nirsevimab – Pediatric Infection Connection

Meh

Bud WiedermannJune 30, 2024June 30, 2024Leave a comment

I had expected last week's ACIP meeting to include more presentations and discussions about which covid strain to include in our fall vaccine. I viewed only a small portion of the meeting live (darn those pesky patient care issues!), so I probably missed any brief mention of strains; the slides themselves didn't address strain selection, other than to go with the FDA's statement for use of JN.1 lineage with preference for KP.2 if possible. I still found some interesting details about covid and nirsevimab and will share those with you. Perhaps meh is a bit of a harsh judgement, but I love the word.

In the meantime, thankfully still not much going on in the pediatric infectious diseases world this summer.

Love That New Technology

The CRISPR technology has been in the news for a long time. In case you had forgotten, like I did, it stands for Clustered Regularly Interspaced Short Palindromic Repeats and is now reported to have high sensitivity and specificity for detecting antiviral drug resistance and influenza subtype rapidly enough to be used as a point-of-need assay. The study itself requires journal subscription (thank you, GWU faculty status) to read in full. Investigators studied influenza isolates from the 2020-21 season looking primarily at AH1N1 and AH3N2 strains. The report is highly technical, beyond my ability to critique the laboratory methods, but the take-home message is important: if such a method is scalable (e.g. cheap enough) to employ across the world, including in resource-poor communities, it would be a boon to early warnings of resistant and/or new flu strains. I'm keeping my fingers crossed.

I must applaud scientists in this realm for their acronym constructions: in addition to CRISPR and others, they also used DETECTR (DNA endonuclease-targeted CRISPR trans reporter) and SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assays. Elementary, my dear Watson. (And, that phrase never appeared in any of Arthur Conan Doyle's writings!)

Dengue HAN

Perfect timing after my mention of dengue last week, the CDC issued a Health Alert Network warning about dengue in the US. According to the Pan American Health Organization, early signs are that cases in the Americas this year will exceed last year's numbers, a year that was already much higher than previous years. Here's an example from the report of what's going on in the Caribbean subregion:

Puerto Rico is under a healthcare emergency because of dengue, and we will certainly have cases of autochthonous (acquired in the US without travel to an endemic area) transmission in the mainland US again this year, primarily in Florida and other southern states. The HAN is worth reading.

This would be a good time to review clinical presentations of dengue and be prepared to investigate/obtain consultation for suspected cases.

Pustules and Vesicles in Afebrile Infants <60 Days of Age

Pediatrics had a nice retrospective review of 183 infants from 6 academic hospital-based pediatric dermatology practices. It's open access and has a nice suggested management algorithm.

Note the first branch in the algorithm details key features to decide whether HSV evaluation and treatment is recommended.

ACIP Meeting Highlights

The regular meeting was spread over 3 days last week. Slides are posted, and I picked out a few that contained interesting new information.

First, even with all the problems of supply chain and late administration, nirsevimab appears to have been incredibly effective in preventing RSV hospitalizations and healthcare visits.

Yes, that's about 98% effectiveness in preventing hospitalization, with very narrow confidence intervals. When this slide was shown it elicited a round of applause from the committee members. This is truly remarkable. Similar results were seen using a different RSV surveillance method. Both the above and below slides are from the Payne presentation on June 28.

It appears we'll have better availability of nirsevimab for the next RSV season, so please prepare for that. I find myself fantasizing of some future day when new pediatric trainees won't see hordes of infants hospitalized with RSV bronchiolitis, with worried parents at the bedside.

Second, although I mentioned I didn't see any new data/discussion about strain selection, the covid vaccine discussion had useful updates about epidemiology and risk factors, mainly from the Haver presentation on June 27.

About half of children hospitalized for covid had no underlying risk factors; we already knew that, but here's a more detailed breakdown. Note that these numbers are for the past year, at time when virtually all US children had some prior antibody from infection and/or vaccine.

Here is the vaccination status, including the low numbers who received the 2023-24 version, of the hospitalized children:

One BIG disappointment for me with the presentations: there was no mention of a control group - i.e. what are the rates of underlying medical conditions and 2023-24 vaccine status in the pediatric population as a whole? Adjusting for rates in the general population would provide a better estimate of the relative contributions of risk factors and vaccination to more serious outcomes and give us a better handle on the magnitude of benefit of vaccination, for example. Still, nothing has changed; for the individual child, covid vaccination is better than not being vaccinated, even factoring in the low rates of serious outcomes and adverse vaccine events in children.

The 2023-24 vaccine was highly effective against emergency department and urgent care visits in all age groups, though waning of protection over time was seen. Lack of enough events of hospitalized children precluded reliable estimates of VE against pediatric hospitalizations. (Link-Gelles presentation June 27.)

Bird Flu

Exciting (to me) news that CDC is collaborating with the Michigan health officials to carry out a seroprevalence study for H5N1 infection in Michigan dairy workers. This should produce much better information about asymptomatic and mild infection in humans and possibly lead to more clues about transmission.

Covid Uptick?

Still a question, but positive test percentages are increasing, albeit at a low level and predominantly driven by western states.

Wastewater variant detection is lacking across the country, see all the block dots (no sequencing data) below, but you can magnify your area of the country and find a few sites with enough data to determine predominant covid strain.

For example, in my neck of the woods most of the sites have no sequencing data. Of the 2 that did, one showed a predominance of KP.2 and the other LB.1. Nationally, KP.3 is starting to exceed KP.2. Again, we're still at low numbers.

A Tip of the Hat to "The Simpsons."

I knew that "meh" might have been adopted from a Yiddish term meaning so-so or unimpressive, but it looks like a 1994 episode of the TV series The Simpsons, featuring ultraconservative Sideshow Bob, popularized the term. Lisa Simpson was investigating voter fraud as the reason Sideshow Bob was elected as Springfield's mayor, and the "meh" word was uttered by a Hall of Records bureaucrat when Lisa expressed disbelief that he would give her the entire mayoral voting records that should have been kept secret. (Thie episode is available only with subscription, but I verified the quote at about 15:30 time in the recording.)

Voter fraud 30 years ago?

Are You an Owl or a Lark?

Bud WiedermannMarch 10, 2024March 10, 2024Leave a comment

Another round of Daylight Saving Time. I came across a new article suggesting that potential harms of DST depend on your individual chronotype, or, more simply, whether you are an owl or a lark. I definitely fall into the lark category. More on this later, but let's dive into what's been happening in pediatric infectious diseases the past week.

New IDSA Laboratory Test Guidelines

Just out is an updated guideline from the Infectious Diseases Society of America. It might be my favorite guideline of all time, but at 244 pages I recognize it's not for everyone. Let me mention a couple items that I notice some frontline healthcare providers may not know about but are important to avoid misleading test results (a garbage-in-garbage-out scenario).

First concerns the use of swabs, starting on page 8 of the pdf guideline document. Always use a swab for sampling throats, conjunctiva, superficial wounds (aerobic culture only), some nose, nasopharynx, and vaginal testing, and sometimes in special circumstances related to institutional- or manufacturer-related instructions for the product. Never use a swab for surgical tissue - submit the tissue itself making sure it doesn't dry out before processing. The same applies for "respiratory fluids and secretions, endophthalmitis and keratitis, nasal sinus, otitis media, biopsy, abscess fluid, fungal and acid-fast bacilli specimens, formed stool, epiglottitis, diarrheal illness, and when anaerobes are suspected opt for tissue or fluid in anaerobic transport... Never submit a swab for analysis that has been dipped into a fluid or exudate. Send an adequate volume of the fluid or exudate instead." There's also an in-between situation where larger volume sampling isn't feasible, such as with an open wound (at least obtain a needle aspirate of leading edge).

The second pertains to urine specimens, the bane of my existence when consulting on possible UTI based on specimens that have sat around for considerable time before processing, such as placed in a lab collection box in an outpatient setting. Some key points, starting on page 119: "Urine collected for culture should not be kept at room temperature for more than 30 minutes. Hold at refrigerator temperatures or utilize a preservative tube if not processed by the laboratory within 30 minutes." The authors also mention the perils of relying on urinalysis because techniques have not been standardized and often require subjective interpretation. Especially if you are dealing with a child with possible UTI, obtain a good mid-stream voided or catheterized urine specimen and, again, don't let it sit at room temperature too long before analysis.

Different considerations arise when sampling urine for sexually transmitted infection - here, the first portion of urine voided is best for detecting pathogens by nucleic antigen amplification testing.

Speaking of Throat Swabs

The biggest problem in diagnosis of streptococcal pharyngitis is performing throat testing in children highly unlikely to have streptococcal pharyngitis. In this setting, a positive result is much more likely to represent a clinically-irrelevant carrier state and result in unnecessary antibiotic exposure for the child. Some heavy hitters in the group A streptococcal world published a review on this recently, but unfortunately it is not available without subscription to the journal. The authors describe differences in GAS testing between the US and Europe, compare and contrast rapid antigen detection and NAAT testing, and again mention situations where testing should not be performed: children less than 3 years of age unless known exposure, children with signs of viral infection including cough, runny nose, or hoarseness, and absence of "bona fide" clinical suspicion for strep throat if you use a clinical scoring system such as Centor or McIsaac.

Nirsevimab Worked Liked We Hoped

Nirsevimab effectiveness was 90% in preventing hospitalization for RSV infection in infants during their first RSV season, according to CDC data on 699 hospitalized infants. This is actually at the upper end of the confidence interval from prior clinical trials.

AI for Otitis Media

I seem to be on a track of personal banes of my existence as a consultant; misdiagnosis of acute OM is near the top. Although I don't see any of us being replaced by artificial intelligence anytime soon, a new report has some glimmer of hope that it might help us with AOM. It uses a not-yet-available iPhone app with an otoscope; you can use voice to control when to take a photo. Watch the video (at the link to the article, not in the screenshot below) to get an idea of what's involved. It's not nearly ready for prime time, but stay tuned.

Is Covid a Risk for Development of Autoimmune Rheumatologic Inflammatory Disorders?

This study of millions of adult patients from Korea and Japan utilizing a claims database would suggest that it is, with adjusted hazard ratios around 1.25 - 1.3. So far this is just an association and does not determine causality. Also, genetic risks for autoimmune disorders differ in Asian versus US populations (think Kawasaki Disease), so the results may not be broadly applicable.

Influenza is Still With Us

I've officially retired my WRIS (Winter Respiratory Infection Season) section. Really we're only waiting for flu to wind down, though we still have too many covid hospitalizations and deaths. Here's the most recent Fluview map, looking a little more encouraging:

In the meantime, the FDA VRBPAC met on March 5 to officially recommend trivalent vaccines for next fall. The disappearance of the B/Yamagata lineage means we won't need a quadrivalent vaccine as in past years. Next up is CDC/ACIP recommendation in June.

Medical Injustices in the Past

It was painful for me to read, but I highly recommend the NEJM series highlighting medical injustices and biases perpetuated in its publications. The current article is about eugenics. Apparently there were a few voices trying to speak up against these practices in the early part of the 20th century, but they were drowned out by the majority, many of them physicians. You don't need a subscription to the journal for this series.

My Inner Lark

On a lighter note, I was delighted to learn that I might not be at such high risk for adverse events of Daylight Saving Time. A recent study looked at the effects of the DST change on sleep and work productivity in 155 full-time workers in Germany utilizing survey methodology. The effects varied with individual chronotype; that is, the "owls" are those that tend to stay up and wake up later than "larks," the early to bed and early to rise group. There's actually a tool to determine chronotype! The study found that us larks are less affected by the shift to DST.

Lots of evidence exists that the DST shift is associated with harmful effects, from medical illness to car crashes to work productivity. However, this is an extremely messy phenomenon. We have good evidence that the shifts are associated with poor circadian rhythms, a biologic plausibility for harmful outcomes, but only an epidemiologic association with these bad outcomes. With too many factors that can't be controlled or accounted for, probably the only way we will know if DST is bad is if the bad outcomes lessen when we quit using DST. I recall 2 prior instances where an epidemiologic association was likely confirmed to be causal: the association of aspirin use with Reye Syndrome in children, and the association of infant sleeping position with Sudden Infant Death Syndrome. The aspirin industry fought against the concept, but Reye Syndrome essentially disappeared when aspirin use for symptom relief in young children ended. SIDS rates plummeted with the Back-to-Sleep programs.

I don't recall ever seeing a lark, but apparently a subspecies of horned lark inhabits Maryland. I guess I'll need to rise early to spy one.

From CornellLab All About Birds.

Another Strange Case of Dr. Jeckyll and Mr. Hyde

Bud WiedermannFebruary 25, 2024February 26, 2024Leave a comment

Maybe chalk it up to old age. Last week I mentioned I'd be reporting on the ACIP meetings, not remembering that they are scheduled for the coming week, not last week.

Still, plenty going on to fill in with, including a strange case I've been investigating for a few weeks now.

New Adult C. difficile Fecal Transplant Guidelines

The American Gastroenterologic Association published new guidelines for use of fecal transplant in adults with C. difficile disease. Although the guidelines do not address pediatric issues they are still useful to consider. Looking at just the summary, fecal microbiota transplant therapy is being recommended for instances of recurrent disease in immunocompetent or mild/moderately immunocompromised individuals, as well as for severe or fulminant infections in individuals not responding to conventional therapy, Fecal transplant use is not recommended for those with certain underlying GI conditions such as ulcerative colitis, Crohn's disease, pouchitis, or irritable bowel syndrome, except as part of clinical trials. I noted that all of the recommendations were conditional with low or very low level of evidence.

Conflicting Nirsevimab Data

The headlines screamed that about 40% of eligible infants received nirsevimab prophylaxis for RSV infection, as of last month, which is much higher than I had thought based on reports and the shortage of the product. On closer examination, it may not be all that good. There are actually 2 sets of information that the CDC published. First is reporting of ongoing telephone surveys of households with infants under 8 months of age, asking if those infants have received nirsevimab or are planning to do so. That's where the 40% figure comes from. The second data source is an ongoing count of nirsevimab doses actually administered. The listing includes jurisdictional data up through December 2023. Here the highest rate is 20% (Alaska) with many states near zero. Presumably this latter count is more accurate than is self-reported survey data. Let's hope things improve next season, where it does appear that supply chain issues that caused so much disruption this season might be somewhat ameliorated.

Also on the nirsevimab front, I saw the first semi-detailed explanation of what went wrong with the supply chain last fall. You recall, and probably experienced, difficulty in receiving an adequate supply of nirsevimab to satisfy your patients' needs. The company simply didn't have enough stock on hand. This Wall Street Journal report offered more information. It seems that, as usual, it was a bad combination of multiple factors. First, the manufacturer underestimated demand. Second, pediatric healthcare providers initially delayed ordering the drug, not sure if third-party payers would cover the circa $500/dose price. When the feds decided in August to add the product to the Vaccines for Children program, it was already too late to reverse the trend for lower production targets. Production was ramped up eventually, and now some states have excess product available due to all the delays plus perhaps some practitioners not being aware of the availability. RSV is still around but clearly nearing the end of the season. Let's hope things go better for next RSV season.

Risk Stratification for Pediatric Covid

The Pediatric Infectious Diseases Society published new guidance related to covid management in children and adolescents, worth reading. In particular, I think the group did a great job explaining risk factors for poor outcomes from SARS-CoV-2 infection. This has been confusing, in part because we lacked data but also due to spillover from adult high risk conditions - I've noticed many practitioners citing adult risk factors for use in the pediatric population, and it's not quite applicable in all situations. Here's the quick breakdown:

Not All Telemedicine is Created Equal

I've been involved with telemedicine since well before the pandemic. It has its uses, and of course it also has limitations. However, some individuals providing so-called telemedicine services are doing more harm than good. I was saddened but not surprised at this article about providing antibiotic prescriptions via telemedicine. The authors searched for online platforms offering antibiotic prescriptions without real time physician examination or verification of patient details and then chose 2 platforms to query.

For the first platform, one "patient" was able to get a prescription for amoxicillin for "URI," answering a few yes/no questions asynchronously and being rewarded with the prescription in less than a half hour. Another "patient" insisted on being prescribed levofloxacin for cough and again was rewarded the prescription with little verification or pushback.

On the second platform, a "patient" with URI was given a link to choices of azithromycin, cefuroxime, amoxicillin, Augmentin, doxycycline, or levofloxacin. After choosing doxycycline the prescription was provided immediately.

These patients were actually some of the study authors, and they had real URI symptoms. They didn't fill the prescriptions and did recover uneventfully from their URIs. I had 2 immediate reactions after reading the article. First, I wanted to cry. Second, I wondered where these telemedicine "doctors" obtained their medical training.

I Told You So

Some people preface that comment with "I hate to say it, but..." Not me, I'll grab credit even if, as in this circumstance, I'm not unique in sounding the measles alarm. The most recent update shows 35 cases in the 15 US jurisdictions this year, as of February 24. This many cases scattered over so many jurisdictions bodes poorly, and the scariest is in a Florida elementary school.

Dr. Ladapo and Mr. .....?

Dr. Josepah A. Ladapo sports both medical and public health degrees from Harvard, an internal medicine residency in Boston, followed by a faculty appointment at NYU. He than transitioned to a mostly research position at the University of Southern California before catching the eye of the Florida governor and becoming both Surgeon General for the state as well as a professor at the University of Florida. He's been on my radar for some bizarre pronouncements that made me want to look deeper.

Looking at his publication list in PubMed and scanning some of the articles, he clearly has good public health knowledge. Most of his publications center around aspects of cardiovascular disease in adults. He does have 3 relatively recent publications related to covid, but I'm deliberately not linking to them, or to his public statements in the past year, because they are either secondary to the conversation or so lacking in scientific merit as to be not worth your time.

His first covid-related publication was in 2021 and analyzed results of a Gallup poll carried out from July to December 2020 regarding adults' misconceptions about covid risk. Curiously, he published another analysis of this same poll in 2022, presenting some of the exact same data. Neither article referenced the other one and made me wonder whether this could be a case of duplicate publication. More importantly, though, why would covid perception data collected in late 2020 have any utility in 2022, unless the authors were analyzing changes over time (which they did not)?

His other covid-related publication from November 2021 was a multi-author effort (he was the 8th out of 12 authors) talking about future priorities in public health management of covid. I was very interested to see that vaccination was seen as the most important intervention given that Dr. Ladapo now disparages most use of covid vaccines, based on nonsensical arguments.

In the past year, Dr. Ladapo has been working actively to discourage covid vaccine use in most instances. You can see some rebuttal from FDA and CDC in early 2023 and separately from FDA more recently.

All of this made me wonder what gives with Dr. Ladapo. He seems to have had good training, and his prior publications show that he does have basic understanding of public health principles. How then to explain his response to a measles outbreak in a Florida elementary school? He left the decision to remain in school up to parents, and he did not encourage measles vaccination. At a minimum, unvaccinated children should be sent home to receive online education until their incubation periods expire. This could effectively stop the school outbreak and prevent further community spread. Every effort should be made to bring all children up to date with measles immunizations. This is pretty basic stuff.

According to news reports, the Manatee Bay Elementary School in Broward County, Florida, has documented several cases of measles. Details about immunization and travel status are lacking, but apparently there is no clear link to foreign travel identified. Remember that measles is the most easily spread infectious disease known. It is thought that at least 95% immunity needs to be present in a community to prevent sustained spread. The vaccination rate in Manatee Bay Elementary is 89.3%. Also, the incubation period is up to 3 weeks following exposure. So, if the outbreak isn't managed immediately, it can stretch on for weeks until every non-immune child is infected. By that time, spread outside the school is certainly likely. Apparently Dr. Lapado isn't concerned about that.

I wanted to understand how the Florida Surgeon General arrived at his decisions. His prior covid vaccine arguments contained a fatal flaw that I always look for to judge how well someone understands public health/vaccine data. This involves an understanding of the Vaccine Adverse Effects Reporting System (VAERS), one of many tools to monitor vaccine side effects in the US. It's a type of early warning system for rare events. It is structured so that anyone can report a potential adverse event as being related to a vaccine; for example, if my neighbor broke a leg skiing and had received a covid vaccine 2 months ago, he or she could report that event to VAERs. Clearly that doesn't prove that the vaccine caused a fractured femur. VAERS is just a way to monitor all potential vaccine problems. Dr. Lapado incorrectly used VAERS data to conclude that covid vaccines killed more people than it helped. No one who understands the structure of VAERS could possibly end up with that idea.

At a loss for understanding Dr. Lapado's logic, I can only suspect he must be having some Mr. Hyde moments. Either he has a dual personality due to some neuropsychological condition, or he is purposely misusing data to achieve political or personal goals. He clearly should know better. I'd love to spend 30 minutes with him to see where he falls on this spectrum. Or, maybe he knows of some unpublished data that refutes the current understanding of measles transmissibility and the role of antibody in providing protection; I'd hope he would have shared that.

WRIS

The Winter Respiratory Infection Season soldiers on. Given the length of this post and relative lack of any new data I'm not going to dive deeply into CDC or other numbers. Suffice to say RSV is still decreasing. flu is a mixed bag across the country, and covid is out there but not surging at the moment.

"Commingled Out of Good and Evil"

Robert Louis Stevenson's "Strange Case of Dr. Jekyll and Mr. Hyde" was one of my favorite books as a child, and it's loaded with great quotes like the one above. I don't like bashing another individual, and I'm also a natural skeptic always willing to entertain new theories based on new data. I just don't think Dr. Ladapo's management of this measles outbreak, or his covid vaccine views, make any sense. For the sake of all Floridians and others they may infect, I hope I'm wrong.

Nest week I'll report any exciting details from the ACIP meeting.

Seeing Spots Before Your Eyes?

Bud WiedermannJanuary 28, 2024January 28, 2024Leave a comment

Washington, DC, had a record high temperature 1 day during our heat wave this past week, and I suppose if you glanced at the sun you might see some spots for a few seconds. But of course I'm referring to different spots in this post.

Measles

I'm probably the only person who has read all of my blog posts over time, so you're forgiven if you don't realize I'm in broken record mode here. I can't count the number of times I've warned providers to be on the lookout for measles cases, and now we are facing a global decline in immunization rates that probably puts us at greatest risk since the modern-day measles vaccine was available in 1968 (the original Enders vaccine appeared in 1963). We've enjoyed some low numbers in the US recently, but that appears to be changing with 9 cases (from Georgia, Missouri, New Jersey, and Pennsylvania) reported to CDC so far this month.

CDC released an alert last week mentioning 23 US cases between December 1 and January 23.

I won't review everything about diagnosis of measles, the CDC website alert is a good resource with links to other sites, but I do want to highlight a few helpful nuances that aren't often mentioned. First, measles is fairly unique among exanthematous infections in that the prodrome interval, the time between onset of first symptoms and appearance of the rash, is long, usually a few days. Most infectious diseases accompanied by rash have very little or no time between onset of symptoms and appearance of the rash, with erythema infectiosum being a notable exception but not easily confused with measles clinically.

The measles prodrome consists of a febrile illness with cough, coryza, conjunctivitis, and Koplik's spots. You can find pictures of Koplik's spots everywhere on the web, but in my experience as an old geezer who has seen many cases of measles in children, they aren't that easy to see or photograph. Therefore, the photos available in textbooks and on line are skewed towards the most obvious. One needs to do a careful oral exam looking for gray or bluish-gray or white fine spots (almost sandpapery) anywhere on the buccal mucosa; the inside of the lower lip is particularly helpful. If you're not sure, find an old geezer clinician to confirm.

In the absence of Koplik spots, or if you don't see the child until the rash appears and the Koplik spots have resolved, pay close attention to the history. Specifically ask for a day-to-day accounting of symptoms; if you feel the parent or patient can recall reliably, noting at least a 2-3 day lag between the onset of high fever, cough, rhinorrhea, and conjunctivitis before the rash appears can be strongly suggestive of measles; the absence of this lag is against the diagnosis. Other alarms to increase your suspicion would be lack of 2 measles immunizations, international travel, and/or exposure to a suspected measles case.

"It ain't what they call you.....

..... it's what you answer to." - attributed to W.C. Fields, though I can't verify the origin.

I thought of Mr. Fields when I heard about administration errors involving the adult RSV vaccine (brand names Abrysvo and Arexvy) given to children and pregnant people. From my viewpoint, it was an accident waiting to happen, due to a name.

In order to speed payment allowance by the Vaccines for Children and other programs, the long-acting monoclonal antibody nirsevimab was officially designated a vaccine. Strictly speaking I guess this is correct: antibody administration is a form of passive immunization. However, the true RSV vaccines are intended only for adults with high risk conditions or for pregnant people to help protect newborns after birth. It was inevitable that confusion would ensue. The notice provides almost no details but does state that most administrations to young infants were "nonserious." Infants who wrongly received an adult RSV vaccine should be considered unprotected and still receive nirsevimab.

WHO Fans the Covid Mask/Distancing Controversy

WHO riled a lot of public health experts with its recent guidance for infection control in healthcare facilities. The main controversial elements involve recommendations to use physical barriers such as plastic windows for areas where patients first present (rated as conditional recommendation, very low certainty of evidence); maintaining a physical distance of at least 1 meter between people ("good practice statement"); and not sufficiently highlighting superiority of respirators (e.g. N95 masks) for general care - this particularly angered those who favor the aerosol, rather than droplet, mode of transmission for SARS-CoV-2. In general it seemed that the WHO panel carried over some details for infection control that do not have strong evidence for use and in some cases (plastic barriers) may be contradicted by other studies.

Note that much of the controversy involves how much weight to give transmission simulation studies - e.g. distances that SARS-CoV-2 travels under experimental conditions rather than real-world evidence which is much more difficult to come by. It's hard for an individual medical practice to make these decisions on their own, best to abide by state or local health department guidance.

Spring Covid Vaccination?

Canada released guidance for covid vaccination this spring, advocating for an additional dose of the XBB.1.5 vaccine recommended last fall. I'd look for the US to make similar recommendations soon. ACIP has a regular meeting scheduled February 28-29, but no agenda is yet available. FDA doesn't have anything scheduled, and they may not need a separate advisory committee meeting for this.

WRIS

In general we seem to be trending downward with our winter respiratory infections, but still lots of runny noses, coughs, and more around.

For RSV I still look primarily at hospitalization rates in young children, the purple line in the graph below, because I think it's the most accurate gauge of RSV. I suspect almost all of these hospitalized children are tested for RSV and flu. The rate clearly is trending down, it's looking like we won't replicate the horrible RSV season of last year.

Influenza-like illness seems to be cooling off as well, as seen in FLUView. Note this measurement includes respiratory illnesses mimicking flu so could be any respiratory virus; there are many more ways to look at flu activity in general, all with their own inaccuracies. In the past I have found this map to be representative of what I've seen clinically in my practice areas.

Covid wastewater (I've said before why I prefer this qualitative measurement) continues to trend downward, and levels are below that seen last year.

All told this is good news for those of you trying to manage your packed patient waiting rooms. Let's just hope you don't have a case of measles sitting in there somewhere!

Do You Even Know What a Broken Record Sounds Like?

I used this term when I said I was sounding like a broken record for repeating over and over my warnings about measles. I harp (pun intended) on this because measles is the most contagious infectious disease known and most younger clinicians in the US have never seen a case, meaning it can be missed easily. However, those same clinicians might never have heard a broken record either. Vinyl records made a bit of a comeback recently but even I no longer have a turntable to play vinyl records; I do have a few moldy vinyl albums from the 1960s and 70s. I'm occasionally tempted to purchase a good turntable, but I have no place for it and it's yet another diversionary rabbit hole I don't need. I ain't gonna call out the name vinyl around here.

Winter Distractions

Bud WiedermannJanuary 7, 2024January 7, 2024Leave a comment

My soon-to-be daughter-in-law recently gave me a bird feeder - not just any bird feeder, but a smart one that has a camera connected to my wifi that takes photos and videos of any birds that show up. I had my first visitors this morning, a few days after I stocked it with birdseed.

In the meantime, winter is here.

WRIS

A lot going on with our Winter Respiratory Infection Season, including some new items.

CDC issued new (or actually old) guidance for use of the long-acting monoclonal antibody nirsevimab for preventing RSV infection in young infants. The change was prompted by the announcement of greater availability of nirsevimab because the manufacturer released an additional 230,000 doses this month. Previously the guidance had indicated that the product should be prioritized for just a subset of infants at higher risk, but now recommendations are to go back to the original plan to administer to all infants less than 8 months of age as well as to infants 8-19 months of age with high risk conditions:

Children who have chronic lung disease of prematurity who required medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) any time during the 6-month period before the start of the second RSV season
Children with severe immunocompromise
Children with cystic fibrosis who have severe disease
American Indian and Alaska Native children

If supply is still limited in your particular area, then prioritization should be used as before. Still a bit vague but very important are all the nuances for ordering, administering, and being reimbursed for the product.

Along that same line, RSV may have peaked nationally.

Even with some good news about RSV slowing down, there's still plenty to go around. Also, influenza continues to drive a lot of healthcare usage for all ages around the country. Here is the percentage of emergency department visits due to the various respiratory infections:

Be aware that this site allows you to look just at your local jurisdiction - here is Maryland:

Covid

This week covid deserves a separate heading with a few new twists. Wastewater tracking once again has accurately predicted a surge in infections.

The JN.1 variant has increased rapidly and is projected to be the predominant covid strain in the US, but without any indication (yet) that it has increased virulence.

This might be a good time to review a bit about variants and also some recent covid findings. Variant nomenclature is confusing to me, I can only imagine how the general public sees this. Here is an evolutionary tree from the same CDC weblink as above.

The nomenclature is from the Pango system, but most people are more familiar with the WHO classification: the delta variant (remember those horrible days?) is B.1.617.2 near the left of the diagram. Omicron is represented in both BA.1 and BA.2. Now here's the important part when we consider new variants, immune-escape, and vaccines: JN.1 has developed on the BA.2 side, just like XBB but on a different branch of the tree. Remember that our current vaccines are based on XBB. As I've mentioned previously, XBB vaccine antibody seems to neutralize JN.1 pretty well in the test tube, but all vaccine (and natural infection) immunity declines significantly within a few months after vaccination or immunization. I would still expect the current vaccine to be pretty good for protecting against severe disease with JN.1 infection.

Although near and dear to my heart, I don't usually talk about old folks in this blog. However, a study of old folks in the Netherlands lends support to the idea that current vaccines are effective against new variants. Without going into details, you can see this study has very recent data and show excellent effectiveness for hospitalization and ICU admission for old folks. It's likely this benefit translates to the younger population that of course has lower rates of hospitalization overall.

Another recent study sheds some light on a question I've been wondering about for some time, namely how common asymptomatic covid infection might be in the omicron era. You might recall that one of the early surprises in 2020 was that asymptomatic infection was both common and very important for viral spread. That made the pandemic much more difficult to control. Now we have data from Hong Kong where rather unique epidemiologic circumstances prevailed. With a population of 7.5 million, Hong Kong officials had still had managed to prevent covid spread very effectively prior to the omicron era, with only about 0.5% of the population having been infected. That ended in early 2022, but it also offered researchers an opportunity to look at rates of asymptomatic infection during the omicron period because virtually none of the population had been infected previously. Using antibody testing, they estimated that 16% of the population was infected during the first 6 months of 2022 and that the percentage of asymptomatic cases was at least 42% (taken from those with reported SARS-CoV-2 infections) and possibly as high as 72% (looking at combined reported and unreported infections). Wow. That doesn't necessarily mean we would have those same rates of asymptomatic infection in the US where we've had a very different epidemiologic curve over the years, but I think it's likely we have a lot of asymptomatic covid surrounding us now.

Some good news about long covid, AKA PCC (post-COVID-19 condition) in children. This Canadian study looked at pediatric emergency department data and found that PCC was present in only 0.67% at the12-month follow-up periods in children testing positive for SARS-CoV-2. That's not the only good news part of this; the rate in a control group of children testing negative for covid was 0.16%, suggesting once again that other infections can trigger some of these long term symptoms. We have NIH-funded studies in the US ongoing now, with good control groups, that should go a long way in giving us guidance for managing PCC as well as other long-term conditions triggered by infections.

The Tipping Point

FDA officials, including Peter Marks who is the director of CBER, recently published a viewpoint article about a vaccination tipping point, i.e. the fact that vaccine hesitancy issues have resulted in a severe decrease in immunization coverage, opening us up to major outbreaks soon. I mention this both because it perfectly supports my views expressed in recent weeks but also it gives me a chance to give credit where credit is due. The term "tipping point," as applied here, often has been credited to Malcolm Gladwell. However, his popularization of the term in a sociologic context earlier this century should go to Morton Grodzins who first adapted this for use in explaining racial integration of neighborhoods in the middle of the 20th century. I'm hoping Gladwell credited him.

In Case You Missed These

Two other articles caught my eye this past week. First is a quality improvement article about shortening treatment duration for children with community acquired pneumonia and skin and soft tissue infections. If you're one of those practitioners who still treats these for 10 days (because we have 10 fingers), check it out.

Secondly, I was attracted to a report about variation in rates of how primary pediatric providers use pediatric subspecialty consultations. Although not the main focus of the report, I was most drawn to the mention that the top 2 conditions for using a pediatric infectious diseases specialist were positive tuberculin skin test and inactive tuberculosis. This jives with my personal experience and certainly points to opportunities to lessen use of subspecialty health care. Multiple resources exist for managing latent tuberculosis infection, including the AAP's Red Book, the CDC, and UCSF's Pediatric TB Resource Page.

For the Birds

My first video stars at the bird feeder were a white-breasted nuthatch, maybe a tufted titmouse (looks a lot like the nuthatch, I couldn't figure it out), and a house finch. When I received the bird feeder, I immediately wondered how best to avoid attracting squirrels and other rodents. I did a bit of web searching and then journeyed to my local bird authorities at the Woodend Nature Sanctuary who of course turned out to be the most helpful. I armed my feeder with capsaicin-treated safflower seeds, not a favorite of squirrels and the like, plus birds can't taste the hot pepper. So far the birds seem to like it.

As for me, it appears I've fallen down another rabbit hole, similar to my butterfly fascination. My wanderings have now included a look at how climate change is affecting our bird populations, as projected by the Audubon Society (apologies for using his name, now controversial, but the Society hasn't yet changed it) in their field guide.

Here is how things will change for the white-breasted nuthatch's winter range with a 1.5 C increase in temperature.

For the tufted titmouse

and the house finch

With more severe temperature increases, the ranges are altered more dramatically. I still hope for some action that will reverse these trends.