

Not to minimize the severity of these events, but I couldn't help thinking about a whole new version of Hitchcock's Psycho shower scene based on this.

Legionella was by far the most common pathogen. The report has detail on every outbreak by year and location, as well as a listing of contributing factors. It's a great roadmap for future prevention.

Measles (Again)

It seems like I could devote every week's post entirely to measles and not run out of things to say. Here's the current US situation.

As I've stated previously, it's the sheer number of unconnected sites that concerns me now. Let's put this into some perspective.

As of March 14, we have 58 cases reported from 17 jurisdictions. In all of 2023, we had the same number, 58, reported from 20 jurisdictions in the US. So, we're way ahead of the game for recent years, but we're also not breaking any records compared to pre-pandemic times.

Looking more closely at the 2 biggest years recently, the 2014 (and somewhat 2015) numbers had a large contribution from a single site, Disneyland. More impressively, the 1274 measles cases in 2019, the highest number in the US since 1992, largely involved orthodox Jewish communities in New York - relatively epidemiologically isolated communities with very low immunization rates. A CDC update in fall 2019 (I couldn't find a final tally) stated that 75% of cases for the entire country that year originated from these communities.

Fingers crossed that we don't eclipse the 2019 figures this year, but with reduced vaccination rates and already widespread measles transmission occurring, it doesn't look good. We're just now coming to the spring break and summer travel season - importation of measles from travelers has been a large contributor to US measles outbreaks in the past.

Pediatric Covid ICU Admissions

A recent report of registry data from 55 hospitals during the first almost 2 years of the pandemic showed that about 8% children <21 years of age admitted to intensive care with covid had immunocompromising conditions (ICC). Secondary bacterial infection was more common (9.5% versus 7.3%) and mortality (11.4% versus 4.6%) was higher in the ICC group.

That Pesky Flu

The map is getting a little greener, apropos of springtime. Note in the link you can animate the map to show progression from the fall to the current week.

Better seen here, we did experience a little pause in our decrease of ILI, now headed down but at 3.7% still above the official "epidemic is over" mark of 2.9% for this year.

Any Chipmunk Sightings?

My 2024 Farmer's Almanac says that the real harbinger of spring in the eastern US is the appearance of the eastern chipmunk (Tamias striatus) above ground. As opposed to their squirrel brethren, chipmunks at my house don't bother my bird feeder, so I'm OK with them. I learned that although they stay below ground for the winter, they aren't true hibernators but rather experience torpor. They may sleep for several days in their bedrooms, followed by a trip to the underground pantry for snacks. Sounds like a good plan for retirement.

Published on Leave a comment on I’m Optimistic

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.

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